Influence of Mycophenolic Acid and FK–506 on Human Platelet Activation in vitro

BACKGROUND/AIM: FK-506 (FK) and mycophenolic acid (MPA) are immunosuppressive agents used in kidney transplant recipients. Their effect on posttransplant thromboembolic complications is either controversial (FK) or has not been described (MPA). Thromboembolic events are among the consequences of platelet hyperaggregability which can be identified by measuring platelet aggregation. The aim of this study was to evaluate the in vitro effects of MPA and FK upon platelet activation in healthy subjects. METHODS: Platelet-rich plasma from healthy volunteers (n = 18) was incubated with FK (70 ng/ml), FK vehicle, and MPA (30 microg/ml) before platelet aggregation was induced by the platelet agonists adenosine diphosphate (2 and 5 microM) and collagen 0.5 and 1.0 microg/ml). Aggregation was measured by recording the optical density. RESULTS: MPA resulted in a significant decrease in the platelet response to collagen (1.0 microg/ml) in platelet-rich plasma, whereas FK significantly increased platelet aggregation in response to collagen (0.5 microg/ml). The vehicle of FK had no influence on platelet aggregation with either agonist. CONCLUSIONS: The decreased platelet-activating response following preincubation with MPA may favor its use in kidney transplant recipients to reduce thromboembolic events. The FK-induced enhancement of platelet aggregation shown in vitro may lead to thromboembolic complications in transplant recipients.