Thrombocytopenia Induced in Mice by Thromboplastin Infusion – Essential Role of the Third Complement Component

Abstract

SummaryStudies were performed in mice to investigate the effects of the slow infusion of brain thromboplastin (tissue factor) on blood platelet levels. Thromboplastin caused pronounced thrombocytopenia in all strains of mice tested without histological evidence of intravascular coagulation. The role of the complement system in the thrombocytopenic response to thromboplastin administration was evaluated by using complement-deficient animals. Depending on experimental conditions, the degree of platelet reduction in C5-deficient mice was similar to or significantly lower than in normocomplementemic animals. C5-deficient mice reconstituted with mouse plasma or purified human C5 had a thrombocytopenic reaction identical to that of normocomplementemic controls. The thrombocytopenic response of B10.D2/new and old line mice could be abrogated by inactivating C3 with cobra venom factor prior to the administration of thromboplastin. We conclude that in mice C3 plays a central role in the thrombocytopenia induced by thromboplastin infusion, while C5 (and/or other late acting components) plays only a minor role. In vivo activation of complement by thromboplastin was indicated by the finding that thromboplastin infusion in B10.D2/new mice caused a significant reduction in total serum hemolytic complement and a slight reduction in C3 measured immunochemically. The platelet counts of uninjected B10.D2/new mice were slightly but significantly higher than in B10.D2/old mice.