Comparative tissue factor pathway inhibitor release potential of heparins

Clin Appl Thromb Hemost. 2005 Jan;11(1):37-47. doi: 10.1177/107602960501100104.

Abstract

Tissue factor pathway inhibitor (TFPI) is released following the administration of unfractionated heparin, low-molecular-weight heparins, defibrotide and PI-88. In this study, the comparative effects of heparin, a low-molecular-weight heparin-gammaparin and a heparin-derived oligosaccharide mixture-subeparin (C3) were studied on functional and immunologic tissue factor pathway inhibitor activity levels in a non-human primate (Macaca mulatta) model. The dose-dependent effect was studied following intravenous and subcutaneous administration. Following the administration of 1 mg/kg of heparin, gammaparin, and C3, the functional levels of TFPI at 5 minutes were 2.40, 2.56, and 1.08 U/mL and the corresponding TFPI immunologic levels were 4.3-, 4.0-, and 2.1-fold, increased, respectively, over the baseline value. From these results, it can be concluded that heparin and gammaparin produced similar levels of TFPI release. Hence, gammaparin and heparin have similar TFPI release potential despite their differences in molecular weight. The influence of molecular weight, charge density, and interactions with heparin cofactor II on TFPI release are also discussed.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Complement C3 / administration & dosage
  • Complement C3 / pharmacology
  • Factor Xa / metabolism
  • Female
  • Heparin / administration & dosage
  • Heparin / analogs & derivatives*
  • Heparin / chemistry
  • Heparin / pharmacology*
  • Injections, Subcutaneous
  • Lipoproteins / immunology
  • Lipoproteins / metabolism*
  • Macaca mulatta
  • Male
  • Prothrombin / metabolism

Substances

  • Complement C3
  • Lipoproteins
  • lipoprotein-associated coagulation inhibitor
  • Prothrombin
  • Factor IIa
  • Heparin
  • Factor Xa