Anemia in Elderly – Iron Deficiency Anemia Causes in Older People

In elderly people there is a notable reduction in the capacity to produce new blood cells. Yet, unless there is substantial physiological stress, the number of circulating cells remains fairly constant. Quantitative deficiencies are only apparent when stress produces a demand that exceeds reserve proliferative capacity. Such a demand might occur during an acute infection or after cytotoxic chemotherapy. Significant qualitative deficiencies in blood cell function are not thought to be a consequence of anemia in elderly, but may be associated with age-associated chronic diseases. The three major types of blood cells are erythrocytes, leukocytes, and platelets. Deficiency or over-production of each of these cell types can lead to major clinical consequences.

The major role of erythrocytes or red blood cells is to transport oxygen. This is accomplished by a complex interaction of oxygen with the primary erythrocyte protein, hemoglobin. The average life span of red cells is 120 days. Therefore, to maintain steady state, approximately 0.8 to 1% of the total circulating red blood cells need to be replaced each day. If they are not, the red cell volume will decline and a condition termed anemia in elderly will develop.

The lower limit of the normal range for hemoglobin concentration in blood, established by the World Health Organization, is 13 g/dl for men and 12 g/dl for women. Anemia occurs when there is a persistent decline in the hemoglobin concentration from the normal range accepted for a particular group. Hemoglobin levels tend to be lower in women and in certain racial groups, but the reasons for this are not fully understood.

Anemia is the most frequently encountered hematologic problem and chronic diseases among elderly. Hemoglobin concentration begins to show a steady decline in the sixth decade and beyond. It remains controversial whether aging results in anemia, but the current prevalent opinion is that the age-associated increase is the result of coexisting disease or nutritional deficiencies and is not a consequence of aging itself. Anemia may be characterized in a number of ways. One useful approach is classification on the basis of erythrocyte size. Accordingly, there are three major categories: microcytic anemia, normocytic anemia, and macrocytic anemia.

Microcytic Anemia

Microcytic anemia is characterized by red blood cells with a mean corpuscular volume of less than 80 fl. The major causes of microcytic anemia in adults are iron deficiency, inflammatory disease, and thalassemia.

The most common cause of microcytic anemia is iron deficiency. This can occur due to inadequate nutritional intake, which is commonly observed in older people due to a change in dietary habits, dental problems, or malabsorption. However, the major iron deficiency anemia cause in elderly is blood loss, primarily through the gastrointestinal (GI) tract. It is very important to survey the GI tract in any case of otherwise unexplained iron deficiency, as iron deficiency anemia is one of the most common presentations of GI malignancy. Uterine or vaginal bleeding can also be the result of a developing cancer and a gynecological exam is warranted in women who present with iron deficiency.

Iron deficiency anemia is usually detected during routine laboratory testing. Although the serum ferritin is considered to be the most useful test in the diagnosis, it can sometimes be misleading, as this protein is also an acute phase reactant and can be elevated in inflammatory states. The measurement of the soluble transferrin receptor appears to be a more sensitive test, but it has yet to gain widespread clinical use.

Once iron deficiency anemia causes is identified and a cause established, the most effective therapy is reversal of the identified cause (e.g., removal of colonic polyp) and the administration of iron supplementation. Usually, this can be accomplished with oral iron preparations. Iron deficiency anemia treatment phase usually takes about 6 months. Oral iron is often not well tolerated, particularly by older patients, primarily because it is associated with constipation. Thus, lack of compliance with iron deficiency anemia treatment recommendations becomes an issue and should be considered if the laboratory indicators do not reflect improvement within 2 months. Absorption may be erratic and, as mentioned, oral preparations may be intolerable for some patients. For these, parenteral preparations are now available, and many physicians are currently prepared to administer these either in their office or at an infusion clinic.

Other causes of microcytic anemia include thalassemia and inflammation. Many chronic diseases are associated with microcytic anemia (e.g., cancer, arthritis, infection, and even atherosclerosis and diabetes). Although some patients will also have iron deficiency, most will have laboratory evidence for adequate total body iron stores. Typically, such patients will have microcytic anemia, a clinically apparent inflammatory or chronic disease, and an elevated erythrocyte sedimentation rate (ESR). The mechanism of inflammation-associated anemia is not completely understood, but likely involves pro-inflammatory cytokines such as interleukin-6 and the newly described liver peptide hepcidin.

Normocytic Anemia

Normocytic anemia is characterized by red blood cells that have mean corpuscular volumes of 80 to 100 fl. Acute blood loss is the most common cause of normocytic anemia. In the absence of acute blood loss, other causes include hemolysis; early nutritional deficiency of iron, vitamin B12, or folic acid; or erythropoietin deficiency secondary to kidney impairment.

Hemolytic anemia can be further defined as either intravascular (red blood cell destruction within blood vessels) or extra vascular (red blood cell destruction within the spleen or liver). These conditions can be acute, sub acute, or chronic and are diagnosed by laboratory tests, e.g., elevated levels of lactate dehydrogenase (LDH), indirect bilirubin, carbon monoxide, and urinary urobilinogen. The reticulocyte count is usually elevated, as the body attempts to compensate for the acute blood loss. Examination of the peripheral blood smear is crucial to help determine the cause of hemolysis. Often, the cause is secondary to an antibody, which either specifically or non-specifically binds to the red blood cell surface, causing direct (intravascular) or indirect (extra vascular) hemolysis. The cause of such antibodies is sometimes associated with drugs (e.g., penicillin) or infection (e.g., Mycoplasma pneumoniae). Drugs may also result in hemolytic anemia directly, without producing antibodies. An offending drug or infectious agent is frequently not uncovered in a condition termed autoimmune hemolytic anemia. Iron deficiency anemia treatment is geared toward stabilization of the underlying disease process, and transfusions are potentially dangerous because of the potential for exaggerating the hemolytic process.

Macrocytic Anemia

Macrocytic anemia is characterized by red blood cells that have mean corpuscular volumes of greater than 100 fl. The three most common causes of macrocytic anemia causes are substance abuse, drug toxicity, and nutritional deficiency.

Substance abuse Both alcohol and tobacco abuse can lead to a macrocytic anemia.

Drug toxicity Drugs that commonly lead to macrocytic anemia symptoms are hydroxyurea, methotrexate, tri- methoprim, and most cytotoxic chemotherapeutic agents.

Nutritional deficiency Vitamin B12 and folic acid deficiency are the two most common nutritional causes of macrocytosis.