Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, UK; The Roald Dahl Haemostasis and Thrombosis Centre, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, UK; The Roald Dahl Haemostasis and Thrombosis Centre, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
J Thromb Haemost. 2024 Aug;22(8):2140-2146. doi: 10.1016/j.jtha.2024.05.014. Epub 2024 May 28.
It is increasingly apparent that the pathologic interplay between coagulation and innate immunity, ie, immunothrombosis, forms the common basis of many challenges across the boundaries of specialized medicine and cannot be fully explained by the conventional concepts of cascade and cell-based coagulation. To improve our understanding of coagulation, we propose a model of coagulation that converges with inflammation and innate immune activation as a unified response toward vascular injury. Evolutionarily integral to the convergent response are damage-associated molecular patterns, which are released as a consequence of injury. Damage-associated molecular patterns facilitate diverse interactions within and between systems, not only to complement and reinforce cell-based clot formation but also to steer the response toward clot resolution and wound healing. By extending coagulation beyond its current boundaries, the convergent model aims to deliver novel diagnostics and therapeutics for contemporary and unexpected challenges across medicine, as exposed by COVID-19 and vaccine-induced immune thrombotic thrombocytopenia.
越来越明显的是,凝血与固有免疫之间的病理相互作用,即免疫血栓形成,构成了许多跨越专科医学界限的挑战的共同基础,不能仅用传统的级联和基于细胞的凝血概念来充分解释。为了增进我们对凝血的理解,我们提出了一个凝血模型,该模型与炎症和固有免疫激活相融合,作为对血管损伤的统一反应。损伤相关的分子模式在趋同反应中是必不可少的,它们是损伤的结果。损伤相关的分子模式促进了系统内和系统间的各种相互作用,不仅有助于补充和加强基于细胞的血栓形成,而且有助于引导反应向血栓溶解和伤口愈合方向发展。通过将凝血扩展到其当前的边界之外,趋同模型旨在为当代和意想不到的医学挑战提供新的诊断和治疗方法,这在 COVID-19 和疫苗诱导的免疫血栓性血小板减少症中得到了体现。