Pearl Toy MD
ESSENTIALS OF DIAGNOSIS
Anemia in elderly people is due to disease and not aging. Conditions that cause anemia are more common in the elderly (eg, malignancy, infection, and gastrointestinal bleeding). Even if there is no apparent clinical disease, anemia in the elderly deserves investigation.
Izaks GJ et al: The definition of anemia in older persons. JAMA 1999;281:1714. [PMID: 10328071] (A study of anemia in 755 patients older than 85.)
Symptoms of anemia increase with severity, beginning with mild fatigue and progressing to decreased mobility, dyspnea on exertion, angina, loss of concentration, cognitive impairment, and confusion. Even in the normovolemic young and healthy adult, acute anemia below a hemoglobin (Hgb) of 7 g/dL impairs cognitive function and memory. If blood loss leads to hypovolemia, patients may have dizziness on standing.
A sign of anemia is tachycardia. Electrocardiography may show ischemic changes. With hypovolemia, orthostatic hypotension occurs. Pallor, although common, is not a reproducible sign among different observers.
Weiskopf RB et al: Acute severe isovolemic anemia impairs cognitive function and memory in humans. Anesthesiology 2000;92:1646. [PMID: 10839915]
World Health Organization: Nutritional anaemias: report of a WHO scientific group. World Health Organization, 1968.
In the anemic patient, initial tests should include Hgb, hematocrit (Hct), red blood cell count and indices, reticulocyte count, white blood cell count and differential, and platelet count.
To assess whether the marrow has increased red cell production in response to anemia, calculate the reticulocyte production index:
Reticulocyte production index (RPI) = % Reticulocytes[circled times]Hct/45[circled times]0.5.
Reticulocyte production index (RPI) = % Reticulocytes [circled times] Hct/45 [circled times] 0.5.
The RPI corrects for the degree of anemia (normalized to a Hct of 45%) and for the doubling in survival of shift reticulocytes. Normal RPI is approximately 1.0. Values>2.0 indicate increased marrow response to anemia.
Bone marrow examination is usually not needed in the evaluation of anemia. Indications for bone marrow aspirate and biopsy include pancytopenia or blast cells in the circulation.
Blood loss is most commonly from the gastrointestinal or genitourinary tract. Iron deficiency implies chronic occult blood loss. Common sources include carcinoma, ulcer, atrophic gastritis, gastritis from drug ingestion, bleeding hemorrhoids, angiodysplasia of the colon, and vaginal bleeding.
Anemia of chronic disease is the most common normocytic anemia in the elderly but becomes microcytic in later stages. Chronic diseases include inflammation and cancer. Anemia is also associated with chronic renal insufficiency and liver disease.
Serum ferritin is normal or elevated in anemia of chronic disease as a result of inflammation or cancer. Subcutaneous erythropoietin is used to treat anemic patients with renal insufficiency or cancer when the Hgb is < 10 g/dL. For cancer patients on chemotherapy with anemic symptoms, subcutaneous erythropoietin 3 times/week (150 U/kg) for a minimum of 4 weeks improves quality of life. Dosage should be titrated once the Hgb concentration reaches 12 g/dL. If there is no response, no benefit is observed beyond a 6- to 8-week trial.
Rizzo JD et al: Use of epoietin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. Blood 2002;100:2303. [PMID: 12239138]
Iron deficiency anemia is characterized by small, pale red cells and depleted iron stores. Serum ferritin reflects iron stores, and a level < 10µg/L is diagnostic of iron deficiency. However, serum ferritin levels are increased in inflammation, liver disease, and states of increased red cell turnover. Iron deficiency implies blood loss if the patient does not have malabsorption and has not had total gastrectomy.
Oral iron therapy is inexpensive, safe, and convenient. Iron sulfate 300 mg (60 mg elemental iron) orally 3 times/day between meals should increase the Hgb concentration approximately 2 g/dL over 3 weeks. Addition of 250 mg ascorbic acid at the time of iron administration enhances iron absorption. For elderly patients, iron sulfate is often given only once daily to minimize gastrointestinal side effects. Gastrointestinal side effects relate to the amount of elemental iron ingested. Patients with gastric side effects may titrate to a tolerable dose with elixir of ferrous sulfate (45 mg of elemental iron per 5 mL). If full replenishment of iron stores is desired, therapy can continue for 6 mo after the Hgb becomes normal.
Both vitamin B12 and folate deficiency cause a macrocytic anemia. Deficiency of either vitamin should be suspected with macrocytosis (with or without anemia), pancytopenia, and unexplained neurological and psychiatric signs and symptoms in the elderly as well as in those with alcoholism and malnutrition. An important distinction is that vitamin B12 causes neurological disease such as dorsal column peripheral neuropathy, incontinence, and dementia, whereas folate does not. Low stomach acidity is present in 15% of elderly persons and is the major cause of vitamin B12 deficiency. Other causes include gastrectomy, small bowel disease of surgery, prolonged use of antacids, and a strict vegan diet. Folate deficiency can be caused by malabsorption, poor nutrition, alcoholism, and chronic hemolysis.
In making a diagnosis, if serum folate is>4 ng/mL and vitamin B12 concentration is > 300 pg/mL, deficiencies of the 2 vitamins are unlikely, and additional testing is not required. If the patient has low or low–normal (< 300 pg/mL) vitamin B12 levels, deficiency can be diagnosed by elevated homocysteine and methylmalonic acid (MMA) levels in patients without renal failure. Among the elderly, estimates of the prevalence of vitamin B12deficiency, defined as increased MMA, vary from 15–44%. Serum or even red blood cell folate levels fluctuate and do not necessarily reflect body stores. In folate deficiency, serum homocysteine is elevated but MMA levels are normal. Because folate does not reverse neurological damage of vitamin B12deficiency, B12 deficiency must be ruled out before treatment with folate.
Both deficiencies can be easily repleted: folate deficiency with folic acid, 1 mg/day, and vitamin B12 deficiency
with a regimen of vitamin B12, 1000 µg/day for the first week, 1000µg/week for 4 weeks or until the Hct is normal, and then 1000 µg/mo for life. Treatment is somewhat controversial in patients with low–normal vitamin B12 but elevated MMA levels (0.40–2.00 µmol/L). Treatment improves test results and neurological symptoms in patients with MMA levels > 0.60µmol/L, but objective neurological tests do not improve.
Hvas AM et al: Vitamin B12 treatment normalizes metabolic markers but has limited clinical effect: a randomized placebo-controlled study. Clin Chem 2001;47:1396. [PMID: 11468228] (In patients with mildly to modestly increased P-MMA [0.40–2.00µmol/L] not previously treated with vitamin B12, vitamin B12 treatment was associated with improved neurological symptoms but not improved neurological tests in patients with MMA > 0.60µmol/L or homocysteine>15µmol/L.)
Whereas young patients can tolerate low Hgb concentrations, the elderly cannot because of underlying cardiopulmonary disease. The red blood cell transfusion trigger is not clear; however, among patients 65 years of age and older with acute myocardial infarction, blood transfusion is associated with a lower short-term mortality rate if the hematocrit on admission is≤30% (Hgb 10 g/dL). In addition, it may be effective in patients with a hematocrit as high as 33% (Hgb 11 g/dL) on admission.
Elderly patients are especially susceptible to fluid overload, and each unit of red blood cell transfusion should be given slowly over 4 h if the patient is not acutely bleeding. In addition, diuretics may be indicated.
Wu WC et al: Blood transfusion in elderly patients with acute myocardial infarction. N Engl J Med 2001;345:1230. [PMID: 11680442]
The mortality risk in elderly anemic patients with or without obvious clinical disease is about twice that of nonanemic patients.
Izaks GJ et al: The definition of anemia in older persons. JAMA 1999;281:1714. [PMID: 10328071] (A study of anemia in 755 older than 85.)