Research and Practice in Thrombosis and Haemostasis最新文献_第4页

The Ottawa score for prediction of recurrent venous thromboembolism in cancer patients treated with tinzaparin: an individual patient data meta-analysis 渥太华评分用于预测接受丁沙肝素治疗的癌症患者静脉血栓栓塞复发：一项个体患者数据荟萃分析

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103278

Céline Chapelle , Philippe Girard , Luis Jara-Palomares , Agnès Y.Y. Lee , Olivier Sanchez , Guy Meyer , Géraldine Poenou , Patrick Mismetti , Isabelle Mahé , Silvy Laporte

Background

Risk of venous thromboembolism (VTE) recurrence remains high in patients with cancer-associated thrombosis (CAT), despite therapeutic anticoagulation. Identifying patients at risk of treatment failure is still a challenge.

Objectives

We aimed to assess the performance of the Ottawa score in predicting VTE recurrence in a large homogeneous population of patients with CAT treated with the same anticoagulant, tinzaparin, for at least 3 months.

Methods

Individual patient data from 3 prospective cohort studies and 1 randomized controlled trial were pooled (PROSPERO: CRD42019119907). Clinical events of interest were adjudicated by independent central adjudication committees in all 4 studies.

Results

Among the 1413 patients included, the Ottawa score could be calculated for 1088 of whom 646 (59.4%) were classified at high risk of recurrence (Ottawa score ≥ 1). The 6-month cumulative incidence of recurrent VTE was 5.0% (95% CI, 3.2-7.8) in the Ottawa low-risk group and 8.5% (95% CI, 6.6-10.8) in the high-risk group. The area under the receiver operating characteristic curve was 0.56 (95% CI, 0.51-0.62). The sensitivity of the dichotomized Ottawa score (score ≥ 1) was 72.8% (95% CI, 62.6%-83.0%), the specificity was 41.9% (95% CI, 37.8%-45.9%), the positive predictive value was 8.6% (95% CI, 6.4%-10.8%), and the negative predictive value was 95.3% (95% CI, 93.3%-97.4%). Introducing additional predictive factors failed to significantly improve the score’s performance.

Conclusions

Despite the large number of patients and anticoagulant treatment standardization, the Ottawa score failed to accurately predict recurrent VTE in patients with CAT treated with tinzaparin.

背景：尽管进行了抗凝治疗，但在癌症相关性血栓形成（CAT）患者中，静脉血栓栓塞（VTE）复发的风险仍然很高。识别有治疗失败风险的患者仍然是一个挑战。目的：我们旨在评估渥太华评分在预测静脉血栓栓塞（VTE）复发方面的表现，这些患者均为接受相同抗凝剂丁沙巴苷治疗至少3个月的CAT患者。方法汇总3项前瞻性队列研究和1项随机对照试验的个体患者数据（PROSPERO: CRD42019119907）。所有4项研究的临床事件均由独立的中央裁决委员会裁决。结果纳入的1413例患者中，1088例可计算渥太华评分，其中646例（59.4%）归为复发高危（渥太华评分≥1）。渥太华低危组6个月累计静脉血栓栓塞复发发生率为5.0% (95% CI, 3.2-7.8)，高危组为8.5% （95% CI, 6.6-10.8）。受试者工作特征曲线下面积为0.56 （95% CI, 0.51 ~ 0.62）。二分法渥太华评分（评分≥1）的敏感性为72.8% (95% CI, 62.6% ~ 83.0%)，特异性为41.9% (95% CI, 37.8% ~ 45.9%)，阳性预测值为8.6% (95% CI, 6.4% ~ 10.8%)，阴性预测值为95.3% （95% CI, 93.3% ~ 97.4%）。引入额外的预测因素未能显著提高分数的表现。结论尽管患者数量众多，抗凝治疗标准化，但渥太华评分不能准确预测丁沙巴苷治疗CAT患者静脉血栓栓塞复发。

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引用次数: 0

High-density lipoprotein subfractions and risk of future venous thromboembolism—the HUNT study 高密度脂蛋白亚组分和未来静脉血栓栓塞的风险- HUNT研究

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103295

Inga A. Røstvold , Ben Brumpton , Kristian Hveem , Bjørn Olav Åsvold , Guro F. Giskeødegård , George Davey Smith , Nicholas J. Timpson , Kaitlin H. Wade , John-Bjarne Hansen , Sigrid K. Brækkan

Background

Previous studies on high-density lipoprotein (HDL) cholesterol levels and the risk of venous thromboembolism (VTE) have shown conflicting results, and it has been suggested that specific HDL subfractions and lipid composition may be more informative with regards to VTE risk.

Objectives

We aimed to investigate the association between HDL subfractions (including particle size, concentration, and lipid composition) and risk of VTE in a population-based cohort.

Methods

The study included 17,032 participants from the Trøndelag Health Study (HUNT3) cohort conducted in 2006-2008 who were followed up until December 31, 2019. HDL subfractions were analyzed in serum using nuclear magnetic resonance spectroscopy. All incident VTEs during follow-up were validated and recorded. Cox proportional hazards regression models estimated hazard ratios (HRs) for the association between HDL metrics and incident VTE, adjusting for age, sex, and body mass index.

Results

During a median follow-up of 12.0 years, 342 incident VTE cases were confirmed. No associations were found among HDL particle size, HDL concentration, HDL lipid composition, apolipoprotein (Apo)A1 levels, and VTE risk. All HRs per 1-SD increase in HDL metrics were within the range of 0.83 to 1.16 and had 95% CIs that included 1. Furthermore, quartile analyses of HDL particles (Q4 vs Q1—HR, 0.89; 95% CI, 0.65-1.21) and ApoA1 (Q4 vs Q1—HR, 0.94; 95% CI, 0.68-1.29) showed no associations with VTE risk.

Conclusion

HDL subfractions, including particle size, concentration, lipid composition, and ApoA1, were not associated with the risk of a first-lifetime VTE event.

背景：先前关于高密度脂蛋白（HDL）胆固醇水平和静脉血栓栓塞（VTE）风险的研究显示出相互矛盾的结果，并且已经表明特定的HDL亚组分和脂质组成可能在VTE风险方面提供更多信息。目的：在以人群为基础的队列中，研究HDL亚组分（包括颗粒大小、浓度和脂质组成）与静脉血栓栓塞风险之间的关系。方法本研究纳入了2006-2008年开展的Trøndelag健康研究（HUNT3）队列中的17032名参与者，随访至2019年12月31日。采用核磁共振波谱法分析血清中HDL亚组分。随访期间的所有事件静脉血栓栓塞均被验证和记录。Cox比例风险回归模型在调整年龄、性别和体重指数后，估计了HDL指标与VTE事件之间的风险比（hr）。结果在中位随访12.0年期间，确认了342例静脉血栓栓塞病例。HDL颗粒大小、HDL浓度、HDL脂质组成、载脂蛋白（Apo）A1水平和静脉血栓栓塞（VTE）风险之间没有相关性。所有HDL指标每增加1- sd的hr范围在0.83 ~ 1.16之间，95% ci包括1。此外，HDL颗粒（Q4 vs Q1-HR, 0.89; 95% CI, 0.65-1.21）和ApoA1 （Q4 vs Q1-HR, 0.94; 95% CI, 0.68-1.29）的四分位数分析显示与静脉血栓栓塞风险无关联。结论hdl亚组分，包括颗粒大小、浓度、脂质组成和ApoA1，与首生命期静脉血栓栓塞事件的风险无关。

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引用次数: 0

Safety and efficacy of direct oral anticoagulants in patients with liver cirrhosis: a meta-analysis 肝硬化患者直接口服抗凝剂的安全性和有效性：一项荟萃分析

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103296

Daniel Tham , Wenhui Yu , Lucy Zhao , Roger Kou , Jayhan Kherani , Pei Yi Li , Shreyas Sreeraman , Ali Eshaghpour , Allen Li , Mark A. Crowther

Background

Direct oral anticoagulants (DOACs) are the standard of care for treatment of venous thromboembolism and stroke prophylaxis in atrial fibrillation. Since patients with Child-Pugh (CP) B or C liver cirrhosis are underrepresented in trials, the safety of DOACs in this population is unclear.

Objectives

This study synthesized primary evidence on the safety profile of DOACs in patients with advanced liver cirrhosis.

Methods

A literature search of MEDLINE and Embase from inception to October 2025 identified randomized and nonrandomized cohort studies comparing DOAC with vitamin K antagonists or low-molecular-weight heparin in patients with liver cirrhosis. Screening and data collection were conducted in duplicate. The primary outcome was major bleeding defined by International Society on Thrombosis and Haemostasis criteria, stratified by CP class. Data were meta-analyzed using a random-effects model, presented as odds ratios (OR) with corresponding 95% CIs.

Results

Of 797 articles captured in the literature search, 15 nonrandomized (n = 17,387) and 1 randomized (n = 70) study were included. DOACs reduced major bleeding in both CP class B and C exclusive subgroup and a subgroup with unspecified CP stages of liver cirrhosis (CP B and C: OR, 0.53; 95% CI, 0.36-0.80; CP unspecified: OR, 0.66; 95% CI, 0.46-0.98).

Conclusion

Based on the findings of this meta-analysis, DOACs may be associated with a reduced risk of major bleeding compared with vitamin K antagonists or low-molecular-weight heparin in patients with liver cirrhosis, including those with CP class B and C cirrhosis. The results of this meta-analysis should be interpreted in the context of methodological limitations. Future analysis should evaluate the impact of specific DOACs and dosage on safety outcomes in this patient population.

背景：直接口服抗凝剂（DOACs）是房颤静脉血栓栓塞治疗和卒中预防的标准护理。由于Child-Pugh (CP) B或C型肝硬化患者在试验中的代表性不足，DOACs在这一人群中的安全性尚不清楚。目的本研究综合了DOACs治疗晚期肝硬化患者安全性的初步证据。方法通过MEDLINE和Embase从成立到2025年10月的文献检索，确定了比较DOAC与维生素K拮抗剂或低分子肝素治疗肝硬化患者的随机和非随机队列研究。筛选和数据收集一式两份进行。主要结局是根据国际血栓和止血学会的标准定义的大出血，并按CP分级。使用随机效应模型对数据进行meta分析，以比值比（OR）表示，相应的ci为95%。结果在797篇文献检索中，纳入15篇非随机研究（n = 17387）和1篇随机研究（n = 70）。DOACs减少了CP B级和C级独家亚组以及未指定CP分期肝硬化亚组的大出血（CP B和C: OR， 0.53; 95% CI, 0.36-0.80； CP未指定：OR， 0.66; 95% CI, 0.46-0.98）。基于这项荟萃分析的结果，与维生素K拮抗剂或低分子肝素相比，DOACs可能与肝硬化患者（包括CP B级和C级肝硬化患者）发生大出血的风险降低有关。本荟萃分析的结果应在方法学局限性的背景下进行解释。未来的分析应评估特定doac和剂量对该患者群体安全性结果的影响。

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引用次数: 0

A cecal slurry mouse model of polymicrobial abdominal sepsis to evaluate the effects of antiplatelet agents 建立多微生物腹腔脓毒症小鼠盲肠浆液模型，评价抗血小板药物的作用

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103292

Alexandre Mansour , Isabelle Gouin-Thibault , Elisa Rossi , Aurore Marchelli , Tiphaine Belleville-Rolland , Nicolas Nesseler , Pascale Gaussem , Christilla Bachelot-Loza

引用次数: 0

Discrepancy between international normalized ratio measurements in a heterozygous carrier of F10:p.Gly244Arg with recurrent venous thromboembolism: a case report 杂合载体F10:p的国际标准化比值测量差异。Gly244Arg伴复发性静脉血栓栓塞1例

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103298

Nikolaj Julian Skrøder Nytofte, Emil List Larsen

Background

The international normalized ratio (INR) is designed to monitor vitamin K antagonist (VKA) treatment. Before patients start a self-managing VKA program, parallel measurements are conducted to compare point-of-care testing (POCT) INR with venous INR samples. Previously, genetic variants in F7 have shown discrepancies in INR measurements when thromboplastins from different species were used. It is unknown whether genetic variants in F10 affect INR measured with thromboplastins from different species.

Key Clinical Question

Does F10:p.Gly244Arg heterozygosity affects the INR when measured using rabbit compared with human thromboplastin?

Clinical Approach

A patient self-managing warfarin treatment had a recurrent venous thromboembolism during VKA treatment. The POCT therapeutic range was low (ie, 1.6-2.4) based on parallel measurements of POCT INR (human thromboplastin) and venous INR (rabbit thromboplastin). Subsequently, it was noted that the patient had a spontaneous increase in INR (1.3), and the patient was found to be a heterozygous carrier of F10:p.Gly244Arg.

Conclusion

Genetic variants in F10 may also interfere with INR or prothrombin time measurements when different thromboplastins are used. This case illustrates that discrepancies in INR measurements with different thromboplastins should prompt consideration of genetic variants in F10 and F7 to ensure sufficient anticoagulant VKA treatment.

国际标准化比值（INR）是用来监测维生素K拮抗剂（VKA）治疗的。在患者开始自我管理VKA计划之前，进行平行测量以比较护理点测试（POCT） INR与静脉INR样本。以前，当使用来自不同物种的凝血酶时，F7的遗传变异显示出INR测量的差异。目前尚不清楚F10基因变异是否会影响来自不同物种的凝血酶测定的INR。关键临床问题[10]；Gly244Arg杂合性对兔血凝血活素INR的影响临床方法1例自我管理华法林治疗的患者在VKA治疗期间静脉血栓栓塞复发。基于POCT INR（人凝血活素）和静脉INR（兔凝血活素）的平行测量，POCT的治疗范围很低（即1.6-2.4）。随后发现患者INR自发升高（1.3），患者为F10:p.Gly244Arg杂合携带者。结论当使用不同的凝血酶时，F10基因变异也可能干扰INR或凝血酶原时间的测定。该病例表明，不同凝血酶的INR测量差异应提示考虑F10和F7的遗传变异，以确保充分的抗凝VKA治疗。

{"title":"Discrepancy between international normalized ratio measurements in a heterozygous carrier of F10:p.Gly244Arg with recurrent venous thromboembolism: a case report","authors":"Nikolaj Julian Skrøder Nytofte, Emil List Larsen","doi":"10.1016/j.rpth.2025.103298","DOIUrl":"10.1016/j.rpth.2025.103298","url":null,"abstract":"<div><h3>Background</h3><div>The international normalized ratio (INR) is designed to monitor vitamin K antagonist (VKA) treatment. Before patients start a self-managing VKA program, parallel measurements are conducted to compare point-of-care testing (POCT) INR with venous INR samples. Previously, genetic variants in <em>F7</em> have shown discrepancies in INR measurements when thromboplastins from different species were used. It is unknown whether genetic variants in <em>F10</em> affect INR measured with thromboplastins from different species.</div></div><div><h3>Key Clinical Question</h3><div>Does <em>F10</em>:p.Gly244Arg heterozygosity affects the INR when measured using rabbit compared with human thromboplastin?</div></div><div><h3>Clinical Approach</h3><div>A patient self-managing warfarin treatment had a recurrent venous thromboembolism during VKA treatment. The POCT therapeutic range was low (ie, 1.6-2.4) based on parallel measurements of POCT INR (human thromboplastin) and venous INR (rabbit thromboplastin). Subsequently, it was noted that the patient had a spontaneous increase in INR (1.3), and the patient was found to be a heterozygous carrier of <em>F10</em>:p.Gly244Arg.</div></div><div><h3>Conclusion</h3><div>Genetic variants in <em>F10</em> may also interfere with INR or prothrombin time measurements when different thromboplastins are used. This case illustrates that discrepancies in INR measurements with different thromboplastins should prompt consideration of genetic variants in <em>F10</em> and <em>F7</em> to ensure sufficient anticoagulant VKA treatment.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103298"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885201","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

Safety, tolerability, pharmacokinetics, and pharmacodynamics of KN060, a humanized anti-FXI/FXIa dual-domain antibody, following single ascending doses in healthy Chinese subjects 人源抗fxi /FXIa双结构域抗体KN060的安全性、耐受性、药代动力学和药效学，在健康中国受试者中单次增加剂量

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103322

Jie Huang , Jinlong Liu , Yaxin Liu , Yichen Cao , Wei Sun , Yanrong Dong , Yuwei Li , Jing Li , Qian Wu , Xiaoyan Yang , Shuang Yang , Chuanpin Chen , Guoping Yang

Background

KN060 is a humanized dual-domain antibody targeting coagulation factor XI (FXI) and factor XIa (FXIa) and is currently being developed for the prevention of thromboembolic diseases.

Objectives

This study aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single intravenous administration of KN060 in healthy Chinese subjects.

Methods

This single-center, randomized, double-blind, placebo-controlled clinical study was conducted in 38 healthy Chinese subjects. The study included 6 dose groups (0.1, 0.3, 1.0, 2.5, 5.0, and 10.0 mg/kg), with KN060 administered via a single ascending-dose regimen.

Results

KN060 demonstrates good tolerability and safety, with no significant treatment-emergent adverse events. A single intravenous infusion of KN060, ranging from 0.1 to 10.0 mg/kg, resulted in an average T_max ranging from 1.02 to 3.34 hours. For a dose range of 0.3 to 10.0 mg/kg, the average half-life ranged from 122.96 to 146.47 hours. Pharmacokinetic and pharmacodynamic analyses revealed that within the dose range of 0.1 to 10.0 mg/kg, drug concentration was positively correlated with activated partial thromboplastin time and negatively correlated with factor (F)XI activity and free FXI content. Immunogenicity analysis showed that all subjects were negative for antidrug antibodies.

Conclusion

The study results demonstrated that KN060 was well tolerated and safe. Based on pharmacokinetic and pharmacodynamic data, KN060 is a promising humanized dual-domain antibody simultaneously targeting FXI/FXIa for the prevention of thromboembolic diseases.

Trial Registration

https://www.chictr.org.cn, identifier: ChiCTR2200056926; http://www.chinadrugtrials.org.cn, identifier: CTR20222339.

kn060是一种靶向凝血因子XI （FXI）和XIa因子（FXIa）的人源化双域抗体，目前正在开发用于预防血栓栓塞性疾病。目的评价中国健康受试者单次静脉给药KN060的安全性、耐受性、药代动力学和药效学。方法采用单中心、随机、双盲、安慰剂对照的临床研究，选取38名健康的中国受试者。研究包括6个剂量组（0.1、0.3、1.0、2.5、5.0和10.0 mg/kg）， KN060采用单次递增给药方案。结果skn060表现出良好的耐受性和安全性，无明显的治疗不良事件。单次静脉输注KN060，范围为0.1 ~ 10.0 mg/kg，导致平均Tmax范围为1.02 ~ 3.34小时。剂量为0.3至10.0 mg/kg时，平均半衰期为122.96至146.47小时。药代动力学和药效学分析显示，在0.1 ~ 10.0 mg/kg剂量范围内，药物浓度与活化的部分凝血活素时间呈正相关，与因子(F)XI活性和游离FXI含量呈负相关。免疫原性分析显示所有受试者抗药物抗体均为阴性。结论研究结果表明，KN060具有良好的耐受性和安全性。基于药代动力学和药效学数据，KN060是一种有希望同时靶向FXI/FXIa的人源化双结构域抗体，可用于预防血栓栓塞性疾病。试用注册https://www.chictr.org.cn，标识符：ChiCTR2200056926；http://www.chinadrugtrials.org.cn，标识符：CTR20222339。

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引用次数: 0

Venous thromboembolism in patients with breast, ovarian, and uterine cancer. A comparative analysis from the Registro Informatizado Enfermedad TromboEmbólica registry 乳腺癌、卵巢癌和子宫癌患者的静脉血栓栓塞。来自Registro Informatizado Enfermedad TromboEmbólica注册表的比较分析

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103301

Olga Gavín Sebastián , Javier Trujillo-Santos , María del Carmen Díaz-Pedroche , Pablo Demelo-Rodríguez , Sonia Otálora , Benjamin Brenner , José María Pedrajas , Alessandra Bura-Riviere , Luis Hernández-Blasco , Manuel Monreal

Background

The risk of recurrent venous thromboembolism (VTE) and bleeding during anticoagulation may vary by the cancer type.

Objectives

We assessed outcomes during anticoagulation in women with breast, ovarian, or uterine cancer and VTE.

Methods

We analyzed data from the Registro Informatizado Enfermedad TromboEmbólica registry on 4721 women with active breast (n = 2929), ovarian (n = 886), or uterine (n = 906) cancer and acute VTE. We assessed VTE recurrences, bleeding, and mortality according to cancer type and anticoagulant type. Multivariate Cox models were adjusted for age, metastases, anemia, renal function, and treatment at VTE onset.

Results

Uterine cancer patients had the highest rates of major bleeding (11.1 per 100 patient-years) and fatal bleeding (1.07 per 100 patient-years), while ovarian cancer patients had the highest rate of VTE recurrences (7.29 per 100 patient-years). In contrast, breast cancer patients had the lowest event rates overall. Among low-molecular-weight heparin–treated patients, major bleeding was higher in uterine (6.37 per 100 patient-years) and ovarian (4.62 per 100 patient-years) cancer than breast cancer patients (1.89 per 100 patient-years). Direct oral anticoagulant use was associated with low recurrence rates in breast cancer (0.58 per 100 patient-years), but outcomes in uterine cancer remained less favorable. Multivariable models confirmed cancer-specific risks.

Conclusions

VTE outcomes vary significantly by cancer type. Patients with uterine cancer face an elevated bleeding risk, potentially impacting anticoagulant continuity and contributing to VTE recurrence. These findings support the need for cancer-specific risk assessment and individualized anticoagulation strategies adapted to the specific cancer type.

背景：抗凝期间静脉血栓栓塞（VTE）和出血复发的风险可能因癌症类型而异。目的：我们评估患有乳腺癌、卵巢癌或子宫癌和静脉血栓栓塞的妇女抗凝治疗的结果。方法：我们分析了来自Registro Informatizado Enfermedad TromboEmbólica登记处的4721名患有活动性乳腺癌（n = 2929）、卵巢癌（n = 886）或子宫癌（n = 906）和急性静脉血栓栓塞的妇女的数据。我们根据癌症类型和抗凝血类型评估静脉血栓栓塞复发、出血和死亡率。多变量Cox模型根据年龄、转移、贫血、肾功能和静脉血栓栓塞发作时的治疗进行调整。结果宫颈癌患者大出血发生率最高（11.1 / 100患者-年），致死性出血发生率最高（1.07 / 100患者-年），而卵巢癌患者静脉血栓栓塞复发率最高（7.29 / 100患者-年）。相比之下，乳腺癌患者的总体发病率最低。在低分子肝素治疗的患者中，子宫癌（6.37 / 100患者-年）和卵巢癌（4.62 / 100患者-年）的大出血高于乳腺癌（1.89 / 100患者-年）。直接口服抗凝剂与乳腺癌的低复发率相关（0.58 / 100患者年），但子宫癌的结果仍然不太有利。多变量模型证实了癌症特异性风险。结论不同肿瘤类型svte预后差异显著。子宫癌患者出血风险升高，可能影响抗凝药物的连续性并导致静脉血栓栓塞复发。这些发现支持癌症特异性风险评估和适应特定癌症类型的个体化抗凝策略的必要性。

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引用次数: 0

Clinical characteristics of thrombocytopenia in tropical diseases and management in resource-limited settings 热带疾病中血小板减少症的临床特征及资源有限地区的管理

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103323

Gerard Gurumurthy , Juditha Gurumurthy , Samantha Gurumurthy , Lianna Reynolds , Dawn Swan , Jecko Thachil

Platelets play a central role in the pathogenesis of tropical infectious diseases. Infections such as malaria, dengue, and leptospirosis are often accompanied by thrombocytopenia. While the platelet count is typically monitored as a measure of thrombocytopenia, other platelet indices may better determine bleeding severity. Platelet dysfunction in these conditions requires a nuanced approach to management. Prophylactic platelet transfusions have shown limited efficacy in preventing hemorrhagic complications and carry additional risks. These include transfusion-transmitted infections, logistical challenges, and the high cost of platelet concentrates. Herein, we review current insights into platelet biology in major tropical infections, examine the varied mechanisms underlying thrombocytopenia in these conditions, and discuss the latest evidence on transfusion guidelines. We also propose evidence-based approaches to thrombocytopenia management and platelet transfusion. We aim to summarize approaches that may improve care for populations disproportionately affected by tropical infectious diseases in resource-limited settings.

血小板在热带传染病的发病机制中起着核心作用。疟疾、登革热和钩端螺旋体病等感染常伴有血小板减少症。虽然血小板计数通常监测作为血小板减少的措施，其他血小板指标可能更好地确定出血严重程度。在这些情况下，血小板功能障碍需要一个细致入微的方法来管理。预防性血小板输注在预防出血性并发症方面显示出有限的功效，并具有额外的风险。这些挑战包括输血传播感染、后勤挑战和血小板浓缩物的高成本。在此，我们回顾了目前对主要热带感染中血小板生物学的见解，检查了这些情况下血小板减少的各种机制，并讨论了输血指南的最新证据。我们还提出以证据为基础的方法来治疗血小板减少症和血小板输注。我们的目标是总结可能改善在资源有限的环境中受热带传染病不成比例影响的人群的护理方法。

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引用次数: 0

Selection and optimization strategy for Rap1-targeting single-domain antibodies as platelet activation markers 靶向rap1的单结构域抗体作为血小板活化标志物的选择与优化策略

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103294

Marie-Christine Alessi , Maxime Moulard , Daniele Boulay-Moine , Cyril Pons , Marielle Margier , Cléa Vessière , Marjorie Poggi , Theo Pigaglio , Francoise Dignat-George , Alain Roussel , Stéphane Burtey , Laurent Bonello , Patrick Chames , Remi Bonjean , Franck Peiretti

Background

Rap1 is critical for platelet activation, functioning as a key node of the platelet activation pathways.

Objectives

This study aimed to develop VHH-Fc (minibodies) against Rap1 for the purpose to quantify active Rap1 levels in platelets.

Methods

We have produced the first generation of VHHs against active Rap1 through a series of negative and positive screenings of a synthetic phage display library, utilizing both inactive and active Rap1B. We performed random mutagenesis, followed by yeast 2-hybrid screening to optimize variants.

Results

Among 122 VHH clones, 2 with the highest redundancy were subcloned as VHH-Fc. Both selectively detected active Rap1B G12V in HeLa cells but failed to recognize the inactive Rap1B S17N isoform. They successfully captured Rap1 from platelet lysates incubated with GTPγS and from thrombin receptor activator peptide 6–stimulated platelets. Further optimization yielded 2 superbinder VHH clones: VHH-Fc B89 and VHH-Fc B14. VHH-Fc B89 exhibited a K_D of 4.4 nM and showed enhanced capacity to capture active GTP-bound Rap1 compared with the original VHH-Fc. Additionally, it was able to detect overexpressed active Rap1B G12V in HeLa cells. An ELISA setup combining VHH-Fc B14 and a commercial monoclonal antibody targeting total Rap1 was highly effective in detecting both GTPγS-bound Rap1 and endogenous active Rap1 in platelets.

Conclusion

This study identifies, that accurately capture active Rap1 in platelets, thereby establishing them as promising tools for future research. We also developed a reliable ELISA test that can facilitate clinical studies to monitor platelet Rap1 activation in various medical contexts.

背景：drap1对血小板激活至关重要，是血小板激活途径的关键节点。目的建立抗Rap1的VHH-Fc（小体），定量测定血小板中Rap1的活性水平。方法利用非活性和活性Rap1B，通过一系列合成噬菌体展示文库的阴性和阳性筛选，制备了第一代抗活性Rap1的vhs。我们进行了随机诱变，然后进行酵母2杂交筛选以优化变异。结果122个VHH克隆中，2个冗余度最高的克隆为VHH- fc。这两种方法都能在HeLa细胞中选择性地检测到活性Rap1B G12V，但无法识别非活性Rap1B S17N亚型。他们成功地从与gtp - γ s孵育的血小板裂解液和凝血酶受体激活肽6刺激的血小板中捕获Rap1。进一步优化得到2个超粘结剂VHH克隆：VHH- fc B89和VHH- fc B14。与原始VHH-Fc相比，VHH-Fc B89的KD值为4.4 nM，具有更强的捕获活性gtp结合Rap1的能力。此外，它能够检测HeLa细胞中过表达的活性Rap1B G12V。结合vhs - fc B14和一种靶向总Rap1的商业单克隆抗体建立的ELISA试剂盒在检测血小板中gtp - γ - s结合的Rap1和内源性活性Rap1中都是非常有效的。本研究确定了准确捕获血小板中活性Rap1的方法，从而将其作为未来研究的有前途的工具。我们还开发了一种可靠的ELISA测试，可以促进临床研究，以监测血小板Rap1在各种医学背景下的激活。

{"title":"Selection and optimization strategy for Rap1-targeting single-domain antibodies as platelet activation markers","authors":"Marie-Christine Alessi , Maxime Moulard , Daniele Boulay-Moine , Cyril Pons , Marielle Margier , Cléa Vessière , Marjorie Poggi , Theo Pigaglio , Francoise Dignat-George , Alain Roussel , Stéphane Burtey , Laurent Bonello , Patrick Chames , Remi Bonjean , Franck Peiretti","doi":"10.1016/j.rpth.2025.103294","DOIUrl":"10.1016/j.rpth.2025.103294","url":null,"abstract":"<div><h3>Background</h3><div>Rap1 is critical for platelet activation, functioning as a key node of the platelet activation pathways.</div></div><div><h3>Objectives</h3><div>This study aimed to develop VHH-Fc (minibodies) against Rap1 for the purpose to quantify active Rap1 levels in platelets.</div></div><div><h3>Methods</h3><div>We have produced the first generation of VHHs against active Rap1 through a series of negative and positive screenings of a synthetic phage display library, utilizing both inactive and active Rap1B. We performed random mutagenesis, followed by yeast 2-hybrid screening to optimize variants.</div></div><div><h3>Results</h3><div>Among 122 VHH clones, 2 with the highest redundancy were subcloned as VHH-Fc. Both selectively detected active Rap1B G12V in HeLa cells but failed to recognize the inactive Rap1B S17N isoform. They successfully captured Rap1 from platelet lysates incubated with GTPγS and from thrombin receptor activator peptide 6–stimulated platelets. Further optimization yielded 2 superbinder VHH clones: VHH-Fc B89 and VHH-Fc B14. VHH-Fc B89 exhibited a <em>K</em><sub>D</sub> of 4.4 nM and showed enhanced capacity to capture active GTP-bound Rap1 compared with the original VHH-Fc. Additionally, it was able to detect overexpressed active Rap1B G12V in HeLa cells. An ELISA setup combining VHH-Fc B14 and a commercial monoclonal antibody targeting total Rap1 was highly effective in detecting both GTPγS-bound Rap1 and endogenous active Rap1 in platelets.</div></div><div><h3>Conclusion</h3><div>This study identifies, that accurately capture active Rap1 in platelets, thereby establishing them as promising tools for future research. We also developed a reliable ELISA test that can facilitate clinical studies to monitor platelet Rap1 activation in various medical contexts.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103294"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022850","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

Direct oral anticoagulant interference and removal in the factor VIII inhibitor assay 直接口服抗凝血剂干扰和去除因子VIII抑制剂试验

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103334

Rick Timmerije , Saskia E.M. Schols , Daniëlle Meijer , Wideke Barteling , An K. Stroobants , Sanna R. Rijpma

Background

Direct oral anticoagulants (DOACs) interfere with clot-based assays, including factor (F)VIII testing and the Nijmegen–Bethesda assay, potentially leading to false-positive results for FVIII inhibitors. Misinterpretation of these results carries serious clinical consequences. Activated charcoal-based products, such as DOAC Remove, may restore assay accuracy, but data supporting their use in FVIII inhibitor assays are limited.

Objectives

In this study, we aim to determine DOAC interference in FVIII inhibitor testing and evaluate effectivity of DOAC removal to restore assay reliability.

Methods

Normal pooled plasma was spiked with therapeutic and supratherapeutic concentrations of apixaban, edoxaban, rivaroxaban, and dabigatran. Plasma pools from persons with acquired hemophilia A were spiked with DOACs and retested with and without DOAC removal treatment to evaluate workflow performance. FVIII inhibitor activity was measured with and without activated charcoal-based DOAC removal to establish DOAC interference and removal efficacy.

Results

Spiking experiments with DOACs caused concentration-dependent false-positive FVIII inhibitor results (>0.6 Nijmegen Bethesda Units/mL), with dabigatran showing the strongest interference and apixaban the weakest. DOAC removal substantially reduced or eliminated interference across all drugs. Post-removal FVIII inhibitor values closely matched baseline concentrations in both spiked normal pooled plasma and pooled patient plasma, with most results within ±20% of the assay variability.

Conclusion

DOACs significantly interfere with FVIII inhibitor assays, potentially causing clinically significant false-positive results. Activated charcoal-based DOAC removal treatment provides a practical solution to restore assay reliability. These findings support the integration of DOAC removal into anti-FVIII testing protocols for patients on anticoagulant therapy.

直接口服抗凝剂（DOACs）干扰基于凝块的检测，包括因子(F)VIII检测和Nijmegen-Bethesda检测，可能导致FVIII抑制剂的假阳性结果。对这些结果的误解会带来严重的临床后果。活性炭基产品，如DOAC Remove，可以恢复测定的准确性，但支持其在FVIII抑制剂测定中的使用的数据有限。目的在本研究中，我们旨在确定DOAC对FVIII抑制剂检测的干扰，并评估去除DOAC的有效性，以恢复检测的可靠性。方法用治疗和超治疗浓度的阿哌沙班、依多沙班、利伐沙班和达比加群加入正常血浆。在获得性血友病A患者的血浆池中加入DOAC，并在去除DOAC和不去除DOAC的情况下重新测试，以评估工作流程的性能。在活性炭基DOAC去除和不去除的情况下，测定了FVIII抑制剂的活性，以确定DOAC干扰和去除效果。结果DOACs脉冲实验导致FVIII抑制剂呈浓度依赖性假阳性（0.6奈美亨贝塞斯达单位/mL），其中达比加群干扰最强，阿哌沙班干扰最弱。DOAC的去除大大减少或消除了所有药物之间的干扰。去除后FVIII抑制剂值与正常血浆和患者血浆中的基线浓度密切匹配，大多数结果在±20%的检测变异性内。结论doacs显著干扰FVIII抑制剂测定，可能导致临床显著的假阳性结果。活性炭基DOAC去除处理提供了恢复测定可靠性的实用解决方案。这些发现支持将DOAC去除纳入抗凝治疗患者的抗fviii检测方案。

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引用次数: 0