JournalTOCs

Seminars in Thrombosis and Hemostasis
Journal Prestige (SJR): 1.159

Citation Impact (citeScore): 3
Number of Followers: 28

Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0094-6176 - ISSN (Online) 1098-9064
Published by Thieme Publishing Group

[233 journals]

Changes in Coagulation in Cancer Patients Undergoing Cytoreductive Surgery
with Hyperthermic Intraperitoneal Chemotherapy Treatment (HIPEC)—A
Systematic Review
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  Authors: Lundbech; Mikkel, Damsbo, Matilde, Krag, Andreas Engel, Hvas, Anne-Mette
  Abstract: Venous thromboembolism and postoperative bleeding are complications of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this systematic review was to summarize current knowledge on the effect of cytoreductive surgery with HIPEC on coagulation and fibrinolysis within 10 days after surgery. Studies were identified in PubMed, Embase, and Web of Science on December 12, 2022. Data on biomarkers of coagulation and fibrinolysis measured preoperatively up to the 10th postoperative day were extracted. Among 15 included studies, 13 studies reported markers of primary hemostasis. Eleven studies found reduced platelet count following cytoreductive surgery with HIPEC and two studies reported reduced platelet function. Twelve studies reported impaired secondary hemostasis until postoperative day 10 indicated by prolonged international normalized ratio, prothrombin time, and activated partial thromboplastin time. Fibrinogen was decreased in three studies from preoperative to postoperative day 3 switching to increased levels until postoperative day 10. In accordance, three studies found reduced maximum amplitude and maximum clot firmness by thromboelastography/thromboelastometry (ROTEM/TEG) on the first postoperative day indicating impaired clot strength. Four studies demonstrated increased d-dimer, factor (F) VIII, and thrombin generation during the 10 postoperative days. Four studies investigated fibrinolysis by ROTEM/TEG and plasminogen activator inhibitor-1 (PAI-1) after cytoreductive surgery with HIPEC reporting contradictive results. In conclusion, a decrease in platelet count and subtle changes in secondary hemostasis were found following cytoreductive surgery with HIPEC. Data on the effect of cytoreductive surgery with HIPEC on fibrinolysis are sparse and this needs to be further investigated.
  Citation: Semin Thromb Hemost ; : -
  PubDate: 2023-02-24T05:10:36+0100
  DOI: 10.1055/s-0043-1764125
The Role of the von Willebrand Factor Collagen-Binding Assay (VWF:CB) in
the Diagnosis and Treatment of von Willebrand Disease (VWD) and Way
Beyond: A Comprehensive 36-Year History
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  Authors: Favaloro; Emmanuel J.
  Abstract: The von Willebrand factor (VWF) collagen binding (VWF:CB) assay was first reported for use in von Willebrand diagnostics in 1986, by Brown and Bosak. Since then, the VWF:CB has continued to be used to help diagnose von Willebrand disease (VWD) (correctly) and also to help assign the correct subtype, as well as to assist in the monitoring of VWD therapy, especially desmopressin (DDAVP). However, it is important to recognize that the specific value of any VWF:CB is predicated on the use of an optimized VWF:CB, and that not all VWF:CB assays are so optimized. There are some good commercial assays available, but there are also some “not-so-good” commercial assays available, and these may continue to give the VWF:CB “a bad reputation.” In addition to VWD diagnosis and management, the VWF:CB found purpose in a variety of other applications, from assessing ADAMTS13 activity, to investigation into acquired von Willebrand syndrome (especially as associated with use of mechanical circulatory support or cardiac assist devices), to assessment of VWF activity in disease states in where an excess of high-molecular-weight VWF may accumulate, and lead to increased (micro)thrombosis risk (e.g., coronavirus disease 2019, thrombotic thrombocytopenic purpura). The VWF:CB turns 37 in 2023. This review is a celebration of the utility of the VWF:CB over this nearly 40-year history.
  Citation: Semin Thromb Hemost ; : -
  PubDate: 2023-02-20T08:48:14+0100
  DOI: 10.1055/s-0043-1763259
Assessment of Hemostatic Profile in Neonates with Intrauterine Growth
Restriction: A Systematic Review of Literature
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  Authors: Karapati; Eleni, Sokou, Rozeta, Iliodromiti, Zoi, Tsaousi, Marina, Sulaj, Alma, Tsantes, Andreas G., Petropoulou, Chrysa, Pouliakis, Abraham, Tsantes, Argirios E., Boutsikou, Theodora, Iacovidou, Nicoletta
  Abstract: Intrauterine growth restriction (IUGR) affects nearly 10 to 15% of pregnancies and is responsible for many short- and long-term adverse consequences, including hemostatic derangement. Both thrombotic and hemorrhagic events are described in the perinatal period in these neonates. The aim of this study was to systematically review the literature on the laboratory studies used to evaluate the hemostatic system of the IUGR small for gestational age neonate. We reviewed the current literature via PubMed and Scopus until September 2022. Following our inclusion/exclusion criteria, we finally included 60 studies in our review. Thrombocytopenia, characterized as hyporegenerative and a kinetic upshot of reduced platelet production due to in utero chronic hypoxia, was the main finding of most studies focusing on growth-restricted neonates, in most cases is mild and usually resolves spontaneously with the first 2 weeks of life. In regard to coagulation, growth-restricted newborns present with prolonged standard coagulation tests. Data regarding coagulation factors, fibrinolytic system, and anticoagulant proteins are scarce and conflicting, mainly due to confounding factors. As thromboelastography/rotational thromboelastometry (TEG/ROTEM) provides a more precise evaluation of the in vivo coagulation process compared with standard coagulation tests, its use in transfusion guidance is fundamental. Only one study regarding TEG/ROTEM was retrieved from this population, where no difference in ROTEM parameters compared with appropriate for gestational age neonates was found. Despite the laboratory aberrations, no correlation could be achieved with clinical manifestations of bleeding or thrombosis in the studies included. More studies are needed to assess hemostasis in IUGR neonates and guide targeted therapeutic interventions.
  Citation: Semin Thromb Hemost ; : -
  PubDate: 2023-02-17T08:32:27+0100
  DOI: 10.1055/s-0043-1762893
The History of Extracorporeal Membrane Oxygenation and the Development of
Extracorporeal Membrane Oxygenation Anticoagulation
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  Authors: Bartlett; Robert, Arachichilage, Deepa J., Chitlur, Meera, Hui, Shiu-Ki Rocky, Neunert, Cindy, Doyle, Andrew, Retter, Andrew, Hunt, Beverley J, Lim, Hoong Sern, Saini, Arun, Renné, Thomas, Kostousov, Vadim, Teruya, Jun
  Abstract: Extracorporeal membrane oxygenation (ECMO) was first started for humans in early 1970s by Robert Bartlett. Since its inception, there have been numerous challenges with extracorporeal circulation, such as coagulation and platelet activation, followed by consumption of coagulation factors and platelets, and biocompatibility of tubing, pump, and oxygenator. Unfractionated heparin (heparin hereafter) has historically been the defacto anticoagulant until recently. Also, coagulation monitoring was mainly based on bedside activated clotting time and activated partial thromboplastin time. In the past 50 years, the technology of ECMO has advanced tremendously, and thus, the survival rate has improved significantly. The indication for ECMO has also expanded. Among these are clinical conditions such as postcardiopulmonary bypass, sepsis, ECMO cardiopulmonary resuscitation, and even severe coronavirus disease 2019 (COVID-19). Not surprisingly, the number of ECMO cases has increased according to the Extracorporeal Life Support Organization Registry and prolonged ECMO support has become more prevalent. It is not uncommon for patients with COVID-19 to be on ECMO support for more than 1 year until recovery or lung transplant. With that being said, complications of bleeding, thrombosis, clot formation in the circuit, and intravascular hemolysis still remain and continue to be major challenges. Here, several clinical ECMO experts, including the “Father of ECMO”—Dr. Robert Bartlett, describe the history and advances of ECMO.
  Citation: Semin Thromb Hemost ; : -
  PubDate: 2023-02-07T05:42:44+0100
  DOI: 10.1055/s-0043-1761488
Drug–Drug Interactions in the Treatment of Cancer-Associated Venous
Thromboembolism with Direct Oral Anticoagulants
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  Authors: Hellfritzsch; Maja, Henriksen, Jakob Nørgaard, Holt, Marianne Ingerslev, Grove, Erik Lerkevang
  Abstract: Venous thromboembolism (VTE) is a frequent complication of cancer, and management of cancer-associated thrombosis (CAT) is challenging due to increased risks of bleeding and recurrent VTE. Recent trials have shown an acceptable efficacy and safety of direct oral anticoagulants (DOACs) in the treatment of CAT compared to low-molecular weight heparin. Although DOACs provide an effective and convenient treatment option in CAT, the need to assess the risk of drug–drug interactions (DDI) with antineoplastic therapies poses a barrier to their use in clinical practice. With the aim of supporting the assessment of CAT patients for treatment with DOAC, this review provides a comprehensive overview of the compatibility of antineoplastic therapies with the individual DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban). Using several data sources, we characterized 100 widely used antineoplastic agents with regard to their effect on p-glycoprotein and cytochrome P450, both important in the transport and elimination of DOACs. This enabled us to evaluate 400 “DOAC-antineoplastic agent”-pairs regarding their likelihood to interact (unlikely, potential, or likely), ultimately leading to clinical recommendations on the appropriateness of concomitant use for each pair. A potential or likely DDI was identified for 12% of the evaluated pairs. For nearly all antineoplastic agents, at least one DOAC was considered compatible.
  Citation: Semin Thromb Hemost ; : -
  PubDate: 2023-02-02T10:15:24+0100
  DOI: 10.1055/s-0043-1762596
Evolution of Hemostasis Testing: A Personal Reflection Covering over 40
Years of History*
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  Authors: Favaloro; Emmanuel J.
  Abstract: There is no certainty in change, other than change is certain. As Seminars in Thrombosis and Hemostasis celebrates 50 years of publication, I felt it appropriate to reflect on my own 40-year plus scientific career. My career in the thrombosis and hemostasis field did not start until 1987, but the subsequent 35 years reflected a period of significant change in associated disease diagnostics. I started in the Westmead Hospital “coagulation laboratory” when staff were still performing manual clotting tests, using stopwatches, pipettes, test tubes, and a water bath, which we transported to the hospital outpatient department to run our weekly warfarin clinic. Several hemostasis instruments have come and gone, including the Coag-A-Mate X2, the ACL-300R, the MDA-180, the BCS XP, and several StaR Evolution analyzers. Some instruments remain, including the PFA-100, PFA-200, the AggRAM, the CS-5100, an AcuStar, a Hydrasys gel system, and two ACL-TOP 750s. We still have a water bath, but this is primarily used to defrost frozen samples, and manual clotting tests are only used to teach visiting medical students. We have migrated across several methodologies in the 45-year history of the local laboratory. Laurel gel rockets, used for several assays in the 1980s, were replaced with enzyme-linked immunosorbent assay assays and most assays were eventually placed on automated instruments. Radio-isotopic assays, used in the 1980s, were replaced by an alternate safer method or else abandoned. Test numbers have increased markedly over time. The approximately 31,000 hemostasis assays performed at the Westmead-based laboratory in 1983 had become approximately 200,000 in 2022, a sixfold increase. Some 90,000 prothrombin times and activated partial thromboplastic times are now performed at this laboratory per year. Thrombophilia assays were added to the test repertoires over time, as were the tests to measure several anticoagulant drugs, most recently the direct oral anticoagulants. I hope my personal history, reflecting on the changes in hemostasis testing over my career to date in the field, is found to be of interest to the readership, and I hope they forgive any inaccuracies I have introduced in this reflection of the past.
  Citation: Semin Thromb Hemost ; : -
  PubDate: 2023-02-02T07:02:15+0100
  DOI: 10.1055/s-0043-1761487
The History of Factor XIII Deficiency
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  Authors: Dorgalaleh; Akbar
  Abstract: Despite the early discovery of factor XIII (FXIII) in 1944, the diagnosis of FXIII deficiency was not made until 1960, after all the other coagulation factor deficiencies, most likely due to the normality of routine coagulation testing in FXIII deficiency. Although the first case was detected by the clot solubility test and this test has long since been used to detect FXIII deficiency, the test is no longer recommended by experts. Over the past 60 years, knowledge about FXIII deficiency has expanded considerably, between 1992, when the first variant was identified, and 2022, 197 mutations have been reported. Almost all missense mutations have a similar effect on FXIII, leading to instability and faster degradation of mutant FXIII protein. Therapeutic options have evolved from historical fresh frozen plasma (FFP), old plasma, whole blood, and cryoprecipitate, to plasma-derived and recombinant FXIII concentrates, respectively available since 1993 and 2012. These concentrate products were respectively approved by the Food and Drug Administration in 2011 and 2013. This historical review covers various aspects of FXIII related disorders, including the discovery of the FXIII, associated disorders, molecular basis, diagnosis, and treatment of FXIII deficiency.
  Citation: Semin Thromb Hemost ; : -
  PubDate: 2023-01-27T07:17:03+0100
  DOI: 10.1055/s-0043-1761217
The Molecular Structure of Fibrinogen
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  Authors: Murano; Genesio
  Pages: Abstract: Seminars in Thrombosis and Hemostasis (STH) celebrates 50 years of publishing in 2024. To celebrate this landmark event, STH is republishing some archival material. This manuscript represents the first full paper ever published in STH. The manuscript published without an abstract, and essentially covered in considerable detail the molecular structure of fibrinogen, as was known at that time. Fittingly, it covers some historical perspectives, the physicochemical properties and structure of fibrinogen across several species of animals (including humans) and its transformation into fibrin. We hope the readers of STH enjoy this journey into the past. This manuscript is accompanied by a Commentary that reflects on this past, as well as the journey towards contemporary understanding of the molecular structure of fibrinogen. As this is a republication of archival material, transformed into a modern format, we apologise in advance for any errors introduced during this transformation.
  Citation: Semin Thromb Hemost ; : -
  PubDate: 2023-11-24T06:24:56+0100
  DOI: 10.1055/s-0043-1776311
  Issue No: Vol. eFirst

The Complex Role of Thrombin in Cancer and Metastasis: Focus on
Interactions with the Immune System

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Authors: Aleksandrowicz; Karolina, Hempel, Dominika, Polityńska, Barbara, Wojtukiewicz, Anna M., Honn, Kenneth V., Tang, Dean G., Wojtukiewicz, Marek Z.
Pages: Abstract: Thrombin, a pleiotropic enzyme involved in coagulation, plays a crucial role in both procoagulant and anticoagulant pathways. Thrombin converts fibrinogen into fibrin, initiates platelet activation, and promotes clot formation. Thrombin also activates anticoagulant pathways, indirectly inhibiting factors involved in coagulation. Tissue factor triggers thrombin generation, and the overexpression of thrombin in various cancers suggests that it is involved in tumor growth, angiogenesis, and metastasis. Increased thrombin generation has been observed in cancer patients, especially those with metastases. Thrombin exerts its effects through protease-activated receptors (PARs), particularly PAR-1 and PAR-2, which are involved in cancer progression, angiogenesis, and immunological responses. Thrombin-mediated signaling promotes angiogenesis by activating endothelial cells and platelets, thereby releasing proangiogenic factors. These functions of thrombin are well recognized and have been widely described. However, in recent years, intriguing new findings concerning the association between thrombin activity and cancer development have come to light, which justifies a review of this research. In particular, there is evidence that thrombin-mediated events interact with the immune system, and may regulate its response to tumor growth. It is also worth reevaluating the impact of thrombin on thrombocytes in conjunction with its multifaceted influence on tumor progression. Understanding the role of thrombin/PAR-mediated signaling in cancer and immunological responses is crucial, particularly in the context of developing immunotherapies. In this systematic review, we focus on the impact of the thrombin-related immune system response on cancer progression.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-11-20T10:13:39+0100
DOI: 10.1055/s-0043-1776875
Issue No: Vol. eFirst

Recommendations on the use of COVID-19 Convalescent Plasma to Treat
Immunocompromised Patients

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1776876

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-11-20T10:13:38+0100
Issue No: Vol. eFirst

The Bleeding Time Test in 2024: A Glorious Past and Current Challenges

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1776877

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-11-15T10:16:28+0100
Issue No: Vol. eFirst

Variable Performance of Lupus Anticoagulant Testing: The
Australasian/Asia-Pacific Experience

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Authors: Favaloro; Emmanuel J., Dean, Elysse, Arunachalam, Sandya
Pages: Abstract: Lupus anticoagulant (LA) is one of three tests identified as laboratory criteria for definite antiphospholipid syndrome (APS). The other two tests are anticardiolipin antibody (aCL) and anti-β2-glycoprotein I (aβ2GPI) antibody. The presence of LA is assessed using clot-based tests, while the presence of aCL and aβ2GPI is assessed by immunological assays. Since no test can be considered 100% sensitive or specific for LA, current guidelines recommend using two different clot-based assays reflecting different principles, with the dilute Russell viper venom time (dRVVT) and activated partial thromboplastin time (aPTT) recommended. Initially, LA-sensitive reagents are used to screen for LA, and then, in “screen-positive” samples, LA-“insensitive” reagents are used to confirm LA. Because LA assays are based on clot detection, anything that can interfere with fibrin clot development may affect test results. In particular, in addition to LA, the tests are also sensitive to the presence of a wide range of clinical anticoagulants, reflecting preanalytical issues for testing. We provide updated findings for LA testing in our geographic region, using recent data from the Royal College of Pathologists of Australasia Quality Assurance Programs, an international external quality assessment program with approximately 120 participants. Data show a wide variety of assays in use, especially for aPTT testing, and variable outcomes in reported numerical values with these assays when assessing proficiency samples. dRVVT testing mostly comprised reagents from three main manufacturing suppliers, which also showed differences in numerical values for the same homogeneous tested samples. Nevertheless, despite the use of different test reagents and processes,>98% of participants correctly identified LA-negative samples as LA-negative and LA-positive samples as LA positive. We hope our findings, reflecting on the heterogeneity of test processes and test data, help improve diagnostic testing for LA in the future.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-11-15T10:16:27+0100
DOI: 10.1055/s-0043-1776406
Issue No: Vol. eFirst

International Council for Standardization in Haematology Guidance for New
Lot Verification of Coagulation Reagents, Calibrators, and Controls

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Authors: Gosselin; Robert C., Castellone, Donna, Dorgalaleh, Akbar, Hickey, Kieron, Lippi, Giuseppe, Moffat, Karen, O'Toole, Rebecca, Rigano, Joe
Pages: Abstract: The clinical laboratory uses commercial products with limited shelf life or certain expiry dates requiring frequent lot changes. Prior to implementation for clinical use, laboratories should determine the performance of the new reagent lot to ensure that there is no significant shift in reagent performance or reporting of patient data. This guideline has been written on behalf of the International Council for Standardization in Haematology (ICSH) to provide the framework and provisional guidance for clinical laboratories for evaluating and verifying the performance of new lot reagents used for coagulation testing. These ICSH Working Party consensus recommendations are based on good laboratory practice, regulatory recommendations, evidence emerged from scientific publications, and expert opinion and are meant to supplement regional standards, regulations, or requirements.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-11-15T10:16:26+0100
DOI: 10.1055/s-0043-1776405
Issue No: Vol. eFirst

Description of an In Vitro Platelet Function Analyzer (PFA-100/PFA-200) 30
Years in the Making

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1776325

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-10-30T05:49:10+0100
Issue No: Vol. eFirst

Erratum: Laboratory Diagnosis of Activated Protein C Resistance and Factor
V Leiden

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1776324

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-10-25T13:33:47+01:00
Issue No: Vol. eFirst

Classification Criteria for the Antiphospholipid Syndrome: Not the Same as
Diagnostic Criteria for Antiphospholipid Syndrome

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1776318

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-10-20T11:08:19+01:00
Issue No: Vol. eFirst

In Search of the Perfect Thrombosis and Bleeding-Associated Cancer Scale

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Authors: Wojtukiewicz; Marek Z., Tesarova, Petra, Karetová, Debora, Windyga, Jerzy
Pages: Abstract: Thrombosis and bleeding are commonly observed in cancer patients, and their management is crucial for positive patient outcomes. A comprehensive, prophylactic, and therapeutic management of venous thrombosis should focus on identifying the patients who would benefit most from treatment to reduce mortality and minimize the risk of thrombosis recurrence without significantly increasing the risk of bleeding. Existing cancer scales provide valuable information for assessing the overall burden of cancer and guiding treatment decisions, but their ability to predict thrombotic and bleeding events remains limited. With increasing knowledge of the pathophysiology of cancer and the availability of advanced anticancer therapies, new risk factors for cancer-associated thrombosis and bleeding are being identified. In this report, we analyze the current literature and identify new risk factors for venous thrombosis and bleeding which are not included in routinely used risk scores. While some existing cancer scales partially capture the risk of thrombosis and bleeding, there is a need for more specific and accurate scales tailored to these complications. The development of such scales could improve risk stratification, aid in treatment selection, and enhance patient care. Therefore, further research and development of novel cancer scales focused on thrombosis and bleeding are warranted to optimize patient management and outcomes.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-10-18T12:28:07+01:00
DOI: 10.1055/s-0043-1776003
Issue No: Vol. eFirst

The Diagnostic Role of Lung Ultrasound and Contrast-Enhanced Ultrasound in
Pulmonary Embolism

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Authors: Boccatonda; Andrea, Andreetto, Lorenzo, Vicari, Susanna, Campello, Elena, Simioni, Paolo, Ageno, Walter
Pages: Abstract: The diagnosis of pulmonary embolism (PE) relies essentially on a probabilistic approach that requires careful clinical assessments, targeted laboratory tests, and the use of appropriate imaging tools. Nowadays, the diagnostic gold standard is computed tomographic pulmonary angiography. Lung ultrasound (LUS) can play a role in the diagnosis of PE mainly by allowing the visualization of peripheral lung infarctions. Hypoechoic, pleural-based parenchymal consolidation is the most typical and common finding of pulmonary infarction. More than 85% of infarct lesions are wedge-shaped, extending to the pleural surface and are localized to where the patient complains of pleuritic chest pain. Contrast-enhanced ultrasound can be performed in addition to basic ultrasound examination to ascertain nonvascularization of the consolidation, thus confirming that the lesion is an infarct. The aim of this narrative review is to summarize the latest evidence on the application of LUS to the diagnosis of PE, focusing purely on thoracic/lung signs.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-10-13T12:31:22+01:00
DOI: 10.1055/s-0043-1776006
Issue No: Vol. eFirst

Trends (2020–2022) toward Reduced Prevalence of Postcoronavirus Disease
Syndrome and Improved Quality of Life for Hospitalized Coronavirus Disease
2019 Patients with Severe Infection and Venous Thromboembolism

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Authors: Bozzani; Antonio, Arici, Vittorio, Tavazzi, Guido, Ragni, Franco, Mojoli, Francesco, Cavallini, Elena, Vugt, Floris van, Cutti, Sara, Figini, Silvia, Venturi, Alessandro, Sterpetti, Antonio V., Arbustini, Eloisa
Pages: Abstract: The coronavirus disease 2019 (COVID-19) pandemic seems to be at its end. During the first outbreak, alfa was the dominant variant, and in the two following years, delta was the dominant variant. Questions remain about the prevalence and severity of post-COVID syndrome (PCS). We compared the medium-term outcomes of a selected group of patients considered at high risk for PCS: hospitalized patients with severe COVID-19 infection who presented clinical evidence of the acute onset of venous thromboembolism. Weighted Cox regression was used to estimate the adjusted hazard ratios for the risk of early and medium-term complications and quality of life (QoL) in COVID-19 patients developing acute venous thrombo-embolism according to the period of admission to the hospital. The primary outcome was the modification of QoL at a median follow-up of 24 months in patients hospitalized for COVID-19. The secondary outcome was the modification of QoL related to COVID-19 severity. The absolute risk of mortality for hospitalized COVID-19 patients was higher during the first outbreak (risk difference, 19% [95% confidence interval [CI], 16–22%]). Patients with acute onset of thromboembolism during the first outbreak had increased mortality, hospital stay, and need for intensive care unit treatment (p
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-10-13T12:31:22+01:00
DOI: 10.1055/s-0043-1776004
Issue No: Vol. eFirst

Platelet Contributions to the (Pre)metastatic Tumor Microenvironment

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Authors: Roweth; Harvey G.
Pages: Abstract: Alongside their conventional roles in thrombosis and hemostasis, platelets have long been associated with nonhemostatic pathologies, including tumor cell metastasis. Numerous mechanistic studies have since demonstrated that the direct binding of platelets to intravascular tumor cells promotes key hallmarks of metastasis, including survival in circulation and tumor cell arrest at secondary sites. However, platelets also interact with nonmalignant cells that make up the stromal and immune compartments within both primary and metastatic tumors. This review will first provide a brief historical perspective on platelet contributions to metastatic disease before discussing the emerging roles that platelets play in creating microenvironments that likely support successful tumor cell metastasis.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-10-13T12:31:21+01:00
DOI: 10.1055/s-0043-1776005
Issue No: Vol. eFirst

Fifty Years of Fibrinogen Structure and Function

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1775857

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-10-09T08:13:27+01:00
Issue No: Vol. eFirst

Whole Blood Viscosity and Cerebral Blood Flow in Acute Ischemic Stroke

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Authors: Gyawali; Prajwal, Lillicrap, Thomas P., Esperon, Carlos G., Bhattarai, Aseem, Bivard, Andrew, Spratt, Neil
Pages: Abstract: Existing effective treatments for ischemic stroke restore blood supply to the ischemic region using thrombolysis or mechanical removal of clot. However, it is increasingly recognized that successful removal of occlusive thrombus from the large artery—recanalization, may not always be accompanied by successful restoration of blood flow to the downstream tissues—reperfusion. Ultimately, brain tissue survival depends on cerebral perfusion, and a functioning microcirculation. Because capillary diameter is often equal to or smaller than an erythrocyte, microcirculation is largely dependent on erythrocyte rheological (hemorheological) factors such as whole blood viscosity (WBV). Several studies in the past have demonstrated elevated WBV in stroke compared with healthy controls. Also, elevated WBV has shown to be an independent risk factor for stroke. Elevated WBV leads to endothelial dysfunction, decreases nitric oxide-dependent flow-mediated vasodilation, and promotes hemostatic alterations/thrombosis, all leading to microcirculation sludging. Compromised microcirculation further leads to decreased cerebral perfusion. Hence, modulating WBV through pharmacological agents might be beneficial to improve cerebral perfusion in stroke. This review discusses the effect of elevated WBV on endothelial function, hemostatic alterations, and thrombosis leading to reduced cerebral perfusion in stroke.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-10-09T08:13:27+01:00
DOI: 10.1055/s-0043-1775858
Issue No: Vol. eFirst

Thrombin Generation Markers as Predictors of Cancer-Associated Venous
Thromboembolism: A Systematic Review

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Authors: Gyldenholm; Tua, Hvas, Anne-Mette, Christensen, Thomas Decker, Larsen, Julie Brogaard
Pages: Abstract: Venous thromboembolism (VTE) is a main contributor to morbidity and mortality in cancer patients. Biomarkers with the potential to predict cancer-associated VTE are continually sought. Of these, markers of thrombin generation present a likely option. The present systematic review examines the ability of three widely used biomarkers of thrombin generation: prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and ex vivo thrombin generation, to predict VTE in both solid and hematologic adult cancer patients. Relevant studies were identified in the PubMed and Embase databases, and the review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Each study was evaluated using the quality assessment tool from the National Heart, Lung, and Blood Institute. The review protocol was published on PROSPERO with identifier CRD42022362339. In total, 24 papers were included in the review: 11 reporting data on F1.2, 9 on TAT, and 12 on ex vivo thrombin generation. The quality ratings of the included studies varied from good (n = 13), fair (n = 8), to poor (n = 3) with a high heterogenicity. However, F1.2, TAT complex, and ex vivo thrombin generation were all found to be associated with the development of VTE. This association was most pronounced for F1.2. Furthermore, the determination of F1.2 was able to improve the precision of several established risk assessment scores. In conclusion, markers of thrombin generation were found to be elevated in cancer patients with VTE, and particularly, F1.2 was found to be a promising predictor of cancer-associated VTE.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-10-09T08:13:26+01:00
DOI: 10.1055/s-0043-1775856
Issue No: Vol. eFirst

The Most Highly Cited Publications from Seminars in Thrombosis and
Hemostasis: A Data Analysis 50 Years in the Making

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1775756

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-09-27T11:52:47+01:00
Issue No: Vol. eFirst

Congenital Bleeding Disorders and COVID-19—A Systematic Literature
Review

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Authors: Dorgalaleh; Akbar, Safdari, Seyed Mehrab, Tabibian, Shadi, Shams, Mahmood, Dabbagh, Ali, Rezazadeh, Azadeh
Pages: Abstract: Hypercoagulability is a prominent feature of coronavirus disease 2019 (COVID-19) and can lead to fatal consequences. Although the impact of COVID-19 on several disorders is well-established, its effect on congenital bleeding disorders (CBDs) is not well-documented. To address this ambiguity, a systematic review was conducted on the available studies to determine the impact of COVID-19 and vaccination aimed to prevent COVID-19 on patients with CBDs. We performed a systematic literature review using relevant keywords and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol. We conducted our search on the PubMed, Scopus, and Web of Science databases until July 2023. Out of 31 included studies, 12 case series covering 770 patients with CBD and COVID-19 were further analyzed. The majority of the patients had hemophilia A (n = 352, ∼46%) or hemophilia B (n = 74, ∼10%), while the remaining patients had von Willebrand disease (n = 43, 5.6%) or rare bleeding disorders (n = 27, 3.5%). A total of 25 deaths (3.2%) and 22 intensive care unit admissions (2.8%) were recorded. Bleeding complications were reported in the majority of the 12 case series (n = 7, 58.3%) and in most of the case reports (n = 8, ∼57%), while thrombotic complications were only reported in two studies (16.6%). The mortality rate ranged from 0% in five studies (41.6%) to 5.7% and the rate of hospitalization ranged from 0 to 40%. Bleeding complications were reported in a range of 0 to 81%, while the thrombotic complication rate in one study was 6.9%. The mortality rate varied from 0 to 5.7%, and the hospitalization rate ranged from 0 to 40%. Bleeding complications were reported in a range of 0 to 81%, while the rate of thrombotic complications in one study was 6.9%. Vaccination was reported in five case series, which included 821 patients with CBDs with the majority having hemophilia A (n = 479; 67.2%) and hemophilia B (n = 85; ∼12%). The most frequently reported side effects were myalgia (6.5%), flu-like symptoms (4.8%), fever (4.7%), and headache (4%). COVID-19 in patients with CBDs appears to provoke thrombotic complications and bleeding events more frequently, as well as a higher rate of hospitalization, which may be partially due to the increased risk of bleeding events. Although it seems that patients with CBD have lower mortality rates, further studies are necessary to fully understand this, especially considering comorbidities and low number of available studies.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-09-27T11:52:47+01:00
DOI: 10.1055/s-0043-1775733
Issue No: Vol. eFirst

ABO Blood Group and the Risk of Thrombosis in Cancer Patients: A
Mini-Review

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Authors: Elsherif; Salah, Zidan, Ali, Saville, Olivia, Othman, Maha
Pages: Abstract: Cancer-associated thrombosis (CT), especially venous thromboembolism (VTE), is a common occurrence with several factors contributing to a wide diversity in thrombosis risk. The association between ABO blood groups and the risk for CT has been examined in various studies, with non-O blood type associated with an increased thrombosis risk; however, these studies have reported varying results with recognized limitations. ABO blood groups are known to be implicated in hemostasis, in an association mediated through von Willebrand factor (VWF). In this narrative review, we aim to summarize the current knowledge surrounding the role of ABO blood groups in VTE, with a particular focus on the role of VWF and other contributing risk factors on VTE occurrence. We found evidence from literature for the impact of ABO blood groups in determining the risk of VTE in healthy populations, with a limited number of studies examining this effect in cancer patients. Additionally, research on the impact of ABO on different cancer types lacks rigor, particularly in regard to other risk factors. Overall, most studies showed strong association of increased risk of VTE amongst cancer patients with non-O blood groups and increased VWF levels. This association was weaker in a few studies. Further research is needed before a solid conclusion can be made about the ABO or ABO-VWF-mediated hypercoagulability and VTE risk in various cancers. These studies will help determine if ABO typing can be an added biomarker to improve VTE risk assessment models in cancer patients.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-09-26T07:26:25+01:00
DOI: 10.1055/s-0043-1775568
Issue No: Vol. eFirst

A Perspective on How Fibrinaloid Microclots and Platelet Pathology May be
Applied in Clinical Investigations

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Authors: Pretorius; Etheresia, Kell, Douglas B.
Pages: Abstract: Microscopy imaging has enabled us to establish the presence of fibrin(ogen) amyloid (fibrinaloid) microclots in a range of chronic, inflammatory diseases. Microclots may also be induced by a variety of purified substances, often at very low concentrations. These molecules include bacterial inflammagens, serum amyloid A, and the S1 spike protein of severe acute respiratory syndrome coronavirus 2. Here, we explore which of the properties of these microclots might be used to contribute to differential clinical diagnoses and prognoses of the various diseases with which they may be associated. Such properties include distributions in their size and number before and after the addition of exogenous thrombin, their spectral properties, the diameter of the fibers of which they are made, their resistance to proteolysis by various proteases, their cross-seeding ability, and the concentration dependence of their ability to bind small molecules including fluorogenic amyloid stains. Measuring these microclot parameters, together with microscopy imaging itself, along with methodologies like proteomics and imaging flow cytometry, as well as more conventional assays such as those for cytokines, might open up the possibility of a much finer use of these microclot properties in generative methods for a future where personalized medicine will be standard procedures in all clotting pathology disease diagnoses.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-09-25T13:46:01+01:00
DOI: 10.1055/s-0043-1774796
Issue No: Vol. eFirst

Post COVID-19 Large Vessel Vasculopathy in a Previously Healthy Young Male

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1774793

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-09-25T13:46:00+01:00
Issue No: Vol. eFirst

What Role Does Microthrombosis Play in Long COVID'

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Authors: Iba; Toshiaki, Connors, Jean M., Levy, Jerrold H.
Pages: Abstract: Soon after the outbreak of coronavirus disease 2019 (COVID-19), unexplained sustained fatigue, cognitive disturbance, and muscle ache/weakness were reported in patients who had recovered from acute COVID-19 infection. This abnormal condition has been recognized as “long COVID (postacute sequelae of COVID-19 [PASC])” with a prevalence estimated to be from 10 to 20% of convalescent patients. Although the pathophysiology of PASC has been studied, the exact mechanism remains obscure. Microclots in circulation can represent one of the possible causes of PASC. Although hypercoagulability and thrombosis are critical mechanisms of acute COVID-19, recent studies have reported that thromboinflammation continues in some patients, even after the virus has cleared. Viral spike proteins and RNA can be detected months after patients have recovered, findings that may be responsible for persistent thromboinflammation and the development of microclots. Despite this theory, long-term results of anticoagulation, antiplatelet therapy, and vascular endothelial protection are inconsistent, and could not always show beneficial treatment effects. In summary, PASC reflects a heterogeneous condition, and microclots cannot explain all the presenting symptoms. After clarification of the pathomechanisms of each symptom, a symptom- or biomarker-based stratified approach should be considered for future studies.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-09-25T13:46:00+01:00
DOI: 10.1055/s-0043-1774795
Issue No: Vol. eFirst

Internal Quality Control in Hemostasis Assays

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Authors: Reilly-Stitt; Christopher, Jennings, Ian, Kitchen, Steve, Walker, Isobel D.
Pages: Abstract: Internal quality control (IQC) for routine and specialist hemostasis testing represents a mandatory requirement for assays offered by clinical laboratories under International Organization for Standardization, Code of Federal Regulations, and Clinical and Laboratory Standards Institute standards. The underlying principle is that regular IQC audits the analytical performance of automated, semiautomated, and manual methods. This review investigates IQC practices, including benefits, limitations, frequency per time period or batch, sources of material used, primary supplier, third party or in-house, plus troubleshooting when IQC falls outside acceptance criteria. To assess IQC practice, the UK National External Quality Assessment Scheme (NEQAS) Blood Coagulation distributed a questionnaire to 1,200 participants enrolled in our scheme that collected details of the local practices for IQC testing. We received returns from 127 centers that described their local practices for the frequency of IQC, the type of IQC material employed, acceptance criteria for IQC data, and troubleshooting protocols for IQC failures. The data collected as part of an NEQAS BC questionnaire confirmed that all the participants returning answers to the questionnaire meet the standards for regular IQC testing for the hemostasis assays they perform.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-09-25T13:45:59+01:00
DOI: 10.1055/s-0043-1774381
Issue No: Vol. eFirst

Editorial Compilation XIV

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1774794

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-09-25T13:45:58+01:00
Issue No: Vol. eFirst

A Novel Variant on the Thrombospondin Type-1 Repeat 2 Domain of ADAMTS13
in a Parturient with Suspected Hereditary Thrombotic Thrombocytopenic
Purpura and Unusually High ADAMTS13 Activity

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1774382

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-09-19T11:43:01+01:00
Issue No: Vol. eFirst

Welcome to Seminars in Thrombosis and Hemostasis 2024: 50 Years of
Publishing

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1772842

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-08-28T09:43:22+01:00
Issue No: Vol. eFirst

Detecting Oxygenator Thrombosis in ECMO: A Review of Current Techniques
and an Exploration of Future Directions

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Authors: Leerson; Jack, Tulloh, Andrew, Lopez, Francisco Tovar, Gregory, Shaun, Buscher, Hergen, Rosengarten, Gary
Pages: Abstract: Extracorporeal membrane oxygenation (ECMO) is a life-support technique used to treat cardiac and pulmonary failure, including severe cases of COVID-19 (coronavirus disease 2019) involving acute respiratory distress syndrome. Blood clot formation in the circuit is one of the most common complications in ECMO, having potentially harmful and even fatal consequences. It is therefore essential to regularly monitor for clots within the circuit and take appropriate measures to prevent or treat them. A review of the various methods used by hospital units for detecting blood clots is presented. The benefits and limitations of each method are discussed, specifically concerning detecting blood clots in the oxygenator, as it is concluded that this is the most critical and challenging ECMO component to assess. We investigate the feasibility of solutions proposed in the surrounding literature and explore two areas that hold promise for future research: the analysis of small-scale pressure fluctuations in the circuit, and real-time imaging of the oxygenator. It is concluded that the current methods of detecting blood clots cannot reliably predict clot volume, and their inability to predict clot location puts patients at risk of thromboembolism. It is posited that a more in-depth analysis of pressure readings using machine learning could better provide this information, and that purpose-built imaging could allow for accurate, real-time clotting analysis in ECMO components.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-08-28T09:43:21+01:00
DOI: 10.1055/s-0043-1772843
Issue No: Vol. eFirst

Celebrating 50 Years of Seminars in Thrombosis and Hemostasis: Part III

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1772841

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-08-28T09:43:20+01:00
Issue No: Vol. eFirst

Same Syndrome, Different Causes and Treatment: Path to Diagnosis and
Management of Two Interesting Cases of Acquired von Willebrand Syndrome

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1772837

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-08-28T09:43:19+01:00
Issue No: Vol. eFirst

Laser-Induced Blood Coagulation for Surgical Application: A Scoping Review

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Authors: Adly; Afnan Sedky, Adly, Mahmoud Sedky, Cuisinier, Frederic, Egea, Jean-Christophe, Panayotov, Ivan, Adly, Aya Sedky, Malthiery, Eve
Pages: Abstract: There is a lack of evidence-based reviews on the effects of laser irradiation on blood coagulation in the literature, despite a large number of clinical trials. We therefore evaluated the available evidence on laser irradiation parameters used in coagulation of blood to optimize physical parameters. We performed a literature search for recent scientific studies indexed between 2017 and 2023 using the databases of PubMed and ScienceDirect. Articles were selected based on defined inclusion and exclusion criteria, and 78 publications in total were eventually included in this scoping review. The following were found to produce significant benefits in blood coagulation for surgical application: (1) dentistry and oral surgeries: 980 nm, 27 s, 2 W, 1502.7 W/cm2, 26.5 J, 622 J/cm2, 400 μm; (2) urogenital disorders: 532 nm, 4 s, 40 W, 10600 W/cm2, 1.3 J, 424 J/cm2, 600 μm; (3) ophthalmic disorders: 810 nm, 1 s, 1 W, 3540 W/cm2, 0.75 J, 1326 J/cm2, 100 μm; (4) embryological surgeries: 1064 nm, 10 s, 25 W, 35400 W/cm2, 262.5 J, 371000 J/cm2, 332.5 μm; (5) dermatological disorders: 1064 nm, 20 W, 2440 W/cm2, 0.1 J, 24 J/cm2, 670 μm; (6) gastrointestinal disorders: 532 nm, 3 s, 20 W, 1051 W/cm2, 120 J, 26500 J/cm2, 760 μm; (7) neurological surgeries: 2.5 s, 1.5 W, 1035 W/cm2, 2 J, 1584 J/cm2, 385 μm; (8) pulmonary disorders: 1320 nm, 5s, 35 W, 12450 W/cm2, 250 J, 65000 J/cm2, 700 μm (9) cardiovascular disorders: 1064 nm, 16.5 s, 5 W, 1980.5 W/cm2, 900 J, 760 J/cm2, 400 μm. In conclusion, our scoping review identifies that combining data from all clinically heterogeneous studies suggests that laser irradiation reflects an effective method for inducing blood coagulation in several medical fields.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-08-23T11:25:34+01:00
DOI: 10.1055/s-0043-1772573
Issue No: Vol. eFirst

Safety and Efficacy of Therapeutic Anticoagulation with Subcutaneous
Unfractionated Heparin in Patients with Renal Failure

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1772706

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

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Semin Thromb Hemost ; : -2023-08-23T11:25:32+01:00
Issue No: Vol. eFirst

In Search of the Holy Grail of Artificial Hearts: Are We There Yet'

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Authors: Volod; Oksana, Colon, Modesto J., Arabía, Francisco A.
Pages: Abstract: The total artificial heart (TAH) has a long and rich history, being the product of decades of innovation, hard work, and dedication. This review examines the history of the TAH, a device that has revolutionized the treatment of end-stage biventricular heart failure. It reviews the development of the device from early concepts to the current state-of-the-art device, the SynCardia TAH, which has been implanted in over 2,000 patients worldwide. The article also discusses the challenges and successes experienced by researchers, clinicians, and patients throughout the development of TAH devices. Our focus will also be on discussing the hemostatic alterations in patients implanted with TAH and anticoagulation strategies to decrease associated thromboembolic risks. The article concludes with a look at other novel TAH devices and the future of TAH as an increasingly viable treatment for end-stage heart failure.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-08-21T09:32:02+01:00
DOI: 10.1055/s-0043-1772456
Issue No: Vol. eFirst

Are Antiphospholipid Antibodies a Surrogate Risk Factor for Thrombosis in
Sepsis'

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Authors: Thachil; Jecko, Favaloro, Emmanuel J., Lippi, Giuseppe
Pages: Abstract: Antiphospholipid syndrome (APS) is a hypercoagulable state caused by antiphospholipid antibodies (aPL). APS clinically manifests with arterial or venous or microvascular thrombi and/or pregnancy complications. It is well-known that the development of aPL can be a transient phenomenon and thus the current diagnostic criterion for APS requires repeat laboratory testing several weeks apart before a definitive diagnosis is made. However, transient presence of aPL may also be pathogenic. In this article, we attempt to give historical and clinical evidence for the importance of these antibodies, even when transient, and call for further research into mechanisms by which these antibodies may promote thrombosis and pregnancy morbidities.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-07-28T12:59:16+01:00
DOI: 10.1055/s-0043-1771268
Issue No: Vol. eFirst

Russell Viper Venom: A Journey from the Bedside to the Bench and Back to
the Bedside

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Authors: Thachil; Jecko
Pages: Abstract: Russel Viper Venom (RVV) is widely used as a diagnostic test for antiphospholipid syndrome (APS). But the history of how this venom came to be discovered is well known. Dr Patrick Russel is responsible for the identification of the venom during his work on snake bites in India while Dr Robert Macfarlane used it to staunch bleeding in persons with haemophilia. The ability to directly activate factor X led RVV to the laboratory diagnosis of APS. More recently, it has come back to clinical world with a potential for an engineered factor X activator from RVV to be used in the treatment of haemophilia.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-07-28T12:59:15+01:00
DOI: 10.1055/s-0043-1771269
Issue No: Vol. eFirst

Ischemic Stroke in Cancer: Mechanisms, Biomarkers, and Implications for
Treatment

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Authors: Costamagna; Gianluca, Navi, Babak B., Beyeler, Morin, Hottinger, Andreas F., Alberio, Lorenzo, Michel, Patrik
Pages: Abstract: Ischemic stroke is an important cause of morbidity and mortality in cancer patients. The underlying mechanisms linking cancer and stroke are not completely understood. Long-standing and more recent evidence suggests that cancer-associated prothrombotic states, along with treatment-related vascular toxicity, such as with chemotherapy and immunotherapy, contribute to an increased risk of ischemic stroke in cancer patients. Novel biomarkers, including coagulation, platelet and endothelial markers, cell-free DNA, and extracellular vesicles are being investigated for their potential to improve risk stratification and patient selection for clinical trials and to help guide personalized antithrombotic strategies. Treatment of cancer-related stroke poses unique challenges, including the need to balance the risk of recurrent stroke and other thromboembolic events with that of bleeding associated with antithrombotic therapy. In addition, how and when to restart cancer treatment after stroke remains unclear. In this review, we summarize current knowledge on the mechanisms underlying ischemic stroke in cancer, propose an etiological classification system unique to cancer-related stroke to help guide patient characterization, provide an overview of promising biomarkers and their clinical utility, and discuss the current state of evidence-based management strategies for cancer-related stroke. Ultimately, a personalized approach to stroke prevention and treatment is required in cancer patients, considering both the underlying cancer biology and the individual patient's risk profile.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-07-28T12:59:15+01:00
DOI: 10.1055/s-0043-1771270
Issue No: Vol. eFirst

Greats in the History of Thrombosis and Hemostasis

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1770772

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

Artikel in Thieme eJournals:
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Semin Thromb Hemost ; : -2023-07-10T06:05:02+01:00
Issue No: Vol. eFirst

Laboratory Diagnosis of Activated Protein C Resistance and Factor V Leiden

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Authors: Bahraini; Mehran, Fazeli, Alieh, Dorgalaleh, Akbar
Pages: Abstract: The factor V Leiden (FVL) polymorphism is known as the most common inherited risk factor for venous thrombosis. In turn, FVL is the leading cause of an activated protein C resistance (APCR) phenotype, in which the addition of exogenous activated protein C to plasma does not result in the expected anticoagulant effect. In the routine laboratory approach to the formal diagnosis of FVL, an initial positive screening plasma-based method for APCR is often performed, and only if needed, this is followed by a confirmatory DNA-based assay for FVL. Multiple methods with accepted sensitivity and specificity for determining an APCR/FVL phenotype are commonly categorized into two separate groups: (1) screening plasma-based assays, including qualitative functional clot-based assays, for APCR, and (2) confirmatory DNA-based molecular assays, entailing several tests and platforms, including polymerase chain reaction-based and non-PCR-based techniques, for FVL. This review will describe the methodological aspects of each laboratory test and prepare suggestions on the indication of APCR and FVL testing and method selection.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-07-10T06:05:02+01:00
DOI: 10.1055/s-0043-1770773
Issue No: Vol. eFirst

Fibrin Clot Properties in Cancer: Impact on Cancer-Associated Thrombosis

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Authors: Ząbczyk; Michał, Undas, Anetta
Pages: Abstract: Cancer is associated with a high risk of venous thromboembolism (VTE) and its recurrence. There is evidence that the prothrombotic fibrin clot phenotype, involving the formation of denser and stiffer clots relatively resistant to lysis, occurs in cancer patients, which is in part related to enhanced inflammation, oxidative stress, and coagulation activation, along with the release of neutrophil extracellular traps, indicating that fibrin-related mechanisms might contribute to cancer-associated thrombosis (CAT). Multiple myeloma and its therapy have been most widely explored in terms of altered fibrin characteristics, but prothrombotic fibrin clot features have also been reported in patients with active solid cancer, including lung cancer and gastrointestinal cancer. Patient-related factors such as advanced age, smoking, and comorbidities might also affect fibrin clot characteristics and the risk of CAT. Prothrombotic fibrin clot features have been shown to predict the detection of cancer in patients following VTE during follow-up. Cancer-specific therapies and anticoagulation can favorably modify the phenotype of a fibrin clot, which may alter the course of CAT. It is unclear whether the fibrin clot phenotype might help identify patients with CAT who are more likely to experience recurrent events. This narrative review summarizes the current knowledge on the role of fibrin clot structure and function in cancer patients in the context of CAT.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-06-23T13:39:24+01:00
DOI: 10.1055/s-0043-1770364
Issue No: Vol. eFirst

D-dimer in Coronavirus 2019: An Acute Phase Reactant'

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1770365

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

Artikel in Thieme eJournals:
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Semin Thromb Hemost ; : -2023-06-23T13:39:23+01:00
Issue No: Vol. eFirst

Epidemiology and Predisposing Factors of Post-COVID Venous Thrombosis: A
Concise Review

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Authors: Lippi; Giuseppe, Favaloro, Emmanuel J.
Pages: Abstract: Long-coronavirus disease 2019 (COVID-19) represents a heterogeneous clinical syndrome characterized by a pathologic continuum of signs, symptoms, and also laboratory/radiologic abnormalities that may persist for a long time after recovering from an acute severe acute respiratory syndrome-coronavirus disease 2 infection. Among the various components of this postviral condition, the risk of venous thromboembolism in patients hospitalized for COVID-19 remains considerably higher after discharge, especially in older individuals, in men, in patients with longer hospital stays and more aggressive treatment (e.g., mechanical ventilation and/or intensive care), when thromboprophylaxis is not used, and in those with a persistent prothrombotic state. Patients who have these predisposing factors should be monitored more closely to intercept any thrombosis that may occur in a post-COVID time-related manner but may also benefit from extended thromboprophylaxis and/or antiplatelet therapy.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-06-16T12:16:59+01:00
DOI: 10.1055/s-0043-1770051
Issue No: Vol. eFirst

Applications of Viscoelastic Testing in Breast Cancer Patients: A

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Authors: Pamulapati; Saagar, Conroy, Meghan, Madireddy, Sathwik, Kamaraju, Sailaja, Cortina, Chandler, Moore, Hunter, Hartmann, Jan
Pages: Abstract: Viscoelastic testing is a clinically available method to assess hypercoagulability. This systematic review aims to provide a comprehensive overview of the existing literature and the potential use of such testing in patients with breast cancer. A systematic literature search for studies investigating the application of viscoelastic testing for patients with breast cancer was conducted. Studies were included as long as they were original, peer-reviewed, and in the English language. Studies were excluded if they were review articles, did not include breast cancer patients, or if the full text was unavailable. This review identified 10 articles that met the inclusion criteria. Two of the studies utilized rotational thromboelastometry, and an additional four studies used thromboelastography, to assess hypercoagulability in patients with breast cancer. Three of the identified articles discussed the use of thromboelastometry in free flap breast reconstruction for patients with breast cancer. One study was a retrospective chart review looking at thromboelastography and microsurgical breast reconstruction. Current literature regarding the application of viscoelastic testing in breast cancer and free flap breast reconstruction is limited, with no randomized trials thus far. However, some studies suggest that there may be potential utility in viscoelastic testing to assess risk for thromboembolism in breast cancer patients, and future research in this area is warranted.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-06-16T12:16:59+01:00
DOI: 10.1055/s-0043-1769937
Issue No: Vol. eFirst

Effects of Recombinant SARS-CoV-2 Spike Protein Variants on Platelet
Morphology and Activation

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Authors: Vettori; Marco, Carpenè, Giovanni, Salvagno, Gian Luca, Gelati, Matteo, Dima, Francesco, Celegon, Giovanni, Favaloro, Emmanuel J., Lippi, Giuseppe
Pages: Abstract: Platelets are central elements of hemostasis and also play a pivotal role in the pathogenesis of thrombosis in coronavirus disease 2019. This study was planned to investigate the effects of different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant spike protein variants on platelet morphology and activation. Citrated whole blood collected from ostensibly healthy subjects was challenged with saline (control sample) and with 2 and 20 ng/mL final concentration of SARS-CoV-2 recombinant spike protein of Ancestral, Alpha, Delta, and Omicron variants. Platelet count was found to be decreased with all SARS-CoV-2 recombinant spike protein variants and concentrations tested, achieving the lowest values with 20 ng/mL Delta recombinant spike protein. The mean platelet volume increased in all samples irrespective of SARS-CoV-2 recombinant spike protein variants and concentrations tested, but especially using Delta and Alpha recombinant spike proteins. The values of both platelet function analyzer-200 collagen-adenosine diphosphate and collagen-epinephrine increased in all samples irrespective of SARS-CoV-2 recombinant spike protein variants and concentrations tested, and thus reflecting platelet exhaustion, and displaying again higher increases with Delta and Alpha recombinant spike proteins. Most samples where SARS-CoV-2 recombinant spike proteins were added were flagged as containing platelet clumps. Morphological analysis revealed the presence of a considerable number of activated platelets, platelet clumps, platelet-monocyte, and platelet-neutrophils aggregates, especially in samples spiked with Alpha and Delta recombinant spike proteins at 20 ng/mL. These results provide support to the evidence that SARS-CoV-2 is capable of activating platelets through its spike protein, though such effect varies depending on different spike protein variants.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-06-16T12:16:58+01:00
DOI: 10.1055/s-0043-1769939
Issue No: Vol. eFirst

Factor XII Structure–Function Relationships

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Authors: Shamanaev; Aleksandr, Litvak, Maxim, Ivanov, Ivan, Srivastava, Priyanka, Sun, Mao-Fu, Dickeson, S. Kent, Kumar, Sunil, He, Tracey Z., Gailani, David
Pages: Abstract: Factor XII (FXII), the zymogen of the protease FXIIa, contributes to pathologic processes such as bradykinin-dependent angioedema and thrombosis through its capacity to convert the homologs prekallikrein and factor XI to the proteases plasma kallikrein and factor XIa. FXII activation and FXIIa activity are enhanced when the protein binds to a surface. Here, we review recent work on the structure and enzymology of FXII with an emphasis on how they relate to pathology. FXII is a homolog of pro-hepatocyte growth factor activator (pro-HGFA). We prepared a panel of FXII molecules in which individual domains were replaced with corresponding pro-HGFA domains and tested them in FXII activation and activity assays. When in fluid phase (not surface bound), FXII and prekallikrein undergo reciprocal activation. The FXII heavy chain restricts reciprocal activation, setting limits on the rate of this process. Pro-HGFA replacements for the FXII fibronectin type 2 or kringle domains markedly accelerate reciprocal activation, indicating disruption of the normal regulatory function of the heavy chain. Surface binding also enhances FXII activation and activity. This effect is lost if the FXII first epidermal growth factor (EGF1) domain is replaced with pro-HGFA EGF1. These results suggest that FXII circulates in blood in a “closed” form that is resistant to activation. Intramolecular interactions involving the fibronectin type 2 and kringle domains maintain the closed form. FXII binding to a surface through the EGF1 domain disrupts these interactions, resulting in an open conformation that facilitates FXII activation. These observations have implications for understanding FXII contributions to diseases such as hereditary angioedema and surface-triggered thrombosis, and for developing treatments for thrombo-inflammatory disorders.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-06-05T06:36:21+01:00
DOI: 10.1055/s-0043-1769509
Issue No: Vol. eFirst

Increased Levels of Inflammatory and Endothelial Biomarkers in Blood of
Long COVID Patients Point to Thrombotic Endothelialitis

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Authors: Turner; Simone, Naidoo, Caitlin A., Usher, Thomas J., Kruger, Arneaux, Venter, Chantelle, Laubscher, Gert J., Khan, M Asad, Kell, Douglas B., Pretorius, Etheresia
Pages: Abstract: The prevailing hypotheses for the persistent symptoms of Long COVID have been narrowed down to immune dysregulation and autoantibodies, widespread organ damage, viral persistence, and fibrinaloid microclots (entrapping numerous inflammatory molecules) together with platelet hyperactivation. Here we demonstrate significantly increased concentrations of von Willebrand factor (VWF), platelet factor 4 (PF4), serum amyloid A (SAA), α-2 antiplasmin (α-2AP), endothelial-leukocyte adhesion molecule 1 (E-selectin), and platelet endothelial cell adhesion molecule (PECAM-1) in the soluble part of the blood. It was noteworthy that the mean level of α-2 antiplasmin exceeded the upper limit of the laboratory reference range in Long COVID patients, and the other 5 were significantly elevated in Long COVID patients as compared to the controls. This is alarming if we take into consideration that a significant amount of the total burden of these inflammatory molecules has previously been shown to be entrapped inside fibrinolysis-resistant microclots (thus decreasing the apparent level of the soluble molecules). We conclude that presence of microclotting, together with relatively high levels of six biomarkers known to be key drivers of endothelial and clotting pathology, points to thrombotic endothelialitis as a key pathological process in Long COVID.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-05-19T11:34:18+01:00
DOI: 10.1055/s-0043-1769014
Issue No: Vol. eFirst

Prevention of Venous Thromboembolism in Medical Patients with
Thrombocytopenia or with Platelet Dysfunction: The Last 10 Years

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Authors: Tufano; Antonella, Brenner, Benjamin
Pages: Abstract: Current guideline recommendations for primary prophylaxis of venous thromboembolism (VTE) are based on randomized clinical trials that usually exclude subjects at a potentially high risk of bleeding complications. For this reason, no specific guideline is available for thromboprophylaxis in hospitalized patients with thrombocytopenia and/or platelet dysfunction. However, except in patients with absolute contraindications to anticoagulant drugs, antithrombotic prophylaxis should always be considered, for example, in hospitalized cancer patients with thrombocytopenia, especially in those with multiple VTE risk factors. Low platelet number, platelet dysfunction, and clotting abnormalities are also very common in patients with liver cirrhosis, but these patients have a high incidence of portal venous thrombosis, implying that cirrhotic coagulopathy does not fully protect against thrombosis. These patients may benefit from antithrombotic prophylaxis during hospitalization. Patients hospitalized for COVID-19 need prophylaxis, but frequently experience thrombocytopenia or coagulopathy. In patients with antiphospholipid antibodies, a high thrombotic risk is usually present, even in the presence of thrombocytopenia. VTE prophylaxis in high-risk conditions is thus suggested in these patients. At variance with severe thrombocytopenia (< 50,000/mm3), mild/moderate thrombocytopenia (≥ 50,000/mm3) should not interfere with VTE prevention decisions. In patients with severe thrombocytopenia, pharmacological prophylaxis should be considered on an individual basis. Aspirin is not as effective as heparins in lowering the risk of VTE. Studies in patients with ischemic stroke demonstrated that thromboprophylaxis with heparins is safe in these patients also during antiplatelet treatment. The use of direct oral anticoagulants in the prophylaxis of VTE in internal medicine patients has been recently evaluated, but no specific recommendation exists for patients with thrombocytopenia. The need for VTE prophylaxis in patients on chronic treatment with antiplatelet agents should be evaluated after assessing the individual risk of bleeding complications. Finally, the selection of patients who require post-discharge pharmacological prophylaxis remains debated. New molecules currently under development (such as the inhibitors of factor XI) may contribute to improve the risk/benefit ratio of VTE primary prevention in this setting of patients.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-05-18T11:30:38+01:00
DOI: 10.1055/s-0043-1769013
Issue No: Vol. eFirst

Human Genetic Variation in F3 and Its Impact on Tissue
Factor–Dependent Disease

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Authors: Park; Jin K., Brake, Marisa A., Schulman, Sol
Pages: Abstract: Tissue factor (TF) is the primary initiator of blood coagulation in humans. As improper intravascular TF expression and procoagulant activity underlie numerous thrombotic disorders, there has been longstanding interest in the contribution of heritable genetic variation in F3, the gene encoding TF, to human disease. This review seeks to comprehensively and critically synthesize small case–control studies focused on candidate single nucleotide polymorphisms (SNPs), as well as modern genome-wide association studies (GWAS) seeking to discover novel associations between variants and clinical phenotypes. Where possible, correlative laboratory studies, expression quantitative trait loci, and protein quantitative trait loci are evaluated to glean potential mechanistic insights. Most disease associations implicated in historical case–control studies have proven difficult to replicate in large GWAS. Nevertheless, SNPs linked to F3, such as rs2022030, are associated with increased F3 mRNA expression, monocyte TF expression after endotoxin exposure, and circulating levels of the prothrombotic biomarker D-dimer, consistent with the central role of TF in the initiation of blood coagulation.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-05-18T11:30:37+01:00
DOI: 10.1055/s-0043-1769079
Issue No: Vol. eFirst

The Role of CD36/GPIV in Platelet Biology

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Authors: Bendas; Gerd, Schlesinger, Martin
Pages: Abstract: CD36 (also known as platelet glycoprotein IV) is expressed by a variety of different cell entities, where it possesses functions as a signaling receptor, but additionally acts as a transporter for long-chain fatty acids. This dual function of CD36 has been investigated for its relevance in immune and nonimmune cells. Although CD36 was first identified on platelets, the understanding of the role of CD36 in platelet biology remained scarce for decades. In the past few years, several discoveries have shed a new light on the CD36 signaling activity in platelets. Notably, CD36 has been recognized as a sensor for oxidized low-density lipoproteins in the circulation that mitigates the threshold for platelet activation under conditions of dyslipidemia. Thus, platelet CD36 transduces atherogenic lipid stress into an increased risk for thrombosis, myocardial infarction, and stroke. The underlying pathways that are affected by CD36 are the inhibition of cyclic nucleotide signaling pathways and simultaneously the induction of activatory signaling events. Furthermore, thrombospondin-1 secreted by activated platelets binds to CD36 and furthers paracrine platelet activation. CD36 also serves as a binding hub for different coagulation factors and, thus, contributes to the plasmatic coagulation cascade. This review provides a comprehensive overview of the recent findings on platelet CD36 and presents CD36 as a relevant target for the prevention of thrombotic events for dyslipidemic individuals with an elevated risk for thrombosis.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-05-16T06:50:56+01:00
DOI: 10.1055/s-0043-1768935
Issue No: Vol. eFirst

Hematohidrosis in 15th Century Renaissance Art and a Review of Modern
Literature

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1768937

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

Artikel in Thieme eJournals:
Inhaltsverzeichnis     Volltext
Semin Thromb Hemost ; : -2023-05-16T06:50:55+01:00
Issue No: Vol. eFirst

Inhibitors of Polyphosphate and Neutrophil Extracellular Traps

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Authors: Vappala; Sreeparna, Smith, Stephanie A., Kizhakkedathu, Jayachandran N., Morrissey, James H.
Pages: Abstract: The contact pathway of blood clotting has received intense interest in recent years as studies have linked it to thrombosis, inflammation, and innate immunity. Because the contact pathway plays little to no role in normal hemostasis, it has emerged as a potential target for safer thromboprotection, relative to currently approved antithrombotic drugs which all target the final common pathway of blood clotting. Research since the mid-2000s has identified polyphosphate, DNA, and RNA as important triggers of the contact pathway with roles in thrombosis, although these molecules also modulate blood clotting and inflammation via mechanisms other than the contact pathway of the clotting cascade. The most significant source of extracellular DNA in many disease settings is in the form of neutrophil extracellular traps (NETs), which have been shown to contribute to incidence and severity of thrombosis. This review summarizes known roles of extracellular polyphosphate and nucleic acids in thrombosis, with an emphasis on novel agents under current development that target the prothrombotic activities of polyphosphate and NETs.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-05-16T06:50:55+01:00
DOI: 10.1055/s-0043-1768936
Issue No: Vol. eFirst

Why Does Rivaroxaban Not Work in Severe Mitral Stenosis'

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Semin Thromb Hemost
DOI: 10.1055/s-0043-1768938

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

Artikel in Thieme eJournals:
Inhaltsverzeichnis     Volltext
Semin Thromb Hemost ; : -2023-05-09T06:43:23+01:00
Issue No: Vol. eFirst

Perioperative Monitoring with Rotational Thromboelastometry in a Severe
Hemophilia A Patient Undergoing Elective Ankle Surgery

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Semin Thromb Hemost
DOI: 10.1055/s-0043-57009

Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

Artikel in Thieme eJournals:
Inhaltsverzeichnis     Volltext
Semin Thromb Hemost ; : -2023-04-19T12:53:14+01:00
Issue No: Vol. eFirst

Plasma Kallikrein as a Forgotten Clotting Factor

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Authors: Kearney; Katherine J., Spronk, Henri M.H., Emsley, Jonas, Key, Nigel S., Philippou, Helen
Pages: Abstract: For decades, it was considered that plasma kallikrein's (PKa) sole function within the coagulation cascade is the activation of factor (F)XII. Until recently, the two key known activators of FIX within the coagulation cascade were activated FXI(a) and the tissue factor–FVII(a) complex. Simultaneously, and using independent experimental approaches, three groups identified a new branch of the coagulation cascade, whereby PKa can directly activate FIX. These key studies identified that (1) FIX or FIXa can bind with high affinity to either prekallikrein (PK) or PKa; (2) in human plasma, PKa can dose dependently trigger thrombin generation and clot formation independent of FXI; (3) in FXI knockout murine models treated with intrinsic pathway agonists, PKa activity results in increased formation of FIXa:AT complexes, indicating direct activation of FIX by PKa in vivo. These findings suggest that there is both a canonical (FXIa-dependent) and non-canonical (PKa-dependent) pathway of FIX activation. These three recent studies are described within this review, alongside historical data that hinted at the existence of this novel role of PKa as a coagulation clotting factor. The implications of direct PKa cleavage of FIX remain to be determined physiologically, pathophysiologically, and in the context of next-generation anticoagulants in development.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-04-18T11:33:27+01:00
DOI: 10.1055/s-0043-57034
Issue No: Vol. eFirst

The Pitfalls of Global Hemostasis Assays in Myeloproliferative Neoplasms
and Future Challenges

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Authors: Tiu; Andrew, Chiasakul, Thita, Kessler, Craig M.
Pages: Abstract: Venous and arterial thromboembolism are major complications of myeloproliferative neoplasms (MPNs), comprising polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Global hemostasis assays, including thrombin generation assay (TGA), rotational thromboelastometry (ROTEM), and thromboelastography (TEG), have been proposed as biomarkers to assess the hypercoagulability and thrombotic risk stratification in MPNs. We performed a systematic literature review on the parameters of TGA, ROTEM, and TEG and their association with thrombotic events and treatment strategies in MPNs. Thirty-two studies (all cross-sectional) were included, which collectively enrolled 1,062 controls and 1,608 MPN patients. Among the 13 studies that reported arterial or venous thrombosis, the overall thrombosis rate was 13.8% with 6 splanchnic thromboses reported. Out of the 27 TGA studies, there was substantial heterogeneity in plasma preparation and trigger reagents employed in laboratory assays. There was a trend toward increased peak height among all MPN cohorts versus controls and higher endogenous thrombin potential (ETP) between ET patients versus controls. There was an overall trend toward lower ETP between PV and PMF patients versus. controls. There were no substantial differences in ETP between JAK2-positive versus JAK2-negative MPNs, prior history versus negative history of thrombotic events, and among different treatment strategies. Of the three ROTEM studies, there was a trend toward higher maximum clot firmness and shorter clot formation times for all MPNs versus controls. The three TEG studies had mixed results. We conclude that the ability of parameters from global hemostasis assays to predict for hypercoagulability events in MPN patients is inconsistent and inconclusive. Further prospective longitudinal studies are needed to validate these biomarker tools so that thrombotic potential could be utilized as a primary endpoint of such studies.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-04-17T08:13:22+01:00
DOI: 10.1055/s-0043-57010
Issue No: Vol. eFirst

Targeting the Contact Pathway of Coagulation for the Prevention and
Management of Medical Device-Associated Thrombosis

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Authors: Goel; Abhishek, Tathireddy, Harsha, Wang, Si-Han, Vu, Helen H., Puy, Cristina, Hinds, Monica T., Zonies, David, McCarty, Owen J.T., Shatzel, Joseph J.
Pages: Abstract: Hemorrhage remains a major complication of anticoagulants, with bleeding leading to serious and even life-threatening outcomes in rare settings. Currently available anticoagulants target either multiple coagulation factors or specifically coagulation factor (F) Xa or thrombin; however, inhibiting these pathways universally impairs hemostasis. Bleeding complications are especially salient in the medically complex population who benefit from medical devices. Extracorporeal devices—such as extracorporeal membrane oxygenation, hemodialysis, and cardiac bypass—require anticoagulation for optimal use. Nonetheless, bleeding complications are common, and with certain devices, highly morbid. Likewise, pharmacologic prophylaxis to prevent thrombosis is not commonly used with many medical devices like central venous catheters due to high rates of bleeding. The contact pathway members FXI, FXII, and prekallikrein serve as a nexus, connecting biomaterial surface-mediated thrombin generation and inflammation, and may represent safe, druggable targets to improve medical device hemocompatibility and thrombogenicity. Recent in vivo and clinical data suggest that selectively targeting the contact pathway of coagulation through the inhibition of FXI and FXII can reduce the incidence of medical device-associated thrombotic events, and potentially systemic inflammation, without impairing hemostasis. In the following review, we will outline the current in vivo and clinical data encompassing the mechanism of action of drugs targeting the contact pathway. This new class of inhibitors has the potential to herald a new era of effective and low-risk anticoagulation for the management of patients requiring the use of medical devices.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-04-12T11:52:22+01:00
DOI: 10.1055/s-0043-57011
Issue No: Vol. eFirst

A Brief History of Hemostasis and Thrombosis at the Mayo Clinic

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Authors: Chen; Dong, Pruthi, Rajiv
Pages: Abstract: Coagulation is a crucial biological mechanism in human bodies to prevent blood loss. Abnormal coagulation can cause bleeding diathesis or thrombosis, common pathologic conditions in our clinical practice. Many individuals and organizations have dedicated their efforts in the past decades to understanding the biological and pathological mechanisms of coagulation and developing laboratory testing tools and treatment options to help patients with bleeding or thrombotic conditions. Since 1926, the Mayo Clinic coagulation group has made significant contributions to the clinical and laboratory practice, basic and translational research on various hemostatic and thrombotic disorders, and the education and collaboration to share and advance our knowledge in coagulation through a highly integrated team and practice model. We would like to use this review to share our history and inspire medical professionals and trainees to join the efforts to advance our understanding of coagulation pathophysiology and improve our care for patients with coagulation disorders.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-03-20T05:51:37+0100
DOI: 10.1055/s-0043-1764470
Issue No: Vol. eFirst

Substrates, Cofactors, and Cellular Targets of Coagulation Factor XIa

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Authors: Lira; André L., Kohs, Tia C.L., Moellmer, Samantha A., Shatzel, Joseph J., McCarty, Owen J.T., Puy, Cristina
Pages: Abstract: Coagulation factor XI (FXI) has increasingly been shown to play an integral role in several physiologic and pathological processes. FXI is among several zymogens within the blood coagulation cascade that are activated by proteolytic cleavage, with FXI converting to the active serine protease form (FXIa). The evolutionary origins of FXI trace back to duplication of the gene that transcribes plasma prekallikrein, a key factor in the plasma kallikrein–kinin system, before further genetic divergence led to FXI playing a unique role in blood coagulation. While FXIa is canonically known for activating the intrinsic pathway of coagulation by catalyzing the conversion of FIX into FIXa, it is promiscuous in nature and has been shown to contribute to thrombin generation independent of FIX. In addition to its role in the intrinsic pathway of coagulation, FXI also interacts with platelets, endothelial cells, and mediates the inflammatory response through activation of FXII and cleavage of high-molecular-weight kininogen to generate bradykinin. In this manuscript, we critically review the current body of knowledge surrounding how FXI navigates the interplay of hemostasis, inflammatory processes, and the immune response and highlight future avenues for research. As FXI continues to be clinically explored as a druggable therapeutic target, understanding how this coagulation factor fits into physiological and disease mechanisms becomes increasingly important.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-03-20T05:51:36+0100
DOI: 10.1055/s-0043-1764469
Issue No: Vol. eFirst

Novel Insights into Heterozygous Factor XIII Deficiency

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Authors: Dorgalaleh; Akbar
Pages: Abstract: The prevalence and clinical significance of heterozygous factor XIII (FXIII) deficiency has long been debated, with controversial reports emerging since 1988. In the absence of large epidemiologic studies, but based on a few studies, a prevalence of 1 per 1,000 to 5,000 is estimated. In southeastern Iran, a hotspot area for the disorder, a study of more than 3,500 individuals found an incidence of 3.5%. Between 1988 and 2023, a total of 308 individuals were found with heterozygous FXIII deficiency, of which molecular, laboratory, and clinical presentations were available for 207 individuals. A total of 49 variants were found in the F13A gene, most of which were missense (61.2%), followed by nonsense (12.2%) and small deletions (12.2%), most occurring in the catalytic domain (52.1%) of the FXIII-A protein and most frequently in exon 4 (17%) of the F13A gene. This pattern is relatively similar to homozygous (severe) FXIII deficiency. In general, heterozygous FXIII deficiency is an asymptomatic condition without spontaneous bleeding tendency, but it can lead to hemorrhagic complications in hemostatic challenges such as trauma, surgery, childbirth, and pregnancy. Postoperative bleeding, postpartum hemorrhage, and miscarriage are the most common clinical manifestations, while impaired wound healing has been rarely reported. Although some of these clinical manifestations can also be observed in the general population, they are more common in heterozygous FXIII deficiency. While studies of heterozygous FXIII deficiency conducted over the past 35 years have shed light on some of the ambiguities of this condition, further studies on a large number of heterozygotes are needed to answer the major questions related to heterozygous FXIII deficiency.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-03-20T05:51:35+0100
DOI: 10.1055/s-0043-1764471
Issue No: Vol. eFirst

Pediatric Presentation of Antiphospholipid Syndrome: A Review of Recent
Literature With Estimation of Local Prevalence

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Authors: Radin; Massimo, Cecchi, Irene, Arbrile, Marta, Montin, Davide, Farinasso, Loredana, Cioffi, Michele, Foddai, Silvia Grazietta, Barinotti, Alice, Menegatti, Elisa, Baldovino, Simone, Sciascia, Savino, Roccatello, Dario
Pages: Abstract: We aimed to investigate the epidemiology, the clinical and laboratory characteristics of the pediatric involvement of antiphospholipid syndrome (APS), by performing a review of the current evidence and reviewing local experience in the Northwest Italy. To achieve this, we performed a detailed literature search to identify articles describing clinical and laboratory characteristics of pediatric APS. In concomitance, we conducted a registry-based study collecting data from the Piedmont and Aosta Valley Rare Disease Registry including pediatric patients diagnosed with APS in the last 11 years. The literature review led to inclusion of six articles with a total of 386 pediatric patients (65% females, 50% with systemic lupus erythematosus (SLE) as concomitant diagnosis). Rates of venous and arterial thrombosis were 57 and 35%, respectively. “Extra-criteria manifestations” included mostly hematologic and neurologic involvement. Almost one-quarter of patients (19%) reported recurrent events and 13% manifested as catastrophic APS. A total of 17 pediatric patients (mean age 15.1 ± 2.8, 76% female) developed APS in the Northwest of Italy. In 29% of cases, SLE was a concomitant diagnosis. Deep vein thrombosis was the most frequent manifestation (28%) followed by catastrophic APS (6%). The estimated prevalence of pediatric APS in Piedmont and Aosta Valley Region is 2.5/100,000 people, whereas the estimated annual incidence is 0.2/100,000 inhabitants. In conclusion, clinical manifestations of pediatric APS seem to be more severe and with a high prevalence of noncriteria manifestations. International efforts are needed to better characterize this condition and to develop new specific diagnostic criteria to avoid missed/delayed diagnosis in children with APS.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-03-20T05:51:34+0100
DOI: 10.1055/s-0043-1764472
Issue No: Vol. eFirst

Platelet Parameters as Biomarkers for Thrombosis Risk in Cancer: A
Systematic Review and Meta-analysis

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Authors: Malte; Anne Lind, Højbjerg, Johanne Andersen, Larsen, Julie Brogaard
Pages: Abstract: Cancer-associated thrombosis (CAT) is a major cause of both morbidity and mortality in cancer patients. Platelet count has been investigated as a predictor of CAT in various settings while knowledge on platelet activation parameters is sparse. This report provides a systematic review and meta-analysis on available literature on associations between platelet count and/or function and arterial and venous thrombosis in adult cancer patients. The review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. PubMed and Embase were searched up to March 2022. The National Heart, Lung, and Blood Institute's tools were used for quality assessment. In total, 100 studies were included which investigated the association between CAT and platelet count (n = 90), platelet indices (n = 19), and platelet function/activation markers (n = 13) in patients with solid cancers (n = 61), hematological cancers (n = 17), or mixed cancer types (n = 22). Eighty-one studies had venous thrombosis as their outcome measure, while 4 had arterial thrombosis and 15 studies had both. We found significantly elevated odds ratio of 1.50 (95% confidence interval: 1.19–1.88) for thrombosis with higher platelet counts. We saw a tendency toward an association between markers of platelet activation in forms of mean platelet volume and soluble P selectin and both arterial and venous thrombosis. Only one study investigated dynamic platelet function using flow cytometry. In conclusion, platelet count is associated with CAT across different cancer types and settings. Platelet function or activation marker analysis may be valuable in assisting thrombosis risk assessment in cancer patients but is sparsely investigated so far.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-03-15T12:20:53+0100
DOI: 10.1055/s-0043-1764381
Issue No: Vol. eFirst

Contraceptives and Thrombosis: An Intertwined Revolutionary Road

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Authors: Barcellona; Doris, Marongiu, Francesco, Grandone, Elvira
Pages: Abstract: The development of oral contraceptives (OCs) began in 1921 and continued in the following years until the first regulatory approval from the Food and Drug Administration was granted in 1960. However, it took several years to realize that OCs presented an important but not frequent risk of venous thrombosis. Several reports ignored this dangerous effect and only in 1967 the Medical Research Council clearly stated this as an important risk. Later, research led to the formulation of second-generation OCs containing progestins, which nevertheless presented an increased thrombotic risk. In early 1980s, OCs containing third-generation progestins were introduced into the market. Only in 1995, it became clear that these new compounds induced a higher thrombotic risk than that related to the second-generation progestins. It appeared clear that the modulating action of progestins was against the procoagulant activity of estrogens. Lastly, at the end of the 2000s, OCs containing natural estrogens and a fourth-generation progestin (dienogest) became available. The prothrombotic effect of those natural products was not different from that of preparations containing second-generation progestins. Moreover, research over the years has produced much data on risk factors associated with OCs use such as age, obesity, cigarette smoking, and thrombophilia. These findings allowed us to better assess the individual thrombotic risk (both arterial and thrombotic) of each woman before offering an OC. Furthermore, research has shown that in high-risk people the use of single progestin is not dangerous as far as thrombosis is concerned. In conclusion, the OCs road has been long and difficult but has led to a great and unthinkable scientific and social enrichment since the 1960s.
Citation: Semin Thromb Hemost ; : -
PubDate: 2023-03-13T06:16:28+0100
DOI: 10.1055/s-0043-1764382
Issue No: Vol. eFirst