Complement in Pathophysiology and Treatment of Transplant-Associated Thrombotic Microangiopathies

Transplant-associated thrombotic microangiopathy (TA-TMA) is a form of microangiopathy specifically occurring in the context of hematopoietic stem cell transplantation. Similarly, to other microangiopathies, TA-TMA is characterized by hemolytic anemia, thrombocytopenia, and organ failure due to endothelial injury. Although its clinical association with medications (eg, calcineurin inhibitors), immune reactions (eg, graft vs host disease) or infectious complications is well established, the pathophysiology remains largely unknown. Recent data have highlighted the role of complement in the pathophysiology of TA-TMA, which are frequently associated with a functional impairment (either inherited or acquired) of the endogenous regulation of the complement classic and alternative pathway. This manuscript will review the data supporting the involvement of complement in the pathophysiology of TA-TMA, as well as the clinical data supporting the use of anticomplement agents in this rare condition.