title: Improved fibrinolytic capacity after withdrawal of steroid immunosuppression in renal transplant recipients.
abstract: BACKGROUND
  Long-term steroid immunosuppression has been associated with the prothrombotic state observed in renal transplant (RT) patients, in whom both hypercoagulability due to an increase of von Willebrand factor/factor VIII complex, and impaired fibrinolysis due to PAI-1 excess have been demonstrated. Our aim was to investigate the effect of steroid withdrawal on fibrinolytic capacity in a group of RT patients.
  
  
  METHODS
  The fibrinolytic study was performed in 28 RT patients under stable immunosuppression therapy with cyclosporine, azathioprine, and methylprednisolone; only 12 of these patients could repeat the study 6 months after steroid withdrawal. Euglobulin lysis time (ELT), tissue plasminogen activator activity (t-PA:act) and antigen (t-PA:Ag), PAI-1 activity (PAI-1:act), and 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 levels was confirmed in RT patients receiving triple immunosuppression therapy. RT patient who stayed off steroids showed a significant shortening of ELT 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 withdrawal.
  
  
  CONCLUSIONS
  Our findings confirm that steroid withdrawal may normalize impaired fibrinolytic capacity in RT patients; this improvement may further contribute to reduce the thrombotic risk associated with renal transplantation.
authors.affiliation: Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Italy.
authors.forename: M T
authors.initials: MT
authors.lastname: Sartori
authors.forename: G M
authors.initials: GM
authors.lastname: Patrassi
authors.forename: P
authors.initials: P
authors.lastname: Rigotti
authors.forename: F
authors.initials: F
authors.lastname: Marchini
authors.forename: M
authors.initials: M
authors.lastname: Fioretti
authors.forename: L
authors.initials: L
authors.lastname: Spiezia
authors.forename: A
authors.initials: A
authors.lastname: Girolami
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects*; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D017395:Plasminogen Activator Inhibitor 1; D016572:Cyclosporine; D010959:Tissue Plasminogen Activator; D001379:Azathioprine; D008775:Methylprednisolone