Eculizumab Reduces Red Blood Cell Transfusions in Non-Renal Solid Organ Transplant Patients Diagnosed with Post Transplant Atypical Hemolytic Uremic Syndrome (PT-aHUS)

INTRODUCTION: Patients who receive non-renal solid organ transplants have a reported 4-30% incidence of post transplant thrombotic microangiopathy (PT-TMA). The development of PT- TMA is associated with a significant increase in early mortality when compared to patients with no PT-TMA. Mortality rates as high as 70% are associated with PT-TMA in spite of plasma exchange therapy. The factors which contribute to this high mortality are poorly understood. New findings suggest that this form of TMA is complement mediated and can be classified as PT-aHUS. We and others have reported the clinical and laboratory benefits of treating PT-aHUS with eculizumab. There are suggestions of a link between PT-TMA and decreased graft survival although the mechanism is not well understood. Theories include: 1) chronic ischemia from TMA, 2) chronic/low grade antibody mediated rejection (perhaps contributed to by alloimmunization from transfusions) and 3) direct damage to graft mediated by complement. The role that multiple post transplant transfusions plays in poor overall and/or poor graft survival in these patients has not been evaluated, but is intriguing.

MATERIALS and METHODS: We report our experience with 9 patients who underwent non renal solid organ transplantation (7 small bowel and 2 orthotopic liver) in 2011 - 2013 at our institution who were diagnosed clinically with PT-aHUS and treated with eculizumab. Blood component use was evaluated from the date of transplant (DOT) to the date of initiation of eculizumab therapy 1-53 months (mean: 11 months) and after initiation of eculizumab therapy 6-24 months (mean: 13 months). Criteria for transfusions and the clinical team were unchanged during the study period.

RESULTS: Red blood cell (RBC) transfusions from the DOT to the date of eculizumab initiation 5-53 units (mean: 31 units), PRBC transfusions post initiation of eculizumab therapy 0-41 units (mean: 11 units). Apheresis platelet (PLT) transfusions from the DOT to the date of eculizumab initiation 0-7 units (mean: 3 units), PLT transfusions post initiation of eculizumab therapy 0-16 units (mean: 2units). Fresh frozen plasma (FFP) infusions from the DOT to the date of eulizumab initiation 0-272 units (mean: 43 units) FFP infusions post initiation of eculizumab therapy 1-10 units (mean: 2units).

CONCLUSIONS: The significant reduction in RBC transfusions after the initiation of eculizumab demonstrates a previously unreported clinical benefit of the complement inhibitory effects of eculizumab in patients with PT-aHUS. While long term results remain to be determined continued monitoring of both overall patient and graft survival in these patients will be interesting. We hypothesize that early treatment of PT-aHUS with eculizumab minimizing the need for transfusion therapy will have a beneficial effect on overall patient as well as graft survival.