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There are few previous studies on the relationship between cerebral infarction and acute anemia. This study presents patients with cerebral infarction in acute anemia due to marked blood loss and aims to clarify the stroke nature and possible mechanism. Patients with acute cerebral infarction and anemia following marked blood loss without systemic hypotension were recruited from 2001 to 2009. Clinical characteristics, particularly hemoglobin level, and neuroimaging findings were reviewed in detail to analyze the stroke nature and verify the possible pathogenesis. Twelve patients (males 8; mean age 74.9 years) were included. Eleven patients had cerebral infarction after acute massive gastrointestinal bleeding, and one had cerebral infarction following postoperative extensive hematoma during hospitalization. In all patients, borderzone infarction was the most characteristic finding: six had unilateral and six had bilateral borderzone infarction. Mean hemoglobin at infarction after acute blood loss was 5.8 g/dl, with 46% reduction from baseline. Of nine patients receiving detailed extracranial and intracranial vascular studies, none had severe carotid stenosis and six had intracranial stenosis. The arterial borderzones are the most vulnerable regions to a fall in cerebral perfusion. Acute anemia may produce cerebral blood flow insufficiency, reduce oxygen-carrying capacity, and result in distal-field tissue ischemic injury when hemoglobin level decreases below a critical level, especially in patients with intracranial stenosis.