Deciphering the correlation between baseline Hb and the clinical spectrum of SCA: a multiregional cohort analysis

Sickle cell anemia (SCA) is characterized by chronic hemolysis, recurrent vaso-occlusion, and progressive organ damage. Although hemoglobin (Hb) is routinely measured in clinical practice, its prognostic relevance remains incompletely defined in Middle Eastern populations. This multicenter retrospective cohort study evaluated the association between steady-state hemoglobin levels and acute and chronic complications among 1,015 Saudi Arabian patients with confirmed sickle cell anemia (HbSS) treated between 2020 and 2025. Mean steady-state Hb was derived from three stable measurements obtained ≥3 months apart, excluding post-transfusion and crisis periods. Patients were categorized into severe (≤8 g/dL), moderate (8–10 g/dL), and mild (>10 g/dL) anemia groups. Multivariable logistic regression adjusted for age, sex and fetal hemoglobin (HbF) was used to assess associations with major complications. Lower Hb categories were consistently associated with greater morbidity. Severe and moderate anemia were associated with increased odds of vaso-occlusive crises (OR 2.16 and 1.95, respectively) and higher transfusion burden (OR 3.30 and 1.90; P < 0.001). Acute chest syndrome and infections were more frequent in lower Hb groups (OR ≈1.7 and 2.4, respectively). Chronic kidney disease demonstrated the strongest association with severe anemia (OR 7.09; P = 0.006), while pulmonary hypertension was most prevalent in the moderate anemia group. Stroke showed an inverse association with low Hb, likely reflecting transfusion-related selection bias. Steady-state hemoglobin is a clinically accessible biomarker that correlates strongly with disease burden and organ-specific risk patterns in patients with sickle cell anemia. Associations between lower hemoglobin categories and major complications remained significant after adjustment for HbF, indicating that anemia severity contributed independently of fetal hemoglobin level.