Iron deficiency anemia overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Iron deficiency anemia occurs when body iron stores are inadequate to meet normal metabolic demands of the body. It is the most common cause of microcytic anemia.
Iron deficiency anemia occurs in the setting of blood loss, insufficient dietary intake or poor oral absorption of iron from food. Symptoms of iron deficiency anemia including fatigue, weakness, shortness of breath, lightheadedness, and pallor. Twenty percent 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 excessive blood loss during menses. In post menopausal women and men, the main cause of iron deficiency are digestive tract diseases.
Iron deficiency anemia is the final stage of iron deficiency. When the body has sufficient iron to meet its needs (functional iron), the remainder is stored for later use in the bone marrow, liver, and spleen. Iron deficiency ranges from iron depletion, which yields little physiological damage, to iron deficiency anemia, which can affect the function of numerous organ systems. Iron depletion causes the amount of stored iron to be reduced, but has no effect on the functional iron. However, a person with no stored iron has no reserves to use if the body requires more iron. In essence, the amount of iron absorbed by the body is not adequate for growth and development or to replace the amount lost.
Historical Perspective
Iron deficiency anemia was discovered in 1852 by Karl Vierordt and his student H. Welcher.
Classification
There is no established system for the classification of iron deficiency. However, based on the pathology, it can be divided into functional and absolute iron deficiency.
Pathophysiology
Iron homeostasis is maintained by a balance of iron absorption and iron loss. Iron absorption is a more active process and is mainly responsible for regulation of iron balance. The absorption of iron is highly regulated by hepcidin, a protein secreted by hepatocytes.
Iron is absorbed in ferrous form (Fe2+) in the small intestine via divalent metal transporter (DMT1). After absorption, depending on iron levels in the body, iron can be sequestered in ferritin or bound to transferrin by ferroportin. Once bound to transferrin, iron is transported to cells that require iron. Iron enters cells when transferrin binds to transferrin receptor (TfR).
Iron deficiency occurs in three stages. In the prelatent stage, ferritin is low but serum iron levels are normal. In the latent stage, transferrin saturation and serum iron are also low in addition to low ferritin. In the last stage, hemoglobin level is below normal along with depletion of iron stores and drop in serum iron and transferrin saturation.
Causes
In developed nations, the main cause of iron deficiency anemia is blood loss. Bleeding from any source can cause iron deficiency anemia. Obvious causes of blood loss like menorrhagia, hematemesis, melena, hematuria, multiple child births, frequent blood donations can be easily recognized with history alone. Occult blood loss from causes like GI bleeding, parasitic infestations etc may be overlooked.
Inadequate dietary iron is the most common cause of iron deficiency anemia in resource poor countries. It is also the most common cause of iron deficiency anemia in toddlers. In toddlers, poor nutritional practices like excessive cow milk intake or snacking contribute to iron deficiency.
Malabsorption due to celiac disease, atrophic gastritis, Helicobacter pylori infection, post-bariatric surgery can also cause iron deficiency.
Drugs which suppress gastric acid can also impair absorption of iron as iron requires an acidic medium for absorption. Certain antibiotics like quinolones, doxycyline, chrloramphenicol etc also diminish the absorption of iron.[1]
Chronic conditions like chronic heart failure, CKD, inflammatory bowel disease, malignancy, rheumatoid arthritis are also associated with iron deficiency anemia.
Other less common cause of iron deficiency include urinary and pulmonary hemosiderosis and genetic conditions like IRIDA due to TMPRSS6 mutations.
Differentiating Iron Deficiency Anemia from other Diseases
Iron deficiency anemia and Thalassemia Minor present with many of the same lab results. It is very important not to treat a patient with Thalassemia with an iron supplement as this can lead to hemochromatosis (accumulation of iron in the liver) A hemoglobin electrophoresis would provide useful evidence in distinguishing these two conditions, along with iron studies.
Epidemiology and Demographics
According to WHO’s Global Burden of Disease Project 2000 (GBD 2000), iron deficiency is responsible for 841,000 deaths worldwide with the major burden of mortality seen in Africa and parts of Asia.
In the US, iron deficiency is seen in 9% of toddlers between age 1 and 2 years. Compared to white toddlers, Hispanic toddlers are twice as likely to have iron deficiency .
The prevalence in adolescent girls and women in reproductive age group is between 9% to 11%. It is most commonly seen in multiparous women from low income minority populations. In males, it is seen in around 1% of population with slightly high prevalence of 2 - 4% in middle aged and older men.
There is a positive correlation between obesity and the risk of developing iron deficiency.
Risk Factors
Risk of iron deficiency anemia is more in those individuals who consume less iron in diet and who are at increased risk of bleeding.
Screening
Screening is recommended in women of reproductive age and toddlers.
Natural History, Complications, and Prognosis
The symptoms of iron deficiency are similar as in any other case of anemia. Iron deficiency anemia has age specific presentations. Iron deficiency anemia can lead to severe complications if not treated. The prognosis of iron deficiency anemia is good if iron supplementation is started.
Diagnosis
Diagnostic criteria
Iron deficiency anemia is diagnosed on the basis of results of CBC, peripheral blood film and iron studies.
History and Symptoms
Iron deficiency anemia may be asymptomatic, or present with very few symptoms or very severe weakness depending on the severity of anemia.
Physical Examination
Patients with iron deficiency anemia may appear normal in some cases but usually if anemia is moderate or severe, the patient would appear pale. All organ systems can be involved by the effects of anemia.
Laboratory Findings
Iron studies are conducted if microcytic hypochromic anemia is found on complete blood count and peripheral blood film. Iron studies are helpful in making the diagnosis of iron deficiency anemia, with serum ferritin levels being the most widely used test.
Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Treatment of iron deficiency anemia includes iron supplementation and treating the cause of the iron deficiency. Treatment is given according to the severity of anemia
Surgery
Prevention
Maintaining adequate iron stores in the body, is the most effective approach to prevent iron deficiency anemia. The source of iron to the body is diet. Consuming iron rich food will prevent iron deficiency anemia.