Iron deficiency; Pernicious anemia
Iron deficiency anemia occurs when the body lacks mineral iron to produce the hemoglobin it needs to make red blood cells. In general, there are three stages leading from iron deficiency to anemia:
Most of the iron used in the body can be recycled from blood and reused. Nevertheless, iron deficiency can occur from a number of conditions.
Inadequate Iron Intake. A healthy diet easily provides enough iron. In general, most people need just 1 mg, and menstruating women need 2 mg of extra iron each day. This means that lack of iron in the diet is not a common cause of iron deficiency anemia, except in infants. In fact, most American adults may be consuming too much iron in their diet. Most of the iron in red blood cells is recycled and reused. Iron-poor diets are a cause of anemia only in people with existing risks for iron deficiency. Children who have not yet eaten iron-fortified formulas or iron-enriched cereal may also become anemic.
Blood Loss. Iron deficiencies most commonly occur from internal blood loss due to other conditions that range in severity. These conditions include:
Impaired Absorption of Iron. Impaired absorption of iron is caused by:
Genetic Causes. Some people are born with iron deficiency. Certain cases may be due to a mutation of the Nramp2 gene, which regulates a protein responsible for delivering iron to the cells.
Anemia of chronic disease (ACD), also called anemia of chronic inflammation (ACI), is a common condition associated with a wide variety of persistent inflammatory diseases. It can be very severe and require transfusions.
The Inflammatory Process and ACD. ACD is not completely understood. In ACD, iron is not efficiently recycled from blood cells, and red blood cell survival is reduced. In addition, there is impaired response to erythropoietin, the hormone that acts in the bone marrow to increase the production of red blood cells. (Abnormal function and low levels of erythropoietin, in fact, may be the most important factor in ACD, with impaired iron utilization being a consequence.)
Diseases Associated with ACD and Inflammation. The chronic diseases that are associated with this process include:
Not all chronic diseases involve the inflammatory process and anemia. For example, high blood pressure is a chronic disease, but it does not affect red blood cells.
Treatment-Related Anemia. Anemia can also result from the therapies used to treat conditions. For example, anemia is a common side effect of cancer treatments. Chemotherapy and radiation can impair the bone marrow's production of red blood cells and contribute to the extreme fatigue that many patients experience during cancer therapy. Patients with hepatitis C frequently receive combination therapy of ribavirin and interferon; ribavirin can induce anemia. Hepatitis C also affects many patients with HIV or AIDS. In addition to ribavirin, patients with HIV or AIDS can develop anemia as a result of highly active anti-retroviral therapy (HAART) and, in particular, from the drug AZT.
Other medications that increase the risk for anemia are certain antibiotics, some antiseizure medications (phenytoin), immunosuppressive drugs (methotrexate, azathioprine), antiarrhythmic drugs (procainamide, quinidine), and anti-clotting drugs (aspirin, warfarin, clopidogrel, heparin).
Megaloblastic anemia is the end-product of deficiencies in the B vitamins folate or vitamin B12 (also called cobalamin), or both. Such deficiencies produce abnormally large red blood cells (megaloblastic) that have a shortened lifespan. Neurologic problems are also associated with these deficiencies. Several conditions can cause these deficiencies.
Causes of Vitamin B12 Deficiency. Conditions that cause vitamin B12 deficiencies include:
Causes of Folate Deficiency. The body stores only about 100 times its daily requirements for folate and can exhaust this supply within about 3 months if the diet is deficient in folate.
Less Common Anemias
Form of Anemia
Description and Diagnosis
Causes and Risk Factors
Bone marrow fails to produce all types of blood cells. Symptoms, in addition to standard anemia, are bleeding in mucous membranes and skin, gingivitis, higher risk for infection, and shortness of breath.
Cause is unknown in half the cases. Known causes include hereditary conditions (Fanconi's anemia), viruses (HIV, hepatitis, Epstein-Barr), autoimmune diseases (lupus, rheumatoid arthritis), medications (valproic acid, tacrolimus, azathioprine) or chemicals (benzene, pesticides).
Transfusions, antibiotics, bone marrow or stem cell transplantation, immunosuppressant drugs.
Genetic blood disease caused by a defect in the rate of production of hemoglobin. The two major forms are thalassemia minor and thalassemia major (Cooley's anemia, beta thalassemia). Thalassemia minor is the more common and milder form, in which lifespan is normal. Thalassemia major can be serious, but is very rare.
Affects males and females equally. Most common in people of Mediterranean descent, especially Italians and Greeks. Both types of thalassemia are found in an area that extends from northern Africa and southern Europe to Thailand, including Iran, Iraq, Indonesia, and southern China. Thalassemia major is more common in families who intermarry.
Transfusions to supply enough red blood cells to achieve moderate anemia and avoid iron overload are standard approaches for thalassemia major. Investigations are ongoing to find alternatives to transfusions. Hydroxyurea, 5-azacytidine, erythropoietin, or butyrate analogues may help some patients. Bone marrow transplantation may be needed for some types of thalassemia.
Hemolytic Anemias: Acquired
Anemia caused by hemolysis (premature destruction of red blood cells). Diagnosis considered when there is marked increase in RBC production by bone marrow.
Autoimmune hemolytic anemia is the primary type, in which antibodies produced by the immune system damage RBCs. Cause unknown or associated with disorders such as systemic lupus erythematosus, lymphoma, and paroxysmal nocturnal hemoglobinuria. Other causes are high exposure to certain metals or chemicals (lead, copper, benzene, naphthalene), snake and insect bites, malaria, transfusions, post-surgical complications, and drugs such as methyldopa. In infants, blood group incompatibility between mother and child or infections in the womb.
Corticosteroids for autoimmune hemolytic anemia. Transfusions beneficial in many cases. Various immunosuppressive drugs may be tried, as well as splenectomy. Eculizumab (Soliris) is approved for treatment of paroxysmal nocturnal hemoglobinuria.
Hemolytic Anemias: Inherited
Hemolysis (premature destruction of RBCs) caused by sphere-shaped RBCs, which have difficulties circulating through the spleen.
Inherited defects include membrane defects, hemoglobin abnormalities, and enzyme deficiencies. Fava beans may trigger symptoms. More likely and more serious in males than females.
Blood transfusions may be necessary for some types of hemolytic anemia. Experimental trials use immune globulin. Removal of the spleen (splenectomy) or bone marrow transplantation may help some patients.
Group of anemias caused by impaired ability of bone marrow to produce normal RBCs. Normal-to-high iron levels, but iron cannot be used to make hemoglobin. In addition to the standard symptoms of anemia are jaundice, enlarged liver and spleen, fever, headache, loss of appetite, vomiting, and leg sores. Symptoms can be mild. Usually appears in childhood. Infections, trauma, and pregnancy may trigger symptoms.
Inherited or acquired after excessive alcohol use, certain medications, including chloramphenicol, or other disorders, including some cancers and rheumatoid arthritis. More common in the elderly.
Deferoxamine (Desferal) is used to remove iron. Effectiveness is increased when ascorbate is added to the regimen. Folate and pyridoxine are used, but their effectiveness is under question.
Sickle Cell Anemia
Serious, life-threatening, inherited disease. The sickle-shaped, inflexible RBC has impaired ability to squeeze through vessels. Short lifespan of RBC (10-20 days) causes anemia. In addition to anemia symptoms, joint and bone pain, infections, and heart failure can occur.
Disease and genetic trait occurs primarily in people of African descent and people from India and Mediterranean regions.
Measures to avoid cycling and control pain. Including hydration, hydroxyurea, NSAIDs and narcotic analgesics. Bone marrow transplantation. [For information, see In-Depth Report #58: Sickle-cell disease.]
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