Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Transcription factor RUNX1 regulates coagulation factor XIII-A (F13A1): decreased platelet-megakaryocyte F13A1 expression and clot contraction in RUNX1 haplodeficiency","authors":"Fabiola Del Carpio-Cano ,&nbsp;Natthapol Songdej ,&nbsp;Liying Guan ,&nbsp;Guangfen Mao ,&nbsp;Lawrence E. Goldfinger ,&nbsp;Jeremy G.T. Wurtzel ,&nbsp;Kiwon Lee ,&nbsp;Michele P. Lambert ,&nbsp;Mortimer Poncz ,&nbsp;A. Koneti Rao","doi":"10.1016/j.rpth.2025.102680","DOIUrl":"10.1016/j.rpth.2025.102680","url":null,"abstract":"<div><h3>Background</h3><div>Germline <em>RUNX1</em> haplodeficiency (RHD) is associated with thrombocytopenia, platelet dysfunction, and predisposition to myeloid malignancies. Platelet expression profiling of an RHD patient showed decreased <em>F13A1</em>, encoding for the A subunit of factor (F)XIII<em>,</em> a transglutaminase that cross-links fibrin and induces clot stabilization. FXIII-A is synthesized by hematopoietic cells, megakaryocytes, and monocytes.</div></div><div><h3>Objectives</h3><div>To understand RUNX1 regulation of <em>F13A1</em> expression in platelets/megakaryocytes and the mechanisms and consequences of decreased <em>F13A1</em> in RHD.</div></div><div><h3>Methods</h3><div>We performed studies in platelets, human erythroleukemia (HEL) cells, and human CD34+ cell-derived megakaryocytes including on clot contraction in cells following small inhibitor RNA knockdown (KD) of RUNX1 or F13A1.</div></div><div><h3>Results</h3><div>Platelet <em>F13A1</em> mRNA and protein were decreased in our index patient and in 2 siblings from an unrelated family with RHD. Platelet-driven clot contraction was decreased in the patient and affected daughter. Promoter studies in HEL cells showed that <em>RUNX1</em> regulates <em>F13A1</em> transcription<em>;</em> RUNX1 overexpression increased, and small inhibitor RNA RUNX1 KD reduced <em>F13A1</em> promoter activity and protein. Following <em>RUNX1</em> or <em>F13A1</em> KD, clot contraction by HEL cells was decreased, as were FXIII-A surface expression, myosin light chain phosphorylation, and PAC1 antibody binding upon activation. <em>F13A1</em> expression and clot contraction were impaired in <em>RUNX1</em> downregulation in human megakaryocytes.</div></div><div><h3>Conclusion</h3><div>RUNX1 regulates platelet-megakaryocyte <em>F13A1</em> expression, which is decreased in RHD, reflecting regulation of a coagulation protein by a hematopoietic transcription factor. Platelet and megakaryocyte clot contraction is decreased in RHD, related to multiple impaired mechanisms including <em>F13A1</em> expression<em>,</em> myosin phosphorylation, and α_IIbβ₃ activation.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102680"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143369823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural bioinformatics for rational drug design","authors":"Soroush Mozaffari ,&nbsp;Agnethe Moen ,&nbsp;Che Yee Ng ,&nbsp;Gerry A.F. Nicolaes ,&nbsp;Kanin Wichapong","doi":"10.1016/j.rpth.2025.102691","DOIUrl":"10.1016/j.rpth.2025.102691","url":null,"abstract":"<div><div>A State of the Art lecture titled “structural bioinformatics technologies for rational drug design: from in silico to in vivo” was presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in 2024. Drug discovery remains a resource-intensive and complex endeavor, which usually takes over a decade and costs billions to bring a new therapeutic agent to market. However, the landscape of drug discovery has been transformed by the recent advancements in bioinformatics and cheminformatics. Key techniques, including structure- and ligand-based virtual screening, molecular dynamics simulations, and artificial intelligence–driven models are allowing researchers to explore vast chemical spaces, investigate molecular interactions, predict binding affinity, and optimize drug candidates with unprecedented accuracy and efficiency. These computational methods complement experimental techniques by accelerating the identification of viable drug candidates and refining lead compounds. Artificial intelligence models, alongside traditional physics-based simulations, now play an important role in predicting key properties such as binding affinity and toxicity, contributing to more informed decision-making, particularly early in the drug discovery process. Despite these advancements, challenges remain in terms of accuracy, interpretability, and the needed computational power. This review explores the state of the art in computational drug discovery, examining the latest methods and technologies, their transformative impact on the drug development pipeline, and the future directions needed to overcome remaining limitations. Finally, we summarize relevant data and highlight cases where various computational approaches were successfully applied to develop novel inhibitors, as presented during the ISTH 2024 Congress.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102691"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophylactic use of recombinant ADAMTS-13 during pregnancy for congenital thrombotic thrombocytopenic purpura","authors":"Éloïse Colliou ,&nbsp;Agnès Ribes ,&nbsp;Clotilde Gaible ,&nbsp;Mathilde Marlas ,&nbsp;David Ribes ,&nbsp;Isabelle Labadens ,&nbsp;Paul Guerby ,&nbsp;Stanislas Faguer","doi":"10.1016/j.rpth.2025.102687","DOIUrl":"10.1016/j.rpth.2025.102687","url":null,"abstract":"<div><h3>Background</h3><div>Congenital thrombotic thrombocytopenic purpura (cTTP) related to ADAMTS-13 deficiency is associated with a maternal risk of death of 10% and a risk of fetal loss greater than 50% without treatment.</div></div><div><h3>Key Clinical Question</h3><div>Is prophylactic use of recombinant (r)ADAMTS-13 during pregnancy in patients with cTTP safe and effective in preventing cTTP relapse?</div></div><div><h3>Clinical Approach</h3><div>rADAMTS-13 was given intravenously weekly (40 Units/kg) from 17 weeks’ gestation. ADAMTS-13 activity was undetectable before the first administration, reached 60% to 90% of normal levels 2 hours after, and became undetectable between days 4 and 6. A full dose was given in the hours preceding the delivery and on day 3. No flare-up of cTTP occurred during the pregnancy, and rADAMTS-13 was tolerated well. No anti–ADAMTS-13 antibodies developed.</div></div><div><h3>Conclusion</h3><div>Prophylactic use of rADAMTS-13 during pregnancy may prevent relapse of cTTP and reduce the risk of fetal loss, but an optimal regimen requires further attention.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102687"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143295797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk assessment and prevention of cancer-associated venous thromboembolism in ambulatory patients with solid malignancies","authors":"Nikola Vladic,&nbsp;Cornelia Englisch,&nbsp;Cihan Ay,&nbsp;Ingrid Pabinger","doi":"10.1016/j.rpth.2024.102664","DOIUrl":"10.1016/j.rpth.2024.102664","url":null,"abstract":"<div><div>Venous thromboembolism remains a major cause of morbidity and mortality among ambulatory cancer patients, necessitating effective risk assessment and prevention strategies. Despite the availability of risk assessment models and guidelines recommending primary thromboprophylaxis with low-molecular-weight heparins or direct oral anticoagulants, the application of these strategies is inconsistent. This review provides an overview of the current state-of-the-art venous thromboembolism risk assessment and thromboprophylaxis in ambulatory patients with cancer, focusing on existing risk assessment models and the latest guideline recommendations. Finally, it summarizes gaps in knowledge, discusses future directions, and highlights recent advances and state-of-the-art research presented at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102664"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Janus kinase inhibitor treatment for inflammatory diseases: excess or no excess risk of venous thromboembolism?","authors":"Yachar Dawudi ,&nbsp;Samuel Benarroch ,&nbsp;Hélène Helfer ,&nbsp;David M. Smadja ,&nbsp;Isabelle Mahé","doi":"10.1016/j.rpth.2024.102667","DOIUrl":"10.1016/j.rpth.2024.102667","url":null,"abstract":"<div><div>Janus kinase inhibitors (JAKis) have revolutionized the treatment landscape for various inflammatory and autoimmune diseases since their introduction in 2012. The expanded indications of JAKis have raised concerns about the associated risk of thrombosis, venous thromboembolic events (VTEs), and arterial thrombosis. This literature review examines studies reporting the risk of VTEs associated with JAKis in patients with inflammatory diseases. Phase I to III trials showed no increased risk of VTEs. However, these studies were not designed to detect adverse events such as VTEs. The pharmacovigilance data indicated that the frequency of VTE reports was higher than that of other adverse events. An increased risk of VTEs was also observed in the ORAL Surveillance study, a randomized, noninferiority, postmarketing phase IV safety study comparing tofacitinib with anti-tumor necrosis factor in patients with rheumatoid arthritis. However, limitations have to be acknowledged: pharmacovigilance data are declarative and subject to bias, VTE was a secondary outcome in the ORAL study, with noncomparable VTE risk factors between groups and increased thrombosis risks only at high doses of tofacitinib. Nevertheless, these data have led regulatory organizations such as the Food and Drug Administration and the European Medicines Agency to issue precautionary measures regarding the use of JAKis in inflammatory diseases. Most well-conducted real-life studies are in rheumatoid arthritis and do not confirm an excess of VTE risk associated with JAKis. Considering those conflicting results and limitations, future research should focus on specific indications and patient profiles, taking into account the complex interaction between drug treatment and underlying disease activity, to be able to draw definite conclusion about the VTE risk associated with JAKis.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102667"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preemptive anticoagulation during antenatal pulmonary embolism diagnostics in a community setting: retrospective cohort study","authors":"Aidan R. Campbell ,&nbsp;Cole J. Florio ,&nbsp;Grace V. Heringer ,&nbsp;Sara T. Woldemariam ,&nbsp;Scott D. Casey ,&nbsp;William B. Stubblefield ,&nbsp;Lauren M. Westafer ,&nbsp;Edward Qiao ,&nbsp;Cydney E. Middleton ,&nbsp;Lara Zekar ,&nbsp;Nachiketa Gupta ,&nbsp;Madeline J. Somers ,&nbsp;Mary E. Reed ,&nbsp;Nareg H. Roubinian ,&nbsp;Ashok P. Pai ,&nbsp;Jeffrey D. Sperling ,&nbsp;David R. Vinson","doi":"10.1016/j.rpth.2025.102695","DOIUrl":"10.1016/j.rpth.2025.102695","url":null,"abstract":"<div><h3>Background</h3><div>Society recommendations for preemptive (or empiric) anticoagulation during antenatal pulmonary embolism (PE) diagnostics rely on expert opinion, which varies widely across guidelines. The American College of Chest Physicians (CHEST), for example, recommends preemptive anticoagulation when PE is highly suspected or when a delay in imaging is anticipated. The American College of Obstetricians and Gynecologists, however, makes no mention of preemptive anticoagulation for suspected PE in their practice bulletin on thromboembolism in pregnancy. Patterns of preemptive anticoagulation in pregnancy are unknown.</div></div><div><h3>Objectives</h3><div>To describe the prevalence of and CHEST-based eligibility for preemptive anticoagulation in pregnancy.</div></div><div><h3>Methods</h3><div>This retrospective cohort study was undertaken across 21 United States community hospitals from October 1, 2021 through March 30, 2023. We included pregnant adults without COVID-19 undergoing definitive diagnostic PE imaging. We used pregnancy-adapted Geneva scores to calculate pretest probability as a proxy for suspicion.</div></div><div><h3>Results</h3><div>We included 326 patients: median age, 31.0 years; 51% were in the third trimester. Diagnostic settings included emergency departments (<em>n</em> = 254; 78%), Labor &amp; Delivery (<em>n</em> = 65; 20%), and outpatient clinics (<em>n</em> = 7; 2%). Median time from emergency department computed tomography order to results was 1.40 hours (IQR: 0.78, 2.06). Prevalence of confirmed or presumed PE was low (<em>n</em> = 8; 2.5%). Only 2 patients (0.6%) received preemptive anticoagulation, whereas by CHEST criteria, 34 patients (10.4%) were eligible.</div></div><div><h3>Conclusion</h3><div>We found rare use of preemptive anticoagulation during antenatal PE diagnostics in this imaged cohort with low PE prevalence and rapid access to diagnostic imaging. More research is needed to explore setting-specific variation in preemptive anticoagulation use.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102695"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of plasma levels of factor VIII according to procoagulant phospholipids on the risk of future venous thromboembolism","authors":"Magnus S. Edvardsen ,&nbsp;Ellen-Sofie Hansen ,&nbsp;Thor Ueland ,&nbsp;Nadezhda Latysheva ,&nbsp;Pål Aukrust ,&nbsp;Omri Snir ,&nbsp;Vânia M. Morelli ,&nbsp;John-Bjarne Hansen","doi":"10.1016/j.rpth.2024.102636","DOIUrl":"10.1016/j.rpth.2024.102636","url":null,"abstract":"<div><h3>Background</h3><div>A high level of plasma coagulation factor (F)VIII is an established and likely causal risk factor for venous thromboembolism (VTE). Procoagulant phospholipids (PPLs) facilitate FVIII activity in coagulation.</div></div><div><h3>Objectives</h3><div>To assess the association between plasma levels of FVIII and risk of future VTE according to PPL clotting time (PPL_CT), an inverse surrogate measure of plasma PPL activity.</div></div><div><h3>Methods</h3><div>A population-based nested case-control study comprising 278 incident VTE cases and 593 randomly selected age- and sex-matched controls were derived from the Tromsø cohort. Exposures were determined from data collected at the cohort baseline. Logistic regression was used to estimate odds ratios (ORs) with 95% CIs for VTE across tertiles of FVIII and PPL_CT.</div></div><div><h3>Results</h3><div>High (tertile 3) vs low (tertile 1) FVIII antigen levels resulted in an age- and sex-adjusted OR of 1.53 (95% CI, 0.78-3.00) in those with high PPL_CT (low PPL activity), while the corresponding OR for those with low PPL_CT (high PPL activity) was 1.88 (95% CI, 0.96-3.66). In the biological interaction analysis, participants with both high FVIII and PPL activity had an OR of 1.86 (95% CI, 0.97-3.57) compared with those with low FVIII and PPL activity. In the joint exposure group, 10% (95% CI, −55% to 75%) of VTEs could be attributable to the interaction between FVIII and PPL activity. Results remained similar after further adjustment for body mass index, C-reactive protein, arterial cardiovascular disease, and cancer.</div></div><div><h3>Conclusion</h3><div>The effect of high FVIII levels on VTE risk was particularly augmented in those with high PPL activity, suggesting that the effect of FVIII on VTE risk might be partially dependent on PPL activity.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102636"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Functional Characterization of Venous Thromboembolic Disease (FUVID) study: rationale, design, and methods of a prospective, observational, multicenter study to evaluate mechanisms of exercise intolerance and dyspnea following pediatric pulmonary embolism","authors":"Ayesha Zia ,&nbsp;Michael D. Nelson ,&nbsp;Jimin Ren ,&nbsp;Song Zhang ,&nbsp;Robert F. Mattrey ,&nbsp;Brian L. Han ,&nbsp;Tarique Hussain ,&nbsp;Joshua S. Greer ,&nbsp;Manal Al-Qahtani ,&nbsp;Kendra Malone ,&nbsp;Sonja E. Stutzman ,&nbsp;Deseray V. Sida ,&nbsp;Sharon Primeaux ,&nbsp;Marcela D. Torres ,&nbsp;Clay T. Cohen ,&nbsp;Shelley Crary ,&nbsp;Jonathan Bernstein ,&nbsp;Hilary B. Whitworth ,&nbsp;Riten Kumar ,&nbsp;Kisha A. Beg ,&nbsp;Song Zhang PhD","doi":"10.1016/j.rpth.2024.102669","DOIUrl":"10.1016/j.rpth.2024.102669","url":null,"abstract":"<div><h3>Background</h3><div>To date, the focus of investigation in pediatric pulmonary embolism (PE) has been on PE recurrence and anticoagulant-related bleeding. While highly relevant, these outcomes do not fully capture functional limitations and the psychological impact that comprises post-PE syndrome.</div></div><div><h3>Objectives</h3><div>The primary objective of the Functional Characterization of Venous Thromboembolic Disease (FUVID) study was to investigate mechanisms of post-PE syndrome in children.</div></div><div><h3>Methods</h3><div>The ongoing FUVID study will prospectively enroll and systematically follow, over 12 months and with standardized pulmonary, cardiac, and muscle testing, a multicenter prospective cohort of 80 pediatric patients with first-episode PE without comorbidities. FUVID has 2 coprimary outcomes: exercise intolerance and exertional dyspnea. Exercise intolerance will be defined objectively as a percent predicted peak oxygen uptake based on ideal body weight or milliliters per minute per kilogram of lean body mass during cardiopulmonary exercise testing. Dyspnea will be objectively quantified using Borg questionnaires and defined as a mean difference of &gt;1 at the end of the warm-up and submaximal work rates during exercise testing, simulating conditions during daily life that induce dyspnea. Pertinent secondary outcomes include anxiety, depression, and quality of life.</div></div><div><h3>Conclusion</h3><div>The FUVID study will investigate the relationship between symptoms (exercise intolerance and exertional dyspnea) and multiple mechanisms—hemodynamic, ventilatory, or peripheral/muscle—within the same patient at rest, submaximal exercise (simulating activities of daily living), and maximal exercise using objective measures. It will provide new evidence for selecting patients for long-term follow-up, including psychological sequelae, after PE, the modalities this follow-up should include, and the findings interpreted as indicating functional limitations after PE.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102669"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venous thromboembolism still leads on maternal death","authors":"Amelia Shard ,&nbsp;Catherine Prodger ,&nbsp;Sue Pavord","doi":"10.1016/j.rpth.2024.102675","DOIUrl":"10.1016/j.rpth.2024.102675","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102675"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges and considerations of genetic testing in von Willebrand disease","authors":"Omid Seidizadeh ,&nbsp;Luciano Baronciani ,&nbsp;Flora Peyvandi","doi":"10.1016/j.rpth.2025.102686","DOIUrl":"10.1016/j.rpth.2025.102686","url":null,"abstract":"<div><div>von Willebrand disease (VWD) is the most common inherited bleeding disorder characterized by defects in the quantity or function of the von Willebrand factor (VWF). The diagnosis of VWD is complex, requiring a battery of tests to evaluate the amount, functions, and multimeric structure of the VWF glycoprotein. The diagnosis can also be accomplished or confirmed by sequencing the VWF gene (<em>VWF</em>). Genetic testing of <em>VWF</em> has been around for 4 decades following the cloning of <em>VWF</em>, and nowadays, it has been integrated into the diagnostic panel of VWD. With the introduction of next-generation sequencing, genetic analysis of the <em>VWF</em> has become more practical than it was in the past, when Sanger sequencing was used. A number of laboratories have applied or started to use genetic testing with next-generation sequencing for VWD diagnosis. Considering the increasing application of genetic testing in VWD and the wide availability and decreasing cost of gene sequencing, we sought to discuss the challenges and considerations involved in applying genetic testing to VWD.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102686"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}