Focus on: Anemia in the Elderly

Anemia is a common finding inelderly patients. The World Health

Organization (WHO) criteria for ane-mia are a hemoglobin of < 120 g/L forwomen and < 130 g/L for men. Usingthese values, the prevalence of anemiaranges from as low as 8% for 70-year-olds, to more than 40% for those overage 85.1-4

What are the symptoms?Fatigue, dyspnea, and other typicalsymptoms often occur with less severeanemia in elderly patients than wouldbe expected with younger adults. Thesymptoms of other diseases may beexacerbated if anemia is also present.Therefore, anemia should be consid-ered when patients present with wors-ening of heart or lung disease. Anemiacan also contribute to problems, suchas decreased mobility, dizziness, cog-nitive impairment, and even depres-sion. These medical conditions, or theaging process itself, are often blamed

The Canadian Journal of Diagnosis / November 2003 83

Peter R. Duggan, MD, FRCPC

As presented at Memorial University’s GeriatricRefresher conference (May 10, 2003)

Focus on:

Anemia in the Elderly

Karen’s caseKaren, 68, has a long history ofrheumatoid arthritis. For severalyears, her disease has been inactive and has not requiredtreatment. However, for the pastsix months, she has experienced worsening jointpain and stiffness, especially inthe mornings, along with progressive fatigue. In additionto active arthritis on physicalexam, she is noted to be paleand tachycardic.

• What is the mostlikely cause of heranemia?

• What treatmentapproach is recommended?

• Is iron replacement therapy required?

• Is colonoscopy/endoscopy orbone marrow biopsy indicated?

For more onKaren, go to page86.

Laboratory investigations

• Rheumatoid factor:Reactive, 640 IU/mL

• White blood cells: 14.2x109/L (4.8-10.8 x109/L)

• Hemoglobin: 98 g/L (120-160 g/L)

• MCV: 76 g/L (81-97 g/L)

• Platelets: 390 x109/L (150-400 x109/L)

• ESR: 71 mm/h (0-20 mm/h)

• Ferritin: 426 g/L (11-307 g/L)

MCV: Mean corpuscular volumeESR: Erythrocyte sedimentation rate

The Canadian Journal of Diagnosis / November 200384


for patients’ complaints, causing the presence ofanemia to be overlooked.

There are many possible causes of anemia(Table 1). Among hospitalized patients, anemiaof chronic disease (ACD) and iron deficiencyanemia (IDA) are the most common findings.5

In about 20% of patients, no underlying causeof anemia can be found.3,5

Renal failure is an important cause of anemiafor patients of all ages. Although renal functionshows a steady decline with age, the overallmagnitude of this decline is small withoutunderlying renal disease.6 Since anemia fromrenal impairment is not seen until more signifi-cant renal dysfunction is present, this age-relat-ed change alone is probably not responsible forsignificant anemia in the elderly.

What investigations canbe done?

The decision to investigate anemia will dependon the severity of anemia and the presence ofother laboratory and clinical findings. It wouldbe reasonable to consider a hemoglobin value of110 g/L to 120 g/L as a threshold for investigat-ing anemia. (Above these values, anemia isunlikely to affect quality of life.) However, thedecision to investigate any patient at any levelof hemoglobin must be based on the individualcase and clinician’s judgement. Observation canbe considered if there are no other blood abnor-malities (Table 2).

The mean corpuscular value (MCV) is usefulfor differentiating between common causes ofanemia and deciding on a course of investiga-tion (Figure 1). In most cases, elderly patients

Table 1

Common causes of anemia

• Anemia of chronic disease

• Iron deficiency anemia

• Vitamin B12 deficiency

• Folate deficiency

• Myelodysplasia

• Bleeding

• Chronic leukemia, lymphoma, or myeloma

Table 2

Indications for investigating anemia

• Hemoglobin < 110-120 g/L

• Progressive anemia

• Leukopenia or leukocytosis

• Thrombocytopenia

• High or low MCV

• Other clinical or laboratory abnormalities

MCV: Mean corpuscular value


Dr. Duggan is an assistant professor, faculty ofmedicine, Memorial University of Newfoundland, andstaff physician, internal medicine, Health SciencesCentre, St. John’s, Newfoundland.

Table 3

Useful investigations

• Complete blood cell count

• Peripheral blood smear

• Reticulocyte count

• Serum ferritin (if low MCV)

• B12, folate (if high MCV)

• Creatinine

• Serum protein electrophoresis

MCV: Mean corpuscular value

Figure 1. Common causes of anemia according to MCV.

Low MCV• Iron deficiency• Anemia of chronic

disease

Normal MCV• Anemia of chronic

disease• Renal failure• Leukemia, lymphoma,

myeloma• Bleeding

Anemia

High MCV• Vitamin B12 deficiency• Folate deficiency• Myelodysplasia• Chronic liver disease

MCV: Mean corpuscular volume



will present with normochromic, normocyticanemia. Occasionally anemia of iron, B12, orfolate deficiency can present before changes inthe MCV are seen, so that the actual diagnosis isnot initially suspected. Tests that may be usefulin the initial investigation of patients are listedin Table 3.

What are the differenttypes of anemia?

IDAThe serum ferritin is the most accurate test fordiagnosing IDA. Ferritin is often low before theMCV becomes abnormal, especially early in thedevelopment of IDA. As the iron deficiencyworsens, the MCV falls along with hemoglobin.Iron deficiency is almost always present whenthe serum ferritin is < 15 g/L. It is less likely, butmay still be present, with serum ferritin as highas 100 g/L. Serum iron is usually low in IDA,but the total iron binding capacity (TIBC) is ele-vated.

Iron deficiency is the cause of anemia in 10%to 15% of elderly patients. It is rarely caused bynutritional deficiency and is usually due to bloodloss through the gastrointestinal (GI) tract. GIblood loss is often occult and is not ruled out bynegative fecal blood tests. Therefore, investiga-tion of the GI tract should usually be undertakenwhen IDA occurs in the elderly, especially to ruleout malignancy. Numerous lesions can be respon-sible (Table 4). Upper GI tract lesions are mostcommon, accounting for IDA in 40% to 50% ofelderly patients. For as many as 40% of patientswith IDA, no source of blood loss can be founddespite extensive investigation. Fortunately thesepatients do well with iron replacement, and repeatinvestigation is not often needed.7,8

Table 4

Sources for GI blood loss

• Esophagitis

• Varices

• Peptic ulcer disease

• NSAID use

• Gastric cancer

• Inflammatory bowel disease

• Angiodysplasia

• Colorectal cancer

• Benign polyps

NSAID: Non-steroidal anti-inflammatory drugGI: Gastrointestinal

A followup on KarenThe patient likely has anemia of chronic disease, acommon finding with active rheumatologic diseases.

Iron deficiency is very unlikely, as the serum ferritinis not low. Iron replacement would not be helpful,and investigation of the gastrointestinal tract is notindicated.

The best therapy for anemia of chronic disease isto treat the underlying cause, in this case thepatient’s rheumatoid arthritis. Bone marrow biopsywould not be needed at this time, but would beconsidered if the anemia does not improve witharthritis treatment.

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Treatment of IDA anemia includes treatingthe source of blood loss once it is identified.Oral iron replacement three times daily is usual-ly effective. This measure often results in consti-pation and other GI side-effects, which can bereduced by lowering the dose to once or twicedaily. If oral iron is not effective or not tolerated,intramuscular and intravenous iron preparationsare available.

ACDACD is caused by inflammatory cytokines pro-duced in response to many acute and chronicconditions

Unlike IDA, the TIBC is usually normalor low in ACD. The serum ferritin is themost useful test for differentiating the two.Ferritin will increase with inflammation asan acute phase reactant and, as a result, isoften high in ACD. A serum ferritin > 100g/L is unlikely to occur in IDA and is morein keeping with ACD. In a minority ofcases, iron studies cannot distinguishbetween IDA and ACD as the cause ofmicrocytic anemia. In these situations, abone marrow aspirate may be required fordiagnosis.

ACD is unlikely to resolve without treat-ment of the underlying disorder. Ironreplacement is not helpful unless iron defi-ciency is also present.

Vitamin B12 and folate deficiencyBoth vitamin B12 and folate deficiency arecommon among the elderly, each occurringin 5% to 10% of patients. These deficien-

cies will usually produce macrocytic anemia.Vitamin B12 and folic acid levels should bechecked when anemia is associated with a highMCV. Occasionally the MCV will be normal,and vitamin deficiencies should be considered incases of normocytic anemia in which no causecan be found. Because neurologic side-effects ofB12 deficiency can occur without anemia, someexperts recommend screening all elderly patientsat least once for occult B12 deficiency. False pos-itive and false negative results are possible withvitamin B12 testing, especially with results in thelow normal range, which may not accuratelyreflect true tissue levels. Serum methylmalonic



acid (MMA) levels can be very helpful in thissetting, as an elevation of serum MMA is veryspecific for vitamin B12 deficiency.

Treatment of vitamin B12 deficiency usuallyinvolves intramuscular injection of vitamin B12,100 g to 1000 g daily for three to seven days, fol-lowed by maintenance injections every one tothree months. Oral preparations are also avail-able. Folate deficiency is treated with oral folicacid, 1 mg daily.

Myelodysplastic syndromesMyelodysplastic syndromes (MDS) usually pres-ents with anemia, along with abnormalities ofwhite blood cells and platelets. MDS is rare beforeage 50, but much more common in the elderly,occurring in up to 5 % of those over 65. MDSshould be suspected in cases of unexplained orunresponsive anemia, or anemia with abnormali-ties of the other blood cells. Bone marrow aspira-tion and biopsy are required for diagnosis.

Numerous therapeutic options exist, includ-ing chemotherapy, immunosuppression, andgrowth factors, such as granulocyte colony-stim-ulating hormone and erythropoietin. Theresponse to most therapies is limited, however,and treatments have not been shown to improvesurvival. For this reason, treatment is limited totransfusion and other supportive care measuresfor most elderly patients.

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For an electronic version of this article, visit: The Canadian Journal of Diagnosis online.

Frequently Asked Questions

1. When is GI tract workup indicated?

A GI tract cause for anemia should be suspected in any elderly patient presentingwith iron deficiency. Iron deficiency should firstbe confirmed with serum ferritin testing. A GItract lesion should also be considered if thereis evidence of GI blood loss or unexplainedabdominal symptoms.

2. Do anemic elderly patients have a poorerquality of life?

Anemia does seem to predict poorer quality oflife and survival in the elderly. Anemia canworsen the outcome of heart and lung disease, as well as other medical problemsand the cause of anemia itself can be associated with poor prognosis.

3. What is the role for erythropoietin therapyin anemic elderly patients?

Erythropoietin is very effective in treating anemia associated with chronic renal failureand can be helpful in treating anemia in cancerpatients and HIV-infected patients. High dosesof erythropoietin may benefit some patientswith ACD or myelodysplasia.

4. Are bone marrow biopsy and aspirate helpful in finding the cause for anemia inthe elderly?

Most anemic elderly patients will not needbone marrow biopsy and aspirate, as thecause of anemia can usually be determinedusing less invasive investigations. Bone marrow biopsy and aspirate should probablybe performed if there is pancytopenia or otherabnormalities of the white blood cells orplatelets, or if a monoclonal gammopathy ispresent.

Dx

References1. Salive ME, Cornoni-Huntley J, Guralnik JM, et al: Anemia and hemo-

globin levels in older persons: Relationship with age, gender, andhealth status. J Am Geriatr Soc 1992; 40(5):489-96.

2. Ania BJ, Suman VJ, Fairbanks VF, et al: Prevalence ofanemia in medical practice: Community versus referralpatients. Mayo Clin Proc 1994; 69(8):730-5.

3. Ania BJ, Suman VJ, Fairbanks VF, et al: Incidence of ane-mia in older people: An epidemiologic study in a welldefined population. J Am Geriatr Soc 1997; 45(7):825-31.

4. Nisson-Ehle H, Jagenburg R, Landahl S, et al: Bloodhemoglobin declines in the elderly: Implications for ref-erence intervals from age 70 to 88. Eur J Haematol2000; 65(5):297-305.

5. Joosten E, Pelemans W, Hiele, M, et al: Prevalence andcauses of anemia in a geriatric hospitalised population.Gerontology. 1992; 38(1-2):111-7.

6. Rowe JW, Andres R, Tobin JD, et al: The effect of age oncreatinine clearance in men: A cross-sectional and lon-gitudinal study. J Gerontol 1976; 31(2):155-63.

7. Gordon S, Bensen S, Smith R: Long-term follow-up ofolder patients with iron deficiency anemia after a neg-ative GI evaluation. Am J Gastroenterol 1996;91(5):885-9.

8. Horwich TB, Fonarow GC, Hamilton MA, et al: Anemia isassociated with worse symptoms, greater impairment infunctional capacity and a significant increase in mortal-ity in patients with advanced heart failure. J Am CollCardiol 2002; 39(11):1780-6.


• Some causes of anemia include chronic disease, iron deficiency, vitamin B12 deficiency,folate deficiency, and myelodysplasia.

• MCV is a useful tool to determine the cause of anemia.• Treatment differs depending on the cause, ranging from iron replacement to supportive care

measures.

Take-home message

Focus on: Anemia in the Elderly

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