Thrombosis and Hemostasis Unit, Rambam Health Care Campus, The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Semin Thromb Hemost. 2021 Apr;47(3):254-260. doi: 10.1055/s-0041-1725065. Epub 2021 Apr 1.
Heparanase, the only mammalian enzyme known to degrade heparan sulfate chains, affects the hemostatic system through several mechanisms. Along with the degrading effect, heparanase engenders release of syndecan-1 from the cell surface and directly enhances the activity of the blood coagulation initiator, tissue factor, in the coagulation system. Upregulation of tissue factor and release of tissue factor pathway inhibitor from the cell surface contribute to the prothrombotic effect. Tissue factor pathway inhibitor and the strongest physiological anticoagulant antithrombin are attached to the endothelial cell surface by heparan sulfate. Hence, degradation of heparan sulfate induces further release of these two natural anticoagulants from endothelial cells. Elevated heparanase procoagulant activity and heparan sulfate chain levels in plasma, demonstrated in cancer, pregnancy, oral contraceptive use, and aging, could suggest a potential mechanism for increased risk of thrombosis in these clinical settings. In contrast to the blood circulation, accumulation of heparan sulfate chains in transudate and exudate pleural effusions induces a local anticoagulant milieu. The anticoagulant effect of heparan sulfate chains in other closed spaces such as peritoneal or subdural cavities should be further investigated.
肝素酶是唯一已知能够降解硫酸乙酰肝素链的哺乳动物酶，通过多种机制影响止血系统。除了降解作用外，肝素酶还导致 syndecan-1 从细胞表面释放，并直接增强凝血系统中凝血起始因子组织因子的活性。组织因子的上调和组织因子途径抑制剂从细胞表面的释放有助于促血栓形成作用。组织因子途径抑制剂和最强的生理抗凝剂抗凝血酶通过硫酸乙酰肝素附着在血管内皮细胞表面。因此，硫酸乙酰肝素的降解进一步导致这两种天然抗凝剂从内皮细胞中释放。在癌症、妊娠、口服避孕药使用和衰老中观察到的血浆中肝素酶促凝活性和硫酸乙酰肝素链水平升高，可能提示这些临床情况下血栓形成风险增加的潜在机制。与血液循环相反，胸腔积液渗出液和漏出液中硫酸乙酰肝素链的积累会诱导局部抗凝环境。肝素硫酸乙酰肝素链在其他封闭空间（如腹膜或硬脑膜腔）中的抗凝作用应进一步研究。
