Suspected immune thrombotic thrombocytopenic purpura (iTTP) creates a dual emergency: treatment must begin before ADAMTS13 confirmation, while lethal mimics must be investigated concurrently. A 44-year-old woman presented with fever, severe thrombocytopenia, progressive limb weakness, and multifocal cerebral infarctions. Although the schistocyte proportion was <1% and her PLASMIC score was 5, iTTP could not be safely excluded. ADAMTS13 activity was sampled before treatment, and plasma exchange plus corticosteroids was started. Blood cultures grew methicillin-susceptible Staphylococcus aureus. Despite three negative transthoracic echocardiograms, transesophageal echocardiography demonstrated a 10-mm mitral vegetation, establishing infective endocarditis (IE). Pretreatment ADAMTS13 activity was 35%, allowing TTP-directed therapy to be withdrawn. IE can produce thrombocytopenia, microangiopathic hemolysis, TMA-like presentations, and occasionally marked ADAMTS13 reduction; conversely, schistocytes may be initially inapparent in true iTTP. Thus, neither a low schistocyte count nor an intermediate prediction score should end diagnostic reasoning. When iTTP and IE remain plausible, pretreatment ADAMTS13 sampling, risk-adapted empiric TTP therapy, blood cultures, antimicrobial treatment, and definitive cardiac imaging should proceed in parallel.