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General Principles in Older Adults
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Anemia is a common condition in older adults and is an increasingly recognized contributor to increased morbidity and mortality. Similar to the younger adult anemic patient, anemia in older adults is most commonly defined according to the 1968 World Health Organization (WHO) criteria of a hemoglobin (Hgb) <13 g/dL in men and <12 g/dL in women. Although anemia has often been considered a normal consequence of aging, its association with adverse clinical outcomes merits a thorough evaluation into the underlying pathophysiology. Recent studies suggest that anemia may arise as a result of accumulated effects of age-related comorbidities acting in concert with poorly understood age-specific changes in early hematopoietic progenitors, that combine to influence erythrocyte production. A greater understanding of the pathogenesis of anemia in older adults will likely have important implications for the prevention, diagnosis, and therapy of this common problem.
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It is estimated that more than 3 million Americans age 65 years and older are anemic, with anemia being highly prevalent in noninstitutionalized, ambulatory older adult populations. The Third National Health and Nutrition Examination Survey (NHANES III) study revealed that the prevalence of anemia in men and women older than age 65 years was 11% and 10.2%, respectively, and rose rapidly after age 50 years, approaching a rate greater than 20% in those individuals age 85 years or older. This finding has been validated in other population-based studies, most of which have shown that the degree of anemia in older adults is relatively mild, with most patients presenting with Hgb >10 g/dL.
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Race appears to significantly influence Hgb levels. In NHANES III, the prevalence of anemia using WHO criteria was found to be 3 times higher in non-Hispanic blacks compared with non-Hispanic whites. Examination of Hgb, hematocrit (Hct), and mean corpuscular volume (MCV) in 1491 black individuals as compared with more than 31,000 white subjects in the Kaiser Permanente database revealed that all 3 parameters were lower in blacks than in age-matched whites, whereas the serum ferritin was higher. Although racial genetic variation may influence an individual’s ability to respond to anemic triggers, it is likely that additional factors besides race significantly contribute to the risk of anemia across various populations.
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Etiology and Risk Factors
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There are presently no studies specifically designed to address causality in older individuals with anemia. The high frequency of comorbid conditions in older populations has also confounded our ability to identify which mechanisms, if any, independently predispose to age-associated reductions in Hgb. Although there appears to be a component of age-related anemia even in healthy individuals, the incidence is much higher in patients with comorbid disease. NHANES III revealed that anemia in older adults is comprised of 3 broad categories: one-third have anemia as a result of nutritional deficiencies (iron, folic acid, or vitamin B12); one-third have anemia of inflammation (AI) on the basis of iron studies; and one-third have unexplained anemia (UA). It is important to remember that these definitions of anemia in NHANES III were based solely on laboratory parameters without the benefit of clinical examination or bone marrow biopsies, making it difficult to evaluate the full clinical impact of anemia in this population. Furthermore, a “hierarchical” categorization of parameters was used to define anemia subtypes, making it difficult to address the independent contributions of factors in subjects with anemia caused by multiple etiologies.
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A Stanford University study examining the etiology ...