OVERVIEW: What every practitioner needs to know
Are you sure your patient has iron deficiency anemia? What are the typical findings for this disease?
Iron deficiency anemia is the most common nutritional deficiency in childhood. This disease is characterized by a microcytic anemia, which can be caused by decreased intake and/or increased loss of iron. Iron deficiency causes a slow progressive form of anemia and thus is generally not associated with significant symptoms until hemoglobin levels are critically low.
Etiology of iron deficiency anemia
Primary causes of iron deficiency anemia can be broken down into decreased supply of iron and/or increased loss of iron.
Decreased Iron Supply
Although equal amounts of iron are present in cow’s milk and breast milk, the iron in breast milk is more readily absorbed. However, even in breast-fed infants the demand exceeds supply in rapid growth phases. Iron supplementation is recommended in children older than the age of 6 months who are exclusively breast-fed. Also, cow’s milk is to be avoided until age 1 year.
Premature infants do not have adequate iron stores to satisfy increased iron requirements in the first year of life due to rapid growth. This results from the fact that most prenatal tissue iron stores develop during the last trimester of pregnancy.
Meat versus vegetable sources also has an effect on availability. Heme from animal tissues is the most easily absorbed form of iron. As a result, vegetarians are at higher risk of iron deficiency.
Decreased gastric pH can also limit iron absorption, which can be a concern in patients receiving aggressive acid blocker for gastrointestinal (GI) disease such as peptic ulcer disease.
Primary bowel disease (e.g., inflammatory bowel disease, celiac sprue, intestinal resection) that damages the small intestine, causing poor nutrient absorption, will directly impair iron absorption.
It is unclear if lead toxicity directly impairs absorption or selectively competes with iron, but it is commonly associated with iron deficiency.
Increased Iron Losses
GI blood loss is the leading cause of iron deficiency. Occult bleeding can be present for a prolonged period before it is clinically detected. Common pediatric causes of GI bleeding include Meckel diverticulum, peptic ulcer disease, superficial arteriovenous malformations, GI irritiation from cow’s milk, GI malignancy, and parasitic infection.
Chronic menorrhagia can lead to iron deficiency.
Urinary blood loss from an underlying renal disorder (Berger and Goodpasture syndromes) can cause iron deficiency associated with gross (versus microscopic) hematuria.
Pulmonary blood loss leading to iron deficiency is extremely rare and may be associated with pulmonary hemosiderosis.
Symptoms of iron deficiency anemia
Since there is a gradual progression of anemia, a patient with iron deficiency anemia can be relatively asymptomatic. General symptoms include pallor, weakness, fatigue, palpitations, and lightheadedness. Rarely patients will have angular stomatitis and glossitis. Patients can also exhibit pica behavior – most classic is eating excessive ice. Studies have shown that iron deficiency (with or without anemia) leads to impaired growth and intellectual development in children. Some of these cognitive effects are not reversible with iron repletion.
What other disease/condition shares some of these symptoms?
Iron deficiency versus thalassemia trait
Iron deficiency anemia is often confused with thalassemia trait. Both are associated with anemia and microcytosis. However, red cell distribution width (RDW) and cell hemoglobin distribution width are normal in thalassemia trait. Iron studies (ferritin, serum iron, total iron binding capacity) should be normal in a child with thalassemia. The mean corpuscular volume (MCV) tends to be disproportionately low compared with the hemoglobin level in thalassemia trait (very low MCV with mild anemia). Patients may have both conditions concurrrently. It is important to note that iron deficiency must be treated adequately before determining if a patient has beta-thalassemia trait, as iron deficiency suppresses hemoglobin A2 synthesis. If after adequate treatment, the patient maintains a microcytic anemia, he/she also likely has coexistent thalassemia trait (see Table I).
|Laboratory Tests||Iron Deficiency||Thalassemia Trait|
|Complete blood count|
MCV = mean corpuscular volume; RDW = red cell distribution width; total iron binding capacity
What caused this disease to develop at this time?
Children at greatest risk for iron deficiency anemia are premature infants, toddlers (aged 1-3 years), and teenage girls who are menstruating.
Premature infants lack the tissue iron stores present in full-term infants, since most iron stored occurs in the third trimester of pregnancy.
Toddlers are at special risk for iron deficiency because of poor iron intake, particularly from excessive intake of cow’s milk. Children have increased iron requirements because of rapid growth. Iron deficiency can occur in children less than 1 year of age who are breast-fed because of poor bioavailability.
Cow’s milk is a poor source of iron. After children transition to cow’s milk, they are at risk for iron deficiency anemia from decreased intake of iron-rich foods. This risk has been mostly eliminated in children younger than 1 year of age with the use of iron-fortified formulas, although infants exclusively breast-fed after the age of 6 months are at risk because of depletion of iron stores from birth, rapid growth, and relatively low iron supply in breast millk (although the iron present is easily absorbed).
Girls with menorrhagia experience iron deficiency because of the relatively iron-poor diet of many US teenagers, along with chronic blood loss issues from heavy periods.
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
In a patient with iron-deficiency anemia, a complete blood count will reveal low MCV and high RDW. Further testing should include reticulocyte count (low for level of hemoglobin), serum iron (low), total iron-binding capacity (high), transferrin (high), and ferritin (low).
Thrombocytosis can also be found in mild to moderate iron deficiency.
Phases of iron deficiency
In early stages of iron loss, tissue stores are depleted without an effect on hemoglobin. The only significant laboratory finding is a low ferritin level.
As iron deficiency progresses, decreased erythropoeisis develops. New erythrocytes are smaller, causing the RDW to increase slightly, as there is a mix of older normocytic cells with younger microcytic cells. Laboratory findings include low ferritin, low MCV, high RDW, and increased transferrin.
A drop in hemoglobin is the final stage of iron-deficiency anemia, which develops after all iron stores are depleted. By then, most erythrocytes have been produced after the onset of the iron-deficient state, so most cells are hypochromic and microcytic. Laboratory findings include low ferritin, low MCV, high RDW, and low hemoglobin levels.
If you are able to confirm that the patient has iron deficiency anemia, what treatment should be initiated?
The causes of iron deficiency need to be identified and corrected to prevent future recurrence of disease (see section on “etiology of iron deficiency” above).
Iron-deficiency anemia can be treated with oral iron supplements alone (6 mEq of elemental iron/kg daily). Formulations include ferrous sulfate, ferrous gluconate, and ferrous fumarate. Within 10 days, reticulocyotosis should be at a maximum. With good compliance, anemia should be completely corrected within 1 month. Supplementation should be continued for an additional 8 weeks with a goal to replete liver iron stores.
In a child who is hemodynamically unstable (tachycardic, tachypneic), transfusion with packed red blood cells may be indicated. Transfusions need to be infused slowly initially – typically 5 mL/kg over 3 hours and slowly increased for future aliquots to a goal of 8 g/dL with the start of oral iron therapy.
Iron supplemetation can be maximized by dividing doses more frequently. It is generally recommended that oral iron be given with vitamin C and at least 1 hour before or after ingestion of dairy products because vitamin C enhances absorption and dairy products inhibit absorption of enteral iron.
Rarely, parenteral iron is needed if oral iron cannot be tolerated or absorption of iron is questioned. Parenteral iron can be associated with anaphylaxis, so a test dose and close monitoring are required.
Iron therapy should be continued after anemia is corrected. Until liver iron stores are replenished, there is a risk of iron deficiency recurring.
Reasons for poor response to oral iron therapy
Severity of underlying condition (i.e., blood loss exceeds correction of red cell production so that patient is still iron deficient)
Inadequate length of therapy
GI absorption impaired (inflammatory bowel disease, lead, high gastric pH)
Wrong diagnosis (consider thalassemia trait, sideroblastic anemia)
What causes this disease and how frequent is it?
Excessive intake of cow’s milk
Vegetarian diet without iron-rich foods
Disruption of enteric absorption (Crohn or celiac disease)
Increased blood loss
Occult GI blood loss (ulcer, inflammatory bowel disease, varices)
Disruption in iron transport
Defects in heme biosynthesis
How do these pathogens/genes/exposures cause the disease?
Poor intake of iron either through excessive intake of iron-poor foods or diet limited in iron-rich foods over a periods of months to years will lead to iron deficiency anemia.
Slow blood loss leads to excessive iron loss. Over a period of months this will lead to iron deficiency.
Poor absorption (antacid, damage to small intestine from bowel disease) can cause iron deficiency.
How can iron deficiency anemia be prevented?
In children younger than 1 year
formula should be fortified with iron
premature babies should start iron supplementation at birth (1 mg/kg/d)
exclusively breast-fed babies should start iron therapy by the age of 6 months
cow’s milk should be avoided until 1 year of age
In children older than 1 year
cow’s milk should be limited to less than 30 ounces daily
iron-rich foods should be encouraged
Adolescent girls should consider
multivitamin with iron
methods to minimize bleeding if menorrhagia is present
What is the evidence?
Andrews, N, Bridges, K, Nathan, DG, Orkin, SH, Look, AT. “Disorders of iron metabolism”. Nathan & Oski's Hematology of Infancy and Childhood. 2003. pp. 437-42. (Standard detailed reference.)
Pappas, D. “Iron deficiency anemia”. Pediatr Rev. vol. 19. 1998. pp. 321-2. (Excellent review.)
Oski, F. “Iron deficiency in infancy and childhood”. N Engl J Med. vol. 329. 1993. pp. 190-3. (Excellent brief review.)
Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved.
No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM.
- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has iron deficiency anemia? What are the typical findings for this disease?
- What other disease/condition shares some of these symptoms?
- What caused this disease to develop at this time?
- What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
- If you are able to confirm that the patient has iron deficiency anemia, what treatment should be initiated?
- What causes this disease and how frequent is it?
- How do these pathogens/genes/exposures cause the disease?
- How can iron deficiency anemia be prevented?
- What is the evidence?