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促凝血血小板是一个新兴的治疗靶点吗?一篇综述,重点阐述其在伴侣动物中的临床意义

Are Procoagulant Platelets an Emerging Therapeutic Target? A General Review with an Emphasis on Their Clinical Significance in Companion Animals.

作者信息

Shaverdian Meg, Viall Austin, Li Ronald H L

机构信息

Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.

Department of Clinical Science, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.

出版信息

Int J Mol Sci. 2025 Sep 9;26(18):8776. doi: 10.3390/ijms26188776.

Abstract

Platelets carry out their aggregatory and procoagulant roles in two distinct phenotypes. Aggregatory platelets initiate adhesion to the injured endothelium and extend the platelet plug, where procoagulant platelets accelerate thrombin formation and fibrinogen cleaving by exposing a procoagulant-rich outer membrane that facilitates coagulation factor assembly. Conventional anti-platelet therapies inhibit the aggregatory phenotype but fall short on restraining procoagulant platelets. Although procoagulant platelets are crucial for normal hemostasis, a shift toward excess procoagulant platelets is associated with human thrombotic disorders such as ischemic stroke. Although veterinary data is limited, recent studies show that feline and canine platelets display similar procoagulant phenotypes in response to potent agonists, suggesting that procoagulant platelets may play similar roles in the pathogenesis of thromboembolic disorders in veterinary species. Species-specific differences in platelet physiology and molecular structures, however, pose significant challenges. This review aims to (1) summarize cross-species evidence on the mechanisms driving procoagulant platelet formation, their defining features, and characteristics, (2) provide perspectives on procoagulant platelets as thrombotic biomarkers and outline the technical challenges of generating and detecting them in small animal medicine, and (3) summarize potential therapeutic targets and highlight priority research areas to advance the diagnosis and management of thromboembolic diseases in veterinary medicine.

摘要

血小板以两种不同的表型发挥其聚集和促凝血作用。聚集性血小板启动与受损内皮的黏附并扩展血小板栓子,而促凝血性血小板通过暴露富含促凝血物质的外膜来加速凝血酶形成和纤维蛋白原裂解,从而促进凝血因子组装。传统的抗血小板疗法抑制聚集性表型,但在抑制促凝血性血小板方面效果不佳。尽管促凝血性血小板对正常止血至关重要,但向促凝血性血小板过度转变与人类血栓性疾病如缺血性中风有关。虽然兽医领域的数据有限,但最近的研究表明,猫和犬的血小板在对强效激动剂的反应中表现出相似的促凝血表型,这表明促凝血性血小板在兽医物种的血栓栓塞性疾病发病机制中可能发挥相似作用。然而,血小板生理学和分子结构的物种特异性差异带来了重大挑战。本综述旨在:(1)总结跨物种证据,说明促凝血性血小板形成的机制、其定义特征和特性;(2)提供关于促凝血性血小板作为血栓生物标志物的观点,并概述在小动物医学中生成和检测它们的技术挑战;(3)总结潜在的治疗靶点,并突出优先研究领域,以推进兽医学中血栓栓塞性疾病的诊断和管理。

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