Borderline Hemoglobin Warrants Evaluation

Mortality was lowest when hemoglobin was slightly above current anemia thresholds.
*Prospective cohort study; Level 2b (OCEBM).

Citation

Ahmad M, Cleland JGF, Maffia P, et al. Association Between Blood Hemoglobin Concentration and Mortality by Age and Sex. Annals of Internal Medicine. Published September 8, 2026. doi:10.7326/ANNALS-26-00057

Background

The World Health Organization anemia thresholds are widely used but were based on older, small studies. This study tested how hemoglobin levels relate to long-term death risk in a large modern population.

Patients

502,188 United Kingdom Biobank adults aged 37 to 73 years; hemoglobin was available for 477,876. No major clinical exclusions were reported; participants with missing hemoglobin were analyzed separately.

Intervention

Baseline hemoglobin categories compared with sex-specific anemia thresholds: below 13.0 g/dL for men and below 12.0 g/dL for women.

Control

Hemoglobin 1 to 3 g/dL above the sex-specific threshold.

Outcome

Primary: all-cause mortality. Secondary: cardiovascular and cancer mortality.

Follow-up Period

Median 13.6 years.

Results

Hemoglobin category 10-year death risk Adjusted hazard ratio
More than 2 g/dL below threshold 12.5%; +8.1 percentage points (95% CI 6.7 to 9.4) HR 2.87 (95% CI 2.54 to 3.25)
1 to 2 g/dL below threshold 11.2%; +6.7 percentage points (95% CI 5.9 to 7.6) HR 2.53 (95% CI 2.33 to 2.75)
0 to 1 g/dL below threshold 7.9%; +3.4 percentage points (95% CI 3.1 to 3.8) HR 1.74 (95% CI 1.67 to 1.82)
0 to 1 g/dL above threshold 5.3%; +0.8 percentage points (95% CI 0.7 to 1.0) HR 1.18 (95% CI 1.15 to 1.21)
1 to 3 g/dL above threshold 4.5%; reference Reference
More than 4 g/dL above threshold 5.7%; +1.2 percentage points (95% CI 0.7 to 1.7) HR 1.31 (95% CI 1.21 to 1.41)

CI = confidence interval; HR = hazard ratio.

Limitations

Observational design cannot prove cause. Hemoglobin was measured once. Participants were mostly White and healthier than average. Iron studies were unavailable. The borderline category’s risk increase was statistically clear but modest.

Funding

No specific study funding; no industry funding reported.

Clinical Application

Do not redefine anemia thresholds, but consider evaluating borderline low hemoglobin, especially in older adults or symptomatic patients.