Transplantation-associated thrombotic microangiopathy: twenty-two years later

Abstract

Summary:A syndrome of microangiopathic hemolytic anemia, renal dysfunction and neurological abnormalities was first noted in bone marrow transplant recipients 22 years ago. Now known as transplantation-associated thrombotic microangiopathy (TA-TMA) to distinguish it from other thrombotic microangiopathies, this disorder responds poorly to conventional treatments for thrombotic thrombocytopenic purpura. In this review, we discuss the incidence and risk factors for TA-TMA and describe a pathophysiologic model of the disorder based on results obtained from laboratory models of the thrombotic microangiopathies. We conclude by suggesting possible approaches to the early diagnosis and treatment of TA-TMA based on this model that may warrant testing in future clinical trials.

Transplant-associated microangiopathy (TAM) in recipients of allogeneic hematopoietic stem cell transplants

“…The strongest risk factors for TAM were age and HSCT from unrelated donors, 1,4,[6][7][8]15,20 both risk factors for aGvHD. TAM was correlated with aGvHD severity.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Thrombotic microangiopathy is characterized by systemic or intrarenal platelet aggregation and a microangiopathic hemolytic anemia, with red blood cell (RBC) fragmentation and a negative direct antiglobulin test. Increased platelet consumption leads to thrombocytopenia.…”

Transplantation-associated thrombotic microangiopathy: effect of concomitant GVHD on efficacy of therapeutic plasma exchange

“…[2][3][4] Similar to idiopathic thrombotic thrombocytopenic purpura (TTP), TA-TMA is also associated with the development of renal dysfunction and neurological complications. [2][3][4] However, as both thrombocytopenia and fragmentation of RBC (the hallmark of MAHA) are extremely common post-SCT, and renal dysfunction and neurological complications post-SCT can occur secondary to a diverse range of aetiologies, definitive diagnosis of TA-TMA is often somewhat uncertain. [1][2][3][4][5][6][7] This uncertainty in diagnosis has led to wide variations in the reported incidence of TA-TMA, a lack of consensus regarding clinical approach to management, and poor understanding of prognostic factors with respect to therapeutic response and survival.…”

“…[1][2][3][4] Diagnosis of TA-TMA is based on the presence of thrombocytopenia and microangiopathic haemolytic anaemia (MAHA) in the absence of an alternative clinically apparent aetiology. [2][3][4] Similar to idiopathic thrombotic thrombocytopenic purpura (TTP), TA-TMA is also associated with the development of renal dysfunction and neurological complications.…”

“…[1][2][3][4] Diagnosis of TA-TMA is based on the presence of thrombocytopenia and microangiopathic haemolytic anaemia (MAHA) in the absence of an alternative clinically apparent aetiology. [2][3][4] Similar to idiopathic thrombotic thrombocytopenic purpura (TTP), TA-TMA is also associated with the development of renal dysfunction and neurological complications. [2][3][4] However, as both thrombocytopenia and fragmentation of RBC (the hallmark of MAHA) are extremely common post-SCT, and renal dysfunction and neurological complications post-SCT can occur secondary to a diverse range of aetiologies, definitive diagnosis of TA-TMA is often somewhat uncertain.…”