Research and Practice in Thrombosis and Haemostasis最新文献

{"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}

{"title":"Anticoagulant management of cancer-associated thrombosis and thrombocytopenia: a retrospective chart review","authors":"Umaima Abbas ,&nbsp;Robin MacKenzie ,&nbsp;Ushra Khan ,&nbsp;Rija Fatima ,&nbsp;Tzu-Fei Wang ,&nbsp;Rong Luo ,&nbsp;Caroline Hamm ,&nbsp;Andrea Cervi","doi":"10.1016/j.rpth.2025.102684","DOIUrl":"10.1016/j.rpth.2025.102684","url":null,"abstract":"<div><h3>Background</h3><div>Patients with cancer-associated thrombosis (CAT) are at an increased risk of recurrent thrombosis and bleeding, especially if there is treatment- or disease-related thrombocytopenia. While direct oral anticoagulants (DOACs) are used in the management of CAT, low molecular weight heparin (LMWH) continues to be recommended for CAT with thrombocytopenia.</div></div><div><h3>Objectives</h3><div>This study aimed to identify the rates of recurrent venous thromboembolism (VTE) and bleeding in patients with CAT and thrombocytopenia treated with DOACs compared with LMWH.</div></div><div><h3>Methods</h3><div>A retrospective review of patients with CAT and thrombocytopenia (platelet count &lt;100,000/μL) was conducted. Primary outcomes included rates of recurrent VTE and major bleeding over 90 days.</div></div><div><h3>Results</h3><div>Forty-two patients met the inclusion criteria; 20 (47.6%) had a solid organ malignancy while 22 (52.4%) had a hematologic malignancy. Within the first 7 days of VTE, 3 (7.1%) patients had a platelet count &lt;25,000/μL, 9 (21.4%) had 25,000 to 50,000/μL, and 19 (45.2%) had 50,000 to 100,000/μL. Sixteen patients (38.1%) received a DOAC for initial treatment, while 19 (45.2%) received LMWH. Among patients treated with DOACs, there were no recurrent VTEs, 2 clinically relevant nonmajor bleeding events (12.5%) within the first 2 weeks, and 1 minor bleed (6.3%) in the second month, while those treated with LMWH had 1 recurrent VTE (5.3%) in the second month and 2 clinically relevant nonmajor bleeding events (10.5%) within the first 2 months.</div></div><div><h3>Conclusion</h3><div>Rates of thrombosis and major bleeding were similar among thrombocytopenic patients with CAT treated with DOACs and LMWH, although differences in baseline patient characteristics can be confounders. Further prospective research on the optimal anticoagulant management of CAT with thrombocytopenia is needed.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102684"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156331","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":"Characterization of the procoagulant phenotype of amniotic fluid across gestation in rhesus macaques and humans","authors":"Chih Jen Yang ,&nbsp;Lyndsey E. Shorey-Kendrick ,&nbsp;Cristina Puy ,&nbsp;Ashley E. Benson ,&nbsp;Phillip A. Wilmarth ,&nbsp;Ashok P. Reddy ,&nbsp;Keith D. Zientek ,&nbsp;Kilsun Kim ,&nbsp;Adam Crosland ,&nbsp;Chaevien S. Clendinen ,&nbsp;Lisa M. Bramer ,&nbsp;Olivia L. Hagen ,&nbsp;Helen H. Vu ,&nbsp;Joseph E. Aslan ,&nbsp;Owen J.T. McCarty ,&nbsp;Joseph J. Shatzel ,&nbsp;Brian P. Scottoline ,&nbsp;Jamie O. Lo","doi":"10.1016/j.rpth.2024.102676","DOIUrl":"10.1016/j.rpth.2024.102676","url":null,"abstract":"<div><h3>Background</h3><div>Amniotic fluid (AF) plays a key role in fetal development, yet the evolving composition of AF and its effects on hemostasis and thrombosis are poorly understood.</div></div><div><h3>Objectives</h3><div>To characterize the procoagulant properties of AF as a function of gestation in humans and nonhuman primates.</div></div><div><h3>Methods</h3><div>We analyzed the proteomes, lipidomes, and procoagulant properties of AF obtained by amniocentesis from rhesus macaque and human pregnancies at gestational age-matched time points.</div></div><div><h3>Results</h3><div>When added to human plasma, both rhesus and human AF accelerated clotting time and fibrin generation. We identified proteomic modules associated with clotting time and enriched for coagulation-related pathways. Proteins known to be involved in hemostasis were highly correlated with each other, and their intensity of expression varied across gestation in both rhesus and humans. Inhibition of the contact pathway did not affect the procoagulant effect of AF. Blocking tissue factor pathway inhibitor reversed the ability of AF to block the generation of activated factor X. The prothrombinase activity of AF was inhibited by phospholipid inhibitors. The levels of phosphatidylserine in AF were inversely correlated with clotting time. AF promoted platelet activation and secretion in plasma.</div></div><div><h3>Conclusion</h3><div>Overall, our findings reveal that the addition of AF to plasma enhances coagulation in a manner dependent on phospholipids as well as the presence of proteases and other proteins that directly regulate coagulation. We describe a correlation between clotting time and expression of coagulation proteins and phosphatidylserine in both rhesus and human AF, supporting the use of rhesus models for future studies of AF biology.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102676"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156252","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":"Clinical management of bleeding manifestations in a family with the thrombomodulin C1611>A (p.Cys537Stop) mutation","authors":"Serge Pierre-Louis ,&nbsp;Johalene Rabout ,&nbsp;Octavio Labrada ,&nbsp;Fatima Radouani ,&nbsp;Emeline Chonville ,&nbsp;Beatrice Ferrey ,&nbsp;Olivier Pierre-Louis ,&nbsp;Yesim Dargaud","doi":"10.1016/j.rpth.2025.102678","DOIUrl":"10.1016/j.rpth.2025.102678","url":null,"abstract":"<div><h3>Background</h3><div>The bleeding disorder described here is due to a heterozygous autosomal dominant C1611&gt;A variant in the thrombomodulin (TM) gene that significantly elevates plasma TM levels, which enhances the activation of protein C. This activation inhibits factors VIIIa and Va, reducing thrombin generation and potentially leading to severe hemorrhagic manifestations.</div></div><div><h3>Key Clinical Question</h3><div>What is the bleeding profile of patients with this rare condition? What are the most frequent clinical signs, and how can they be treated?</div></div><div><h3>Clinical Approach</h3><div>We present a case study of an index patient with the <em>TM</em> C1611&gt;A variant and his 20 family members. We detail the hemostatic strategies employed during various bleeding episodes and surgical procedures.</div></div><div><h3>Conclusion</h3><div>Sharing clinical experiences is crucial for hematologists managing similar cases, as it provides valuable insights into effective treatment strategies.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102678"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156332","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":"Real-world andexanet alfa utilization and the association between delay in administration due to hospital transfer and all-cause inpatient mortality","authors":"Huiqiao Fan,&nbsp;Youssef Bessada,&nbsp;Craig I. Coleman","doi":"10.1016/j.rpth.2025.102688","DOIUrl":"10.1016/j.rpth.2025.102688","url":null,"abstract":"<div><h3>Background</h3><div>Evaluations of andexanet alfa for the reversal of factor Xa inhibitor-associated bleeding have been small, with cohorts drawn from single/limited sites. Delays in providing anticoagulation reversal due to hospital transfer may result in poorer outcomes.</div></div><div><h3>Objectives</h3><div>To describe the characteristics and outcomes of andexanet alfa users and evaluate the association between delay in andexanet alfa administration due to transfer from a different acute care hospital and the incidence of all-cause inpatient mortality.</div></div><div><h3>Methods</h3><div>This was a retrospective study using National Inpatient Sample data. Hospitalizations with procedural codes for andexanet alfa and a billing code for bleeding were included. Descriptive analysis was performed, as was multivariable logistic regression, to estimate the odds ratio and 95% CI for the association between andexanet alfa delayed due to transfer from a different acute care hospital and all-cause inpatient mortality.</div></div><div><h3>Results</h3><div>From 2019 to 2021, 4210 hospitalizations occurred in adults receiving andexanet alfa and a bleed. Most were hospitalized with intracranial hemorrhage (62.0%). The incidence of all-cause inpatient mortality was 16.6% (95% CI, 14.3%-19.3%), mean hospital stays lasted 9.1 days (95% CI, 8.4-9.8), and mean hospital costs were $73,600 (95% CI, $65,000-$82,200). Of all cases, 18.5% were transferred from a different acute care hospital prior to receiving andexanet alfa. Cases with hospital transfer had an 82% increased odds of all-cause inpatient mortality (95% CI, 17%-183%) but did not reach statistical significance when the population was limited to intracranial hemorrhage (odds ratio, 1.51; 95% CI, 0.88-2.60).</div></div><div><h3>Conclusion</h3><div>Delay in administering andexanet alfa due to hospital transfer may be associated with increased all-cause mortality.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102688"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445817","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":"Reduced- versus full-dose anticoagulants for the extended treatment of cancer-associated venous thromboembolism in Thai patients","authors":"Kawin Vichaidit,&nbsp;Pichika Chantrathammachart,&nbsp;Pimjai Niparuck,&nbsp;Teeraya Puawilai,&nbsp;Pantep Angchaisuksiri MD,&nbsp;Kochawan Boonyawat","doi":"10.1016/j.rpth.2024.102643","DOIUrl":"10.1016/j.rpth.2024.102643","url":null,"abstract":"<div><h3>Background</h3><div>Reduced-dose anticoagulant therapy for extended treatment of cancer-associated venous thromboembolism (VTE) has been used to avoid bleeding. However, it may increase the risk of recurrent VTE.</div></div><div><h3>Objectives</h3><div>To study the rate of recurrent VTE and bleeding complications in Thai patients with cancer-associated VTE who were treated with full-dos/e or reduced-dose anticoagulants.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted in a single-center academic hospital. Electronic medical records were reviewed from 2016-2023. Patients with cancer-associated VTE who received anticoagulants for at least 3 months were evaluated. Reduced-dose anticoagulant was defined as a dose that was lower than the recommended standard dosage. The primary outcome was recurrent VTE. The secondary outcomes were major bleeding and clinically relevant nonmajor bleeding.</div></div><div><h3>Results</h3><div>A total of 229 patients were included. The median age was 65 years (IQR, 54-72). In the reduced-dose group, age and history of previous bleeding were higher than in the full-dose group. There were 169 (74%) patients and 60 (26%) patients who received full- and reduced-dose anticoagulants. The median time to reduce the dose was 3.6 months (IQR, 0.7-5.5). Of a total of 7 (3.1%) recurrent VTEs, 4 (2.4%) occurred in the full-dose and 3 (5.0%) in the reduced-dose groups (<em>P</em> = .4), respectively. The median time to recurrent VTE was 7.2 months (IQR, 3.5-12.4). There were 8 (3.5%) bleeding events, 7 (4.1%) and 1 (1.7%) in the full and reduced-dose anticoagulant groups (<em>P</em> = .35), respectively. The median follow-up time was 1.5 years (IQR, 1-3.1).</div></div><div><h3>Conclusion</h3><div>Older age and a history of previous bleeding were associated with the use of reduced-dose anticoagulants. Patients with cancer-associated VTE receiving reduced-dose anticoagulants had a numerically higher risk of recurrent VTE and lower bleeding outcomes compared with those receiving full-dose anticoagulants.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102643"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932615","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":"Andexanet alfa: trials just leave us with more questions","authors":"Richard J. Buka","doi":"10.1016/j.rpth.2024.102628","DOIUrl":"10.1016/j.rpth.2024.102628","url":null,"abstract":"<div><div>Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor (ANNEXA-I), the first ever randomized controlled trial of a reversal agent for direct oral anticoagulants, was published in 2024. The trial, which randomized patients with intracranial hemorrhage to andexanet alfa or usual care, was mandated by the United States Food and Drug Administration as part of its conditional approval in 2018. This approval was originally based on the single-arm trial, The Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors (ANNEXA-4). ANNEXA-I was stopped early for benefit and showed a reduction in the number of patients with significant hematoma expansion. However, the study was not powered for clinical endpoints such as disability or death and showed no difference in these outcomes. It did, however, show an increased risk of thrombosis, predominantly stroke with andexanet alfa. In this perspective, I reflect on some of the key criticisms of the trial and the implications for its interpretation.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102628"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047731","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":"Transfusion in trauma: empiric or guided therapy?","authors":"Liam Barrett ,&nbsp;Nicola Curry","doi":"10.1016/j.rpth.2024.102663","DOIUrl":"10.1016/j.rpth.2024.102663","url":null,"abstract":"<div><div>A state of the art lecture titled “Transfusion therapy in trauma—what to give? Empiric vs guided” was presented at the International Society on Thrombosis and Haemostasis Congress in 2024. Uncontrolled bleeding is the commonest preventable cause of death after traumatic injury. Hemostatic resuscitation is the foundation of contemporary transfusion practice for traumatic bleeding and has 2 main aims: to immediately support the circulating blood volume and to treat/prevent the associated trauma-induced coagulopathy. There are 2 broad types of hemostatic resuscitation strategy: empiric ratio-based therapy, often using red blood cells and fresh frozen plasma in a 1:1 ratio, and targeted therapy where the use of platelets, plasma, or fibrinogen is guided by laboratory or viscoelastic hemostatic tests. There are benefits, and limitations, to each strategy and neither approach has yet been shown to improve outcomes across all patient groups. Questions remain, and future directions for improving transfusion therapy are likely to require novel approaches that have greater flexibility to evaluate and treat heterogeneous trauma cohorts. Such approaches may include the integration of machine learning technologies in clinical systems, with real-time linkage of clinical and laboratory data, to aid early recognition of patients at the greatest risk of bleeding and to direct and individualize transfusion therapies. Greater mechanistic understanding of the underlying pathobiology of trauma-induced coagulopathy and the direct effects of common treatments on this process will be of equal importance to the development of new treatments. Finally, we summarize relevant new data on this topic presented at the 2024 ISTH Congress.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102663"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067431","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":"Validation of the 5-SNP score for the prediction of venous thromboembolism in a Danish fast-track cohort of 6789 total hip and total knee arthroplasty patients","authors":"Mark J.R. Smeets ,&nbsp;Pelle B. Petersen ,&nbsp;Christoffer C. Jørgensen ,&nbsp;Suzanne C. Cannegieter ,&nbsp;Sisse R. Ostrowski ,&nbsp;Henrik Kehlet ,&nbsp;Banne Nemeth","doi":"10.1016/j.rpth.2024.102644","DOIUrl":"10.1016/j.rpth.2024.102644","url":null,"abstract":"<div><h3>Background</h3><div>Venous thromboembolism (VTE) is a serious complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Despite improvements with fast-track treatment protocols, 0.5% of patients still develop a VTE within 90-days postoperatively. Previously, the 5-single nucleotide polymorphism (SNP) genetic risk scores (weighted and simplified) were developed to identify people at a high risk for VTE within the general population.</div></div><div><h3>Objectives</h3><div>We aimed to assess whether the 5-SNP scores could be used to identify high-risk patients in a cohort of fast-track THA/TKA patients.</div></div><div><h3>Methods</h3><div>A subset of patients from the Lundbeck Centre for Fast-track Hip and Knee Replacement Database was included based on the availability of genetic information. The 5-SNP scores were calculated for these patients, and their discriminatory performance was determined by c-statistic. Furthermore, the 5-SNP scores were added to a simple logistic prediction model containing clinical predictors to assess the added predictive value.</div></div><div><h3>Results</h3><div>A total of 7753 THA and TKA procedures (6798 patients) were included in this study. The c-statistics for the weighted and simple 5-SNP scores were 0.50 (95% CI, 0.39-0.61) and 0.48 (95% CI, 0.38-0.58), respectively. For the model with clinical predictors, the c-statistic was 0.67 (95% CI, 0.56-0.77). Addition of either of the 5-SNP scores did not improve discrimination in this model.</div></div><div><h3>Conclusion</h3><div>These findings do not support genetic risk profiling in fast-track THA/TKA patients to predict VTE. Hence, efforts should be directed at optimizing prediction models with clinical predictors.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102644"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984634","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":"Intermediate-dose immune tolerance induction outperforms with faster success, less bleeding, and no added cost in comparison with low dose: a multicenter randomized clinical trial","authors":"Zhengping Li ,&nbsp;Zekun Li ,&nbsp;Xiaoling Cheng ,&nbsp;Heng Zhang ,&nbsp;Can Yang ,&nbsp;Qian Xu ,&nbsp;Zhenping Chen ,&nbsp;Yingzi Zhen ,&nbsp;Gang Li ,&nbsp;Guoqing Liu ,&nbsp;Wanru Yao ,&nbsp;Min Zhou ,&nbsp;Jiao Jin ,&nbsp;Jie Huang ,&nbsp;Yongjun Fang ,&nbsp;Liangzhi Xie ,&nbsp;Man-Chiu Poon ,&nbsp;Runhui Wu","doi":"10.1016/j.rpth.2024.102639","DOIUrl":"10.1016/j.rpth.2024.102639","url":null,"abstract":"<div><h3>Background</h3><div>Low-dose (LD) or intermediate-dose (MD) immune tolerance induction (ITI) is effective in children with severe hemophilia A (SHA) with high-titer inhibitors (HTIs) and is attractive in countries with economic constraints. However, high-quality evidence of their use is lacking.</div></div><div><h3>Objectives</h3><div>This was a multicenter randomized clinical trial comparing the efficacy, safety, and medication cost between LD-ITI and MD-ITI for SHA-HTI children.</div></div><div><h3>Methods</h3><div>Children with SHA aged &lt;8 years with historical/pre-ITI inhibitor titer 5 to 200 Bethesda Units/mL in 3 centers were randomized 1:1 to receive LD-ITI (recombinant factor VIII [rFVIII] 50 IU/kg every other day) or MD-ITI (rFVIII 100 IU/kg/d) from January 2022 to June 2024 (ChiCTR2200056603, <span><span>https://www.chictr.org.cn</span><svg><path></path></svg></span>).</div></div><div><h3>Results</h3><div>Thirty-one patients (16 in MD-ITI and 15 in LD-ITI) were enrolled and followed for &gt;24 months (median, 26.9; range, 24.0-29.5 months). The 2 groups had similar baseline clinical characteristics and similar success rates (93.8% [MD-ITI] vs 86.7% [LD-ITI]). Compared with LD-ITI, MD-ITI patients took a shorter median time to success (4.2 months vs 10.1 months) and partial success (2.7 months vs 6.6 months) and had lower mean rates for all bleeding (0.38/mo vs 1.40/mo) and joint bleeding (0.11/mo vs 0.83/mo). Between the 2 groups, although the MD-ITI group had higher rFVIII consumption (12,775 vs 7680 IU/kg), their total medication costs to success were similar (3626.49 vs 3240.38 US$/kg).</div></div><div><h3>Conclusion</h3><div>For SHA-HTI children, the success rate and cost for MD-ITI and LD-ITI regimens were similar. MD-ITI regimen would be a priority for regions with economic constraints, considering the shorter time to success, better bleeding control, and no increase in medication cost.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102639"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984631","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}