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HTRS2025.P1.3 Abstract of Distinction Clinical Outcomes Over 3 Years of Once-Weekly Efanesoctocog Alfa Treatment in Adults and Adolescents from North America with Severe Hemophilia A in the Phase 3 XTEND-ed Long-Term Extension Study 在一项为期3年的XTEND-ed长期扩展研究中,每周一次Efanesoctocog Alfa治疗北美成人和青少年严重血友病A的临床结果差异摘要
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rpth.2025.103023
Janice Staber , Angela Weyand , Jennifer Dumont , Davide Matino
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引用次数: 0
HTRS2025.P1.26 Iron Deficiency in Adolescents Presenting to the Emergency Department with Acute Heavy Menstrual Bleeding: a 5-year experience 急诊科出现急性月经大量出血的青少年缺铁:5年的经验
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rpth.2025.103046
Morgan Buchanan , Maeve McNamara , Anna Schwartz , Julia Shuford , Robert Sidonio , Megan Brown
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引用次数: 0
HTRS2025.P1.45 Suboptimal Direct Oral Anticoagulant Adherence in Children: A Single-Center Experience 儿童直接口服抗凝药物依从性的次优:单中心经验
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rpth.2025.103065
Ying Lee , Anh Hoang , Niavana Salas , Allison Anschutz , Ayesha Zia
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引用次数: 0
Comparative safety of enoxaparin versus other low-molecular-weight heparins in cancer-associated venous thromboembolism: a real-world cohort study from RIETE 依诺肝素与其他低分子肝素在癌症相关静脉血栓栓塞中的比较安全性:一项来自RIETE的真实世界队列研究
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rpth.2025.103244
Manuel Monreal , Benjamin Brenner , Covadonga Gómez-Cuervo , Najib Dally , Alicia Alda-Lozano , María Lourdes Pesce , Joaquín Alfonso-Megido , Jacinto Hernández-Borge , Raphael L.E. Mao , Paolo Prandoni

Background

Low-molecular-weight heparins (LMWHs) are widely used in the treatment of cancer-associated venous thromboembolism (VTE), yet their long-term safety profiles remain insufficiently compared in clinical practice.

Objectives

The primary outcome was major bleeding over a 6-month follow-up. Secondary outcomes included VTE recurrence, non-major clinically relevant bleeding, and all-cause mortality.

Methods

We analyzed 7287 patients with active cancer and acute VTE from the RIETE registry (2009-2022) who were treated with full-dose enoxaparin (n = 5628) or tinzaparin/dalteparin (n = 1659). Analyses were adjusted using multivariable Cox models, Fine-Gray competing risk models, frailty models clustered by center, and propensity score approaches.

Results

Major bleeding occurred in 3.84% of patients receiving enoxaparin versus 2.53% in the tinzaparin/dalteparin group (adjusted hazard ratio [aHR] 1.56; 95% CI: 1.11-2.19), with consistent findings across all sensitivity analyses. Enoxaparin was also associated with higher all-cause mortality (28.3% vs 25.1%; aHR 1.22; 95% CI: 1.09-1.37). No significant differences were observed in VTE recurrence (3.59% vs 3.07%) or non-major bleeding (3.98% vs 3.25%). Importantly, during the first 10 days of therapy, major bleeding occurred in 1.2% of patients treated with enoxaparin twice-daily, compared to 0.4% with once-daily dosing and 0.1% in the tinzaparin/dalteparin group (P < .001).

Conclusion

In this large, observational study, enoxaparin, particularly in twice-daily regimens, was associated with significantly increased risks of bleeding and mortality compared to tinzaparin/dalteparin. These findings may help refine LMWH selection and dosing strategies in patients with cancer-associated VTE and warrant further investigation in prospective studies.
背景低分子肝素(LMWHs)广泛用于治疗癌症相关性静脉血栓栓塞(VTE),但其长期安全性在临床实践中仍未得到充分比较。目的:在6个月的随访中,主要结局为大出血。次要结局包括静脉血栓栓塞复发、非主要临床相关出血和全因死亡率。方法:我们分析了来自RIETE登记处(2009-2022)的7287例活动性癌症和急性静脉血栓栓塞患者,这些患者接受了全剂量依诺肝素(n = 5628)或丁沙肝素/达特帕林(n = 1659)的治疗。采用多变量Cox模型、Fine-Gray竞争风险模型、中心聚类脆弱性模型和倾向评分方法对分析结果进行调整。结果接受依诺肝素治疗的患者发生大出血的比例为3.84%,而接受丁扎肝素/达特帕林治疗的患者发生大出血的比例为2.53%(校正风险比[aHR] 1.56; 95% CI: 1.11-2.19),所有敏感性分析结果一致。依诺肝素也与较高的全因死亡率相关(28.3% vs 25.1%; aHR 1.22; 95% CI: 1.09-1.37)。静脉血栓栓塞复发(3.59% vs 3.07%)或非大出血(3.98% vs 3.25%)无显著差异。重要的是,在治疗的前10天,每日两次依诺肝素治疗的患者中有1.2%发生大出血,而每日一次给药组为0.4%,丁沙肝素/达特帕林组为0.1% (P < .001)。结论:在这项大型观察性研究中,依诺肝素,特别是在每日两次的方案中,与丁沙肝素/达特帕林相比,出血和死亡率的风险显著增加。这些发现可能有助于改进癌症相关性静脉血栓栓塞患者低分子肝素的选择和给药策略,并值得在前瞻性研究中进一步研究。
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引用次数: 0
Rituximab-first versus eltrombopag monotherapy in pediatric persistent/chronic immune refractory thrombocytopenia after first-line therapy: a prospective multicenter cohort study 一线治疗后顽固性/慢性免疫难治性血小板减少症的儿童利妥昔单抗与头孢巴格单药治疗:一项前瞻性多中心队列研究
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rpth.2025.103241
Jingyao Ma , Zhifa Wang , Juntao Ouyang , Zheyan Lin , Lingling Fu , Zhenping Chen , Yan Liu , Lijuan Wang , Xi Lin , Xiaoling Cheng , Yu Hu , Shuyue Dong , Jinxi Meng , Jie Ma , Runhui Wu

Background

Immune thrombocytopenia (ITP) in children is an autoimmune disorder in which a significant subset develops persistent or chronic disease requiring second-line therapies, yet the optimal sequencing of agents such as rituximab (RTX) and eltrombopag (ELT) to achieve sustained remission off-treatment remains (SRoT) undefined.

Objectives

This study assessed whether RTX-first sequential therapy outperforms upfront ELT monotherapy in achieving durable remission for pediatric persistent/chronic ITP (p/cITP) after first-line failure.

Methods

This nonrandomized multicenter prospective cohort study enrolled 55 children (April 2020 to July 2023) with refractory p/cITP until first-line therapy. They were assigned to RTX-first (RfG, n = 35: single RTX dose, then ELT for nonresponders) or ELT monotherapy (ELT-first group [EfG], n = 20) groups, with 12-month follow-up. Primary endpoints were SRoT and treatment duration (TD), and secondary endpoints were response rate and safety. The study is registered at ChiCTR2100048162.

Results

Among the 55 enrolled children (RfG = 35, EfG = 20), RfG had superior SRoT (30%; 95% CI, 15.6%-48.7%) than ELT-monotherapy group (0%; 95% CI, 0%-18.7%; P = .016), although 12-month remission rates were comparable (84.8% vs 87.5%; P = .804). RfG had a shorter TD (median 18 vs 34 weeks; P = .009), even in severe cases (baseline platelets 20 ×109/L vs 29 ×109/L; P = .034). Early ELT (≤96 days) in RfG nonresponders improved outcomes (P = .024). Both treatments had favorable safety (grade 1-2 adverse events, <15%).

Conclusions

RTX-first treatment yields a better SRoT and shorter TD than ELT monotherapy for pediatric p/cITP, with comparable remission and safety.
背景:儿童免疫性血小板减少症(ITP)是一种自身免疫性疾病,其中一个重要的亚群会发展为持续性或慢性疾病,需要二线治疗,但利妥昔单抗(RTX)和伊曲博帕(ELT)等药物的最佳序列仍未确定,以实现持续的治疗缓解(SRoT)。目的:本研究评估在一线治疗失败后,儿童持续性/慢性ITP (p/cITP)的持续缓解方面,rtx优先序贯治疗是否优于前期ELT单药治疗。方法:这项非随机多中心前瞻性队列研究纳入了55名顽固性p/ ctp患儿(2020年4月至2023年7月),直至一线治疗。他们被分为RTX优先组(RfG, n = 35:单次RTX剂量,无反应者再服用ELT)或ELT单药治疗组(ELT优先组[EfG], n = 20),随访12个月。主要终点是SRoT和治疗时间(TD),次要终点是有效率和安全性。这项研究的注册号码是ChiCTR2100048162。结果在55名入组儿童(RfG = 35, EfG = 20)中,RfG组的SRoT (30%, 95% CI, 15.6%-48.7%)优于elt单药治疗组(0%,95% CI, 0%-18.7%, P = 0.016),尽管12个月缓解率相当(84.8% vs 87.5%, P = 0.804)。RfG的TD较短(中位18周vs 34周;P = 0.009),即使在严重的病例中(基线血小板20 ×109/L vs 29 ×109/L; P = 0.034)。RfG无应答者的早期ELT(≤96天)改善了结果(P = 0.024)。两种治疗均具有良好的安全性(1-2级不良事件,15%)。结论srtx优先治疗儿童p/ ctp的疗效优于ELT单药治疗,且缓解期和安全性相当。
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引用次数: 0
AOZORA study: 3-year interim analysis of safety and joint health in pediatric people with hemophilia A receiving emicizumab prophylaxis AOZORA研究:接受emicizumab预防的儿童A型血友病患者的安全性和关节健康的3年中期分析
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rpth.2025.103228
Midori Shima , Hideyuki Takedani , Kaoru Kitsukawa , Masashi Taki , Akira Ishiguro , Chiai Nagae , Azusa Nagao , Daisuke Nosaka , Yui Kyogoku , Hiroki Oki , Keisuke Iwasaki , Keiji Nogami

Background

Recurrent joint bleeding in people with hemophilia A (PwHA) can cause hemophilic arthropathy, resulting in limited movement and chronic pain. Emicizumab is a bispecific monoclonal antibody bridging activated factor (F)IX and FX to substitute for deficient activated FVIII in PwHA, thereby improving hemostasis.

Objectives

This 3-year interim analysis of the ongoing, open-label, phase IV AOZORA study (jRCT1080224629) analyzes medium-term safety and joint health in pediatric PwHA without FVIII inhibitors receiving emicizumab.

Methods

PwHA aged <12 years with severe hemophilia A without FVIII inhibitors were eligible. Participants entered AOZORA as emicizumab-naïve or having previously initiated emicizumab during the HOHOEMI study. Endpoints included safety, and joint health, as assessed by magnetic resonance imaging and Hemophilia Joint Health Score (HJHS). Participants will receive emicizumab for 6 years.

Results

A total of 30 male PwHA were enrolled. Data cutoff was the last day of week 145 for each participant. Median (range) age was 4.2 (0.7-11.1) years, and 27 of the 30 (90.0%) had received prior FVIII prophylaxis. The emicizumab safety profile was confirmed. No thrombotic events/microangiopathies occurred. All joints with synovial hypertrophy and hemosiderin resolved or improved by week 145. HJHS remained at 0 from week 1 to week 145 for 18 (66.7%) participants; overall, there was no worsening trend in HJHS over time. Model-based annualized bleeding rate (95% CI) for treated bleeds was 3.6 (2.04-6.46) prior to emicizumab and 0.8 (0.47-1.22) after receiving emicizumab.

Conclusion

Emicizumab is well tolerated and appears to maintain or improve joint health in pediatric PwHA.
血友病A (PwHA)患者复发性关节出血可引起血友病关节病,导致活动受限和慢性疼痛。Emicizumab是一种双特异性单克隆抗体桥接活化因子(F)IX和FX,用于替代PwHA中缺乏活化的FVIII,从而改善止血。这项为期3年的开放标签IV期AOZORA研究(jRCT1080224629)的中期分析分析了接受emicizumab治疗的无FVIII抑制剂的儿科PwHA患者的中期安全性和关节健康状况。方法12岁无FVIII抑制剂的严重A型血友病患者。参与者以emicizumab-naïve身份进入AOZORA,或者在HOHOEMI研究期间已经开始使用emicizumab。终点包括安全性和关节健康,通过磁共振成像和血友病关节健康评分(HJHS)进行评估。参与者将接受为期6年的emicizumab治疗。结果共纳入30例男性产妇。数据截止日期为每个参与者第145周的最后一天。中位(范围)年龄为4.2(0.7-11.1)岁,30人中有27人(90.0%)曾接受过FVIII预防。emicizumab的安全性得到了证实。无血栓形成事件/微血管病变发生。所有滑膜肥大和含铁血黄素的关节在第145周消退或改善。从第1周到第145周,18名参与者(66.7%)的HJHS保持在0;总体而言,HJHS没有随着时间的推移而恶化的趋势。基于模型的治疗出血年化出血率(95% CI)在使用艾美珠单抗前为3.6(2.04-6.46),接受艾美珠单抗后为0.8(0.47-1.22)。结论:emicizumab耐受性良好,可维持或改善儿童PwHA患者的关节健康。
{"title":"AOZORA study: 3-year interim analysis of safety and joint health in pediatric people with hemophilia A receiving emicizumab prophylaxis","authors":"Midori Shima ,&nbsp;Hideyuki Takedani ,&nbsp;Kaoru Kitsukawa ,&nbsp;Masashi Taki ,&nbsp;Akira Ishiguro ,&nbsp;Chiai Nagae ,&nbsp;Azusa Nagao ,&nbsp;Daisuke Nosaka ,&nbsp;Yui Kyogoku ,&nbsp;Hiroki Oki ,&nbsp;Keisuke Iwasaki ,&nbsp;Keiji Nogami","doi":"10.1016/j.rpth.2025.103228","DOIUrl":"10.1016/j.rpth.2025.103228","url":null,"abstract":"<div><h3>Background</h3><div>Recurrent joint bleeding in people with hemophilia A (PwHA) can cause hemophilic arthropathy, resulting in limited movement and chronic pain. Emicizumab is a bispecific monoclonal antibody bridging activated factor (F)IX and FX to substitute for deficient activated FVIII in PwHA, thereby improving hemostasis.</div></div><div><h3>Objectives</h3><div>This 3-year interim analysis of the ongoing, open-label, phase IV AOZORA study (jRCT1080224629) analyzes medium-term safety and joint health in pediatric PwHA without FVIII inhibitors receiving emicizumab.</div></div><div><h3>Methods</h3><div>PwHA aged &lt;12 years with severe hemophilia A without FVIII inhibitors were eligible. Participants entered AOZORA as emicizumab-naïve or having previously initiated emicizumab during the HOHOEMI study. Endpoints included safety, and joint health, as assessed by magnetic resonance imaging and Hemophilia Joint Health Score (HJHS). Participants will receive emicizumab for 6 years.</div></div><div><h3>Results</h3><div>A total of 30 male PwHA were enrolled. Data cutoff was the last day of week 145 for each participant. Median (range) age was 4.2 (0.7-11.1) years, and 27 of the 30 (90.0%) had received prior FVIII prophylaxis. The emicizumab safety profile was confirmed. No thrombotic events/microangiopathies occurred. All joints with synovial hypertrophy and hemosiderin resolved or improved by week 145. HJHS remained at 0 from week 1 to week 145 for 18 (66.7%) participants; overall, there was no worsening trend in HJHS over time. Model-based annualized bleeding rate (95% CI) for treated bleeds was 3.6 (2.04-6.46) prior to emicizumab and 0.8 (0.47-1.22) after receiving emicizumab.</div></div><div><h3>Conclusion</h3><div>Emicizumab is well tolerated and appears to maintain or improve joint health in pediatric PwHA.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 8","pages":"Article 103228"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prognostic value of the pan-immune-inflammation value for mortality in sepsis-induced coagulopathy: a Medical Information Mart for Intensive Care study 在脓毒症引起的凝血病中,泛免疫-炎症值对死亡率的预后价值:一项重症监护研究的医学信息集市
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rpth.2025.103257
Jian-Yue Yang, Li-Li Li, Su-Zhen Fu

Background

Sepsis is a life-threatening condition characterized by organ dysfunction caused by a dysregulated host response to infection. Its associated coagulopathy, known as sepsis-induced coagulopathy (SIC), significantly increases mortality risk. The pan-immune-inflammation value (PIV), a composite biomarker reflecting systemic immune and inflammatory status, has been linked to prognosis in various diseases.

Objectives

This study aimed to evaluate the prognostic significance of PIV in patients with SIC and to develop predictive models accordingly.

Methods

This retrospective study utilized data from the Medical Information Mart for Intensive Care IV database and included 4554 patients diagnosed with sepsis. Patients were stratified into high- and low-PIV groups based on the median PIV, and clinical characteristics were compared between groups. Kaplan–Meier survival analysis and Cox regression were employed to assess the association between PIV and patient outcomes. Least absolute shrinkage and selection operator regression was used to identify key variables for constructing a nomogram model. Additionally, machine learning algorithms, including random forest, were applied to build and validate predictive models.

Results

Patients in the high-PIV group had significantly higher 30-day and 90-day mortality rates. Kaplan–Meier analysis showed that patients with lower PIVs had markedly better survival, and a nonlinear positive correlation was observed between PIV and mortality risk. Least absolute shrinkage and selection operator regression identified 8 key variables, including Acute Physiology Score III, lactate, red cell distribution width, mean corpuscular volume, acute kidney injury, and continuous renal replacement therapy. The nomogram based on these variables achieved areas under the receiver operating characteristic curve of 0.84 and 0.87 in the training and validation cohorts, respectively. Among machine learning models, the random forest algorithm exhibited the best predictive performance, with areas under the curve of 0.837 and 0.947 in the training and validation sets, respectively. External validation using a real-world cohort from Xingtai People’s Hospital further confirmed the association between elevated PIV and increased mortality and SIC, with consistent survival trends and nonlinear patterns observed in both Kaplan–Meier and restricted cubic spline analyses.

Conclusion

To our knowledge, this study is the first to incorporate PIV into the prognostic assessment of patients with SIC. The development of a visual nomogram and machine learning-based models provides clinicians with practical tools for early identification of patients at high risk for SIC, potentially aiding in the optimization of treatment strategies.
脓毒症是一种危及生命的疾病,其特征是由宿主对感染反应失调引起的器官功能障碍。其相关的凝血功能障碍,被称为败血症诱导凝血功能障碍(SIC),显著增加死亡风险。泛免疫炎症值(PIV)是一种反映全身免疫和炎症状态的复合生物标志物,与多种疾病的预后有关。目的探讨PIV对SIC患者预后的影响,并建立相应的预测模型。方法本回顾性研究利用重症监护医学信息市场IV数据库的数据,纳入4554例诊断为败血症的患者。根据中位PIV将患者分为高、低PIV组,比较两组患者的临床特征。Kaplan-Meier生存分析和Cox回归评估PIV与患者预后的关系。最小绝对收缩和选择算子回归用于确定关键变量,以构建一个nomogram模型。此外,机器学习算法,包括随机森林,被应用于建立和验证预测模型。结果高piv组患者的30天和90天死亡率显著高于对照组。Kaplan-Meier分析显示,PIV较低的患者生存期明显较好,且PIV与死亡风险呈非线性正相关。最小绝对收缩和选择算子回归确定了8个关键变量,包括急性生理评分III、乳酸、红细胞分布宽度、平均红细胞体积、急性肾损伤和持续肾替代治疗。基于这些变量的nomogram在训练组和验证组的受试者工作特征曲线下的面积分别为0.84和0.87。在机器学习模型中,随机森林算法的预测性能最好,训练集和验证集的曲线下面积分别为0.837和0.947。来自邢台市人民医院的真实世界队列的外部验证进一步证实了PIV升高与死亡率和SIC升高之间的关联,Kaplan-Meier和限制性三次样条分析均观察到一致的生存趋势和非线性模式。据我们所知,本研究首次将PIV纳入SIC患者的预后评估。视觉图和基于机器学习的模型的发展为临床医生提供了早期识别SIC高风险患者的实用工具,可能有助于优化治疗策略。
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引用次数: 0
HTRS2025.P1.49 Transcriptomic analysis reveals Complement C5a Augments TLR3-Mediated Thrombo-Inflammatory and Antiviral Responses in Macrophages 转录组学分析显示补体C5a增强巨噬细胞tlr3介导的血栓炎症和抗病毒反应
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rpth.2025.103069
Saravanan Subramaniam , Asha Jose
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引用次数: 0
Title page 标题页
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rpth.2025.103159
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引用次数: 0
HTRS2025.P1.19 A New Fibrinogen Concentrate for Congenital Fibrinogen Deficiency: Pharmacokinetic Parameters and Efficacy 一种治疗先天性纤维蛋白原缺乏的新型纤维蛋白原浓缩物:药动学参数和疗效
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rpth.2025.103039
Wolfgang Miesbach , Claudia Djambas Khayat , Abderrahim Khelif , Heike Boehm , Silke Aigner , Salomon Abraha , Fabian Bohlaender , Joerg Schuettrumpf
{"title":"HTRS2025.P1.19 A New Fibrinogen Concentrate for Congenital Fibrinogen Deficiency: Pharmacokinetic Parameters and Efficacy","authors":"Wolfgang Miesbach ,&nbsp;Claudia Djambas Khayat ,&nbsp;Abderrahim Khelif ,&nbsp;Heike Boehm ,&nbsp;Silke Aigner ,&nbsp;Salomon Abraha ,&nbsp;Fabian Bohlaender ,&nbsp;Joerg Schuettrumpf","doi":"10.1016/j.rpth.2025.103039","DOIUrl":"10.1016/j.rpth.2025.103039","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 ","pages":"Article 103039"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145711971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Research and Practice in Thrombosis and Haemostasis
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