title: Platelet activation markers after conversion from azathioprine to sirolimus based immunosuppression in renal transplant recipients.
abstract: OBJECTIVE
  Under immunosupression with sirolimus (rapamycin) procoagulant effects and platelet activation have been controversially discussed.
  
  
  METHODS
  We evaluated patients of a prospectly designed substudy as part of a randomized trial investigating the effect of a switch from non-mTOR-based immunosuppression to sirolimus in renal transplant recipients. Our substudy consisted of 7 patients who switched therapy from azathioprine to sirolimus (conversion group) and 8 patients who remained on azathioprine (controls) before (V1) and after (V2) 3 months of treatment. In all patients we assessed flowcytometric markers of platelet activation (PAC-1), platelet degranulation (CD62P), formation of platelet leukocyte-aggregates (PLA), monocyte activation (CD11b), endogenous thrombin potential (ETP) and platelet aggregation.
  
  
  RESULTS
  Both groups were similar in terms of baseline demographics and had stable transplant function for at least 6 months. CD62P increased significantly in the control group (p < 0.03). PLA were significantly reduced in the sirolimus conversion group at V2 (p < 0.02), whereas no effect was seen in the controls. Expression of PAC-1, CD11b, ETP-peak, ETP-time to peak, ETP-AUC and platelet aggregation showed no significant changes in both groups compared to V2.
  
  
  CONCLUSIONS
  From clinical data, performing in depth platelet function testing, we found no evidence for increased platelet activation parameters in RTR who switched therapy from azathioprine to sirolimus.
authors.affiliation: Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University, Frankfurt am Maim, Germany. graff@em.uni-frankfurt.de
authors.forename: Jochen
authors.initials: J
authors.lastname: Graff
authors.forename: Sebastian
authors.initials: S
authors.lastname: Harder
authors.forename: Claudia
authors.initials: C
authors.lastname: Reiche
authors.forename: Ernst-Heinrich
authors.initials: EH
authors.lastname: Scheuermann
authors.forename: Jan
authors.initials: J
authors.lastname: Gossmann
mesh_terms: D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000627:therapeutic use*; D039481:CD11b Antigen / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D010974:Platelet Aggregation; D020123:Sirolimus / Q000627:therapeutic use*
chemical_list: D039481:CD11b Antigen; C509295:ITGAM protein, human; D007166:Immunosuppressive Agents; D019007:P-Selectin; C546937:SELP protein, human; D001379:Azathioprine; D020123:Sirolimus