Inhibitors of ADAMTS13: a potential factor in the cause of thrombotic microangiopathy in a renal allograft recipient.

BACKGROUND

Thrombotic microangiopathy (TMA) is a well-known complication after renal allograft transplantation. In most cases, calcineurin inhibitor is believed to play a role in the development of this disorder. Recent studies have shown that a deficiency in the activity of the von Willebrand factor-cleaving metalloprotease ADAMTS13 causes thrombotic thrombocytopenic purpura. A similar mechanism occurring in patients who develop TMA after renal transplantation has not been described.

METHODS

Analysis of plasma samples from a patient who developed TMA after receiving a cadaveric renal allograft revealed undetectable ADAMTS13 activity and the presence of its inhibitors.

RESULTS

Discontinuation of cyclosporine and daily plasma exchange increased the ADAMTS13 activity, which was followed by resolution of the microangiopathic hemolysis and improvement of the graft function. At 3-month follow-up, the ADAMTS13 activity remained in the normal range and no inhibitors were detected.

CONCLUSIONS

This is the first case to demonstrate a correlation between the presence of ADAMTS13 inhibitors and transplant-associated TMA. Autoimmune inhibitors of ADAMTS13 should be considered in patients with transplant-associated thrombotic microangiopathy. The role of calcineurin inhibitor in the formation of autoantibodies to ADAMTS13 remains to be explored.