Improved fibrinolytic capacity after withdrawal of steroid immunosuppression in renal transplant recipients

Background. Long-term steroid immunosuppression has been associated with th e prothrombotic state observed in renal transplant (RT) patients, in whom b oth hypercoagulability due to an increase of von Willebrand factor/factor W I complex, and impaired fibrinolysis due to PAI-1 excess have been demonstr ated. Our aim was to investigate the effect of steroid withdrawal on fibrin olytic capacity in a group of RT patients. Methods. The fibrinolytic study was performed in 28 RT patients under stabl e immunosuppression therapy with cyclosporine, azathioprine, and methylpred nisolone; only 12 of these patients could repeat the study 6 months after s teroid withdrawal, Euglobulin lysis time (ELT), tissue plasminogen activato r activity (t-PA:act) and antigen (t-PA:Ag), PAI-1 activity (PAI-1:act), an d antigen (PAI-1:Ag) were assayed on blood samples drawn before and 20 min after the venous occlusion test (VO). Results. An hypofibrinolytic state due to a significant increase in PAI-1 l evels was confirmed in RT patients receiving triple immunosuppression thera py. RT patient who stayed off steroids showed a significant shortening of E LT both before (P=0.01) and 20' after VO (P=0.005) at the 6-month control. Moreover, after steroid withdrawal, PAI-1:Ag levels decreased significantly (P=0.002) and normalized; in a similar manner PAI-1:act levels also showed a significant decrease both before (P=0.001), and after VO (P=0.0001). The prevalence of RT patients with impaired fibrinolytic capacity was as high as 83.3% during steroid treatment, and dropped to 16.7% after steroid withd rawal. Conclusions. Our findings confirm that steroid withdrawal may normalize imp aired fibrinolytic capacity in RT patients; this improvement may further co ntribute to reduce the thrombotic risk associated with renal transplantatio n.