PROTHROMBOTIC AND FIBRINOLYTIC FUNCTION OF NORMAL AND PERTURBED ENDOTHELIUM

Endothelium mediates thrombosis and fibrinolysis in part through cell-based production and binding of coagulation factors and anticoagulant moieties. A variety of biologically active agents (homocysteine, interleukin-1, and endotoxin) and environmental factors (mechanical injury and hypoxia) can upset the homeostasis of the coagulation system leading in vitro and in vivo to abnormal propensity for thrombin formation. None of the above agents or any similar agents have been demonstrated to inhibit clotting factors or thrombosis formation. As one would expect, injury to endothelium even on a sublethal basis promotes a procoagulant response. This procoagulant response appears to be multifactorial and multiphasic. Gross injury leads to factor release by dead or dying cells with rapid promotion of thrombosis by neighboring infact cells. A more subtle prothrombotic state promulgated by viable cells appears after sublethal perturbation and is characterized by protein synthesis-dependent production of endothelial-produced clotting factors in the early stages of injury with subsequent return to normal levels of these factors by 24 hr. A second phase of abnormal levels of fibrinolysis inhibitors and possible reduction in fibrinolysis promoters appears to follow up to 48 hr after the initial injury. Thus the cell can be viewed as producing means of promoting thrombus formation followed by preventing thrombus dissolution. The data presented in this article are primarily cell culture data and are thus limited both in physiologic applicability and in ability to define over long periods the relevance of those findings to other cells in the hemostatic system. Nonetheless, in vivo data of endothelial perturbation correlate with the in vitro findings. Further definition of the procoagulant state following endothelial injury, with respect to local and systemic release of endothelial products, might lead to a better understanding of the perioperative thrombotic events which continue to vex all physicians caring for patients with vascular disease. © 1992.