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.