Original Article: Streptokinase Modifies in Vitro Platelet Aggregation by Two Mechanisms: Reduced Aggregation due to Fibrinogenolysis and Enhanced Aggregation via an Immunological Reaction

Abstract

Both inhibition and enhancement of platelet aggregation have been observed after exposure to streptokinase (SK) in vitro. Recently we have shown that inhibition of aggregation appears to be related to the fraction containing the fibrinogen degradation product, fragment E. In addition, SK may initiate platelet aggregation by a mechanism involving specific anti-SK antibodies and plasminogen. Two monoclonal antibodies (MoAbs) (PL2-49 and LeoA1) were used to assess the immunological activation of platelets in SK-induced platelet aggregation and in SK-enhanced ADP-induced platelet aggregation. The anti-SK titers in healthy volunteers' and patients' (previously treated with SK for acute myocardial infarction) plasma, were measured using a one-site non-competitive ELISA. Serum from patients was used for the purification of IgG anti-SK by affinity chromatography.

We confirmed that the degree of fibrinogen degradation is a major determinant of the aggregation inhibition induced by SK. SK-induced platelet aggregation and SK-enhanced ADP-induced platelet aggregation require the interaction of the Fc domain of the anti-SK antibodies with the FcyRII located on the platelet membrane, since they are blocked by the MoAb IV-3 directed against FcyRII. Classification of the subjects according to their responses to specific MoAbs (PL2-49 and LeoA1) supports the essential role played by immunological activation of platelets in SK-induced platelet aggregation and in SK-enhanced ADP-induced platelet aggregation. The ability of anti-SK antibodies to promote SK-induced platelet aggregation and SK-enhanced ADP-induced platelet aggregation, seems to result from the interaction between two separate mechanisms: the fist mechanism is based on immunological activation of platelets and the second is related to the intervention of a defined subset of anti-SK antibodies.