Is borderline anemia being overlooked?

Clinical takeaway: Consider evaluating patients with hemoglobin levels near the lower end of the normal range, particularly older adults and those with cardiovascular disease, rather than automatically reassuring them that results are normal.

Current WHO anemia thresholds were established decades ago and are widely used to determine when further investigation is warranted. However, whether those cutoffs align with long-term health outcomes in contemporary populations has remained uncertain.

In this prospective cohort study of more than 500,000 UK Biobank participants followed for a median of 13.6 years, researchers found a U-shaped relationship between hemoglobin concentration and mortality. The lowest risk of death occurred among adults whose hemoglobin levels were 1 to 3 g/dL above current WHO anemia thresholds, while mortality increased at both lower and higher concentrations.

Notably, risk appeared to rise even among people whose hemoglobin levels remained technically above the anemia threshold. Participants with hemoglobin levels just 0 to 1 g/dL above the WHO cutoff had a 10-year mortality rate of 5.3%, compared with 4.5% among those in the lowest-risk range. Over the full follow-up period, they experienced an approximately 18% higher adjusted risk of death.

The association was more pronounced among older adults, men of all ages, and women aged 60 years or older. Similar patterns were observed for cardiovascular and cancer mortality. By contrast, findings were less consistent in women younger than 60 years, potentially reflecting the greater influence of menstrual blood loss and iron deficiency in this group.

The authors stressed that the findings should not be used to redefine anemia thresholds. Instead, they suggest that “borderline anemia” may warrant closer clinical attention, particularly when accompanied by symptoms or conditions associated with iron deficiency, inflammation, kidney disease, blood loss, or other underlying disorders. As the investigators conclude, values up to 1 g/dL above the current WHO definition of anemia “may warrant investigation rather than automatic reassurance.”

Source: Ahmad M, et al. (2026 Sep 8) Ann Intern Med. Association Between Blood Hemoglobin Concentration and Mortality by Age and Sex: A Prospective Cohort Study