SPECIES-SPECIFIC IMMUNOASSAYS TO MEASURE BLOOD-PLATELET AND COAGULATION ACTIVATION IN THE RAT

The purpose of this study was to develop specific and sensitive immuno assays to detect early indices of hypercoagulability in the rat. Rat p latelet factor 4 (rPF4) and rat fibrinopeptide A (rFPA) assays, tools for the detection of activation of platelets and coagulation respectiv ely, were designed using antibodies raised against purified rPF4 and a gainst synthetic rFPA. The relevance of these new assays and of the co mmercially available ELISA kit for thrombin-antithrombin III (TAT) com plexes was demonstrated in a rat model of a prethrombotic state induce d by intravenous infusion of varying doses of thromboplastin (90 to 24 00 mu L/kg/h). In this model, the immunoassays allowed simultaneous de tection of low levels of rFPA and rPF4 which were correlated with fibr inogen and platelet consumption and TAT generation and further proved to be of higher sensitivity than the classical methods of platelet cou nt or measurement of fibrinogen levels. Plasma concentrations of rFPA, rPF4 and TAT were dependent on infusion time and thromboplastin dose, while hirudin (1 mg/kg) prevented their appearance. Thus the new spec ific immunoassays for rPF4 and rFPA and the commercial human TAT assay represent useful tools for pathophysiological studies or the screenin g of antithrombotic drugs in rats.