CYCLOSPORINE-A AND FK-506 AFFECT PLATELET FUNCTIONS IN-VITRO

Cyclosporine A (CyA) is known to be associated with an increased risk of thrombotic complications, whereas FK 506 therapy is believed to cause vasculitis. The aim of the study was to evaluate platelet aggregation in platelet rich plasma (PRP) and in whole blood and ATP release in healthy volunteers. CyA added in different concentrations resulted in a dose-dependent enhancement in platelet response to different agonists in PRP, whereas FK 506 did not influence platelet aggregation when added at a concentration of 2 ng/ml, Preincubation with FK 506 at concentrations of 15 and 50 ng/ml significantly inhibited platelet response to serotonin and epinephrine, Preincubation with both CyA and FK 506 did not affect platelet aggregation either in PRP or in whole blood, CyA at every concentration studied resulted in dose-dependent enhancement in ADP-induced platelet aggregation in whole blood, whereas platelet responses to other agonists were found to be increased only with the highest concentration of CyA together with ATP release. FK 506 (50 ng/ml) resulted in a significant decline in platelet aggregation, whereas lower concentrations did not affect platelet aggregatory responses. Platelet hyperreactivity in response to CyA may contribute, at least in part, to the increased incidence of thrombosis events. Platelet effects of FK 506 in vivo are not yet known, whereas in vitro this drug seems to inhibit aggregation of normal human platelets.