Inhibition of streptokinase-induced, antibody-mediated platelet aggregation with tirofiban after exposure to streptokinase or streptococcal infection

Study Objective. To evaluate the effect of tirofiban (a glycoprotein IIb-IIIa inhibitor) in preventing streptokinase-induced, antibody-mediated platelet aggregation after administration of streptokinase or development of a streptococcal infection. Design. Prospective analysis. Setting. Research center of a Canadian hospital. Participants. Forty-five healthy volunteers, 45 patients who had received streptokinase within the past 3 years, and 13 patients who had a severe streptococcal infection also within the past 3 years. Intervention. Blood samples were drawn to measure the extent of inhibition of streptokinase-induced, antibody-mediated platelet activation and aggregation by tirofiban. Measurements and Main Results. Platelet aggregation was measured by using a turbidimetric method. The extent of inhibition by tirofiban was measured by incubating tirofiban for 2 minutes before adding streptokinase 5000 U/ml. Also, tirofiban was added 2 minutes before adding adenosine 5'-diphosphate (ADP) 2 muM/L into the last tube as a comparison. Streptokinase-induced, antibody-mediated platelet aggregation was observed in 10 (22%) of the 45 patients treated with streptokinase, in 3 (23%) of the 13 patients with streptococcal infection, and in none of the 45 healthy volunteers. Tirofiban inhibited streptokinase-induced, antibody-mediated platelet aggregation by 89 +/- 14% (p<0.001). Similarly, ADP-induced platelet aggregation was inhibited by 92 +/- 6% (p<0.001) with tirofiban. Conclusion. Streptokinase-induced, antibody-mediated platelet aggregation occurred in 13 (22%) of 58 patients who received streptokinase or were exposed to a streptococcal infection in the past 3 years. Such patients may not benefit from streptokinase therapy. In these patients, tirofiban significantly decreased the extent of antistreptokinase antibody-mediated platelet aggregation. Hence, patients undergoing streptokinase therapy may benefit from tirofiban as adjunctive therapy.