Transplant-associated TMA: the conundrum of diagnosis and treatment

Transplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic cell transplantation is characterized by microangiopathic hemolytic anemia (MAHA) with persistent schistocytosis, elevated markers of hemolysis, thrombocytopenia, and microvascular thrombosis leading to ischemic injuries in the kidneys and other organs. The initial evaluation of the disease requires confirmation of non-immune MAHA and careful examination of known secondary causes of TMA. Due to increased likelihood of long-term renal failure and overall mortality, a rapid diagnosis and treatment of the underlying trigger is needed. However, the diagnostic criteria proposed to define TA-TMA remain insufficient. sC5b9, the soluble form of the membrane attack complex of the terminal complement pathway, is the most studied prognostic biomarker for the disease, though its sensitivity and specificity remain suboptimal for clinical use. Current evidence does not support the cessation of calcineurin inhibitors without cause or the use of therapeutic plasma exchange. Many recent single-arm studies targeting the complement pathway inhibition have been reported, and larger randomized controlled trials are ongoing. This review aims to provide an evidence-based discussion from both adult and pediatric perspectives on the advances and conundrums in TA-TMA diagnosis and treatment.