Abstract

DRUG-INDUCED THROMBOTIC MICROANGIOPATHY: A NARRATIVE REVIEW OF PATHOPHYSIOLOGY, CAUSATIVE DRUGS, DIAGNOSIS, AND TREATMENT

^*Shibin Biju, Sneha Elisa Bency, Rini Sara John, Jiji Alfred

Abstract

Drug-induced thrombotic microangiopathy (DITMA) is a rare and potentially life-threatening condition that is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombi leading to variable degrees of dysfunction in organs, especially acute renal failure. DITMA represents a heterogeneous group of disorders, which can be caused by several medications through immune-mediated or dose-dependent toxic mechanisms that lead to endothelial injury and thrombus formation. In recent times, there has been an increase in the types of drugs involved, including targeted anti-cancer medications, immune checkpoint inhibitors, VEGF inhibitors, proteasome inhibitors, calcineurin inhibitors, and CAR-T cell therapy. Diagnosis of this condition is quite difficult due to overlapping clinical features with thrombotic microangiopathies such as thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome. Management involves stopping the causative agent immediately, as well as supportive care and management of the organ-related complications. Recent studies have shown that complement activation plays a role in the development of certain types of DITMA, thus justifying the use of complement pathway inhibition therapy with eculizumab and ravulizumab in certain patients. This narrative review comprehensively summarizes the history, epidemiology, pathophysiology, etiologic agents, symptoms, diagnostics, complications, and current treatment methods of DITMA. Additionally, recent advances in the field of complement biology, biomarker discovery, precision medicine, and new treatments for DITMA have been addressed to help clinicians gain a better understanding of this complicated disease.

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