Assessment of thrombogenicity of prothrombin complex concentrates in a porcine model

Infusion of prothrombin complex concentrates into pigs resulted in evidence of disseminated intravascular coagulation manifested by positive fibrin monomer tests, depletion of coagulation factors and platelets, and the presence of fibrin in small blood vessels at autopsy. All of the nine prothrombin complex concentrates were found to be thrombogenic. The response appeared to be dose-related, and the two activated materials were more thrombogenic than the non-activated products. In contrast, a purified factor IX concentrate resulted in minimal transient changes in only 2 of 5 animals tested, and autopsy findings were negative for fibrin deposition in all. Four of these animals received 200 factor IX units/kg, which was twice the dose used for any of the other products. Control animals received human plasma or albumin with no evidence of coagulation changes or fibrin deposition at autopsy. The porcine model is more sensitive than other animal models for detection of the thrombogenic effects of prothrombin complex concentrates and may be useful for testing new products found to be non-thrombogenic in other test procedures.