Transplant-Associated Thrombotic Microangiopathy (TA-TMA): Pathophysiology and Diagnostic Criteria An estimated 18,000 hematopoietic stem cell transplant (HSCT) procedures are performed in the United States each year. Transplant-associated thrombotic microangiopathy (TA-TMA) is the result of a systemic vascular endothelial injury following transplantation. The true incidence of TA-TMA is currently unknown due to a lack of awareness of the condition and due to non-standardized diagnostic criteria. Single center and registry studies have reported rates between 1 and 20%. Severe TA-TMA, leading to multi-organ failure is associated with mortality rates above 80%. The clinical presentation of TA-TMA is similar to that of other TMAs and includes thrombocytopenia, Coombs-negative hemolysis, the presence of schistocytes on peripheral blood smear, and acute renal failure, mental status changes, or both. Early treatment can improve outcomes. However, clinical manifestations that overlap with those of other TMAs and the lack of specific diagnostic criteria hinder the early diagnosis of TA-TMA. The pathophysiology of TA-TMA is thought to involve an endothelial injury stemming from the conditioning regimen or other endothelial activating events (i.e, infections, drug or graft versus host disease).3 Endothelial activation induces cytokine release along with other proinflammatory changes and capillary flow obstruction, as a result of fibrin-related aggregates and platelet and leukocyte adhesion, which then lead to organ dysfunction. Other inflammatory changes, such as changes in nitric oxide (NO) levels and excessive complement activation, can also play a role in the pathophysiology of TA-TMA.
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