TTP/HUS occurring in a simultaneous pancreas/kidney transplant recipient after clopidogrel treatment: evidence of a nonimmunological etiology.

BACKGROUND: One recently reported thrombotic thrombocytopenia purpura/hemolytic uremic syndrome (TTP/HUS) case involved a patient who underwent simultaneous pancreas/kidney (SPK) transplant followed by pancreas rejection and clopidogrel treatment, an antiplatelet agent that has been associated with immunologically mediated TTP/HUS. We present a second case of TTP/HUS developing in an SPK recipient who was also receiving clopidogrel. METHODS: After a stroke, a 48-year-old male SPK transplant recipient received clopidogrel. Four months later, thrombosis and rejection of the transplanted pancreas occurred. One week after a pancreatectomy, TTP/HUS developed that resolved with clopidogrel and sirolimus discontinuation and lowering of the tacrolimus dose. RESULTS: A plasma sample revealed von Willebrand factor cleaving metalloproteinase activity, although no immunoglobulins to the protease were identified. The patient continues taking tacrolimus with normal renal function 1 year after the incident. DISCUSSION: Our findings suggest a nonimmunological etiology for TTP/HUS in clopidogrel-treated transplant recipients. Furthermore, mechanistic focused laboratory studies can facilitate interpretation of case report findings.