Coagulation Properties of Chemically Modified Heparins
Divalent carbonic acid halides have been used to fix heparin onto biomaterials of biological origin, however, the effect of this process on the coagulation profile induced by heparin has not yet been clearly determined. To investigate this, commercially available unfractionated and low molecular weight heparins were treated with the corresponding halides of adipic and glutaric acid. Clotting tests and chromogenic substrate assays were used to characterize the influence of these derivatives on the clotting mechanism. In a thrombosis model in rats, the anticoagulant and antithrombotic effects of these substances were also analyzed. The in vitro data indicate a loss of the anticoagulant profile. Heparin-catalyzed acceleration of thrombin and factor Xa-inhibition by AT III were diminished following derivatization, although the heparin cofactor II activity was unaltered. However, in an animal model the antithrombotic properties of these heparin derivatives were reduced but still significant. These experiments were repeated with acetylchloride derivatization revealing comparable results.
KeywordsAdipic Acid Glutaric Acid Dose Response Effect Thrombosis Model Coagulation Property
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- 1.M. Bar-Ner, A. Eldor, L. Wasserman, Y. Matzner, J. R. Cohen, Z. Fuks and J. Vlodaysky, Blood, 70, 551–557 (1987). “Inhibition of Heparinase - Medicated Degradation of Extracellular Matrix Heparansulfate by Non-Anticoagulated Heparin Species.”Google Scholar
- 2.G. Harbauer, W. Hiller, U. J. Uhl, and E. Wenzel, in: Standardization of Animal Models of Thrombosis, K. Breddin and R. Zimmermann, Eds, Schattauer, Stuttgart, 1985, pp. 115–119. “A Venous Thrombosis Model in the Rabbit.”Google Scholar
- 3.T. Irimura, M. Nakajima, and G. L. Nicolson, Biochem., 25, 5322–5328 (1986). “Chemically Modified HepBtins as Inhibitors of Heparan Sulfate Specific Endo-ß-Glucuronidase (Heparinase) of Metastatic Melanoma Cells.”Google Scholar
- 4.S. W. Levy and L. B. Jaques, Thromb. Res., 13, 429–441 (1978). “Appearance of Heparin Antithrombin-Active Chains in vivo After Injection of Commercial Heparin and in Anaphylaxis.”Google Scholar
- 5.Y. Matzner, G. Marx, R. Drexler and A. Eldor, Thromb. Haemostas, 52, 134–137 (1984). “The Inhibitory Effect of Heparin and Related Glycosaminoglycans on Neutrophil Chemotaxis.”Google Scholar
- 6.A. Stemberger, A. Riedl, S. Haas, K. Breddin, J. Walenga and G. Blümel„ Sem. Thrombos. Hemos., 17, Suppl 1, 80–84 (1991). “Action of Modified Heparins on Coagulation: In vitro and in vivo Studies.”Google Scholar
- 7.M. S. Sy, E. Schneeberger, R. McCluskey, M. J. Greene, R. D. Rosenberg and B. Benacerraf, Cell. Immunol., 82, 23–32 (1983). “Inhibition of Delayed-Type Hypersensitivity by Heparin Depleted of Anticoagulant Activity.”Google Scholar