Influence of mycophenolic acid and FK-506 on human platelet activation in vitro

Background/Aim: FK-506 (FK) and mycophenolic acid (MPA) are immunosuppressi ve agents used in kidney transplant recipients. Their effect on posttranspl ant thromboembolic complications is either controversial (FK) or has not be en described (MPA), Thromboembolic events are among the consequences of pla telet hyperaggregability which can be identified by measuring platelet aggr egation. 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 mu g/ml) before platelet aggregation was induced by the platelet agonists adenosine diphosphate (2 and 5 mu M) and collagen 0. 5 and 1.0 mu g/ml). Aggregation was measured by recording the optical densi ty. Results: MPA resulted in a significant decrease in the platelet respons e to collagen (1.0 mu g/ml) in platelet-rich plasma, whereas FK significant ly increased platelet aggregation in response to collagen (0.5 mu g/ml). Th e vehicle of FK had no influence on platelet aggregation with either agonis t, Conclusions: The decreased platelet-activating response following preinc ubation with MPA may favor its use in kidney transplant recipients to reduc e thromboembolic events. The FK-induced enhancement of platelet aggregation shown in vitro may lead to thromboembolic complications in transplant reci pients, Copyright (C) 2000 S. Karger AG, Basel.