An endothelial cell-dependent pathway of coagulation.

Abstract

Although the endothelial cell is considered antithrombogenic, endothelium participates in procoagulant reaction. Cultured bovine aortic endothelial cells propagate a procoagulant pathway starting with factor XIa, leading to activation of factors IX, VIII, X and prothrombin, culminating in fibrinopeptide A cleavage from fibrinogen and formation of a fibrin clot. EM studies demonstrated that fibrin strands are closely associated with the endothelial cells. Endotoxin-treated endothelial cells, having acquired tissue factor activity, generated fibrinopeptide A in the presence of factors VIIa, IX, VIII, X, prothrombin and fibrinogen. Factor X activation by factor VIIa and tissue factor expressed by endothelial cells is 10 times greater in the presence of factors IX and VIII than in their absence. On the perturbed endothelial cell surface, factors IX and VIII do have an important role in the activation of factor X. Addition of platelets (108/ml) augmented thrombin formation seen in the presence of endothelium alone by .apprx. 15-fold. Anti-human factor V IgG decreased this enhanced thrombin formation in the presence of platelets, indicating that factor V from platelets was playing an important role in thrombin formation. Endothelial cells can actively participate in procoagulant reactions. Although platelets can augment thrombin formation by these endothelial cell-dependent reactions, endothelial cells alone can lead to formation of a cell-associated fibrin clot. The endotoxin-treated endothelial cell provides a model of the thrombotic state supplying tissue factor to initiate coagulation and propagating the reactions leading to fibrin formation. This endothelial cell-dependent pathway suggests a central role for factors VIII and IX consistent with their importance in hemostasis.