Anemia is generally defined as a medical condition in which the number or function of erythrocytes or red blood cells (RBCs) is inadequate to meet tissue oxygenation needs. The body is unable to compensate for this reduction in the number of circulating erythrocytes.

The World Health Organization (WHO) defines anemia as a hemoglobin (Hgb) level less than 12 g/dL for women and less than 13 g/dL for men. An Hgb level of 10–11.9 g/dL for women and 11–12.9 g/dL for men is classified as mild anemia. However, it is important to note that the use of Hgb level to define anemia has been controversial. In countries in which nutritional deficiencies, infection, or congenital blood disorders are common, it may be difficult to apply a universal Hgb cutpoint.

Chronic severe anemia in the elderly may lead to cardiac functional abnormalities. The reduction in tissue oxygen delivery and the compensatory tachycardia that invariably follows may, in time, lead to impaired ventricular systolic function.Functional cardiac abnormalities occur when Hgb levels fall below 7–10 g/dL in patients without heart disease. In the presence of heart disease, the Hgb level should be kept above 10 g/dL.

SIGNS AND SYMPTOMS OF ANEMIA

Elderly patients with anemia may have vague, non-specific symptoms, and because the symptoms are non-specific, they are often overlooked or of limited help in differentiating between the types of anemia. Older patients are at greater risk for falls, cognitive decline, fatigue, and weakness as a result of advanced age, making the identification of anemia even more difficult. Patients with mild anemia may remain asymptomatic. New-onset, easy fatigue, increased weakness, and shortness of breath are useful clues. Other symptoms may include tachycardia, bradycardia, dyspnea, chest pain, dizziness, headache, cold hands and feet, restless legs syndrome, and tarry stools. On occasion, patients may complain of visible changes in or discomfort of the tongue or lips, indicative of atrophic glottis and cheilitis. The severity of symptoms is dependent on the rapidity of onset, degree of anemia, physical status, and age of the patient. Because anemia may be multifactorial, complete evaluation is necessary.

MOST COMMON CAUSES OF ANEMIA IN ELDERLY

The most common causes of anemia in the elderly include gastrointestinal bleeding, renal insufficiency, chronic inflammation, blood disorder, medication adverse effects, drug/alcohol abuse, and dietary deficiency. Depending on the cause, anemia may be acute or chronic. Acute blood loss can create an emergency situation requiring immediate attention. In contrast, patients with chronic anemia lose blood over an extended period of time, and the risks are less immediate.

Blood loss commonly occurs in the gastrointestinal tract secondary to gastric ulcers, gastritis, colitis, diverticulitis, and cancer. Anemia may also develop secondary to hemolysis, or the destruction of erythrocytes characterized by RBCs’ failure to live the usual 120 days. It can have various causes, ranging from genetic disorders to mechanical heart valve and medication side effects.

A reduction in RBC production can also result in anemia. This may be related to bone marrow suppression due to medication adverse effects and myelodysplasia, or decreased bone marrow production associated with aging. In some older patients, reduced kidney function will result in decreased erythropoietin production, which in turn causes decreased production of RBCs in the bone marrow.

CHRONIC INFLAMMATION

Anemia of inflammation and chronic disease (AI/ACD) is commonly seen in older patients. It is defined as a low serum iron and RBC levels despite iron stores that are normal or high, the result of blocked delivery of iron to developing RBCs and reduced intestinal absorption.

Older adults tend to have increased levels of pro-inflammatory cytokines secondary to multiple comorbid illnesses. Cytokines are chemical messengers of the body that mediate immune or inflammatory response and include tumor necrosis factor, interleukin-1, and the interferons. Over time, the presence of these messengers reduces absorption of iron, decreases the release of iron, and interferes with RBC production. As a result, AI/ACD is significantly more common in older patients, particularly those with chronic disorders. AI/ACD may be diagnosed only when other etiologies of anemia are excluded. In difficult cases, bone marrow aspiration/biopsy may be necessary to confirm the diagnosis.

NUTRIENT-DEFICIENCY ANEMIA

Nutrient-deficiency anemia is a significant cause of anemia, especially in the elderly. Iron, folate, and vitamin B12 deficiencies may be seen alone, but more often a combination of these deficiencies is present.

Iron Deficiency

An estimated 15% to 23% of anemic elders have iron deficiency. Iron-deficiency anemia is characterized by depletion of iron stores. Microcytic, hypochromic (smaller and paler) RBCs are often present due to the decreasing iron supply. Serum ferritin concentrations of 25–45 mg/dL are suspicious for iron-deficiency anemia. Levels greater than 100 mg/dL indicate sufficient iron stores and the likelihood of iron-deficiency anemia is reduced. However, infectious or inflammatory responses will increase serum ferritin concentration, making measurements potentially unreliable. In patients with infectious or inflammatory disorders, plasma transferrin receptor concentration may be a more useful measure.

The most common cause of iron-deficiency anemia in the elderly is occult blood loss from the gastrointestinal tract. Blood loss from the gastrointestinal tract may be chronic or acute depending on the underlying etiology. It may be the result of nonsteroidal anti-inflammatory drug (NSAID) use, a gastric ulcer, colon cancer, diverticulosis, or angiodysplasia (i.e., vascular malformation in the gastrointestinal tract). In one study, gastrointestinal malignancy was present in 6% of patients with iron-deficiency anemia. Referral to gastroenterology for endoscopic evaluation is crucial for all patients with iron-deficiency anemia (but particularly those with family histories of gastrointestinal cancers), and colonoscopy is recommended, regardless of age, to evaluate for possible bowel malignancy if upper endoscopy does not reveal a source of bleeding. Stool should be tested for occult blood in the initial anemia work-up. It is important to also consider other potential causes of microcytic anemia during the evaluation of elderly patients with iron-deficiency anemia.

Vitamin B12 Deficiency

Vitamin B12 (also called cobalamin) is necessary for DNA synthesis, RBC maturation, and normal functioning of the neurologic system. Older adults are at increased risk for developing vitamin B12 deficiencies for many reasons, including atrophic gastritis, which results in a reduced ability to absorb vitamin B12 from food sources. Vitamin B12 deficiency can also result from inadequate dietary intake and defects in metabolism. In addition to anemia, vitamin B12 deficiency can cause damage to the brain and nervous system.

Folate Deficiency

Folate (also known as folic acid or vitamin B9) is a B vitamin that is necessary for RBC production. Folate deficiency usually results from inadequate dietary intake or malabsorption and is more common in the elderly and chronically ill. In adults, it often occurs with alcoholism and during pregnancy and breastfeeding. Less often, folate deficiency may develop in individuals taking medications such as methotrexate, phenytoin, and trimethoprim, which interfere with the absorption of folate. Methotrexate in particular is used for a wide variety of conditions (including rheumatoid arthritis, lupus, psoriasis, and asthma) that may be more common in elderly patients. Dialysis patients are also at risk of deficiency, as folate is lost in dialysis fluid.

MYELODYSPLASIA

Bone marrow is a blood-forming (hematopoietic) organ responsible for the production of most of the cellular components of the blood, including erythrocytes, leukocytes, and platelets. As an individual ages, he or she will produce a decreased amount of functional bone marrow, and disorders of hematopoiesis are more common in the elderly. Myelodysplastic syndromes (MDS) are one such group of disorders and a cause of anemia in older patients, although it is relatively uncommon. These disorders are characterized by one or more peripheral blood cytopenias resulting from bone marrow dysfunction. According to the French-American-British (FAB) classification system, MDS is further classified according to cellular morphology, etiology, and clinical presentation. Myelodysplasia is more common in elderly patients, and more than 75% of patients with MDS are older than 60 years of age at diagnosis. Patients may be asymptomatic, and the disease is often found as the result of routine blood tests. When present, signs and symptoms include fatigue, pallor, frequent infections, easy bruising, and petechiae. An estimated 30% of cases will progress to acute leukemia.

CHRONIC KIDNEY DISEASE

Kidney function and glomerular filtration rate (GFR) naturally decreases with age, and it may be further decreased in the presence of chronic illnesses such as hypertension and diabetes, the two main causes of chronic kidney disease. With declining kidney function there is a decreased production of erythropoietin from the kidneys, and this is the primary etiology of anemia associated with chronic kidney disease. It can be difficult to differentiate the effects of normal aging on the kidneys from chronic kidney disease. Although GFR decreasing with age is considered normal, the diagnostic criteria for chronic kidney disease are not modified according to a patient’s age. Chronic kidney disease is defined as kidney damage or a GFR less than 60 mL/minute/1.73 m2 for more than three months. It is further staged according to severity of GFR impairment and other symptoms.

BONE MARROW FAILURE

Aplastic anemia is a life-threatening condition that occurs due to unexplained bone marrow failure. The bone marrow’s stem cells are damaged as the result of an inherited condition or may be caused by an acquired condition, including an autoimmune disorder, exposure to toxic chemicals, chemotherapy or radiation exposure, infection, or in rare cases, pregnancy. In some patients the cause of aplastic anemia remains unknown. Hereditary aplastic anemia is very rare; the acquired type is more prevalent. However, only 4 of every 1 million Americans will be diagnosed with any type of aplastic anemia annually. As with other anemias, patients with aplastic anemia are susceptible to bleeding, fatigue, and infections. Pancytopenia is present when there are low counts of RBCs, WBCs, and platelets. The diagnosis of aplastic anemia is confirmed by bone marrow examination.

Adapted from Anemia in the Elderly, NETCE, 2019