Endothelial cell injury in cardiovascular surgery: the procoagulant response

Abstract

The vascular endothelium plays a critical role in the regulation of coagulation through the constitutive expression and release of anticoagulants and the inducible expression of procoagulant substances. Cardiopulmonary bypass dysregulates this process by activating endothelial cells, initially promoting bleeding and then thrombosis. Endothelial cell activation in response to circulating inflammatory mediators leads to the initiation of coagulation when tissue factor is expressed throughout the intravascular space. This results in the widespread consumption of coagulation factors. Additionally, there is a cardiopulmonary bypass-related qualitative platelet defect that is exacerbated by thrombocytopenia as platelets are consumed from the circulation by clot and adherence to the cardiopulmonary bypass circuit. Finally, cardiopulmonary bypass results in the endothelial release of plasminogen activators, which lead to an increase in systemic fibrinolysis. The diffuse generation of thrombin, driven by the inducible intravascular expression of tissue factor, plays a major role in all of these processes. Efforts to understand the critical role of the endothelium in coagulation may lead to novel therapies to prevent bleeding or thrombosis in cardiovascular surgery patients.