Anemia - Treatment

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Bloodless Medicine. Bloodless medicine and surgery is a new field designed to reduce or minimize blood loss and transfusions. It also attempts to address the problems in treating certain religious groups, such as Jehovah's Witnesses, who refuse transfusions. Some techniques involved in this field include new surgical procedures or drugs that minimize blood loss, the use of erythropoietin, volume expanders (administration of fluids to dilute blood), using tiny blood samples for testing, and methods (Cell Saver) for recovering and recycling blood during surgery.

Erythropoiesis-Stimulating Drugs

Erythropoietin is the hormone that acts in the bone marrow to increase the production of red blood cells. It has been genetically engineered as recombinant human erythropoietin (rHuEPO) and is available as epoetin alfa (Epogen, Procrit, and Eprex). Novel erythropoiesis stimulating protein (NESP), also called darbepoetin alfa (Aranesp), lasts longer in the blood than epoetin alfa and requires fewer injections. These medications are also called “erythropoiesis-stimulating drugs.”

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Levels of erythropoietin are reduced in anemia of chronic disease. Injections of synthetic erythropoietin can help reduce the need for blood transfusions and improve quality of life measures. Erythropoietin is currently used for treating patients with anemia related to the following conditions:

• Chronic kidney disease and diabetes. Erythropoietin is an important treatment for patients on dialysis and has proven to reduce the risk of death from heart disease and improve quality of life.
• Cancer. Erythropoietin is administered to manage the anemia associated with chemotherapy and other cancer treatments.
• Chronic heart failure. Erythropoietin and intravenous iron may improve cardiac and renal (kidney) function.
• Myelodysplastic syndromes (MDS). MDS is a blood and bone marrow disease that is related to leukemia. In MDS, the bone marrow does not produce enough blood cells. Patients require frequent blood transfusions, which can lead to anemia. Erythropoietin is given to produce more red blood cells along with drugs that stimulate white blood cells. Darbepoetin alfa (Aranesp) is also showing promise in treating the anemia associated with MDS
• Rheumatoid arthritis (RA). Erythropoietin may be used in combination with intravenous iron supplementation to treat both adult and juvenile RA.
• Inflammatory bowel disease. Erythropoietin plus iron supplementation can be beneficial for treating anemia associated with Crohn's disease and ulcerative colitis.
• Hepatitis C. Erythropoietin may mitigate the effects of ribavirin-induced anemia.
• HIV/AIDS. HIV-positive patients may develop anemia as a side effect of treatment with AZT or ribavirin (for co-infection with hepatitis C). Recent research has indicated that weekly injections of epoetin alfa may be as effective as a three times per week regimen.

Although these drugs are used to treat anemia, they can sometimes cause severe anemia. If patients taking these drugs do develop severe anemia, the doctor will immediately stop drug treatment. The risk of drug-caused anemia is greatest for patients with chronic kidney failure who receive these drugs through under-the-skin injections. To reduce the risk of anemia, epoetin alfa and darbepoetin alfa should be given intravenously to patients on dialysis.

Dosing target levels of erythropoiesis-stimulating drugs are controversial, especially for patients with chronic kidney disease. In 2006, two important New England Journal of Medicine (NEJM ) studies indicated that aggressive dosing to completely normalize hemoglobin levels does not work better than standard dosing that only partially corrects anemia. In addition, the higher dosing approach was associated with increased risk for serious cardiovascular events including heart failure, heart attack, and fatal stroke.

In response to these NEJM studies, the FDA issued the following warnings to doctors and patients:

• Erythropoiesis-stimulating drugs should be used to maintain hemoglobin levels of between 10 - 12 g/dL. (The NEJM studies found that patients dosed to hemoglobin target levels of 13.5 g/dL had a greater risk of serious heart problems than patients whose levels did not exceed 12 g/dL.)
• Patients who take these drugs should receive frequent blood tests to monitor their hemoglobin levels, to make sure they are in a safe range.
• Patients should immediately contact their doctors if they experience worsening in shortness of breath, pain, swelling in the legs, or increases in blood pressure.

Epoetin may increase the risk for blood clots. Some experts are also concerned that certain patients may develop antibodies that react against epoetin. This may be more of a problem with some brands (Eprex) than others.

Antibiotics for H. Pylori

H. pylori, the bacteria that cause peptic ulcers, is associated with anemias from vitamin B12 deficiency and iron deficiency. People whose anemia is associated with H. pylori infection, however, do not respond to iron therapy. Studies indicate that the eradication of H. pylori infection with antibiotics can reverse anemia in such patients and may lead to long-lasting recovery.

Vitamin Replacement for Megaloblastic Anemia

Vitamin B12 Therapy. Injections of vitamin B12 (usually formulations called cyanocobalamin or hydroxocobalamin), oral folic acid therapy, or both, rapidly reverse the production of abnormally large red blood cells. (Treatments still may not reverse neurologic symptoms if they are extensive or have continued for too long.)

A typical regimen for vitamin B12 replacement is as follows:

• If diagnostic tests indicate pernicious anemia and neurologic symptoms are present, vitamin B12 therapy should begin immediately. (Usually vitamin therapy is not an emergency, however.)
• Cyanocobalamin or hydroxocobalamin injections are given every day for up to 2 weeks. Only small doses are needed.
• This is followed by injections twice a week for another month. (Hemoglobin levels rise in the first week of therapy and reach normal levels in 8 weeks.)
• After that, injections are usually given monthly.
• During recovery, there is a risk of potassium deficiency as the new red cells take up the existing supply, so potassium supplements may be needed.

Other forms of vitamin B12 are also available and can be used to treat B12 deficiency. Vitamin B12 nasal spray offers the same advantage of avoiding the need for absorbing the vitamin in the GI tract without the inconvenience of the injections. Some experts feel that even oral B12 in high doses (2,000 mcg/day) can maintain B12 levels once the deficiency is treated.

The injections are safe and have no adverse side effects, but they may mask an underlying medical or psychological condition.

Some doctors give vitamin B12 injections for fatigue and other vague symptoms of general mild discomfort. In one study, 10% of patients in a rural clinic were given regular B12 shots, with 6% of patients having no medical need for them.

Folic Acid Treatment. Folate deficiency is easily remedied in 4 - 5 weeks with daily oral doses of 1 - 2 milligrams of folic acid. Many doctors give vitamin B12 along with folic acid unless B12 deficiency is definitely ruled out.

Review Date: 01/17/2007
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital