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Anemia

Description

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

Alternative Names

Iron deficiency; Pernicious anemia

Treatment

Oral iron supplements are the best way to restore iron levels for people who are iron deficient, but they should be used only when dietary measures have failed. However, iron supplements cannot correct anemias that are not due to iron deficiency.

One study reported that doctors prescribed iron pills for 64% of patients with anemia without performing tests to confirm whether iron deficiency was actually the cause. The study suggested that iron replacement was appropriate in less than half of these patients. Iron replacement therapy can cause gastrointestinal problems, sometimes severe ones. Excess iron may also contribute to heart disease, diabetes, and certain cancers. Experts generally advice against iron supplements in anyone with a healthy diet and no indications of iron deficiency anemia. However, a 2003 study suggested that supplements help reduce fatigue in women with low iron stores but no signs of anemia.

Treatment of Anemia of Chronic Disease. In general, the best treatment for anemia of chronic diseases is treating the disease itself. In some cases, iron deficiency accompanies the condition and requires iron replacement. Erythropoietin, most often administered with intravenous iron, is used for some patients.

Treatment of Megaloblastic Anemia. The standard treatments for megaloblastic anemia are vitamin B12 injections and folic acid replacement.

Iron Supplements

Supplement Forms. To replace iron, the preferred forms of iron tablets are ferrous salts, usually ferrous sulfate (Feosol, Fer-In-Sol, Mol-Iron). Other forms include ferrous fumarate (Femiron, FerroSequels, Feostat, Fumerin, Hemocyte, Ircon), ferrous gluconate (Fergon, Ferralet, Simron), polysaccharide-iron complex (Niferex, Nu-Iron), and carbonyl iron (Elemental Iron, Feosol Caplet, Ferra-Cap). Specific brands and forms may have certain advantages. The following are some examples:

• Prolonged-release ferrous sulfate (Slow Fe) may enhance iron absorption with fewer side effects than standard ferrous sulfate pills.
• FerroSequels contains a stool softener, which helps prevent constipation.
• Polysaccharide-iron complex has fewer side effects and equal absorption rates compared to ferrous salts. It is very expensive, however.
• Carbonyl iron is composed of very fine tiny uniform spheres of iron powder and may prove to be less toxic than ferrous iron.
• Coated or combination pills do not appear to offer any additional advantages and may hinder absorption of the iron.

Regimen. The general guidelines for iron replacement are as follows:

• For adults, doctors usually advise one ferrous sulfate tablet (300 mg) three times a day.
• Iron replacement doses for children with deficiencies are significantly lower. In general, they are given as drops or syrup administered three times a day. A single-dose daily regimen is showing promise. IMPORTANT: As few as three adult iron tablets can poison children, even fatally. This includes any form of iron pill.
• No one, even adults, should take a double dose of iron if one is missed.

Other tips for taking iron are as follows:

• For best absorption, iron should be taken between meals. (Iron may cause stomach and intestinal disturbances, however, and some experts believe that low doses of ferrous sulfate can be taken with food and are still absorbed but with fewer side effects.)
• Always drink a full 8 ounces of fluid with an iron pill. Taking orange juice with an iron pill may help increase iron absorption. (Some doctors also recommend taking a vitamin C supplement with the iron pill.)
• Tablets should be kept in a cool place. (Bathroom medicine cabinets may be too warm and humid, which may cause the pills to disintegrate.)

Full recovery takes 6 - 8 weeks. Recovery will take longer in people with internal bleeding that is not under control. Iron replacement therapy must continue for about 6 months, even if anemia has been reversed. Treatment must be continued indefinitely for people with chronic bleeding; in such cases, iron levels should be closely monitored.

Side Effects. Common side effects of iron supplements include the following:

• Constipation and diarrhea are very common. They are rarely severe, although iron tablets can aggravate existing gastrointestinal problems such as ulcers and ulcerative colitis.
• Nausea and vomiting may occur with high doses, but can be controlled by taking smaller amounts. Switching to ferrous gluconate may help some people with severe gastrointestinal problems.
• Black stools are normal when taking iron tablets. In fact, if they do not turn black, the tablets may not be working effectively. This tends to be a more common problem with coated or long-acting iron tablets.
• If the stools are tarry looking as well as black, if they have red streaks, or if cramps, sharp pains, or soreness in the stomach occur, gastrointestinal bleeding may be causing the iron deficiency and the patient should call the doctor promptly.
• Acute iron poisoning is rare in adults but can be fatal in children who take adult-strength tablets.

Interactions with Other Drugs. Certain medications, including antacids, can reduce iron absorption. Iron tablets may also reduce the effectiveness of other drugs, including the antibiotics tetracycline, penicillamine, and ciprofloxacin and the Parkinson's disease drugs methyldopa, levodopa, and carbidopa. At least 2 hours should elapse between doses of these drugs and iron supplements.

Supplements. The following vitamin and mineral supplements may improve iron absorption:

• Adding either ascorbic acid (vitamin C) or succinic acid to ferrous sulfate therapy will improve absorption of iron stores.
• Some studies have found that the addition of zinc to iron supplements increases hemoglobin levels more than iron alone. Some evidence for this suggests that zinc affects a hormone called insulin-like growth factor-I (IGF-I), which plays a role in the regulation of red blood cell production.

Intravenous or Injected Iron

In some cases, iron is administered through muscular injections or intravenously. Intravenous iron has the advantage of causing less gastrointestinal discomfort and inconvenience. It may be in the form of iron dextran (Dexferrum, InFed), sodium ferric gluconate complex in sucrose (Ferrlecit), or iron sucrose (Venofer). Ferrlecit or Venofer are proving to be at least equally effective and safer than iron dextran.

Candidates. The injected or intravenous forms should be limited to the following patients with iron deficiency:

• People with iron deficiency anemia in whom oral therapy has clearly failed.
• Patients with bleeding disorders in which blood loss continues to exceed the rate at which oral iron is absorbed.
• In emergencies, when people need red blood cells but transfusion is not appropriate or available.
• In people with serious gastrointestinal disorders, such as inflammatory bowel disease, who cannot take iron therapy by mouth.
• People undergoing hemodialysis who receive supplemental erythropoietin therapy. Sodium ferric gluconate complex in sucrose (Ferrlecit) or iron sucrose (Venofer) is specifically approved as first-line therapy for these patients. One 2003 study suggested that a combination of iron and vitamin C by mouth might be sufficient to maintain adequate iron and vitamin C stores.

Certain patients, even if they meet these qualifications, may not be appropriate candidates or should be monitored closely for complications. They include:

• Patients with any underlying autoimmune disease.
• Malnourished patients who also have an underlying infection.
• Patients who are at risk for iron overload.

Side Effects. Some side effects differ depending on how the iron is administered and include the following:

• Muscular injections include pain at the site.
• Intravenous administration can cause pain in the vein, flushing, and metallic taste, all of which are brief.

For both methods, side effects and serious complications can include:

• Blood clots
• Fever
• Joint aches
• Headache
• Rashes
• A delayed reaction of joint and muscle aches, headache, and malaise occurs 1 - 2 days after the infusion (most commonly with iron dextran) in about 10% of patients. These symptoms respond quickly to NSAIDs, such as ibuprofen or naproxen, in most people.
• Iron toxicity. Symptoms include nausea, dizziness, and a sudden drop in blood pressure. Sodium ferric gluconate in sucrose (Ferrlecit) or iron sucrose (Venofer) may pose a lower risk for toxicity than iron dextran.
• Allergic reactions. Allergic reactions that occur with intravenous iron can be very serious and, in rare cases, even fatal. Iron dextran appears to pose a much higher risk than sodium ferric gluconate complex in sucrose or iron sucrose, although allergic reactions can also occur with the latter forms.

Oral and injected iron should never be given at the same time. Intravenous iron therapy may be appropriate for some pregnant women who meet these requirements, depending on the pregnancy term and other factors.

Transfusions and Bloodless Medicine

Transfusions are used to replace blood loss due to injuries and during certain surgeries. They are also commonly used to treat severely anemic patients who have thalassemia, sickle cell disease, myelodysplastic syndromes, or other types of anemia. Some patients require frequent blood transfusions. Iron overload can be a side effect of these frequent blood transfusions. If left untreated, iron overload can lead to liver and heart damage.

Iron chelation therapy is used to remove the excess iron caused by blood transfusions. Patients take a drug that binds to the iron in the blood. The excess iron is then removed from the body by the kidneys. For many years, deferoxamine (Desferal) was the only drug used in chelation therapy. This drug is usually injected intravenously, using an infusion pump. The infusion can last 8 - 12 hours and may be needed 5 - 7 days a week until iron levels are normal. A new drug, deferasirox (Exjade), was approved in 2005 for children and adults as a once-daily treatment for iron overload due to blood transfusions. It does not require injections. Patients mix the deferasirox tablets in liquid and drink the medicine. Doctors hope that this new drug may make it easier for patients to tolerate chelation therapy. Studies have shown that deferasirox works as well as deferoxamine in ridding the body of excess iron.

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.”

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

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