PL-14 Heparanase procoagulant activity

Abstract

Heparanase that was cloned from and is abundant in the placenta is implicated in cell invasion, tumor metastasis and angiogenesis. We have recently demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. Heparanase was shown to up-regulate tissue factor (TF) expression and interact with tissue factor pathway inhibitor (TFPI) on cell surface, leading to dissociation of TFPI from cell membrane of endothelial and tumor cells, resulting in increased cell surface coagulation activity. We have lately shown that heparanase directly enhances TF activity resulting in increased factor Xa production and activation of the coagulation system. Data indicate increased plasma levels of heparanase suggesting its possible involvement in pregnancy vascular complications. Elevation in heparanase levels and procoagulant activity was also documented in orthopedic surgery patients receiving prophylactic doses of enoxaparin. Taking into account the pro-metastatic and pro-angiogenic functions of heparanase, with over-expression in human malignancies and abundance in platelets and placenta, its involvement in the coagulation machinery is an intriguing novel platform for further research.