Anemia in the Elderly
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Pages 25 - 28
Anemia in older persons is common and is often incorrectly attributed to the ravages of normal aging. Hemoglobin levels should not vary due to age in elderly patients who are free of disease with bone marrow that is not stressed. Whether anemia is a marker or mediator of disease is not always clear, but even in centenarians it is usually a signal of pathology and is associated with increased morbidity and mortality.1,2 A simple evaluation will identify the majority of causes and facilitate appropriate treatment.
The World Health Organization (WHO) has identified the lower limits of normal hemoglobin as 13 g/dL in men and 12 g/dL in women. While the WHO criteria was based on a small group of younger patients, anemia as defined by WHO criteria is associated with an increased mortality risk in people older than 85 years, indicating that the thresholds are still appropriate for even the very aged.3,4
The prevalence of anemia increases with advancing age. Under age 75 years, anemia is more common in females, but over age 75 years it is more common in males.5 Anemia increases dramatically after age 85 in both sexes, in some studies present in 17% of women and 28% of men.6
In addition to age, anemia prevalence varies as a reflection of the general health of the patient population. The highest rates occur in hospitals and nursing homes, while the lowest are in patients who live at home or in independent living sites.7
Hematopoiesis and Cytokines in Older Persons
Just as other aging organ systems experience a decline in organ function reserve, the hematopoietic system loses its capacity to respond to stress. While hemoglobin, white blood cell count, and platelets are normal under usual circumstances, older patients may take longer to recover from a bleeding episode, or the white blood cell count may not demonstrate a brisk leukocytosis in the face of sepsis.
There are several potential reasons. Normal hematopoiesis requires the coordinated interaction of stem cells, modulating cytokines, and an intact hematopoietic microenvironment. Disruption of any of these three variables may cause abnormalities in the blood counts. Older people may have an overall reduction in stem cell concentration, hematopoietic growth factor production, and sensitivity to hematopoietic cytokines.8 Pro-inflammatory cytokines such as interleukin (IL)-1, tumor necrosis factor-alpha, and IL-6 regulate the inflammatory process during infection, trauma, and stress. Increased levels of each of these cytokines are associated with a number of diseases that are common in older persons, including atherosclerosis, diabetes mellitus, and cancer. The regulation of these cytokines decreases with age. In one population-based, case-control study of adults age 74 years and older, frail subjects had significantly higher IL-6 and lower hemoglobin levels than non-frail subjects.9 This cytokine is one of the likely mediators in the pathogenesis of the frailty syndrome of decreased bone mineral density, reduced lean body mass, low serum cholesterol and albumen, and anemia.10
In the Baltimore Longitudinal Study of Aging (BLSA), patients examined at 1-2–year intervals for 8-30 years had serum erythropoietin levels that increased significantly with aging, but increased less significantly in those patients with hypertension or diabetes. The increase in serum erythropoietin with aging may indicate compensation for subclinical blood loss, increased red cell turnover, or increased erythropoietin resistance of red cell precursors. The less significant rise in those patients with hypertension and diabetes may reflect an age-acquired renal impairment associated with the underlying disorder.
1. Wieczorowska-Tobis K, Niemir Z, Mossakowska M, et al. Anemia in centenarians. J Am Geriatr Soc 2002;50:1311-1313.
2. Nissenson AR, Goodnough LT, Dubois RW. Anemia: Not just an innocent bystander [published correction appears in Arch Intern Med 2003;163(15):1820]? Arch Intern Med 2003;163(12):1400-1404.
3. Izaks GJ, Westendorp RG, Knook DL. The definition of anemia in older persons. JAMA 1999;281:1714-1717.
4. World Health Organization. Nutritional Anaemas: Report of a WHO Scientific Group. World Health Organization Website. http://whqlibdoc.who.int/trs/WHO_TRS_405.pdf. Published 1968. Accessed July 7, 2009.
5. Guralnik JM, Ershler WB, Schrier SL, Picozzi VJ. Anemia in the elderly: A public health crisis in hematology. Hematology Am Soc Hematol Educ Program 2005:528-532.
6. Balducci L. Epidemiology of anemia in the elderly: Information on diagnostic evaluation. J Am Geriatr Soc 2003;51(3 suppl):S2-S9.
7. Beghé C, Wilson A, Ershler WB. Prevalence and outcomes of anemia in geriatrics: A systematic review of the literature. Am J Med 2004;116(suppl 7A):3S-10S.
8. Balducci L, Hardy CL, Lyman GH. Hemopoietic reserve in the older cancer patient: Clinical and economic considerations. Cancer Control 2000;7:539-547.
9. Leng S, Chaves P, Koenig K, Walston J. Serum interleukin-6 and hemoglobin as physiological corrrelates in the geriatric syndrome of frailty: A pilot study. J Am Geriatr Soc 2002;50:1268-1271.
10. Ershler WB. Biological interactions of aging and anemia: A focus on cytokines. J Am Geriatr Soc 2003;51(3 suppl):S18-S21.
11. Ershler WB, Sheng S, McKelvey J, et al. Serum erythropoietin and aging: A longitudinal analysis. J Am Geriatr Soc 2005;53(8):1360-1365.
12. Lipschitz D. Medical and functional consequences of anemia in the elderly. J Am Geriatr Soc 2003;51(3 suppl):510-513.
13. Ettinger MP. Aging bone and osteoporosis: Strategies for preventing fractures in the elderly. Arch Intern Med 2003;163:2237-2246.
14. Cesari M, Pahor M, Lauretani F, et al. Bone density and hemoglobin levels in older persons: Results from the InCHIANTI study. Osteoporos Int 2005;16:691-699. Published Online: September 28, 2004.
15. Cesari M, Penninx BW, Lauretani F, et al. Hemoglobin levels and skeletal muscle: Results from the InCHIANTI study. J Gerontol A Biol Sci Med Sci 2004;59:249-254.
16. Penninx BW, Guralnik JM, Onder G, et al. Anemia and decline in physical performance among older persons. Am J Med 2003;115:104-110.
17. Chaves PH, Ashar B, Guralnik JM, Fried LP. Looking at the relationship between hemoglobin concentration and prevalent mobility difficulty in older women. Should the criteria currently used to define anemia in older people be reevaluated? J Am Geriatr Soc 2002;50:1257-1264.
18. Penninx BW, Pluijm SM, Lips P, et al. Late-life anemia is associated with increased risk of recurrent falls. J Am Geriatr Soc 2005;53:2106-2111.
19. Duh MS, Mody SH, Lefebvre P, et al. Anemia in the elderly and the risk of injurious falls. Poster presented at: 2005 American Society of Hematology; December 10-13, 2005; Atlanta, GA.
20. Atti AR, Palmer K, Volpato S, et. al. Anaemia increases the risk of dementia in cognitively intact elderly. Neurobiol Aging 2006;27:278-284.
21. Chaves PH, Carlson MC, Ferrucci L, et al. Association between mild anemia and executive function impairment in community-dwelling older women: The Women’s Health and Aging Study II. J Am Geriatr Soc 2006;54:1429-1435.
22. Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med 2006;119:327-334.
23. Kosiborod M, Smith GL, Radford MJ, et al. The prognostic importance of anemia in patients with heart failure. Am J Med 2003;114:112-119.
24. Muzzarelli S, Pfisterer M; TIME Investigators. Anemia as independent predictor of major events in elderly patients with chronic angina. Am Heart J 2006;152:991-996.
25. Cavusoglu E, Chopra V, Gupta A, et al. Usefulness of anemia in men as an independent predictor of two-year cardiovascular outcome in patients presenting with acute coronary syndrome. Am J Cardiol 2006;98:580-584. Published Online: June 28, 2006.
26. Chaves PH, Xue Q, Guralnik JM, et al. What constitutes normal hemoglobin concentration in community-dwelling disabled older women? J Am Geriatr Soc 2004;52:1811-1916.
27. Penninx BW, Pahor M, Woodman RC, Guralnik JM. Anemia in old age is associated with increased mortality and hospitalization. J Gerontol A Biol Sci Med Sci 2006;61:474-479.
28. Kikuchi M, Inagaki T, Shinagawa N. Five-year survival of older people with anemia: Variation with hemoglobin concentration. J Am Geriatr Soc 2001;49:1226-1228.
29. Scarlett JD, Read H, O’Dea K. Protein-bound cobalamin absorption declines in the elderly. Am J Hematol 1992;39:79-83.
30. Valuck RJ, Ruscin JM. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. J Clin Epidemiol 2004;57:422-428.
31. Ruscin JM, Page RL, Valuck RJ. Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor. Ann Pharmacother 2002;36:812-816.
32. Artz AS, Fergusson D, Drinka PJ, et al. Mechanisms of unexplained anemia in the nursing home. J Am Geriatr Soc 2004;52:423-427.
33. Rothstein G. Disordered hematopoiesis and myelodysplasia in the elderly. J Am Geriatr Soc 2003;51(3 suppl):S22-S26.
34. Tilly-Gentric A, Malo JP, Marion V. Primary myelodysplasia: Management and outcome at 3 years in 45 patients age 65 and older. J Am Geriatr Soc 2001;49:1358-1360.
35. Woodman R, Ferrucci L, Guralnik J. Anemia in older adults. Curr Opin Hematol 2005;12:123-128.
36. Guralnik JM, Eisenstaedt RS, Ferrucci L, et al. Prevalence of anemia in persons 65 years and older in the United States: Evidence for a high rate of unexplained anemia. Blood 2004;104:2263-2268. Published Online: July 6, 2004.
37. Kuzminski AM, Del Giacco EJ, Allen RH, et al. Effective treatment of cobalamin eeficiency with oral cobalamin. Blood 1998;92:1191-1198.
38. Kuzminski AM, Del Giacco EJ, Allen RH, Sabler SP. Oral cobalamin therapy in patients who absorb it normally. Blood 1998;92:4879-4880.