Page 2615 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 161

HEMATOLOGY IN AGING

Andrew S. Artz and William B. Ershler

7,8
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Although most classifications consider patients “older” once their age reduction of 19 × 10 /L in those 70–90 years of age. A study of
exceeds 65 or 70 years, age-related changes are not discrete. A central Sardinian villages revealed an increasing incidence of thrombocyto-
tenet of gerontology (the study of normal aging) is that biologic penia with aging, approaching 6% in the seventh decade and 8% for
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measures show increased variation with advancing age, but age-related octogenarians. Interestingly, neutropenia (less than 1.5 × 10 /L)
variations are of insufficient magnitude to result in disease per se. appears less common with advancing age, such that the prevalence in
Hematologic conditions in older adults have unique features and community-dwelling older adults 75 years and older has been
frequently require a modified approach relative to younger adults. approximated at 0.5%.
Anemia in older adults with advancing age is one of the most common
hematologic problems associated.
PATHOBIOLOGY
EPIDEMIOLOGY Hematopoietic Changes With Aging
Aging The study of older adults illustrates an overriding paradox, that
although aging alone does not cause clinically significant cytopenias,
The median life expectancy continues to rise throughout the world. aging predisposes to reduced hematopoietic reserves and to diseases,
In the United States, the Centers for Disease Control and Preven- both of which increase the tendency to encounter significantly lower
tion estimates life expectancy at 77.9 years for children born in blood counts in older adults. Major hematopoietic changes occurring
2007. The proportion and absolute number of older adults is with aging are listed in Table 161.2.
increasing, and life expectancy of adults who have reached an The attention to the hematopoietic system must be understood
advanced age may be considerable. Accordingly, we advocate in the context that organ systems are integrated to maintain homeo-
estimating life expectancy for older adults who have hematologic stasis. For example, decreased bone mass and heightened systemic
conditions, by using several calculators available online (e.g., inflammation may adversely influence hematopoiesis. Whether
http://eprognosis.ucsf.edu). 1 hematopoietic perturbations are linked to a global decline or the
factors promoting functional decline of marrow function cannot be
easily deciphered. Reduced neutrophil responses to granulocyte
Anemia Definition colony-stimulating factors have long been appreciated as predisposing
to infection with advancing age, but this occurs in the setting of a
Historically, criteria for diagnosing anemia in older and younger decline in immune function that occurs with aging.
adults used by the World Health Organization (WHO) were hemo-
globin (Hb) threshold levels below 13 g/dL for men and less than
2
12 g/dL for women. It was widely recognized that these criteria Clonal Hematopoiesis and Aging
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required modification, and Beutler and Waalen evaluated two large
databases to develop population-based threshold levels, defining the Myeloid bias has emerged as a hallmark of hematopoiesis and advanc-
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fifth percentile as the lower limit of normal after excluding anemia- ing. Impairment of the lymphoid compartment may explain
causing conditions, as shown in Table 161.1. immune deficits that occur with aging, and at the same time, an
increased number of myeloid progenitors likely influences the mark-
edly higher rate of myeloid malignancies in older individuals. The
Anemia Prevalence discovery of several mutations involving DNMT3A and TET2, com-
monly found in preleukemic hematopoietic stem cells, has formed a
Most reports of anemia prevalence use the historical WHO threshold critical link to understanding the pathway of hematopoietic changes
levels of less than 13 g/dL of Hb for men and less than 12 g/dL for associated with aging that result in hematologic malignancy. 11,12 The
women. For adults 65 years and older, the prevalence of anemia is observation of TET2 mutations in women with clonal hematopoiesis
around 10%–11% and rises to 20%–25% for those 85 years and by X-chromosome inactivation lends support to the presence of a
older, and 50% for those in nursing homes. 4,5 preleukemic state in the hematopoietic compartment in some older
Race/ethnicity also influences anemia prevalence. Studies from patients. 13
4,6
Europe and Japan indicate a fairly similar anemia prevalence in A series of studies employing whole-exome sequencing have
older adults, whereas African-Americans have lower median Hb compellingly demonstrated a strong link of advancing age and the
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values and a threefold higher prevalence of anemia. A substantial emergence of blood cell mutations associated with hematologic
portion of African-Americans with lower Hb levels have the malignancies. 14–16 Specifically, 10% of individuals 70 years and older
α-thalassemia trait, with one or two deletions contributing to the and up to 18% in those 90 years and older have clonal expansion of
degree of anemia. cells bearing these mutations, most frequently DNMT3A and TET2.
The incidence of hematologic malignancies, particularly myeloid
malignancies, rises about 10-fold in the presence of a detectable
Neutropenia and Thrombocytopenia mutation. 15,16 However, screening for somatic mutations cannot be
recommended, as even in older adults the rate of hematologic malig-
The incidence of thrombocytopenia, defined as a platelet count below nancy for those with evidence of clonal hematopoiesis is approximately
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150 × 10 /L, does not appreciably change with age with an average 0.5%–1% per year. 15
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