Platelet activation markers after conversion from azathioprine to sirolimus based immunosuppression in renal transplant recipients

Int J Clin Pharmacol Ther. 2012 Dec;50(12):873-9. doi: 10.5414/CP201768.

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.

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Azathioprine / therapeutic use*
  • CD11b Antigen / blood
  • Female
  • Flow Cytometry
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • P-Selectin / blood
  • Platelet Activation*
  • Platelet Aggregation
  • Sirolimus / therapeutic use*

Substances

  • CD11b Antigen
  • ITGAM protein, human
  • Immunosuppressive Agents
  • P-Selectin
  • SELP protein, human
  • Azathioprine
  • Sirolimus