To discuss causes of immune mediated stroke.

A 57-year-old woman with hyperlipidemia, hypothyroidism, pulmonary right to left shunt, protein S deficiency on Apixaban, and two prior embolic cryptogenic strokes, developed sudden onset slurred speech, left lower facial weakness, and right gaze preference, while being hospitalized for microangiopathic hemolytic anemia. Her National Institute of Health Stroke Scale (NIHSS) score was 4. 

CT head showed new hypodensity in the right middle cerebral (MCA) territory. CT angiogram showed right MCA M2 branch occlusion and intracranial atherosclerosis. Patient also had anemia (Hgb 10.7 g/dL), thrombocytopenia (53x10³/L), and purpuric lower extremity lesions, and was diagnosed with thrombotic thrombocytopenic purpura (TTP). The diagnosis was confirmed by serum ADAMTS13 activity <5%. Due to thrombocytopenia and recent Apixaban intake, administration of recombinant tissue-type plasminogen activator was contraindicated. Endovascular intervention was deferred due to low NIHSS. TTP was treated with PLEX and three days of IV steroids with improvement of platelet count to 229x10³/L. The patient was discharged home with minimal residual neurological deficits.

Several circumstances may have contributed to the patient’s strokes, including intracranial atherosclerosis, paradoxical embolism in the setting of pulmonary shunt and protein S deficiency and immune mediated microangiopathic hemolytic anemia. Acute causes of immune mediated stroke include TTP, heparin induced thrombocytopenia (HIT), and chronic causes such as antiphospholipid syndrome (APLS). While TTP is characterized by anemia, thrombocytopenia and reduced ADAMTS activity, HIT is characterized by thrombocytopenia in the setting of heparin products use, and detection of antibodies against PF4 or heparin. Finally, APLS is diagnosed by one thrombotic event and two positive serum tests at least three months apart that detect lupus anticoagulant, anti-beta2glycoprotein, or anti-cardiolipin antibodies.

The presence of one thrombophilia disorder does not preclude the development of a second – in this case, process requiring targeted immune therapy.