The cell-based coagulation model

Abstract

Hemostasis has traditionally been divided into primary and secondary hemostasis. In primary hemostasis, once subendothelial collagen is exposed to blood by vascular injury, von Willebrand factor (vWF) binds to collagen and platelets to form vWF-platelet clots. In secondary hemostasis, MacFarlane’s “Cascade Model” and Davie and Ratnoff’s “Waterfall Sequence Model” suggest that coagulation factors interact by mutual sequential activation via two pathways (intrinsic and extrinsic), which finally lead to thrombin activation. Thrombin converts fibrinogen to fibrin, thereby stabilizing the vWF-platelet clots. The recent “Cell-Based Model,” however, proposes three overlapping phases of coagulation. Exposition of tissue factor to blood leads to activation of factor VII and other factors (initiation). The resulting small amounts of thrombin activate platelets which bind factors Va, VIIIa, and IXa at their surface (amplification). Bound to the activated platelets’ surface (“cell-based”), these coagulation factors are able to convert large amounts of prothrombin into thrombin (propagation). The resulting thrombin burst then accounts for sufficient conversion of fibrinogen to fibrin and activation of factor XIII.