Comparative Tissue Factor Pathway Inhibitor Release Potential of Heparins

• Published in: Clinical and applied thrombosis/hemostasis Vol. 11; no. 1; pp. 37 - 47
• Main Authors: Tobu, M., Ma, Q., Iqbal, O., Schultz, C., Jeske, W., Hoppensteadt, D. A., Fareed, J.
• Format: Journal Article
• Language: English
• Published: Thousand Oaks, CA SAGE Publications 01.01.2005; SAGE PUBLICATIONS, INC
• Subjects: 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; Molecular weight; Prothrombin - metabolism; Extrinsic pathway activation; Tissue factor pathway inhibitor; Tissue factor; Coagulation; Factor VII
• ISSN: 1076-0296; 1938-2723
• DOI: 10.1177/107602960501100104

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.