Unexplained Anemia of Aging

Etiology, Health Consequences, and Diagnostic Criteria

Jack Guralnik MD, PhD; William Ershler MD; Andrew Artz MD; Alejandro Lazo-Langner MD; Jeremy Walston MD; Marco Pahor MD; Luigi Ferrucci MD, PhD; William J. Evans PhD


J Am Geriatr Soc. 2022;70(3):891-899. 

In This Article

Clinical Consequences of Mild Anemia

These studies demonstrate that anemia is associated with elevated morbidity and mortality in older men and women. It is important to note that these risks are also present for patients on the mild end of the anemia spectrum. Awareness of these clinical consequences is particularly important because of the high prevalence of mild anemia among patients with anemia. The vast majority of UAA cases (91.7%) are classified as mild (Hb ≥ 10 g/dl),[7] with most patients presenting with hypoproliferative anemia with normocytic indices.[5] Moreover, the proportion of patients with anemia that can be classified as mild (Hb ≥ 10 g/dl) increases with age (Figure 1).

Relative to age-matched nonanemic people, patients with mild anemia experience declines in mobility and physical performance.[4] Moreover, mild anemia is prospectively associated with clinically relevant outcomes such as risk of hospitalization and all-cause mortality[38] (Table 3). Mortality increases steadily as Hb declines: in women over 65, Hb of 11 g/dl is associated with significantly greater mortality than the low-normal WHO cutoff of 12 g/dl; conversely, women with Hb of 14 g/dl experienced a 24% reduction in mortality relative to patients below the cutoff.[54] The significant differences in mortality risk among people near the threshold for anemia diagnosis strongly implies that the overall health consequences of anemia cannot be attributed to individuals with severely low Hb.

Among both male and female participants in the Cardiovascular Health Study, baseline Hb status was strongly associated with health-related outcomes, and a decrease in Hb over 3 years was associated with decline in cognitive function.[3] The authors concluded that reduced blood Hb was present in many older patients who were at elevated risk for adverse outcomes but who would not have been identified as anemic according to the WHO criteria.

Together, these associations with poor clinical outcomes indicate that mild anemia should receive clinical attention rather than simply being considered a normal part of aging.[4]