anemia

Definition

Anemia is a condition characterized by abnormally low levels of healthy red blood cells or hemoglobin (the component of red blood cells that delivers oxygen to tissues throughout the body).

Description

The tissues of the human body need a regular supply of oxygen to stay healthy. Red blood cells, which contain hemoglobin that allows them to deliver oxygen throughout the body, live for only about 120 days. When they die, the iron they contain is returned to the bone marrow and used to create new red blood cells. Anemia develops when heavy bleeding causes significant iron loss or when something happens to slow down the production of red blood cells or to increase the rate at which they are destroyed.

Anemia can be mild, moderate, or severe enough to lead to life-threatening complications. More than 400 different types of anemia have been identified. Many of them are rare.

IRON DEFICIENCY ANEMIA. Iron deficiency anemia is the most common form of anemia in the world. In the United States, iron deficiency anemia affects about 240,000 toddlers between one and two years of age and3.3 million women of childbearing age. This condition is less common in older children and in adults over 50 and rarely occurs in teenage boys and young men.

The onset of iron deficiency anemia is gradual and, at first, there may not be any symptoms. The deficiency begins when the body loses more iron than it derives from food and other sources. Because depleted iron stores cannot meet the red blood cell's needs, fewer red blood cells develop. In this early stage of anemia, the red blood cells look normal, but they are reduced in number. Then the body tries to compensate for the iron deficiency by producing more red blood cells, which are characteristically small in size. Symptoms develop at this stage.

FOLIC ACID DEFICIENCY ANEMIA. Folic acid deficiency anemia is the most common type of megaloblastic anemia (in which red blood cells are bigger than normal). It is caused by a deficiency of folic acid, a vitamin that the body needs to produce normal cells.

Folic acid anemia is especially common in infants and teenagers. Although this condition usually results from a dietary deficiency, it is sometimes due to inability to absorb enough folic acid from such foods as:

• cheese
• eggs
• fish
• green vegetables
• meat
• milk
• mushrooms
• yeast

Smoking raises the risk of developing this condition by interfering with the absorption of Vitamin C, which the body needs to absorb folic acid. Folic acid anemia can be a complication of pregnancy, when a woman's body needs eight times more folic acid than it does otherwise.

VITAMIN B₁₂DEFICIENCY ANEMIA. Less common in this country than folic acid anemia, vitamin B₁₂ deficiency anemia is another type of megaloblastic anemia that develops when the body doesn't absorb enough of this nutrient. Necessary for the creation of red blood cells, B₁₂ is found in meat and vegetables.

Large amounts of B₁₂ are stored in the body, so this condition may not become apparent until as much as four years after B₁₂ absorption stops or slows down. The resulting drop in red blood cell production can cause:

• loss of muscle control
• loss of sensation in the legs, hands, and feet
• soreness or burning of the tongue
• weight loss
• yellow-blue color blindness

The most common form of B₁₂ deficiency is pernicious anemia. Since most people who eat meat or eggs get enough B₁₂ in their diets, a deficiency of this vitamin usually means that the body is not absorbing it properly. This can occur among people who have had intestinal surgery or among those who do not produce adequate amounts of intrinsic factor, a chemical secreted by the stomach lining that combines with B₁₂ to help its absorption in the small intestine.

Pernicious anemia usually strikes between the ages of 50–60. Eating disorders or an unbalanced diet increases the risk of developing pernicious anemia. So do:

• diabetes mellitus
• gastritis, stomach cancer, or stomach surgery
• thyroid disease
• family history of pernicious anemia

VITAMIN C DEFICIENCY ANEMIA. A rare disorder that causes the bone marrow to manufacture abnormally small red blood cells, Vitamin C deficiency anemia results from a severe, long-standing dietary deficiency.

HEMOLYTIC ANEMIA. Some people are born with hemolytic anemia. Some acquire this condition, in which infection or antibodies destroy red blood cells more rapidly than bone marrow can replace them.

Hemolytic anemia can enlarge the spleen, accelerating the destruction of red blood cells (hemolysis). Other complications of hemolytic anemia include:

• pain
• shock
• gallstones and other serious health problems

THALASSEMIAS. An inherited form of hemolytic anemia, thalassemia stems from the body's inability to manufacture as much normal hemoglobin as it needs. There are two categories of thalassemia, depending on which of the amino acid chains is affected. (Hemoglobin is composed of four chains of amino acids.) In alpha-thalassemia, there is an imbalance in the production of the alpha chain of amino acids; in beta-thalassemia, there is an imbalance in the beta chain. Alpha-thalassemias most commonly affect blacks (25% have at least one gene); beta-thalassemias most commonly affect people of Mediterranean ancestry and Southeast Asians.

Characterized by production of red blood cells that are unusually small and fragile, thalassemia only affects people who inherit the gene for it from each parent (auto-somal recessive inheritance).

AUTOIMMUNE HEMOLYTIC ANEMIAS. Warm antibody hemolytic anemia is the most common type of this disorder. This condition occurs when the body produces autoantibodies that coat red blood cells. The coated cells are destroyed by the spleen, liver, or bone marrow.

Warm antibody hemolytic anemia is more common in women than in men. About one-third of patients who have warm antibody hemolytic anemia also have lymphoma, leukemia, lupus, or connective tissue disease.

In cold antibody hemolytic anemia, the body attacks red blood cells at or below normal body temperature. The acute form of this condition frequently develops in people who have had pneumonia, mononeucleosis, or other acute infections. It tends to be mild and short-lived, and disappears without treatment.

Chronic cold antibody hemolytic anemia is most common in women and most often affects those who are over 40 and who have arthritis. This condition usually lasts for a lifetime, generally causing few symptoms. However, exposure to cold temperatures can accelerate red blood cell destruction, causing fatigue, joint aches, and discoloration of the arms and hands.

SICKLE CELL ANEMIA. Sickle cell anemia is a chronic, incurable condition that causes the body to produce defective hemoglobin, which forces red blood cells to assume an abnormal crescent shape. Unlike normal oval cells, fragile sickle cells can't hold enough hemoglobin to nourish body tissues. The deformed shape makes it hard for sickle cells to pass through narrow blood vessels. When capillaries become obstructed, a life-threatening condition called sickle cell crisis is likely to occur.

Sickle cell anemia is hereditary. It almost always affects blacks and people of Mediterranean descent. A child who inherits the sickle cell gene from each parent will have the disease. A child who inherits the sickle cell gene from only one parent carries the sickle cell trait, but does not have the disease.

APLASTIC ANEMIA. Sometimes curable by bone marrow transplant, but potentially fatal, aplastic anemia is characterized by decreased production of red and white blood cells and platelets (disc-shaped cells that allow the blood to clot). This disorder may be inherited or acquired as a result of:

• recent severe illness
• long-term exposure to industrial chemicals
• use of anticancer drugs and certain other medications

ANEMIA OF CHRONIC DISEASE. Cancer, chronic infection or inflammation, and kidney and liver disease often cause mild or moderate anemia. Chronic liver failure generally produces the most severe symptoms.

— Maureen Haggerty

[New Latin, from Greek anaimiā : an-, without; see a-¹ + haima, blood.]

For more information on anemia, visit Britannica.com.

Key Terms: Cytokines, Cytomegalovirus, Erythropoiesis, Erythropoietin, Hematocrit.

Description

Anemia is characterized by an abnormally low number of red blood cells in the circulating blood. It frequently affects patients with cancer. In fact, in many cancer diagnoses such as multiple myeloma and acute leukemia, the presence of anemia may be what initially prompts a doctor to suspect an underlying tumor (neoplasm). Whether or not anemia develops depends on the type of cancer found, the treatment used, and the presence or absence of other underlying medical disorders.

Symptoms of malignancy-associated anemia may range from weakness, paleness, and fatigue to shortness of breath and increased heart rate. Symptoms of anemia can compromise a patient's ability to tolerate treatment, and may severely interfere with activities of daily living. Anemia may be particularly problematic in older individuals with cancer. The incidence and severity of anemia tends to increase as the cancer progresses.

Blood is comprised of three major cell types: white blood cells, which help the body fight infection; platelets, which help the blood to clot when necessary; and red blood cells, which transport oxygen from the lungs to the tissues in the body, and then transport carbon dioxide from those tissues back to the lungs. This exchange is enabled by the most important component of red blood cells—the protein called hemoglobin that binds easily to oxygen and carbon dioxide.

Red blood cells are produced in the bone marrow through a process called erythropoiesis. When the bone marrow functions normally, it continuously replaces red blood cells to maintain a normal level that allows for adequate oxygenation of the tissues. The hormone erythropoietin stimulates red blood cell production and sends a message to the bone marrow to increase production when oxygen levels in the body are low. This mechanism is often impaired in patients with cancer.

Causes

The causes of anemia are multiple, and often the factors act in conjunction with one another. Generally, anemia may result from a direct effect of a cancerous tumor, or from an indirect effect of the tumor. The cancer process may directly cause anemia through two main mechanisms: blood loss or bone marrow replacement. However, most cases of anemia in cancer patients result from the indirect effects of the cancer.

Direct Effects of the Tumor

Anemia is a frequent complication of cancers due to bleeding. Cancers of the head and neck, the gastrointestinal and genitourinary system, and the cervix are frequently associated with endogenous bleeding, or bleeding that occurs within the body. Bleeding occasionally develops within the tumor itself, particularly in sarcomas, melanomas, and ovarian and liver carcinomas.

A second direct cause of anemia in cancer is bone marrow replacement, which inhibits the body's ability to appropriately produce red blood cells. Certain cancers, such as acute leukemia, lymphoma and myeloma, directly suppress bone marrow function, thereby causing anemia. Other types of cancer, such as prostate or breast cancer, often spread to the bone marrow, inhibiting red blood cell production by actually replacing the bone marrow itself.

Indirect Effects of the Tumor

Anemia of chronic disease, also called anemia of malignancy, is the most common type of anemia seen in individuals with cancer. It is a diagnosis made only after other possible causes are ruled out and if very specific conditions are met. The presence of low levels of iron coupled with normal levels of storage iron helps distinguish anemia of chronic disease from iron deficiency anemia. Factors that cause anemia of chronic disease are not entirely clear. However, it is believed that cytokines (non-antibody proteins) produced by the tumor reduce production of and impair responsiveness to erythropoietin. Typically, this type of anemia develops slowly. Rapid development of anemia may indicate an other cause.

Treatments used to manage cancer have been implicated in the development of anemia in cancer patients. Radiation therapy to large areas of bone marrow, as in the hip area, may suppress bone marrow function and lead to anemia. Chemotherapy can also cause bone marrow suppression, and some drugs specifically target red blood cell production. Studies have shown that 10% to 40% of patients taking cisplatin develop significant anemia. Cisplatin, a chemotherapy drug with potentially toxic effects to the kidneys, is believed to reduce the production of the hormone erythropoietin in the kidneys. Although most treatment-induced bone marrow suppression is short term, there is some evidence to support the possibility of long-term problems with blood cell production.

Treatment can increase the risk of anemia in other ways. Chemotherapy, for example, causes bone marrow suppression that may reduce the immune system's ability to fight off opportunistic infection. The resulting infections can impact the bone marrow's functioning, possibly leading to the development of anemia.

Hemolytic anemia is a type of anemia in which the red blood cell has a shortened life span (normal life span is 90-120 days). Because the bone marrow is not able to compensate by producing more red blood cells, anemia results. Abnormalities in the red blood cells may originate in the body (intrinsic) or may be caused by environmental factors such as auto-antibodies to red blood cells or damage from chemotherapy.

Although one factor may have a greater influence, it is important to realize that several factors may be causing anemia. For example, approximately 70% of patients with multiple myeloma are anemic at the time of diagnosis. Anemia in these cases is caused by a combination of mechanisms including bone marrow replacement with cancer cells, bone marrow suppression from chemotherapy, and impaired production of erythropoietin.

Treatments

Treatment of the anemia is directed at the underlying cause. In many cases, treating or removing the cancer corrects the red blood cell deficit. Management of autoimmune hemolytic anemia, which can be associated with chronic lymphocytic leukemia, may range from the administration of corticosteroids to the surgical removal of the spleen. More commonly, cancer-related anemias are treated with blood transfusions and/or a drug called epoetin alfa.

Blood Transfusions

Blood transfusions have been the principle treatment for anemia for many years. Until the 1960s, only whole blood was given. Then, methods of separating whole blood were devised, allowing only particular components, such as platelets, red blood cells, or plasma, to be transfused.

Blood transfusions are not without risk, and must be used carefully. Many patients react to the white blood cell antigens by developing a fever. This is so common that patients are routinely premedicated to prevent fever from developing. Individuals with long-term transfusion needs, such as patients with leukemia, may be given blood products with a reduced number of white blood cells to reduce the risk of sensitization to transfused blood.

Cytomegalovirus (CMV) is a virus that may be present in blood products. Although it has no effect on individuals with normally functioning immune systems, cancer patients often have a diminished ability to fight infection. These patients may be at risk for CMV if they are CMV negative and receive CMV-positive blood.

Transfusion-associated graft-versus-host disease (TA-GvHD) is another risk factor associated with blood transfusions in cancer patients. Although it is very rare, it is often fatal. With TA-GvHD, the patient's immune system does not recognize the white blood cells in the donor blood as "nonself." The donor white blood cells, however, recognize the patient as "nonself," and an immune-mediated reaction ensues. To prevent this reaction in at-risk patients, blood may be irradiated prior to transfusion.

Epoetin Alfa

As mentioned previously, erythropoietin is a protein produced in the kidneys that stimulates red blood cell production. Using DNA technology, this hormone has been replicated to create the drug epoetin alfa for the treatment of anemia in select cancer patients. (The drug is also called erythropoietin.) The use of this drug in the cancer setting has shown great promise, both in the treatment of cancer-related anemia, and in the reduction in the need for blood transfusion.

However, epoetin alfa therapy is not advisable for everyone. This drug is not recommended for use in cancer-related anemia caused by bleeding, hemolysis, or iron deficiencies. Nor is it recommended for patients with hypertension or albumin sensitivity. Because no human studies are available to determine its effect on a fetus, women taking epoetin alfa should take measures to prevent pregnancy.

Cancer patients with anemia who are undergoing chemotherapy may benefit from this drug. Studies have shown an increased hematocrit (the volume percentage of red blood cells in whole blood) level and a decreased need for blood transfusions after the first month of therapy in this population. Epoetin alfa may be injected up to three times a week, and throughout therapy, blood cell counts are monitored closely. In 2004, it was reported that a form of the drug could be injected only once every two weeks in some cancer patients with the same effect, making its use more convenient.

Resources

Books

Abeloff, M., et al., editors. "Hematopoietic Dysfunction by Hematologic Lineage." In Clinical Oncology. 2nd ed. New York: Churchill Livingstone Publishers, 2000.

Lee, G., and C. Bennett, editors. "Nonmetastatic Effects of Cancer: Other Systems." In Cecil Textbook of Medicine. 21st ed. Philadelphia, PA: W. B. Saunders Co., 2000.

Lee, G., et al., editors. Wintrobe's Clinical Hematology. Baltimore, MD: Williams & Wilkins Publishing, 1999.

Periodicals

"Studies: Aranesp Dosed Semiweekly Is Comparable to Epoetin Alfa Once a Week." Obesity, Fitness & Wellness Week July 10, 2004:59.

—Tamara Brown, R.N.; Teresa G. Odle

A reduction in the total quantity of hemoglobin or of red blood cells (erythrocytes) in the circulation. Because it generally is impractical to measure the total quantity, measures of concentration are used instead. Hemoglobin is contained in red blood cells, which are suspended in plasma, the liquid component of blood. Therefore, concentration is affected not only by quantities of hemoglobin and red blood cells but also by plasma volume. Thus, the apparent anemia found in many women in the third trimester of pregnancy is not really anemia at all: the red cell mass is actually increased, but the plasma volume is expanded even more. In other words, hemodilution is present. Conversely, in dehydration and other circumstances of hemoconcentration, the plasma volume is reduced, thereby tending to mask anemia. See also Blood; Hemoglobin.

The three measures of concentration most often employed are the hemoglobin, the red blood cell count, and the volume of packed red cells. In a group of healthy individuals, the values for hemoglobin, red cell count, and hematocrit approximate a “normal” distribution. Values that are less than 2.5 standard deviations below the mean are indicative of anemia if other clinical factors do not indicate a condition of hemodilution. The mean values are greater for adult males than for adult females, and greater for adults than children. (Lower atmospheric oxygen tension at higher altitudes results in higher mean values for hemoglobin, red cells, and hematocrit in healthy individuals living under these conditions; hence, anemia would be defined at a higher value). In the state of health, the rate of production of new red blood cells (erythropoiesis) equals the rate of removal of senescent red blood cells. Anemia occurs if the rate of erythropoiesis is reduced below normal. It also occurs if hemorrhage or destruction (hemolysis) of red blood cells within the body increases the rate of loss of erythrocytes and the rate of erythropoiesis does not increase enough to compensate.

Mechanisms

Red blood cell production may be affected by several different mechanisms. Erythropoietin, a growth factor produced by healthy kidneys, stimulates the bone marrow to produce more erythroblasts and accelerates their maturation. The proliferative response of the bone marrow to anemia may be defective or absent if the production of erythropoietin is diminished or absent, as occurs in chronic renal disease and some endocrine disorders. Ineffective erythropoiesis also results when, in the intact, stimulated bone marrow, red blood cell precursors either fail to mature, or die in the bone marrow prior to their delivery to the circulation as erythrocytes.

Aplastic anemia occurs when the bone marrow stem cells that give rise to precursors of erythroblasts are markedly diminished in number or respond inadequately to erythropoietin. This condition occurs when the bone marrow is adversely affected by certain chemicals or autoantibodies; is injured by irradiation; atrophies, or is replaced by fat; is replaced by fibrous (scar) tissue; or is infiltrated by cancer cells.

Defective synthesis of deoxyribonucleic acid (DNA) and abnormal nuclear maturation result from malabsorption of vitamin B₁₂ (as in pernicious anemia) or dietary deficiency of folic acid or its malabsorption (sprue). These anemias are generally characterized by large red blood cells (macrocytes) and a specific morphological abnormality of the nuclear chromatin of erythroblasts which characterizes them as megaloblasts, and the condition as megaloblastic anemia.

Defective synthesis of hemoglobin impairs cytoplasmic maturation. The majority of cases are due to deficiency of body stores of iron and to abnormal release of iron from reticuloendothelial stores. The former occurs in iron-deficiency anemia, and the latter in the anemia of chronic inflammatory diseases.

Acute blood loss reduces the total blood volume and produces symptoms of weakness, dizziness, thirst, faintness, and shock, in that order, according to increasing magnitude of blood loss. The anemia which results is not detectable by measures of concentration until hemodilution occurs over subsequent days, or more rapidly if replacement fluids are given intravenously. The proliferative response of the healthy marrow will correct the anemia in 2–6 weeks, depending upon the size of the deficit and provided there are sufficient body stores of iron, folic acid, and vitamin B₁₂, required for hemoglobin synthesis. Chronic blood loss results in iron-deficiency anemia.

Hemolysis, the accelerated destruction of red blood cells, also induces a proliferative response from the marrow. However, it differs from hemorrhage because red blood cells are lost without plasma, and it thus diminishes the measures of concentration at the outset.

Diagnosis and treatment

Pallor, weakness, and fatigue are common to all anemias. They may not be noticed until anemia is advanced, if it is of gradual onset and there has been time for cardiovascular and biochemical adaptation. Faint jaundice in the sclerae is a feature of hemolytic anemia, whereas in anemia due to lack of vitamin B₁₂, glossitis and neuropathy may be noted.

Macrocytic anemias are often found to be megaloblastic and due to deficiency of vitamin B₁₂ or folic acid. Administration of one of those vitamins will only cure individuals in whom its specific deficiency is established. Microcytic-hypochromic anemias are most often due to iron deficiency. The administration of iron will resolve iron-deficiency anemia. Prednisone and other adrenal corticosteroids are helpful in hemolytic anemias associated with autoantibodies.

Hereditary disorders are generally not amenable to therapy, except for those hemolytic diseases which may benefit after splenectomy. In all other cases, the treatment of the anemia is achieved by treating the underlying disease, such as hypothyroidism, rheumatoid arthritis, or leukemia. Blood transfusions are reserved for acute blood loss when symptoms of hypovolemia and shock are present, or in chronic anemia if there are signs of inadequate cardiovascular or pulmonary compensation and an underlying cause cannot be found or treated. See also Clinical pathology; Hematologic disorders.

A term indicating that the concentration of hemoglobin or the number of red blood cells is below the accepted normal value with respect to age and sex. In true anemia the total concentration of hemoglobin, or the total number of erythrocytes, is below normal regardless of concentration values. Symptoms, which may not be evident, include weakness, pallor, anorexia, and those related to the cause of the anemia.

Definition

Anemia is a condition characterized by abnormally low levels of healthy red blood cells or hemoglobin.

Description

The tissues of the human body need a regular supply of oxygen to stay healthy. Red blood cells, which contain hemoglobin that allows them to deliver oxygen throughout the body, live for only about 120 days. When they die, the iron they contain is returned to the bone marrow and used to create new red blood cells. Anemia can develop when heavy bleeding causes significant iron loss. It also occurs when something happens to slow down the production of red blood cells or to increase the rate at which they are destroyed.

Anemia can be mild, moderate, or severe enough to lead to life-threatening complications. Over 400 different types of anemia have been identified. Many of them are rare. More common anemia types include:

• iron deficiency anemia
• folic acid deficiency anemia
• vitamin B₁₂ deficiency anemia
• vitamin C deficiency anemia
• autoimmune hemolytic anemia
• hemolytic anemia
• sickle cell anemia
• aplastic anemia
• anemia of chronic disease

Causes & Symptoms

Anemia is caused by bleeding, decreased red blood cell production, or increased red blood cell destruction. Poor diet can contribute to vitamin deficiency and iron deficiency anemia, in which fewer red blood cells are produced. Hereditary disorders and certain diseases can cause increased blood cell destruction. However, excessive bleeding is the most common cause of anemia, and the speed with which blood loss occurs has a significant effect on the severity of symptoms. Chronic blood loss may be caused by:

• heavy menstrual flow
• hemorrhoids
• nosebleeds
• cancer
• gastrointestinal tumors
• diverticulosis
• polyposis
• stomach ulcers
• long-term alcohol abuse

Acute blood loss is usually the result of:

• childbirth
• injury
• ruptured blood vessel
• surgery

Iron Deficiency Anemia

Iron deficiency anemia is the most common form of anemia in the world. In the United States, iron deficiency anemia affects about 240,000 toddlers between one and two years of age and 3.3 million women of childbearing age. This condition is less common in older children and in adults over 50, and it rarely occurs in teenage boys and young men.

The onset of iron deficiency anemia is gradual. The deficiency begins when the body loses more iron than it gains from food and other sources. Because depleted iron stores cannot meet the red blood cells' needs, fewer red blood cells develop. In this early stage of anemia, the red blood cells look normal, but they are reduced in number. Then the body tries to compensate for the iron deficiency by producing more red blood cells, which are characteristically small in size.

Weakness, fatigue, and a run-down feeling may be signs of mild anemia. Other signs include skin that is pasty or sallow, or lack of color in the creases of the palm, gums, nail beds, or lining of the eyelids. Someone who is weak, tires easily, is often out of breath, and feels faint or dizzy may be severely anemic. Other symptoms of anemia are:

• angina pectoris (chest pain)
• headache
• inability to concentrate and/or memory loss
• inflammation of the mouth (stomatitis) or tongue (glossitis)
• insomnia
• irregular heartbeat
• loss of appetite
• nails that are dry, brittle, or ridged
• rapid breathing
• sores in the mouth, throat, or rectum
• sweating
• swelling of the hands and feet
• thirst
• tinnitus (ringing in the ears)
• unexplained bleeding or bruising
• pica (a craving to chew ice, paint, or dirt)

Folic Acid Deficiency Anemia

Folic acid deficiency anemia is the most common type of megaloblastic anemia, in which red blood cells are bigger than normal. It is caused by a deficiency of folic acid, a vitamin that the body needs to produce normal cells.

Folic acid anemia is especially common in infants and teenagers. Although this condition usually results from a dietary deficiency, it is sometimes due to an inability to absorb enough folic acid from foods such as:

• eggs
• fish
• green vegetables
• meat
• milk and cheese
• mushrooms
• yeast

Smoking raises the risk of developing this condition by interfering with the absorption of vitamin C, which the body needs to absorb folic acid. Folic acid anemia can be a complication of pregnancy, when a woman's body needs eight times more folic acid than it does otherwise.

Vitamin B₁₂ Deficiency Anemia

Less common in this country than folic acid anemia, vitamin B₁₂ deficiency anemia is another type of megaloblastic anemia that develops when the body does not absorb enough of this nutrient. Necessary for the creation of red blood cells, B₁₂ is found in meat and vegetables.

Large amounts of B₁₂ are stored in the body, so this condition may not become apparent until as long as four years after B₁₂ absorption slows down or stops. The resulting drop in red blood cell production can cause:

• loss of muscle control
• loss of sensation in the legs, hands, and feet
• soreness or burning of the tongue
• weight loss
• yellow-blue color blindness

The most common form of B₁₂ deficiency is pernicious anemia. Since most people who eat meat or eggs get enough B₁₂ in their diets, a deficiency of this vitamin usually means that the body is not absorbing it properly. This can occur among people who have had intestinal surgery or those who do not produce adequate amounts of intrinsic factor, a chemical secreted by the stomach lining that combines with B₁₂ to help its absorption in the small intestine. Symptoms of pernicious anemia include problems with movement or balance, a slick tongue, tingling in the hands and feet, confusion, depression, and memory loss. Pernicious anemia can also damage the spinal cord. A doctor should be notified whenever symptoms of this condition occur.

Pernicious anemia usually strikes people 50–60 years of age. Eating disorders or an unbalanced diet increases the risk of developing pernicious anemia. So do diabetes mellitus, gastritis, stomach cancer, stomach surgery, thyroid disease, and family history of pernicious anemia.

Vitamin C Deficiency Anemia

A rare disorder that causes the bone marrow to manufacture abnormally small red blood cells, vitamin C deficiency anemia results from a severe, long-standing dietary deficiency.

Hemolytic Anemia

Some people are born with hemolytic anemia. Some acquire this condition, in which infection or antibodies destroy red blood cells more rapidly than bone marrow can replace them.

Hemolytic anemia can enlarge the spleen and accelerate the destruction of red blood cells (hemolysis). Other complications of hemolytic anemia may include pain, shock, gallstones, and other serious health problems.

Thalassemias

An inherited form of hemolytic anemia, thalassemia stems from the body's inability to manufacture as much normal hemoglobin as it needs. There are two categories of thalassemia, depending on which of the amino acid chains is affected. (Hemoglobin is composed of four chains of amino acids.) In alpha-thalassemia, there is an imbalance in the production of the alpha chain of amino acids; in beta-thalassemia, there is an imbalance in the beta chain. Alpha-thalassemias most commonly affect blacks (25% have at least one gene); beta-thalassemias most commonly affect people of Mediterranean and Southeast Asian ancestry.

Characterized by production of red blood cells that are unusually small and fragile, thalassemia only affects people who inherit the gene for it from each parent (autosomal recessive inheritance).

Autoimmune Hemolytic Anemia

Warm antibody hemolytic anemia is the most common type of this disorder. This condition occurs when the body produces autoantibodies that coat red blood cells. The coated cells are destroyed by the spleen, liver, or bone marrow.

Warm antibody hemolytic anemia is more common in women than in men. About one-third of patients who have warm antibody hemolytic anemia also have lymphoma, leukemia, lupus, or connective tissue disease.

In cold antibody hemolytic anemia, the body attacks red blood cells at or below normal body temperature. The acute form of this condition frequently develops in people who have had pneumonia, mononucleosis, or other acute infections. It tends to be mild and short-lived, and disappears without treatment.

Chronic cold antibody hemolytic anemia is most common in women and most often affects those who are over 40 and have arthritis. This condition usually lasts for a lifetime, generally causing few symptoms. However, exposure to cold temperatures can accelerate red blood cell destruction, causing fatigue, joint aches, and discoloration of the arms and hands.

Sickle Cell Anemia

Sickle cell anemia is a chronic, incurable condition that causes the body to produce defective hemoglobin, which forces red blood cells to assume an abnormal crescent shape. Unlike normal oval cells, fragile sickle cells cannot hold enough hemoglobin to nourish body tissues. The deformed shape makes it hard for sickle cells to pass through narrow blood vessels. When capillaries become obstructed, a life-threatening condition called sickle cell crisis is likely to occur.

Sickle cell anemia is hereditary. It almost always affects people of African or Mediterranean descent. A child who inherits the sickle cell gene from each parent will have the disease, but a child who inherits the gene from only one parent will carry the sickle cell trait, but will not have the disease.

Aplastic Anemia

Sometimes curable by bone marrow transplant, but potentially fatal, aplastic anemia is characterized by decreased production of red and white blood cells and platelets (disc-shaped cells that allow the blood to clot). This disorder may be inherited or acquired as a result of recent severe illness, long-term exposure to industrial chemicals, or use of anticancer drugs and certain other medications.

Anemia of Chronic Disease

Cancer, chronic infection or inflammation, and kidney and liver disease often cause mild or moderate anemia. Chronic liver failure generally produces the most severe symptoms.

Diagnosis

Personal and family health history may suggest the presence of certain types of anemia. Laboratory tests that measure the percentage of red blood cells or the amount of hemoglobin in the blood are used to confirm diagnosis and determine which type of anemia is responsible for a patient's symptoms. X rays and examinations of bone marrow may be used to identify the source of bleeding.

Treatment

Anyone who has anemia caused by poor nutrition should modify his or her diet to include more vitamins, minerals, and iron. Foods such as lean red meats, dried beans and fruits, liver, poultry, and enriched breads and cereals are all good sources of iron. In addition, eating foods rich in vitamin C such as citrus fruits and juices can promote the absorption of iron.

Patients diagnosed with iron-deficiency anemia should undergo a thorough physical examination and medical history to determine the cause of the anemia, particularly if chronic or acute blood loss is suspected. The cause of a specific anemia will determine the type of treatment recommended.

Anemia due to nutritional deficiencies can usually be treated at home with iron supplements or self administered injections of vitamin B₁₂. People with folic acid anemia should take oral folic acid replacements. Vitamin C deficiency anemia can be cured by taking daily supplements of vitamin C.

Many therapies for iron-deficiency anemia focus on adding iron-rich foods to the diet or on techniques to improve circulation and digestion. Iron supplementation, especially with iron citrate (less likely to cause constipation), can be given in combination with herbs that are rich in iron. Some examples of iron-rich herbs are dandelion (Taraxacum officinale), parsley (Petroselinum crispum), and nettle (Urtica dioica). The homeopathic remedy ferrum phosphoricum (iron sulfate) can also be helpful.

An iron-rich herbal tonic can also be made using the following recipe:

• Soak one-half ounce of yellow dock root and one-half ounce dandelion root in 1 qt of boiled water for 4–8 hours.
• Simmer until the amount of liquid is reduced to 1 cup.
• Remove from heat and add one-half cup black strap molasses, mixing well.
• Store in refrigerator; take one-quarter cup daily.

Other herbal remedies known to promote digestion are prescribed to treat iron-deficiency anemia. Gentian (Gentiana lutea) is widely used in Europe to treat anemia and other nutritionally-based disorders. The bitter qualities of gentian help stimulate the digestive system, making iron and other nutrients more available for absorption. This bitter herb can be brewed into tea or purchased as an alcoholic extract (tincture).

Other herbs recommended to promote digestion include:

• anise (Pimpinella anisum)
• caraway (Carum carvi)
• cumin (Cuminum cyminum)
• linden (Tilia spp.)
• licorice (Glycyrrhiza glabra)

Traditional Chinese treatments for anemia include:

• acupuncture to stimulate a weakened spleen
• asian ginseng (Panax ginseng) to restore energy
• dong quai (Angelica sinensis) to control heavy menstrual bleeding
• a mixture of dong quai and Chinese foxglove (Rehmannia glutinosa) to clear a sallow complexion
• astragalus (Astragalus membranaceus) to treat pallor and dizziness

Allopathic Treatment

Surgery may be necessary to treat anemia caused by excessive loss of blood. Transfusions of red blood cells may be used to accelerate production of red blood cells.

Medication or surgery may also be necessary to control heavy menstrual flow, repair a bleeding ulcer, or remove polyps (growths or nodules) from the bowels.

Patients with thalassemia usually do not require treatment. However people with a severe form may require periodic hospitalization for blood transfusions and/or bone marrow transplantation.

Sickle Cell Anemia

Treatment for sickle cell anemia involves regular eye examinations, immunizations for pneumonia and infectious diseases, and prompt treatment for sickle cell crises and infections of any kind. Psychotherapy or counseling may help patients deal with the emotional impact of this condition.

Vitamin B₁₂ Deficiency Anemia

A life-long regimen of B₁₂ shots is necessary to control symptoms of pernicious anemia. The patient may be advised to limit physical activity until treatment restores strength and balance.

Aplastic Anemia

People who have aplastic anemia are especially susceptible to infection. Treatment for aplastic anemia may involve blood transfusions and bone marrow transplant to replace malfunctioning cells with healthy ones.

Anemia of Chronic Disease

There is no specific treatment for anemia associated with chronic disease, but treating the underlying illness may alleviate this condition. This type of anemia rarely becomes severe. If it does, transfusions or hormone treatments to stimulate red blood cell production may be prescribed.

Hemolytic Anemia

There is no specific treatment for cold-antibody hemolytic anemia. About one-third of patients with warm-antibody hemolytic anemia respond well to large doses of intravenous and oral corticosteroids, which are gradually discontinued as the patient's condition improves. Patients with this condition who do not respond to medical therapy must have the spleen surgically removed. This operation controls anemia in about half of the patients on whom it is performed. Immune-system suppressants are prescribed for patients whose surgery is not successful.

Expected Results

Folic Acid and Iron Deficiency Anemia

It usually takes three to six weeks to correct folic acid or iron deficiency anemia. Patients should continue taking supplements for another six months to replenish iron reserves and should have periodic blood tests to make sure the bleeding has stopped and the anemia has not recurred.

Pernicious Anemia

Although pernicious anemia is considered incurable, regular B₁₂ shots will alleviate symptoms and reverse complications. Some symptoms will disappear almost as soon as treatment begins.

Aplastic Anemia

Aplastic anemia can sometimes be cured by a bone marrow transplant. If the condition is due to immunosuppressive drugs, symptoms may disappear after the drugs are discontinued.

Sickle Cell Anemia

Although sickle cell anemia cannot be cured, effective treatments enable patients with this disease to enjoy longer, more productive lives.

Thalassemia

People with mild thalassemia (alpha thalassemia trait or beta thalassemia minor) lead normal lives and do not require treatment. Those with severe thalassemia may require bone marrow transplantation. Genetic therapy is being investigated and may soon be available.

Hemolytic Anemia

Acquired hemolytic anemia can generally be cured when the cause is removed.

Prevention

Inherited anemia cannot be prevented. Genetic counseling can help parents cope with questions and concerns about passing on disease-causing genes to their children.

Avoiding excessive use of alcohol, eating a balanced diet that contains plenty of iron-rich foods, and taking a daily multivitamin can help prevent anemia.

Methods of preventing specific types of anemia include:

• Avoiding lengthy exposure to industrial chemicals and drugs known to cause aplastic anemia.
• Not taking medication that has triggered hemolytic anemia and not eating foods that have caused hemolysis (breakdown of red blood cells).
• Receiving regular B₁₂ shots to prevent pernicious anemia resulting from gastritis or stomach surgery.

Resources

Books

Fauci, Anthony S. et al., eds. Harrison's Principles of Internal Medicine. New York: McGraw-Hill, 1998.

Tierney, Lawrence M., Jr. Current Medical Diagnosis & Treatment, 1998. Stamford, Conn.: Appleton & Lange, 1998.

[Article by: Paula Ford-Martin]

Definition

Anemia is a blood disorder characterized by abnormally low levels of healthy red blood cells (RBCs) or reduced hemoglobin (Hgb), the iron-bearing protein in red blood cells that delivers oxygen to tissues throughout the body. Reduced blood cell volume (hematocrit) is also considered anemia. The reduction of any or all of the three blood parameters reduces the oxygen-carrying capability of the blood, causing reduced oxygenation of body tissues, a condition called hypoxia.

Description

All tissues in the human body need a regular supply of oxygen to stay healthy and perform their functions. RBCs contain Hgb, a protein pigment that allows the cells to carry oxygen (oxygenate) tissues throughout the body. RBCs live about 120 days and are normally replaced in an orderly way by the bone marrow, spleen, and liver. As RBCs break down, they release Hgb into the blood stream, which is normally filtered out by the kidneys and excreted. The iron released from the RBCs is returned to the bone marrow to help create new cells. Anemia develops when either blood loss, a slow-down in the production of new RBCs (erythropoiesis), or an increase in red cell destruction (hemolysis) causes significant reductions in RBCs, Hgb, iron levels, and the essential delivery of oxygen to body tissues.

Anemia can be mild, moderate, or severe enough to lead to life-threatening complications. More than 400 different types of anemia have been identified. Many of them are rare. Most are caused by ongoing or sudden blood loss. Other causes include vitamin and mineral deficiencies, inherited conditions, and certain diseases that affect red cell production or destruction.

Anemia in newborn infants is noted when hemoglobin levels are lower than expected for the birth weight and postnatal age. Premature or low birth-weight infants may have lower hemoglobin levels. The normal newborn Hgb is 16.8 dL, which may be 1 to 2 dL lower if birth weight is abnormally low. Anemia may be the first sign of certain disorders in the newborn, such as blood loss that has occurred from transplacental hemorrhage, a condition in which the infant's blood bleeds back into the mother's circulation; bleeding from ruptures in the liver, spleen, adrenals, or kidneys; or hemorrhage within the brain (intracranial hemorrhage). Anemia can also be caused by the destruction of red blood cells or reduced red blood cell production. Newborns may also have low red blood cell volume (hematocrit or Hct) if they were born by cesarean section. It must be noted, however, that hemoglobin decreases naturally (physiologic decrease) in infants by eight to 12 weeks of age, leveling at a normal value of 11 g/dL or better.

Iron-Deficiency Anemia

Iron deficiency anemia is the most common form of anemia worldwide. In the United States, it affects thousands of toddlers between one and two years of age and more than 3 million women of childbearing age. This condition is less common in older children and in adults over 50 and rarely occurs in teenage boys and young men.

The onset of iron deficiency anemia is gradual and may not have early symptoms. The deficiency begins when the body loses more iron than it derives from food and other sources. Because depleted iron stores cannot meet the red blood cell's needs, fewer red blood cells develop. In this early stage of anemia, the red blood cells look normal, but they are reduced in number. Then the body tries to compensate for the iron deficiency by producing more red blood cells, which are characteristically small in size (spherocytosis). Symptoms of anemia, especially weakness and fatigue, develop at this stage. Individuals may be given iron preparations by injection or advised to take oral iron supplements. It sometimes helps to take vitamin C along with oral iron supplementation to encourage better absorption of the iron. Taking iron supplements can result in diarrhea, cramps, or vomiting.

Folic Acid Deficiency Anemia

Folic acid deficiency anemia is the most common type of megaloblastic anemia, arising from a problem with the synthesis of deoxyribonucleic acid (DNA) within the cells of the body. It is characterized by RBCs that are larger than normal and is caused by a deficiency of folic acid, a vitamin that the body needs to produce normal cells and normal DNA.

Folic acid anemia is especially common in infants and teenagers. This condition usually results from a dietary deficiency but may also be due to an inability to absorb (malabsorption) folic acid. Folic acid is available in many foods, such as cheese, eggs, fish, green vegetables, meat, milk, mushrooms, and yeast. Smoking raises the risk of developing this condition by interfering with the absorption of vitamin C, which the body needs to absorb folic acid. Folic acid anemia can be a complication of pregnancy, when a woman's body needs eight times more folic acid than it does otherwise. Folic acid deficiency in pregnant women may lead to birth defects in their children. Supplementation of folic acid is recommended during pregnancy.

Vitamin B₁₂ Deficiency Anemia

Less common in the United States than folic acid anemia, vitamin B₁₂ deficiency anemia is another type of megaloblastic anemia that develops when the body does not absorb enough of this nutrient. Necessary for the creation of healthy RBCs, B₁₂ is found in meat, eggs, whole grains, and most vegetables. Large amounts of B₁₂ are stored in the body, so this condition may not become apparent until up to four years after B₁₂ absorption stops or slows down. The resulting drop in RBC production can cause loss of muscle control; loss of sensation in the legs, hands, and feet; soreness, slickness, or burning of the tongue; weight loss; or yellow-blue color blindness. Confusion, depression, and memory loss may also be associated with the deficiency.

Pernicious anemia is the most common form of B₁₂ deficiency. Since most people who eat meat or eggs get enough B₁₂ in their diets, a deficiency of this vitamin usually means that the body is not absorbing it properly. This condition can be found in those who do not produce adequate amounts of a chemical secreted by the stomach lining that combines with B₁₂ to help its absorption in the small intestine. Pernicious anemia is diagnosed more often in adults between ages 50 and 60 than in children or young people, although there is the possibility of inheriting the condition, with symptoms not appearing until later in life.

Vitamin C Deficiency Anemia

Anemia due to vitamin C deficiency is a rare disorder that causes the bone marrow to manufacture abnormally small red blood cells. Vitamin C deficiency anemia results from a severe, long-standing dietary deficiency or malabsorption of this essential vitamin. It is usually easily corrected with supplementation.

Hemolytic Anemia

Hemolytic anemia can be present at birth (congenital hemolytic anemia or spherocytosis) or acquired later in life. It is the result of either infection or the presence of antibodies that destroy RBCs more rapidly than bone marrow can replace them. Hemolytic anemia can enlarge the spleen, an organ that also produces red blood cells when necessary. Production of cells by the spleen will increase to meet the demands of accelerated RBC destruction (hemolysis). Complications of hemolytic anemia in older children or adults include pain, gallstones, and other serious health problems.

Hemolytic disease of the newborn is a specific variation of hemolytic anemia in which an incompatibility exists between antigens on the cells of the mother and baby, causing antibodies to develop in the mother's circulation. The antibodies are produced as an immune response to what the body views as foreign antigens on the surface of the infant's RBCs. Several specific antigens are responsible for the incompatibilities: Rh type incompatibility, ABO blood group incompatibility, and other incompatibilities involving antigens known as Kell, Duffy, M, N, and P, among many others. Hemolytic disease of the newborn and the anemia that results is detectable within the first few days after birth. Depending on the strength of the antibody, the anemia may clear up on its own or exchange transfusions may be necessary to replace the newborn's blood.

Thalassemia

An inherited form of hemolytic anemia, thalassemia comes from the production of abnormal hemoglobin. It is characterized by low hemoglobin and unusually small and fragile RBCs (microcytosis), although the RBC count may be normal. Thalassemia has several types that involve imbalances in the four chains of amino acids that comprise hemoglobin (alpha- and beta-globins). In thalassemia minor or thalassemia trait (heterozygous thalassemia), also called alpha-thalassemia, there is an imbalance in the production of the alpha chain of amino acids. In thalassemia minor, fetal hemoglobin (HbF), the hemoglobin form that circulates in the fetus, does not decrease normally after birth and may remain high in later life. A child may inherit thalassemia trait when only one parent has the genes responsible for it. It is usually not treated and does not have serious consequences. Thalassemia major (homozygous thalassemia or Cooley's anemia) occurs in children in whom both parents pass on the genes responsible. It is known as beta-thalassemia, because of an imbalance in the beta chain amino acids of hemoglobin. It also involves the persistence of HbF with larger than normal amounts appearing in the child's circulation. Alpha-thalassemias occur most commonly in African Americans; beta-thalassemias most commonly affect people of Mediterranean or middle-Eastern ancestry and Southeast Asians. Hemoglobin H disease is another form of thalassemia in which three of the four beta-globin genes are missing.

Sickle Cell Anemia

Sickle cell anemia is an inherited, chronic, incurable blood disorder that causes the body to produce defective hemoglobin, the abnormal HgbS, which occurs primarily in African Americans. The condition is characterized by abnormal, crescent-shaped RBCs. Unlike normal oval cells, fragile sickle cells cannot hold enough hemoglobin to nourish body tissues. The deformed shape makes it hard for sickle cells to pass through narrow blood vessels. When capillaries become obstructed, a life-threatening condition called sickle cell crisis is likely to occur. A child who inherits the sickle cell gene from each parent will have the disease. A child who inherits the sickle cell gene from only one parent carries the sickle cell trait but does not have the disease.

Aplastic Anemia

Sometimes curable by bone marrow transplant, but potentially fatal, aplastic anemia is characterized by decreased production of red and white blood cells and platelets (disc-shaped cells that are a key component of blood coagulation). This disorder may be inherited or acquired as a result of the following:

• recent severe illness
• long-term exposure to industrial chemicals
• chemotherapy, use of anticancer drugs, and certain other medications

Anemia of Chronic Disease

Cancer, chronic infection or inflammation, and kidney and liver disease often cause mild or moderate anemia. Chronic liver failure generally produces the most severe symptoms because the production of RBCs is directly affected.

Causes and Symptoms

Anemias do not all stem from the same causes. Anemia can be the result of injuries, chronic or acute illnesses, complications of surgery or childbirth, metabolic disturbances or deficiencies, and adverse response to drug therapy administered for other conditions. Causes may include sudden or ongoing loss of blood, nutritional deficiencies, decreased red blood cell production, or increased red blood cell destruction. Malnutrition or malabsorption of nutrients can contribute to vitamin deficiency anemia and iron deficiency anemias. Although red cell destruction and replacement is an ongoing process in the body, hereditary disorders and certain diseases can accelerate blood cell destruction, resulting in anemia. However, excessive bleeding is the most common cause of severe anemia, and the speed with which blood loss occurs has a significant effect on the severity of symptoms. Chronic blood loss may be a consequence of the following:

• cancer
• gastrointestinal tumors
• diverticulosis
• polyposis
• heavy or frequent menstrual flow
• hemorrhoids
• nosebleeds
• stomach ulcers
• long-standing alcohol abuse

Acute blood loss may occur as a result of injury, a ruptured blood vessel, or a complication of surgery or childbirth. When a lot of blood is lost within a short time, blood pressure and the amount of oxygen in the body drop suddenly, sometimes leading to heart failure or death. Loss of even one third of the body's blood volume in the space of several hours can be fatal. Gradual blood loss is less threatening, because the body has time to replace RBCs and blood volume.

Symptoms

Weakness, fatigue, and a run-down feeling may be the first signs of anemia. Pasty or sallow skin color, or the absence of color in the gums, nail beds, creases of the palm, or lining of the eyelids are other signs of anemia. Individuals who appear to be weak, easily tired, often out of breath, and who may feel faint or dizzy on movement may be severely anemic.

Other symptoms of anemia may include the following:

• unusual cravings for ice (chewing on ice cubes), paint, or earth (actually eating dirt)
• headache
• inability to concentrate, memory loss
• inflammation of the mouth (stomatitis) or tongue (glossitis)
• insomnia
• irregular heartbeat
• loss of appetite
• dry, brittle, or ridged nails
• rapid breathing
• sores in the mouth, throat, or rectum
• perspiration, especially around the head and neck
• swelling of hands and feet
• constant thirst
• ringing in the ears (tinnitus)
• unexplained bleeding or bruising
• angina pectoris, i.e., chest pain accompanied by a choking sensation that may provoke anxiety

Demographics

Acquired anemias affect about 4 million individuals in the United States, and over 50 percent of these are under age 45, although less than 10 percent of cases occur in children and adolescents. In the United States, iron deficiency anemia is the most prevalent type of anemia, affecting about 240,000 toddlers between one and two years of age and 3.3 million women of childbearing age. Anemia due to gradual blood loss is more common in women than in men, particularly pregnant women or women of menstruating age. Pernicious anemia is more common in women and in African Americans and is less common in other racial groups. Folate deficiency is not common in young people who eat an adequate diet and is usually associated with malnutrition, pregnancy, and alcoholism. Sickle cell anemia is more frequently diagnosed than thalassemias and occurs most often among African Americans. Thalassemia occurs in four out of 100,000 individuals in the United States, particularly among those of Mediterranean, Asian, or middle Eastern descent.

When to Call the Doctor

When a child exhibits weakness, dizziness, listlessness, or fatigue, it may be the first sign of anemia. The pediatrician should be consulted if the child is also extremely pale or has little or no color in the gums, nail beds, creases of the palm, or lining of the eyelids. Any prolonged bleeding or sudden blood loss requires examination by a physician and testing for anemia.

Diagnosis

The child's medical history will be taken, including the child's age, symptoms, illnesses, and general state of health, and a family history of ancestry and known inherited anemias will be noted. Symptoms noticed in children by their parents may include fatigue, weight loss, inability to concentrate, loss of appetite, and light-headedness when standing up. The physical examination may reveal paleness, lack of color in the creases of the palm, gums, and the linings of the eyelids. The child's breathing rate may be increased and, in advanced cases, the spleen or liver may be enlarged when palpated. If anemia is due to chronic disease, there may be evidence of infection or inflammation. Urine output may be reduced in severe anemia.

Diagnostic testing begins with a complete blood count (CBC) and differential to reveal the RBC count, white blood cell (WBC) count, hemoglobin (Hgb), and hematocrit (Hct); any of these counts can be altered, and in most anemias the RBC and hemoglobin will be reduced. The mean corpuscular volume (MCV) will be measured to compare the size of RBCs with normal RBCs. A reticulocyte (young RBCs) count will help determine if anemia is caused by impaired RBC production or increased RBC destruction. Iron, vitamin C, vitamin B₁₂, and folate levels will be measured to evaluate and identify possible deficiencies. Diagnosing thalassemia and sickle cell anemia, both of which involve disorders of hemoglobin, will require measuring the different types of hemoglobin through a laboratory testing method called hemoglobin electrophoresis. In some anemias, a bone marrow sample will be removed (bone marrow biopsy) for microscopic examination, especially to confirm iron deficiency anemia or the megaloblastic anemias. Kidney function tests, coagulation tests, and stool examinations for occult blood may also be performed.

Treatment

Surgery may be necessary to correct blood losses caused by injury or hemorrhage (nose bleeds, aneurysm, cerebral hemorrhage, bleeding ulcer) or childbirth. Transfusions of packed red blood cells or whole blood may also be used to replace blood volume and to stimulate the body's own production of red blood cells. Medication or surgery may also be necessary to control heavy menstrual flow or to remove polyps (growths or nodules) from the bowels.

Anemia due to nutritional deficiencies can usually be treated with iron replacement therapy, specific vitamin supplements, or self-administered injections of vitamin B₁₂. People with folic acid anemia may be advised to take oral folic acid.

Vitamin B₁₂ deficiency anemia requires a life-long regimen of B₁₂ shots to maintain vitamin levels and control symptoms of pernicious anemia. The patient may be advised to limit physical activity until treatment restores strength and balance.

Anemia resulting from chronic disease is typically corrected by treating the underlying illness. This type of anemia rarely becomes severe. If it does, transfusions or hormone treatments to stimulate red blood cell production may be given.

Thalassemia minor is typically not treated. Thalassemia major may be treated with regular transfusions, surgical resection of the spleen to avoid its removal of RBCs from circulation, and sometimes iron chelation therapy. Symptoms are treated as they occur. Children or young adults with thalassemia major may require periodic hospitalization to receive blood transfusions or, in some cases, bone marrow transplants.

Sickle cell anemia will be monitored by regular eye examinations and diagnostic blood work. Immunizations for pneumonia and infectious diseases are part of treatment along with prompt treatment for sickle cell crises and infections of any kind. Psychotherapy or counseling may help older children deal with the emotional symptoms characteristic of this condition.

Children with aplastic anemia are especially susceptible to infection. Treatment for aplastic anemia may involve blood transfusions and bone marrow transplantation to replace malfunctioning cells with healthy ones.

Hemolytic anemia of the warm-antibody type may be treated with large doses of intravenous and oral corticocosteroids (cortisone). Individuals who do not respond to medical therapy, may undergo surgery to remove the spleen, which controls the anemia in some individuals by helping to add more RBCs to the circulation. Immune-system suppressants are prescribed when surgery is not successful. There is no specific treatment for cold-anti-body hemolytic anemia.

Treatment of newborn anemia depends on the severity of symptoms, the level of Hgb, and the presence of any other diseases that may affect oxygen delivery, such as lung or heart disease or hyaline membrane disease. Transfusions may be given in certain situations or exchange transfusions if hemolytic disease of the newborn is not quickly resolved. The risk of transfusion (such as transfusion reactions, potential toxins, and infections such as HIV or hepatitis) are carefully weighed against the severity of the anemia in the infant.

Alternative Treatment

Vitamin C is noted for helping to absorb iron and folate supplements. Cooking in a cast iron skillet may leach small amounts of absorbable iron into the diet. Folic acid can be readily absorbed from raw salad greens such as lettuce, spinach, arugula, alfalfa sprouts, and others. Blackstrap molasses is a good source of iron and B vitamins. Herbal supplements that will benefit individuals who have anemia include bilberry, dandelion, goldenseal, mullein, nettle, Oregon grape root, red raspberry, and yellow dock. Herbs are available as tinctures and teas or in capsules.

Nutritional Concerns

The diet is a ready source of nutrients that prevent and treat anemia. Children with anemia can include more of these nutrients in their diet by eating a broad variety of whole grains, fruits and vegetables, beans, lean meat, poultry and fish, and supplementing the diet regularly with vitamins, minerals, and iron (as recommended). Pediatricians should be consulted before iron supplements are taken, however, because of the difficulty in absorbing non-food sources of iron. Vitamin C can stimulate iron absorption. Good food sources of iron include: almonds, broccoli, dried beans, raisins, dried apricots, seaweed (as soup stock), whole-grain breads and cereals, brown rice, lean red meat, liver, potatoes, poultry, and shellfish.

Because light and heat destroy folic acid, fruits and vegetables should be eaten raw or cooked as little as possible to help assimilation of folic acid. Folic acid can also be taken as a supplement.

Prognosis

Most anemias can be treated or managed. The prognosis for anemias generally depends upon the severity of the anemia, the type of anemia, and the response to treatment. The hereditary anemias, such as the thalassemias and sickle cell anemia, may require life-long treatment and monitoring whereas other types of anemia, once treated, are apt not to recur. Thalassemia major may cause deformities and may shorten life expectancy. Severe anemia may lead to other serious conditions, particularly if oxygen delivery is compromised for long periods of time or RBC destruction is more rapid than can be controlled by normal RBC replacement or specific treatment. Severe blood loss or prolonged anemia can result in life-threatening complications.

Prevention

Safety is the primary preventive measure for blood loss by injury. A wholesome, balanced diet rich in nutrients can help prevent dietary deficiencies that lead to anemia. Hereditary anemias cannot be prevented; parents can seek genetic testing and counseling if they are concerned about inherited anemias noted in their families or ethnic background.

Nutritional Concerns

Sources of iron such as liver, red meat, whole grains, and poultry may help maintain hemoglobin levels and reduce the likelihood of deficiency-related anemias. Vitamin C is noted for helping to improve assimilation of iron taken as supplements.

Parental Concerns

Parents may be particularly concerned about the possibility of inherited anemias. Genetic testing is available to address their doubts. Nutrition education is readily available from public health sources, books, and the reliable Internet sources for parents who are concerned about providing essential nutrients for children who may be susceptible to deficiency anemias. Regular physical examinations can help evaluate a child's overall health and reveal possible signs or symptoms of anemia.

Resources

Books

"Blood Disorders." The Merck Manual of Medical Information, 2nd Home ed. Edited by Mark H. Beers et al. White House Station, NJ: Merck & Co., 2003.

Hill, Shirley, A. Managing Sickle Cell Disease in Low-Income Families. Philadelphia: Temple University Press, 2003.

Lande, Bruce. Aplastic Anemia and Other Autoimmune Diseases: Help Your Body Heal Itself. Syracuse, NY: Action Enterprises, 2003.

Ross, Allison J. Everything You Need to Know about Anemia. New York: Rosen Publishing Group, 2001.

Wick, M., et al. Iron Metabolism, Anemias, Clinical Aspects and Laboratory. New York: Springer, 2003.

Organizations

National Heart, Lung, and Blood Institute (NHLBI). 6701 Rockledge Drive, PO Box 30105, Bethesda, MD 20824–0105. Web site: .

Web Sites

"Anemia." KidsHealth. Available online at (accessed October 10, 2004).

"Understanding Anemia: Your Life May Depend on It." Anemia Lifeline. Available online at www.anemia.com (accessed October 10, 2004).

[Article by: L. Lee Culvert Maureen Haggerty]

A condition in which the capacity of the blood to carry oxygen is decreased because of too few red blood cells in circulation or because of too little hemoglobin.

A reduction below normal in the number or volume of erythrocytes or in the quantity of hemoglobin in the blood. Clinically it is manifested by weakness, exercise intolerance, hyperpnea which is only moderate, pallor of mucosae, tachycardia and a large increase in the intensity of the heart sounds. There are often accompanying signs related to the site of blood or hemoglobin loss.

• aplastic a. — a form of anemia generally unresponsive to specific antianemia therapy. It is often chronic, accompanied by granulocytopenia and thrombocytopenia, in which the bone marrow is usually acellular or hypoplastic. It may, however, be rapidly fatal. The term is actually all-inclusive and most probably encompasses several clinical syndromes. See pure red cell aplasia.
• autoimmune hemolytic a. — immune-mediated hemolytic anemia, which occurs in many species, particularly dogs, in which autoantibodies directed against red blood cells are produced. Different classes of immunoglobulins may be involved giving rise to differing clinical syndromes. Signs include pallor, lethargy, splenomegaly, and sometimes icterus, bilirubinuria and hemoglobinuria. There may also be an accompanying thrombocytopenia with bleeding tendencies. Diagnosis is based on a positive Coombs test.
• avian infectious a. — see chicken anemia.
• blood loss a. — see hemorrhagic anemia (below).
• a. of chronic disease — see anemia of inflammatory disease (below).
• cold antibody a. — an immune-mediated hemolytic anemia in which the antibody is maximally active at temperatures below 98.6°F (37°C). See also cold agglutinin disease.
• cold (or cold water) a. — a disease of cattle, especially calves, housed in warm barns and given near freezing water to drink. Dyspnea and the passage of red urine occur several hours after a large drink.
• Coombs-positive a. — immunoglobulin-mediated anemia that gives a positive reaction to Coombs tests, indicating the presence of immunoglobulins on the red cell surface. See also autoimmune hemolytic anemia (above), alloimmune hemolytic anemia of the newborn.
• deficiency a. — nutritional anemia.
• drug-induced hemolytic a. — some drugs such as quinine, quinidine, para-aminosalicylic acid, phenacetin, penicillin, insecticides, chlorpromazine, sulfonamides and dipyrone may be directly injurious to red cells or act to initiate an immune response in which red cells are destroyed.
• familial nonspherocytic a. of Basenji dogs — an inherited pyruvate kinase deficiency causes a hemolytic anemia with shortened red cell life span. In early stages, the disease is characterized by very active erythropoiesis but eventually, usually by the second or third year of life, a terminal myelofibrosis and osteosclerosis develops. The disease is inherited as an autosomal recessive trait.
• feline infectious a. — see feline infectious anemia.
• fragmentation a. — see microangiopathic anemia (below).
• Heinz body a. — hemolytic anemia resulting from oxidation of globin and formation of Heinz bodies, which are seen in blood smears as dark refractile intracytoplasmic bodies and stain with new methylene blue. Some common causes are ingestion of onions and plants in the Brassicaeae family, phenazopyridine, methylene blue and acetaminophen (paracetamol). Cats are particularly susceptible to Heinz body formation.
• hemolytic a. — see hemolytic anemia.
• hemorrhagic a. — is caused by loss of whole blood. If this is very rapid hypovolemic shock develops. At a slower rate there is anemic anoxia and the animal is suffering from anemia. Called also blood loss anemia.
• hypochromic a. — anemia in which the decrease in hemoglobin is proportionately much greater than the decrease in number of erythrocytes.
• hypoplastic a. — anemia due to incapacity of blood-forming organs, i.e. inactivity of the bone marrow. See also aplastic anemia (above).
• idiopathic immune a. — see autoimmune hemolytic anemia (above).
• infectious equine a. — see equine infectious anemia.
• a. of inflammatory disease — a nonregenerative, usually mild, anemia that occurs in association with malignancy or chronic infection. Although other causes of anemia such as hemolysis and blood loss may also occur with these conditions, there is altered iron metabolism with decreased serum iron and iron-binding capacity but with increased iron storage that results in decreased erythropoiesis.
• iron-deficiency a. — a form characterized by low or absent iron stores, low serum iron concentration, low transferrin saturation, elevated transferrin (iron-binding capacity), low hemoglobin concentration or hematocrit, and hypochromic, microcytic red blood corpuscles, and thrombocytosis. See also iron.
• isoimmune hemolytic a. — see alloimmune hemolytic anemia of the newborn.
• lizard viral a. — produces inclusion bodies in erythrocytes, commonly mistaken for protozoan parasites.
• macrocytic a. — anemia in which the erythrocytes are much larger than normal. The MCV (mean corpuscular volume) and MCH (mean corpuscular hemoglobin) are increased and the MCHC (mean corpuscular hemoglobin concentration) is normal.
• megaloblastic a. — anemia characterized by the presence of megaloblasts in the bone marrow and macrocytic erythrocytes. It occurs in vitamin B₁₂, cobalt and folic acid deficiencies and in some myeloproliferative disorders in cats.
• microangiopathic a. — anemia due to fragmentation of erythrocytes in blood vessels whose endothelium has been badly damaged, usually by an infectious disease such as septicemias, disseminated intravascular coagulation and salmonellosis. Called also fragmentation anemia.
• microcytic a. — anemia characterized by decrease in size of the erythrocytes.
• myelopathic a., myelophthisic a. — anemia due to destruction or crowding out of hematopoietic tissues by space-occupying lesions, neoplasms and fibrosis.
• nonregenerative a. — one occurring without an appropriate erythropoietic response by the bone marrow.
• normochromic a. — that in which the hemoglobin content of the red cells as measured by the MCHC and MCH is within the normal range.
• normocytic a. — the anemia in which the red blood cells are normal in size.
• nutritional a. — anemia due to a deficiency of an essential substance in the diet, which may be caused by poor dietary intake or by malabsorption; called also deficiency anemia. See also pyridoxine, vitamin b12, folic acid, copper, iron.
• parasitic a. — hemorrhagic anemia due to blood loss caused by blood-sucking parasites such as fleas, hookworms and Haemonchus contortus.
• pernicious a. — see pernicious anemia.
• physiological a. — the anemia which occurs as part of a natural event, e.g. in neonates.
• piglet a. — see iron nutritional deficiency.
• primary immune a. — see autoimmune hemolytic anemia (above).
• regenerative a., responsive a. — associated with active erythropoiesis with increased numbers of reticulocytes, nucleated red blood cells, anisocytosis and polychromasia in the peripheral blood.
• spur-cell a. — anemia in which the red cells have a bizarre spiculated shape and are destroyed prematurely, primarily in the spleen; it is an acquired form occurring in severe liver disease, and represents an abnormality in the cholesterol content of the red cell membrane.
• unresponsive a. — see nonregenerative anemia (above).

Anemia is a disease of the blood that has come, in some quarters, to be associated with vampirism. Anemia is caused by a reduction of either red blood cells or hemoglobin (the oxygen-carrying pigment of the cells) relative to the other ingredients in the blood. The symptoms include a pale complexion, fatigue, and in its more extreme instances, fainting spells. All are symptoms usually associated with a vampire attack. In Bram Stoker's novel, Dracula during the early stages of Lucy Westenra's illness, Dr. John Seward hypothesized that possibly she was suffering from anemia. He later concluded that she was not suffering from the loss of red blood cells, but from the loss of whole blood. Dr. Abraham Van Helsing agreed with his friend, "I have made careful examination, but there is no functional cause. With you I agree that there has been much blood lost; it has been, but is not. But the conditions of her are in no way anaemic." (Chapter 9) Thus, the association of anemia and vampirism was dismissed.

For other uses, see Anemia (disambiguation).

It has been suggested that Refractory anemia be merged into this article or section. (Discuss)

This article needs additional citations for verification. Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (January 2008)

Anemia
Classification and external resources
Peripheral blood smear microscopy of a patient with iron-deficiency anemia.
ICD-10	D50.-D64.
ICD-9	280-285
DiseasesDB	663
MedlinePlus	000560
eMedicine	med/132 emerg/808 emerg/734
MeSH	D000740

Anemia (pronounced /əˈniːmiə/, also spelled anaemia or anæmia; from Ancient Greek ἀναιμία anaimia, meaning "lack of blood") is a decrease in normal number of red blood cells (RBCs) or less than the normal quantity of hemoglobin in the blood.^[1][2] However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin deficiency.

Since hemoglobin (found inside RBCs) normally carries oxygen from the lungs to the tissues, anemia leads to hypoxia (lack of oxygen) in organs. Since all human cells depend on oxygen for survival, varying degrees of anemia can have a wide range of clinical consequences.

The three main classes of anemia include excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss), excessive blood cell destruction (hemolysis) or deficient red blood cell production (ineffective hematopoiesis).

Anemia is the most common disorder of the blood. There are several kinds of anemia, produced by a variety of underlying causes. Anemia can be classified in a variety of ways, based on the morphology of RBCs, underlying etiologic mechanisms, and discernible clinical spectra, to mention a few.

There are two major approaches: the "kinetic" approach which involves evaluating production, destruction and loss^[3], and the "morphologic" approach which groups anemia by red blood cell size. The morphologic approach uses a quickly available and cheap lab test as its starting point (the MCV). On the other hand, focusing early on the question of production may allow the clinician more rapidly to expose cases where multiple causes of anemia coexist.

Contents 1 Signs and symptoms 2 Diagnosis 3 Classification 3.1 Production vs. destruction or loss 3.2 Red blood cell size 3.2.1 Microcytic anemia 3.2.2 Macrocytic anemia 3.2.3 Normocytic anemia 3.2.4 Dimorphic anemia 3.2.5 Heinz body anemia 4 Specific anemias 5 Possible complications 6 Anemia during pregnancy 7 Treatments for anemia 7.1 Blood transfusions for anemia 7.2 Hyperbaric oxygenation 8 See also 9 References 10 External links

Signs and symptoms

Main symptoms that may appear in anemia.^[4]

Anemia goes undetected in many people, and symptoms can be small and vague. The signs and symptoms can be related to the anemia itself, or the underlying cause.

Most commonly, people with anemia report non-specific symptoms of a feeling of weakness, or fatigue, general malaise and sometimes poor concentration. They may also report shortness of breath, dyspnea, on exertion. In very severe anemia, the body may compensate for the lack of oxygen carrying capability of the blood by increasing cardiac output. The patient may have symptoms related to this, such as palpitations, angina (if preexisting heart disease is present), intermittent claudication of the legs, and symptoms of heart failure.

On examination, the signs exhibited may include pallor (pale skin, mucosal linings and nail beds) but this is not a reliable sign. There may be signs of specific causes of anemia, eg koilonychia (in iron deficiency), jaundice (when anemia results from abnormal break down of red blood cells — in haemolytic anemia), bone deformities (found in thalassaemia major) or leg ulcers (seen in sickle cell disease).

In severe anemia, there may be signs of a hyperdynamic circulation: a fast heart rate (tachycardia), flow murmurs, and cardiac enlargement. There may be signs of heart failure.

Pica, the consumption of non-food based items such as dirt, paper, wax, grass, ice, and hair, may be a symptom of iron deficiency, although it occurs often in those who have normal levels of hemoglobin.

Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced scholastic performance in children of school age.

Restless legs syndrome is more common in those with iron deficiency anemia.

Less common symptoms may include swelling of the legs or arms, chronic heartburn, vague bruises, vomiting, increased sweating, and blood in stool.

Diagnosis

Generally, clinicians request complete blood counts in the first batch of blood tests in the diagnosis of an anemia. Apart from reporting the number of red blood cells and the hemoglobin level, the automatic counters also measure the size of the red blood cells by flow cytometry, which is an important tool in distinguishing between the causes of anemia. Examination of a stained blood smear using a microscope can also be helpful, and is sometimes a necessity in regions of the world where automated analysis is less accessible.

In modern counters, four parameters (RBC count, hemoglobin concentration, MCV and RDW) are measured, allowing others (hematocrit, MCH and MCHC) to be calculated, and compared to values adjusted for age and sex. Some counters estimate hematocrit from direct measurements.

WHO's Hemoglobin thresholds used to define anemia^[5] (1 g/dL = 0.6206 mmol/L)^{[citation needed]}

Age or gender group	Hb threshold (g/dl)	Hb threshold (mmol/l)
Children (0.5-5.0 yrs)	11.0	6.8
Children (5-12 yrs)	11.5	7.1
Children (12-15 yrs)	12.0	7.4
Women, non-pregnant (>15yrs)	12.0	7.4
Women, pregnant	11.0	6.8
Men (>15yrs)	13.0	8.1

Reticulocyte counts, and the "kinetic" approach to anemia, have become more common than in the past in the large medical centers of the United States and some other wealthy nations, in part because some automatic counters now have the capacity to include reticulocyte counts. A reticulocyte count is a quantitative measure of the bone marrow's production of new red blood cells. The reticulocyte production index is a calculation of the ratio between the level of anemia and the extent to which the reticulocyte count has risen in response. If the degree of anemia is significant, even a "normal" reticulocyte count actually may reflect an inadequate response.

If an automated count is not available, a reticulocyte count can be done manually following special staining of the blood film. In manual examination, activity of the bone marrow can also be gauged qualitatively by subtle changes in the numbers and the morphology of young RBCs by examination under a microscope. Newly formed RBCs are usually slightly larger than older RBCs and show polychromasia. Even where the source of blood loss is obvious, evaluation of erythropoiesis can help assess whether the bone marrow will be able to compensate for the loss, and at what rate.

When the cause is not obvious, clinicians use other tests: ESR, ferritin, serum iron, transferrin, RBC folate level, serum vitamin B12, hemoglobin electrophoresis, renal function tests (e.g. serum creatinine).

When the diagnosis remains difficult, a bone marrow examination allows direct examination of the precursors to red cells.

Classification

Production vs. destruction or loss

The "kinetic" approach to anemia yields what many argue is the most clinically relevant classification of anemia. This classification depends on evaluation of several hematological parameters, particularly the blood reticulocyte (precursor of mature RBCs) count. This then yields the classification of defects by decreased RBC production versus increased RBC destruction and/or loss. Clinical signs of loss or destruction include abnormal peripheral blood smear with signs of hemolysis; elevated LDH suggesting cell destruction; or clinical signs of bleeding, such as guiaic-positive stool, radiographic findings, or frank bleeding.

The following is a simplified schematic of this approach:

Anemia

Reticulocyte production index shows inadequate production response to anemia.

Reticulocyte production index shows appropriate response to anemia = ongoing hemolysis or blood loss without RBC production problem.

No clinical findings consistent with hemolysis or blood loss: pure disorder of production.

Clinical findings and abnormal MCV: hemolysis or loss and chronic disorder of production*.

Clinical findings and normal MCV= acute hemolysis or loss without adequate time for bone marrow production to compensate**.

Macrocytic anemia (MCV>100)

Normocytic anemia (80<MCV<100)

Microcytic anemia (MCV<80)

* For instance, sickle cell anemia with superimposed iron deficiency; chronic gastric bleeding with B12 and folate deficiency; and other instances of anemia with more than one cause.
** Confirm by repeating reticulocyte count: ongoing combination of low reticulocyte production index, normal MCV and hemolysis or loss may be seen in bone marrow failure or anemia of chronic disease, with superimposed or related hemolysis or blood loss.

Red blood cell size

In the morphological approach, anemia is classified by the size of red blood cells; this is either done automatically or on microscopic examination of a peripheral blood smear. The size is reflected in the mean corpuscular volume (MCV). If the cells are smaller than normal (under 80 fl), the anemia is said to be microcytic; if they are normal size (80-100 fl), normocytic; and if they are larger than normal (over 100 fl), the anemia is classified as macrocytic. This scheme quickly exposes some of the most common causes of anemia; for instance, a microcytic anemia is often the result of iron deficiency. In clinical workup, the MCV will be one of the first pieces of information available; so even among clinicians who consider the "kinetic" approach more useful philosophically, morphology will remain an important element of classification and diagnosis.

Here is a schematic representation of how to consider anemia with MCV as the starting point:

Anemia

Macrocytic anemia (MCV>100)

Microcytic anemia (MCV<80)

Normocytic anemia (80<MCV<100)

High reticulocyte count

Low reticulocyte count

Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal white blood cells may point to a cause in the bone marrow.

Microcytic anemia

Main article: Microcytic anemia

Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies:

• Heme synthesis defect
  • Iron deficiency anemia
  • Anemia of chronic disease (more commonly presenting as normocytic anemia)
• Globin synthesis defect
  • alpha-, and beta-thalassemia
  • HbE syndrome
  • HbC syndrome
  • and various other unstable hemoglobin diseases
• Sideroblastic defect
  • Hereditary sideroblastic anemia
  • Acquired sideroblastic anemia, including lead toxicity
  • Reversible sideroblastic anemia

Iron deficiency anemia is the most common type of anemia overall and it has many causes. RBCs often appear hypochromic (paler than usual) and microcytic (smaller than usual) when viewed with a microscope.

• Iron deficiency anemia is caused by insufficient dietary intake or absorption of iron to replace losses from menstruation or losses due to diseases.^[6] Iron is an essential part of hemoglobin, and low iron levels result in decreased incorporation of hemoglobin into red blood cells. In the United States, 20% of all women of childbearing age have iron deficiency anemia, compared with only 2% of adult men. The principal cause of iron deficiency anemia in premenopausal women is blood lost during menses. Studies^[who?] have shown that iron deficiency without anemia causes poor school performance and lower IQ in teenage girls. Iron deficiency is the most prevalent deficiency state on a worldwide basis. Iron deficiency is sometimes the cause of abnormal fissuring of the angular (corner) sections of the lips (angular stomatitis).
• Iron deficiency anemia can also be due to bleeding lesions of the gastrointestinal tract. facel occult blood testing, upper endoscopy and lower endoscopy should be performed to identify bleeding lesions. In men and post-menopausal women the chances are higher that bleeding from the gastrointestinal tract could be due to colon polyp or colorectal cancer.
• Worldwide, the most common cause of iron deficiency anemia is parasitic infestation (hookworm, amebiasis, schistosomiasis and whipworm).^[7]

Macrocytic anemia

Main article: Macrocytic anemia

• Megaloblastic anemia, the most common cause of macrocytic anemia, is due to a deficiency of either vitamin B12, folic acid (or both). Deficiency in folate and/or vitamin B12 can be due either to inadequate intake or insufficient absorption. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does.
  • Pernicious anemia is caused by a lack of intrinsic factor. Intrinsic factor is required to absorb vitamin B12 from food. A lack of intrinsic factor may arise from an autoimmune condition targeting the parietal cells (atrophic gastritis) that produce intrinsic factor or against intrinsic factor itself. These lead to poor absorption of vitamin B12.
  • Macrocytic anemia can also be caused by removal of the functional portion of the stomach, such as during gastric bypass surgery, leading to reduced vit B12/folate absorption. Therefore one must always be aware of anemia following this procedure.
• Hypothyroidism
• Alcoholism commonly causes a macrocytosis, although not specifically anemia. Other types of Liver Disease can also cause macrocytosis.
• Methotrexate, zidovudine, and other drugs that inhibit DNA replication.

Macrocytic anemia can be further divided into "megaloblastic anemia" or "non-megaloblastic macrocytic anemia". The cause of megaloblastic anemia is primarily a failure of DNA synthesis with preserved RNA synthesis, which result in restricted cell division of the progenitor cells. The megaloblastic anemias often present with neutrophil hypersegmentation (6-10 lobes). The non-megaloblastic macrocytic anemias have different etiologies (i.e. there is unimpaired DNA globin synthesis,) which occur, for example in alcoholism.

In addition to the non-specific symptoms of anemia, specific features of vitamin B12 deficiency include peripheral neuropathy and subacute combined degeneration of the cord with resulting balance difficulties from posterior column spinal cord pathology.^[8] Other features may include a smooth, red tongue and glossitis.

The treatment for vitamin B12-deficient anemia was first devised by William Murphy who bled dogs to make them anemic and then fed them various substances to see what (if anything) would make them healthy again. He discovered that ingesting large amounts of liver seemed to cure the disease. George Minot and George Whipple then set about to chemically isolate the curative substance and ultimately were able to isolate the vitamin B12 from the liver. All three shared the 1934 Nobel Prize in Medicine.^[9]

Normocytic anemia

Main article: Normocytic anemia

Normocytic anemia occurs when the overall hemoglobin levels are always decreased, but the red blood cell size (Mean corpuscular volume) remains normal. Causes include:

• Acute blood loss
• Anemia of chronic disease
• Aplastic anemia (bone marrow failure)
• Hemolytic anemia

Dimorphic anemia

When two causes of anemia act simultaneously, e.g., macrocytic hypochromic, due to hookworm infestation leading to deficiency of both iron and vitamin B12 or folic acid ^[10] or following a blood transfusion more than one abnormality of red cell indices may be seen. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), which suggests a wider-than-normal range of red cell sizes.

Heinz body anemia

Heinz bodies form in the cytoplasm of RBCs and appear like small dark dots under the microscope. There are many causes of Heinz body anemia, and some forms can be drug induced. It is triggered in cats by eating onions^[11] or acetaminophen (Tylenol). It can be triggered in dogs by ingesting onions or zinc, and in horses by ingesting dry red maple leaves.

Specific anemias

• Anemia of prematurity occurs in premature infants at 2 to 6 weeks of age and results from diminished erythropoietin response to declining hematocrit levels.
• Aplastic anemia is a condition generally unresponsive to anti-anemia therapies where bone marrow fails to produce enough red blood cells.
• Fanconi anemia is a hereditary disorder or defect featuring aplastic anemia and various other abnormalities.
• Hemolytic anemia causes a separate constellation of symptoms (also featuring jaundice and elevated LDH levels) with numerous potential causes. It can be autoimmune, immune, hereditary or mechanical (e.g. heart surgery). It can result (because of cell fragmentation) in a microcytic anemia, a normochromic anemia, or (because of premature release of immature red blood cells from the bone marrow), a macrocytic anemia.
• Hereditary spherocytosis is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the spleen. This leads to a decrease in the number of circulating RBCs and, hence, anemia.
• Sickle-cell anemia, a hereditary disorder, is due to homozygous hemoglobin S genes.
• Warm autoimmune hemolytic anemia is an anemia caused by autoimmune attack against red blood cells, primarily by IgG.
• Cold agglutinin hemolytic anemia is primarily mediated by IgM.
• Pernicious anemia is a form of megaloblastic anemia due to vitamin B12 deficiency dependent on impaired absorption of vitamin B12.
• Myelophthisic anemia or Myelophthisis is a severe type of anemia resulting from the replacement of bone marrow by other materials, such as malignant tumors or granulomas.
• Anemia of Pregnancy is anemia that is induced by blood volume expansion experienced in pregnancy.

Possible complications

Anemia diminishes the capability of individuals who are affected to perform physical activities. This is a result of one's muscles being forced to depend on anaerobic metabolism. The lack of iron associated with anemia can cause many complications, including hypoxemia, brittle or rigid fingernails, cold intolerance, and possible behavioral disturbances in children. Hypoxemia resulting from anemia can worsen the cardio-pulmonary status of patients with pre-existing chronic pulmonary disease. Cold intolerance occurs in one in five patients with iron deficiency anemia, and becomes visible through numbness and tingling.^{[citation needed]}

Anemia during pregnancy

Anemia affects 20% of all females of childbearing age in the United States. Because of the subtlety of the symptoms, women are often unaware that they have this disorder, as they attribute the symptoms to the stresses of their daily lives. Possible problems for the fetus include increased risk of growth retardation, prematurity, intrauterine death, rupture of the amnion and infection.

During pregnancy, women should be especially aware of the symptoms of anemia, as an adult female loses an average of two milligrams of iron daily. Therefore, she must intake a similar quantity of iron in order to make up for this loss. Additionally, a woman loses approximately 500 milligrams of iron with each pregnancy, compared with a loss of 4-100 milligrams of iron with each period. Possible consequences for the mother include cardiovascular symptoms, reduced physical and mental performance, reduced immune function, fatigue, reduced peripartal blood reserves and increased need for blood transfusion in the postpartum period. This will severely affect the health of the child in some way or another.

Treatments for anemia

There are many different treatments for anemia and the treatment depends on severity and the cause.

Iron deficiency from nutritional causes is rare in non-menstruating adults (men and post-menopausal women). The diagnosis of iron deficiency mandates a search for potential sources of loss such as gastrointestinal bleeding from ulcers or colon cancer. Mild to moderate iron deficiency anemia is treated by iron supplementation with ferrous sulfate or ferrous gluconate. Vitamin C may aid in the body's ability to absorb iron.

Vitamin supplements given orally (folic acid) or subcutaneously (vitamin B-12) will replace specific deficiencies.

In anemia of chronic disease, anemia associated with chemotherapy, or anemia associated with renal disease, some clinicians prescribe recombinant erythropoietin, epoetin alfa, to stimulate red cell production.

In severe cases of anemia, or with ongoing blood loss, a blood transfusion may be necessary.

Blood transfusions for anemia

Doctors attempt to avoid blood transfusion in general, since multiple lines of evidence point to increased adverse patient clinical outcomes with more intensive transfusion strategies. The physiological principle that reduction of oxygen delivery associated with anemia leads to adverse clinical outcomes is balanced by the finding that transfusion does not necessarily mitigate these adverse clinical outcomes.

In severe, acute bleeding, transfusions of donated blood are often lifesaving. Improvements in battlefield casualty survival is attributable, at least in part, to the recent improvements in blood banking and transfusion techniques.^{[citation needed]}

Transfusion of the stable but anemic hospitalized patient has been the subject of numerous clinical trials, and transfusion is emerging as a deleterious intervention.

Four randomized controlled clinical trials have been conducted to evaluate aggressive versus conservative transfusion strategies in critically ill patients. All four of these studies failed to find a benefit with more aggressive transfusion strategies.^{[12][13][14][15]}

In addition, at least two retrospective studies have shown increases in adverse clinical outcomes with more aggressive transfusion strategies.^[16][17]

Hyperbaric oxygenation

Treatment of exceptional blood loss (anemia) is recognized as an indication for hyperbaric oxygen (HBO) by the Undersea and Hyperbaric Medical Society.^[18][19] The use of HBO is indicated when oxygen delivery to tissue is not sufficient in patients who cannot be transfused for medical or religious reasons. HBO may be used for medical reasons when threat of blood product incompatibility or concern for transmissible disease are factors.^[18] The beliefs of some religions (ex: Jehovah's Witnesses) may prohibit the receipt of transfused blood products.^[18]

In 2002, Van Meter reviewed the publications surrounding the use of HBO in severe anemia and found that all publications report a positive result.^[20]

See also

• Hematology
• Human iron metabolism
• Heme
• Hemoglobin

References

1. ^ MedicineNet.com --> Definition of Anemia Last Editorial Review: 12/9/2000 8:31:00 AM
2. ^ merriam-webster dictionary --> anemia Retrieved on May 25, 2009
3. ^ eMedicine - Anemia, Chronic : Article by Fredrick M Abrahamian, DO, FACEP
4. ^ eMedicineHealth > anemia article Author: Saimak T. Nabili, MD, MPH. Editor: Melissa Conrad Stöppler, MD. Last Editorial Review: 12/9/2008. Retrieved on 4 April, 2009
5. ^ World Health Organization (2008). Worldwide prevalence of anaemia 1993-2005. Geneva: World Health Organization. ISBN 9789241596657. http://whqlibdoc.who.int/publications/2008/9789241596657_eng.pdf. Retrieved 2009-03-25. 
6. ^ Recommendations to Prevent and Control Iron Deficiency in the United States MMWR 1998;47 (No. RR-3) p. 5
7. ^ Iron Deficiency Anaemia: Assessment, Prevention, and Control: A guide for programme managers
8. ^ eMedicine - Vitamin B-12 Associated Neurological Diseases : Article by Niranjan N Singh, MD, DM, DNB July 18, 2006
9. ^ Physiology or Medicine 1934 - Presentation Speech
10. ^ Dorlands Medical Dictionary
11. ^ Onions are Toxic to Cats
12. ^ Hébert PC, Wells G, Blajchman MA, et al. (1999). "A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group". N. Engl. J. Med. 340 (6): 409–17. PMID 9971864. 
13. ^ Bush RL, Pevec WC, Holcroft JW (1997). "A prospective, randomized trial limiting perioperative red blood cell transfusions in vascular patients". Am. J. Surg. 174 (2): 143–8. doi:10.1016/S0002-9610(97)00073-1. PMID 9293831. 
14. ^ Bracey AW, Radovancevic R, Riggs SA, et al. (1999). "Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome". Transfusion 39 (10): 1070–7. doi:10.1046/j.1537-2995.1999.39101070.x. PMID 10532600. 
15. ^ McIntyre LA, Fergusson DA, Hutchison JS, et al. (2006). "Effect of a liberal versus restrictive transfusion strategy on mortality in patients with moderate to severe head injury". Neurocritical care 5 (1): 4–9. doi:10.1385/NCC:5:1:4. PMID 16960287. 
16. ^ Corwin HL, Gettinger A, Pearl RG, et al. (2004). "The CRIT Study: Anemia and blood transfusion in the critically ill--current clinical practice in the United States". Crit. Care Med. 32 (1): 39–52. doi:10.1097/01.CCM.0000104112.34142.79. PMID 14707558. 
17. ^ Vincent JL, Baron JF, Reinhart K, et al. (2002). "Anemia and blood transfusion in critically ill patients". JAMA 288 (12): 1499–507. doi:10.1001/jama.288.12.1499. PMID 12243637. 
18. ^ ^{a b c} Undersea and Hyperbaric Medical Society. "Exceptional Blood Loss — Anemia". http://www.uhms.org/ResourceLibrary/Indications/ExceptionalBloodLossAnemia/tabid/277/Default.aspx. Retrieved 2008-05-19. 
19. ^ Hart GB, Lennon PA, Strauss MB. (1987). "Hyperbaric oxygen in exceptional acute blood-loss anemia". J. Hyperbaric Med 2 (4): 205–210. http://archive.rubicon-foundation.org/4352. Retrieved 2008-05-19. 
20. ^ Van Meter KW (2005). "A systematic review of the application of hyperbaric oxygen in the treatment of severe anemia: an evidence-based approach". Undersea Hyperb Med 32 (1): 61–83. PMID 15796315. http://archive.rubicon-foundation.org/4038. Retrieved 2008-05-19. 

External links

• National Anemia Action Council (USA)
• Hemoglobin Calculator for Diagnosis of Anemia

v • d • e Pathology: hematology · hematologic diseases of RBCs and megakaryocytes / MEP (D50-69,74, 280-287) Red blood cells ↑ Polycythemia Polycythemia vera ↓ Anemia Nutritional Micro-: Iron deficiency anemia (Plummer-Vinson syndrome) Macro-: Megaloblastic anemia (Pernicious anemia) Hemolytic (mostly Normo-) Hereditary enzymopathy: G6PD · glycolysis (PK, TI, HK) hemoglobinopathy: Thalassemia (alpha, beta, delta)  · Sickle-cell disease/trait · HPFH membrane: Hereditary spherocytosis (Minkowski-Chauffard syndrome) · Hereditary elliptocytosis (Ovalocytosis) · Hereditary stomatocytosis Acquired Autoimmune (WAHA, CAD, PCH) membrane (PNH) MAHA · TM (HUS) Drug-induced autoimmune · Drug-induced nonautoimmune Hemolytic disease of the newborn Aplastic (mostly Normo-) Hereditary: Fanconi anemia · Diamond-Blackfan anemia Acquired: PRCA · Sideroblastic anemia · Myelophthisic Blood tests MCV (Normocytic, Microcytic, Macrocytic) · MCHC (Normochromic, Hypochromic) Other Methemoglobinemia · Sulfhemoglobinemia · Reticulocytopenia Coagulation/ coagulopathy/ bleeding diathesis ↑ Thrombocytosis Essential thrombocytosis Hypercoagulability primary: Antithrombin III deficiency · Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden · Hyperprothrombinemia acquired: DIC (Congenital afibrinogenemia, Purpura fulminans) · autoimmune (Antiphospholipid) ↓ Thrombocytopenia and purpura Nonthrombocytopenic purpura: Henoch-Schönlein purpura Thrombocytopenic purpura: ITP (Evans syndrome) · TM (TTP) Heparin-induced thrombocytopenia · May-Hegglin anomaly Platelet function adhesion (Bernard-Soulier syndrome) · aggregation (Glanzmann's thrombasthenia) · platelet storage pool deficiency (Hermansky-Pudlak syndrome, Gray platelet syndrome) Clotting factor Hemophilia (A/VIII, B/IX, C/XI) • Von Willebrand disease • Hypoprothrombinemia/II · XIII myeloid navs: cells/physio, disease of RBCs+megakaryocytes/monocytes+granulocytes/neoplasia, symptoms+signs/eponymous ↑ means increased, ↓ means decreased

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Dansk (Danish)
n. - anæmi, blodmangel

Nederlands (Dutch)
bloedarmoede

Français (French)
n. - anémie

Deutsch (German)
n. - Blutarmut, Anämie

Ελληνική (Greek)
n. - (παθολ.) αναιμία

Italiano (Italian)
anemia

Português (Portuguese)
n. - anemia (f) (Med.)

Русский (Russian)
анемия

Español (Spanish)
n. - anemia

Svenska (Swedish)
n. - blodbrist

中文（简体）(Chinese (Simplified))
贫血, 贫血症

中文（繁體）(Chinese (Traditional))
n. - 貧血, 貧血症

한국어 (Korean)
n. - 빈혈, 결핍

日本語 (Japanese)
n. - 貧血, 生気のなさ

idioms:

• sickle-cell anaemia/anemia    鎌状赤血球貧血

العربيه (Arabic)
‏(الاسم) انيميا : فقر الدم‏

עברית (Hebrew)
n. - ‮חוסר-דם, מיעוט-דם, אנמיה‬

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