REVIEW

CURRENT
OPINION Anemia in the elderly
Wendy W. Pang and Stanley L. Schrier

Purpose of review
There have been several large-scale epidemiologic studies, including the National Health and Nutrition
Examination Survey III (NHANES III), which have described the prevalence and impact of anemia in the
elderly. The information derived has been critically important. However, given the large number of patients
surveyed, these reports necessarily relied substantially on the laboratory-based screening evaluations. There
are now two recent reports describing the cause of anemia in elderly outpatients, and although the
numbers are smaller than the large scale surveys, they constitute comprehensive hematologic evaluations
with therapeutic interventions and clinical follow-up. The purpose of this review is to compare these
different analyses.
Recent findings
There are distinct differences and similarities in the two types of studies, which are derived from patients
seen in hematology clinics. Despite comprehensive hematologic evaluation, the puzzling entity of
unexplained anemia of the elderly is confirmed and found to account for 30–46% of patients. NHANES III
classified iron-deficiency anemia with other nutritional anemias, a classification that might be correct in the
developing third world, but in North America and Western Europe, iron deficiency is more often caused by
blood loss and the cause must be sought and dealt with. The myelodysplastic syndromes are an important
cause of anemia in the elderly, with a prevalence of at least 4%.
Summary
Large-scale screening studies of anemia in the elderly are of great importance, and when complemented
by comprehensive hematologic evaluations, provide a more accurate picture of the clinical situation.
Keywords
anemia of chronic inflammation, iron-deficiency anemia, myelodysplastic syndrome, unexplained anemia
of the elderly, vitamin B12 (cobalamin) deficiency

INTRODUCTION aged 65–84 [6]. Additionally, the prevalence of ane-

The prevalence of anemia in the elderly, generally
considered to be age 65 and older, ranges between
2.9 and 61%, depending on the population studied
and definition of anemia [1]. Anemia is most com-
monly defined according to the World Health
Organization (WHO) criteria as hemoglobin values
less than 12 g/dl in women and less than 13 g/dl in
men [2]. However, this definition of anemia has
been called into question recently, with some stud-
ies suggesting that the hemoglobin levels of African-
Americans are physiologically lower than those of
Caucasians [3–5], thus potentially explaining why
the prevalence of anemia in the elderly is signifi-
cantly higher in the African-American population
compared to the Caucasian population [6]. Using
the WHO criteria, anemia affects approximately
10% of community-dwelling elderly individuals in
the United States, and the prevalence increases with
age, with the frequency of anemia doubling in indi-
viduals age 85 and older compared to individuals
mia in the elderly is drastically greater in the nursing
home setting than that in the community setting
[1,7,8].
Although typically mild with hemoglobin levels
remaining above 10 g/dl in most cases [6], anemia in
the elderly is frequently associated with negative
outcomes, including decreased physical perform-
ance with exaggerated worsening over time [9,10],
increased number of falls [11], increased frailty [12],
increased hospitalization [13,14], increased cogni-
tive impairment [15,16], and even increased
mortality [13,14,17]. None of these studies were
Department of Medicine, Stanford University, Stanford, California,
USA
Correspondence to Stanley L. Schrier, MD, Stanford Cancer Center,
875 Blake Wilbur Drive, Stanford, CA 94305, USA. E-mail: sschrier@
stanford.edu
Curr Opin Hematol 2012, 19:133–140
DOI:10.1097/MOH.0b013e3283522471

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 Erythroid system and its diseases
KEY POINTS
 Anemia of the elderly, although usually mild, is
associated with quite severe increases in mortality and
morbidity, but it is not proven that the anemia per se is
the cause of these important alterations in
normal function.
 Iron-deficiency, as a cause of anemia in the elderly, is
difficult to diagnose because the usual indicators are
relatively ambiguous. Making the diagnosis and finding
the source of blood loss can be life-saving.
 The accurate diagnosis of anemia of inflammation in
the elderly should not rest on arbitrary measurement of
iron indices, but should rest on solid clinical findings;
when anemia of inflammation is diagnosed, the cause
should be sought and, when found, treated.
 Although not identified in NHANES III, MDS as a cause
of anemia of the elderly has been found, with a
prevalence of about 5%, and patients suspected of
having MDS may account for an additional 15–20% of
anemic elderly, who may also have unexplained
macrocytosis or unidentified cytopenias.
 Undiagnosed anemia of the elderly (UAE) appears with
a prevalence of approximately 30–50% in virtually all
studies, but it is not clear whether this is a ‘waste
basket’ for several entities or whether UAE is a single
defined entity, and without a clear understanding of its
pathophysiology one cannot design rational therapy.
designed to determine causality, and it remains
unknown whether anemia plays a causative role
in the development or exacerbation of comorbid
diseases or it is merely a marker. However, identify-
ing the cause of anemia in the elderly individual is
important for the institution of appropriate therapy,
if available, and prompting, if necessary, further
evaluation. One classical example of this is the
accurate diagnosis of vitamin B12 (cobalamin)
deficiency leading to the appropriate therapy.
CAUSE OF ANEMIA IN THE ELDERLY
The National Health and Nutrition Examination
Survey III (NHANES III) was a large population-based
survey of anemia in a representative sample of com-
munity-dwelling elderly individuals in the United
States, and it classified the cause of anemia into the
four main categories of nutrient deficiencies (iron,
folate, and vitamin B12), anemia secondary to renal
disease, anemia of chronic inflammation/disease,
and, in the absence of other identifiable causes,
unexplained anemia [6]. Although the NHANES
III study provided a critical overview of the preva-
lence of different causes of anemia in community-
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dwelling elderly, thus guiding our approach to the
diagnosis and treatment of these conditions, the
criteria used to define the various causative divisions
have several important limitations, including lack of
clinical background, evaluation of the peripheral
blood smear, or an evaluation of the reticulocyte
response to anemia, which are all key pieces of
information in the clinical evaluation of the anemic
patient. Thus, the NHANES III categories do not
include other possible underlying causes of anemia
in the elderly, such as myelodysplasia, leukemia,
and hemolysis, that may have been uncovered if
more extensive clinical and hematological examin-
ations were conducted. Two recently published pro-
spective cross-sectional studies have sought to
clarify the distribution of the different causes of
anemia in the elderly following comprehensive
& &
hematological investigation [18 ,19 ]. These studies
differed from the NHANES III analysis in that they
evaluated patients in referral hematology clinic
settings at academic centers. Artz and Thirman
&
[18 ] evaluated racially diverse elderly anemic
patients, the majority of whom were African-Amer-
&
ican women, and Price et al. [19 ] evaluated elderly
anemic patients who were predominantly white
men referred to the Veterans Affairs clinic or referred
to a university hematology clinic. Starting with the
NHANES III study as a basis, these two careful
clinical and comprehensive hematologic analyses
have allowed us to refine and even redefine our
understanding of the causes of anemia in the
elderly.
Despite fairly distinct criteria for defining the
various causes of anemia, the proportion of patients
with unexplained anemia of the elderly was similar
in these two studies compared to the NHANES III
study (Fig. 1). In contrast, the prevalence of nutrient
deficiencies, anemia of inflammation, and anemia
secondary to renal disease are reduced in the two
recent studies compared to the NHANES III study;
and myelodysplasia and hematologic malignancy
are important causes of anemia in the elderly
(Fig. 1).
Iron-deficiency anemia
Although iron-deficiency anemia is technically a
nutrient deficiency and is certainly a nutritional
disorder in the developing world, iron-deficiency
anemia in the more affluent Western world is more
often due to bleeding and necessitates a careful search
for a source of blood loss [20,21], followed by its
correction. Therefore, iron-deficiency anemia should
be separated from the nutrient deficiency category in
NHANES and similar studies, as the evaluation of
iron-deficiency anemia in the elderly requires
Volume 19  Number 3  May 2012

UAE
IDA NHANES III
AI
AI & CKD
CKD
14%
Folate and/or
8%
B12 deficiency
Hem Malig
4%
Thal
Susp MDS 20%
Other 20%
Incomplete
Therapy for
non-Hem Malig
FIGURE 1. Prevalence of anemia in the elderly by cause identified in three studies. Studies shown are NHANES III [6],
Chicago [18 ], and SHC/VAPAHCS [19 ]. AI, anemia of inflammation; CKD, anemia secondary to renal disease; Hem
& &
Malig, hematologic malignancy; IDA, iron-deficiency anemia; Susp MDS, suspicious for myelodysplastic syndrome; Thal,
thalassemia; UAE, unexplained anemia of the elderly.
looking beyond poor iron intake, absorption, or
processing.
Diagnosis of iron-deficiency anemia in the
elderly remains quite challenging because of the
low sensitivity of current methods identifying iron
deficiency in the elderly, including the measure-
ment of iron indices, such as serum iron level, total
iron binding capacity, transferrin saturation, and
serum ferritin [22]. Although the serum soluble
transferrin receptor (sTfR)–log ferritin index has
been shown to be more sensitive than standard iron
indices for identifying iron deficiency in the anemic
elderly [22,23], the regular implementation of this
assay is hindered by the lack of standardized
reagents for the sTfR assay [24,25]. The gold stand-
ard for diagnosing iron-deficiency anemia is the
absence of iron on an appropriately and adequately
stained bone marrow aspirate sample [26] (an inva-
sive method rarely conducted for the sole purpose of
diagnosing iron deficiency) or an unambiguous
hemoglobin response to a trial of iron.
&
In their recent study, Price et al. [19 ] made the
diagnosis in 22% of patients with iron-deficiency
anemia, who did not have aberrant iron indices,
solely based on their response to iron supplement-
ation. Interestingly, this study also found that in
iron-deficiency anemia patients who had their iron
stores repleted as indicated by improved iron
indices, only 50% of them had full correction of
&
their anemia [19 ], suggesting that some patients’
anemia was in fact because of other causes in
addition to iron deficiency. Nonetheless, iron-
deficiency anemia is an important cause to identify
in the elderly anemic individual not only because
the anemia can potentially be corrected with iron
supplementation, but also because it is critical to
identify any sources of bleeding. A carefully
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Anemia in the elderly Pang and Schrier
Chicago SHC/VAPAHCS
6% 11%
3%
8% 4%
34%
5% 6% 35%
44%
10%
16%
6% 12%
25% 4% 6%
conducted trial of iron supplementation remains a
useful diagnostic and therapeutic modality. When
iron-deficiency anemia is diagnosed, the source of
the blood loss must be identified and corrected if
possible. In these elderly patients, the likely source
of blood loss is the gastrointestinal tract and the
likely cause is cancer [20,21].
Nutrient deficiency: folate and vitamin B12
Folate and vitamin B12 deficiencies are exceedingly
rare in the elderly anemic population in the United
States. Approximately 10–20% of elderly individ-
uals have been found in one study to have vitamin
B12 deficiency, as defined by reduced serum levels of
vitamin B12; however, only 10% (1–2% overall) of
these individuals have anemia because of the
deficiency, as defined by a clear-cut response to
vitamin B12 replacement [27,28]. Such a response
must include an improvement in hemoglobin, a
return of the mean corpuscular volume (MCV) to
normal, and a disappearance of hypersegmented
neutrophils. In the study by Artz and Thirman
&
[18 ], only 1 out of 174 elderly individuals with
anemia was found to have true vitamin B12
deficiency, with hematologic response to supple-
mental vitamin B12, and the patient was sub-
sequently found to be positive for antibodies
against intrinsic factor, confirming a diagnosis of
pernicious anemia. Similarly, in the study by Price
&
et al. [19 ], only 1 out of 190 elderly anemic indi-
viduals had anemia because of vitamin B12
deficiency. Although there is a very low incidence
of vitamin B12 deficiency in the elderly population,
it is an important diagnosis that must not be missed.
Interestingly, folate deficiency was not identified in
& &
any patients in either of these studies [18 ,19 ],
www.co-hematology.com 135
 Erythroid system and its diseases
perhaps because of the current policy of folate
supplementation in flour. Of note, the patients in
these studies were enrolled from referral hematol-
ogy clinics and therefore these frequencies are not
likely to be reflective of either the general popu-
lation or of a general internal medicine practice.
Anemia of inflammation and anemia
secondary to renal disease
Anemia of inflammation, also known as anemia of
chronic disease or anemia of chronic inflammation
(ACD/ACI), is a very difficult clinical diagnosis to
make and a difficult cause to characterize consist-
ently because of the variable criteria used in each
study. There are currently no standardized peri-
pheral blood laboratory criteria that can be applied
to diagnose anemia of inflammation. Anemia of
inflammation was classically defined by Cartwright
[29] as anemia associated with low serum iron,
reduced bone marrow sideroblasts, and increased
reticuloendothelial iron, all within the appropriate
clinical context of systemic inflammation. In con-
trast, many recent epidemiologic studies of anemia
in the elderly have modified the diagnostic criteria
for anemia of inflammation to include any case in
which serum iron is less than 60 mg/dl, serum ferri-
tin is normal or elevated, and there is the absence of
other causes [6,30,31]. In the NHANES III study, the
anemia of inflammation accounts for 24% of all
anemia in the elderly [6]. The issue is further com-
plicated because normal aging has been associated
with increased markers of inflammation and
healthy nonanemic elderly individuals have been
found to have higher levels of inflammatory
markers such as interleukin-6 [32] and fibrinogen
[33]. Additionally, elderly anemic individuals have
higher levels of circulating inflammatory markers
compared to elderly nonanemic individuals, regard-
less of the cause of the anemia [34,35]. However,
whether this degree of inflammation is adequate to
produce the clinical syndrome of anemia of inflam-
mation is not well documented. By using low serum
iron to define anemia of inflammation, the NHANES
III and other similar studies using similar criteria
likely overestimate the prevalence of this condition.
Thus, when the diagnosis of anemia of inflam-
mation is made based on more restricted criteria
and only in those cases in which an active inflam-
matory disease, such as infection, autoimmune
disease, or malignancy is present, anemia of inflam-
mation decreases dramatically to 6–10% of all ane-
& &
mia in the elderly [18 ,19 ]. This distinction is
clinically important because when anemia of
inflammation is identified, its cause must be sought
and corrected if possible. Of note, one recent study
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found that proinflammatory markers were actually
not markedly elevated in anemia of inflammation
[34].
Anemia secondary to renal disease can also be a
difficult clinical diagnosis to make. Decreasing level
of renal function has been clearly shown to be
associated with lower erythropoietin levels [36],
but the degree of renal dysfunction in elderly
patients that definitively leads to anemia remains
controversial. Although chronic kidney disease is
usually easy to identify, if the estimated glomerular
filtration rate (eGFR) is less than 30 ml/min/1.73 m2
calculated using the Modification of Diet in Renal
Disease (MDRD) equation [37,38], it is much more
difficult to diagnose anemia due to renal disease if
the eGFR is 30–60 ml/min/1.73 m2. It is possible
that diabetes or hypertension can compound mild
renal insufficiency in impairing erythropoietin pro-
duction leading to the development of anemia
[39,40]. Nevertheless, only eGFR less than 30 ml/
min/1.73 m2 has been clearly associated with ane-
mia in the elderly [37]. Using estimated creatinine
clearance (CrCl) less than 30 ml/min, the NHANES
III study found that anemia secondary to renal dis-
ease was present in 12.5% of anemia in the elderly
[6]. In the two recent studies of anemia in the elderly
in the referral hematology clinic setting and using
the criteria of eGFR less than 30 ml/min/1.73 m2,
only 3–4% of cases of anemia in the elderly were
& &
found to be secondary to renal disease [18 ,19 ], also
lower than NHANES III study estimates.
Although the primary pathogenesis of anemia
secondary to renal disease is impaired erythropoie-
tin production, inflammation may be an important
contributing factor to the development of anemia in
these patients. In the study by Ferrucci et al. [34], the
highest levels of inflammatory markers were found
in the category of patients with anemia due to renal
disease. Increased inflammation has been shown to
be associated with poor responses to exogenous
erythropoietin therapy in patients with anemia
secondary to renal disease [41,42]. Anemia of
inflammation and anemia secondary to renal dis-
ease are clearly important diagnoses to make, as
these causes specifically have been significantly
associated with increased mortality [43].
Myelodysplasia and hematologic malignancy
Myelodysplasia and hematologic malignancy were
not included among the causative divisions
delineated by the NHANES III study. However, there
has been speculation that some or much of unex-
plained anemia cases could have been attributed to
myelodysplastic syndromes (MDS), had a more
detailed workup been done [6,44,45]. The recent
Volume 19  Number 3  May 2012

&
studies by Artz and Thirman [18 ] and Price et al.
&
[19 ] found that 7.5 and 6%, respectively, of anemia
in the elderly cases could be definitively attributed
to hematologic malignancy, with most cases ident-
ified as MDS. The referral clinic setting in these two
studies may overestimate the prevalence of MDS
and acute myeloid leukemia in the elderly anemic
population as a whole. However, MDS and hema-
tologic malignancy, although relatively uncommon
causes of anemia in the elderly, are not rare, and can
be detected only with a comprehensive hematologi-
cal evaluation of elderly anemic patients.
The diagnosis of MDS can be extremely difficult
if the classic signs of cytopenias, dysplasia, or cyto-
genetic abnormalities are not present. Artz and Thir-
& &
man [18 ] and Price et al. [19 ] found that 9 and 16%,
respectively, of elderly anemic patients studied had
peripheral blood and/or bone marrow evaluations
that were suspicious but not diagnostic for MDS. In
the Price et al. study, the category of ‘suspicious for
MDS’ included patients with findings such as unex-
plained macrocytic anemia or bicytopenia or pan-
cytopenia, whereas in the Artz and Thirman study,
patients with those findings were included in un-
explained anemia of the elderly. Other studies have
estimated between 5 and 15% of elderly anemic
patients have findings that lead one to suspect a
diagnosis of MDS [6,46–48]. In one retrospective
review of bone marrow samples from elderly
patients over a 4-year period, 23 of 209 (11%) were
found to be suspicious but not diagnostic for MDS at
the time of bone marrow sampling [47]. Of these
patients, 44% of which were eventually diagnosed
with MDS at median 18.77 months follow-up, high
MCV, high red cell distribution width, and high
lactate dehydrogenase were all important predictors
of MDS in these samples [47]. Prospective longitudi-
nal cohort studies of elderly anemic patients suspi-
cious for MDS, including baseline bone marrow
evaluations, will be important for better character-
ization of the natural history of this condition and
identification of risk factors associated with pro-
gression to overt MDS.
Unexplained anemia of the elderly
In many cases of anemia in the elderly, the cause of
anemia is known and the anemia is treatable, as in
the case of iron-deficiency anemia. Nevertheless,
many different cross-sectional studies using a
variety of methods and populations have found
that, in approximately one-third of elderly adults
with anemia, the cause cannot be found
[6,8,31,43,49–53]. This condition has been variably
labeled as unexplained anemia of the elderly (UAE),
senile anemia, or anemia of unknown cause.
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Anemia in the elderly Pang and Schrier
Without clear cause of the anemia, it is impossible
to initiate any targeted therapy in patients with
UAE. The two recent studies by Artz and Thirman
& &
[18 ] and Price et al. [19 ] have prospectively and
rigorously evaluated anemia in the elderly to try to
identify cases that may be misclassified as UAE, such
as drug toxicity, alcohol use, myelodysplasia, and
hematologic malignancy, but they notably found
UAE frequencies of 30 and 46%, respectively, despite
intensive hematologic investigation, which are
remarkably similar to previous estimates. Of note,
the prevalence of UAE among anemic elderly in the
Artz and Thirman study is still 37%, even if those
cases that they classified as suspicious for MDS are
excluded from the UAE category, as the Price et al.
study had done.
There has been speculation that inflammation
[35], defect in hypoxia sensing or response [39],
undiagnosed or ‘early’ MDS [6,44,45], hormonal
&
deficiency [54,55 ], or hematopoietic stem and pro-
genitor cell defects may explain some or all of the
cases of UAE. It remains unclear whether UAE is a
uniform diagnosis or whether it consists of multiple
causes and involves multiple pathways. UAE has
been described sometimes as a ‘waste-basket’ diag-
nosis, but there is some early evidence that suggests
UAE may be a definite clinical entity and cases of
UAE potentially share a unifying cause. Although
the pathophysiology of UAE remains an area of
ongoing investigation, studies on UAE are remark-
ably consistent, characterizing the anemia as hypo-
proliferative with a hypocellular bone marrow, low
serum erythropoietin levels for the degree of ane-
mia, and nonelevated inflammatory markers
& & &
[18 ,19 ,35,55 ]. In a recent study by Waalen et al.
&
[55 ], the authors found that elderly men with UAE
had lower testosterone levels compared to nonane-
mic controls, suggesting that hormonal deficiency
may be a contributing factor to the development of
UAE in men. Another possible cause of unexplained
anemia in the elderly may be because of dysregu-
lated growth hormone/insulin-like growth factor-1
(IGF-1) control of hepatic erythropoietin secretion
[56], because low levels of IGF-1 have been associ-
ated with anemia in elderly individuals [57]. The
expected hematologic course of UAE remains
unknown. It is also unknown whether UAE is
specifically associated with poor functional out-
comes and increased mortality risk. It is also unclear
whether therapeutic interventions would be able to
improve hematologic and functional outcomes in
UAE. One small study involving mostly elderly
African-American women, some of whom had
UAE, showed some improvements in fatigue and
quality of life following treatment with exogenous
erythropoietin [30].
www.co-hematology.com 137
 Erythroid system and its diseases
Other causes and considerations
Anemia in the elderly because of hemolysis is
extremely rare, identified in only 2% of cases in
&
the Artz and Thirman study [18 ]. Comorbid con-
ditions complicate the analysis of anemia in the
elderly. For example, androgen-deprivation therapy
for the treatment of prostate cancer has been shown
&
to be associated with anemia [58]. Price et al. [19 ]
found that prior treatment for nonhematologic
malignancies, such as for breast or prostate cancer,
was the cause of anemia for 11% of the patients
they studied.
CONCLUSION
Evaluation of anemia in the elderly requires
thorough hematologic evaluation. Complete blood
count with peripheral smear, red cell indices, iron
indices, and calculation of renal function are most
useful in identifying the cause of anemia in the
elderly. Myelodysplasia and hematologic malig-
nancy are not rare diagnoses in this population.
The prevalence of anemia of inflammation and
anemia secondary to renal disease may be lower
than previously estimated, albeit the diagnoses of
anemia of inflammation and anemia secondary to
mild renal impairment are very difficult to make,
such as when creatinine clearance is 30–60 ml/min.
&
Price et al. [19 ] found that analysis of thyroid func-
tion, by measuring thyroid stimulating hormone,
was not likely to be helpful, nor was ordering serum
protein electrophoresis as screening tests.
Although usually mild or even considered ‘triv-
ial’, anemia of the elderly is associated with signifi-
cant increases in morbidity and mortality. It is still
unclear whether the anemia per se is the cause of the
alterations in normal function seen in anemic
patients, and it is unclear whether correction of
the anemia results in reduction of associated mor-
bidity and mortality. Nevertheless, it makes sense to
identify the cause of the anemia in the elderly,
because doing so may lead to identification of
potentially serious underlying conditions, which
then could be addressed. It will be important to
discover if correction of the anemia does lead to
improvement in physical function and even cogni-
tion. Many cases of anemia in the elderly are because
of iron deficiency, which can be difficult to diagnose
because the usual indicators of iron indices have
relatively low sensitivity. Nevertheless, the finding
of iron-deficiency anemia in the elderly is not only
treatable with iron supplementation, but also leads
directly to a careful search for sources of bleeding,
the identification of which can be life-saving.
Renal disease as a cause of anemia in the elderly
is easy to diagnose when the creatinine clearance is
less than 30 ml/min, but the contribution of renal
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disease to anemia when creatinine clearance is
30–60 ml/min is less well described, and the under-
lying pathophysiology may not simply be due to
reduced expression of erythropoietin. Inflammatory
mediators are very high in patients with anemia
secondary to renal disease. The role of inflammation
in the development of anemia of the elderly remains
unclear, partly because studies of normal non-
anemic elderly show mild but distinct increases in
established biomarkers of inflammation. The accu-
rate diagnosis of anemia of inflammation in the
elderly should not rest on arbitrary measurement
of iron indices, but should rest on solid clinical
findings. When anemia of inflammation is diag-
nosed, the cause should be sought and, when found,
treated.
MDS has been found to be an important cause of
anemia of the elderly, following comprehensive
hematologic evaluations. Partly because of patient
and physician reluctance, marrow examination has
thus far not been performed on the majority of
patients suspected of having MDS, which may
account for an additional 15–20% of anemic elderly
with unexplained macrocytosis or unidentified
cytopenias. Definite studies on the abnormal hem-
atopoiesis in MDS patients will likely be important
for developing methods that can more easily
identify and diagnose MDS.
Interestingly, what remains most consistent
among the studies of anemia in the elderly is that
UAE comprises approximately one-third of elderly
anemic individuals, even when cases suspicious but
not diagnostic for MDS are removed. UAE is a
uniformly hypoproliferative anemia with a distinc-
tive low erythropoietin response for the degree of
anemia. However, it remains unclear whether UAE
is a combination of several entities, including
some with underlying MDS, or whether UAE is a
single defined entity. Better understanding of the
pathogenesis of UAE will likely require additional
biological analysis and longitudinal clinical evalu-
ation of patients with UAE. The roles of inflam-
mation and low testosterone in the pathogenesis
of UAE still need to be clarified. Distinguishing
between cases that are suspicious for MDS and
UAE will likely require not only bone marrow evalu-
ation, but also better diagnostic testing to detect
MDS. Development of rational therapy for the treat-
ment of UAE will require a better understanding of
its pathophysiology. Definitive studies on hemato-
poiesis in UAE will likely clarify this entity.
Acknowledgements
This work was supported by NIH Grant five R01
AG029124-03. The authors would like to thank
Elizabeth Price and Andrew Artz for helpful discussions.
Volume 19  Number 3  May 2012

Conflicts of interest
There are no conflicts of interest.
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Volume 19  Number 3  May 2012