Transplant-associated thrombotic microangiopathy: elucidating prevention strategies and identifying high-risk patients

Abstract

Introduction: Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) is a severe complication of transplant. TA-TMA is a multifactorial disease where generalized endothelial dysfunction leads to microangiopathic hemolytic anemia, intravascular platelet activation, and formation of microthrombi leading to end-organ injury. It is essential to identify patients at risk for this complication and to implement early interventions to improve TA-TMA associated transplant outcomes.

Areas covered: Recognition of TA-TMA and associated multi-organ injury, risk predictors, contributing factors, differential diagnosis and targeting complement pathway in TA-TMA by summarizing peer reviewed manuscripts.

Expert opinion: TA-TMA is an important transplant complication. Diagnostic and risk criteria are established in children and young adults and risk-based targeted therapies have been proposed using complement blockers. The immediate goal is to extend this work into adult stem cell transplant recipients by implementing universal TA-TMA screening practices. This will facilitate early TA-TMA diagnosis and targeted interventions, which will further improve survival. While complement blocking therapy is effective, about one third of patients are refractory to treatment and those patients commonly die. The next hurdle for the field is identifying reasons for failure, optimizing strategies for complement modifying therapy and searching for additional targetable pathways of endothelial injury.

Keywords: Thrombotic microangiopathy; complement; eculizumab; endothelial injury; stem cell transplant; vasculopathy.