Evidence for chronic platelet hyperaggregability and in vivo activation in cyclosporin-treated renal allograft recipients.
Evidence for chronic in vivo platelet activation and hyperaggregability has been assessed in 21 renal allograft recipients. All patients received long term immunosuppression with cyclosporin (CS) and low dose prednisolone and were studied serially for 1 year post-transplantation. Spontaneous platelet aggregation in PRP was observed on 10 occasions in 5 patients. Platelet aggregation responses in PRP to low doses of ADP (0.5 and 1.0 microM) were significantly increased up to 1 year post-transplantation (p less than 0.02-less than 0.002). Total platelet nucleotide (ATP and ADP) content and release to 20 micrograms/ml of collagen were significantly decreased for 2 months post-transplantation, indicative of in vivo platelet activation (p less than 0.05-less than 0.002), and plasma PF4 levels were increased up to 1 year post-transplantation suggesting continued platelet activation of a lesser degree. Platelet sensitivity to the prostacyclin analogue Iloprost decreased after 1 month (p less than 0.05) and this persisted up to 1 year (p less than 0.01) compared with sensitivity at 1 week post-transplantation. These prothrombotic changes persisted when trough whole blood CS levels were within the therapeutic range and plasma creatinine levels were approaching or were in the normal range. These data indicate that CS-treated renal allograft recipients exhibit chronic platelet hyperactivity.
D000227:Adenine Nucleotides / Q000097:blood; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D003524:Cyclosporins / Q000009:adverse effects*; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D006801:Humans; D016285:Iloprost; D066298:In Vitro Techniques; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D013927:Thrombosis / Q000209:etiology; D013997:Time Factors
D000227:Adenine Nucleotides; D003524:Cyclosporins; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D016285:Iloprost