Chemotherapy-Associated Thrombotic Microangiopathy

Abstract

Thrombotic microangiopathy (TMA) is a syndrome of microangiopathic hemolytic anemia and thrombocytopenia with end-organ dysfunction. Although the advent of plasma exchange, immunosuppression, and complement inhibition has improved morbidity and mortality for primary TMAs, the management of secondary TMAs, particularly drug-induced TMA, remains less clear. TMA related to cancer drugs disrupts the antineoplastic treatment course, increasing the risk of cancer progression. Chemotherapeutic agents such as mitomycin-C, gemcitabine, and platinum-based drugs as well as targeted therapies such as antiangiogenesis agents and proteasome inhibitors have been implicated in oncotherapy-associated TMA. Among TMA subtypes, drug-induced TMA is less well-understood. Treatment generally involves withdrawal of the offending agent and supportive care targeting blood pressure and proteinuria reduction. Immunosuppression and therapeutic plasma exchange have not shown clear benefit. The terminal complement inhibitor, eculizumab, has shown promising results in some cases of chemotherapy-associated TMA including in re-exposure. However, the data are limited, and unlike in primary atypical hemolytic uremic syndrome, the role of complement in the pathogenesis of drug-induced TMA is unclear. Larger multicenter studies and unified definitions are needed to elucidate the extent of the problem and potential treatment strategies.