APROTININ INHIBITS PLASMIN-INDUCED PLATELET ACTIVATION DURING CARDIOPULMONARY BYPASS

Background In the past few years, aprotinin has been used in cardiac s urgery with impressive results of reducing blood loss, but several adv erse effects of aprotinin also have been reported. One of the most lik ely mechanisms is the inhibition of plasmin by aprotinin, although thi s indirect effect has not been reproduced in all experimental studies. Methods and Results We evaluated the platelet function and fibrinolyt ic activity during human cardiac surgery, with or without aprotinin. D uring cardiopulmonary bypass (CPB) in humans without aprotinin (n=16), decrease of platelet aggregation induced by thrombin, increase of alp ha-granule secretion of platelet and microparticle formation, and incr ease of plasmin/alpha(2)-antiplasmin complex (PIG) were observed. In c ontrast, low-dose aprotinin (1.0x10(6) KTU), which was administered on ly into the priming fluid of extracorporeal circuits (n=10), maintaine d platelet aggregation induced by thrombin and reduced a-granule secre tion and microparticle formation of platelets during CPB. In vitro, pl asmin (0.8 CU/mL) released a-granules of washed platelets, and this ac tivation was completely inhibited by aprotinin (10 KIU/mL). Conclusion s Aprotinin has indirect effects to inhibit platelet activation, and t his may partly explain the reduction of blood loss during cardiac surg ery. To prevent the adverse effects, a single and minimal use of aprot inin is important. The results of in vivo and in vitro studies suggest that platelet preservation was demonstrated by the lower concentratio n of aprotinin (1.0x10(6) KIU per patient or 10 KIU/mL) compared with the concentration that inhibits plasma fibrinolysis.