A(nother) Test Meant to Fill the Gap between In Vivo and Ex Vivo Hemostasis

[摘要] Clot formation and dissolution in vivo can be considered as a highly integrated cellular/humoral process that acts through 3 interrelated pathways: primary hemostasis, coagulation, and fibrinolysis. Primary hemostasis is defined as the platelet–vessel wall interaction at the site of vascular injury that initiates when flowing platelets recognize (through their receptors) and bind (through the adhesive protein von Willebrand factor) subendothelial collagen. Any perturbation of this interaction may result in hypo- or hyperactivity, which increase the risk of hemorrhage or thrombosis, respectively.Coagulation acts through 2 opposing drivers. The first, represented by the procoagulant factors, is triggered by tissue factor (TF),3 a cellular receptor in damaged tissues that forms a complex with activated factor VII (FVIIa) at the site of injury (Fig. 1A). TF-FVIIa starts a series of reactions mediated by negatively charged phospholipids on the membranes of activated platelets that lead to thrombin generation and fibrinogen-to-fibrin conversion (Fig. 1A). The anticoagulant driver originates from thrombin that, once complexed with its endothelial receptor thrombomodulin (TM), activates protein C (PC) bound to the endothelial PC receptor (EPCR) (Fig. 1B). Activated PC (APC) is a potent anticoagulant that, in combination with its cofactor protein S (PS), downregulates thrombin generation through the inhibition of the activated forms of FVIII and FV (Fig. 1, B and C). The anticoagulant driver is also potentiated by antithrombin (AT) that, in complex with endothelial heparin-like substances, inhibits thrombin directly and indirectly through the inactivation of the activated forms of the coagulation FVII, FIX, and FX (Fig. 1C). Thrombin generation is also downregulated by the tissue factor pathway inhibitor (TFPI), which inhibits TF-FVIIa and FXa (Fig. 1C). The balance between the pro- and anticoagulant drivers is essential to prevent unwanted thrombin formation in physiologic conditions. Again, any perturbation of this balance may …

[学科分类] 过敏症与临床免疫学