Quantitative Estimation of Thrombin-Antithrombin III and Plasmin-Alpha1-Antiplasmin Complexes in Human Plasma

Abstract

During activation of the coagulation or fibrinolytic system in human plasma neo-antigens evolve, associated with the thrombin-antithrombin III (T-AT) and plasmin-α1-antiplasmin (P-AP) complexes (D. Collen and P. De Cock, Thromb, Res., 5, 777, 1974), A tanned red cell hemagglutination inhibition immunoassay (TRCHII) has been adapted to the quantitation of these complexes in plasma. Experiments with partially absorbed antisera revealed that fresh plasma had a titer of 4 to 32 in the TRCHII for T-AT and of 4 to 16 in the TRCHII for P-AP. Serum reacted 8 to 16 times better than plasma in the TRCHII for T-AT and urokinase activated plasma 32 to 128 times better than plasma in the TRCHII for P-AP.During streptokinase (SK) therapy in 3 patients (infusion of 600,000 HI Kabikinase® over 30 min) a marked increase in the P-AP complex titer, approaching or equalling that of the subject’s plasma activated in vitro with urokinase, was observed at the end of the SK infusion. The titer remained high during the first three hours and was still higher than the pre-infusion value after 24 hours, suggesting that this complex has a half-life of several hours in vivo. During reptilase therapy in 3 patients (infusion of 2 ml Defibrase® over 1 hour) the P-AP complex titer increased gradually but submaximally over a period of several hours and remained elevated for at least 48 hours, indicating that the plasminogen consumption observed during reptilase therapy is due, at least in part, to a secondary fibrinolytic response.Further studies to show whether these assays can be converted to rapid, simple and specific tests for the diagnosis of low grade or regional in vivo coagulation or fibrinolysis in clinical conditions are in progress.