Endothelial cell damage in heparin-induced thrombocytopenia

Abstract

Heparin-induced thrombocytopenia type II is a severe complication of heparin treatment that may result in thrombosis. When thrombosis occurs it carries a 50% mortality rate. The exact pathophysiology is not fully understood but in the majority of cases it is associated with the production of heparin/platelet factor 4 antibodies. The endothelium provides a protective anticoagulant surface over which blood flows. Perturbation of the endothelial cells causes a reversal of the anticoagulant properties of the cells to that of a procoagulant surface. This is often due to release or down-regulation of the anticoagulant membrane proteins such as thrombomodulin and up-regulation of procoagulant factors such as tissue factor. We studied 10 patients in our cardiothoracic institute with clinically and laboratory-confirmed heparin-induced thrombocytopenia type II for evidence of endothelial cell damage. There was a statistically significant rise in the concentrations of von Willebrand factor (P < 0.0001) and soluble thrombomodulin (P = 0.004) when patients with heparin-induced thrombocytopenia type II were compared with healthy laboratory controls and patients having had cardiopulmonary bypass surgery (von Willebrand factor 324 versus 103 versus 108 U/dl and soluble thrombomodulin 9.5 versus 2.3 versus 1.2 ng/ml, respectively). Our findings suggest that endothelial cell damage is a major factor in the pathophysiology of heparin-induced thrombocytopenia.