Examination of the causes of early pregnancy-associated thrombocytopenia in mice.

In mice, neither the bleeding time nor the clotting time of whole blood was different on Day 2 of pregnancy compared with pseudopregnancy. Standardization of the platelet concentration to 10(6)/microliters plasma resulted in a significant reduction in the clotting time of plasma from pregnant animals. This reduction was not due to an increase in the intrinsic or extrinsic pathways of the coagulation cascade but to enhanced platelet factor III activity, indicating increased platelet activation and consumption. Increased activation was not due to immunological recognition of the embryo because thrombocytopenia occurred after syngeneic and allogeneic matings of inbred strains of mice and also after parthenogenetic activation of ova in situ. Injection of embryo culture medium into splenectomized mice induced a significant dose-dependent thrombocytopenia. It occurred within 10 min after injection and persisted for up to 2 h. There was no reduction in platelet count when animals were injected with culture media in which unfertilized ova had been incubated. Early pregnancy-associated thrombocytopenia was caused by the production of platelet-activating factors by the fertilized eggs. The induction of thrombocytopenia by embryo culture media displayed a dose-response curve that was parallel to that of the platelet-activating factor, 1-0-alkyl-2-acetyl-sn-glycero(3)phosphocholine.