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Anemia

Description

An in-depth report on the types, diagnosis, treatment, and prevention of anemia.

Alternative Names

Iron deficiency; Pernicious anemia

Diagnosis

The first step in any diagnosis is a physical examination to determine if the patient has symptoms of anemia and any complications. Because anemia may be the first symptom of a serious illness, determining its cause is very important. This may be difficult, particularly in the elderly, malnourished, or people with chronic diseases, whose anemia may be caused by one or more factors. A detailed medical, personal, and dietary history should report:

• Any family or personal history of anemia
• A history of gallbladder disease, jaundice, or enlarged spleen
• Heavy menstrual bleeding in women
• Any occurrence of blood in the stool or other signs of internal bleeding. (Even if the patient has not observed any bleeding, nonvisible blood may be present, so a rectal exam and stool test are essential.)
• Any dietary history, particularly in people who are elderly, poor, or both

The doctor should examine the patient carefully, especially checking for swollen lymph nodes, an enlarged spleen, and pale skin and nail color.

Blood Tests to Determine the Presence of Any Anemia

For anemia from any cause, specific blood tests are given to determine anemia from any cause.

Blood and Hemoglobin Counts. A complete blood count (CBC) test is performed to determine the presence of anemia. The red blood cells, or erythrocytes , and their iron-bearing component, hemoglobin , are measured.

For example, severe anemia in adults is defined by the World Health Organization as:

• Hemoglobin concentrations below 7.5 mmol/L (12 g/dL) in women. (Some evidence suggests that in older women anemia should be diagnosed at 13 g/dL and below.)
• Below 8.1 mmol/L (13 g/dL) in men.

A low red blood cell (RBC) count could indicate a number of problems, including bleeding or a failure by bone marrow to manufacture red blood cells.

Hematocrit. Calculating the percentage of red blood cells in blood plasma (a measurement called the hematocrit ) is also important. Plasma is the liquid portion of blood. People with a high volume of plasma may be anemic even if their blood count is normal because the blood cells have become diluted.

Normal percentages are highest in the very youngest individuals and decline as people age. They also vary by gender. The following are some examples of normal range:

• Newborns: 42 - 60%
• Children: 35 - 45%
• Adult males: 41 - 53%
• Adult women: 36 - 46%

Smokers, people at high altitudes, and those who are dehydrated tend to have higher than normal hematocrit levels. Those at greater risk for low hematocrit levels include pregnant women and patients with cirrhosis, heart failure, and splenomegaly.

Reticulocyte Count. Reticulocytes are immature red blood cells, and their count reflects the rate of red blood cell production. The upper normal limit is about 100,000/mL. A low count, when bleeding isn't the cause, suggests problems in production in the bone marrow. An abnormally high count indicates that the red blood cells are being destroyed in high numbers and indicates hemolytic anemia. New research suggests that the reticulocyte hemoglobin content (CHr) test may be more accurate than a standard hemoglobin test for detecting iron deficiency in infants. This test may help identify babies who are at risk for becoming anemic and help them get treated earlier.

Blood Morphology. A blood smear viewed under a microscope allows an expert to classify the blood by its color, size, and shape (its morphology ). Generally red blood cells are categorized as:

• Pale-colored ( hypochromic ) and abnormally small ( microcytic )
• Normal colored and normal sized ( normochromic , normocytic )
• Abnormally large ( macrocytic )

The shape of the red blood cells, which can be distorted in many blood disorders, is also important in determining a diagnosis.

Diagnosing Iron Deficiency Anemia and its Causes

There are two steps in making a diagnosis in patients with symptoms of iron deficiency anemia:

• The first step is to determine if a person is actually deficient in iron.
• If iron stores are low, the second step is to diagnose the cause of the iron deficiencies, which will help determine treatment.

Determining if Iron Stores are Low. The following findings are important in determining that a person is iron deficient:

• Blood cells viewed under the microscope are pale ( hypochromic ) and abnormally small ( microcytic ). They are also mostly uneven in shape. (These findings suggest iron deficiency, they but can also appear in anemia of chronic disease and thalassemia.)
• Hemoglobin and iron levels are low. (These findings further suggest iron deficiency, but they can also occur in cases due to anemia due to chronic disease.)
• Ferritin levels are low. Ferritin is a protein that binds to iron. Low levels typically mean reduced iron stores. High ferritin levels in the blood do not always mean sufficient iron stores. For example, pregnant women may have high ferritin levels into their third trimester but still be iron deficient. Ferritin levels may also be normal or even elevated in patients with inflammation from anemia of chronic disease, even if they also have low iron stores.
• In children with iron deficiencies, reticulocyte hemoglobin levels are low. Reticulocytes are immature red blood cells, and this test may be the most effective approach for diagnosing iron deficiency in children.
• A test that measures a factor called serum transferrin receptor (TfR) is proving to be very sensitive in identifying iron deficiency in problematic patients, including the elderly with chronic diseases and possibly pregnant women. (It is often very difficult to identify iron deficiencies in patients who also have anemia of chronic diseases because their ferritin levels are often normal or even high.) For example, levels of TfR are high in patients with ACD and iron deficiency anemia, but they are normal or only slightly raised in ACD alone. The test is expensive, however, and some experts recommend it should be used only when there is a high suspicion of iron deficiency in the elderly.
• Measuring erythrocyte zinc protoporphyrin (ZPP), a product of abnormal heme synthesis, is under investigation and may prove to be a simple and precise measure of iron deficiencies, particularly in children.

Determining Causes of Iron Deficiency. When iron deficiency anemia is diagnosed, the next step is to determine what causes the iron deficiency itself.

• Dietary iron deficiency is most common in children and infants. It is rare in adults.
• Heavy menstrual or abnormal uterine bleeding is usually the cause of iron deficiencies in young women. Increased need for iron during pregnancy is also a common cause in this population.
• If internal bleeding is suspected as the cause, the gastrointestinal tract is usually the first suspect as the source. A diagnosis in these cases can often be made if the patient has noticed blood in the stools, which can be black and tarry or red-streaked. Often, however, bleeding may be present but not visible. If so, stool tests for this hidden ( occult ) blood are required. Additional tests may then be needed to diagnose the precipitating condition. Endoscopy, in which a fiber optic tube is used to view into the gastrointestinal tract, is helpful in many patients, particularly when the source of bleeding is unclear. A colonoscopy may also be recommended to rule out colorectal cancer.

If the patient's diet suggests low iron intake and other causes cannot be established using inexpensive or noninvasive techniques, then the patient may simply be given a monthly trial of iron supplements. If the patient fails to respond, further evaluation is needed.

Diagnosing Anemia of Chronic Disease (ACD)

Usually anemia of chronic disease is recognized during the management of the primary disease and, if the anemia is mild, additional diagnostic tests are rarely needed. The following are typical findings in ACD:

• The blood cells are normal looking.
• Blood tests may typically show low levels of iron in the blood, but ferritin levels are normal or even high. (Low levels of ferritin, a protein that binds to iron, indicate iron deficiency.)

Diagnosing Vitamin B-Related Anemias

Doctors need a multi-step diagnostic procedure for determining vitamin B deficiencies and the anemias that cause or are caused by them. Doctors may arrive at a diagnosis of vitamin B12 or folic acid deficiencies from different routes:

• They may diagnose deficiencies after detecting megaloblastic anemia from abnormal blood tests.
• They may suspect vitamin deficiencies first from symptoms and history and then look for anemia.

Diagnosing Megaloblastic Anemia. Very large oval red blood cells indicate megaloblastic anemia. Abnormally shaped neutrophils (certain white blood cells) may also be present. Bone marrow aspiration may need to be performed if the disease is strongly suspected but the diagnosis is not clear.

Determining Vitamin Deficiency. Once megaloblastic anemia has been diagnosed, the doctor will need to determine which vitamin deficiency is causing it. This is extremely important, because if a vitamin B12-deficient patient receives folate replacement only, then irreversible nerve injuries may develop. Even if blood tests for megaloblastic anemia are normal, patients with neurologic and psychiatric abnormalities that have no detectable cause should still be tested for vitamin B12 deficiency.

Deficiencies may be suggested by the presence of other disorders:

• Malnutrition, alcohol abuse, pregnancy, a history of sprue, severe psoriasis, or the use of antiseizure drugs may indicate a folic acid deficiency.
• A history of stomach surgery, eating raw fish (which raises the possibility of tapeworm), inflammatory bowel disease, or hypothyroidism suggests vitamin B12 deficiency.

Often, vitamin B deficiencies cannot be determined by a history or symptoms alone. Blood tests are the primary indicators of both vitamin B12 and folic acid deficiencies, but even blood tests for these vitamins are not always straightforward:

• Folic acid and vitamin B12 levels must always be measured at the same time because each vitamin may affect the other.
• Folate levels may be temporarily low in some people who are not truly deficient.
• Folate levels may temporarily rise in deficient people if they have just eaten foods containing the vitamin.
• Antibiotics can interfere with B12 levels.

Measuring methylmalonic acid and homocysteine, substances in the blood that increase when levels of one or both vitamins are low, improves accuracy.

Tests for Pernicious Anemia. Once a vitamin B12 deficiency has been established and the doctor has not found any intestinal abnormalities or other factors to account for the deficiency, the doctor presumes a diagnosis of pernicious anemia. Pernicious anemia may also be diagnosed through various blood (such as complete blood count) or urine tests.

Pernicious anemia is treated with vitamin replacement, but the condition is easily missed, particularly in patients whose diets are rich in folic acid. Folic acid can mask the early symptoms of pernicious anemia but not cure it. Consequently the disease may persist until serious neurologic symptoms occur. With folic acid now a required additive in many commercial foods, some experts are concerned about an increased incidence in pernicious anemia.

• Review Date: 1/17/2007
• Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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