Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Thrombotic microangiopathic anemia in patients with sickle cell disease and its variants during a vaso-occlusive crisis","authors":"Wouhabe Bancheno , Donna Alexander , Mekdem Melaku , Bary Malik","doi":"10.1016/j.rpth.2025.102734","DOIUrl":"10.1016/j.rpth.2025.102734","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102734"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777616","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":"Ex vivo lentiviral gene therapy for severe hemophilia A: an alternative to recombinant adeno-associated viral-based strategies?","authors":"Benjamin J. Samelson-Jones","doi":"10.1016/j.rpth.2025.102716","DOIUrl":"10.1016/j.rpth.2025.102716","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102716"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683527","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":"High preoperative D-dimer increases the risk of venous thromboembolism after gynecological tumor surgeries: a meta-analysis of cohort studies","authors":"Zeyu Meng ,&nbsp;Lu Liu ,&nbsp;Xu Yang ,&nbsp;Xingxu Hu ,&nbsp;Yaping Xi ,&nbsp;Qinglin Yang ,&nbsp;Yun Luo ,&nbsp;Donghong Wang ,&nbsp;Jun Liu","doi":"10.1016/j.rpth.2025.102690","DOIUrl":"10.1016/j.rpth.2025.102690","url":null,"abstract":"<div><div>The role of preoperative D-dimer in the prediction of postoperative venous thromboembolism (VTE) with gynecological tumor remains unclear. This meta-analysis sought to assess the association between preoperative D-dimer and the risk of VTE after gynecological tumor surgeries and to identify prognostic significance of D-dimer in the prediction of postoperative VTE. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. Eight electronic databases were searched for cohort studies from the date of inception to April 2024. The Newcastle-Ottawa Scale scoring tool and the Risk of Bias in Non-Randomized Studies–Intervention tool were used to assess the quality of the literature and the risk of bias in cohort studies, respectively. The relative risk and 95% CIs of the highest vs the lowest category and per milligram per liter of D-dimer were pooled relative to the VTE risk after gynecological tumor surgeries. Fifteen studies that met the criteria were included. Among these studies, D-dimer was considered as a continuous variable in 8 studies. The random-effect model results showed that the VTE risk was increased by 42% (15%-69%) per milligram per liter increase in D-dimer. Furthermore, based on the cutoff thresholds of D-dimer, 7 studies that reported the effect estimates of postoperative VTE in women with gynecological tumor by D-dimer were categorized as binary variables. Compared with the reference levels, the pooled relative risk of VTE after gynecological tumor surgeries for the higher level was 2.58 (95% CI, 1.49-4.47). Elevated preoperative D-dimer was associated with higher VTE risks after gynecological tumor surgeries.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102690"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747393","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":"Concizumab prophylaxis in people with hemophilia A or B without inhibitors: patient-reported outcome results from the phase 3 explorer8 study","authors":"Pantep Angchaisuksiri ,&nbsp;Sylvia von Mackensen ,&nbsp;Shashikant Apte ,&nbsp;Gary Benson ,&nbsp;Hermann Eichler ,&nbsp;Amy Findley ,&nbsp;Tadashi Matsushita ,&nbsp;Camila M. Mazini Tavares ,&nbsp;Morten Puggaard Ravn ,&nbsp;Jameela Sathar ,&nbsp;Laura Villarreal Martinez ,&nbsp;Guy Young","doi":"10.1016/j.rpth.2025.102705","DOIUrl":"10.1016/j.rpth.2025.102705","url":null,"abstract":"<div><h3>Background</h3><div>Patient-reported outcomes (PROs) can provide useful insights into patient perception of concizumab, an anti–tissue factor pathway inhibitor monoclonal antibody intended for once-daily, subcutaneous prophylaxis for hemophilia A (HA) or hemophilia B (HB), with and without inhibitors.</div></div><div><h3>Objectives</h3><div>To evaluate PROs from the phase 3 explorer8 study (NCT04082429).</div></div><div><h3>Methods</h3><div>Male patients aged ≥12 years with HA/HB without inhibitors were enrolled and randomized 1:2 to no prophylaxis/on-demand treatment (arm 1) or concizumab prophylaxis (arm 2) or allocated to concizumab prophylaxis (arms 3 and 4). PRO questionnaires included the 36-item short-form health survey version 2, Haemophilia Quality of Life Questionnaire for Adults, Hemophilia Treatment Experience Measure, and Haemophilia Patient Preference Questionnaire.</div></div><div><h3>Results</h3><div>Estimated treatment difference for change in 36-item short-form health survey version 2 “bodily pain” and “physical functioning” from baseline to week 24 between patients in arms 1 and 2 was 9.5 points (95% CI, 2.4 to 16.7) and 0.3 points (95% CI, −5.1 to 5.6), respectively. Estimated treatment difference at week 24 between patients in arms 1 and 2 was −18.0 points (95% CI, −26.4 to −9.5) for Haemophilia Quality of Life Questionnaire for Adults “total score” and −16.8 points (95% CI, −32.2 to −1.4) for “physical health.” Hemophilia Treatment Experience Measure and Haemophilia Patient Preference Questionnaire results favored concizumab prophylaxis over no prophylaxis or previous treatment.</div></div><div><h3>Conclusion</h3><div>PRO data from the phase 3 explorer8 study provided additional support for concizumab prophylaxis compared with no prophylaxis as a treatment option for patients with HA/HB.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102705"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620576","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":"Identification and characterization of factor XI autoantibodies in 2 patients with systemic lupus erythematosus: insights into mechanisms of acquired factor XI deficiency","authors":"Priyanka Srivastava ,&nbsp;Amy Zhou ,&nbsp;Christine Fuja ,&nbsp;Charles S. Eby ,&nbsp;Gail Baxter ,&nbsp;Anton Matafonov ,&nbsp;Serena Fedorov ,&nbsp;Miriam Brown ,&nbsp;Michael Pettit ,&nbsp;Benjamin F. Tillman ,&nbsp;David Gailani ,&nbsp;Jeremy W. Jacobs","doi":"10.1016/j.rpth.2025.102703","DOIUrl":"10.1016/j.rpth.2025.102703","url":null,"abstract":"<div><h3>Background</h3><div>Factor (F)XI is a zymogen that contributes to thrombin generation through activation of FIX. Patients with a complete absence of FXI are prone to developing alloantibody inhibitors after replacement therapy. Acquired FXI autoantibodies are less common, and data regarding their mechanisms of action are lacking.</div></div><div><h3>Objectives</h3><div>We describe 2 patients with severe acquired FXI deficiency and identify the FXI domains to which the autoantibodies bind.</div></div><div><h3>Methods</h3><div>FXI and prekallikrein (PK) are homologs with similar structures. We prepared recombinant human FXI and PK, as well as chimeric molecules in which individual domains within FXI or PK are replaced with the corresponding domain from the other protein. Patient plasma and normal plasma were used as antibody sources, and their capacities to recognize recombinant proteins on Western blots were compared.</div></div><div><h3>Results</h3><div>Patients 1 and 2 were females with systemic lupus erythematous and no bleeding history. FXI activity in both cases was undetectable by one-stage clotting assay, with autoantibody titers of 64 Bethesda Units and 11.4 Bethesda Units, respectively. In both cases, the autoantibody appeared to clear FXI protein from plasma. Immunoglobulin G in patient 1 targeted the FXI catalytic domain, while the autoantibody in patient 2 was likely oligoclonal with components that recognized the FXI apple 2 and apple 3 domains.</div></div><div><h3>Conclusion</h3><div>These autoantibodies inhibited FXI function and promoted its clearance. The inhibitors targeted the 2 most important FXIa domains for FIX activation and demonstrated properties similar to those described in patients with FXI alloantibody inhibitors.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 2","pages":"Article 102703"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549335","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":"Carbon dioxide alleviates platelet storage lesions via stimulating fatty acid metabolism and reducing platelet glucose consumption","authors":"Shunli Gu,&nbsp;Jinmei Xu,&nbsp;Erxiong Liu,&nbsp;Xuejia Hou,&nbsp;Ning An,&nbsp;Yaozhen Chen,&nbsp;Zhixin Liu,&nbsp;Wenting Wang,&nbsp;Xingbin Hu,&nbsp;Wen Yin","doi":"10.1016/j.rpth.2025.102681","DOIUrl":"10.1016/j.rpth.2025.102681","url":null,"abstract":"<div><h3>Background</h3><div>The timely administration of platelet transfusions is critical for patient survival, and the clinical demand for platelet transfusions has been steadily increasing. However, platelet storage lesions (PSLs) that develop during <em>in vitro</em> preservation exacerbate these shortages. The PSL is significantly influenced by various factors, including temperature, gas composition, and buffering systems. Strategies to mitigate PSLs and improve platelet storage have been actively explored in recent years.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate whether elevated carbon dioxide (CO₂) levels improve platelet quality and functionality during storage.</div></div><div><h3>Methods</h3><div>Platelet concentrates from 28 donors were stored under control or 3% CO₂ conditions at 22 ± 2 °C for up to 7 days. Platelet quality was evaluated through scanning electron microscopy, adhesion, aggregation, clot contraction, activation, apoptosis assays, blood gas, adenosine triphosphate, metabolomics analyses, and <em>in vivo</em> thrombosis and survival tests.</div></div><div><h3>Results</h3><div>Our findings indicate that increasing the CO₂ concentration in the storage environment mitigates PSLs and improves platelet quality.</div></div><div><h3>Conclusion</h3><div>Our study highlights the potential benefits of utilizing a high CO₂ storage environment to improve platelet preservation, offering a promising method to address clinical platelet shortages.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102681"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387615","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":"Measurement of factor XIII for the diagnosis and management of deficiencies: insights from a retrospective review of 10 years of data on consecutive samples and patients","authors":"Mohammed Abdullah Al Sharif ,&nbsp;Natalie Mathews ,&nbsp;Subia Tasneem ,&nbsp;Karen A. Moffat ,&nbsp;Stephen A. Carlino ,&nbsp;Siraj Mithoowani ,&nbsp;Catherine P.M. Hayward","doi":"10.1016/j.rpth.2025.102689","DOIUrl":"10.1016/j.rpth.2025.102689","url":null,"abstract":"<div><h3>Background</h3><div>Factor XIII (FXIII) deficiency is a challenge in the diagnosis of rare bleeding disorders with inherited and acquired causes.</div></div><div><h3>Objectives</h3><div>We evaluated consecutive cases tested for FXIII deficiency for insights on diagnosis.</div></div><div><h3>Methods</h3><div>With ethics approval, we retrospectively reviewed FXIII tests performed between 2013 and 2023 and local patient records for insights into causes and presentations of FXIII deficiency.</div></div><div><h3>Results</h3><div>Two thousand one hundred ninety-one samples from 1915 patients (ages: 0-90 years; 38% local) were tested. The FXIII activity (FXIII:Act; Berichrom FXIII, Siemens Healthcare) was low in 14%/9.7% of tested samples/patients. FXIII subunit A antigen (FXIII-A:Ag; Werfen HemosIL FXIII antigen; low in 45% of 251 samples) helped characterize FXIII deficiency severity and identify type 2 deficiencies from acquired FXIII inhibitors. Urea clot solubility tests (18.2% requested without FXIII:Act) were largely noninformative as all abnormal samples (<em>n</em> = 7) had undetectable FXIII-A:Ag levels. Excluding FXIII inhibitor patients, FXIII:Act showed strong correlation with FXIII-A:Ag (<em>R</em>² = 0.84, <em>P</em> &lt; .001) and weak correlation with plasma fibrinogen (<em>R</em>² = .005, <em>P</em> &lt; .001). Some patients had combined acquired FXIII and fibrinogen deficiencies from consumption or major bleeding. FXIII-deficient and nondeficient patients had similar bleeding except for more umbilical and gastrointestinal bleeding among deficient patients (<em>P</em> &lt; .05). Most FXIII deficiencies were acquired (92%), and although several were autoimmune, most were from consumption, major bleeds, or severe infections or had uncertain significance, with bleeding sometimes attributable to other causes.</div></div><div><h3>Conclusion</h3><div>Congenital and acquired FXIII deficiency are associated with bleeding. Local practices were changed to ensure that FXIII:Act is used to screen for FXIII deficiency and that deficient patients have FXIII:Act and FXIII-A:Ag quantified and compared.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102689"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387616","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":"A cell-based model to study mechanisms of endothelial-dependent thrombin generation in response to inflammation and its modulation by hydroxychloroquine","authors":"Deepa J. Arachchillage ,&nbsp;Golzar Mobayen ,&nbsp;Mike Laffan ,&nbsp;Anna M. Randi ,&nbsp;Josefin Ahnström ,&nbsp;Charis Pericleous","doi":"10.1016/j.rpth.2024.102665","DOIUrl":"10.1016/j.rpth.2024.102665","url":null,"abstract":"<div><h3>Background</h3><div>Inflammation is a driver of thrombosis, but the phenomenon of thromboinflammation has been defined only recently, bringing together the multiple pathways involved. <em>In vitro</em> models can support the development of new therapeutics targeting the endothelium and also assess the existing immunomodulatory drugs, such as hydroxychloroquine, in modulating the inflammation-driven endothelial prothrombotic phenotype.</div></div><div><h3>Objectives</h3><div>To develop a model for thrombin generation (TG) on the surface of human endothelial cells (ECs) to assess pro/antithrombotic properties in response to inflammation. Furthermore, to elucidate the mechanisms of TG regulation and its modulation by immunomodulatory therapies.</div></div><div><h3>Methods</h3><div>Cytokine-induced (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and interferon-γ) effects on ECs isolated from umbilical veins or human aortic tissue were assessed using calibrated automated thrombography in platelet-poor plasma. The expression of key coagulant and inflammatory regulators was measured at the mRNA level. Tissue factor (TF) protein levels were further assessed by flow cytometry.</div></div><div><h3>Results</h3><div>Endothelial stimulation with TNF-α or IL-1β caused ECs to trigger TG without the addition of exogenous TF, with higher TG observed after 6 hours of stimulation than 24 hours. IL-1β induced higher peak thrombin (170 ± 5.9 nM vs 115 ± 4.9 nM), endogenous thrombin potential (1632 ± 35 nM ∗ min vs 1370 ± 23 nM ∗ min) presented as mean ± SD, and TF expression (∼2.8-fold higher) compared with TNF-α at 6 hours. Interferon-γ stimulation failed to induce TG and TF expression. The immunomodulatory drug, hydroxychloroquine, reduced cytokine-induced TG and downregulated TF expression.</div></div><div><h3>Conclusion</h3><div>We provide detailed optimization of a robust <em>in vitro</em> model to assess the induction of an inflammation-driven endothelial prothrombotic phenotype that is also sensitive to immunomodulatory therapies, providing a tool for investigating mechanisms of disease and new drugs.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102665"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060628","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":"No correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapy","authors":"Konrad van der Zwet ,&nbsp;Mark Roest ,&nbsp;Dana Huskens ,&nbsp;Roger E.G. Schutgens ,&nbsp;Lize F.D. van Vulpen ,&nbsp;Kathelijn Fischer ,&nbsp;Rolf T. Urbanus","doi":"10.1016/j.rpth.2024.102658","DOIUrl":"10.1016/j.rpth.2024.102658","url":null,"abstract":"<div><h3>Background</h3><div>Emicizumab, a bispecific antibody that mimics factor (F)VIII, has significantly improved hemophilia A management. Although emicizumab levels can be measured, tools for estimating the hemostatic efficacy of emicizumab are lacking. Thrombin generation (TG) assays can distinguish bleeding phenotypes in persons with hemophilia A on FVIII prophylaxis and may also be used during emicizumab therapy.</div></div><div><h3>Objectives</h3><div>To assess the association between TG parameters, emicizumab levels, and bleeding in patients on emicizumab therapy.</div></div><div><h3>Methods</h3><div>A single-center longitudinal cohort study was conducted, with samples collected during the steady-state phase of emicizumab therapy. TG was measured using tissue factor (TF; TF-TG, 1 pM) and FXIa (FXIa-TG, 200 pM). Emicizumab concentrations were determined with mass spectrometry. Only treated bleeds were recorded. Pearson correlations (rho, <em>r</em>) were reported.</div></div><div><h3>Results</h3><div>Eighty-five samples from 49 patients were analyzed during a median of 1 year of emicizumab therapy. Most bleeds were traumatic (97%; <em>n</em> = 30), whereas 1 bleed was spontaneous. At 12 months, TF-TG (<em>r</em> = 0.42) showed a borderline correlation, and FXIa-TG (<em>r</em> = 0.15) showed no correlation with emicizumab concentrations. Although FXIa-TG showed a 9% higher endogenous thrombin potential in patients with zero vs ≥1 treated bleed (endogenous thrombin potential: 957 vs 878 nM/min, <em>P</em> = .045), neither the FXIa-peak height nor TF-TG showed any association with traumatic bleeding.</div></div><div><h3>Conclusion</h3><div>TG parameters showed no clinically relevant correlations with emicizumab plasma concentrations, were not associated with traumatic bleeding, and showed considerable intrapatient variability. Therefore, TG was not considered useful for monitoring coagulation potential in patients on steady-state emicizumab prophylaxis.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102658"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029455","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":"Global prevalence of platelet-type von Willebrand disease","authors":"Omid Seidizadeh ,&nbsp;Andrea Cairo ,&nbsp;Maha Othman ,&nbsp;Flora Peyvandi","doi":"10.1016/j.rpth.2025.102682","DOIUrl":"10.1016/j.rpth.2025.102682","url":null,"abstract":"<div><h3>Background</h3><div>Platelet-type von Willebrand disease (PT-VWD) is a rare autosomal dominant disorder. It is caused by gain-of-function gene variants in the platelet <em>GP1BA</em>, which results in excessive binding between GPIbα and von Willebrand factor (VWF). The prevalence of PT-VWD is unknown.</div></div><div><h3>Objectives</h3><div>To establish the worldwide and within distinct ethnic groups prevalence of PT-VWD.</div></div><div><h3>Methods</h3><div>We used available exome and genome sequencing data of 807,162 (730,947 exomes and 76,215 genomes) subjects from the Genome Aggregation Database (gnomAD-v4.1).</div></div><div><h3>Results</h3><div>Among the 1,614,324 alleles analyzed in the gnomAD population, there were 1397 distinct <em>GP1BA</em> variants. Of them, 4 variants (p.Arg127Gln, p.Leu194Phe, p.Gly249Val, and p.Met255Ile) have been previously reported to cause PT-VWD. Considering these 4 known pathogenic variants, we estimated a global PT-VWD prevalence of 136 cases/10⁶. The highest estimated prevalence of PT-VWD was found in Africans/African Americans (160/10⁶), Finnish (156/10⁶), Europeans (149/10⁶), and South Asians (110/10⁶), followed by Ashkenazi Jewish (68/10⁶) and East Asian (45/10⁶) ethnicities. In the population with no assigned ethnicity, a prevalence of 126/10⁶ was estimated. Since no pathogenic <em>GP1BA</em> variants that were previously reported to cause PT-VWD were found in Admixed American and Middle Eastern ethnicities, we were unable to estimate the PT-VWD prevalence in these 2 populations. We found a global prevalence of 2.5/10⁶ for severe PT-VWD and 134/10⁶ for the mild form.</div></div><div><h3>Conclusion</h3><div>This population-based genetic epidemiology analysis indicates a substantially higher than expected frequency of PT-VWD. This novel finding suggests that a large number of PT-VWD patients are still under- or misdiagnosed.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102682"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155814","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}