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.


CONCLUSIONS
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.
D019703:Calcineurin / Q000009:adverse effects; D000077144:Clopidogrel; D006084:Graft Rejection; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology*; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000009:adverse effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D011697:Purpura, Thrombotic Thrombocytopenic / Q000209:etiology*; D013988:Ticlopidine / Q000009:adverse effects* / Q000031:analogs & derivatives
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D019703:Calcineurin; D013988:Ticlopidine