Diagnosis and management of thrombotic microangiopathy following hematopoietic stem cell transplantation

Abstract

Thrombotic microangiopathy (TMA) is microvascular occlusive disorder characterized by thrombocytopenia, hemolytic anemia, and systemic or intrarenal platelet-rich thrombi. In addition to the two major forms of TMA, thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), transplantation-associated TMA (TA-TMA) is a well-recognized complication of hematopoietic stem cell transplantation. Acquired TTP is associated with a deficiency in ADAMTS13 caused by the production of autoantibodies. Despite the initial identification of TA-TMA as TTP, it is not associated with ADAMTS13 deficiency and it is largely unresponsive to plasma exchange compared to TTP. Currently, the pathogenesis of TA-TMA is not well understood. However, endothelial cell injury caused by graft-versus-host disease, chemoradiotherapy, infection, and calcineurin inhibitors were all implicated for their crucial roles in pathogenesis of this disease. Although a standard treatment strategy of TA-TMA has not yet been established, it is clear that early diagnosis and treatment improve prognosis. There is a consensus that calcineurin inhibitors should be discontinued and replaced with an alternate immunotherapy. In a small retrospective study to identify novel therapies for TA-TMA, recombinant soluble thrombomodulin, rituximab, and eculizumab were reported as putative alternative treatments.