Beyond Hemoglobin Levels: Integrating Anemia Phenotyping Into Prognostic Models for Patients With Stroke Following Intravenous Thrombolysis

BACKGROUND: Anemia predicts poor outcomes after intravenous thrombolysis in acute ischemic stroke. Whether morphological anemia subtypes differentially affect prognosis remains unclear. We evaluated the impact of microcytic, normocytic, and macrocytic anemia on outcomes in patients with acute ischemic stroke receiving intravenous thrombolysis. METHODS: In this multicenter, prospective cohort study of 1367 patients with acute ischemic stroke treated with intravenous thrombolysis, anemia was defined using World Health Organization criteria and classified by mean corpuscular volume. Multivariable logistic regression and mediation analyses were performed. RESULTS: Among 1367 patients (median age 66 years, 64.7% male), 379 (27.7%) had anemia: 123 (8.9%) microcytic, 202 (14.7%) normocytic, and 54 (3.9%) macrocytic. After full adjustment, microcytic and normocytic anemia were independently associated with increased risks of 3-month death or severe disability (microcytic: adjusted odds ratio [aOR], 2.13 [95% CI, 1.34-3.38]; normocytic: aOR, 2.07 [95% CI, 1.39-3.09]) and 3-month mortality (microcytic: aOR, 1.76 [95% CI, 1.05-2.96]; normocytic: aOR, 1.88 [95% CI, 1.21-2.91]). Normocytic anemia was additionally associated with in-hospital neurological deterioration (aOR, 1.83 [95% CI, 1.10-3.04]), stroke-associated pneumonia (aOR, 2.35 [95% CI, 1.57-3.51]), and in-hospital gastrointestinal bleeding (aOR, 2.58 [95% CI, 1.18-5.64]). Stroke-associated pneumonia mediated 22.09%, 45.91% and 27.05% of the effect of normocytic anemia on 3-month death or severe disability, 3-month mortality, and in-hospital neurological deterioration, respectively. Macrocytic anemia showed no significant associations with outcomes. CONCLUSIONS: Morphological anemia subtypes have distinct prognostic implications in intravenous thrombolysis-treated patients with acute ischemic stroke. Microcytic and normocytic anemia are independently associated with poor outcomes and mortality, with in-hospital complications, particularly stroke-associated pneumonia, mediating substantial risk. REGISTRATION: URL: https://www.chictr.org.cn/; Unique Identifier: ChiCTR2000033456.