When “Normal” Hemoglobin May Not Be Enough: Sex-Specific Anemia Thresholds and Outcomes in Cardiac Surgery

Background/Objectives: Sex-specific anemia criteria classify women with hemoglobin (Hb) 12.0–12.9 g/dL as non-anemic. We assessed whether World Health Organization (WHO) criteria underrecognize red blood cell (RBC) transfusion risk compared with a uniform patient blood management (PBM) threshold of Hb <13.0 g/dL in elective open cardiac valve surgery (CVS). Methods: This nationwide retrospective cohort included adults undergoing elective open CVS in 40 Spanish centers (2016–2024), 32 of which reported preoperative Hb. Hb was modeled continuously and in three strata (<12.0, 12.0–12.9, ≥13.0 g/dL). The primary outcome was RBC transfusion; secondary outcomes were postoperative complications, length of stay, and in-hospital mortality within 30 days. Mixed-effects models adjusted for age, comorbidity burden, surgical complexity, valve position, year of surgery, and center. Results: Among 29,757 eligible patients, 20,017 had available Hb measurements; 9247 (46.2%) were women, including 2333 (25.2%) with Hb 12.0–12.9 g/dL. In this stratum, 68.0% of women and 52.7% of men received RBC transfusions. The adjusted between-sex probability difference was 15.1 percentage points (95% CI, 11.4–18.9; adjusted odds ratio, 1.85; 95% CI, 1.59–2.16). The categorical sex × Hb interaction was significant (p < 0.001), whereas the continuous interaction was not (p = 0.486). Sex did not significantly modify the Hb associations with complications or in-hospital mortality within 30 days. Conclusions: Women with Hb 12.0–12.9 g/dL had substantial transfusion risk despite being classified as non-anemic by the WHO criteria. Hb <13.0 g/dL may be a pragmatic sex-inclusive trigger for perioperative risk recognition and etiologic evaluation, not a proven therapeutic target.