Elderly Anemia: Evaluation & Management Guidelines - Essay Sample

Abstract

Anemia is now recognized as a risk factor for a number of adverse outcomes in the elderly, including hospitalization, morbidity, and mortality. What constitutes appropriate evaluation and management for an elderly patient with anemia, and when to initiate a referral to a hematologist, are significant issues. Attempts to identify suggested hemoglobin levels for blood transfusion therapy have been confounded for elderly patients with their comorbidities. Since no specific recommended hemoglobin threshold has stood the test of time, prudent transfusion practices to maintain hemoglobin thresholds of 9-10 g/dL in the elderly are indicated, unless or until evidence emerges to indicate otherwise. Am. J. Hematol. 89:88-96, 2014. 2013 Wiley Periodicals, Inc.

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Introduction

Anemia is now recognized as a risk factor for a number of adverse outcomes in older adults, including hospitalization, morbidity, and mortality 1-7. The elderly is an important demographic population that is growing rapidly in the context of increasing prevalence of anemia with age 8. An analysis of two databases found that normal ranges for hemoglobin values are unchanged for aging populations, with the exceptions of minor adjustments for males (Table 1) 9. More than 10% of communitydwelling adult 65 years of age have a World Health Organization (WHO)-defined anemia (hemoglobin <12 g/dL in women and <13 g/dL in men). After 50 years of age, prevalence of anemia increases with advancing age and exceeds 20% in those 85 years of age 10. As illustrated in Fig. 1 11, there is a Jshaped correlation of anemia with mortality in older men and women. A recent study has analyzed the impact of declines (rather than an absolute level) in hemoglobin in 3,759 nonanemic elderly participants from the Cardiovascular Health Study 12, a prospective randomized cohort of communitydwelling elderly patients 65 years of age followed for up to 16 years. The authors found that hemoglobin decreases identified a large group of elderly individuals at risk for subsequent adverse outcomes (worse cognitive function) who would not be identified using the WHO anemia criteria.

Lower Limits of Normal for Hemoglobin Concentration for White and Black Adults

Group Hemoglobin (g/dL)

White men (yr) 20-59 13.7

60+ 13.2

White women (yr) 20-49 12.2

50+ 12.2

Black men (yr) 20-59 12.9

60+ 12.7

Black women (yr) 20-49 11.5

50+ 11.5

From Beutler et al. 9.

Figure 1

Open in figure viewerPowerPointRelationship between hemoglobin (Hb) concentration and 5year allcause mortality in communitydwelling, disabled older women. Graphical display of relative risk estimates for the mortality linked to specific Hb concentrations compared with the risk linked to Hb of 12 g/dL. The curve represents smoothed relative mortality hazards across Hb concentrations, and the bars indicate their 95% confidence intervals. Indicated also is the 13.9 g/dL Hb threshold at which the slope of mortality risk decline was no longer statistically significant (i.e., the 95% confidence interval for the slope of the tangent included 0). The yaxis was transformed so that, for example, the graphical display of an increase in risk of the magnitude of two (hazard ratio [HR] 52) would be equivalent to that of a decrease in risk of the same magnitude (HR 50.5) in terms of scale size. Reproduced from Chaves et al. 11.

With increasing recognition of the importance of anemia in the general population, guidelines have been published for the detection, evaluation, and management of anemia in medical 13 and surgical 14 patients. However, for elderly patients, attempts to identify suggested hemoglobin levels for management of anemia, including blood transfusion therapy, have been confounded by increased risks from anemia, along with additional comorbidities. What constitutes an appropriate workup for an elderly patient with anemia; and when to refer the patient to a hematologist, given the potentially large number of subjects involved, are significant costsbenefit issues 15. In this review, we summarize our approach for management of anemia in the elderly, with a focus on transfusion therapy.

Characterization of Anemia in the Elderly

An important contribution was made by the NHANES III investigators who did a laboratory evaluation of over 5,000 communitydwelling elderly subjects, 10% of whom had anemia according to the WHO criteria. For the most part the anemia is mild, with hemoglobin levels infrequently <10 g/dL 8. Nevertheless, this mild anemia has been associated with significant negative outcomes, including decreased physical performance 16, increased number of falls 17, increased frailty 18, decreased cognition 18, increased dementia 19, increased hospitalization 1, and increased mortality 7. The NHANES III investigators used fixed laboratory measures to determine that about onethird of these anemic patients have evidence of a nutritional deficiency, primarily that of iron; onethird have chronic inflammation or chronic kidney disease (CKD); and onethird have unexplained anemia 8.

Unexplained anemia of the elderly (UAE) is a real entity characterized by a hypoproliferative normocytic anemia that is not due to the nutritional deficiency, CKD or inflammatory disease; and in which the erythropoietin response to anemia appears to be blunted. In a study of 124 anemic elderly (65 years) persons, 42 (37%) had UAE 20. These patients had significantly lower Creactive protein (CRP) levels than nonanemic controls. Additionally, hepcidin levels do not seem to increase with age in the general population. Hepcidin levels in the anemia of aging change with comorbid conditions (low in irondeficiency anemia and higher in inflammatory conditions); however, in patients with UAE, who have no identifiable comorbidities, hepcidin levels remain in the normal range 20-22. These observations could be because UAE is heterogeneous, in which diverse underlying causes such as impaired erythropoietin response to anemia and or an underlying stem cell disorder, may confound an effect from hepcidin 21. The role of testosterone deficiency in males is currently being studied by an National Institute of Aging (NIA) funded consortium.

Typically, in persons 65 years of age or older there is an underlying etiology for the anemia such as chronic disease, iron deficiency, or myelodysplastic syndromes that can be identified by further investigation 23. In a study of 232 patients aged 65 to 98 (median 81) years of age, 24% were found to be anemic 24. Of these, after a comprehensive workup 17% did not have an identifiable underlying cause. The major causes of anemia and their prevalence in the elderly are illustrated in Fig. 2 25: prevalence ranges from three studies 8, 26, 27 are for UAE (34%-44%); iron deficiency (12%-25%); CKD (4%-8%); MDS (9%-16%); malignant hematologic (e.g., chronic lymphocytic leukemia) disorder (2%); or inflammation (6%-20%). Interestingly, folic acid deficiency has disappeared in the U.S. population, probably as a result of fortification of flour 26, 27. While 10%-20% of elderly patients have been described as Vitamin B12 deficient (defined by reduced serum levels of Vitamin B12) 28, 29, clinically significant Vitamin B12 deficiency is uncommon, diagnosed in only 1/190 26 and 1/174 subjects 27 in two studies, respectively. For emphasis that means that as a cause of macrocytosis, Vitamin B12 deficiency is much less common than MDS or ethanol abuse.

Figure 2

Open in figure viewerPowerPointPrevalence of anemia in the elderly. Prevalence of anemia in the elderly by cause identified in three studies. Studies shown are National Health and Nutrition Survey (NHANES) III 8, Chicago 27, and Stanford Hospital & Clinics, VA Palo Alto Health Care System (SHC/VAPAHCS) 26. AI, anemia of inflammation; CKD, anemia secondary to renal disease; Hem Malig, hematologic malignancy; IDA, irondeficiency anemia; Susp MDS, suspicious for myelodysplastic syndrome; Thal, thalassemia; UAE, UAE. Reproduced, From Pang, Schrier 25. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Studies at two academic institutions using comprehensive clinical and hematologic analyses have refined the prevalence and causes of anemia in the elderly 26, 27. Iron deficiency anemia represented the most common cause of anemia in the elderly, at 25.3% 27. Iron deficiency may be due to the nutritional deficiency or blood loss; in the relatively affluent Western world, blood loss is the major issue. The cause of blood loss must be identified since in this patient group, iron deficiency could be a sign of a serious disorder such as colon cancer 30-33. Furthermore, in this patient group one cannot use simple laboratory tests based on transferrin saturation and ferritin levels to readily differentiate between iron deficiency and inflammation as a cause of anemia.

A number of studies have demonstrated that IL6 levels increase with aging, and are correlated with the development of anemia in the elderly 23, including healthy women 34, such as the Framingham Heart Study 35, and the Established Populations for Epidemiologic Studies of the Elderly (EPESE) 36. More recently, studies of IL6 and hepcidin levels have not been found these to be elevated in elderly patients who do not have comorbid diseases 20-22. There may be several reasons for these discrepant results. First, if aging is associated with only small increases in IL6, one would need a large sample size for detection. Additionally, currently these assays measure the monomeric form of IL6, which also exists as a multimer complicating the analysis.

Evaluation of Anemia

Commonly identified when the elderly are scheduled for elective surgical procedures. Anemia is a common condition in surgical patients and is independently associated with increased perioperative mortality 37. When preadmission testing prior to elective surgery reveals anemia, it should therefore be viewed as a significant and treatable medical condition, rather than as simply an abnormal laboratory value 38. The diagnosis of an unexpected anemia in patients scheduled for elective surgery in which significant blood loss is anticipated, should be considered an indication for rescheduling elective surgery until evaluation and management of anemia is accomplished.

In traditionally taught approaches to evaluating a patient with anemia, the mean corpuscular volume (MCV) typically has been used as a starting indice 39, followed by biochemical analysis. The MCV has been shown to add value to the red cell distribution width (RDW) for evaluation of macrocytosis 40. However, for microcytic anemias, MCV is of less value, particularly for patients with iron deficiency who have comorbidities. Twentytwo percent of elderly patients can be identified as having iron deficiency anemia by their response to a course of ORAL iron therapy, despite not having the typical laboratory findings of transferrin saturation <16% and ferritin <30 ng/mL 25. When transferrin saturation is low (<16%) and the ferritin level is high (>200 ng/mL), the diagnosis of anemia of inflammation is generally considered 41. However, the MCV is normal in 70% of patients with anemia of inflamm...