Heparanase modulates heparinoids anticoagulant activities via non-enzymatic mechanisms

Thromb Haemost. 2007 Dec;98(6):1193-9.


A key element for the physiological restriction of blood coagulation at the endothelial cell surface is its non-thrombogenic property, mainly attributed to cell surface heparan sulfate proteoglycans. Heparanase is an endo-beta-D-glucuronidase with specific heparan sulfate degrading activity, which is produced and stored in platelets, and is released upon their activation. We examined the effects of heparanase pro-enzyme on coagulation functions, predominantly under physiological conditions. While heparanase pro-enzyme does not directly affect coagulation protein activities, it has profound effects on heparinoid-mediated regulation of coagulation responses, apparently via mechanisms that do not involve its enzymatic activity. Heparanase pro-enzyme reverses the anti-coagulant activity of unfractionated heparin on the coagulation pathway as well as on thrombin activity. In addition, heparanase pro-enzyme abrogated the factor X inhibitory activity of low-molecular-weight heparin (LMWH). The pro-coagulant effects of the non-active heparanase were also exerted by its major functional heparin-binding peptide. Finally, the effects of heparanase on the activity of factor VII activating protease that is auto-activated by heparinoids indicated a complete antagonistic action of heparanase in this system. Altogether, heparanase pro-coagulant activities that were also demonstrated in plasma samples from patients under LMWH treatment, point to a possible use of this molecule as antagonist for heparinoid treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / pharmacology*
  • Blood Coagulation / drug effects*
  • Blood Platelets / drug effects*
  • Blood Platelets / enzymology
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Enzyme Precursors / metabolism*
  • Factor X / antagonists & inhibitors
  • Factor X / metabolism
  • Glucuronidase / blood
  • Glucuronidase / metabolism*
  • Heparin Antagonists / blood
  • Heparin Antagonists / metabolism*
  • Heparin Antagonists / pharmacology
  • Heparin, Low-Molecular-Weight / pharmacology*
  • Heparinoids / pharmacology*
  • Humans
  • Partial Thromboplastin Time
  • Peptide Fragments / metabolism
  • Protamines / pharmacology
  • Prothrombin Time
  • Serine Endopeptidases / blood
  • Thrombin / metabolism
  • Thrombin Time


  • Anticoagulants
  • Enzyme Precursors
  • Heparin Antagonists
  • Heparin, Low-Molecular-Weight
  • Heparinoids
  • Peptide Fragments
  • Protamines
  • Factor X
  • heparanase
  • Glucuronidase
  • HABP2 protein, human
  • Serine Endopeptidases
  • Thrombin