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134 Part III: Epochal Hematology Chapter 9: Hematology in Older Persons 135

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micronuclei formation, any of which could result in cellular dysfunc- TABLE 9–2. Anemia Prevalence in the Elderly Using the
tion. Furthermore, growth hormone production declines with age, and
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this, too, is linked with deposition of fat within the marrow. Adminis- WHO* Criteria
tration of growth hormone to old rats reduces marrow fat and increases Age
hematopoietic tissue. 167 Study (Years) Population Prevalence
Guralnik, 2004 127 ≥65 Community- 10.6%
BLOOD CELL CHANGES WITH AGE dwelling elderly
Red Cells American
Anemia is a significant health problem in the elderly because of a high Ferrucci, 2007 299 ≥70 Community- 11%
prevalence and significant associated morbidity, including reduced dwelling elderly
quality of life, clinical depression, falls, functional impairment, slower Italian
walking speed, reduced grip strength, loss of mobility, worsening Denny 300 ≥71 Community 24%
comorbidities, and mortality. 168,169 dwelling
In older men and women, anemia defined using the World Health Joosten 128 ≥65 Hospitalized 24% (defined
Organization (WHO) criteria of hemoglobin levels less than 13 g/dL for as hemoglobin
men and 12 g/dL for women is associated with an increase in mortal- <11.5 g/dL)
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ity. 171–176 It has been pointed out that the WHO criteria do not take into Artz 126 Most ≥65 Nursing home 48%
account inherent ethnic variations, particularly with respect to Americans
of African descent who have lower levels of hemoglobin without signifi- Robinson 182 ≥65 Nursing home 59.6%
cant adverse outcomes. 177,178 In a study that analyzed 1018 Americans of *World Health Organization anemia criteria; hemoglobin <13 g/dL for
African descent and 1583 Americans of European descent adults aged adult men and <12 g/dL for adult women.
71 to 82 years, anemia defined by the WHO criteria was associated
with increased mortality in those of European descent but not those of
African descent. 177,178 The reasons for these ethnic differences are unde- other factors, such as shortened red cell survival, refractoriness of the
fined. However, the difference is one of degree. In general, the impact erythroid precursors to erythropoietin stimulation, and/or the presence
of anemia on functional status and mortality in Americans of African of as yet undiagnosed illness.
descent becomes apparent at hemoglobin levels approximately 1 g/dL
lower than in whites. The issue of establishing criteria for the diagnosis Serum Erythropoietin and Aging
of anemia is relevant in the context of age, as well. Older women, for Data on erythropoietin levels in nonanemic older persons are incon-
example, have better physical performance and function at hemoglobin sistent. Some suggest that nonanemic older persons have higher ery-
values between 13 and 15 g/dL than at between 12.0 and 12.9 g/dL, thropoietin levels compared to younger adults, 189–191 but other studies
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suggesting perhaps that the cut off level of 12 g/dL is too low. Neverthe- fail to confirm these findings. 10–12 One longitudinal analysis clearly
less, the WHO definition remains the standard used in most current demonstrates that serum erythropoietin levels rose gradually in healthy
epidemiologic surveys and many clinical laboratories. individuals who maintained normal hemoglobin levels but the rise was
not observed in those who were to develop diabetes or hypertension
Prevalence of Anemia during the evaluation period. An explanation for the rise in serum
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In the third National Health and Nutrition Examination Survey erythropoietin with age is not established, but in theory, it could be the
(NHANES III) database, a nationally representative sample of commu- result of age-associated shortened red cell survival or reduced sensitiv-
nity-dwelling persons and determined age- and sex-specific prevalence ity of erythroid progenitor cells to the erythropoietin signal. Studies in
rates of anemia in the total U.S. population, of those individuals older older subjects are ongoing to define the basis for the increasing need for
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than age 65 years approximately 11 percent were anemic by WHO crite- erythropoietin to maintain normal levels of red cells.
ria (see Table 9–1). The prevalence of anemia was lowest (1.5%) among
males between 17 and 49 years of age and highest (26.1%) in males older Leukocytes
than 85 years. Among those 65 years and older, the prevalence rate was Although no significant change is seen in the blood leukocyte count
notably higher in Americans of African descent as compared to Amer- with normal aging, 193,194 among those who acquire features of frailty, an
icans of European descent and Americans of Hispanic descent. Preva- increased neutrophil count may be observed. 157,195 Furthermore, sev-
lence rates of anemia in the elderly vary in community-dwelling and eral qualitative neutrophil defects have been described. For example,
institutionalized populations. Also, anemia is more common among a decreased respiratory burst response to soluble signals, defective
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frail elderly. In the nursing home, for example, anemia prevalence phagocytosis, and impaired neutrophil migration to sites of stress
194
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approaches 50 percent or higher. 126,180–182 have been described in accordance with advanced age. Although the
exact cause for these functional changes has not been clarified, it may
Unexplained Anemia be associated with an age-related alteration in actin cytoskeleton and
Hematologists are usually successful in uncovering the cause of anemia receptor expression in leukocytes. A mild decrease in the blood lym-
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in young adults. However, in older populations a specific explanation phocyte count is first noticeable in the fourth decade with a gradually
cannot be defined by routine evaluation in approximately one-third progressive decrease thereafter throughout the remainder of the life-
of anemic patients (Table 9–2). 20,183,184 Typically, this anemia is mild span. Qualitative alterations in T-lymphocyte function in the elderly
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(hemoglobin concentration in the 10–12 g/dL range), normocytic, and have also been demonstrated. 199
hypoproliferative (low reticulocyte index). It has been postulated that
the cause relates to a number of factors including declining testoster- Platelets
one level, occult inflammation, impaired renal function with inap- At present, knowledge about the influence of age on platelet counts has
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185
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propriately low serum erythropoietin, or incipient myelodysplasia. been limited to cross-sectional data derived from selected populations.
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Likely, unexplained anemia represents an amalgam of these and perhaps From those data, no or very limited changes in platelet number are

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