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

Unexplained Anemia is Prevalent in Aging Populations

Anemia, defined by the World Health Organization criteria as circulating hemoglobin (Hb) <12 g/dl in women and <13 g/dl in men, is common among individuals over the age of 60.[1–3] The prevalence of anemia increases with age and is particularly common among the oldest and most frail: in a retrospective study of more than 19,000 hospital patients, the incidence of anemia rose from 15% at the ages of 64–69 to 37% in those over aged 90 (Figure 1). Many anemia cases have no clear underlying cause, a population that we will refer to as unexplained anemia of aging (UAA).

Figure 1.

Prevalence of anemia increases with age. Prevalence of anemia (WHO criteria: Hb < 12 g/dl in women and <13 g/dl in men) and severe anemia (Hb < 10 g/dl) in a cohort of 19,758 inpatients and outpatients aged ≥64 years with complete blood counts treated at Innsbruck Medical University Hospital between October 1, 2004 and September 29, 2005. Source: Data from Reference 8

In one of the first population-based studies to describe UAA, Guralnik et al. examined the third National Health and Nutrition Examination Survey (NHANES) of 4199 community-dwelling men and women over the age of 65 years.[4] One third of cases of anemia could be attributed to nutritional causes, and another third were associated with inflammation or chronic kidney disease (CKD). This left one third of cases without a clear etiology. A comparable proportion of mild anemia (defined as a Hb concentration of 10.0–11.9 g/dl in women and 10.0–12.9 g/dl in men) is unexplained: in an Italian cohort of 8744 individuals between aged 65–84, mild anemia had no identifiable cause in 26.4% of cases.[5]

In a wide range of population-based studies of anemia, 25%–44% of cases could be classified as UAA (Table 1). This holds true whether the study population is community-based, hospital inpatient, or long-term care residents. Importantly, the prevalence of UAA remains high even when the potential cause of anemia is rigorously examined. In study populations consisting of hematology clinic outpatients and patients referred to anemia referral clinics, in which cohorts were subjected to comprehensive examinations, the frequency of UAA is 35%–44%. For example, Artz et al.[6] examined a community-dwelling, predominantly African-American (69%) group of patients over the age of 65 who had been referred to an anemia clinic and even after intensive evaluations of causes, UAA was the most common category in both white and African-American patients. Michalak et al.[7] retrospectively examined medical records of 981 patients over the age of 60 and found that anemia was unexplained in 48 of 169 patients, with a UAA prevalence of 4.9%. The prevalence of UAA increased from 2.9% in those between 60 and 69 to 12.3% in patients ≥80 years of age.