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15 - Musculoskeletal and Connective Tissue Disorders |
477
101. Anderson J, Caplan L, Yazdany J, et al. Rheumatoid
arthritis disease activity measures: American College
of Rheumatology recommendations for use in clinical
practice. Arthritis Care Res (Hoboken). 2012;64:640–
647.
102.
Kavanaugh A, Smolen JS. e when and how of
biologic agent withdrawal in rheumatoid arthritis:
learning from large randomised controlled trials. Clin
Exp Rheumatol. 2013;31:S19–21.
103.
Allaart CF, Lems WF, Huizinga TW. e BeSt way
of withdrawing biologic agents. Clin Exp Rheumatol.
2013;31:S14–18.
104.
Radovits BJ, Kievit W, Laan RF. Tumour necrosis
factor-alpha antagonists in the management of rheu-
matoid arthritis in the elderly: a review of their ecacy
and safety. Drugs Aging. 2009;26:647–664.
105.
Pincus T. e American College of Rheumatology
(ACR). Core data set and derivative “patient only”
indices to assess rheumatoid arthritis. Clin Exp Rheu-
matol. 2005;23:S109–113.
106. Diaz-Borjon A. Guidelines for the use of conventional
and newer disease-modifying antirheumatic drugs
in elderly patients with rheumatoid arthritis. Drugs
Aging. 2009;26:273–293.
107. Crowson CS, Liao KP, Davis JM III, et al. Rheuma-
toid arthritis and cardiovascular disease. Am Heart J.
2013;166:622–628.e621.
108. Bernatsky S, Hudson M, Suissa S. Anti-rheumatic
drug use and risk of serious infections in rheumatoid
arthritis. Rheumatology (Oxford). 2007;46:1157–1160.
109. Townsend HB, Saag KG. Glucocorticoid use in rheu-
matoid arthritis: benets, mechanisms, and risks. Clin
Exp Rheumatol. 2004;22:S77–82.
110. van Hulst LT, Kievit W, van Bommel R, et al. Rheu-
matoid arthritis patients and rheumatologists approach
the decision to escalate care dierently: results of a
maximum dierence scaling experiment. Arthritis Care
Res (Hoboken). 2011;63:1407–1414.
111.
Cramp F, Hewlett S, Almeida C, et al. Nonphar-
macological interventions for fatigue in rheu-
matoid arthritis. Cochrane Database Syst Rev.
2013;8:Cd008322.
112.
Manning VL, Hurley MV, Scott DL, et al. Educa-
tion, self-management, and upper extremity exercise
training in people with rheumatoid arthritis: a
randomized controlled trial. Arthritis Care Res
(Hoboken). 2014;66:217–227.
113. Middleton KR, Ward MM, Haaz S, et al. A pilot
study of yoga as self-care for arthritis in minority
communities. Health Qual Life Outcomes. 2013;11:55.
114. Wang C. Role of Tai Chi in the treatment of rheuma-
tologic diseases. Curr Rheumatol Rep. 2012;14:598–
603.
115.
Blaizot A, Monsarrat P, Constantin A, et al. Oral
health-related quality of life among outpatients with
rheumatoid arthritis. Int Dent J. 2013;63:145–153.
116.
Whittle SL, Richards BL, Husni E, et al. Opioid
therapy for treating rheumatoid arthritis pain. Cochrane
Database Syst Rev. 2011:Cd003113.
117.
Mittendorf T, Dietz B, Sterz R, et al. Personal and
economic burden of late-stage rheumatoid arthritis
among patients treated with adalimumab: an
evaluation from a patient’s perspective. Rheumatology
(Oxford). 2008;47:188–193.
118.
Kermani TA, Warrington KJ. Polymyalgia rheumatica.
Lancet. 2013;381:63–72.
119.
Schmidt J, Warrington KJ. Polymyalgia rheumatica
and giant cell arteritis in older patients: Diagnosis
and pharmacological management. Drugs Aging.
2011;28:651–666.
120. Salvarani C, Pipitone N, Versari A, et al. Clinical
features of polymyalgia rheumatica and giant cell
arteritis. Nat Rev Rheumatol. 2012;8:509–521.
121. Waldman CW, Waldman SD, Waldman RA. Giant
cell arteritis. Med Clin North Am. 2013;97:329–335.
122. Jaul E. Assessment and management of pressure
ulcers in the elderly: Current strategies. Drugs Aging.
2010;27:311–325.
123. Niederhauser A, VanDeusen Lukas C, Parker V, et
al. Comprehensive programs for preventing pressure
ulcers: a review of the literature. Adv Skin Wound Care.
2012;25:167–188; quiz 189–190.
124. Jaul E. Who determines the treatment for pressure
ulcers in the elderly? Isr Med Assoc J. 2013;15:512–515.
125.
Braga IA, Pirett CC, Ribas RM, et al. Bacterial coloni-
zation of pressure ulcers: assessment of risk for blood-
stream infection and impact on patient outcomes. J
Hosp Infect. 2013;83:314–320.
126. Braden BJ, Bergstrom N, Ball J. Prevention plus.
http://www.bradenscale.com/index.htm. Accessed
January 27, 2014.
127. e Norton pressure sore risk-assessment scale scoring
system. http://www.nutrition411.com/wrc/pdf/
w0513_norton_presure_sore_risk_assessment_scale_
scoring_system.pdf. Accessed January 27, 2014.
128.
Dorner B, Posthauer ME, omas D. e role of
nutrition in pressure ulcer prevention and treatment:
national pressure ulcer advisory panel white paper
2009;1–15. http://www.npuap.org/wp-content/
uploads/2012/03/Nutrition-White-Paper-Website-
Version.pdf. Accessed January 27, 2014.
129. VanGilder C, MacFarlane GD, Harrison P, et al. e
demographics of suspected deep tissue injury in the
United States: an analysis of the International Pressure
Ulcer Prevalence Survey 2006–2009. Adv Skin Wound
Care. 2010;23:254–261.
https://t.me/medicina_free
478
| Fundamentals of Geriatric Pharmacotherapy
130. Jenkins ML, O’Neal E. Pressure ulcer prevalence
and incidence in acute care. Adv Skin Wound Care.
2010;23:556–559.
131.
National Pressure Ulcer Advisory Panel and European
Pressure Ulcer Advisory Panel. Pressure ulcer treat-
ment: technical report. 2009;http://www.npuap.org/
wp-content/uploads/2012/03/Final-2009-Treatment-
Technical-Report1.pdf. Accessed January 27, 2014.
132.
National Pressure Ulcer Advisory Panel. Pressure
ulcer category/staging illustrations. http://www.npuap.
org/resources/educational-and-clinical-resources/
pressure-ulcer-categorystaging-illustrations/. Accessed
October 30, 2014.
133.
Gorecki C, Brown JM, Nelson EA, et al. Impact of
pressure ulcers on quality of life in older patients: a
systematic review. J Am Geriatr Soc. 2009;57:1175–
1183.
134.
National Pressure Ulcer Advisory Panel. Pressure ulcer
prevention points. http://www.npuap.org/wp-content/
uploads/2012/03/PU_Prev_Points.pdf. Accessed
January 27, 2014.
135. Sibbald RG, Goodman L, Norton L, et al. Prevention
and treatment of pressure ulcers. Skin erapy Lett.
2012;17:4-7.
136.
Choo TS, Hayter M, Watson R. e eectiveness of
nutritional intervention(s) and the treatment of pres-
sure ulcers—a systematic literature review. Int J Nurs
Pract. 2013;19(suppl 1):19–27.
137. AMDA (e Society for Post-Acute and Long-Term
Care Medicine). Pressure ulcers in the long-term care
setting: clinical practice guideline. AMDA clinical
practice guideline. Revised 2007.
138.
Mao CL, Rivet AJ, Sidora T, et al. Update on pressure
ulcer management and deep tissue injury. Ann Phar-
macother. 2010;44:325–332.
139.
Gist S, Tio-Matos I, Falzgraf S, et al. Wound care in
the geriatric client. Clin Interv Aging. 2009;4:269–287.
140.
Sibbald RG, Goodman L, Woo KY, et al. Special
considerations in wound bed preparation 2011: an
update(c). Adv Skin Wound Care. 2011;24:415–436;
quiz 417–418.
141.
National Quality Forum. Serious reportable events.
http://www.qualityforum.org/Topics/SREs/Serious_
Reportable_Events.aspx. Accessed January 27, 2014.
142.
Zarraga IG, Kron J. Oral anticoagulation in elderly
adults with atrial brillation: integrating new options
with old concepts. J Am Geriatr Soc. 2013;61:143–150.
143. Blank C. Correct techniques for measuring human
height. 2013. http://www.ehow.com/list_5813937_
correct-techniques-measuring-human-height.html.
Accessed January 27, 2014.
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A P
T
SUM LAM, JAMES J. NAWARSKAS, and
ANGELA CHENG-LAI
L O
1. Characterize the common causes and complications of anemia and their prevalence in the elderly patient.
2. Develop a treatment plan for a patient with anemia that includes pharmacologic and nonpharmacologic therapy.
3. Summarize the current recommendations on immunization for older adults.
4. Given a patient case, recommend appropriate immunizations and monitoring parameters.
5.
Describe various cancer screening tests that are recommended for the geriatric population, including associated
problems and barriers.
6.
Describe various cancer prevention measures, including medications and vitamin supplements.
16
K T D
CANCER CHEMOPREVENTION: Use of natural, synthetic, or biologic chemical agents to reverse, suppress, or
prevent carcinogenic progression to invasive cancer.
ERYTHROPOIESIS: The process of producing red blood cells.
ERYTHROPOIETIN: Protein secreted by the kidneys that stimulates the production of red blood cells.
FERRITIN: Main intracellular iron storage protein in the body.
HEMATOPOIETIC: Relating to the formation and maturation of blood cells and their derivatives.
HEPCIDIN: Hormone produced by the liver that regulates iron hemostasis. Hepcidin inhibits ferroportin, a
protein found on enterocytes and macrophages that transports iron out of storage cells. Inhibition of ferroportin
prevents iron release from macrophages as well as secretion of iron from the intestines into the hepatic portal
system, thereby reducing iron absorption.
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HUMORAL: Relating to the fluids of the body.
INTRINSIC FACTOR: Protein produced by the stomach that is necessary for the absorption of vitamin B12 in
the terminal ileum.
MYELODYSPLASIA: Condition characterized by dysfunctional production of cells in the bone marrow and,
thereby, ineffective hematopoiesis.
TRANSFERRIN: Plasma protein that binds to and transports iron in the body.
I
D
iseases of the hematologic and immune
systems are common in the older adult. In
addition, system decline theories of aging focus
on failures with these systems as potential expla-
nations for the frailty seen in many of the very old
population. Anemia, cancer, and loss of immune
function are common with aging but have yet to be
identified as normal diseases associated with the
aging process. Causes of anemia in the elderly
patient and its proper treatment are reviewed
in the first section of this chapter, followed by a
section on immunizations. The chapter ends with
a focus on cancer screenings appropriate for
older adults. The tenets of public health provide
the necessary prevention of infections and early
detection of cancer that will aid older adults to
live healthier, longer lives.
A
Prevalence, Pathogenesis, and
Etiology of Anemia Specic to
Geriatrics
Prevalence
Anemia in the elderly has been termed a public
health crisis due to its high prevalence and
possibility for adverse consequences.
1
As
with many chronic diseases, the prevalence
of anemia increases with increasing age.
2
Third National Health and Nutrition Examina-
tion Survey (NHANES III) of 2.8 million elderly
patients with anemia documented an anemia
prevalence rate of 10.6% in community-dwelling
adults age 65 years or older, with prevalence
rates increasing to 20% in women and 26% in
men aged 85 years and older.
2,3
Other reports
have described substantially higher rates of
anemia in the homebound elderly (39.6%) and in
nursing home residents (48% to 63%).
4-7
With regard to sex, there is a crossover in
which anemia is more common in females less
than 65 years of age but is more common in
males over 75 years of age.
2,3
This may be due
to the sex-specific definition of anemia used
by the World Health Organization (WHO), of a
hemoglobin concentration of <13 g/dL in men
and <12 g/dL in women.
8
Although this distinc-
tion in defining anemia may be reasonable pre-
menopause, some have questioned whether this
is appropriate for postmenopausal females.
2
If
anemia is defined as a hemoglobin concentra-
tion of <13 g/dL regardless of sex, then the rates
of anemia in women would appear to be higher
than men regardless of age.
2,9
Some have also
questioned the value of using these hemoglobin
thresholds so widely for diagnosing anemia, as
the WHO criteria were developed for patients with
nutritional anemia without the intent of becoming
a diagnostic standard for all types of anemia.
10
Also, as discussed later in this chapter, these
hemoglobin cutoffs do not necessarily repre-
sent therapeutic goals nor thresholds at which
to begin treatment. Racial differences have
also been demonstrated with regard to anemia
prevalence in the elderly, with a remarkably
higher rate seen in African American individuals
(Figure 16-1).
2,3
The racial differences in hemo-
globin concentration between African Ameri-
cans and non-Hispanic Caucasians is believed
to be due to genetic mutations that have evolved
secondary to environmental pressures in Africa
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481
and Europe rather than due to health, nutrition,
or behavioral or socioeconomic factors.
2,9
Some
have therefore advocated for racial distinctions
in defining anemia, which is further supported
by recent data demonstrating that a hemoglobin
concentration below the current WHO threshold
for anemia is associated with increased mortality
in African American patients.
9,10
Pathogenesis and Etiology
The fundamental cause of most anemia in
elderly patients is defective or deficient red
blood cell production, otherwise known as dimin-
ished erythropoiesis.
11
Age-related changes in
erythropoiesis may be considered in the context
of two broad categories: (1) changes intrinsic
to erythroid progenitor or hematopoietic stem
cells, and (2) changes in humoral control
mechanisms.
11
With regard to alterations in
progenitor and stem cells, morphologic studies
have shown a decrease in hematopoietic tissue
in the bone marrow of elderly patients, although
erythropoietic activity is not necessarily dimin-
ished.
11,12
Whereas some studies have shown a
decrease in erythroid burst-forming and colony-
forming units in anemic elderly patients, other
studies have shown no changes.
13-16
One study
in particular showed a lower number of CD34+
progenitor cells in the blood of elderly (but not
necessarily anemic) individuals with an increase
in serum stem cell factor concentrations, which
may be a compensatory mechanism to stimulate
erythroid cell differentiation. In this study, CD34+
cells, in the presence of optimal concentrations
of recombinant hematopoietic growth factors,
were able to form erythroid burst-forming units
and colony-forming units at a rate similar to that
seen in young individuals. This would indicate
that humoral mechanisms may be more likely
responsible for the hematopoietic changes seen
in the elderly as opposed to an unresponsive-
ness of hematopoietic progenitors to growth
factors.
16
From a humoral perspective, erythropoietin
concentrations generally increase with aging,
although studies have shown mixed results in this
Figure 16-1. Prevalence of anemia in individuals aged 65 or older in the United States by self-declared racial
or ethnic group.
Source: Data from references 2 and 3.
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| Fundamentals of Geriatric Pharmacotherapy
regard.
11
Confounding this issue is that worsening
renal function, which is often present in the elderly,
corresponds to a blunted erythropoietin response
to anemia and lower erythropoietin concentra-
tions.
17-19
It has been theorized that the increase
in erythropoietin concentrations seen with aging
is a consequence of a state of relative erythroid
resistance to erythropoietin, thereby resulting in
increased erythropoietin secretion. Anemia then
develops when this feedback loop is interrupted,
which may occur in the presence of renal disease,
diabetes, or hypertension.
11
Other humoral links to anemia have been made
with testosterone, growth hormone, and inflamma-
tory mediators. The androgenic hormones may
play a role in erythropoiesis and their secretion
decreases with aging. Associations have been
made with low testosterone concentrations and
anemia and, independently, growth hormone
administration has been shown to reverse anemia
in adults with growth hormone deficiency.
20,21
However, direct links between androgen hormone
deficiency and the development of anemia are
lacking and require further study. Conversely,
concentrations of inflammatory mediators are
known to be chronically, albeit mildly, elevated
in elderly individuals even in the absence of an
acute illness or autoimmune disease.
22-25
Concen-
trations of interleukin (IL)-6, IL-1β, tumor-necrosis
factor (TNF)-α, C-reactive protein (CRP), and
macrophage migration inhibitory factor (MIF) have
been shown to be elevated in elderly patients with
anemia compared to nonanemic counterparts,
26-28
although compared with other types of anemia,
inflammatory markers do not seem to be elevated
in patients with anemia of unexplained etiology.
29
In addition, elevated cytokine concentrations
may impede erythropoietin production and impair
erythropoiesis.
30,31
Specifically, MIF and TNF-α
interfere with erythroid colony formation and IL-6
and IL-1 increase hepatic synthesis of hepcidin, a
polypeptide that inhibits both iron absorption from
the gut as well as the release of iron from bone
marrow macrophages to erythroid progenitors.
28,32
Anemia in the elderly, especially anemia of inflam-
mation, has also been associated with vitamin
D deficiency, presumably due to the abilities of
vitamin D to suppress inflammatory pathways
and to regulate iron homeostasis by suppressing
hepcidin.
33,34
The major causes of anemia in the elderly
can be divided into four general categories: (1)
iron-deficiency anemia, (2) nutrient-deficiency
anemia (folate and/or vitamin B12), (3) anemia
of chronic inflammation/kidney disease, and (4)
unexplained anemia. Studies have documented
the following regarding prevalence of anemia
in the elderly: iron-deficiency anemia 12% to
25%, nutrient-deficiency anemia 1% to 18%, and
anemia of chronic inflammation/kidney disease
10% to 32%. The most common etiology in these
studies was unexplained anemia, occurring at a
prevalence of 34% to 44%.
2,35,36
Sometimes and
perhaps inaccurately included in the category of
unexplained anemia is anemia due to hemato-
logic malignancy, the prevalence of which has
been documented at 8% to 22% of patients
referred to a hematology clinic.
35,36
Some cate-
gorizations include iron-deficiency anemia as a
nutrient-deficiency anemia, although a nutritional
deficiency of iron is usually not the cause of this
anemia in the vast majority of patients. In devel-
oping countries, iron-deficiency anemia may in
fact be related to a dietary deficiency of iron,
but nutritional iron deficiency is rare in Western
society and most cases of iron-deficiency
anemia in this population are due to bleeding
and should be evaluated with this in mind.
37
Regarding nutrient-deficiency anemia,
NHANES III documented an 18% prevalence of
folate and/or vitamin B12 deficiency in elderly
patients with anemia.
2
However, more recent
studies have placed the prevalence of folate and
vitamin B12 deficiency anemia at less than 1%
in the elderly American population referred to
specialty hematology clinics.
35,36
However, these
patients are likely representative of neither the
general population nor of the population seen
by a general practitioner.
37
It is also believed
that in 30% to 50% of elderly anemic patients,
multiple etiologies are responsible.
38
Most cases
of anemia in the elderly are mild; about 90% of
patients have a hemoglobin of 11 g/dL or greater
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483
and about 98% have a hemoglobin of 10 g/dL
or greater.
2
Iron-Deciency Anemia
Iron-deficiency anemia is usually due to bleeding,
typically from the gastrointestinal tract, either from
gastritis, ulcer disease, arteriovenous malforma-
tions, colon polyps, colorectal cancer, or hemor-
rhoids. If blood loss cannot be detected, then
disorders involving iron absorption and bioavail-
ability should be considered. In the elderly, atro-
phic gastritis may reduce iron absorption, and
this condition is present in 20% to 48% of the
elderly.
39-41
Although the gold standard for diag-
nosing iron-deficiency anemia is the absence of
iron on a stained bone marrow aspirate sample
(rarely done) or an unambiguous hemoglobin
response to a trial of iron,
37
a clinical diagnosis
is typically made by a standard blood test that
demonstrates low serum iron and ferritin concen-
trations and a high total iron binding capacity
(TIBC). However, in the elderly this is complicated
by the fact that serum ferritin concentrations rise
with advancing age, probably as a consequence
of low-grade inflammatory processes.
39
Conse-
quently, serum ferritin concentrations below
45 mcg/L are usually indicative of iron deficiency
in the elderly, whereas much lower concentrations
may define iron deficiency in younger individ-
uals.
39,42
Measuring serum transferrin receptor
(sTfr) concentrations has been proposed as
a more sensitive estimate of iron stores in the
elderly, but the lack of standardized reagents for
this assay have obstructed the widespread use
of this test in clinical practice.
37,43
KEY POINT:
Iron deciency anemia
is typically not due to poor dietary iron
intake but a result of blood loss, most
often from the gastrointestinal tract.
Vitamin B12- and Folate-Deciency
Anemia
Although vitamin B12 deficiency may result
from dietary deficiency or a complica-
tion of gastrointestinal surgery, the most
common cause worldwide is pernicious anemia,
accounting for 76% of cases of vitamin B12-defi-
ciency anemia.
44,45
The median age range for
pernicious anemia is 70–80 years, demonstrating
a predilection for the elderly. A greater preva-
lence (about 4%) of pernicious anemia has also
been documented in elderly persons of African or
European ancestry compared to those of Asian
ancestry.
44
Pernicious anemia is an autoimmune
gastritis characterized by the reduced ability of
intrinsic factor to bind ingested vitamin B12 as
a result of gastric parietal cell destruction.
44
This
leads to malabsorption of vitamin B12 that takes
years to manifest. This is due to the relatively large
body stores of vitamin B12 (about 2,500 mcg) in
relation to the daily requirement (1 mcg). The
recommended daily allowance of vitamin B12 of
2.4 mcg is to account for the incomplete ability
of intrinsic factor to facilitate the absorption of
vitamin B12. Individuals with pernicious anemia
lack intrinsic factor and only absorb about 1.2%
of ingested vitamin B12.
45
Testing for pernicious
anemia involves testing for anti-intrinsic factor
or anti-parietal-cell antibodies.
44
Although not as
severe as pernicious anemia, up to 20% of the
elderly may suffer from a milder form of atrophic
gastritis with hypochlorhydria, which leads to an
inability to efficiently release vitamin B12 from
food, thereby resulting in mild malabsorption and
a delayed and often subclinical manifestation of
vitamin B12 deficiency.
44,45
KEY POINT:
Vitamin B12-deciency
anemia is the only nutritional anemia more
prevalent among elderly and is usually
caused by vitamin B12 malabsorption
due to autoimmune gastritis.
Currently, folic acid fortification of dietary
sources (especially flour) causes folate-defi-
ciency anemia to be rare in all age groups. In
fact, only 0.1% to 0.4% of folate tests ordered
by providers demonstrate low folate concentra-
tions.
46,47
Compared to younger adults, older
adults have been shown to have higher folate
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| Fundamentals of Geriatric Pharmacotherapy
concentrations both before and after the intro-
duction of folic acid fortification.
48,49
Anemia of Inammation and Anemia of
Chronic Kidney Disease
These types of anemia are sometimes grouped
together under the broad heading of anemia
of chronic disease because of the difficulty
in establishing a clinical diagnosis; also, it is
possible for them to occur together. Anemia of
inflammation (a.k.a. anemia of chronic inflamma-
tion) has been described as a state of elevated
inflammatory cytokines that stimulates the
production of hepcidin in the liver, leading to a
reduction in the intestinal absorption of iron and
release of iron from macrophages. This manifests
as low concentrations of serum iron in the pres-
ence of normal or increased total iron stores.
2
The distinction of anemia of chronic inflamma-
tion and iron-deficiency anemia, therefore, is a
diagnostic conundrum in the elderly, especially
in the patient with a serum ferritin concentration
in the intermediate range (e.g., 20–100 mcg/L),
which can be seen with both types of anemia.
Many epidemiologic studies are now defining
anemia of inflammation as a serum iron <60 mg/
dL along with a normal or elevated serum ferritin
and the absence of other causes of anemia.
37
As
mentioned above, the sTfr index may be helpful
in distinguishing these types of anemia, but is not
widely used. Further complicating a diagnosis
are the findings that: (1) inflammatory markers
may normally increase with aging without neces-
sarily being associated with anemia, (2) inflam-
matory markers may be elevated with anemia
regardless of its etiology, and (3) inflammatory
markers may not be markedly elevated with
anemia of inflammation.
37,50
The lack of standard-
ized criteria for a diagnosis of anemia of inflam-
mation helps to explain the difference in preva-
lence rates reported in the literature. NHANES
III reported that 24% of all cases of anemia in
the elderly are due to inflammation,
2
but when
stricter criteria are employed that base a diag-
nosis of anemia of inflammation on the presence
of an active inflammatory condition such as
infection, autoimmune disease, or malignancy,
the prevalence drops to 6% to 10%.
35,36
Anemia of chronic kidney disease is believed
to be due to reduced erythropoietin production
in the kidney, which is responsible for about
90% of the production of this hormone. In this
setting, the kidney loses the ability to effec-
tively produce erythropoietin in response to
decreased oxygenation.
51
In the elderly, anemia
associated with chronic kidney disease repre-
sents 12.5% of all anemia cases,
2
although esti-
mates from specialty hematology clinics have
been as low as 3% to 4%.
35,36
In patients over 50,
even mild degrees of renal insufficiency (creati-
nine clearance of 30–50 mL/min) are associated
with anemia, and a direct association between
degree of renal insufficiency and prevalence of
anemia has been documented.
52
The relation-
ship of renal function, erythropoietin, and anemia
in the elderly was investigated in the InCHIANTI
study, which showed a progressive increase in
anemia prevalence and a progressive decrease
in renal function and hemoglobin with advancing
age.
53
A linear inverse relationship was seen with
regard to anemia prevalence and kidney func-
tion (i.e., decreased kidney function = increased
anemia prevalence), with creatinine clearances
of 30 mL/min or lower.
53
Inflammation may also
contribute to anemia of chronic kidney disease,
because high levels of inflammatory markers
have been observed in these patients.
50
A diag-
nosis of anemia of chronic kidney disease is
made when chronic kidney disease is present
and the hemoglobin concentration is <13.0 g/dL
in males and <12.0 g/dL in females.
54
Unexplained Anemia
The term unexplained anemia refers to anemia
that has not been attributed to some other cause
and is the most common anemia occurring in
the elderly.
2,35,36
It is believed that with an appro-
priate hematological evaluation many cases of
unexplained anemia may be attributed to myelo-
dysplasia.
36,37
However, even with an intensive
hematologic investigation, an underlying cause
cannot be found in 35% to 44% of patients.
35,36
Unexplained anemia is somewhat of a misnomer
because this type of anemia is more likely due
to the interplay of many different causes as
opposed to ignorance of the cause. Although
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16 - Anemia and Preventive Therapy |
485
some have coined unexplained anemia as a
waste-basket diagnosis, it may actually be a
distinct clinical entity with all cases sharing a
unifying cause.
37
Hormonal deficiency (e.g.,
low testosterone) and dysregulation of growth
hormone/insulin-like growth factor-1 control
of hepatic erythropoietin secretion have been
proposed as possible causes of unexplained
anemia.
37,55,56
Unexplained anemia is usually
mild, with hemoglobin concentrations about 1 g/
dL lower than the standard set forth by the WHO,
likely resulting in underdiagnosis.
57
Age-related
factors that contribute to unexplained anemia in
the elderly are:
• renal dysfunction leading to a reduced
response to erythropoietin,
•
reduction in hematopoietic stem cell prolif-
erative and regenerative function,
• lower androgen levels, resulting in a decline
in hemoglobin concentration of up to 1 g/dL,
• chronic inflammation and cytokine dysregu-
lation, and
• myelodysplasia.
Additionally, other comorbidities and medi-
cations as well as nutritional deficits and alcohol
abuse may further contribute to the etiology of
unexplained anemia. As most of these contribu-
tors are age-related, the prevalence of unex-
plained anemia is directly related to age, most
common in the very old and virtually nonexistent
in those less than 50 years of age.
57
Summary of Standard Treatment
in General Adult Population and
Considerations in the Elderly
Iron-Deciency Anemia
The treatment of iron deficiency anemia involves
iron supplementation to correct the anemia and
replenish body stores.
58
This can be done through
diet in some cases but is usually achieved
through iron supplements. Iron supplementa-
tion is typically via the oral route, but can also
be given parenterally in patients with malabsorp-
tion or intolerance to oral preparations. Histori-
cally, in younger adults, iron-deficiency anemia
was treated with a total oral daily dosage of 200
mg elemental iron, given in two or three divided
doses. Lower dosages are recommended in the
elderly patient to improve tolerability and reduce
the risk of constipation, with the understanding
that iron stores will replenish at a slower rate.
59,60
More recent recommendations, however, favor
lower daily dosages for all adult patients and
recommend administering no more than 325 mg/
day of iron sulfate (65 mg elemental iron).
61
Daily
dosages of elemental iron as low as 15 mg have
been shown to be effective and well tolerated in
the elderly, resulting in comparable increases in
hemoglobin compared with 50-mg and 150-mg
daily dosages, but with significantly lower rates
of gastrointestinal adverse effects.
62
In addition,
a 20-mg daily dosage of elemental iron has been
shown to be effective and safe in preventing
iron deficiency anemia in pregnant women,
supporting the use of low-dose iron therapy in
the younger adult population.
63
Preferably, iron
should be administered at least 1 hour before
meals because food will reduce iron absorp-
tion.
59
However, gastrointestinal adverse effects
may be minimized by taking iron products
with food, necessitating this strategy in some
patients. Because acid conditions improve iron
absorption, the administration of ascorbic acid
(250–500 mg twice daily) or orange juice with the
iron preparation may be used, but its effective-
ness in the treatment of iron-deficiency anemia
is unknown.
58
Oral iron should be continued for 3 months
after the iron deficiency has been corrected,
to replenish body stores.
58
Restoration of iron
stores and subsequent improvement in hemo-
globin may take about 4 months, with expected
increases in hemoglobin of 1–2 g/dL every
couple of weeks.
64
Should oral iron therapy fail or
not be tolerated, parenteral iron may be admin-
istered, although this form of therapy is more
expensive and cumbersome to administer than
oral therapy and possesses a risk of anaphy-
lactic reactions. Although the initial rise in hemo-
globin is more rapid with parenteral iron, the rise
in hemoglobin at 12 weeks is similar to that seen
with oral iron administration.
58
Severe cases of
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486
| Fundamentals of Geriatric Pharmacotherapy
iron-deficiency anemia may necessitate red blood
cell transfusion. When choosing a treatment plan
for a patient with iron-deficiency anemia, the dura-
tion of therapy should not be longer than neces-
sary, and a thorough risk-benefit analysis should
be performed in any patient to determine whether
high-dose oral therapy (i.e., greater than 65 mg
elemental iron daily), parenteral iron therapy, or
even red blood cell transfusion is really necessary
given the higher risks of each of these treatments
compared to low-dose oral iron supplementation.
Overly aggressive therapy with iron products may
result in high body stores of iron, which could lead
to adverse clinical effects such as hemochroma-
tosis, coronary artery disease, diabetes, Parkinson
disease, and recurrent infections.
62
Vitamin B12- and Folate-Deciency
Anemia
In general, the treatment of anemia of nutritional
etiology does not differ between elderly patients
and younger adults. The treatment of vitamin
B12 deficiency anemia is administration of exog-
enous vitamin B12. This can be obtained through
food sources or more efficiently through high-
dose oral or parenteral supplementation. High-
dose oral and intramuscular administrations
are equally effective.
44,65
Oral vitamin B12 may
be obtained without a prescription, and injec-
tions may be self-administered in many patients.
Given that the majority of cases in the elderly
are due to pernicious anemia, lifelong therapy
is usually necessary and daily oral or monthly
subcutaneous/intramuscular injections of 1 mg
vitamin B12 are indicated. In these individuals,
dietary fortification is usually an insufficient
means of restoring vitamin B12 stores because of
the malabsorptive nature of the condition.
66
It has
been recommended that individuals 50 years of
age and older consume vitamin B12 in its crys-
talline form, which does not require gastric acid
or enzymes for digestion.
67
Patients with severe
abnormalities should receive injections of 1 mg
at least several times per week for 1–2 weeks,
then weekly until improvement is shown, then
monthly thereafter.
44
With treatment, reticulocyte
count increases in 1 week, with reversal of the
anemia usually occurring in about 6–8 weeks.
44
KEY POINT:
e treatment of anemia
in adults diers little based on patient
age, although considerations need to
be made for the multiple comorbidities
often occurring in the elderly.
Folate-deficiency anemia is treated with oral
folic acid or, rarely, with parenteral folic acid. The
dosage is typically 1 mg daily but may be as high
as 5 mg daily in cases of malabsorption. Given
the infrequency of this type of anemia, underlying
causes should be considered prior to the initia-
tion of folate therapy. Specifically, malabsorp-
tion and alcoholism, which interferes with folate
absorption and metabolism, should be ruled
out, and drug-induced causes should also be
considered. Methotrexate, pentamidine, trim-
ethoprim, and triamterene are folate antagonists.
Azathioprine, 6-mercaptopurine, 5-fluorouracil,
hydroxyurea, and reverse transcriptase inhibitors
(e.g., stavudine, lamivudine, and zidovudine)
may cause folate deficiency by directly inhibiting
DNA synthesis. Cholestyramine, metformin, and
sulfasalazine may decrease folate absorption.
The anticonvulsants phenytoin, phenobarbital,
primidone, and valproic acid may cause folate
deficiency through impaired vitamin absorption
and/or altered metabolism.
59,68
Anemia of Chronic Kidney Disease,
Anemia of Inammation, and
Unexplained Anemia
Anemia of chronic kidney disease has been
associated with reduced quality of life, increased
cardiovascular risk, and possibly reduced
survival.
69
Treatment is therefore targeted at
improving these outcomes and typically involves
a combination of iron supplementation and
erythropoietic-stimulating agents (ESAs).
54
Oral iron therapy in this situation is often inad-
equate because of poor absorption, and
parenteral therapy is often employed. Paren-
teral iron improves the response to ESAs and
also provides a dose-sparing effect for these
agents.
70
The use of ESAs for treating chronic
kidney disease is based on the need to stimu-
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