Comparison of antithrombotic activity of two heparin fragments PK 10169 (mol. wt. 5,000) and EMT 680 (mol. wt. 2,500) and unfractionated heparin in a rabbit experimental thrombosis model: relative importance of systemic anti-Xa and anti-IIa activities.
Two fragments obtained by chemical depolymerization of heparin from porcine mucosal origin PK 10169 (mol. wt. 5,000) and EMT 680 (mol. wt. 2,500) were compared to the original heparin in a rabbit experimental thrombosis model. Thrombosis was induced either by human serum or by bovine Xa. Various doses of heparins (6 animals per dose and per inducer) were injected in order to find the lowest systemic levels of anti-Xa and anti-IIa activities able to inhibit venous-induced thrombogenesis. The systemic activities associated with an inhibition of 50% of the generated thrombi were as follows: 0.17 +/- 0.02 anti-Xa and 0.16 +/- 0.03 anti-IIa units obtained after injection of 97 micrograms/kg (14 anti-Xa and anti-IIa units/kg) of unfractionated heparin, 0.28 +/- 0.04 anti-Xa and 0.14 +/- 0.03 anti-IIa units obtained after injection of 250 micrograms/kg (15 anti-Xa and 7.5 anti-IIa units/kg of PK 10169, and 2.6 +/- 0.2 anti-Xa and 0.06 +/- 0.01 anti-IIa units obtained after injection of 5000 micrograms/kg (260 anti-Xa and 5 anti-IIa units/kg) of EMT 680. These results suggest that the presence of an anti-IIa activity associated with the anti-Xa activity strongly increases the thrombogenesis inhibition in the serum and Xa-induced thrombosis for the heparin fragments of low and very low molecular weight used in this study.
D000818:Animals; D005170:Factor X / Q000037:antagonists & inhibitors*; D015951:Factor Xa; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use*; D011516:Prothrombin / Q000037:antagonists & inhibitors*; D011817:Rabbits; D013927:Thrombosis / Q000188:drug therapy*
D005343:Fibrinolytic Agents; D011516:Prothrombin; D005170:Factor X; C025337:Factor IIa; D006493:Heparin; D015951:Factor Xa