Abstract
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.
Keywords
heparanase - heparan sulfate - tissue factor - tissue factor pathway inhibitor - antithrombin
