Sex-specific hemoglobin thresholds and longitudinal trajectories in intracerebral hemorrhage outcomes: a multicenter cohort study

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BACKGROUND: We aim to investigate the association between admission hemoglobin and outcomes after primary intracerebral hemorrhage (ICH), including 3-month outcome and long-term survival and recurrence. METHODS: Utilizing a multicenter stroke registry database, we retrospectively analyzed patients with spontaneous ICH confirmed within 48 h of symptom onset who had admission hemoglobin measurements and baseline neuroimaging. Cox proportional hazards regression models were employed to evaluate associations between admission hemoglobin levels and risks of all-cause mortality and ICH recurrence during follow-up. Nonlinear relationships were assessed using threshold effect models with inflection point determination. Sensitivity analyses were restricted to patients who underwent repeated routine blood testing during hospitalization to examine whether increased hemoglobin levels during hospitalization correlated with improved clinical outcomes. RESULTS: The cohort comprised 2,407 patients (mean age 64 ± 14 years; 65.1% male) with spontaneous ICH, followed for a median duration of 2.0 years (IQR 0.8-3.2). Threshold analysis revealed a nonlinear L-shaped association between admission hemoglobin and mortality. Below 14.3 g/dL, hemoglobin elevation correlated with reduced mortality risk (adjusted HR 0.88 per 1-g/dL increase, 95% CI 0.81-0.95). Above this threshold, no significant association was observed (HR 1.13, 95% CI 0.98-1.31). Lower admission hemoglobin was independently associated with higher ICH recurrence risk (HR 0.88 per 1-g/dL decrease, 95% CI 0.775-0.998). In sensitivity analyses of 954 patients with serial hemoglobin measurements, improved 3-month functional outcomes and reduced long-term mortality were observed in patients with longitudinal elevation during hospitalization. CONCLUSIONS: Admission hemoglobin demonstrates a L-shaped association with post-ICH mortality, with inflection point observed near 14.3 g/dL. Lower hemoglobin independently predicts higher hemorrhage recurrence risk. Longitudinal hemoglobin elevation during hospitalization correlates with improved functional outcomes and survival. TRIAL REGISTRATION: Clinical trials NCT06548737 (retrospectively registered).

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