Subjects -> MEDICAL SCIENCES (Total: 8196 journals)
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HEMATOLOGY (160 journals)                     

Showing 1 - 151 of 151 Journals sorted alphabetically
Acta Angiologica     Open Access   (Followers: 2)
Acta Haematologica     Full-text available via subscription   (Followers: 23)
Acta Haematologica Polonica     Open Access  
Adipocyte     Open Access  
Advances in Hematology     Open Access   (Followers: 13)
Africa Sanguine     Full-text available via subscription  
American Journal of Hematology     Hybrid Journal   (Followers: 52)
Anemia     Open Access   (Followers: 6)
Annals of Hematology     Hybrid Journal   (Followers: 15)
Archives of Hematology Case Reports and Reviews     Open Access  
Arteriosclerosis, Thrombosis and Vascular Biology     Full-text available via subscription   (Followers: 29)
Artery Research     Hybrid Journal   (Followers: 4)
Artificial Cells, Nanomedicine and Biotechnology     Hybrid Journal   (Followers: 4)
ASAIO Journal     Hybrid Journal   (Followers: 2)
Best Practice & Research Clinical Haematology     Hybrid Journal   (Followers: 5)
Blood     Hybrid Journal   (Followers: 290)
Blood Advances     Open Access   (Followers: 6)
Blood and Lymphatic Cancer : Targets and Therapy     Open Access   (Followers: 7)
Blood Cancer Journal     Open Access   (Followers: 18)
Blood Cells, Molecules, and Diseases     Hybrid Journal   (Followers: 8)
Blood Coagulation & Fibrinolysis     Hybrid Journal   (Followers: 60)
Blood Pressure     Open Access  
Blood Pressure Monitoring     Hybrid Journal   (Followers: 1)
Blood Purification     Full-text available via subscription   (Followers: 6)
Blood Reviews     Hybrid Journal   (Followers: 26)
BMC Hematology     Open Access   (Followers: 7)
BMJ Open Diabetes Research & Care     Open Access   (Followers: 29)
Bone Marrow Transplantation     Hybrid Journal   (Followers: 17)
British Journal of Diabetes & Vascular Disease     Open Access   (Followers: 21)
British Journal of Haematology     Hybrid Journal   (Followers: 60)
British Journal of Primary Care Nursing - Cardiovascular Disease, Diabetes and Kidney Care     Full-text available via subscription   (Followers: 10)
Canadian Journal of Diabetes     Hybrid Journal   (Followers: 28)
Case Reports in Hematology     Open Access   (Followers: 10)
Clinical and Applied Thrombosis/Hemostasis     Open Access   (Followers: 32)
Clinical Diabetes     Full-text available via subscription   (Followers: 39)
Clinical Diabetes and Endocrinology     Open Access   (Followers: 20)
Clinical Lymphoma & Myeloma     Full-text available via subscription   (Followers: 2)
Clinical Lymphoma Myeloma and Leukemia     Hybrid Journal   (Followers: 5)
Clinical Medicine Insights : Blood Disorders     Open Access   (Followers: 1)
Conquest : The Official Journal of Diabetes Australia     Full-text available via subscription   (Followers: 3)
Current Angiogenesis     Hybrid Journal   (Followers: 1)
Current Diabetes Reports     Hybrid Journal   (Followers: 24)
Current Diabetes Reviews     Hybrid Journal   (Followers: 27)
Current Hematologic Malignancy Reports     Hybrid Journal   (Followers: 2)
Current Opinion in Hematology     Hybrid Journal   (Followers: 20)
Cytotherapy     Full-text available via subscription   (Followers: 2)
Der Diabetologe     Hybrid Journal   (Followers: 2)
Diabetes     Full-text available via subscription   (Followers: 404)
Diabetes aktuell     Hybrid Journal   (Followers: 3)
Diabetes and Vascular Disease Research     Hybrid Journal   (Followers: 20)
Diabetes Care     Full-text available via subscription   (Followers: 462)
Diabetes Case Reports     Open Access  
Diabetes Educator     Hybrid Journal   (Followers: 27)
Diabetes Management     Full-text available via subscription   (Followers: 15)
Diabetes Research and Clinical Practice     Hybrid Journal   (Followers: 71)
Diabetes Spectrum     Full-text available via subscription   (Followers: 16)
Diabetes Technology & Therapeutics     Hybrid Journal   (Followers: 50)
Diabetes Therapy     Open Access   (Followers: 23)
Diabetic Foot & Ankle     Open Access   (Followers: 10)
Diabetic Medicine     Hybrid Journal   (Followers: 143)
Diabetologia     Hybrid Journal   (Followers: 201)
Diabetologia Kliniczna     Hybrid Journal  
Diabetologie und Stoffwechsel     Hybrid Journal   (Followers: 2)
Egyptian Journal of Haematology     Open Access  
eJHaem     Open Access  
European Journal of Haematology     Hybrid Journal   (Followers: 16)
Experimental Hematology     Hybrid Journal   (Followers: 6)
Experimental Hematology & Oncology     Open Access   (Followers: 6)
Expert Review of Hematology     Hybrid Journal   (Followers: 5)
Fluids and Barriers of the CNS     Open Access   (Followers: 1)
Global Journal of Transfusion Medicine     Open Access   (Followers: 1)
Haematologica - the Hematology journal     Open Access   (Followers: 33)
Haemophilia     Hybrid Journal   (Followers: 66)
Hematologia     Full-text available via subscription   (Followers: 3)
Hematología     Open Access  
Hematology     Open Access   (Followers: 15)
Hematology Reports     Open Access   (Followers: 4)
Hematology, Transfusion and Cell Therapy     Open Access   (Followers: 2)
Hematology/Oncology and Stem Cell Therapy     Open Access   (Followers: 6)
Hemodialysis International     Hybrid Journal   (Followers: 3)
Hepatitis Monthly     Open Access   (Followers: 3)
Immunohematology : Journal of Blood Group Serology and Molecular Genetics     Hybrid Journal   (Followers: 1)
Indian Journal of Hematology and Blood Transfusion     Hybrid Journal   (Followers: 2)
Info Diabetologie     Full-text available via subscription   (Followers: 1)
InFo Hämatologie + Onkologie : Interdisziplinäre Fortbildung von Ärzten für Ärzte     Full-text available via subscription  
Integrated Blood Pressure Control     Open Access  
International Blood Research & Reviews     Open Access  
International Journal of Clinical Transfusion Medicine     Open Access   (Followers: 3)
International Journal of Diabetes in Developing Countries     Hybrid Journal   (Followers: 6)
International Journal of Diabetes Research     Open Access   (Followers: 8)
International Journal of Hematologic Oncology     Open Access   (Followers: 2)
International Journal of Hematology     Hybrid Journal   (Followers: 4)
International Journal of Hematology Research     Open Access   (Followers: 2)
International Journal of Hematology-Oncology and Stem Cell Research     Open Access   (Followers: 2)
International Journal of Laboratory Hematology     Hybrid Journal   (Followers: 25)
Iraqi Journal of Hematology     Open Access  
JMIR Diabetes     Open Access  
Journal of Blood Disorders & Transfusion     Open Access   (Followers: 3)
Journal of Applied Hematology     Open Access   (Followers: 2)
Journal of Blood Medicine     Open Access   (Followers: 1)
Journal of Cerebral Blood Flow & Metabolism     Hybrid Journal   (Followers: 3)
Journal of Diabetes     Open Access   (Followers: 20)
Journal of Diabetes and its Complications     Hybrid Journal   (Followers: 25)
Journal of Diabetes and Metabolic Disorders     Open Access   (Followers: 8)
Journal of Diabetes Investigation     Open Access   (Followers: 12)
Journal of Diabetes Mellitus     Open Access   (Followers: 5)
Journal of Diabetes Research     Open Access   (Followers: 13)
Journal of Diabetes Research     Open Access   (Followers: 9)
Journal of Hematological Malignancies     Open Access  
Journal of Hematology     Open Access   (Followers: 2)
Journal of Hematology and Transfusion Medicine     Open Access   (Followers: 1)
Journal of Hematopathology     Hybrid Journal   (Followers: 3)
Journal of Hypo & Hyperglycemia     Partially Free  
Journal of Pediatric Hematology/Oncology     Hybrid Journal   (Followers: 8)
Journal of Social Health and Diabetes     Open Access   (Followers: 1)
Journal of Thrombosis and Haemostasis     Hybrid Journal   (Followers: 80)
Journal of Thrombosis and Thrombolysis     Hybrid Journal   (Followers: 35)
Journal of Transfusion Medicine     Full-text available via subscription  
Kidney and Blood Pressure Research     Open Access   (Followers: 4)
Leukemia     Hybrid Journal   (Followers: 22)
Leukemia and Lymphoma     Hybrid Journal   (Followers: 12)
Leukemia Research     Hybrid Journal   (Followers: 8)
Leukemia Research Reports     Open Access   (Followers: 1)
Leukemia Supplements     Full-text available via subscription  
Mediterranean Journal of Hematology and Infectious Diseases     Open Access  
Nederlands Tijdschrift voor Diabetologie     Hybrid Journal  
Nutrition & Diabetes     Open Access   (Followers: 20)
Oncohematology     Open Access   (Followers: 1)
Open Diabetes Journal     Open Access  
Open Hematology Journal     Open Access   (Followers: 1)
Open Hypertension Journal     Open Access  
Open Journal of Blood Diseases     Open Access  
Pediatric Blood & Cancer     Hybrid Journal   (Followers: 8)
Pediatric Hematology Oncology Journal     Open Access   (Followers: 3)
Peritoneal Dialysis International     Hybrid Journal  
Platelets     Hybrid Journal   (Followers: 3)
Practical Diabetes     Hybrid Journal   (Followers: 7)
Primary Care Diabetes     Hybrid Journal   (Followers: 26)
Research & Reviews : Journal of Oncology and Hematology     Full-text available via subscription   (Followers: 1)
Research and Practice in Thrombosis and Haemostasis     Open Access   (Followers: 1)
Revista Cubana de Hematología, Inmunología y Hemoterapia     Open Access  
Seminars in Hematology     Hybrid Journal   (Followers: 12)
Seminars in Thrombosis and Hemostasis     Hybrid Journal   (Followers: 45)
Thalassemia Reports     Open Access   (Followers: 1)
The Lancet Haematology     Full-text available via subscription   (Followers: 38)
Therapeutic Advances in Hematology     Hybrid Journal  
Thrombosis & Haemostasis     Hybrid Journal   (Followers: 140)
Thrombosis Research     Hybrid Journal   (Followers: 47)
Transfusionsmedizin - Immunhämatologie, Hämotherapie, Immungenetik, Zelltherapie     Hybrid Journal  
Transplantation and Cellular Therapy     Hybrid Journal   (Followers: 13)
Veins and Lymphatics     Open Access   (Followers: 1)

           

Similar Journals
Journal Cover
Thrombosis & Haemostasis
Number of Followers: 140  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0340-6245 - ISSN (Online) 2567-689X
Published by Thieme Publishing Group Homepage  [233 journals]
  • Pentosan Polysulfate Inhibits Attachment and Infection by SARS-CoV-2 In
           Vitro: Insights into Structural Requirements for Binding

    • Free pre-print version: Loading...

      Authors: Bertini; Sabrina, Alekseeva, Anna, Elli, Stefano, Pagani, Isabel, Zanzoni, Serena, Eisele, Giorgio, Krishnan, Ravi, Maag, Klaus P., Reiter, Christian, Lenhart, Dominik, Gruber, Rudolf, Yates, Edwin A, Vicenzi, Elisa, Naggi, Annamaria, Bisio, Antonella, Guerrini, Marco
      Pages: 984 - 997
      Abstract: Two years since the outbreak of the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, there remain few clinically effective drugs to complement vaccines. One is the anticoagulant, heparin, which in 2004 was found able to inhibit invasion of SARS-CoV (CoV-1) and which has been employed during the current pandemic to prevent thromboembolic complications and moderate potentially damaging inflammation. Heparin has also been shown experimentally to inhibit SARS-CoV-2 attachment and infection in susceptible cells. At high therapeutic doses however, heparin increases the risk of bleeding and prolonged use can cause heparin-induced thrombocytopenia, a serious side effect. One alternative, with structural similarities to heparin, is the plant-derived, semi-synthetic polysaccharide, pentosan polysulfate (PPS). PPS is an established drug for the oral treatment of interstitial cystitis, is well-tolerated, and exhibits weaker anticoagulant effects than heparin. In an established Vero cell model, PPS and its fractions of varying molecular weights inhibited invasion by SARS-CoV-2. Intact PPS and its size-defined fractions were characterized by molecular weight distribution and chemical structure using nuclear magnetic resonance spectroscopy and liquid chromatography–mass spectrometry, then employed to explore the structural basis of interactions with SARS-CoV-2 spike protein receptor-binding domain (S1 RBD) and the inhibition of Vero cell invasion. PPS was as effective as unfractionated heparin, but more effective in inhibiting cell infection than low-molecular-weight heparin (on a weight/volume basis). Isothermal titration calorimetry and viral plaque-forming assays demonstrated size-dependent binding to S1 RBD and inhibition of Vero cell invasion, suggesting the potential application of PPS as a novel inhibitor of SARS-CoV-2 infection.
      Citation: Thromb Haemost 2022; 122: 984-997
      PubDate: 2022-07-04T09:03:43+01:00
      DOI: 10.1055/a-1807-0168
      Issue No: Vol. 122, No. 06 (2022)
       
  • Joint effect of multiple prothrombotic genotypes and mean platelet volume
           on the risk of incident venous thromboembolism

    • Free pre-print version: Loading...

      Authors: Jakobsen; Lisa, Frischmuth, Tobias, Brækkan, Sigrid Kufaas, Hansen, John-Bjarne, Morelli, Vania Maris
      Abstract: Background: A high mean platelet volume (MPV), a marker of increased platelet reactivity, is a risk factor for venous thromboembolism (VTE). Whether established prothrombotic single nucleotide polymorphisms (SNPs) further increase the VTE risk in subjects with high MPV because of biological interaction remains unknown. Aim: To investigate the joint effect of high MPV and prothrombotic genotypes, comprising a 5-SNP genetic risk score (GRS), on the risk of VTE in a population-based case-cohort.Methods: Incident VTE cases (n=653) and a subcohort (n=1774) were derived from the Tromsø Study (1994-2012). DNA was genotyped for rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2036914 (F11) and rs2066865 (FGG). Hazard ratios (HRs) for VTE with 95% confidence intervals (CIs) were estimated according to predefined MPV-strata (
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-31T13:18:12+01:00
      DOI: 10.1055/a-1863-2052
       
  • Anticoagulant Effects of Dabigatran on Coagulation Laboratory Parameters
           in Pediatric Patients: Combined Data from Five Pediatric Clinical Trials

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      Authors: Mitchell; Lesley G., Röshammar, Daniel, Huang, Fenglei, Albisetti, Manuela, Brandão, Leonardo R., Bomgaars, Lisa, Chalmers, Elizabeth, Halton, Jacqueline, Luciani, Matteo, Joseph, David, Tartakovsky, Igor, Gropper, Savion, Brueckmann, Martina
      Abstract: Background Dabigatran etexilate, a direct oral thrombin inhibitor, is approved to treat venous thromboembolism (VTE) in both adults and children. Objectives This population analysis characterized relationships between dabigatran total plasma concentrations and coagulation laboratory parameters (activated partial thromboplastin time [aPTT]; diluted thrombin time [dTT]; ecarin clotting time [ECT]). Methods Data from three phase 2a and one single-arm and one randomized, comparative phase 2b/3 pediatric studies (measurements: aPTT 2,925 [N = 358]; dTT 2,348 [N = 324]; ECT 2,929 [N = 357]) were compared with adult data (5,740 aPTT, 3,472 dTT, 3,817 ECT measurements; N = 1,978). Population models were fitted using nonlinear mixed-effects modeling. Covariates (e.g., sex, age) were assessed on baseline and drug-effect parameters, using a stepwise covariate model-building procedure. Results Overall, relationships between dabigatran, aPTT, dTT, and ECT were similar in children and adults. For children aged
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-31T13:15:19+01:00
      DOI: 10.1055/s-0042-1744542
       
  • Autoimmune acquired factor XIII/13 deficiency after SARS-CoV-2 mRNA
           vaccination

    • Free pre-print version: Loading...

      Authors: Nakamura; Shingen, Sugasaki, Motoki, Souri, Masayoshi, Akazawa, Hirohito, Sogawa, Maiko, Hori, Taiki, Yamagami, Hiroki, Takishita, Makoto, Aihara, Ken-ichi, Abe, Masahiro, Yasumoto, Atsushi, Morishita, Eriko, Ichinose, Akitada
      Abstract: not required
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-31T13:10:30+01:00
      DOI: 10.1055/a-1863-7265
       
  • Clopidogrel monotherapy versus Aspirin monotherapy in patients with
           established cardiovascular disease: systematic review and meta-analysis

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      Authors: Tasoudis; Panagiotis, Kyriakoulis, Ioannis, Sagris, Dimitrios, Diener, Hans-Christoph, Ntaios, George
      Abstract: Background: The is no clear consensus on whether Aspirin offers better outcomes in terms of secondary cardiovascular disease prevention compared to Clopidogrel.Objective: The aim of the study was to compare the safety and efficacy of Clopidogrel versus Aspirin in patients with established cardiovascular disease.Patients/Methods: A systematic review of MEDLINE (via PubMed), Scopus, and Cochrane Library databases (last search date: August 28th, 2021) was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement for randomized control trials (RCTs) of Clopidogrel versus Aspirin as monotherapy in patients with established cardiovascular disease. Random-effects meta-analyses were performed.Results: Five RCTs incorporating 26,855 patients (Clopidogrel: 13,426; Aspirin: 13,429) were included. No statistically significant difference was observed between Clopidogrel and Aspirin in terms of all-cause mortality (odds ratio [OR]: 1.01 [95% Confidence Interval (95%CI):0.91-1.13]; p=0.83), ischemic stroke (OR: 0.87 [95%CI:0.71-1.06]; p=0.16) and major bleeding rates (OR: 0.77 [95%CI:0.56-1.06]; p=0.11). Patients receiving Clopidogrel had borderline lower risk for major adverse cardiovascular events (MACE) (OR: 0.84 [95%CI:0.71-1.00]; p=0.05) and lower risk for non-fatal myocardial infarction (OR: 0.83 [95%CI:0.71-0.97]; p=0.02, relative-risk-reduction=16.9%, absolute-risk-reduction=0.5%, number-needed-to-treat=217 for a mean period of 20 months) compared to patients receiving Aspirin.Conclusions: In patients with established cardiovascular disease, Clopidogrel was associated with a 17% relative-risk reduction for non-fatal MI, borderline decreased risk for MACE and similar risk for all-cause mortality, stroke and major bleeding compared to Aspirin.Keywords: Clopidogrel; Aspirin; monotherapy; cardiovascular disease; efficacy; myocardial infarction; stroke; mortality; safety; major bleeding
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-31T13:07:22+01:00
      DOI: 10.1055/a-1853-2952
       
  • Inhibition of HIF prolyl hydroxylase modulates platelet function

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      Authors: Gu; Wei, Qi, Jiaqian, Zhang, Sixuan, Ding, Yangyang, Qiao, Jianlin, Han, Yue
      Abstract: Hypoxia-inducible factors-1α (HIF-1α) involves in redox reaction. Considering the role of reactive oxygen species (ROS) in platelet function, whether it regulates platelet function remains unclear. Using an inhibitor of HIF prolyl hydroxylase IOX-2, we intend to investigate its effect on platelet function. Human platelets were treated with IOX-2 (0, 10, 25, and 50 M) followed by analysis of platelet aggregation, granule secretion, receptor expression, platelet spreading or clot retraction. Additionally, IOX-2 (10 mg/kg) was injected intraperitoneally into mice to measure tail bleeding time and arterial thrombosis. IOX-2 significantly inhibited collagen-related peptide (CRP, 0.25 μg/ml) or thrombin (0.03 U/ml)-induced platelet aggregation and ATP release dose dependently without affecting P-selectin expression and the surface levels of glycoprotein (GP)Ib, GPVI or IIb3. In addition, IOX-2-treated platelets presented significantly decreased spreading on fibrinogen or collagen and clot retraction. Moreover, IOX-2 administration into mice significantly impaired the in vivo hemostatic function of platelets and arterial thrombus formation without affecting the number of circulating platelets and coagulation factor (FVIII and FIX). Further, IOX-2 significantly upregulated HIF-1 in platelets, decreased ROS generation and downregulated NOX1 expression. Finally, IOX-2 increased the phosphorylation level of VASP (Ser157/239), and inhibited the phosphorylation of p38 (Thr180/Tyr182), ERK1/2 (Thr202/Tyr204), AKT (Thr308/Ser473) and PKC (Thr505) in CRP- or thrombin-stimulated platelets. In conclusion, inhibition of HIF prolyl hydroxylase modulates platelet function and arterial thrombus formation, possibly through upregulation of HIF-1α expression and subsequent inhibition of ROS generation, indicating that HIF-1α might be a novel target for the treatment of thrombotic disorders.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-31T12:55:30+01:00
      DOI: 10.1055/a-1837-7797
       
  • Early rhythm control and the risks of ischaemic stroke, heart failure,
           mortality and adverse events when performed early (

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      Authors: Chao; Tze-Fan, Chan, Yi-Hsin, Chiang, Chern-En, Tuan, Ta-Chuan, Liao, Jo-Nan, Chen, Tzeng-Ji, Lip, Gregory YH, Chen, Shih-Ann
      Abstract: Background: In EAST-AFNET 4 trial, early rhythm control was associated with better clinical outcomes for patients with atrial fibrillation (AF). However, whether the better outcomes of patients assigned to rhythm control were solely due to “early” intervention or because of more regular and structured follow up was unclear. Objective: To investigate whether the findings of EAST trial are applicable to the ‘real world’ clinical setting, where a less structured management protocol is operated. Methods: From 2001 to 2016, 301,064 newly-diagnosed AF patients were identified from Taiwan National Health Insurance Research Database. Among these patients, 62,649 AF patients receiving antiarrhythmic drugs or catheter ablation within 1 year after AF being diagnosed were categorized as the early rhythm control group, and the remaining 238,415 patients were defined as usual care group. Risk of clinical events were compared.Results: Compared to usual care, early rhythm control was associated with a lower adjusted risk of ischemic stroke(aHR 0.771; p
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-30T16:36:56+01:00
      DOI: 10.1055/a-1807-0336
       
  • Bacterial-Type Long-Chain Polyphosphates Bind Human Proteins in the
           Phosphatidylinositol Signaling Pathway

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      Thromb Haemost
      DOI: 10.1055/s-0042-1751280



      Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

      Artikel in Thieme eJournals:
      Inhaltsverzeichnis     Volltext

      Thromb Haemost ; : -2022-07-30T16:29:00+01:00
       
  • Cucurbitacins elicit anti-platelet activity via perturbation of the actin
           cytoskeleton and integrin function.

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      Authors: Kriek; Neline, Nock, Sophie, Sage, Tanya, Khalifa, Badrija, Bye, Alexander, Mitchell, Joanne L, Thomson, Steven, McLaughlin, Mark G, Jones, Sarah, Gibbins, Jonathan Martin, Unsworth, Amanda
      Abstract: Cucurbitacins are dietary compounds that have been shown to elicit a range of anti-tumour, anti-inflammatory and anti-atherosclerotic activities. Originally identified as STAT inhibitors, a variety of mechanisms of action have since been described, including dysregulation of the actin cytoskeleton and disruption of integrin function. Integrin outside-in signalling and cytoskeletal rearrangements are critical for the propagation of stable thrombus formation and clot retraction following platelet adhesion at the site of vessel damage. The effects of cucurbitacins on platelet function and thrombus formation are unknown. We report for the first time anti-platelet and anti-thrombotic effects of cucurbitacins B, E and I in human platelets. Treatment of platelets with cucurbitacins resulted in attenuation of platelet aggregation, secretion and fibrinogen binding following stimulation by ADP, TRAP6, collagen and CRP-XL. Cucurbitacins were also found to potently inhibit other integrin- and cytoskeleton-mediated events, including adhesion, spreading and clot retraction. Further investigation of cytoskeletal dynamics found treatment with cucurbitacins altered cofilin phosphorylation, enhanced activation, and increased F actin polymerisation and microtubule assembly. Disruption to cytoskeletal dynamics has been previously shown to impair integrin activation, platelet spreading and clot retraction. Anti-platelet properties of cucurbitacins were found to extend to a disruption of stable thrombus formation, with an increase in thrombi instability and de-aggregation under flow. Our research identifies novel, anti-platelet and anti-thrombotic actions of cucurbitacins that appear to be linked to dysregulation of cytoskeletal dynamics and integrin function.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-30T16:24:11+01:00
      DOI: 10.1055/a-1788-5322
       
  • Is there Clinically Relevant Plasma Interference with ELISA Detection of
           APS Antibodies' Reproducibility of Real-World Paired Serum and Plasma
           Testing

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      Authors: Pham; Michael, Orsolini, Giovanni, Crowson, Cynthia S., Moder, Kevin, Pruthi, Rajiv Kumar, Snyder, Melissa
      Abstract: No Abstract
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-30T16:11:20+01:00
      DOI: 10.1055/a-1874-8548
       
  • Continuous Infusion of Factor VIII and von Willebrand Factor in Surgery:
           Trials with pdFVIII LFB or pdVWF LFB in Patients with Bleeding Disorders

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      Authors: Windyga; Jerzy, Guillet, Benoît, Rugeri, Lucia, Fournel, Alexandra, Stefanska-Windyga, Ewa, Chamouard, Valérie, Pujol, Sonia, Henriet, Céline, Bridey, Françoise, Négrier, Claude
      Abstract: Background A plasma-derived factor VIII product (pdFVIII; Factane 100 or 200 IU/mL) and a plasma-derived von Willebrand factor product (pdVWF; Wilfactin 100 IU/mL) are approved for replacement therapy by intravenous bolus injections in hemophilia A (HA) and von Willebrand disease (VWD), respectively. However, in situations requiring intensive treatment, continuous infusion (CI) may be desirable to better control target plasma factor levels. Aim To evaluate the perioperative hemostatic efficacy and safety of these concentrates administered by CI. Methods Three phase III trials were conducted. Adults with HA (FVIII:C 
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-24T17:02:11+01:00
      DOI: 10.1055/a-1865-6978
       
  • Enrichment of Complement, Immunoglobulins, and Autoantibody Targets in the
           Proteome of Platelets from Patients with Systemic Lupus Erythematosus

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      Authors: Linge; Carl Petrus, Jern, Andreas, Tydén, Helena, Gullstrand, Birgitta, Yan, Hong, Welinder, Charlotte, Kahn, Robin, Jönsen, Andreas, Semple, John W., Bengtsson, Anders A.
      Abstract: Background Systemic lupus erythematosus (SLE) is a complex disease characterized by autoimmunity toward apoptotic cells, excessive amounts of circulating immune complexes, and complement activation. A decreased platelet size has been observed in SLE and their nonhemostatic functions may play an active role in the disease. The main objective of this study was to find clues that could explain their decreased size and functional role, analyzing the entire platelet proteome. Methods Platelets were isolated from 23 patients with SLE. The five individuals with the highest and lowest average platelet forward scatter were selected for further analysis. Platelet protein content was analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) and compared with platelets from five healthy controls. Data are available via ProteomeXchange with identifier PXD031202. Results Out of 2,572 proteins identified, 396 had significantly different levels (ANOVA q-value ≤ 0.01). Forty proteins, including immunoglobulin-, complement- and phosphatidylserine-binding proteins had higher abundance in platelets from SLE patients, largely independent of size (fold difference of ≥1.5 and a t-test p-value of ≤0.05 as cut-off). Functional characterization revealed increased degranulation and skewed hemostatic balance in platelets from SLE patients. In the SLE proteome, immunoglobulin proteins were negatively correlated to serum complement C3 and C4 and the highest relative levels were detected in platelets of normal size. Conclusion Platelets from SLE patients shared a specific protein profile, including immunoglobulins, complement proteins, and autoantigens, largely independent of the platelet size and in agreement with an integrated role for platelets in SLE.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-24T16:59:40+01:00
      DOI: 10.1055/a-1825-2915
       
  • Interleukin 1 Receptor 8 Deficiency Does not Impact Atherosclerosis

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      Thromb Haemost
      DOI: 10.1055/a-1827-7205



      Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

      Artikel in Thieme eJournals:
      Inhaltsverzeichnis     Volltext

      Thromb Haemost ; : -2022-07-18T08:10:00+01:00
       
  • THE ADA (AGE-D-DIMER-ALBUMIN) SCORE TO PREDICT THROMBOSIS IN SARS-CoV-2.

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      Authors: Violi; Francesco, Pignatelli, Pasquale, Vestri, Annarita, Spagnoli, Alessandra, Cipollone, Francesco, Ceccarelli, Giancarlo, Oliva, Alessandra, amitrano, maria, Pirro, Matteo, Taliani, Gloria, Cangemi, Roberto, Lichtner, Miriam, Pugliese, Francesco, Falcone, Marco, Venditti, Mario, Mastroianni, Claudio Maria, Loffredo, Lorenzo
      Abstract: Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2)-related pneumonia is associated with venous and arterial thrombosis . Aim of the study was to find-out a new score for predicting thrombosis in patients with SARS-CoV-2. Methods: We included a cohort of 674 patients affected by SARS-CoV-2, not requiring intensive care units, and followed-up during the hospitalization until discharge. Routinary analyses performed at in-hospital admission included also serum albumin and D-dimer while arterial and venous thromboses were the end-points of the study. Results: During the follow-up thrombotic events 110 were registered; patients with thrombotic events were older and had lower albumin and higher D-dimer, compared to thrombotic event-free ones. On multivariable logistic regression with step by stepwise procedure age, serum albumin, D-dimer, were independently associated with thrombotic events. The linear combination of age, D-dimer, albumin allowed to build-up the ADA score, whose AUC was 0.752 (95% CI, 0.708-0.795). ADA score was internally validated by bootstrap sampling procedure giving an AUC of 0.752 (95% CI: 0.708 - 0.794). Conclusions: Combination of age, D-dimer, albumin in the ADA score allows identifying SARS-CoV-2 patients at higher risk of thrombotic events.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-18T07:59:41+01:00
      DOI: 10.1055/a-1788-7592
       
  • The Platelet Lipidome Is Altered in Patients with COVID-19 and Correlates
           with Platelet Reactivity

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      Authors: Schuurman; Alex R., Léopold, Valentine, Pereverzeva, Liza, Chouchane, Osoul, Reijnders, Tom D. Y., Brabander, Justin de, Douma, Renée A., Weeghel, Michel van, Wever, Eric, Schomaker, Bauke V., Vaz, Frédéric M., Wiersinga, Willem Joost, Veer, Cornelis van't, Poll, Tom van der
      Abstract: Background Activated platelets have been implicated in the proinflammatory and prothrombotic phenotype of coronavirus disease 2019 (COVID-19). While it is increasingly recognized that lipids have important structural and signaling roles in platelets, the lipidomic landscape of platelets during infection has remained unexplored. Objective To investigate the platelet lipidome of patients hospitalized for COVID-19. Methods We performed untargeted lipidomics in platelets of 25 patients hospitalized for COVID-19 and 23 noninfectious controls with similar age and sex characteristics, and with comparable comorbidities. Results Twenty-five percent of the 1,650 annotated lipids were significantly different between the groups. The significantly altered part of the platelet lipidome mostly comprised lipids that were less abundant in patients with COVID-19 (20.4% down, 4.6% up, 75% unchanged). Platelets from COVID-19 patients showed decreased levels of membrane plasmalogens, and a distinct decrease of long-chain, unsaturated triacylglycerols. Conversely, platelets from patients with COVID-19 displayed class-wide higher abundances of bis(monoacylglycero)phosphate and its biosynthetic precursor lysophosphatidylglycerol. Levels of these classes positively correlated with ex vivo platelet reactivity—as measured by P-selectin expression after PAR1 activation—irrespective of disease state. Conclusion Taken together, this investigation provides the first exploration of the profound impact of infection on the human platelet lipidome, and reveals associations between the lipid composition of platelets and their reactivity. These results warrant further lipidomic research in other infections and disease states involving platelet pathophysiology.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-18T07:13:36+01:00
      DOI: 10.1055/s-0042-1749438
       
  • Assessment and Mitigation of Bleeding Risk in Atrial Fibrillation and
           Venous Thromboembolism: Executive Summary of a European and Asia-Pacific
           Expert Consensus Paper

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      Authors: Gorog; Diana A., Gue, Ying X., Chao, Tze-Fan, Fauchier, Laurent, Ferreiro, Jose Luis, Huber, Kurt, Konstantinidis, Stavros V., Lane, Deirdre A., Marin, Francisco, Oldgren, Jonas, Potpara, Tatjana, Roldan, Vanessa, Rubboli, Andrea, Sibbing, Dirk, Tse, Hung-Fat, Vilahur, Gemma, Lip, Gregory Y. H.
      Abstract: While there is a clear clinical benefit of oral anticoagulation in patients with atrial fibrillation (AF) and venous thromboembolism (VTE) in reducing the risks of thromboembolism, major bleeding events (especially intracranial bleeds) may still occur and be devastating. The decision for initiating and continuing anticoagulation is often based on a careful assessment of both thromboembolism and bleeding risk. The more common and validated bleeding risk factors have been used to formulate bleeding risk stratification scores, but thromboembolism and bleeding risk factors often overlap. Also, many factors that increase bleeding risk are transient and modifiable, such as variable international normalized ratio values, surgical procedures, vascular procedures, or drug–drug and food–drug interactions. Bleeding risk is also not a static “one-off” assessment based on baseline factors but is dynamic, being influenced by aging, incident comorbidities, and drug therapies. In this executive summary of a European and Asia-Pacific Expert Consensus Paper, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in patients with AF and VTE, with a view to summarizing “best practice” when approaching antithrombotic therapy in these patients. We address the epidemiology and size of the problem of bleeding risk in AF and VTE, and review established bleeding risk factors and summarize definitions of bleeding. Patient values and preferences, balancing the risk of bleeding against thromboembolism, are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-06T08:20:52+01:00
      DOI: 10.1055/s-0042-1750385
       
  • Performance of a Qualitative Point-of-Care Strip Test to Detect DOAC
           Exposure at the Emergency Department: A Cohort-Type Cross-Sectional
           Diagnostic Accuracy Study

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      Authors: Merrelaar; Anne E., Bögl, Magdalena S., Buchtele, Nina, Merrelaar, Marieke, Herkner, Harald, Schoergenhofer, Christian, Harenberg, Job, Douxfils, Jonathan, Siriez, Romain, Jilma, Bernd, Spiel, Alexander O., Schwameis, Michael
      Abstract: An accurate point-of-care test for detecting effective anticoagulation by direct oral anticoagulants (DOACs) in emergencies is an unmet need. We investigated the accuracy of a urinary qualitative strip test (DOAC Dipstick) to detect relevant DOAC exposure in patients who presented to an emergency department. In this prospective single-center cohort-type cross-sectional study, adults on DOAC treatment were enrolled. We assessed clinical sensitivity and specificity of DOAC Dipstick factor Xa and thrombin inhibitor pads to detect DOAC plasma levels ≥30 ng/mL using urine samples as the testing matrix. Liquid chromatography coupled with tandem-mass spectrometry was used as the reference standard method for plasma and urine measurement of DOAC concentrations. Of 293 patients enrolled, 265 patients were included in the analysis, of whom 92 were treated with rivaroxaban, 65 with apixaban, 77 with edoxaban, and 31 with dabigatran. The clinical sensitivity and specificity of the dipstick on urine samples to detect ≥30 ng/mL dabigatran plasma levels were 100% (95% confidence interval [CI]: 87–100%) and 98% (95% CI: 95–99%), respectively. The sensitivity and specificity of the dipstick to detect ≥30 ng/mL factor Xa inhibitor plasma levels were 97% (95% CI: 94–99%) and 69% (95% CI: 56–79%), respectively. The DOAC Dipstick sensitively identified effective thrombin and factor Xa inhibition in a real-world cohort of patients presenting at an emergency department. Therefore, the dipstick might provide a valuable test to detect relevant DOAC exposure in emergencies, although further studies will be needed to confirm these findings.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-04T09:19:07+01:00
      DOI: 10.1055/s-0042-1750327
       
  • Resumption of Antiplatelet Therapy after Major Bleeding

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      Authors: Geisler; Tobias, Poli, Sven, Huber, Kurt, Rath, Dominik, Aidery, Parwez, Kristensen, Steen D., Storey, Robert F., Ball, Alex, Collet, Jean-Philippe, Berg, Jurriën ten
      Abstract: Major bleeding is a common threat in patients requiring antiplatelet therapy. Timing and intensity with regard to resumption of antiplatelet therapy represent a major challenge in clinical practice. Knowledge of the patient's bleeding risk, defining transient/treatable and permanent/untreatable risk factors for bleeding, and weighing these against thrombotic risk are key to successful prevention of major adverse events. Shared decision-making involving various disciplines is essential to determine the optimal strategy. The present article addresses clinically relevant questions focusing on the most life-threatening or frequently occurring bleeding events, such as intracranial hemorrhage and gastrointestinal bleeding, and discusses the evidence for antiplatelet therapy resumption using individual risk assessment in high-risk cardiovascular disease patients.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-07-04T09:19:06+01:00
      DOI: 10.1055/s-0042-1750419
       
  • Rivaroxaban Underdose for Atrial Fibrillation with Stable Coronary
           Disease: The AFIRE Trial Findings

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      Authors: Arashi; Hiroyuki, Yamaguchi, Junichi, Hagiwara, Nobuhisa, Yasuda, Satoshi, Kaikita, Koichi, Akao, Masaharu, Ako, Junya, Matoba, Tetsuya, Nakamura, Masato, Miyauchi, Katsumi, Kimura, Kazuo, Hirayama, Atsushi, Matsui, Kunihiko, Ogawa, Hisao
      Abstract: Background Rivaroxaban monotherapy was noninferior to combination therapy (rivaroxaban plus antiplatelet therapy) in efficacy but superior in safety in the Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial. Among 2,215 patients with atrial fibrillation (AF) and stable coronary artery disease (CAD), 1,378 had baseline creatinine clearance (CrCl) ≥50 mL/min and received 10 (underdose) or 15 mg/d (standard-dose) rivaroxaban. We aimed to assess the effects of rivaroxaban underdose on clinical outcomes. Methods We assessed efficacy endpoint (a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, and death from any cause) and major bleeding in the subgroup of patients with preserved renal function in the AFIRE trial. Results Age ≥75 years, female sex, lower CrCl, heart failure, and percutaneous coronary intervention history were associated with the underdose prescription. The underdose group had a similar incidence of the efficacy endpoint (3.62 vs. 3.51% per patient-year; p = 0.871) and significantly lower incidence of major bleeding (0.82 vs. 2.17% per patient-year; p = 0.022) than the standard-dose group. In patients receiving monotherapy, the incidences of efficacy endpoint and major bleeding were similar between the groups, whereas in those receiving combination therapy, the incidence of major bleeding was significantly lower in the underdose group than that in the standard-dose group. Conclusion In patients with AF, stable CAD, and preserved renal function, rivaroxaban underdose was associated with similar rates of thrombotic events but a lower incidence of hemorrhagic events than the standard dose. Clinical Trial Registration AFIRE UMIN Clinical Trials Registry (https://www.umin.ac.jp/ctr/), number UMIN000016612, and ClinicalTrials.gov, number NCT02642419.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-13T09:31:45+01:00
      DOI: 10.1055/s-0042-1744543
       
  • The Lesson Learned from the New c.2547-1G > T Mutation Combined with
           p.R854Q: When a Type 2N Mutation Reveals a Quantitative von Willebrand
           Factor Defect

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      Authors: Casonato; Alessandra, Cozzi, Maria Rita, Ferrari, Silvia, Rubin, Beatrice, Gianesello, Lisa, De Marco, Luigi, Daidone, Viviana
      Abstract: Type 2N is a rare von Willebrand disease (VWD) variant involving an impairment in the factor VIII (FVIII) carrier function of von Willebrand factor (VWF). It has a phenotype that mimics hemophilia A, and FVIII binding to VWF (VWF:FVIIIB) is tested to differentiate between the two disorders. Type 2N VWF defects may also be associated with quantitative VWF mutations (type 2N/type 1), further complicating the identification of cases. We report on a new quantitative VWF mutation (c.2547–1G > T) revealed by a p.R854Q type 2N mutation acting as homozygous despite being carried as a heterozygous defect. The proband had near-normal VWF levels (initially ruling out a defective VWF synthesis) and slightly reduced FVIII levels, while a VWF:FVIIIB test showed significantly reduced binding. Routine tests on type 2N homozygotes or heterozygotes combined with quantitative VWF defects in our cohort showed reduced FVIII levels in both groups, but it was only in the former that the FVIII/VWF antigen (VWF:Ag) ratio was always significantly reduced. The two tests are therefore not enough to identify all forms of type 2N VWD. While relatives of type 2N homozygotes usually have normal FVIII levels and FVIII/VWF:Ag ratios, relatives of type 2N/type 1 may have high FVIII/VWF:Ag ratios, but their VWF:FVIIIB and/or VWF:FVIIIB/VWF:Ag ratios are always low. Measuring FVIII and VWF levels may therefore suggest type 2N VWD in patients carrying type 2N mutations alone, but not in type 2N combined with quantitative VWF defects. The VWF:FVIIIB test should consequently be included when exploring VWF function, whatever VWD patient's phenotype.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-13T09:27:51+01:00
      DOI: 10.1055/a-1777-6881
       
  • Safety and Efficacy of Selective, Clopidogrel-Based Strategies in Acute
           Coronary Syndrome: A Study-Level Meta-analysis

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      Authors: Patti; Giuseppe, Grisafi, Leonardo, Spinoni, Enrico Guido, Rognoni, Andrea, Mennuni, Marco
      Abstract: Objectives To investigate outcomes with selective, clopidogrel-based therapies versus conventional treatment in patients undergoing percutaneous coronary intervention (PCI), especially for acute coronary syndrome. Background Safety and efficacy of alternative, selective, clopidogrel-based therapies after PCI are not robustly established. Methods We performed a study-level meta-analysis on six randomized trials investigating selective clopidogrel-based therapies (three on unguided de-escalation, N = 3,473; three on guided clopidogrel therapy, N = 7,533). Control groups received ticagrelor or prasugrel treatment. Main endpoints were major bleeding, any bleeding, major adverse cardiovascular events (MACE), and net clinical endpoint. Results The incidence of major bleeding and MACE was similar in the selective, clopidogrel-based therapy versus the conventional treatment arm (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.51–1.01, p = 0.06; OR: 0.93, 0.72–1.20, p = 0.58; respectively). The rates of any bleeding were lower in the selective, clopidogrel-based therapy versus conventional treatment group (OR: 0.57, 95% CI: 0.40–0.80, p = 0.001); this greater safety was significant for unguided de-escalation (OR: 0.43, 95% CI: 0.32–0.58, p = 0.00001) and nonsignificant for guided clopidogrel therapy (OR: 0.72, 95% CI: 0.51–1.02, p = 0.07; p for interaction: 0.03). The incidence of the net clinical endpoint was fewer in the selective, clopidogrel-based therapy versus the conventional treatment arm (OR: 0.59, 95% CI: 0.41–0.85, p = 0.004); this benefit was significant for unguided de-escalation (OR: 0.50, 95% CI: 0.39–0.64, p 
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-13T09:16:56+01:00
      DOI: 10.1055/a-1827-8041
       
  • Outcome of Cancer-Associated Venous Thromboembolism Is More Favorable
           among Patients with Hematologic Malignancies than in Those with Solid
           Tumors

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      Authors: Lecumberri; Ramón, Ruiz-Artacho, Pedro, Tzoran, Inna, Brenner, Benjamin, Farge-Bancel, Dominique, Ay, Cihan, Rosa, Vladimir, Francisco, Iria, Hernández-Blasco, Luis Manuel, Trujillo-Santos, Javier, Monreal, Manuel
      Abstract: Background The natural history of patients with hematologic cancer and venous thromboembolism (VTE) has not been consistently evaluated. We aimed to compare the rates of symptomatic recurrent VTE, major bleeding, or death during anticoagulant therapy in patients with VTE associated with hematologic versus solid cancers. Methods Consecutive patients with active cancer recruited in RIETE were evaluated. Their baseline characteristics, treatments, and outcomes during the course of anticoagulation were compared. Univariate and multivariate competing-risk analyses were performed. Results As of December 2020, 16,694 patients with cancer and VTE were recruited. Of these, 1,062 (6.4%) had hematologic cancers. Hematologic patients were less likely to initially present with pulmonary embolism (46 vs. 55%) and more likely with upper extremity deep vein thrombosis (25 vs. 18%). They also were more likely to have severe thrombocytopenia at baseline (5.6 vs. 0.7%) or to receive chemotherapy (67 vs. 41%). During the course of anticoagulation (median, 150 vs. 127 days), 1,071 patients (6.4%) developed VTE recurrences, 806 (4.8%) suffered major bleeding, and 4,136 (24.8%) died. Patients with hematologic cancers had lower rates of recurrent VTE (rate ratio [RR]: 0.73; 95% confidence interval [CI]: 0.56–0.95), major bleeding (RR: 0.72; 95% CI: 0.53–0.98), or all-cause death (RR: 0.49; 95% CI: 0.41–0.57) than those with solid cancers. Patients with multiple myeloma showed the best outcomes. Conclusion Patients with hematologic cancers, particularly multiple myeloma, and VTE had better outcomes than those with solid cancers. These findings are relevant for the interpretation of previous clinical trials and the design of future studies.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-13T09:10:55+01:00
      DOI: 10.1055/a-1777-4006
       
  • Managing Uncertainty: Physicians' Decision Making for Stroke Prevention
           for Patients with Atrial Fibrillation and Intracerebral Hemorrhage

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      Authors: Ivany; Elena, Lotto, Robyn R., Lip, Gregory Y.H., Lane, Deirdre A.
      Abstract: Background Stroke prevention in patients with atrial fibrillation (AF) post-intracerebral hemorrhage (ICH) is an area of clinical equipoise. Little is known about the tools and processes that physicians use to make decisions regarding anticoagulation in this high-risk patient population. Objective To explore physicians' decision-making process regarding stroke prevention in patients with AF and a recent history of ICH. Methods Qualitative study, utilizing semistructured interviews and analyzed using Framework analysis. Results Twenty physicians from five European countries (Austria, France, Germany, Spain, United Kingdom) participated. The overarching theme “Managing uncertainty,” addressed the process of making high-risk clinical decisions in the context of little available robust clinical evidence for best practice. Three subthemes were identified under the umbrella theme: (1) “Computing the risks,” captured the challenge of balancing the risks of ischemic stroke with the risk of recurrent ICH in a complex patient population; (2) “Patient factors” highlighted the influence that physician-perceived patients' beliefs and previous experience of stroke had on physicians' decisions; and (3) “Making a decision” explored the process of reaching a final decision regarding initiation of OAC therapy or not. Conclusion Physicians described the process of deciding on stroke prevention in patients with AF post-ICH as “challenging” due to considerable “clinical equipoise.” Key factors that affected decision making were patient comorbidities, functional status, and patient willingness to engage with OAC therapy. Shared decision making was believed to be beneficial, but physicians believed that the ultimate responsibility to decide on stroke prevention lay with the clinician.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-13T09:03:50+01:00
      DOI: 10.1055/a-1789-4824
       
  • Effectiveness and Safety of Apixaban versus Rivaroxaban in Patients with
           Atrial Fibrillation and Type 2 Diabetes Mellitus

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      Authors: Chowdhury; Krishna Roy, Michaud, Jonathan, Yu, Oriana Hoi Yun, Yin, Hui, Azoulay, Laurent, Renoux, Christel
      Abstract: Aims To evaluate the effectiveness and safety of apixaban versus rivaroxaban among patients with nonvalvular atrial fibrillation (NVAF) and type 2 diabetes mellitus (T2DM). Methods and Results Using the United Kingdom's Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository, and the Office for National Statistics database, we identified a cohort of patients with NVAF and T2DM newly treated with apixaban or rivaroxaban between 2013 and 2020. Propensity scores with standardized mortality ratio weighting were used to control for confounding. We used weighted Cox proportional hazards models to estimate separately the hazard ratios (HRs) with 95% confidence intervals (CIs) of ischemic stroke, major bleeding, and major adverse limb events associated with the use of apixaban compared with rivaroxaban. We also evaluated whether the risk was modified by age, sex, duration of diabetes, microvascular and macrovascular complications of diabetes, nephropathy, CHA2DS2-VASc and HAS-BLED scores, and by dose (standard vs. low dose). Results The cohort included 11,561 apixaban and 8,265 rivaroxaban users. Apixaban was associated with a similar risk of stroke (HR: 0.99, 95% CI: 0.79–1.23), and a 32% reduced risk of major bleeding (HR: 0.68, 95% CI: 0.59–0.78), compared with rivaroxaban. The risk of major adverse limb events was similar between apixaban and rivaroxaban (HR: 0.75, 95% CI: 0.54–1.04). Overall, the risk of ischemic stroke and major bleeding was consistent in stratified analyses. Conclusion Among patients with NVAF and T2DM, apixaban was associated with a similar risk of stroke and a lower risk of major bleeding compared with rivaroxaban.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-13T08:17:02+01:00
      DOI: 10.1055/a-1798-2116
       
  • Immunity in Stroke: The Next Frontier

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      Authors: Li; Ting, Liesz, Arthur
      Abstract: Translational stroke research has long been focusing on neuroprotective strategies to prevent secondary tissue injury and promote recovery after acute ischemic brain injury. The inflammatory response to stroke has more recently emerged as a key pathophysiological pathway contributing to stroke outcome. It is now accepted that the inflammatory response is functionally involved in all phases of the ischemic stroke pathophysiology. The immune response is therefore considered a breakthrough target for ischemic stroke treatment. On one side, stroke induces a local neuroinflammatory response, in which the inflammatory activation of glial, endothelial and brain-invading cells contributes to lesion progression after stroke. On the other side, ischemic brain injury perturbs systemic immune homeostasis and results in long-lasting changes of systemic immunity. Here, we briefly summarize current concepts in local neuroinflammation and the systemic immune responses after stroke, and highlight two promising therapeutic strategies for poststroke inflammation.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-10T11:15:33+01:00
      DOI: 10.1055/s-0042-1748890
       
  • Adverse Events and All-Cause Mortality in Danish Patients with Cerebral
           Venous Thrombosis: A Nationwide Cohort Study

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      Authors: Ording; Anne Gulbech, Skjøth, Flemming, Andersen, Søren Due, Larsen, Torben Bjerregaard
      Abstract: Background Cerebral venous thrombosis (CVT) is a rare manifestation of stroke and venous thromboembolism (VTE), compared with deep vein thrombosis (DVT) and pulmonary embolism (PE). We examined whether CVT was associated with adverse cardiovascular events. Methods A Danish cohort study with adult patients diagnosed with CVT (N = 1,015) between 1997 and 2017. We matched 10 patients with VTE (DVT and PE) to each patient with CVT for age, sex, and diagnosis year. We also matched 10 individuals from the general population to each patient with CVT. We computed cumulative incidence and estimated hazard ratios (HRs) with 95% confidence intervals (95% CIs) at 5 years for major bleeding, intracranial bleeding, ischemic stroke, and cardiovascular events. Death was examined separately. Results Major bleeding risks were 1.2% for CVT and 0.7% for VTE at 6 months; these risks increased to 2.7% and 2.6%, respectively, at 5 years. Although rare, intracranial bleeding risks were markedly higher for CVT (2.9%) than for VTE (0.4%) at 5 years (HR = 8.9, 95% CI: 5.3–15.1). Incidences of ischemic stroke were 5.9% for CVT and 0.3% for VTE, at 6 months; and 10.0% and 1.4%, respectively, at 5 years (HR = 9.5, 95% CI: 7.1–12.7). In contrast, incidence of cardiac events was lower for CVT that VTE (1.7% vs. 3.6% at 5 years). Mortality risk was higher after CVT compared with VTE, at 6 months (6.6% vs. 3.8%), but the risks differed little at 5 years (14.3% vs. 14.1%). Conclusion Intracranial bleeding, ischemic stroke, and mortality risks were higher for patients with CVT than matched patients with VTE and the general population, particularly within 6 months after diagnosis.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-10T10:16:57+01:00
      DOI: 10.1055/s-0042-1743473
       
  • Growth Differentiation Factor-15: a Novel Biomarker for Predicting Risk of
           Venous Thromboembolism and Bleeding in Patients with Cancer

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      Authors: Nopp; Stephan, Pabinger, Ingrid
      Abstract: No Abstract
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-10T10:11:29+01:00
      DOI: 10.1055/a-1827-7328
       
  • Growth Differentiation Factor-15, High-Sensitivity Cardiac Troponin T, and
           N-Terminal pro-B-type Natriuretic Peptide for Predicting Risk of Venous
           Thromboembolism in Ambulatory Cancer Patients Receiving Chemotherapy

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      Authors: Roy; Danielle Carole, Wang, Tzu-Fei, Mallick, Ranjeeta, Carrier, Marc, Mollanji, Eisi, Liu, Peter, Zhang, Liyong, Hawken, Steven, Wells, Philip
      Abstract: Growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (hs-TnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with increased risk of venous thromboembolism (VTE) in noncancer patients. However, the performance of these biomarkers in cancer patients is unknown. Our objective was to assess performance of these biomarkers in predicting VTE in cancer patients at intermediate to high risk for VTE (Khorana Score ≥ 2). We used 1-month plasma samples from AVERT trial patients to determine if GDF-15, NT-proBNP, and hs-TnT levels are associated with VTE incidence between 1 and 7 months from the start of chemotherapy. The minimal Euclidean distance of the receiver operating characteristic curve was used to derive optimal cut-offs for GDF-15 and NT-proBNP given there was no evidence of a commonly used cut-off. Logistic and Fine and Gray competing risk regression analyses were used to calculate odds ratios (ORs) and subdistribution hazard ratios, respectively, while adjusting for age, sex, anticoagulation, and antiplatelet therapy. We tested in two groups: all patients (n = 476, Model 1) and all patients with nonprimary brain cancers (n = 454, Model 2). In models 1 and 2, GDF-15 ≥2,290.9 pg/mL had adjusted ORs for VTE of 1.65 (95% confidence interval [CI]: 0.89–3.08), and 2.28 (95% CI: 1.28–4.09), respectively. hs-TnT ≥14.0 pg/mL was associated with higher odds of VTE in models 1 and 2 (adjusted ORs: 2.26 [95% CI: 1.40–3.65] and 2.03 [95% CI: 1.07–3.84], respectively). For NT-proBNP, levels ≥183.5 pg/mL were not associated with VTE. Similar results were observed in the Fine and Gray analysis. Our results indicate that increased GDF-15 and hs-TnT levels predicted increased VTE risk.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-05-31T00:00:00+01:00
      DOI: 10.1055/a-1792-7720
       
  • Association of Combined Lifestyle and Polygenetic Risk with Incidence of
           Venous Thromboembolism: A Large Population-Based Cohort Study

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      Authors: Zhang; Yu-Jie, Li, Zhi-Hao, Shen, Dong, Zhang, Pei-Dong, Fu, Shi-Hui, Yao, Yao, Wang, Jing-Xin, Chen, Pei-Liang, Zhang, Pei, Zhang, Xi-Ru, Mao, Chen
      Abstract: As one of the fatal complications, venous thromboembolism (VTE) is associated with increased mortality. However, the combined effects of adopting multiple healthy lifestyles have not been firmly demonstrated. This study was to evaluate the association of combined healthy lifestyles and genetic risk factors with VTE and to investigate their interaction. A prospective cohort study from UK Biobank with a total of 442,963 men and women aged between 38 to 73 years were recruited from 2006 to 2010 and followed up through 2017 or 2018. A polygenic risk score was constructed and a weighted healthy lifestyle score, including no current smoking, regular physical exercises, healthy diet, and healthy body mass index, was categorized. During a median follow-up 9.0 years (3,912,396 person-years), there were 6,736 (172 per 100,000 person-years) incident VTE cases recorded. Among the participants with an unfavorable lifestyle, 1.80% developed VTE, versus 1.03% of the participants with a favorable lifestyle (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.48–1.68). Of the participants with high genetic risk, 2.42% developed VTE, versus 0.97% of the participants with low genetic risk (HR: 2.60; 95% CI: 2.39–2.81). Moreover, of the participants with high genetic risk and unfavorable lifestyle, 2.90% developed VTE, versus 0.66% of the participants with low genetic risk and favorable lifestyle (HR: 4.09; 95% CI: 3.48–4.79). No significant interaction between genetic risk and lifestyle factors was observed (p for interaction = 0.727). An unfavorable lifestyle was associated with a substantially higher risk of VTE, regardless of the genetic risk strata.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-05-27T00:00:00+01:00
      DOI: 10.1055/s-0042-1744377
       
  • Platelet Activation via Glycoprotein VI Initiates Thrombin Generation: A
           Potential Role for Platelet-Derived Factor IX'

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      Authors: Li; Li, Roest, Mark, Meijers, Joost C. M., de Laat, Bas, Urbanus, Rolf T., de Groot, Philip G., Huskens, Dana
      Abstract: Collagen triggers coagulation via activation of factor (F) XII. In a platelet-rich environment, collagen can also trigger coagulation independently of FXII. We studied a novel mechanism of coagulation initiation via collagen-dependent platelet activation using thrombin generation (TG) in platelet-rich plasma. Collagen-induced coagulation is minimally affected by active-site inactivated FVIIa, anti-FVII antibodies, or FXIIa inhibition (corn trypsin inhibitor). Activation of platelets via specific glycoprotein (GP) VI agonists initiates TG, FX activation, and fibrin formation. To determine the platelet-derived trigger of coagulation, we systematically reconstituted factor-deficient plasmas with washed platelets. TG triggered by GPVI-activated platelets was significantly affected in FIX- and FVIII-deficient plasma but not in FVII- and FXII-deficient plasma. In a purified system composed of FX and FVIII, we observed that absence of FIX was compensated by GPVI-activated platelets, which could be inhibited by an anti-FIX antibody, suggesting FIXa activity from activated platelets. Furthermore, with the addition of FVIII in FIX-deficient plasma, TG induced by GPVI-activated platelets was restored, and was inhibited by the anti-FIX antibody. In conclusion, GPVI-activated platelets initiate TG, probably via platelet-derived FIXa activity.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-05-05T00:00:00+01:00
      DOI: 10.1055/s-0042-1744379
       
  • JAK2V617F Is a Risk Factor for TIA/Stroke in Young Patients

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      Authors: Shapira Cohen; Tamar, Chodick, Gabriel, Steinberg, David M., Grossman, Ehud, Shohat, Mordechai, Salomon, Ophira
      Abstract: The objective of this study was to assess the risk of arterial thrombosis in patients who harbor the JAK2V617F allele burden ≥1% detected during workup for myeloproliferative neoplasms (MPNs). We conducted a large cross-sectional analysis consisted of 5,220 patients who were tested for JAK2V617F and 1,047,258 people matched in age from health care insurance provider, taking into account age, sex, hypertension, diabetes, atrial fibrillation. Compared with noncarriers, mutation carriers were older, less likely to be current or past smokers and had lower body mass index. There was no significant difference between the groups regarding myocardial infarction and peripheral vascular disease. However, JAK2V617F ≥1% at age 34 to 54 years was associated with eightfold more likely to have transient ischemic attack (TIA)/stroke history unrelated to hypertension, diabetes, or atrial fibrillation. Association of JAK2V617F with TIA/stroke was also observed in the older age group, albeit a weaker association and not statistically significant. Prevalence of TIA/stroke was higher in patients with JAK2V617F negative, with odds ratio of 3.93 when compared with the general population after confounder adjustments. Further research is warranted to verify the relation between allele burden of JAK2V617F mutation and TIA/stroke and the role of JAK2V617F per se as a risk factor for arterial thrombosis in the absence of overt MPN. Also, consideration should be paid to the screened group with JAK2V617F negative due to the high incidence of TIA/stroke among them in comparison to the general population.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-03-14T00:00:00+0100
      DOI: 10.1055/s-0042-1743470
       
  • One Year Prevalence of Venous Thromboembolism in Hospitalized COVID-19
           Patients in France: Patients' Characteristics, Time Trends, and Outcomes

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      Authors: Gabet; Amélie, Grave, Clémence, Tuppin, Philippe, Olié, Valérie, Emmerich, Joseph
      Abstract: Background Patients hospitalized with coronavirus disease-2019 (COVID-19) are at high risk of deep venous thrombosis (DVT) and pulmonary embolism (PE). Objectives The aims were to provide time trends in the 2020 nation-wide prevalence of venous thromboembolism (VTE) in patients hospitalized with a COVID-19 diagnosis in France, and to describe in-hospital and up to 30-day postdischarge death. Methods All patients hospitalized in France with a COVID-19 diagnosis in 2020 were selected. Crude and age-adjusted prevalence of VTE and PE was computed by 4-week intervals and for the overall study period using Poisson regression. Time trends in in-hospital and 30-day postdischarge case-fatality rates were evaluated by comparing each 4-week intervals to weeks 10 to 14 corresponding to the first part of the first lockdown using logistic regression models. Results Among the 287,638 patients hospitalized with a COVID-19 diagnosis in 2020 in France, 14,985 (5.2%) had a concomitant VTE, with 10,453 (3.6%) having PE and 4,532 (1.6%) having DVT. In patients admitted to intensive care units, the crude prevalence of VTE and PE reached 16.1 and 11.0% respectively during the first lockdown. After adjustment, the prevalence of VTE and PE decreased during the year 2020 but a rebound was observed during the second lockdown. In-hospital case-fatality rates among hospitalized COVID-19 patients with PE globally decreased between the first and the second epidemic waves. Conclusion Our study showed a decrease in the incidence of symptomatic VTE and PE in hospitalized COVID-19 patients, and a decreased time trend of outcomes during the second wave compared with the first one.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-03-14T00:00:00+0100
      DOI: 10.1055/s-0042-1743475
       
  • Assessing Clinically Meaningful Hypercoagulability after COVID-19
           Vaccination: A Longitudinal Study

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      Authors: Campello; Elena, Bulato, Cristiana, Simion, Chiara, Spiezia, Luca, Radu, Claudia Maria, Gavasso, Sabrina, Sartorello, Francesca, Saggiorato, Graziella, Zerbinati, Patrizia, Fadin, Mariangela, Tormene, Daniela, Simioni, Paolo
      Abstract: A large number of daily requests to exclude possible prothrombotic risk factors for coronavirus disease 2019 (COVID-19) vaccines were received. Our aim was to longitudinally evaluate coagulation profiles in a series of healthy subjects who received COVID-19 vaccination and assess hypercoagulability thereafter. Volunteers awaiting a first or second dose of either the ChAdOx1 or BNT162b2 vaccine were enrolled. Venous samples were obtained at baseline (before the vaccine) and longitudinally 3 ± 2 days (T1) and 10 ± 2 days after the vaccine (T2). Global coagulation monitoring was assessed via platelet count, whole blood thromboelastometry and impedance aggregometry, plasma thrombin generation, and anti-platelet factor 4 (PF4)/heparin immunoglobulin G antibodies. One hundred and twenty-two subjects were enrolled (61 [50%] ChAdOx1 and 61 BNT162b2). The ChAdOx1 cohort showed a slight but transient increase in thrombin generation (mainly endogenous thrombin potential [ETP] with thrombomodulin and ETP ratio) at T1, which promptly decreased at T2. In addition, the second dose of either vaccine was associated with increased thrombin peak, ETP with thrombomodulin, and ETP ratio. At baseline, 3.2% of the ChAdOx1 cohort and 1.6% BNT162b2 cohort were positive for PF4/heparin antibodies with a stable titer through T1 and T2. No relevant differences were detected in platelet count and aggregation, or thromboelastometry parameters. No thrombotic or hemorrhagic events occurred. We can confirm that no clinically meaningful hypercoagulability occurred after either vaccine, albeit keeping in mind that thrombin generation may increase in the first days after the second dose of either vaccine and after the first dose of the ChAdOx1 vaccine.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-03-04T00:00:00+0100
      DOI: 10.1055/a-1788-5206
       
  • Aspirin for Primary Cardiovascular Prevention in Patients with Diabetes:
           Uncertainties and Opportunities

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      Authors: Del Bianco-Rondeau; Mélina, Robert-Halabi, Maxime, Bloom, Samara, Rabasa-Lhoret, Remi, Tardif, Jean-Claude, Lordkipanidzé, Marie, Marquis-Gravel, Guillaume
      Abstract: The use of the antiplatelet agent aspirin (acetylsalicylic acid) was previously routinely recommended for the primary prevention of cardiovascular (CV) events in patients with diabetes, but recent large-scale randomized trials have failed to demonstrate a sizeable net clinical benefit with a once-daily, low-dose (81–100 mg) regimen in this population. Previous pharmacokinetic and pharmacodynamic studies have suggested that the aspirin formulation (enteric-coated) and dosing schedule (once daily) studied in randomized trials for primary prevention of CV events defining contemporary clinical practice may not leverage the full potential of the drug, particularly in patients with diabetes. Indeed, the diabetic platelets bear characteristics that increase their thrombotic potential and alter their pharmacologic response to the drug. Consequently, the appropriateness of studying a uniform aspirin regimen in landmark primary prevention trials needs to be revisited. In this review, we present the evidence showing that diabetes not only increases baseline platelet reactivity, but also alters platelet response to aspirin through different mechanisms including a faster platelet turnover rate. Obesity, which is frequently associated with diabetes, also impacts its pharmacokinetics via an increase in distribution volume. Small-scale pharmacokinetic and pharmacodynamic studies have suggested that the relative aspirin resistance phenotype observed in patients with diabetes may be reversed with a twice-daily dosing schedule, and with nonenteric-coated aspirin formulations. Properly powered randomized controlled trials investigating the efficacy and safety of aspirin dosing schedules and formulations tailored to the population of patients with diabetes are urgently required to optimize patient care.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-03-04T00:00:00+0100
      DOI: 10.1055/s-0042-1743469
       
  • State-of-the-Art Mini Review: Dual-Pathway Inhibition to Reduce Arterial
           and Venous Thromboembolism

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      Authors: Goldin; Mark, Koulas, Ioannis, Weitz, Jeffrey I., Spyropoulos, Alex C.
      Abstract: Venous thromboembolism (VTE) and arterial thromboembolism (ATE) are linked by the common mechanism of thrombin generation. Historically these entities have been treated as separate pathophysiologic processes requiring different treatments: VTE, as the formation of fibrin-/coagulation-factor-derived thrombus in low-flow vasculature, requiring anticoagulants; versus ATE, as largely platelet-derived thrombus in high-flow vasculature, requiring antiplatelet agents. Observational studies have elucidated shared risk factors and comorbidities predisposing individuals with VTE to ATE, and vice versa, and have bolstered the strategy of dual-pathway inhibition (DPI)—the combination of low-dose anticoagulants with antiplatelet agents—to reduce thrombotic outcomes on both sides of the vasculature. Randomized clinical trials have evaluated the efficacy and safety of such regimens—mostly rivaroxaban and aspirin—in high-risk groups of patients, including those with recent acute or chronic coronary syndrome, as well as those with peripheral artery disease with or without revascularization. Studies of extended VTE prophylaxis in acutely ill medical patients have also contributed to the evidence evaluating DPI. The totality of available data supports the concept that DPI can reduce major and fatal thromboembolic outcomes, including stroke, myocardial infarction, VTE, and cardiovascular death in key patient cohorts, with acceptable risk of bleeding. Further data are needed to refine which patients derive the best net clinical benefit from such an approach. At the same time, other novel agents such as contact pathway inhibitors that reduce thrombin generation without affecting hemostasis—and thus maximize safety—should be assessed in appropriate populations.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-02-21T00:00:00+0100
      DOI: 10.1055/a-1778-1083
       
  • Changes in endocan and dermatan sulfate are associated with biomechanical
           

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      Authors: Metschl; Susanne, Bruder, Lukas, paloschi, valentina, Jakob, Katharina, Reutersberg, Benedikt, Reeps, Christian, Maegdefessel, Lars, Gee, Michael, Eckstein, Hans-Henning, Pelisek, Jaroslav
      Abstract: Background and aims: The study aimed to assess the potential of proteoglycans (PG) and collagens as serological biomarkers in the abdominal aortic aneurysm (AAA). Furthermore, we investigated the underlying mechano-biological interactions and signaling pathways.Methods: Tissue and serum samples from patients with ruptured AAA (rAAA, n=29), elective AAA (eAAA, n=78), and healthy individuals (n=8) were evaluated by histology, immunohistochemistry and Enzyme-linked Immunosorbent Assay (ELISA), mechanical properties were assessed by tensile tests. Regulatory pathways were determined by membrane-based sandwich immunoassay.Results: In AAA samples, collagen type I and III (Col1, Col3), chondroitin sulfate (CS), and dermatan sulfate (DS) were significantly increased compared to controls (3.0-, 3.2-, 1.3-, and 53-fold; p
      Citation: Thromb Haemost ; : -
      PubDate: 2022-02-15T00:00:00+0100
      DOI: 10.1055/a-1772-0574
       
  • Human Atheromatous Plaques Expressed Sensing Adaptor STING, a Potential
           Role in Vascular Inflammation Pathogenesis

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      Thromb Haemost
      DOI: 10.1055/a-1772-1192



      Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

      Artikel in Thieme eJournals:
      Inhaltsverzeichnis     Volltext

      Thromb Haemost ; : -2022-02-15T00:00:00+0100
       
  • Active FXI Can Independently Predict Ischemic Stroke in Anticoagulated
           Atrial Fibrillation Patients: A Cohort Study

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      Authors: Ząbczyk; Michał Tomasz, Hanarz, Maksymilian, Malinowski, Krzysztof P., Pociask, Elżbieta, Butenas, Saulius, Gajos, Grzegorz, Undas, Anetta
      Abstract: Background Atrial fibrillation (AF) is associated with a prothrombotic state. Presence of active tissue factor (TF), activated factor IX (FIXa) and FXIa in circulating blood contributes to thrombosis. We investigated a prognostic value of these factors in AF patients. Methods In this cohort study, 284 AF patients (aged 63.3 ± 8.8 years) treated with oral anticoagulants were enrolled. Plasma levels of active coagulation factors were evaluated using thrombin generation assay. Concentrations of fibrinogen, D-dimer, interleukin-6 (IL-6), and endothelial damage markers, including von Willebrand factor (VWF) and soluble (s)E-selectin, were also measured. Ischemic stroke and cardiovascular death, analyzed separately or as a composite endpoint, were recorded during a mean follow-up of 47 months. Results Cerebrovascular events were observed in 20 patients (1.8%/year) who had at baseline higher fibrinogen, D-dimer, and VWF levels. Active TF and FXIa at enrollment were detectable in 12 (60%) and 15 (75%) patients who experienced ischemic stroke during follow-up. The composite endpoint observed in 23 patients (2.1%/year) was associated with increased concentrations of the above laboratory variables, along with 26% higher IL-6 levels. sE-selectin did not differ between the studied groups. On multivariable regression analysis, advanced age, anticoagulation discontinuation, and detectable FXIa, but not active TF, independently predicted the composite endpoint. No associations of FIXa with the study endpoints were observed. Conclusion FXIa present in circulating blood is associated with increased risk of ischemic stroke and cardiovascular death in anticoagulated AF patients during long-term follow-up. FXIa inhibition could be useful in cardiovascular prevention in AF beyond the current oral anticoagulation.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-02-14T00:00:00+0100
      DOI: 10.1055/s-0042-1742366
       
  • CM-352 Efficacy in a Mouse Model of Anticoagulant-Associated Intracranial
           Hemorrhage

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      Authors: Navarro-Oviedo; Manuel, Marta-Enguita, Juan, Roncal, Carmen, Rodríguez, Jose A., Zandio, Beatriz, Lecumberri, Ramón, Hermida, Jose, Oyarzabal, Julen, Pineda-Lucena, Antonio, Páramo, Jose A., Muñoz, Roberto, Orbe, Josune
      Abstract: Background Intracranial hemorrhage (ICH) is one of the major devastating complications of anticoagulation. Matrix metalloproteinase (MMP) inhibition has been proposed as a novel pharmacological approach for ICH treatment. Objectives We evaluated the effects of CM-352 (MMP-fibrinolysis inhibitor) in an experimental ICH model associated with oral anticoagulants as compared with clinically used prothrombin complex concentrate (PCC). Methods ICH was induced by collagenase injection into the striatum of wild type (C57BL/6J) anticoagulated mice (warfarin or rivaroxaban) and Mmp10 −/− mice. Hematoma volume and neurological deficits were measured 24 hours later by diaminobenzidine staining and different behavioral tests. Circulating plasminogen activator inhibitor-1 (PAI-1) activity and interleukin-6 (IL-6) were measured in plasma samples and local inflammation was assessed by neutrophil infiltration. Finally, fibrinolytic effects of MMP-10 and rivaroxaban were evaluated by thromboelastometry and thrombin-activatable fibrinolysis inhibitor (TAFI) activation assays. Results Only PCC reduced hemorrhage volume and improved functional outcome in warfarin-ICH, but both PCC and CM-352 treatments diminished hemorrhage volume (46%, p 
      Citation: Thromb Haemost ; : -
      PubDate: 2022-02-03T00:00:00+0100
      DOI: 10.1055/a-1759-9962
       
  • Bleeding risk assessment in end-stage kidney disease: validation of
           existing risk scores and evaluation of a machine learning-based approach

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      Authors: Nopp; Stephan, Spielvogel, Clemens, Schmaldienst, Sabine, Klauser-Braun, Renate, Lorenz, Matthias, Bauer, Benedikt, Pabinger, Ingrid, Säemann, Marcus, Königsbrügge, Oliver, Ay, Cihan
      Abstract: BackgroundPatients with end-stage kidney disease (ESKD) on hemodialysis (HD) are at increased risk for bleeding. However, despite relevant clinical implications regarding dialysis modalities or anticoagulation, no bleeding risk assessment strategy has been established in this challenging population.MethodsAnalyses on bleeding risk assessment models were performed in the population-based Vienna InVestigation of Atrial fibrillation and thromboemboLism in patients on hemoDialysIs (VIVALDI) study including 625 patients. In this cohort study, patients were prospectively followed for a median observation period of 3.5 years for the occurrence of major bleeding. First, performances of existing bleeding risk scores (i.e., HAS-BLED, HEMORR2HAGES, ATRIA, and four others) were evaluated in terms of discrimination and calibration. Second, four machine learning-based prediction models that included clinical, dialysis-specific, and laboratory parameters were developed and tested using Monte-Carlo cross-validation.ResultsOf 625 patients (median age: 66 years, 38% women), 89 (14.2%) developed major bleeding, with a 1-year, 2-year, and 3-year cumulative incidence of 6.1% (95%CI 4.2-8.0), 10.3% (95%CI 8.0-12.8), and 13.5% (95%CI 10.8-16.2), respectively. C-statistics of seven contemporary bleeding risk scores ranged between 0.54 and 0.59 indicating poor discriminatory performance. The HAS-BLED score showed the highest C-statistics of 0.59 (95% 0.53-0.56). Similarly, all four machine learning-based predictions models performed poorly in internal validation (C-statistics ranging from 0.49-0.55).ConclusionsExisting bleeding risk scores and a machine learning approach including common clinical parameters fail to assist in bleeding risk prediction of patients on HD. Therefore, new approaches, including novel biomarkers, to improve bleeding risk prediction in patients on HD are needed.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-01-28T00:00:00+0100
      DOI: 10.1055/a-1754-7551
       
  • DOAC Dipstick Testing Can Reliably Exclude the Presence of Clinically
           Relevant DOAC Concentrations in Circulation

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      Authors: Margetić; Sandra, Ćelap, Ivana, Huzjan, Arijana Lovrenčić, Puretić, Marijana Bosnar, Goreta, Sandra Šupraha, Glojnarić, Anesa Čajević, Brkljačić, Diana Delić, Mioč, Pavao, Harenberg, Job, Hetjens, Svetlana, Weiss, Christel
      Abstract: In certain clinical situations, it is necessary to determine whether clinically relevant plasma levels of direct oral anticoagulants (DOACs) are present. We examined whether qualitative testing of DOACs in urine samples can exclude DOAC plasma concentrations of ≥30 ng/mL. This prospective single-center cohort study included consecutive patients treated with an oral direct factor Xa inhibitor (DXI) (apixaban, n = 31, rivaroxaban, n = 53) and direct thrombin inhibitor (DTI) (dabigatran, n = 44). We aimed to define the negative predictive value (NPV) and other statistical parameters of detecting DXIs and DTIs by DOAC Dipstick at plasma concentrations of ≥30 ng/mL. We also determined the best-fit threshold plasma levels using chromogenic substrate assays by logistic regression analysis. Between July 2020 and July 2021, 128 eligible patients (mean age 66 years, 55 females) were included into the study. The NPVs and sensitivities for DXI and DTI of DOAC Dipstick were 100% at ≥30 ng/mL plasma, for specificities 6 and 21% and for positive predictive values 62 and 72%, respectively. All diagnostic statistical tests improved to values between 86 and 100% at best-fitting plasma thresholds of ≥14 ng/mL for DXI and ≥19 ng/mL for DTI. Visual analysis using the DOAC Dipstick was 100% in agreement with that of the optoelectronic DOASENSE Reader for all the three DOACs.DOAC Dipstick testing can reliably exclude the presence of DOACs in urine samples at best-fitting thresholds of>14 and>19 ng/mL in plasma. The performance of the DOAC Dipstick at detecting lower DOAC concentrations in plasma requires confirmation.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-01-27T00:00:00+0100
      DOI: 10.1055/a-1753-2748
       
  • Novel GNE Gene Variants Associated with Severe Congenital Thrombocytopenia
           and Platelet Sialylation Defect

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      Authors: Zieger; Barbara, Boeckelmann, Doris, Anani, Waseem, Falet, Hervé, Zhu, Jieqing, Glonnegger, Hannah, Full, Hermann, Andresen, Felicia, Erlacher, Miriam, Lausch, Ekkehart, Fels, Salome, Strahm, Brigitte, Lang, Peter, Hoffmeister, Karin M.
      Abstract: The GNE gene encodes an enzyme that initiates and regulates the biosynthesis of N-acetylneuraminic acid, a precursor of sialic acids. GNE mutations are classically associated with Nonaka myopathy and sialuria, following an autosomal recessive and autosomal dominant inheritance pattern. Reports show that single GNE variants cause severe thrombocytopenia without muscle weakness. Using panel sequencing, we identified two novel compound heterozygous variants in GNE in a young girl with life-threatening bleedings, severe congenital thrombocytopenia, and a platelet secretion defect. Both variants are located in the nucleotide-binding site of the N-acetylmannosamin kinase domain of GNE. Lectin array showed decreased α-2,3-sialylation on platelets, consistent with loss of sialic acid synthesis and indicative of rapid platelet clearance. Hematopoietic stem cell transplantation (HSCT) normalized platelet counts. This is the first report of an HSCT in a patient with an inherited GNE defect leading to normal platelet counts.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-01-20T00:00:00+0100
      DOI: 10.1055/s-0041-1742207
       
  • A Meta-Analysis of Plasma Homocysteine in Buerger's Disease

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      Thromb Haemost
      DOI: 10.1055/s-0041-1742165



      Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

      Artikel in Thieme eJournals:
      Inhaltsverzeichnis     Volltext

      Thromb Haemost ; : -2022-01-20T00:00:00+0100
       
  • Impact of Fibrinogen Infusion on Thrombin Generation and Fibrin Clot
           Structure in Patients with Inherited Afibrinogenemia

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      Authors: Khayat; Claudia, Marchi, Rita, Durual, Stéphane, Lecompte, Thomas, Neerman-Arbez, Marguerite, Casini, Alessandro
      Abstract: Introduction Inherited afibrinogenemia is a very rare disease characterized by complete absence of fibrinogen in the circulation and an increased risk in both thrombosis and bleeding. Infusion of fibrinogen concentrate (FC) is the main approach for prevention and management of bleeding; however, it has been reported to carry a thrombotic risk. Methods We investigated the impact of a standard dose (40–100 mg/kg) of FC infusion on the thrombin generation (TG) parameters and the fibrin clot structure formed in plasma samples of patients with afibrinogenemia. Blood samples were collected from 20 patients before (T0) and 1 hour after infusion of FC (T1). TG was studied with calibrated automated thrombography. Fibrin clot structure was assessed with turbidimetry and scanning electron microscopy. Results FC infusions (mean Clauss fibrinogen plasma level: 1.21 g/L at T1) led to a statistically significant increase in endogenous thrombin potential (ETP) (p 
      Citation: Thromb Haemost ; : -
      PubDate: 2022-01-19T00:00:00+0100
      DOI: 10.1055/a-1745-0420
       
  • Incidence and Outcomes Associated with 6,841 Isolated Distal Deep Vein
           Thromboses in Patients with 13 Common Cancers

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      Authors: Mahajan; Anjlee, Brunson, Ann, Eldredge, Joanna, White, Richard H., Keegan, Theresa H. M., Wun, Ted
      Abstract: Introduction The epidemiology of isolated distal deep venous thrombosis (iDDVT) among cancer patients is not well described, particularly the incidence of recurrent venous thromboembolism (rVTE) and effect on mortality by cancer type. Methods The cumulative incidence (CI) of iDDVT was determined for patients with 13 common cancers between 2005 and 2017 using the California Cancer Registry linked to the California Patient Discharge and Emergency Department Utilization datasets. The CI of rVTE was calculated and association of incident cancer-associated thrombosis (CT) location with rVTE was determined using Cox proportional hazards regression models. The association of incident CT location with overall and cancer-specific mortality was determined using Cox models, stratified by cancer site, and adjusted for individual characteristics. Results Among 942,109 cancer patients, CT occurred in 62,003 (6.6%): of these, 6,841 (11.0%) were iDDVT. Compared with more proximal sites of CT, iDDVT was associated with similar risk for rVTE. IDDVT was associated with increased mortality across all cancer types when compared with patients without CT (hazard ratio: 1.56–4.60). The effect of iDDVT on mortality was similar to that of proximal DVT (pDVT) for most cancers except lung, colorectal, bladder, uterine, brain, and myeloma, where iDDVT was associated with a lesser association with mortality. Conclusion iDDVT represented 11% of CT. The risk of rVTE after iDDVT was similar to other sites of CT and rVTE occurred in more proximal locations after an incident iDDVT. IDDVT was associated with increased mortality and this effect was similar to that of pulmonary embolism or pDVT for most cancer types.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-01-17T00:00:00+0100
      DOI: 10.1055/a-1742-0177
       
  • Rare Causes of Acute Coronary Syndrome: The JAK2 V617F Mutation-Positive
           Myeloproliferative Neoplasms: A Cardio-Hematological Perspective

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      Thromb Haemost
      DOI: 10.1055/a-1742-0361



      Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

      Artikel in Thieme eJournals:
      Inhaltsverzeichnis     Volltext

      Thromb Haemost ; : -2022-01-17T00:00:00+0100
       
  • External Validation of the Patient-Reported Villalta Scale for the
           Diagnosis of Postthrombotic Syndrome

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      Authors: Ng; Sara, Rodger, Marc A., Ghanima, Waleed, Kovacs, Michael J., Shivakumar, Sudeep, Kahn, Susan R., Sandset, Per Morten, Kearon, Clive, Mallick, Ranjeeta, Delluc, Aurélien
      Abstract: Introduction The Villalta scale is the endorsed tool to diagnose and grade the severity of postthrombotic syndrome (PTS); however, assessing presence and severity of PTS is time-consuming and relies on both the clinician and patient's assessments. The patient-reported Villalta scale version 2 (PRV2) is a visually assisted form that enables patients to self-assess presence and severity of PTS. Herein, we report on external validation of this tool. Methods We assessed the agreement and kappa values of PRV2 to diagnose and assess severity of PTS compared with the original Villalta score in a cohort of 181 patients (196 limbs) who participated in the SAVER pilot randomized control trial. Presence of PTS was defined as PRV2 ≥5 or a Villalta score ≥5. Results PTS prevalence was 42% using PRV2 and 33% using the Villalta scale. The corresponding kappa and percentage agreement were 0.60 (95% confidence interval [CI]: 0.49–0.71) and 81% (95% CI: 76–87), respectively. Kappa values and percentage agreements between PRV2 and Villalta scale increased with increasing severity of PTS. The sensitivity of PRV2 to detect PTS of any severity was 84% (95% CI: 73–92) with a specificity of 79% (95% CI: 71–86). Conclusion We conclude that the PRV2 is an acceptable tool for diagnosing and grading the severity of PTS.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-01-12T00:00:00+0100
      DOI: 10.1055/a-1738-1313
       
  • All that clots is not blood: Bone cement implantation syndrome presenting
           as an intracardiac mass and pulmonary embolism

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      Authors: Cheong; May Anne, Chew, Kenneth Michael
      Abstract: Bone cement implantation syndrome (BCIS) is a rare and potentially fatal perioperative complication of cemented orthopaedics surgery. A CT-pulmonary angiogram and echocardiogram images were acquired from an 88-year-old patient who had a perioperative collapse while undergoing a revision operation for a peri-implant fracture of the right femoral neck. Findings were suggestive of an intracardiac clot connected to a saddle pulmonary artery embolus. Patient also developed disseminated intravascular coagulation. Overall findings were suggestive of bone cement implantation syndrome.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-01-12T00:00:00+0100
      DOI: 10.1055/a-1738-1777
       
  • Thrombotic risk determined by protein C receptor (PROCR) variants among
           middle-aged and older adults: a population-based cohort study

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      Authors: Manderstedt; Eric, Hallden, Christer, Lind-Hallden, Christina, Elf, Johan, svensson, peter, Engström, Gunnar, Melander, Olle, Baras, Aris, Luca, Lotta, Zöller, Bengt Anders
      Abstract: Background: The protein C (PC) anticoagulant system has a key role in maintaining hemostatic balance. One missense (Ser219Gly) variant in the protein C receptor (PROCR) was associated with venous thromboembolism (VTE) in genome-wide association studies. Objectives: This study aimed to determine the thrombotic risk of rare and common PROCR variants in a large population-based cohort of middle-aged and older adults.Patients/Methods: The exonic sequence of PROCR was analyzed for the Ser219Gly variant and other qualifying variants in 28,794 subjects (born 1923-1950, 60% women) without previous VTE, who participated in the Malmö Diet and Cancer study (1991-1996). Incidence of VTE was followed up until 2018. Qualifying variants were defined as loss-of-function or non-benign (PolyPhen-2) missense variants with minor allele frequencies (MAF) < 0.1%.Results: Resequencing identified 36 PROCR variants in the study population (26,210 non-VTE exomes and 2584 VTE exomes), 11 synonymous, 22 missense and three loss-of-function variants. Kaplan-Meier analysis of the known Ser219Gly variant (rs867186) showed that homozygosity for this variant increased the risk of disease whereas heterozygosity showed no effect. Cox multivariate regression analysis revealed an adjusted hazard ratio of 1.5 (95%CI 1.1-2.0). Fifteen rare variants were classified as qualifying and were included in collapsing analysis (burden test and SKAT-O). They did not contribute to risk. However, a Arg113Cys missense variant (rs146420040; MAF=0.004) showed an increased VTE risk (HR=1.3; 95%CI 1.0-1.9). Conclusions: Homozygosity for the Ser219Gly variant and a previously identified functional PROCR variant (Arg113Cys) was associated with VTE. Other variants did not contribute to VTE.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-01-12T00:00:00+0100
      DOI: 10.1055/a-1738-1564
       
  • NETs in the infarct-related coronary artery – a marker or mediator
           of adverse outcome'

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      Authors: Gorog; Diana Adrienne, Massberg, Steffen
      Abstract: No Abstract
      Citation: Thromb Haemost ; : -
      PubDate: 2022-01-10T00:00:00+0100
      DOI: 10.1055/a-1733-9217
       
  • Effectiveness and safety of oral anticoagulants in the treatment of acute
           venous thromboembolism: A nationwide comparative cohort study in France

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      Authors: Bertoletti; Laurent, Gusto, Gaelle, Khachatryan, Artak, Quignot, Nadia, Chaves, Jose, Moniot, Audrey, Mokgokong, Ruth
      Abstract: Introduction: Data from clinical trials indicate that direct oral anticoagulants (DOACs) are non-inferior and safer than conventional therapy (low-molecular weight heparin followed by a vitamin K antagonist [VKA]) for treating venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism (PE). This study compared the effectiveness and safety of DOACs and conventional therapy in a real-world setting.Materials and Methods: This observational study used French national claims data of adult, treatment-naïve patients diagnosed with VTE (majority PE) who were hospitalized and treated for VTE with a DOAC (apixaban or rivaroxaban) or VKAs during 2013–2018. Patients with active cancer were excluded. After propensity score matching for each DOAC-VKA comparison, risks of bleeding, recurrent VTE, and all-cause mortality were compared at 6 months. Cox proportional-hazards regression was used to estimate adjusted hazard ratios of the endpoints.Results: 58137 patients were included (10775 VKAs, 10440 apixaban, 36922 rivaroxaban). Propensity score-matched cohort sizes were 7503 for apixaban and 9179 for rivaroxaban. The hazard ratio (95% confidence interval) was significantly lower for apixaban than VKAs for bleeding requiring hospitalization (0.43 [0.32-0.59]), all-cause death (0.61 [0.51-0.74]), and first-recurrent VTE (0.67 [0.52-0.85]). The hazard ratio was also significantly lower for rivaroxaban than VKAs for all-cause death (0.63 [0.53-0.74]) but not for bleeding requiring hospitalization (0.86 [0.69-1.07]) or first-recurrent VTE (0.91 [0.74-1.13]). Conclusions: Apixaban was associated with superior safety and effectiveness than VKAs. All-cause mortality was lower in both DOACs than VKAs. Our results support recommendations to use DOACs over VKAs for the treatment of VTE.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-01-04T00:00:00+0100
      DOI: 10.1055/a-1731-3922
       
  • Pharmacodynamic Profiles of Dual-Pathway Inhibition with or without
           Clopidogrel versus Dual Antiplatelet Therapy in Patients with
           Atherosclerotic Disease

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      Authors: Galli; Mattia, Franchi, Francesco, Rollini, Fabiana, Been, Latonya, Jaoude, Patrick Abou, Rivas, Andrea, Zhou, Xuan, Jia, Sida, Maaliki, Naji, Lee, Chang Hoon, Pineda, Andres M., Suryadevara, Siva, Soffer, Daniel, Zenni, Martin M., Geisler, Tobias, Jennings, Lisa K., Bass, Theodore A., Angiolillo, Dominick J.
      Abstract: Aim Inhibition of thrombin-mediated signaling processes using a vascular dose of rivaroxaban in adjunct to antiplatelet therapy, known as dual-pathway inhibition (DPI), reduces atherothrombotic events in patients with stable atherosclerotic disease. However, there are limited data on the pharmacodynamic (PD) effects of this strategy and how it compares to standard dual antiplatelet therapy (DAPT). Methods and Results This investigation was conducted in selected cohorts of patients (n = 40) with stable atherosclerotic disease—enrolled within a larger prospective, open-label, parallel-group PD study—who were treated with either aspirin plus clopidogrel (DAPT), aspirin plus rivaroxaban 2.5 mg/bid (DPI), or DAPT plus rivaroxaban 2.5 mg/bid. Multiple PD assays providing a comprehensive assessment of markers of thrombosis were used. PD endpoints included platelet-mediated global thrombogenicity measured by light transmittance aggregometry (LTA) following stimuli with CATF (collagen-related peptide + adenosine diphosphate [ADP] + tissue factor [TF]), markers of P2Y12 reactivity, markers of platelet aggregation using LTA following several stimuli (arachidonic acid, ADP, collagen, TF, and thrombin receptor-activating peptide [TRAP]), thrombin generation, and thrombus formation. There was no difference in platelet-mediated global thrombogenicity between groups. Rivaroxaban significantly reduced thrombin generation and was associated with a trend toward reduced TF-induced platelet aggregation. Clopidogrel-based treatments reduced markers of P2Y12 signaling and TRAP-induced platelet aggregation. There were no differences between groups on markers of cyclooxygenase-1-mediated activity. Conclusion Compared with DAPT, DPI does not result in any differences in platelet-mediated global thrombogenicity, but reduces thrombin generation. These PD observations suggest that modulating thrombin generation—by means of factor Xa inhibition—in adjunct to antiplatelet therapy provides effective antithrombotic effects, supporting the efficacy and safety findings of a DPI strategy observed in clinical trials.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-01-04T00:00:00+0100
      DOI: 10.1055/a-1730-8725
       
  • Pregnancy after Combined Oral Contraceptive-Associated Venous
           Thromboembolism: An International Retrospective Study of Outcomes

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      Authors: Gris; Jean-Christophe, Bourguignon, Chloé, Bouvier, Sylvie, Nouvellon, Eva, Laurent, Jeremy, Perez-Martin, Antonia, Mousty, Eve, Nikolaeva, Mariya, Khizroeva, Jamilya, Bitsadze, Victoria, Makatsariya, Alexander
      Abstract: Background Few data are available on thrombotic outcomes during pregnancy and puerperium occurring after an initial provoked venous thromboembolic (VTE) event. Objectives To describe thrombotic outcomes during pregnancy after a first combined oral contraceptive (COC)-associated VTE and the factors associated with recurrence. Methods This was an international multicentric retrospective study on patients referred for thrombophilia screening from January 1, 2010 to January 1, 2021 following a first COC-associated VTE, including women with neither inherited thrombophilia nor antiphospholipid antibodies and focusing on those who had a subsequent pregnancy under the same thromboprophylaxis treatment. Thrombotic recurrences during pregnancy and puerperium as well as risk factors for recurrence were analyzed. Results We included 2,145 pregnant women. A total of 88 thrombotic events, 58 antenatal and 29 postnatal, occurred, mostly during the first trimester of pregnancy and the first 2 weeks of puerperium. Incidence rates were 49.6 (37–62) per 1,000 patient-years during pregnancy and 118.7 (78–159) per 1,000 patient-years during puerperium. Focusing on pulmonary embolism, incidence rates were 1.68 (1–4) per 1,000 patient-years during pregnancy and 65.5 (35–97) per 1,000 patient-years during puerperium.Risk factors for antenatal recurrences were maternal hypercholesterolemia and birth of a very small-for-gestational-age neonate. A risk factor for postnatal recurrence was the incidence of preeclampsia. Conclusion Our multicentric retrospective data show significant rates of VTE recurrence during pregnancy and puerperium in women with a previous VTE event associated with COC, despite a unique low-molecular-weight heparin-based thromboprophylaxis. These results may provide benchmarks and valuable information for designing future randomized controlled trials.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-30T18:00:25+01:00
      DOI: 10.1055/a-1835-8808
      Issue No: Vol. eFirst
       
  • Risk of Thromboembolic Events in Cancer Patients Treated with Immune
           Checkpoint Inhibitors: A Meta-analysis of Randomized Controlled Trials

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      Authors: Ma; Zhuo, Sun, Ximu, Zhang, Yi, Li, Hao, Sun, Dan, An, Zhuoling, Zhang, Yuhui
      Abstract: Background The association between immune checkpoint inhibitors (ICIs) and thromboembolic events (TEEs) remains controversial. Objective The goal of this study was to assess the risk of major TEEs associated with ICIs. Methods We explored ICI-related TEEs in randomized controlled trials available in ClinicalTrials.gov and electronic databases up to June 30, 2021. Meta-analysis was performed by using Peto odds ratios (ORs) with 95% confidence intervals (CIs). Results A total of 61 studies were included. Patients treated with ICIs had a similar risk of venous thromboembolism (VTE) but a significantly increased risk of arterial thromboembolism (ATE) (Peto OR: 1.58 [95% CI: 1.21–2.06]) compared with non-ICI regimens. Stratified by different regimens, only PD-L1 (programmed cell death ligand 1) inhibitors showed a significant increase in ATE (Peto OR: 2.07 [95% CI: 1.26–3.38]). The incidence of VTE was higher in PD-1/PD-L1 inhibitor and CTLA-4 (cytotoxic T lymphocyte antigen 4) inhibitor combination therapies compared with monotherapies (Peto OR: 2.23 [95% CI: 1.47–3.37]). Stratified by tumor, for pulmonary embolism (PE) and cerebral ATE, the statistically significant results were only seen in lung cancer patients (Peto OR: 1.42 [95% CI: 1.02–1.97]; Peto OR: 2.10 [1.07–4.12]), and for myocardial infarction, the statistically significant result was only seen in other tumor types (Peto OR: 2.66 [95% CI: 1.68–4.20], p 
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-30T17:54:06+01:00
      DOI: 10.1055/s-0042-1749185
      Issue No: Vol. eFirst
       
  • Katacine Is a New Ligand of CLEC-2 that Acts as a Platelet Agonist

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      Authors: Morán; Luis A., Di, Ying, Sowa, Marcin A., Hermida-Nogueira, Lidia, Barrachina, María N., Martin, Eleyna, Clark, Joanne C., Mize, Todd H., Eble, Johannes A., Moreira, David, Pollitt, Alice Y., Loza, María I., Domínguez, Eduardo, Watson, Steve P., García, Ángel
      Abstract: Background CLEC-2 is a platelet receptor with an important role in thromboinflammation but a minor role in hemostasis. Two endogenous ligands of CLEC-2 have been identified, the transmembrane protein podoplanin and iron-containing porphyrin hemin, which is formed following hemolysis from red blood cells. Other exogenous ligands such as rhodocytin have contributed to our understanding of the role of CLEC-2. Objectives To identify novel CLEC-2 small-molecule ligands to aid therapeutic targeting of CLEC-2. Methods ALPHA screen technology has been used for the development of a high-throughput screening (HTS) assay recapitulating the podoplanin–CLEC-2 interaction. Light transmission aggregometry was used to evaluate platelet aggregation. Immunoprecipitation and western blot were used to evaluate direct phosphorylation of CLEC-2 and downstream protein phosphorylation. Autodock vina software was used to predict the molecular binding site of katacine and mass spectrometry to determine the polymeric nature of the ligand. Results and Conclusion We developed a CLEC-2–podoplanin interaction assay in a HTS format and screened 5,016 compounds from a European Union-open screen library. We identified katacine, a mixture of polymers of proanthocyanidins, as a novel ligand for CLEC-2 and showed that it induces platelet aggregation and CLEC-2 phosphorylation via Syk and Src kinases. Platelet aggregation induced by katacine is inhibited by the anti-CLEC-2 monoclonal antibody fragment AYP1 F(ab)′2. Katacine is a novel nonprotein ligand of CLEC-2 that could contribute to a better understanding of CLEC-2 activation in human platelets.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-28T06:19:36+01:00
      DOI: 10.1055/a-1772-1069
      Issue No: Vol. eFirst
       
  • HemosIL VWF:GPIbR Assay Has a Greater Sensitivity than VWF:RCo Technique
           to Detect Acquired von Willebrand Syndrome in Myeloproliferative Neoplasms
           

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      Authors: Laporte; Pierre, Tuffigo, Marie, Ryman, Anne, Fiore, Mathieu, Rivière, Etienne, James, Chloé, Guy, Alexandre
      Abstract: Background Acquired von Willebrand syndrome (AVWS) is frequent in patients with myeloproliferative neoplasms (MPNs). For von Willebrand factor (VWF) functional evaluation, ristocetin cofactor activity by aggregometry (VWF:RCo) is considered the gold standard but has limitations, and automated activity measurement has been developed such as the HemosIL VWF:RCo Werfen with particle agglutination (VWF:GPIbR). Objectives To evaluate the performance of VWF:GPIbR with HemosIL VWF:RCo Werfen (VWF:GPIbR) versus VWF:RCo in patients with thrombocytosis in the context of MPNs (T-MPNs) and in patients with secondary thrombocytosis (ST). Methods MPN patients with thrombocytosis>450 G/L (T-MPNs) were compared with patients with ST due to inflammation or iron deficiency. VWF activity (VWF:Act) was analyzed using VWF:RCo or VWF:GPIbR. VWF analysis was completed by analysis of VWF multimers and VWF collagen binding (CB) assay (VWF:CB). Results A total of 33 T-MPNs and 18 ST patients were included. Compared with aggregometry, evaluation of VWF:Act by VWF:GPIbR led to lower values in T-MPN patients, but also in ST patients. Interestingly, although the VWF:RCo/VWF:Ag ratio did not reveal differences between T-MPNs and ST patients, the VWF:GPIbR/VWF:Ag ratio analysis allowed us to suspect AVWS only in T-MPN patients. Using the distribution of VWF multimer analysis and VWF:CB, we here demonstrated that VWF:GPIbR allows AVWS diagnosis in nine T-MPNs as opposed to aggregometry. Conclusion Evaluation of VWF:Act using VWF:GPIbR has a greater sensitivity compared with aggregometry to detect AVWS in T-MPN patients.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-28T06:10:36+01:00
      DOI: 10.1055/a-1806-9972
      Issue No: Vol. eFirst
       
  • Clinical Delphi on aPL Negativization: Report from the APS Study Group of
           the Italian Society for Rheumatology (SIR-APS)

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      Authors: Sciascia; Savino, Foddai, Silvia Grazietta, Alessandri, Cristiano, Alunno, Alessia, Andreoli, Laura, Barinotti, Alice, Calligaro, Antonia, Canti, Valentina, Carubbi, Francesco, Cecchi, Irene, B. Chighizola, Cecillia, Conti, Fabrizio, Emmi, Giacomo, Fioravanti, Antonella, Fischetti, Fabio, Franceschini, Franco, Gerosa, Maria, Hoxha, Ariela, Larosa, Maddalena, Lazzaroni, Maria-Grazia, Nalli, Cecilia, Pazzola, Giulia, Radin, Massimo, Raffeiner, Bernd, Ramoni, Veronique L., Rubini, Elena, Sebastiani, Gian Domenico, Truglia, Simona, Urban, Maria Letizia, Roccatello, Dario, Tincani, Angela
      Abstract: Background The rate of antiphospholipid antibody (aPL) negativization in antiphospholipid syndrome (APS) patients is uncertain, but it is estimated to be as high as 8%. Currently, a consensus definition of aPL negativization is lacking, as well as international recommendations on how to approach treatment in patients with a persistent aPL-negative seroconversion. Aim The aim of the Delphi survey was to evaluate the clinical approach and level of consensus among experts from the APS Study Group of the Italian Society for Rheumatology (SIR-APS) in different clinical scenarios. Methods Experts of SIR-APS were contacted using a survey methodology. Results A structured survey was circulated among 30 experts. Up to 90% of the interviewed experts agreed on defining aPL negativization as the presence of two negative determinations, 1 year apart (90%). Almost full consensus exists among experts in some clinical settings, including: (1) the role of aPL negativization in the management of a thrombotic event determined by concomitant presence of cardiovascular risk factors, both modifiable and not modifiable (90%); (2) approach to young patients with triple aPL positivity who experienced pulmonary arterial thrombotic events and tested negative for aPL detection after 5 years of vitamin K antagonist (VKA) treatment (90%); (3) the use of “extra criteria” aPL antibody testing before pondering VKA suspension (93%). Conclusion A substantial agreement exists among experts on how to define aPL negativization. VKA suspension should be embraced with extreme caution, particularly in case of previous thrombotic events and/or triple aPL positivity. Nevertheless, VKA cessation might be considered when risk factors are carefully monitored/treated and the presence of “extra criteria” aPL is ruled out.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-28T05:37:55+01:00
      DOI: 10.1055/a-1798-2400
      Issue No: Vol. eFirst
       
  • Anticoagulation for Thromboprophylaxis in Patients with Intracerebral
           Hemorrhage: Less Room for Scepticism

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      Authors: Proietti; Marco, Ntaios, George
      Abstract: No abstract
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-28T05:33:34+01:00
      DOI: 10.1055/a-1834-4923
      Issue No: Vol. eFirst
       
  • Identification of the Novel G250R Variant Indicates a Role for
           Thrombomodulin in Modulating the Risk for Venous Thromboembolism

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      Thromb Haemost
      DOI: 10.1055/a-1827-7109



      Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

      Artikel in Thieme eJournals:
      Inhaltsverzeichnis     Volltext

      Thromb Haemost ; : -2022-06-28T05:29:49+01:00
      Issue No: Vol. eFirst
       
  • Long-Read Sequencing Identifies the First Retrotransposon Insertion and
           Resolves Structural Variants Causing Antithrombin Deficiency

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      Authors: de la Morena-Barrio; Belén, Stephens, Jonathan, de la Morena-Barrio, María Eugenia, Stefanucci, Luca, Padilla, José, Miñano, Antonia, Gleadall, Nicholas, García, Juan Luis, López-Fernández, María Fernanda, Morange, Pierre-Emmanuel, Puurunen, Marja, Undas, Anetta, Vidal, Francisco, Raymond, Frances Lucy, Vicente, Vicente, Ouwehand, Willem H., Corral, Javier, Sanchis-Juan, Alba
      Abstract: The identification of inherited antithrombin deficiency (ATD) is critical to prevent potentially life-threatening thrombotic events. Causal variants in SERPINC1 are identified for up to 70% of cases, the majority being single-nucleotide variants and indels. The detection and characterization of structural variants (SVs) in ATD remain challenging due to the high number of repetitive elements in SERPINC1. Here, we performed long-read whole-genome sequencing on 10 familial and 9 singleton cases with type I ATD proven by functional and antigen assays, who were selected from a cohort of 340 patients with this rare disorder because genetic analyses were either negative, ambiguous, or not fully characterized. We developed an analysis workflow to identify disease-associated SVs. This approach resolved, independently of its size or type, all eight SVs detected by multiple ligation-dependent probe amplification, and identified for the first time a complex rearrangement previously misclassified as a deletion. Remarkably, we identified the mechanism explaining ATD in 2 out of 11 cases with previous unknown defect: the insertion of a novel 2.4 kb SINE-VNTR-Alu retroelement, which was characterized by de novo assembly and verified by specific polymerase chain reaction amplification and sequencing in the probands and affected relatives. The nucleotide-level resolution achieved for all SVs allowed breakpoint analysis, which revealed repetitive elements and microhomologies supporting a common replication-based mechanism for all the SVs. Our study underscores the utility of long-read sequencing technology as a complementary method to identify, characterize, and unveil the molecular mechanism of disease-causing SVs involved in ATD, and enlarges the catalogue of genetic disorders caused by retrotransposon insertions.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-28T05:22:08+01:00
      DOI: 10.1055/s-0042-1749345
      Issue No: Vol. eFirst
       
  • Systematic Review and Meta-Analysis of Thromboprophylaxis with Heparins
           Following Intracerebral Hemorrhage

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      Authors: Chi; Gerald, Lee, Jane J., Sheng, Shi, Marszalek, Jolanta, Chuang, Michael L.
      Abstract: Background The efficacy and safety of pharmacological thromboprophylaxis in patients with intracerebral hemorrhage (ICH) remains unclear. Methods A literature search was performed to collect studies comparing the effect of thromboprophylaxis in patients with ICH. The primary endpoints were deep vein thrombosis (DVT), pulmonary embolism (PE), and hematoma expansion or rebleeding. A meta-analytic approach was employed to estimate the relative risk (RR) by fitting fixed-effects (FE) and random-effects (RE) models. Results A total of 28 studies representing 3,697 hospitalized patients with ICH were included. Thromboprophylaxis was initiated within 4 days following hospital presentation and continued for 10 to 14 days in most of studies. Compared with control, thromboprophylaxis was associated with a reduced risk of DVT (47/1,399 [3.4%] vs. 202/1,377 [14.7%]; FE: RR, 0.24; 95% CI, 0.18–0.32; RE: RR, 0.27; 95% CI, 0.19–0.39) as well as PE (9/953 [0.9%] vs. 37/864 [4.3%]; FE: RR, 0.33; 95% CI, 0.19–0.57; RE: RR, 0.37; 95% CI, 0.21–0.66). Thromboprophylaxis was not associated with increased risk of hematoma expansion or rebleeding (32/1,319 [2.4%] vs. 37/1,301 [2.8%]; FE: RR, 0.75; 95% CI, 0.48–1.18; RE: RR, 0.80; 95% CI, 0.49–1.30) or mortality (117/925 [12.6%] vs. 139/904 [15.4%]; FE: RR, 0.82; 95% CI, 0.65–1.03; RE: RR, 0.83; 95% CI, 0.66–1.04). Conclusion Thromboprophylaxis was effective in preventing DVT and PE without increasing the risk of hematoma expansion or bleeding among ICH patients. Future studies should explore the long-term effects of thromboprophylaxis in this population, particularly on the functional outcomes.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-19T08:31:17+01:00
      DOI: 10.1055/s-0042-1744541
      Issue No: Vol. eFirst
       
  • N-Glycosylation Deficiency Reduces the Activation of Protein C and
           Disrupts the Endothelial Barrier Integrity

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      Authors: Pascreau; Tiffany, Saller, François, Bianchini, Elsa P., Lasne, Dominique, Bruneel, Arnaud, Reperant, Christelle, Foulquier, François, Denis, Cécile V., De Lonlay, Pascale, Borgel, Delphine
      Abstract: Phosphomannomutase 2 (PMM2) deficiency is the most prevalent congenital disorder of glycosylation. It is associated with coagulopathy, including protein C deficiency. Since all components of the anticoagulant and cytoprotective protein C system are glycosylated, we sought to investigate the impact of an N-glycosylation deficiency on this system as a whole. To this end, we developed a PMM2 knockdown model in the brain endothelial cell line hCMEC/D3. The resulting PMM2low cells were less able to generate activated protein C (APC), due to lower surface expression of thrombomodulin and endothelial protein C receptor. The low protein levels were due to downregulated transcription of the corresponding genes (THBD and PROCR, respectively), which itself was related to downregulation of transcription regulators Krüppel-like factors 2 and 4 and forkhead box C2. PMM2 knockdown was also associated with impaired integrity of the endothelial cell monolayer—partly due to an alteration in the structure of VE-cadherin in adherens junctions. The expression of protease-activated receptor 1 (involved in the cytoprotective effects of APC on the endothelium) was not affected by PMM2 knockdown. Thrombin stimulation induced hyperpermeability in PMM2low cells. However, pretreatment of cells with APC before thrombin simulation was still associated with a barrier-protecting effect. Taken as a whole, our results show that the partial loss of PMM2 in hCMEC/D3 cells is associated with impaired activation of protein C and a relative increase in barrier permeability.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-19T08:24:14+01:00
      DOI: 10.1055/s-0042-1744378
      Issue No: Vol. eFirst
       
  • DNA Methylation and Ischemic Stroke Risk: An Epigenome-Wide Association
           Study

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      Authors: Cullell; Natalia, Soriano-Tárraga, Carolina, Gallego-Fábrega, Cristina, Cárcel-Márquez, Jara, Torres-Águila, Nuria P., Muiño, Elena, Lledós, Miquel, Llucià-Carol, Laia, Esteller, Manel, Castro de Moura, Manuel, Montaner, Joan, Fernández-Sanlés, Alba, Elosua, Roberto, Delgado, Pilar, Martí-Fábregas, Joan, Krupinski, Jerzy, Roquer, Jaume, Jiménez-Conde, Jordi, Fernández-Cadenas, Israel
      Abstract: Background Ischemic stroke (IS) risk heritability is partly explained by genetics. Other heritable factors, such as epigenetics, could explain an unknown proportion of the IS risk. The objective of this study is to evaluate DNA methylation association with IS using epigenome-wide association studies (EWAS). Methods We performed a two-stage EWAS comprising 1,156 subjects. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) were assessed using the Infinium 450K and EPIC BeadChip in the discovery cohort (252 IS and 43 controls). Significant DMPs were replicated in an independent cohort (618 IS and 243 controls). Stroke subtype associations were also evaluated. Differentially methylated cell-type (DMCT) was analyzed in the replicated CpG sites using EpiDISH. We additionally performed pathway enrichment analysis and causality analysis with Mendelian randomization for the replicated CpG sites. Results A total of 957 CpG sites were epigenome-wide-significant (p ≤ 10−7) in the discovery cohort, being CpG sites in the top signals (logFC = 0.058, p = 2.35 × 10−22; logFC = 0.035, p = 3.22 × 10−22, respectively). ZFHX3 and MAP3K1 were among the most significant DMRs. In addition, 697 CpG sites were replicated considering Bonferroni-corrected p-values (p 
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-19T08:21:48+01:00
      DOI: 10.1055/s-0042-1749328
      Issue No: Vol. eFirst
       
  • Hematopoiesis of Indeterminate Potential and Atherothrombotic Risk

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      Authors: Murphy; Andrew J., Dragoljevic, Dragana, Natarajan, Pradeep, Wang, Nan
      Abstract: Hematopoiesis is the process of blood production, essential for the continued supply of immune cells and red blood cells. However, the proliferative nature of hematopoietic stem cells (HSCs) renders them susceptible to developing somatic mutations. HSCs carrying a mutation can gain a selective advantage over normal HSCs and result in hematological disorders. One such disorder is termed clonal hematopoiesis of indeterminate potential (CHIP), a premalignant state associated with aging, where the mutant HSCs are responsible for producing a small portion of mature immune cells in the circulation and subsequently in tissues. People with CHIP have been shown to have an increased risk of mortality due to cardiovascular disease (CVD). Why this occurs is under rigorous investigation, but the majority of the studies to date have suggested that increased atherosclerosis is due to heightened inflammatory cytokine release from mutant lesional macrophages. However, given CHIP is driven by several mutations, other hematopoietic lineages can be altered to promote CVD. In this review we explore the relationship between mutations in genes causing CHIP and atherothrombotic disorders, along with potential mechanisms of enhanced clonal outgrowth and potential therapies and strategies to slow CHIP progression.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-18T20:19:25+01:00
      DOI: 10.1055/a-1830-2147
      Issue No: Vol. eFirst
       
  • Risk Factors of Cardiovascular Death after Venous Thromboembolism: Results
           from a Prospective Cohort Study

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      Authors: Noumegni; Steve Raoul, Mansourati, Vincent, Tromeur, Cécile, Mao, Raphael Le, Hoffmann, Clément, Moigne, Emmanuelle Le, Nasr, Bahaa, Gentric, Jean-Christophe, Guegan, Marie, Poulhazan, Elise, Bressollette, Luc, Lacut, Karine, Couturaud, Francis, Didier, Romain
      Abstract: Background Cardiovascular deaths (CVDTs) are more frequent in patients with venous thromboembolism (VTE) than in the general population; however, risk factors associated with this increased risk of CVDT in patients with VTE are not described. Methods To determine the risk factors of CVDT in patients with VTE from a multicenter prospective cohort study, Fine and Gray subdistribution hazard models were conducted. Results Of the 3,988 included patients, 426 (10.7%) died of CVDT during a median follow-up of 5 years. The risk factors of CVDT after multivariate analyses were: age of 50 to 65 years (vs. 65 years (vs. 3 months). Conclusion Risk factors of CVDT after VTE include some traditional cardiovascular risk factors and other risk factors that are related to characteristics of VTE, and patients' comorbidities.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-18T20:11:53+01:00
      DOI: 10.1055/s-0042-1748889
      Issue No: Vol. eFirst
       
  • Perioperative Coagulation Profile in Major Liver Resection for Cancer: A
           Prospective Observational Study

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      Authors: Tzimas; Petros, Lefkou, Eleftheria, Karakosta, Agathi, Argyrou, Stellios, Papapetrou, Evangelia, Pantazi, Despoina, Tselepis, Alexandros, Dreden, Patrick Van, Stratigopoulou, Panagiota, Gerotziafas, Grigoris, Glantzounis, Georgios
      Abstract: Hepatectomy-induced coagulation disturbances have been well studied over the past decade. Cumulative evidence supports the superiority of global coagulation analysis compared with conventional coagulation tests (i.e., prothrombin time or activated partial thromboplastin time) for clinical decision making. Cancer, however, represents an acquired prothrombotic state and liver resection for cancer deserves a more thorough investigation. This prospective observational study was conducted to assess the perioperative coagulation status of patients undergoing major hepatectomies for primary or metastatic hepatic malignancy. Patients were followed up to the 10th post-operative day by serial measurements of conventional coagulation tests, plasma levels of coagulation factors, and thrombin generation assay parameters. An abnormal coagulation profile was detected at presentation and included elevated FVIII levels, decreased levels of antithrombin, and lag time prolongation in thrombin generation. Serial hematological data demonstrated increased Von Willebrand factor, FVIII, D-dimer, fibrinogen and decreased levels of natural anticoagulant proteins in the early post-operative period predisposing to a hyper-coagulable state. The ratio of the anticoagulant protein C to the procoagulant FVIII was low at baseline and further declined post-operatively, indicating a prothrombotic state. Though no bleeding complications were reported, one patient experienced pulmonary embolism while under thromboprophylaxis. Overall, patients with hepatic carcinoma presenting for elective major hepatectomy may have baseline malignancy-associated coagulation disturbances, aggravating the hyper-coagulable state documented in the early post-operative period.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-18T17:27:55+01:00
      DOI: 10.1055/a-1839-0355
      Issue No: Vol. eFirst
       
  • High-Density Lipoprotein Particle Subclasses in Statin-Treated Patients
           with Peripheral Artery Disease Predict Long-Term Survival

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      Authors: Zierfuss; Bernhard, Höbaus, Clemens, Herz, Carsten T., Koppensteiner, Renate, Stangl, Herbert, Schernthaner, Gerit-Holger
      Abstract: Low-density lipoprotein-cholesterol reduction showed a strong reduction of cardiovascular (CV) event rates in CV disease. However, the residual risk of future CV events remains high, which especially extends to peripheral arterial disease (PAD). Nuclear magnetic resonance (NMR) spectroscopy offers a novel method for analysis of the lipoprotein spectrum. This study investigates lipoprotein subclasses using NMR spectroscopy and assesses implications for long-term survival in PAD. NMR spectroscopy was performed by Nightingale Inc., in 319 patients with stable PAD and well-controlled CV risk factors. Patients were followed-up for 10 years. During that period, 123 patients (38.5%) died, of those 68 (21.3%) were defined as CV deaths. Outcome data were analyzed by the Kaplan–Meier method and multivariable Cox-regression for lipoprotein particles. Small and medium high-density lipoprotein-particles (S-HDL-P and M-HDL-P) showed a significant inverse association with all-cause mortality in Cox-regression analyses after multivariable adjustment (S-HDL-P, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.57–0.88; M-HDL-P, HR: 0.72, 95% CI: 0.58–0.90) for each increase of one standard deviation. In contrast, cholesterol-rich X-large HDL-particles (XL-HDL-P) showed a positive association with all-cause mortality (HR: 1.51, 95% CI: 1.20–1.89). Only the association between XL-HDL-P and CV death sustained multivariable adjustment (HR: 1.49, 95% CI: 1.10–2.02), whereas associations for S-HDL-P and M-HDL-P were attenuated (HR: 0.76, 95% CI: 0.57–1.01; HR: 0.80, 95% CI: 0.60–1.06). This study shows a novel association for a beneficial role of S-HDL-P and M-HDL-P but a negative association with higher cholesterol-rich XL-HDL-P for long-term outcome in well-treated patients with PAD. Thus, these results provide evidence that NMR-measured HDL particles identify patients at high CV residual risk beyond adequate lipid-lowering therapy.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-18T17:24:11+01:00
      DOI: 10.1055/a-1827-7896
      Issue No: Vol. eFirst
       
  • Do Antiangiogenics Promote Clot Instability' Data from the TESEO
           Prospective Registry and Caravaggio Clinical Trial

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      Authors: Carmona-Bayonas; Alberto, Verso, Melina, Sánchez Cánovas, Manuel, Rubio Pérez, Jaime, García de Herreros, Marta, Martínez del Prado, Purificación, Fernández Pérez, Isaura, Quintanar Verduguez, Teresa, Obispo Portero, Berta, Pachón Olmos, Vanessa, Gómez, David, Ortega, Laura, Serrano Moyano, Marta, M. Brozos, Elena, Biosca, Mercedes, Antonio Rebollo, Maite, Teijeira Sanchez, Lucía, Hernández Pérez, Carolina, David Cumplido Burón, José, Martínez Lago, Nieves, García Pérez, Estefanía, Muñoz Langa, Jose, Pérez Segura, Pedro, Martínez de Castro, Eva, Jimenez-Fonseca, Paula, Agnelli, Giancarlo, Muñoz, Andrés
      Abstract: Background Venous thromboembolism (VTE) is a common complication in cancer patients. Much of its morbidity stems from the development of fatal pulmonary embolisms (PE). Little is known about the factors involved in clot stability, with angiogenesis possibly being implicated. Methods The database is from the TESEO prospective registry that recruits cancer patients with VTE from 41 Spanish hospitals. Independent validation was conducted in a cohort from the Caravaggio trial. The objective is to evaluate the association between exposure to antiangiogenic therapies and the PE/VTE proportion in oncological patients. Results In total, 1,536 subjects were evaluated; 58.4% (n = 894) had a PE and 7% (n = 108) received antiangiogenic therapy (bevacizumab in 75%). The PE/VTE proportion among antiangiogenic-treated individuals was 77/108 (71.3%) versus 817/1,428 (57.2%) among those receiving other alternative therapies (p = 0.004). The effect of the antiangiogenics on the PE/VTE proportion held up across all subgroups except for active smokers or those with chronic obstructive pulmonary disease. Exposure to antiangiogenics was associated with increased PEs, odds ratio (OR) 2.27 (95% CI, 1.42–3.63). In the Caravaggio trial, PE was present in 67% of the individuals treated with antiangiogenics, 50% of those who received chemotherapy without antiangiogenic treatment, and 60% without active therapy (p = 0.0016). Conclusion Antiangiogenics are associated with increased proportion of PE in oncological patients with VTE. If an effect on clot stability is confirmed, the concept of thrombotic risk in cancer patients should be reconsidered in qualitative terms.
      Citation: Thromb Haemost ; : -
      PubDate: 2022-06-18T17:08:44+01:00
      DOI: 10.1055/a-1816-8347
      Issue No: Vol. eFirst
       
  • Plasma Homocysteine in Behcet's Disease: A Systematic Review and
           Meta-Analysis

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      Authors: Merashli; Mira, Bucci, Tommaso, Pastori, Daniele, Pignatelli, Pasquale, Arcaro, Alessia, Gentile, Fabrizio, Marottoli, Vincenzo, Ames, Paul R. J.
      Abstract: Aim To evaluate the relevance of plasma homocysteine (HC) in Behcet's disease (BD) and its clinical manifestations. Methods Systematic review of EMBASE and PubMed databases according to PRISMA guidelines from inception to July 2021; random-effects meta-analyses for continuous outcomes. Results The search strategy retrieved 48 case–control (2,669 BD and 2,245 control participants) and 5 cohort studies (708 BD participants). Plasma HC was higher in BD than in controls (p 1.5; some pooled ethnicities explained a small part of the heterogeneity (I2  = 16.3%). Active BD participants had higher HC than inactive ones (p 
      Citation: Thromb Haemost ; : -
      PubDate: 2022-01-07T00:00:00+0100
      DOI: 10.1055/s-0041-1740637
      Issue No: Vol. eFirst
       
  • Knockdown and Knockout of Tissue Factor Pathway Inhibitor in Zebrafish

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      Authors: Raman; Revathi, Fallatah, Weam, Qaryoute, Ayah Al, Ryon, Mia, Jagadeeswaran, Pudur
      Abstract: Tissue factor pathway inhibitor (TFPI) is an anticoagulant that inhibits factor VIIa and Xa in the blood coagulation pathways. TFPI contains three Kunitz domains, K1, K2, and K3. K1 and K2 inhibit factor VIIa and Xa, respectively. However, the regulation of TFPI is poorly studied. Since zebrafish has become an alternate model to discover novel actors in hemostasis, we hypothesized that TFPI regulation could be studied using this model. As a first step, we confirmed the presence of tfpia in zebrafish using reverse transcription polymerase chain reaction. We then performed piggyback knockdowns of tfpia and found increased coagulation activity in tfpia knockdown. We then created a deletion mutation in tfpia locus using the CRISPR/Cas9 method. The tfpia homozygous deletion mutants showed increased coagulation activities similar to that found in tfpia knockdown. Taken together, our data suggest that tfpia is a negative regulator for zebrafish coagulation, and silencing it leads to thrombotic phenotype. Also, the zebrafish tfpia knockout model could be used for reversing this thrombotic phenotype to identify antithrombotic novel factors by the genome-wide piggyback knockdown method.
      Citation: Thromb Haemost ; : -
      PubDate: 2021-12-16T00:00:00+0100
      DOI: 10.1055/a-1723-4075
       
  • Polyvalent immunoglobulin preparations inhibit pneumolysin-induced
           platelet destruction

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      Authors: Wiebe; Friederike, Handtke, Stefan, Wesche, Jan, Schnarre, Annabel, Palankar, Raghavendra, Wolff, Martina, Jahn, Kristin, Voß, Franziska, Weißmüller, Sabrina, Schüttrumpf, Jörg, Greinacher, Andreas, Hammerschmidt, Sven
      Abstract: Platelets play an important role in the development and progression of respiratory distress. Functional platelets are known to seal inflammatory endothelial gaps and loss of platelet function has been shown to result in loss of integrity of pulmonary vessels. This leads to fluid accumulation in the pulmonary interstitium, eventually resulting in respiratory distress. Streptococcus pneumoniae is one of the major pathogens causing community-acquired pneumonia. Previously, we have shown that its major toxin pneumolysin forms pores in platelet membranes and renders them non-functional. In vitro, this process was inhibited by polyvalent intravenous immunoglobulins (IVIG). In this study, we compared the efficacy of a standard intravenous immunoglobulin preparation (IVIG, 98% IgG; Privigen, CSL Behring, USA) and an IgM/IgA-enriched immunoglobulin preparation (21% IgA, 23% IgM, 56% IgG; trimodulin, Biotest AG, Germany) to inhibit pneumolysin-induced platelet destruction. Platelet destruction and functionality were assessed by flow cytometry, intracellular calcium release, aggregometry, platelet viability, transwell, and flow chamber assays. Overall, both immunoglobulin preparations efficiently inhibited pneumolysin-induced platelet destruction. The capacity to antagonize pneumolysin mainly depended on the final IgG content. As both polyvalent immunoglobulin preparations efficiently prevent pneumolysin-induced platelet destruction and maintain platelet function in vitro, they represent promising candidates for clinical studies on supportive treatment of pneumococcal pneumonia to reduce progression of respiratory distress.
      Citation: Thromb Haemost ; : -
      PubDate: 2021-12-16T00:00:00+0100
      DOI: 10.1055/a-1723-1880
       
  • The story of the fibrin(ogen) αC-domains: evolution of our view on their
           structure and interactions

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      Authors: Medved; Leonid, Weisel, John W
      Abstract: Although much has been established concerning the overall structure and function of fibrinogen, much less has been known about its two αC regions, each consisting of an αC-connector and αC-domain, but new information has been accumulating. This review summarizes the state of our current knowledge of the structure and interactions of fibrinogen’s αC regions. A series of studies with isolated αC regions and their fragments demonstrated that the αC-domain forms compact ordered structures consisting of N- and C-terminal sub-domains including β sheets and suggested that the αC-connector has a poly(L-proline) type II structure. Functionally, the αC-domains interact intramolecularly with each other and with the central region of the molecule, first demonstrated by electron microscopy and then quantified by optical trap force spectroscopy. Upon conversion of fibrinogen into fibrin, the αC-domains switch from intra- to intermolecular interactions to form ordered αC polymers. The formation of αC polymers occurs mainly through the homophilic interaction between the N-terminal sub-domains; interaction between the C-terminal sub-domains and the αC-connectors also contributes to this process. Considerable evidence supports the idea that the αC-regions accelerate fibrin polymerization and affect the final structure of fibrin clots. The interactions between αC-regions are important for the mechanical properties of clots, increasing their stiffness and extensibility. Conversion of fibrinogen into fibrin results in exposure of multiple binding sites in its αC regions, providing interaction of fibrin with different proteins and cell types during hemostasis and wound healing. This heretofore mysterious part of the fibrinogen molecule is finally giving up its secrets.
      Citation: Thromb Haemost ; : -
      PubDate: 2021-12-13T00:00:00+0100
      DOI: 10.1055/a-1719-5584
       
  • Prevention of the post thrombotic syndrome with anticoagulation: a
           narrative review

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      Authors: Makedonov; Ilia, Kahn, Susan R, Abdulrehman, Jameel, Schulman, Sam, Delluc, Aurélien, Gross, Peter L, Galanaud, Jean Philippe
      Abstract: The post thrombotic syndrome (PTS) is chronic venous insufficiency secondary to a prior deep vein thrombosis (DVT). It is the most common complication of VTE and, while not fatal, it can lead to chronic, unremitting symptoms as well as societal and economic consequences. The cornerstone of PTS treatment lies in its prevention after DVT. Specific PTS preventative measures include the use of elastic compression stockings (ECS) and pharmacomechanical catheter directed thrombolysis (PCDT). However, the efficacy of these treatments has been questioned by large RCTs. So far, anticoagulation, primarily prescribed to prevent DVT extension and recurrence, appears to be the only unquestionably effective treatment for the prevention of PTS. In this literature review we present pathophysiological, biological, radiological and clinical data supporting the efficacy of anticoagulants to prevent PTS and the possible differential efficacy among available classes of anticoagulants (vitamin K antagonists (VKA), low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs)). Data suggest that LMWHs and DOACs are superior to VKAs, but no head-to-head comparison is available between DOACs and LMWHs. Owing to their potentially greater anti-inflammatory properties, LMWHs could be superior to DOACs. This finding may be of interest particularly in patients with extensive DVT at high risk of moderate to severe PTS, but needs to be confirmed by a dedicated RCT.
      Citation: Thromb Haemost ; : -
      PubDate: 2021-12-01T00:00:00+0100
      DOI: 10.1055/a-1711-1263
       
  • The PAR4 Platelet Thrombin Receptor Variant rs773902 does not Impact the
           Incidence of Thrombotic or Bleeding Events in a Healthy Older Population

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      Authors: Selvadurai; Maria V., Riaz, Moeen, Xie, Sophia, Tonkin, Andrew M., McNeil, John J., Lacaze, Paul, Hamilton, Justin R.
      Abstract: Background Protease-activated receptor 4 (PAR4) is a platelet thrombin receptor important for thrombosis and a target of antiplatelet drug development. A frequently occurring single-nucleotide polymorphism (rs773902) causes a PAR4 sequence variant (NC_000019.10:p.Ala120Thr) whereby platelets from Thr120-expressing individuals are hyperresponsive to PAR4 agonists versus platelets from Ala120-expressing individuals. However, whether this enhanced platelet responsiveness translates to increased thrombotic risk or decreased bleeding risk remains unknown. Objectives This article examines the association of rs773902 with adjudicated cardiovascular events and aspirin use in a randomized trial population of healthy older individuals. Methods We analyzed 13,547 participants in the ASPirin in Reducing Events in the Elderly trial. Participants had no previous cardiovascular events at enrollment and were randomized to either 100 mg daily aspirin or placebo for a median follow-up of 4.7 years. Total genotypes were 8,761 (65%) GG (Ala120 variant), 4,303 (32%) heterozygotes, and 483 (4%) AA (Thr120 variant). Cox proportional hazard regression tested the relationship between rs773902 and thrombotic events (major adverse cardiovascular events [MACE] and ischemic stroke [IS]) and bleeding (major hemorrhage [MHEM] and intracranial bleeding [ICB]). Results No statistically significant association was observed overall or by treatment group between rs773902 and any thrombotic or bleeding event examined. Further, there was no significant interaction between rs773902 and treatment for any of MACE, IS, MHEM, or ICB. Conclusion This post hoc analysis of a prospective cohort study suggests that, despite sensitizing platelet activation, the rs773902 PAR4 variant is not associated with thrombotic cardiovascular or bleeding events in a healthy older population.
      Citation: Thromb Haemost ; : -
      PubDate: 2021-12-01T00:00:00+0100
      DOI: 10.1055/a-1711-1395
       
  • Exploring Pleiotropic Effects of Lipid Modifiers and Targets on Measures
           of the Coagulation System with Genetics

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      Authors: Schooling; C. Mary, Au Yeung, Shiu Lun, Zhao, Jie V.
      Abstract: Background Statins have long been suspected to have pleiotropic effects via thrombotic factors. Randomized controlled trials are too limited to be definitive. We examined the associations of genetically mimicking effects of statins, PCSK9 inhibitors, and alternative lipid targets (in genes LDLR, APOC3, and LPL) on key indicators of coagulation system function, i.e., prothrombin time (PT) and activated partial thromboplastin time (aPTT). Methods We assessed the effect of established genetic mimics of effects of lipid modifiers and alternative lipid treatment targets on PT (n = 58,110) and aPTT (n = 37,767), all transformed to z-scores, using Mendelian randomization taking advantage of Biobank Japan. Ischemic heart disease (IHD) was a control outcome. Results Genetically mimicked effects of statins increased PT by 0.31 standard deviation (SD) per SD increase in low-density lipoprotein (95% confidence interval [CI]: 0.10–0.51) based on rs12916 but did not affect aPTT. Genetically mimicking effects of targeting LDLR increased PT based on rs688 (0.33 SD per SD increase in triglyceride, 95% CI: 0.03–0.63) but did not affect aPTT. Genetically mimicking effects of PCSK9 inhibitors or targeting APOC3 or LPL had no effect on PT or aPTT. Genetically mimicking effects of statins, PCSK9 inhibitors, and alternative lipid targets reduced risk of IHD in Biobank Japan. Conclusion Statins, and possibly targeting LDLR, may also act via a coagulation cascade factor, likely specific to the extrinsic or common pathway. Further elucidation of the mechanistic pathway may facilitate development of new interventions and inform use of statins particularly in relation to use of other anticoagulants.
      Citation: Thromb Haemost ; : -
      PubDate: 2021-12-01T00:00:00+0100
      DOI: 10.1055/a-1711-0946
       
  • Prognostic Implications of Neutrophil Extracellular Traps in Coronary
           Thrombi of Patients with ST-Elevation Myocardial Infarction

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      Authors: Blasco; Ana, Coronado, María-José, Vela, Paula, Martín, Paloma, Solano, Jorge, Ramil, Elvira, Mesquida, Aína, Santos, Adrián, Cózar, Beatriz, Royuela, Ana, García, Diego, Camarzana, Susana, Parra, Carolina, Oteo, Juan F., Goicolea, Javier, Bellas, Carmen
      Abstract: Aims The mechanisms of coronary thrombosis can influence prognosis after ST-elevation myocardial infarction (STEMI) and allow for different treatment groups to be identified; an association between neutrophil extracellular traps (NETs) and unfavorable clinical outcomes has been suggested. Our aim was to determine the role played by NETs in coronary thrombosis and their influence on prognosis. The role of other histological features in prognosis and the association between NETs and bacteria in the coronary thrombi were also explored. Methods and Results We studied 406 patients with STEMI in which coronary thrombi were consecutively obtained by aspiration during angioplasty between 2012 and 2018. Analysis of NETs in paraffin-embedded thrombi was based on the colocalization of specific NET components by means of confocal microscopy. Immunohistochemistry stains were used to identify plaque fragments. Fluorescence in situ hybridization was used to detect bacteria.NETs were detected in 51% of the thrombi (NET density, median [interquartile range]: 25% [17–38%]). The median follow-up was 47 months (95% confidence interval [CI] 43–51); 105 (26%) patients experienced major adverse cardiac events (MACE). A significant association was found between the presence of NETs in coronary aspirates and the occurrence of MACE in the first 30 days after infarction (hazard ratio 2.82; 95% CI 1.26–6.35, p = 0.012), mainly due to cardiac deaths and stent thrombosis. Conclusion The presence of NETs in coronary thrombi was associated with a worse prognosis soon after STEMI. In some patients, NETs could be a treatment target and a feasible way to prevent reinfarction.
      Citation: Thromb Haemost ; : -
      PubDate: 2021-11-30T00:00:00+0100
      DOI: 10.1055/a-1709-5271
       
  • Coagulation Factor V (F5) is an Estrogen-Responsive Gene in Breast Cancer
           Cells

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      Authors: Andresen; Marianne S., Sletten, Marit, Sandset, Per Morten, Iversen, Nina, Stavik, Benedicte, Tinholt, Mari
      Abstract: Most breast cancers express estrogen receptor (ER) where estrogen signaling plays an important role. Cancer contributes to activation of the coagulation system leading to an imbalance in the hemostatic system, and coagulation factor (F) V, which is a key regulator of blood coagulation, has been shown to be increased in breast tumors. Thus, the molecular association between estrogens and FV was explored. Stimulation with 17-β-estradiol (E2) or 17-β-ethinylestradiol (EE2) resulted in a time- and dose-dependent increase in F5 messenger RNA and FV protein in ERα-positive MCF-7 cells. Pretreatment with the ER antagonist fulvestrant or knockdown of ERα prior to stimulation with E2 counteracted this effect. Three ERα-binding half-sites were identified in the promoter region of the F5 gene in silico. Reporter gene analysis showed that all three half-sites were involved in the estrogen-induced gene regulation in vitro, as the effect was abolished only when all half-sites were mutated. High F5 levels in ER-positive breast tumors were associated with increased relapse-free survival of breast cancer patients.
      Citation: Thromb Haemost ; : -
      PubDate: 2021-11-26T00:00:00+0100
      DOI: 10.1055/a-1707-2130
       
  • Retrospective Analysis of the Effectiveness of a Reduced Dose of
           Idarucizumab in Dabigatran Reversal

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      Authors: Stone; Louisa, Merriman, Eileen, Hanna, Merit, Royle, Gordon, Chan, Henry
      Abstract: Background The recommended dose of idarucizumab, the specific reversal agent for dabigatran etexilate, is 5 g. However, published data showed biochemical reversal after an initial 2.5 g dose. Objectives This study aims to retrospectively compare the clinical effectiveness of 2.5 and 5 g doses of idarucizumab used in dabigatran reversal in three hospitals in Auckland, New Zealand. Methods All patients receiving idarucizumab for dabigatran reversal between April 1, 2016 and December 31, 2018 were included. The primary outcome was the likelihood of receiving a second dose of idarucizumab during the same admission. Secondary outcomes included normalization of coagulation profiles, and 30-day thrombotic, bleeding, and mortality rates. Results Of 329 patients included, 206 received an initial 2.5 g dose and 123 received a 5 g dose. The median age was 78 years and median creatinine clearance was 50 mL/min. Most patients (62.6%) required idarucizumab for an urgent procedure, while 37.4% presented with bleeding. A 2.5 g dose was not associated with an increased rate of receiving a second dose (odds ratio [OR]: 0.686, 95% confidence interval [CI]: 0.225–2.090). A similar proportion of patients in each group achieved a normal activated partial thromboplastin time (73.8 vs. 80.0%, p = 0.464) and dilute thrombin clotting time (95.9 vs. 91.4%, p = 0.379) following idarucizumab infusion. There was no increase in the rate of death (OR: 0.602, 95% CI: 0.292–1.239), thrombosis (OR: 0.386, 95% CI: 0.107–1.396), or bleeding (OR: 0.96, 95% CI: 0.27–3.33) in the 2.5 g dose group compared with the 5 g dose group. Conclusion An initial 2.5 g dose of idarucizumab appears effective for dabigatran reversal in the real-world setting.
      Citation: Thromb Haemost ; : -
      PubDate: 2021-11-23T00:00:00+0100
      DOI: 10.1055/a-1704-0630
       
  • Transient Bacteremia Promotes Catheter-Related Central Venous Thrombosis
           through Neutrophil Extracellular Traps

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      Authors: Chen; Jeng-Wei, Hsu, Chih-Chieh, Su, Chien-Chia, Hsu, Ron-Bin, Chiu, Yen-Ling, Jung, Chiau-Jing, Chia, Jean-San
      Abstract: Formation of intravenous catheter-related thrombosis leads to central venous stenosis in patients requiring renal replacement therapy or chemotherapy infusion, yet the triggers or mechanisms remain unclear, especially in patients without symptoms of infection. In this study, we found that neutrophil extracellular traps (NETs) could be detected in the fibrin sheaths from dialysis patients without clinical manifestations of infection. Confocal microscopy revealed bacteria imbedded in NETs in the fibrin sheaths. Thirty-nine of 50 (78%) fibrin sheath specimens contained bacteria detectable by 16S ribosomal RNA genome typing with a predominance of Staphylococcus aureus (69%). In rat models, transient bacteremia of S. aureus induced NETs in enlarged fibrin sheaths, and treatment with DNase I alone significantly reduced both NET and fibrin sheath formation surrounding the catheter. Therefore, transient bacteremia could be a silent trigger that induces NET-related immunothrombosis enhancing catheter-related central venous stenosis.
      Citation: Thromb Haemost ; : -
      PubDate: 2021-11-12T00:00:00+0100
      DOI: 10.1055/a-1695-8612
       
  • Validation of Risk Assessment Models Predicting Venous Thromboembolism in
           Inpatients with Acute Exacerbation Of Chronic Obstructive Pulmonary
           Disease: A Multicenter Cohort Study in China

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      Authors: Zhou; Chen, Yi, Qun, Ge, Huiqing, Wei, Hailong, Liu, Huiguo, Zhang, Jianchu, Luo, Yuanming, Pan, Pinhua, Zhang, Jiarui, Peng, Lige, Aili, Adila, Liu, Yu, Wang, Maoyun, Tang, Yongjiang, Wang, Lan, Zhong, Xia, Wang, Yixi, Zhou, Haixia
      Abstract: Background Inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are at increased risk for venous thromboembolism (VTE); however, the prophylaxis for VTE is largely underused in China. Identifying high-risk patients requiring thromboprophylaxis is critical to reduce the mortality and morbidity associated with VTE. This study aimed to evaluate and compare the validities of the Padua Prediction Score and Caprini risk assessment model (RAM) in predicting the risk of VTE in inpatients with AECOPD in China. Methods The inpatients with AECOPD were prospectively enrolled from seven medical centers of China between September 2017 and January 2020. Caprini and Padua scores were calculated on admission, and the incidence of 3-month VTE was investigated. Results Among the 3,277 eligible patients with AECOPD, 128 patients (3.9%) developed VTE within 3 months after admission. The distribution of the study population by the Caprini risk level was as follows: high, 53.6%; moderate, 43.0%; and low, 3.5%. The incidence of VTE increased by risk level as high, 6.1%; moderate, 1.5%; and low, 0%. According to the Padua RAM, only 10.9% of the study population was classified as high risk and 89.1% as low risk, with the corresponding incidence of VTE of 7.9 and 3.4%, respectively. The Caprini RAM had higher area under curve compared with the Padua RAM (0.713 ± 0.021 vs. 0.644 ± 0.023, p = 0.029). Conclusion The Caprini RAM was superior to the Padua RAM in predicting the risk of VTE in inpatients with AECOPD and might better guide thromboprophylaxis in these patients.
      Citation: Thromb Haemost ; : -
      PubDate: 2021-11-10T00:00:00+0100
      DOI: 10.1055/a-1693-0063
       
  • Pathophysiology of the Antiphospholipid Antibody Syndrome

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      Authors: Green; David
      Abstract: The antiphospholipid syndrome is characterized by antibodies directed against phospholipid-binding proteins and phospholipids attached to cell membrane receptors, mitochondria, oxidized lipoproteins, and activated complement components. When antibodies bind to these complex antigens, cells are activated and the coagulation and complement cascades are triggered, culminating in thrombotic events and pregnancy morbidity that further define the syndrome. The phospholipid-binding proteins most often involved are annexins II and V, β2-glycoprotein I, prothrombin, and cardiolipin. A distinguishing feature of the antiphospholipid syndrome is the “lupus anticoagulant”. This is not a single entity but rather a family of antibodies directed against complex antigens consisting of β2-glycoprotein I and/or prothrombin bound to an anionic phospholipid. Although these antibodies prolong in vitro clotting times by competing with clotting factors for phospholipid binding sites, they are not associated with clinical bleeding. Rather, they are thrombogenic because they augment thrombin production in vivo by concentrating prothrombin on phospholipid surfaces. Other antiphospholipid antibodies decrease the clot-inhibitory properties of the endothelium and enhance platelet adherence and aggregation. Some are atherogenic because they increase lipid peroxidation by reducing paraoxonase activity, and others impair fetal nutrition by diminishing placental antithrombotic and fibrinolytic activity. This plethora of destructive autoantibodies is currently managed with immunomodulatory agents, but new approaches to treatment might include vaccines against specific autoantigens, blocking the antibodies generated by exposure to cytoplasmic DNA, and selective targeting of aberrant B-cells to reduce or eliminate autoantibody production.
      Citation: Thromb Haemost ; : -
      PubDate: 2021-11-18T00:00:00+0100
      DOI: 10.1055/a-1701-2809
      Issue No: Vol. eFirst
       
  • The risk of venous thromboembolism attributed to established prothrombotic
           genotypes

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      Authors: Evensen; Line Holted, Arnesen, Carl Arne Lochen, Rosendaal, Frits R., Gabrielsen, Maiken Elvestad, Brumpton, Ben Michael, Hveem, Kristian, Hansen, John-Bjarne, Brækkan, Sigrid Kufaas
      Abstract: Background: The proportion of venous thromboembolism (VTE) events that can be attributed to established prothrombotic genotypes has been scarcely investigated in the general population. We aimed to estimate the proportion of VTEs in the population that could be attributed to established prothrombotic genotypes using a population-based case-cohort.Methods: Cases with incident VTE (n=1,493) and a randomly sampled sub-cohort (n=13,069) were derived from the Tromsø Study (1994-2012) and the Nord-Trøndelag Health (HUNT) Study (1995-2008). DNA-samples were genotyped for 17 single nucleotide polymorphism (SNPs) associated with VTE. Hazard ratios with 95% confidence intervals (CIs) were estimated in Cox regression models. Population attributable fraction (PAF) with 95% bias-corrected CIs (based on 10,000 bootstrap samples) were estimated using a cumulative model where SNPs significantly associated with VTE were added one-by-one in ranked order of the individual PAFs.Results: Six SNPs were significantly associated with VTE (rs1799963 [Prothrombin], rs2066865 [FGG], rs6025 [FV Leiden], rs2289252 [F11], rs2036914 [F11] and rs8176719 [ABO]. The cumulative PAF for the six-SNP model was 45.3% (95% CI 19.7-71.6) for total VTE and 61.7% (95% CI 19.6-89.3) for unprovoked VTE. The PAF for prothrombotic genotypes was higher for DVT (52.9%) than for PE (33.8%), and higher for those aged
      Citation: Thromb Haemost ; : -
      PubDate: 2021-11-16T00:00:00+0100
      DOI: 10.1055/a-1698-6717
      Issue No: Vol. eFirst
       
  • The proportion of low and intermediate molecular weight von Willebrand
           Factor multimers are different in neonates and infants compared to adults.
           

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      Authors: Letunica; Natasha, Van Den Helm, Suelyn, Barton, Rebecca, Weaver, Asami, Karlaftis, Vasiliki, Monagle, Paul, Ignjatovic, Vera
      Abstract: N/A
      Citation: Thromb Haemost ; : -
      PubDate: 2021-11-09T00:00:00+0100
      DOI: 10.1055/a-1692-1199
      Issue No: Vol. eFirst
       
 
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