VA Boston Healthcare System, Harvard Medical School, Boston, MA, United States.
Blood Rev. 2019 Jan;33:1-5. doi: 10.1016/j.blre.2018.05.001. Epub 2018 May 24.
Hemophilia A is caused by decreased or dysfunctional blood coagulation factor VIII (FVIII). Recent developments in the understanding of FVIII biology, in particular the nature of FVIII binding sites on platelets, may provide new insight into the limitations of current assays. Recent data suggest that the phospholipid vesicles, which represent nonphysiologic membranes of high phosphatidylserine (PS) content, poorly reflect functional FVIII binding sites critical to coagulation. This narrative review describes the function of FVIII in clotting and discusses our evolving understanding of FVIII binding sites and their clinical implications. Refined models of FVIII binding sites have the potential to improve FVIII assays, possibly improving bleeding risk stratification for patients with mild and moderate hemophilia A. They may also support earlier and more accurate detection of inhibitors, before they are clinically evident.
血友病 A 是由凝血因子 VIII（FVIII）减少或功能障碍引起的。近年来对 FVIII 生物学的理解，特别是血小板上 FVIII 结合位点的性质，可能为当前检测方法的局限性提供新的见解。最近的数据表明，磷脂囊泡代表具有高磷脂酰丝氨酸（PS）含量的非生理膜，不能很好地反映对凝血至关重要的功能性 FVIII 结合位点。本叙述性综述描述了 FVIII 在凝血中的功能，并讨论了我们对 FVIII 结合位点及其临床意义的不断发展的认识。FVIII 结合位点的改良模型有可能改善 FVIII 检测，可能改善轻度和中度血友病 A 患者的出血风险分层。它们还可能支持在抑制剂在临床上出现之前更早、更准确地检测到它们。
