Tacrolimus thrombotic

A 47-year-old multiparous Hispanic woman received a living-unrelated kidney transplant for end-stage renal disease secondary to polycystic kidney disease. On the day of transplantation she received intravenous daclizumab 1 mg/kg plus methylprednisolone 300 mg and mycophenolate mofetil 3 g/day, and on day 3 ciclosporin emulsion 4 mg/kg/day. On day 8 she developed thrombotic microangiopathy without evidence of rejection. Ciclosporin was withdrawn. Plasmapheresis with fresh frozen plasma was started. Daclizumab on day 14 was postponed for 24 hours and plasmapheresis was stopped to avoid clearance of daclizumab. Thereafter she was given tacrolimus, without recurrence of hemolysis. 

In 16 renal transplant patients with suspected ciclosporin nephrotoxicity, the addition of mycophenolate allowed safe reduction in the dosage of ciclosporin, with subsequent improvement in renal function and arterial blood pressure over 6 months (1). It might allow the rapid withdrawal of glucocorticoids in patients taking ciclosporin or tacrolimus, and therefore reduce the incidence of glucocorticoid-induced post-transplant diabetes, hypercholesterolemia, and hypertension (2). There have been several reports of patients with ciclosporin-associated thrombotic micro-angiopathy/hemolytic-uremic syndrome in whom mycophenolate was successfully substituted (3,4). 

Pham PT, Peng A, Wilkinson AFI, Gritsch FIA, Lassman C, Pham PC, Danovitch GM. Cyclosporine and tacrolimus-associated thrombotic microangiopathy. Am J Kidney Dis 2000 36 844-850. 

T. Thrombotic microangiopathy developing in early stage after renal transplantation with a high trough level of tacrolimus. Clin Exp Nephrol. 2008 (in presss). 

Paramesh AS, Grosskreutz C, Florman SS, Gondolesi GE, Sharma S, Kaufman SS, Fishbein TM.Thrombotic microangiopathy associated with combined sirolimus and tacrolimus immunosuppression after intestinal transplantation. Transplantation 2004 77 129-131. 

Hematologic Thrombotic microangiopathy occurred in a 56-year-old woman after therapy with tacrolimus for 6 days, associated with a high trough concentration [83" ]. 

Thrombotic thrombocytopenic purpura has been attributed to tacrolimus in a 61-year-old woman [84" ]. 

Go O, Naqvi A, Tan A, Amzuta I, Lenox R. The spectrum of thrombotic thrombocytopenic purpura a clinicopatho-logic demonstration of tacrolimus-induced thrombotic thrombocytopenic purpura in a lung transplant patient. South Med J 2008 101(7) 744-7. 

Maeda M, Furuichi Y, Noto T et al (2009) Tacrolimus (FK506) suppresses rt-PA-induced hemorrhagic transformation in a rat thrombotic ischemia stroke model. Brain Res 1254 99-108... 

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