The factor XIa antibody osocimab strongly inhibits clotting in extracorporeal circuits with human blood and in baboons

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis Pub Date : 2025-05-01 DOI:10.1016/j.rpth.2025.102932

Eslam Samaha , Michael Schwameis , Sabine Schranz , Katarina D. Kovacevic , Bruno Watschinger , Martin Stoiber , Christopher Wolf , Michael Wallisch , András Gruber , Erik I. Tucker , Anja Buchmüller , Bernd Jilma

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引用次数: 0

Abstract

Background

Effective anticoagulant approaches in extracorporeal circuits with little impact on hemostasis are still an unmet medical need. Targeted inhibition of activated factor (F)XI might represent an attractive alternative or addition to conventional anticoagulation.

Objectives

We aimed to evaluate the additional antithrombotic effect of the monoclonal anti-FXIa antibody osocimab in in vitro and in vivo models of extracorporeal circulation.

Methods

This study compared the additional antithrombotic effect of a novel monoclonal antibody, osocimab (anti-FXIa), with that of low-molecular-weight heparin in 3 in vitro models of extracorporeal blood circulation (hemodialysis [HD], left ventricular assist devices [LVADs], and extracorporeal membrane oxygenation [ECMO]). Whole blood donated by healthy volunteers was spiked with enoxaparin ± osocimab and circulated for several hours in extracorporeal circuits. The primary endpoint was time to filter clotting. Furthermore, we performed in vivo ECMO perfusion studies in baboons using unfractionated heparin and osocimab.

Results

Of 40 subjects screened, 34 (50% male; mean age, 32 years [±9 SD]) were enrolled in the study. The addition of osocimab significantly prolonged the time to filter clotting from 120 minutes (IQR, 105-150) to 180 minutes (IQR, 180-180; n = 10) in HD circuits, from 127 minutes (IQR, 38-210) to 180 minutes (IQR, 69-240; n = 12) in ECMO circuits, and from 36 minutes (IQR, 18-59) to 113 minutes (IQR, 51-120; n = 12) in LVAD circuits. Furthermore, it preserved fibrinogen concentrations (HD: 227 mg/dL vs 170 mg/dL; LVADs: 229 mg/dL vs 50 mg/dL; ECMO: 221 mg/dL vs 170 mg/dL) and platelet aggregation and prolonged clotting times in thromboelastometry. In baboons, osocimab significantly reduced the oxygenator’s platelet deposition and terminal fibrin content.

Conclusion

Osocimab effectively inhibited clotting due to extracorporeal circulation.

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因子XIa抗体osociimab强烈抑制人类血液和狒狒体外循环中的凝血

背景体外循环中有效且对止血影响小的抗凝方法仍然是一个未满足的医学需求。靶向抑制活化因子(F)XI可能是传统抗凝剂的一种有吸引力的替代或补充。目的评价单克隆抗fxia抗体osociimab在体外和体内体外循环模型中的附加抗血栓作用。方法本研究比较了一种新型单克隆抗体osocimab（抗fxia）与低分子肝素在3种体外血液循环模型（血液透析[HD]、左心室辅助装置[lvad]和体外膜氧合[ECMO]）中的附加抗血栓作用。健康志愿者捐献的全血加入依诺肝素±奥索单抗，在体外循环中循环数小时。主要终点是过滤凝血时间。此外，我们使用未分离肝素和osociimab在狒狒体内进行ECMO灌注研究。结果在筛选的40例受试者中，34例(50%为男性；平均年龄32岁[±9 SD])。osocimab的加入显著延长了过滤凝血的时间，从120分钟（IQR, 105-150）延长到180分钟（IQR, 180-180）；n = 10)，从127分钟（IQR, 38-210）到180分钟（IQR, 69-240）；n = 12)，从36分钟（IQR, 18-59）到113分钟(IQR, 51-120；在LVAD电路中n = 12)。此外，它还能保持纤维蛋白原浓度(HD: 227 mg/dL vs 170 mg/dL；lvad: 229 mg/dL vs 50 mg/dL；ECMO: 221 mg/dL vs 170 mg/dL)和血小板聚集和延长血栓弹性测定的凝血时间。在狒狒中，osocimab显著降低了氧合器的血小板沉积和末端纤维蛋白含量。结论osociimab能有效抑制体外循环引起的凝血。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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