Atypical Presentation of Drug-Induced Thrombotic Microangiopathy: Time Does Not Matter

Introduction: Thrombotic Microangiopathy (TMA) is a disorder that causes disseminated occlusive microvascular thrombosis, thrombocytopenia, and end organ damage, commonly in the kidneys and brain. In cancer patients, especially those in multi-drug chemotherapy regimens, TMA is a diagnostic challenge due to overlap with other thrombotic disorders such as TTP, aHUS, and DIC. TMA can occur as a manifestation of the cancer itself and has been reported in mucin-producing adenocarcinomas. Chemotherapy-associated TMA can occur due to immune-mediated reaction or dose-dependent toxicity. TMA secondary to VEGF inhibitors has been described; however, literature reporting TMA due to Tyrosine Kinase Inhibitors (TKI) is limited. We present a case of TMA secondary to lenvatinib and bevacizumab. Case Description: We report a case of a 31-year-old man with history of metastatic hepatocellular adenocarcinoma who was referred to the hospital with nephrotic-range proteinuria. Prior therapy regimen included bevacizumab and more recently Lenvatinib, last dose 3 weeks prior presentation of AKI. Creatinine increased to 4 mg/dL from a baseline of 1.5 mg/dL. Coagulation panel, ADAMST13 were normal. ALP and LDH were elevated. Other bloodwork revealed new thrombocytopenia and hypoalbunemia. TTP, aHUS and DIC were ruled out. Due to unclear cause, patient underwent renal biopsy that showed Chronic thrombotic microangiopathy with FSGS. After confirmation of results, patient remained on therapy for HCC and was offered hemodialysis. Discussion: This case highlights the importance of evaluating the etiology of TMA, particularly in patients on chemotherapy independent of the time of administration of therapy. Distinguishing the cause of AKI in this patient is clinically important for appropiate treatment and avoidance of future drug toxicity. It also shows that renal biopsy can aid in the diagnosis. Restarting the offending medication a lower dose may help to avoid recurrent TMA.