Association between Anemia and Hematologic Traits at Hospital Discharge with One-Year Mortality Among Survivors of Critical Illness

Background: Molecular markers and mediators of adverse post-hospital outcomes following critical illness remain incompletely characterized. Anemia and red blood cell (RBC) indices integrate inflammation, nutritional status, and hematopoietic function, and may represent biological processes that influence long-term outcomes. We therefore examined whether pre-discharge anemia and hematologic clusters derived from correlated RBC indices were associated with one-year mortality among critical illness survivors. Methods: We conducted an exploratory, retrospective cohort study of adult ICU patients discharged alive using MIMICIV. Pre-hospital discharge RBC indices (hemoglobin, red cell distribution width (RDW), mean corpuscular volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), and RBC count) were analyzed. Hemoglobin and anemia were first evaluated, followed by Gaussian mixture modeling of standardized RBC indices to identify patient clusters in a derivation cohort (70%) and validated findings in a held-out cohort (30%). Associations with one-year mortality were assessed using multivariable-adjusted Cox models. Results: Among 20,233 ICU survivors with available pre-discharge hemoglobin (median age, 67 years), based on the WHO definition of anemia, 17,247 (85.2%) critical illness survivors were anemic at hospital discharge. Anemia was associated with higher one-year mortality (adjusted HR 1.42, p<0.001). Mortality was 20% overall and decreased across increasing hemoglobin quartiles, from 28.8% to 12.5% (log-rank P<0.005); lower hemoglobin was associated with progressively higher adjusted one-year mortality risk. Six hematologic clusters derived from RBC indices were identified with one-year mortality ranging from 10.1% to 31.4% (log-rank p<0.005). Compared with the lowest-risk group, the cluster characterized by elevated RDW and MCV had a twofold higher adjusted mortality risk (HR 2.14; 95% CI, 1.81-2.53). Conclusion: Both anemia and hematologic clusters derived from standard RBC indices at hospital discharge are associated with one-year mortality following critical illness. These hypothesis-generating findings support further investigation of RBC indices as potential biomarkers for post-discharge risk stratification and of the underlying biological pathways as possible therapeutic targets.