TMAs are a rare but severe cause of acute ischemic stroke. While common etiologies such as cardioembolism or large-artery atherosclerosis dominate clinical practice, strokes from TMAs can be rapidly progressive and catastrophic when diagnosis and treatment are delayed. We report a 63-year-old female with significant cardiovascular comorbidities and prior strokes who initially presented with encephalopathy and focal neurological deficits. Neurological examination revealed an NIHSS score of 19, global aphasia, leftward gaze deviation, and right-sided paralysis. MRI revealed bilateral ischemic infarcts, left temporal-occipital lesions and right frontal-parietal strokes. Despite thrombectomy, she remained comatose with worsening cerebral ischemia on imaging. Laboratory findings revealed schistocytes, thrombocytopenia, indirect hyperbilirubinemia, and coagulation dysfunction. ADAMTS13 activity returned 55%, potentially confounded by prior plasma infusion. The overlapping features of TMA subtypes complicated diagnosis and delayed TMA-directed therapy. Plasma exchange and corticosteroids were initiated, but subsequent neuroimaging showed progression of neurological insult leading to irreversible cerebral injury. Given the poor prognosis, care was transitioned to comfort measures.

This case presents the diagnostic and therapeutic dilemma of strokes caused by TMAs when clinical laboratory results point to overlapping subtypes. Standard stroke therapies such as thrombolysis or antiplatelets are ineffective or contraindicated against microthrombi caused by TMA. Clinicians should Initiate TMA-directed treatment promptly as per guidelines, even if confirmatory testing is inconclusive. The fulminant course of TMA-related strokes necessitates early recognition and targeted therapy when concurrently presenting with thrombocytopenia, hemolysis, and coagulopathy. Clinical suspicion for TMA causing stroke can help prevent irreversible brain injury and improve survival rates through interdisciplinary management with hematology and neurology.