Acute myocardial infarction (AMI) induced by thrombotic thrombocytopenic purpura (TTP) has been previously reported, but comorbidity with autoimmune hemolytic anemia is rare. The index patient, a 55-year-old woman, presented with acute ST-elevation myocardial infarction (STEMI). A diagnosis of TTP was established on the presence of thrombocytopenia, microangiopathic hemolytic anemia, acute kidney injury, fever, and neurologic symptoms (ischemic stroke); autoimmune hemolytic anemia was established based on Comboost test. Percutaneous coronary intervention and dual antiplatelet therapy were not initiated due to elevated risk of bleeding. Instead, the patient was treated with glucocorticosteroid and plasmapheresis. Despite the treatment, the patient suffered a watershed acute cerebral infarction, and finally died of gastrointestinal bleeding. This case highlights the challenges in managing STEMI in TTP patients.