Feature Articles

Tracking and Treating Anemia in Elderly Patients

January 7, 2009

Physician advising elderly patientsArtz quoteIncreasing evidence indicates that anemia is common in the elderly population. Anemia is often considered to be relatively harmless and a normal part of the aging process, but anemia is neither normal nor harmless and may have far-reaching effects. According to Dr. Andrew Artz, a geriatric hematologist and Assistant Professor of Medicine at the University of Chicago, “Anemia is an important sign in the elderly that often points to a serious and possibly treatable medical condition.”

Prevalence and Risk Factors

Anemia is defined by the World Health Organization (WHO) as a hemoglobin (Hb) concentration of <12 g/dL for women and <13 g/dL for men.1 Anemia is a common condition in people over age 65, affecting more than 3 million people in the United States.2 As expected, higher rates are found in hospitalized patients, and in the oldest patients.3-6 Although the prevalence of anemia does increase with age, successful aging is not usually associated with anemia. In contrast to anemia in younger people, anemia in elderly persons is more common in men than women.2 Anemia is also approximately three times more prevalent in elderly African Americans than among non-Hispanic Caucasians.

Causes of Anemia in the Elderly

Anemia in the elderly is more commonly observed than appreciated and is often multifactorial, with multiple factors contributing to the problem in the individual patient. Dr Artz stated that “In elderly persons the etiology of anemia differs sufficiently from younger adults to warrant considering anemia in elderly persons as a distinct entity.” More than two-thirds of anemia in the elderly can be attributed to two major causes, nutritional deficiencies, and anemia of chronic disease.7 Nutritional deficiencies account for approximately 34% of cases of anemia in the elderly, while anemia of chronic disease, with or without renal insufficiency, accounted for an additional 33%. As many as 33% of geriatric anemias remain unexplained, and their pathogenesis remains speculative.7

Anemia causes pie chartNutritional Deficiencies
Iron deficiency, either alone or in combination with vitamin B12 and/or folate deficiency accounts for nearly 20% of all geriatric anemia.7 While iron deficiency anemia (IDA) is a common cause of geriatric anemia, in the United States, it is rarely the result of dietary deficiency.8 The majority of elderly patients with IDA have an underlying gastrointestinal tract abnormality, and their IDA is most often the result of chronic blood loss secondary conditions such as esophagitis, gastritis, ulcer, and malignancy.9

Vitamin B12 and folic acid deficiency are less common, and often occur in combination with iron deficiency. Low levels of B12 occur in 10-15% of the elderly, but it is estimated that only 1-2% of the elderly are anemic due to vitamin B12 deficiency.2 Anemias due to folic acid deficiency are also relatively uncommon in elderly patients.2

Types of Anemia in Persons 65+
Type of Anemia  % 
Nutritional Deficiency/Blood Loss
   Iron deficiency (+/- folate, B12 def.)
   Folate and/or B12 deficiency only
34
  (20)
  (14)
Chronic Disease (EPO Deficiency)
   Chronic kidney disease (CKD)
   Anemia of chronic disease (ACD)
   CKD and ACD
32
  (8)
  (20)
  (4)
Unexplained Anemia (Idiopathic) 34
NHANES III via Guralnick et al2

Chronic Disease
Because elderly persons often suffer from multiple chronic comorbidities, it is not surprising that the anemia of chronic disease (ACD) is a common cause of geriatric anemia, accounting for more than one-third of cases.10 ACD appears to be primarily related to inflammation, and usually develops in the presence of disorders such as chronic infections, malignancy, autoimmune and inflammatory disorders. ACD is a hypoproliferative anemia characterized by low serum iron and adequate to increased iron stores. Inflammation inhibits erythropoiesis through a variety of mechanisms. Inflammatory markers implicated in anemia of chronic inflammation include tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) interferon gamma (IFN-gamma), and IL-6. Recently, it has been suggested that hepcidin may be the key mediator in ACD. Hepcidin is a key regulator of iron balance, and abnormalities in hepcidin gene expression are associated with clinical abnormalities in iron parameters and anemia. Hepcidin is an acute phase reactant, and inflammation, especially with IL-6, increased hepcidin expression.11

Chronic kidney disease (CKD) is exceedingly common in the elderly, since renal function declines with age. CKD commonly leads to anemia, and is another important cause in this population. There is a clear linear relationship between the prevalence of anemia and kidney function; anemia increases with declining kidney function. The primary cause of anemia in CKD appears to be a decline in the renal production of erythropoietin (EPO).10

Unexplained Anemia
There is a high rate of unexplained anemia in elderly individuals. Dr Artz stated that “It has long been recognized that a proportion of patients, usually older, have anemia that does not meet diagnostic criteria for a specific etiology. Multiple studies of anemia in elderly persons over the past 30 years have confirmed that unexplained anemia represents a considerable proportion of cases of anemia in elderly persons.” The cause of the anemia is not determined in as many as one-third of geriatric anemias. Unexplained anemia is generally a condition of elderly persons. It appears more commonly with advancing age and is rarely, if ever, encountered in younger adults.12 Whether unexplained anemia represents a spectrum of undiagnosed etiologies or has a unifying pathogenesis remains unclear. Several theories have been postulated to explain this phenomenon, including decreased production of hematopoietic growth factors, the presence of inflammatory cytokines, marrow abnormalities and androgen deficiencies.10 It is also thought that some of these cases may actually be unrecognized CKD, early stage ACD, or undiagnosed myelodysplasia.10 Myelodysplastic syndrome (MDS) is characterized by ineffective production of myeloid blood cells and a risk of transformation to acute myelogenous leukemia. Anemia requiring blood transfusion is present in 90% of MDS patients. MDS is more common in older adults, and may be an important cause of unexplained anemia in the elderly.2

Adverse Outcomes Related to Anemia in Elderly Patients

Morbidity and Mortality Related to Geriatric Anemia
  • Increased mortality
  • Increased hospitalization
  • Cardiovascular disease
  • Falls
  • Functional impairment
  • Cognitive impairment and mood dysfunction

Anemia has several consequences in the elderly. It has been associated with increased mortality, a higher incidence and more severe cardiovascular disease, cognitive impairment, decreased physical function, and an increased risk of falls and fractures.10 These adverse effects were seen in patients with mild anemia as well as those with more severe anemia.10

A study in the Journal of the American Medical Association found a 2-fold increase in mortality risk in elderly patients with anemia as compared to persons with a normal hemoglobin. The mortality risk in these patients was increased as their hemoglobin decreased.13 Even mild anemia is associated with a broad range of poorer health related outcomes. For example, elderly patients with heart failure who have low hemoglobin levels have more symptoms, poorer hemodynamics, and greater mortality than those with higher hemoglobin levels.14 Geriatric anemia has been associated with increased frailty, poorer exercise performance, diminished cognitive function, risk of developing dementia, decreased mobility, increased risk of recurrent falls, and an increased rate of major depression.14

Elderly woman explaining symptomsTreatment for Elderly Patients

Currently, there are no specific clinical guidelines to help clinicians manage geriatric anemia. The choice of management is complicated by the fact that the underlying etiology of the anemia is unknown in up to one-third of patients. It is clear that anemia in the elderly should be evaluated, and the underlying cause should be identified and treated whenever possible. Patients with nutritional deficiencies (iron, B12, or folate) or severe anemia secondary to CKD or inflammation should receive supplementation with the deficient nutrient or with an erythropoiesis-stimulating agent (ESA).14 However, due to the recent safety concerns with ESA’s as well as the cost associated with therapy, ESA’s should be used judiciously, especially in patients with mild anemia.14

Anemia is a common problem in elderly patients but it should not be accepted as a normal consequence of aging. Clinicians should be aware that anemia in elderly persons is associated with poorer quality of life, significant morbidities, and increased mortality. Failure to recognize and evaluate anemia in the elderly could lead to delayed diagnosis of potentially treatable conditions.

References

  1. World Health Organization. Worldwide Prevalence of Anaemia 1993-2005: WHO Global Database on Anaemia. Edited by Bruno de Benoist, Erin McLean, Ines Egli and Mary Cogswell. Link.
  2. Guralnik JM, Ershler WB, Schrier SL, Picozzi VJ. Anemia in the elderly: a public health crisis in hematology. Hematology Am Soc Hematol Educ Program. 2005:528-32. Link.
  3. Sahadevan S, Choo PW, Jayaratnam FJ. Anaemia in the hospitalised elderly. Singapore Med J. 1995 Aug;36(4):375-78. Link.
  4. Smieja MJ, Cook DJ, Hunt DL, Ali MA, Guyatt GH. Recognizing and investigating iron-deficiency anemia in hospitalized elderly people. CMAJ. 1996 Sep 15;155(6):691-96. Link.
  5. Dallman PR, Barr GD, Allen CM, Shinefield HR. Hemoglobin concentration in white, black, and Oriental children: is there a need for separate criteria in screening for anemia? Am J Clin Nutr. 1978 Mar;31(3):377-80. Link.
  6. Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med. 2006 Apr;119(4):327-34. Link.
  7. Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004 Oct 15;104(8):2263-68. Link.
  8. Rimon E, Levy S, Sapir A, Gelzer G, Peled R, Ergas D, Sthoeger ZM. Diagnosis of iron deficiency anemia in the elderly by transferrin receptor-ferritin index. Arch Intern Med. 2002 Feb 25;162(4):445-49. Link.
  9. Rockey DC, Cello JP. Evaluation of the gastrointestinal tract in patients with iron-deficiency anemia. N Engl J Med. 1993 Dec 2;329(23):1691-95. Link.
  10. Eisenstaedt R, Penninx BW, Woodman RC. Anemia in the elderly: current understanding and emerging concepts. Blood Rev. 2006 Jul;20(4):213-26. Link.
  11. Means RT Jr. Hepcidin and anaemia. Blood Rev. 2004 Dec;18(4):219-25. Link.
  12. Artz A, Ershler W. Anemia in Elderly Persons. Available at: Link. Accessed December 16, 2008.
  13. Izaks GJ, Westendorp RG, Knook DL. The definition of anemia in older persons. JAMA. 1999 May 12;281(18):1714-17. Link.
  14. Steensma DP, Tefferi A. Anemia in the elderly: how should we define it, when does it matter, and what can be done? Mayo Clin Proc. 2007 Aug;82(8):958-66. Link.