Haemostasis Research Group, Department of Molecular and Cellular Therapeutics, Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, Dublin, Ireland.
Br J Haematol. 2019 Jul;186(1):24-36. doi: 10.1111/bjh.15872. Epub 2019 Mar 28.
Blood clot formation to stem bleeding from an injured blood vessel arises from a complex series of cellular and biochemical events, which, when dysregulated, predispose to an increased risk of thrombosis or bleeding. Similarly, haemostatic regulation of clot growth and size is exquisitely controlled by a series of anticoagulant 'checkpoints', that exert their inhibitory activity at distinct stages in the steps leading to clot formation. Although the major plasma protein constituents required for haemostasis have now been largely elucidated and the molecular events that lead to clot formation are well understood, defining a fuller appreciation of the importance, location and regulation of each haemostatic process remains a fertile area of ongoing research. In this review article, we first provide an overview of the original 'waterfall' or 'cascade' hypothesis of blood coagulation as it was defined in the 1960s. We subsequently discuss how this original model has been refined over time to incorporate accumulating data that has enabled a more nuanced consideration of the role of specific proteins, receptors and lipids in dictating the spatial and temporal development of a blood clot.
血液从受损血管中凝结以止血，这源自一系列复杂的细胞和生化事件。这些事件如果失调，会增加血栓形成或出血的风险。同样，止血过程中对血栓生长和大小的调节受到一系列抗凝“检查点”的精细控制，这些检查点在导致血栓形成的步骤中的不同阶段发挥抑制作用。虽然目前已经基本阐明了止血所需的主要血浆蛋白成分，并且对导致血栓形成的分子事件有了很好的理解，但要充分了解每个止血过程的重要性、位置和调节仍然是一个正在进行的研究热点。在这篇综述文章中，我们首先概述了 20 世纪 60 年代定义的血液凝固的原始“瀑布”或“级联”假说。随后，我们讨论了随着时间的推移，这个原始模型是如何被改进的，以纳入不断积累的数据，这些数据使我们能够更细致地考虑特定蛋白质、受体和脂质在决定血栓形成的空间和时间发展中的作用。
