Cyclosporine A enhances platelet aggregation.
In view of the reported increase in thromboembolic episodes following cyclosporine A (CyA) therapy, the effect of this drug on platelet aggregation and thromboxane A2 release was investigated. The addition of CyA, at therapeutic concentrations to platelet rich plasma from normal subjects in vitro was found to increase aggregation in response to adrenaline, collagen and ADP. Ingestion of CyA by healthy volunteers was also associated with enhanced platelet aggregation. The CyA-mediated enhancement of aggregation was further enhanced by the addition in vitro of therapeutic concentrations of heparin. Platelets from renal allograft recipients treated with CyA also showed hyperaggregability and increased thromboxane A2 release, which were most marked at "peak" plasma CyA concentration and less so at "trough" concentrations. Platelet hyperaggregability in renal allograft patients on long-term CyA therapy tended to revert towards normal following the replacement of CyA with azathioprine. Hypertensive patients with renal allografts on nifedipine therapy had normal platelet function and thromboxane release in spite of CyA therapy. These observations suggest that CyA-mediated platelet activation may contribute to the pathogenesis of the thromboembolic phenomena associated with the use of this drug. The increased release of thromboxane A2 (a vasoconstrictor) may also play a role in mediating CyA-related nephrotoxicity.
Grace
A A
AA
Department of Nephrology and Transplantation, Royal Free Hospital and School of Medicine, London, United Kingdom.
Barradas
M A
MA
Mikhailidis
D P
DP
Jeremy
J Y
JY
Moorhead
J F
JF
Sweny
P
P
Dandona
P
P
D000328:Adult; D001379:Azathioprine / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D003524:Cyclosporins / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D013928:Thromboxane A2 / Q000097:blood
D003524:Cyclosporins; D013928:Thromboxane A2; D006493:Heparin; D009543:Nifedipine; D001379:Azathioprine; D002118:Calcium