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

Maternal thrombocytopenia is not predictive of neonatal thrombocytopenia: a single-center Irish study 母体血小板减少不能预测新生儿血小板减少：一项爱尔兰单中心研究

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-11-01 DOI: 10.1016/j.rpth.2024.102622

Ligia Nechifor , Daniel O’Reilly , John O’Loughlin , Fionnuala Ní Áinle , Naomi Mc Callion , Lyudmyla Zakharchenko

Background

Maternal thrombocytopenia during pregnancy is common. However, the relationship between maternal and neonatal thrombocytopenia is poorly understood.

Objectives

We aimed to determine whether an association exists between platelet counts of neonates born to mothers with moderate-to-severe thrombocytopenia (<100 × 10⁹/L) and neonatal platelet counts.

Methods

We identified records from 557 patients with moderate-to-severe thrombocytopenia (maternal platelet count <100 × 10⁹/L) and the 338 associated newborn charts from 2018 to 2022 in a single large maternity center. Pregnant people with a platelet count of <100 × 10⁹/L prior to delivery during present gestation were included. Any thrombocytopenia that occurred outside of pregnancy or in the postpartum period was excluded. A logistic regression was then generated to examine the association between maternal thrombocytopenia and neonatal thrombocytopenia. A receiver operating characteristic (ROC) curve was generated to assess accuracy of (i) lowest maternal platelet count and (ii) trimester of thrombocytopenia onset in predicting neonatal thrombocytopenia.

Results

A total of 550 full blood count assessments were taken in neonates of pregnant people with thrombocytopenia. Sixteen neonates with clinically significant thrombocytopenia (platelet count <100 × 10⁹/L) were identified. A binomial logistic regression was fitted that demonstrated limited association between lowest maternal platelet count and trimester of onset of maternal thrombocytopenia and the development of neonatal thrombocytopenia. An ROC curve was generated to determine the accuracy of maternal platelet count at identifying neonatal thrombocytopenia. The coordinates of the best platelet count threshold for this dataset were then derived from the ROC curve and determined that a threshold of 77.5 × 10⁹/L maternal platelets offered the best accuracy.

Conclusion

Neonatal full blood count assessment based on maternal platelet counts of <100 × 10⁹/L has a poor diagnostic yield with no statistically significant association in this cohort on logistic regression analysis. A lower threshold of 77.5 × 10⁹/L may be of higher clinical utility and improve laboratory and clinical workflow.

背景：妊娠期母体血小板减少症很常见。然而，产妇和新生儿血小板减少症之间的关系尚不清楚。目的探讨中度至重度血小板减少症（100 × 109/L）母亲所生新生儿血小板计数与新生儿血小板计数之间是否存在关联。方法对某大型妇产中心2018 - 2022年557例中重度血小板减少症患者（母体血小板计数100 × 109/L）的记录和338例相关新生儿图表进行分析。本研究纳入了妊娠期分娩前血小板计数为100 × 109/L的孕妇。排除妊娠期外或产后发生的任何血小板减少症。然后产生逻辑回归来检查母体血小板减少症和新生儿血小板减少症之间的关系。生成受试者工作特征（ROC）曲线，以评估(i)最低母体血小板计数和（ii）血小板减少发作的三个月在预测新生儿血小板减少方面的准确性。结果共对孕妇血小板减少症新生儿进行了550次全血细胞计数评估。16例新生儿有明显的临床血小板减少症（血小板计数100 × 109/L）。二项logistic回归拟合表明，最低的母体血小板计数与母体血小板减少症发病的三个月和新生儿血小板减少症的发展之间存在有限的关联。生成ROC曲线以确定母体血小板计数在鉴别新生儿血小板减少症方面的准确性。然后从ROC曲线中导出该数据集的最佳血小板计数阈值坐标，并确定77.5 × 109/L母体血小板阈值具有最佳准确性。结论基于母亲血小板计数100 × 109/L评估新生儿全血细胞计数诊断符合率较低，经logistic回归分析该队列无统计学意义。较低的阈值77.5 × 109/L可能具有更高的临床效用，并改善实验室和临床工作流程。

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引用次数: 0

Efficacy, safety, and quality of life 4 years after valoctocogene roxaparvovec gene transfer for severe hemophilia A in the phase 3 GENEr8-1 trial 在GENEr8-1期临床试验中，valoccogene roxaparvovec基因转移治疗严重血友病A后4年的疗效、安全性和生活质量

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-11-01 DOI: 10.1016/j.rpth.2024.102615

Andrew D. Leavitt , Johnny Mahlangu , Priyanka Raheja , Emily Symington , Doris V. Quon , Adam Giermasz , Maria Fernanda López Fernández , Gili Kenet , Gillian Lowe , Nigel S. Key , Carolyn M. Millar , Steven W. Pipe , Bella Madan , Sheng-Chieh Chou , Robert Klamroth , Jane Mason , Hervé Chambost , Flora Peyvandi , Elaine Majerus , Dominic Pepperell , Margareth C. Ozelo

Background

Valoctocogene roxaparvovec, an adeno-associated virus-mediated gene therapy for severe hemophilia A, enables endogenous factor (F)VIII expression and provides bleed protection.

Objectives

Determine valoctocogene roxaparvovec durability, efficacy, and safety 4 years after treatment.

Methods

In the phase 3 GENEr8-1 trial, 134 adult male persons with severe hemophilia A without inhibitors and previously using FVIII prophylaxis received a 6 × 10¹³ vg/kg infusion of valoctocogene roxaparvovec. Efficacy endpoints included annualized bleed rate, annualized FVIII infusion rate, FVIII activity, and the Haemophilia-Specific Quality of Life Questionnaire for Adults. Adverse events and immunosuppressant use were assessed. Change from baseline was assessed after participants discontinued prophylaxis (scheduled for week 4).

Results

Median follow-up was 214.3 weeks; 2 participants discontinued since the previous data cutoff. Declines from baseline in mean treated annualized bleed rate (−82.6%; P < .0001) and annualized FVIII infusion rate (−95.5%; P < .0001) were maintained from previous years in the primary analysis population of 112 participants who enrolled from a noninterventional study. During year 4, 81 of 110 rollover participants experienced 0 treated bleeds. Week 208 mean and median chromogenic FVIII activity were 16.1 IU/dL and 6.7 IU/dL, respectively, in 130 modified intention-to-treat participants. Seven participants resumed prophylaxis since the previous data cutoff. Mean change from baseline to week 208 in Haemophilia-Specific Quality of Life Questionnaire for Adults Total Score (P < .0001) remained clinically meaningful for modified intention-to-treat participants. Alanine aminotransferase elevation was the most common adverse event during year 4 (56/131 participants); none required immunosuppressants.

Conclusion

Valoctocogene roxaparvovec provides persistent FVIII expression, hemostatic control, and health-related quality of life improvements with no new safety signals.

valoccogene roxaparvovec是一种腺相关病毒介导的治疗严重血友病A的基因疗法，可使内源性因子(F)VIII表达并提供出血保护。目的评价伐罗替克治疗4年后的疗效、安全性和耐受性。方法在GENEr8-1 iii期临床试验中，134名患有严重血友病A且未使用抑制剂且先前使用过FVIII预防药物的成年男性患者接受了6 × 1013vg /kg的缬罗替克输注。疗效终点包括年化出血率、年化FVIII输注率、FVIII活性和成人血友病特异性生活质量问卷。评估不良事件和免疫抑制剂的使用情况。在受试者停止预防治疗（计划第4周）后，评估与基线的变化。2名参与者自上次数据截止后停止。与基线相比，平均治疗年化出血率下降(- 82.6%；P & lt;0.0001)和年化FVIII输注率(−95.5%；P & lt;.0001)的数据与前几年的非干预性研究纳入的112名参与者的主要分析人群保持一致。在第4年，110名轮转参与者中有81人经历了0次治疗出血。在第208周，130名修改意向治疗的参与者中，显色FVIII活性的平均值和中位数分别为16.1 IU/dL和6.7 IU/dL。自上次数据截止以来，7名参与者恢复了预防。成人血友病特异性生活质量问卷总分从基线到第208周的平均变化(P <；0.0001)对于修改意向治疗的参与者仍然具有临床意义。丙氨酸转氨酶升高是第4年最常见的不良事件（56/131参与者）；不需要免疫抑制剂。结论伐罗替克提供持续的FVIII表达、止血控制和健康相关生活质量改善，无新的安全信号。

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引用次数: 0

The anticoagulant effects of milvexian, a novel small molecule factor XIa inhibitor, are neutralized by activated prothrombin complex concentrates and recombinant factor VIIa in human plasma and whole blood in vitro 新型小分子因子XIa抑制剂milvexian的抗凝作用可通过活化凝血酶原复合物浓缩物和重组因子VIIa在人血浆和体外全血中中和

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-11-01 DOI: 10.1016/j.rpth.2024.102600

Matthew Bunce, Zheng Huang Devine, Madhu Chintala

Background

The development of anticoagulants that provide antithrombotic efficacy without a concomitant bleeding risk remains an unmet clinical need in thrombosis. Although direct oral anticoagulants (DOACs) have a reduced incidence of major bleeding compared with warfarin, they still carry a bleeding risk, resulting in a suboptimal therapeutic index. Epidemiologic data suggest that inhibiting activated factor XI (FXIa) may offer an improved safety profile with respect to bleeding risk compared with current-generation DOACs. Additionally, a phase II trial of milvexian in patients undergoing elective total knee replacement demonstrated robust dose-dependent efficacy with no statistically significant increase in bleeding. Nevertheless, the ability to rapidly and effectively correct FXIa inhibitor–induced anticoagulation may still be important in situations where patients experience uncontrolled bleeding or require emergency surgery.

Objectives

We assessed the ability to normalize the anticoagulant effects of the novel small-molecule FXIa inhibitor milvexian (BMS-986177/JNJ-70033093) in vitro using commercially available prohemostatic agents.

Methods

Milvexian-associated anticoagulation and correction was evaluated in activated partial thromboplastin time clotting assays, thromboelastography, and kaolin-initiated thrombin generation assays.

Results

Activated prothrombin complex concentrates (PCCs) and recombinant factor (rF)VIIa corrected the anticoagulant effects of milvexian in activated partial thromboplastin time clotting assays, thromboelastography, and kaolin-initiated thrombin generation assays. In contrast, other agents, including PCCs, rFIX, and rFVIII, demonstrated either modest or no correction of milvexian-associated anticoagulation.

Conclusion

This study demonstrated that currently available activated PCCs and rFVIIa normalize the anticoagulation induced by milvexian in vitro. The clinical utility of these agents remains to be established.

开发具有抗血栓疗效而不伴有出血风险的抗凝剂仍然是血栓形成的未满足的临床需求。尽管与华法林相比，直接口服抗凝剂（DOACs）的大出血发生率降低，但仍存在出血风险，导致治疗指数不理想。流行病学数据表明，与当前一代doac相比，抑制活化因子XI （FXIa）在出血风险方面可能提供更高的安全性。此外，milvexian在选择性全膝关节置换术患者中的II期试验显示出强大的剂量依赖性疗效，没有统计学上显著的出血增加。然而，快速有效纠正FXIa抑制剂诱导抗凝的能力在患者出现无法控制的出血或需要紧急手术的情况下仍然是重要的。目的评估新型小分子FXIa抑制剂milvexian （BMS-986177/JNJ-70033093）在体外使用市售的止血前药物的抗凝作用。方法采用活化的部分凝血活素时间凝血试验、血栓弹性成像和高岭土启动的凝血酶生成试验，对smilvexian相关抗凝和校正效果进行评价。结果活化凝血酶原复合物浓缩物（PCCs）和重组因子（rF）VIIa在活化部分凝血酶活时间凝血试验、血栓弹性成像和高岭土启动凝血酶生成试验中纠正了米尔维昔安的抗凝作用。相比之下，其他药物，包括PCCs、rFIX和rFVIII，显示出适度或没有纠正米尔韦昔酮相关抗凝。结论本研究表明，现有的活化PCCs和rFVIIa可使密尔维昔酮诱导的体外抗凝作用正常化。这些药物的临床应用仍有待确定。

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引用次数: 0

Bleeding disorder of unknown cause: an illustrated review on current practice, knowledge gaps, and future perspectives 原因不明的出血性疾病：对当前实践、知识差距和未来前景的图解回顾

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-11-01 DOI: 10.1016/j.rpth.2024.102625

Amaury L.L. Monard , Caroline M.A. Mussert , Tirsa T. van Duijl , Marieke J.H.A. Kruip , Yvonne M.C. Henskens , Maartje van den Biggelaar , Roger E.G. Schutgens , Saskia E.M. Schols , Karin J. Fijnvandraat , Karina Meijer , Paul L. den Exter , Laurens Nieuwenhuizen , Iris van Moort , Ross I. Baker , James S. O’Donnell , Marjon H. Cnossen , Floor C.J.I. Heubel-Moenen , BDUC-iN Study group

In more than half of the individuals with a clinically relevant bleeding tendency who are referred to hemostasis experts, no biological etiology can be found after extensive laboratory testing. These persons are diagnosed with an unexplained bleeding tendency or “bleeding disorder of unknown cause” (BDUC). The mucocutaneous bleeding phenotype of individuals with BDUC is generally comparable to that of individuals with inherited bleeding disorders such as von Willebrand disease or platelet function disorders. BDUC definitions applied in literature are heterogeneous, but all comprise 2 main criteria: (1) there is an increased bleeding tendency based on the clinical view of the physician and/or an increased bleeding score; (2) no abnormalities are found with available hemostasis laboratory tests. This is reflected in the recent published BDUC definition by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis, stating that BDUC is a diagnosis of exclusion, characterized by normal hemostatic investigations despite a clinically significant bleeding tendency. Importantly, other nonhemostatic and acquired causes of bleeding should be excluded, but details on exclusion criteria and associated diagnostic testing remain undefined. Patients and health care providers are challenged by the uncertainty and lack of formal diagnosis particularly as there is no clear consensus regarding treatment. Research on the diagnostic value of new laboratory tests in individuals with BDUC has not yet been productive. In this illustrative review, the current practice and knowledge gaps in BDUC are addressed, previous research on BDUC is outlined and future directions with outstanding questions for future research in BDUC are highlighted.

在超过一半的有临床相关出血倾向的个体中，经广泛的实验室检测后，没有发现生物学病因。这些人被诊断为不明原因的出血倾向或“原因不明的出血障碍”（BDUC）。BDUC患者的粘膜皮肤出血表型通常与遗传性出血性疾病（如血管性血友病或血小板功能障碍）患者相当。文献中应用的BDUC定义各不相同，但都包括两个主要标准：(1)根据医生的临床观点和/或出血评分增加，出血倾向增加；(2)可用的止血实验室检查未发现异常。这反映在国际血栓与止血学会科学与标准化委员会最近公布的BDUC定义中，指出BDUC是一种排除性诊断，其特征是尽管临床上有明显的出血倾向，但止血检查正常。重要的是，应排除其他非止血和获得性出血原因，但排除标准和相关诊断检测的细节仍未明确。患者和卫生保健提供者受到不确定性和缺乏正式诊断的挑战，特别是在对治疗没有明确共识的情况下。新的实验室检查对BDUC患者的诊断价值的研究尚未取得成果。在这篇说明性的综述中，阐述了BDUC目前的实践和知识空白，概述了BDUC的既往研究，并强调了BDUC未来研究的方向和突出问题。

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引用次数: 0

External validation of the Leiden Thrombosis Recurrence Risk Prediction models (L-TRRiP) for the prediction of recurrence after a first venous thrombosis in the Heart and Vascular Health study 莱顿血栓复发风险预测模型（L-TRRiP）用于预测心脏和血管健康研究中首次静脉血栓形成后的复发情况的外部验证

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-11-01 DOI: 10.1016/j.rpth.2024.102610

J. Louise I. Burggraaf-van Delft , Kerri L. Wiggins , Nienke van Rein , Saskia le Cessie , Nicholas L. Smith , Suzanne C. Cannegieter

Background

Long-term outcome after a first venous thromboembolism (VTE) might be optimized by tailoring anticoagulant treatment duration on individual risks of recurrence and major bleeding. The L-TRRiP models (A–D) were previously developed in data from the Dutch Multiple Environment and Genetic Assessment of Risk Factors for Venous thrombosis study to predict VTE recurrence.

Objectives

We aimed to externally validate models C and D using data from the United States Heart and Vascular Health (HVH) study.

Methods

Data from participants with a first VTE who discontinued initial anticoagulant therapy were used to determine model performance. Missing data were imputed, and results were pooled according to Rubin’s rules. To determine discrimination, Harrell’s C-statistic was calculated. To assess calibration, the observed/expected (O/E) ratio was estimated, and calibration plots were created, in which we accounted for the competing risk of death. A stratified analysis based on age <70 or >70 years was performed.

Results

Of 1430 participants from the HVH study, 187 experienced an unprovoked VTE recurrence during follow-up. The C-statistics of L-TRRIP models C and D were 0.62 (95% CI, 0.56-0.67) and 0.61 (95% CI, 0.55-0.67), respectively. The O/E ratio (1.00; 95% CI, 0.84-1.17 and 1.09; 95% CI, 0.91-1.27, respectively) and calibration plots indicated good calibration. The discrimination was similar between participants <70 or >70 years, whereas overall calibration was lower in participants <70 years.

Conclusion

The L-TRRiP models showed moderate discrimination and good calibration in a different population and can be used to guide clinical decision making. To assess the added value in daily clinical practice, a management study is needed.

背景首次静脉血栓栓塞症（VTE）后的长期预后可通过根据复发和大出血的个体风险调整抗凝治疗时间来优化。L-TRRiP 模型（A-D）之前是根据荷兰静脉血栓形成风险因素的多重环境和遗传评估研究的数据开发的，用于预测 VTE 复发。对缺失数据进行估算，并根据鲁宾规则对结果进行汇总。为确定区分度，计算了 Harrell 的 C 统计量。为评估校准情况，我们估算了观察/预期（O/E）比率，并绘制了校准图，其中考虑了死亡的竞争风险。结果在 HVH 研究的 1430 名参与者中，有 187 人在随访期间经历了无诱因 VTE 复发。L-TRRIP 模型 C 和 D 的 C 统计量分别为 0.62（95% CI，0.56-0.67）和 0.61（95% CI，0.55-0.67）。O/E比值（分别为1.00；95% CI，0.84-1.17和1.09；95% CI，0.91-1.27）和校准图显示校准效果良好。结论 L-TRRiP 模型在不同人群中显示出适度的区分度和良好的校准性，可用于指导临床决策。要评估其在日常临床实践中的附加值，还需要进行管理研究。

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引用次数: 0

In-depth characterization of N-glycosylation and sialic acid content in fetal and adult fibrinogen 胎儿和成人纤维蛋白原n-糖基化和唾液酸含量的深入表征

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-11-01 DOI: 10.1016/j.rpth.2024.102618

Tana V. Palomino , Anastasia Sheridan , David C. Muddiman , Ashley C. Brown

Background

Fetal fibrinogen is a variant present in neonates. Blood products used in neonates are tailored for adults and do not seamlessly integrate into neonatal clots. Increased sialic acid content has been found in fetal fibrinogen compared with adult fibrinogen. However, the extent or location of sialic acids on fibrinogen remains unknown.

Objectives

To investigate differences in glycosylation and sialic acid content between fetal and adult fibrinogen.

Methods

Glycans were eluted from human cord blood-isolated fetal fibrinogen and commercially available adult fibrinogen using filter-aided N-linked glycan separation. A

α

, B

β

, and

λ

chains were isolated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and in-gel enzymatic digestion was performed. Infrared matrix-assisted laser desorption electrospray ionization mass spectrometry was used for analysis.

Results

In total, 39 and 22 glycans were detected in fetal and adult fibrinogen, respectively. Fetal fibrinogen glycans were most abundant in the lower molecular weight range <4 kDa. After isolating the Aα, Bβ, and λ chains, increased glycosylation and sialic acid content was found in fetal fibrinogen. Increased glycosylation was detected across all 3 chains, and increased sialic acid content was found in the Bβ chain.

Conclusion

Sialylation in the Bβ chain of fetal fibrinogen supports previous findings showing more knob ‘B’ interactions occur in fetal fibrinogen than in adult fibrinogen during clot polymerization. This is also the first detection of glycosylation in the Aα chain of fibrinogen. By elucidating the fibrinogen N-linked glycome, this study found where sialic acid content differs the most between adult and fetal fibrinogen. This can ultimately be used to develop blood products that are neonatal-compatible.

胎儿纤维蛋白原是存在于新生儿中的一种变体。用于新生儿的血液制品是为成人定制的，不能无缝地整合到新生儿凝块中。与成人纤维蛋白原相比，胎儿纤维蛋白原中唾液酸含量增加。然而，唾液酸在纤维蛋白原上的作用范围和位置尚不清楚。目的探讨胎儿和成人纤维蛋白原糖基化和唾液酸含量的差异。方法采用过滤辅助n链聚糖分离法从人脐带血分离的胎儿纤维蛋白原和市售的成人纤维蛋白原中洗脱多糖。采用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分离A α、B β和λ链，并进行凝胶酶切。采用红外基质辅助激光解吸电喷雾电离质谱法进行分析。结果胎儿纤维蛋白原和成人纤维蛋白原中分别检出39个和22个聚糖。胎儿纤维蛋白原聚糖在低分子量范围（4 kDa）中含量最多。分离Aα、Bβ和λ链后，发现胎儿纤维蛋白原糖基化和唾液酸含量增加。3条链的糖基化程度均有所增加，而Bβ链的唾液酸含量有所增加。结论胎儿纤维蛋白原Bβ链的甲基化支持了先前的研究结果，即在凝块聚合过程中，胎儿纤维蛋白原比成人纤维蛋白原发生更多的knob ‘ B ’相互作用。这也是首次在纤维蛋白原Aα链中检测到糖基化。通过阐明纤维蛋白原n -联糖，本研究发现成人和胎儿纤维蛋白原唾液酸含量差异最大的地方。这最终可以用于开发与新生儿相容的血液制品。

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引用次数: 0

International normalized ratio measurement during perioperative anticoagulation bridging with low-molecular-weight heparin in patients undergoing heart valve replacement surgery 心脏瓣膜置换术患者低分子肝素抗凝桥围手术期国际标准化比值测定

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-11-01 DOI: 10.1016/j.rpth.2024.102616

Liza Rijvers , Sanna R. Rijpma , Herbert B. van Wetten , Yvonne M.C. Henskens , An K. Stroobants

Background

Surgical procedures in anticoagulated patients require specific attention due to increased bleeding risk. Preoperative anticoagulation interruption in high-risk patients is often necessary. Bridging anticoagulation with low-molecular-weight heparin (LMWH) minimizes thromboembolic risk, but its effect on international normalized ratio (INR) measurement is not well established, necessitating careful monitoring and individual assessment.

Objectives

To investigate the effect of heparin bridging on INR measurements in anticoagulated patients on vitamin K antagonist (VKA) and in in vitro spiking experiments.

Methods

Thirty-eight anticoagulated patients on VKA undergoing valve replacement surgery were studied using 2 plasma-based INR assays and 1 whole blood point-of-care INR method at multiple time points after postoperatively resuming VKA. In addition, INR levels in pooled plasma of both normal and VKA-treated individuals were compared, with 7 spiked concentrations of LMWH or unfractionated heparin (UFH) in 4 INR assays.

Results

In LMWH-bridged anticoagulated patients, the INR results obtained with HemosIL RecombiPlasTin and point-of-care Coaguchek were significantly higher than those obtained with STA Hepato Prest within 3 days after restart of VKA. After spiking LMWH or UFH in various concentrations into pooled plasma, only the STA Hepato Prest assay showed no interference in INR measurement within the therapeutic range (1.0-2.0 international units/mL) in both VKA and normal plasma. All other assays showed substantial interference, with the Thromborel S assay being the most heparin-sensitive assay.

Conclusion

Differences between INR methods are seen within 72 hours after restarting VKA in postoperative patients who receive LMWH bridging. In vitro experiments using LMWH and UFH show the interference of heparin in multiple INR methods, even with concentrations below the suppliers’ stated heparin interference limits.

背景：抗凝患者的外科手术需要特别注意，因为出血风险增加。高危患者术前中断抗凝治疗往往是必要的。桥接抗凝与低分子肝素（LMWH）可将血栓栓塞风险降至最低，但其对国际标准化比率（INR）测量的影响尚未得到很好的确定，需要仔细监测和个体评估。目的探讨肝素桥接对抗凝患者维生素K拮抗剂（VKA） INR测定的影响及体外尖峰实验。方法对38例VKA抗凝患者行瓣膜置换术，术后恢复VKA后多个时间点采用2项血浆INR测定和1项全血护理点INR测定。此外，比较了正常和vka治疗个体血浆中的INR水平，在4次INR检测中有7次低分子肝素或未分离肝素（UFH）浓度升高。结果在低分子肝素桥接抗凝患者中，在VKA重新启动后3天内，使用hemsil recombbiplastin和Coaguchek获得的INR结果显著高于使用STA Hepato presst获得的INR结果。在将不同浓度的低分子肝素或UFH注入混合血浆后，只有STA Hepato Prest检测在治疗范围（1.0-2.0国际单位/mL）内对VKA和正常血浆的INR测量没有干扰。所有其他检测都显示出明显的干扰，其中血小板相关性S检测是肝素最敏感的检测。结论在术后接受低分子肝素桥接的患者重新启动VKA后72小时内，INR方法之间存在差异。使用低分子肝素和UFH进行的体外实验表明，即使在低于供应商规定的肝素干扰限值的浓度下，肝素也会干扰多种INR方法。

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引用次数: 0

Prophylaxis in von Willebrand disease with von Willebrand factor concentrate and nonfactor therapies 用冯-威廉因子浓缩液和非因子疗法预防冯-威廉氏病

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-11-01 DOI: 10.1016/j.rpth.2024.102599

Calvin B. van Kwawegen, Frank W.G. Leebeek

This manuscript summarizes the current status of prophylaxis and novel potential therapies to prevent bleeding in patients with von Willebrand disease (VWD). VWD is the most common inherited bleeding disorder, which is associated mainly with mucocutaneous bleeding and bleeding during surgical and dental interventions. More severely affected VWD patients, mostly those with type 2 and type 3, can also suffer from joint, muscle, and gastrointestinal bleeds. Most patients with mild and moderate VWD are treated with desmopressin. The majority of patients with type 2 and 3 are treated with von Willebrand factor concentrates, with or without factor VIII. These patients suffer from severe and frequent bleeds and may require regular infusions of von Willebrand factor concentrate to prevent bleeding, so-called prophylaxis, 1 to 3 times per week. In this article, we review the current status of prophylaxis in VWD. We will also discuss emerging treatments that may be used as long-term prophylaxis in patients with severe VWD. We include relevant new data on this topic that were presented during the 2024 International Society on Thrombosis and Haemostasis (ISTH) Congress.

本手稿总结了预防von Willebrand病（VWD）患者出血的现状和新型潜在疗法。VWD 是最常见的遗传性出血性疾病，主要与皮肤粘膜出血以及手术和牙科治疗过程中的出血有关。病情较重的 VWD 患者（主要是 2 型和 3 型患者）还会出现关节、肌肉和胃肠道出血。大多数轻度和中度 VWD 患者都接受去氨加压素治疗。大多数 2 型和 3 型患者接受冯-威廉因子浓缩物（含或不含第八因子）治疗。这些患者出血严重且频繁，可能需要定期输注冯-威廉因子浓缩液以防止出血，即所谓的预防性治疗，每周 1 至 3 次。在本文中，我们将回顾 VWD 预防疗法的现状。我们还将讨论可用于严重 VWD 患者长期预防的新兴疗法。我们还将在 2024 年国际血栓与止血学会 (ISTH) 大会上介绍该主题的相关新数据。

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引用次数: 0

Oral invasive procedures in Glanzmann thrombasthenia: a retrospective observational study 格兰兹曼血栓形成症的口腔侵入程序：一项回顾性观察研究

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-11-01 DOI: 10.1016/j.rpth.2024.102619

Maxime Delarue , François Severac , Martine Soell , Léa Pierre , Dominique Desprez , Bornert Fabien

Background

Glanzmann thrombasthenia (GT) is a very rare autosomal inherited bleeding disease affecting megakaryocyte lineage with impacts on oral health such as gingival bleeding, which requires specific management protocols. Very few clinical cases have been published in the dental and hematologic literature.

Objectives

This study focuses on a series of 21 patients affected specifically by GT and their hemorrhagic prophylaxis management with the use of recombinant activated factor VII (rFVIIa) for dental extractions and full-mouth debridement.

Methods

Data were collected from medical and dental records. rFVIIa was administered prophylactically for oral procedures, following a standardized protocol. Each sessions were performed by experienced oral surgeons, and outcomes were analyzed with a focus on bleeding complications and adverse events.

Results

Forty-one full-mouth debridements and 176 dental extractions were performed during 102 sessions of dental care in an outpatient setting. A total of 226 injections of rFVIIa was delivered. The mean number of injections was 2.2 (range, 1-4) per dental procedure. The overall rate of bleeding complications was 5.9% (n = 6). All 6 hemorrhagic complications were classified as minor bleeding. No thromboembolic event or allergic reaction was observed.

Conclusion

The data presented in this retrospective observational study support the efficacy and safety of rFVIIa for the prevention of bleeding during invasive dental procedures in patients affected by GT. The rFVIIa protocol presented here seems to be a safe and efficient protocol for the prevention of bleeding during invasive oral procedures.

背景格兰兹曼血栓形成症（GT）是一种非常罕见的常染色体遗传性出血性疾病，影响巨核细胞系，对口腔健康有影响，如牙龈出血，需要特殊的管理方案。本研究主要关注 21 例受 GT 影响的患者，以及他们在拔牙和全口清创术中使用重组活化因子 VII（rFVIIa）进行出血预防管理的情况。每个疗程都由经验丰富的口腔外科医生进行，结果主要针对出血并发症和不良事件进行分析。结果在门诊牙科护理的 102 个疗程中，共进行了 41 次全口清创和 176 次拔牙。共注射了 226 支 rFVIIa。每个牙科手术的平均注射次数为 2.2 次（1-4 次不等）。出血并发症的总发生率为 5.9%（n = 6）。所有 6 例出血并发症均被归类为轻微出血。结论这项回顾性观察研究提供的数据支持 rFVIIa 在预防 GT 患者侵入性牙科手术中出血方面的有效性和安全性。本文介绍的 rFVIIa 方案似乎是一种安全有效的预防口腔侵入性手术中出血的方案。

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引用次数: 0

Incidence and risk factors of ischemic stroke in patients with cancer-associated venous thromboembolism: from the Contemporary Management and Outcomes in Patients With Venous Thromboembolism Registry-2 癌症相关静脉血栓栓塞症患者缺血性中风的发病率和风险因素：来自静脉血栓栓塞症患者当代管理与疗效登记处-2的数据

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-11-01 DOI: 10.1016/j.rpth.2024.102617

Toru Sato , Yoshito Ogihara , Yugo Yamashita , Takeshi Morimoto , Ryuki Chatani , Kazuhisa Kaneda , Yuji Nishimoto , Nobutaka Ikeda , Yohei Kobayashi , Satoshi Ikeda , Kitae Kim , Moriaki Inoko , Toru Takase , Shuhei Tsuji , Maki Oi , Takuma Takada , Kazunori Otsui , Jiro Sakamoto , Takeshi Inoue , Shunsuke Usami , Kaoru Dohi

Background

Ischemic stroke is a serious complication in patients with cancer-associated venous thromboembolism (CAVTE), although data remain scarce in the direct oral anticoagulant era.

Objectives

This study aimed to investigate the incidence and identify predictive risk factors of ischemic stroke in patients with CAVTE.

Methods

From the Contemporary Management and Outcomes in Patients With Venous Thromboembolism Registry-2 enrolling 5197 venous thromboembolism (VTE) patients across 31 centers in Japan between January 2015 and August 2020, we selected 1507 patients with active cancer. We calculated the cumulative incidence function of ischemic stroke accounting for the competing risk of death and investigated risk factors for ischemic stroke in a subdistribution hazard model of multivariable analysis.

Results

During a median follow-up period of 1020 days, 71 patients (4.7%) developed ischemic stroke, and the cumulative incidence of ischemic stroke was 4.0% at 1 year and 4.7% at 3 years. Independent risk factors of ischemic stroke included pancreatic cancer (hazard ratio [HR], 4.24; 95% CI, 2.13-8.43), ovarian cancer (HR, 2.82; 95% CI, 1.31-6.08), lung cancer (HR, 2.35; 95% CI, 1.20-4.57), dyslipidemia (HR, 1.76; 95% CI, 1.01-3.09), metastasis (HR, 1.70; 95% CI, 1.02-2.82), higher D-dimer at VTE diagnosis (HR, 1.09; 95% CI, 1.04-1.14), and younger age (HR, 0.84; 95% CI, 0.71-0.999).

Conclusion

In this large VTE registry in the direct oral anticoagulant era, the cumulative incidence of ischemic stroke was 4.0% at 1 year and 4.7% at 3 years in patients with CAVTE, and several independent risk factors of ischemic stroke were identified, including pancreatic cancer, ovarian cancer, lung cancer, dyslipidemia, metastasis, higher D-dimer at VTE diagnosis, and younger age.

背景缺血性卒中是癌症相关性静脉血栓栓塞症（CAVTE）患者的一种严重并发症，尽管在直接口服抗凝剂时代相关数据仍然很少。方法2015 年 1 月至 2020 年 8 月期间，日本 31 个中心的 5197 名静脉血栓栓塞症（VTE）患者参加了静脉血栓栓塞症患者当代管理和结果登记-2，我们从中选择了 1507 名活动性癌症患者。我们计算了缺血性卒中的累积发病率函数，考虑了死亡的竞争风险，并在多变量分析的子分布危险模型中研究了缺血性卒中的风险因素。结果在中位随访 1020 天期间，71 名患者（4.7%）发生了缺血性卒中，1 年和 3 年的缺血性卒中累积发病率分别为 4.0% 和 4.7%。缺血性卒中的独立危险因素包括胰腺癌（危险比 [HR]，4.24；95% CI，2.13-8.43）、卵巢癌（HR，2.82；95% CI，1.31-6.08）、肺癌（HR，2.35；95% CI，1.20-4.57）、血脂异常（HR，1.76；95% CI，1.01-3.09）、转移（HR，1.70；95% CI，1.02-2.82）、VTE 诊断时较高的 D-二聚体（HR，1.09；95% CI，1.04-1.14）和年龄较小（HR，0.84；95% CI，0.71-0.999）。结论在直接口服抗凝剂时代的这一大型 VTE 登记中，CAVTE 患者缺血性卒中的累积发生率在 1 年为 4.0%，3 年为 4.7%，发现了几个缺血性卒中的独立危险因素，包括胰腺癌、卵巢癌、肺癌、血脂异常、转移、VTE 诊断时 D-二聚体较高和年龄较小。

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引用次数: 0