Iron-deficiency anemia
Iron-deficiency anemia | |
---|---|
Other names | Iron-deficiency anaemia,
FeDA, Sideropenic Anemia |
Frequency | 1.48 billion (2015)[6] |
Deaths | 54,200 (2015)[7] |
Iron-deficiency anemia is
Iron-deficiency anemia is caused by
Iron deficiency anemia can be prevented by eating a diet containing sufficient amounts of iron or by iron supplementation.
Iron-deficiency anemia affected about 1.48 billion people in 2015.[6] A lack of dietary iron is estimated to cause approximately half of all anemia cases globally.[12] Women and young children are most commonly affected.[3] In 2015, anemia due to iron deficiency resulted in about 54,000 deaths – down from 213,000 deaths in 1990.[7][13]
Signs and symptoms
Iron-deficiency anemia may be present without a person experiencing symptoms.[14] It tends to develop slowly; therefore the body has time to adapt, and the disease often goes unrecognized for some time.[15] If symptoms present, patients may present with the sign of pallor (reduced oxyhemoglobin in skin or mucous membranes),[16] and the symptoms of feeling tired, weak, dizziness, lightheadedness, poor physical exertion, headaches, decreased ability to concentrate, cold hands and feet, cold sensitivity, increased thirst and confusion.[14][16] None of these symptoms (or any of the others below) are sensitive or specific.
In severe cases, shortness of breath can occur.[17] Pica may also develop; of which consumption of ice, known as pagophagia, has been suggested to be the most specific for iron deficiency anemia.[15]
Other possible symptoms and signs of iron-deficiency anemia include:[3][15][17][18]
- Irritability
- Angina (chest pain)
- Palpitations (feeling that the heart is skipping beats or fluttering)
- Breathlessness
- Tingling, numbness, or burning sensations
- Glossitis (inflammation or infection of the tongue)
- Angular cheilitis (inflammatory lesions at the mouth's corners)
- Koilonychia (spoon-shaped nails) or nails that are brittle
- Poor appetite
- Dysphagia (difficulty swallowing) due to formation of esophageal webs (Plummer–Vinson syndrome)
- Periorbital hyperpigmentation (darkening of the skin around the eyes), the cause is unknown and assumed to be related to the iron-deficiency induced worse blood oxygenation and vitamin B12[19]
- Restless legs syndrome[20]
Child development
Iron-deficiency anemia is associated with poor neurological development, including decreased learning ability and altered motor functions.[21][22] This is because iron deficiency impacts the development of the cells of the brain called neurons. When the body is low on iron, the red blood cells get priority on iron, and it is shifted away from the neurons of the brain. Exact causation has not been established, but there is a possible long-term impact from these neurological issues.[22]
Cause
A diagnosis of iron-deficiency anemia requires further investigation into its cause.
Parasitic disease
The leading cause of iron-deficiency anemia worldwide is a
Blood loss
Menstrual bleeding
Menstrual bleeding is a common cause of iron deficiency anemia in women of child-bearing age.
Gastrointestinal bleeding
The most common cause of iron deficiency anemia in men and
Diet
The body normally gets the iron it requires from food. If a person consumes too little iron, or iron that is poorly absorbed (non-heme iron), they can become iron deficient over time. Examples of iron-rich foods include meat, eggs,
The National Academy of Medicine updated Estimated Average Requirements and Recommended Dietary Allowances in 2001. The current EAR for iron for women ages 14–18 is 7.9 mg/day, 8.1 for ages 19–50, and 5.0 thereafter (post menopause). For men the EAR is 6.0 mg/day for ages 19 and up. The Recommended Dietary Allowance is 15.0 mg/day for women ages 15–18, 18.0 for 19–50, and 8.0 thereafter; for men, 8.0 mg/day for ages 19 and up. (Recommended Dietary Allowances are higher than Estimated Average Requirements so as to cover people with higher than average requirements.) The Recommended Dietary Allowance for pregnancy is 27 mg/day, and during lactation, 9 mg/day. For children ages 1–3 years it is 7 mg/day, 10 for ages 4–8 and 8 for ages 9–13.[34] The European Food Safety Authority refers to the collective set of information as Dietary Reference Values, with Population Reference Intakes instead of Recommended Dietary Allowances, and Average Requirements instead of Estimated Average Requirements. For women the Population Reference Intake is 13 mg/day ages 15–17 years, 16 mg/day for women ages 18 and up who are premenopausal, and 11 mg/day postmenopausal; for pregnancy and lactation, 16 mg/day. For men the Population Reference Intake is 11 mg/day ages 15 and older. For children ages 1 to 14 the Population Reference Intake increases from 7 to 11 mg/day. The Population Reference Intakes are higher than the US Recommended Dietary Allowances, with the exception of pregnancy.[35]
Iron malabsorption
Iron from food is absorbed into the bloodstream in the small intestine, primarily in the duodenum.[36] Iron malabsorption is a less common cause of iron-deficiency anemia, but many gastrointestinal disorders can reduce the body's ability to absorb iron.[37] There are different mechanisms that may be present.
In
Bariatric surgery is associated with an increased risk of iron deficiency anemia due to malabsorption of iron.[39] During a Roux-en-Y anastamosis, which is commonly performed for weight management and diabetes control, the stomach is made into a small pouch and this is connected directly to the small intestines further downstream (bypassing the duodenum as a site of digestion). About 17–45% of people develop iron deficiency after a Roux-en-Y gastric bypass.[40]
Pregnant women
Without iron supplementation, iron-deficiency anemia occurs in many pregnant women because their iron stores need to serve their own increased blood volume and be a source of hemoglobin for the growing baby and placental development.[32] Other less common causes are intravascular hemolysis and hemoglobinuria. Iron deficiency in pregnancy appears to cause long-term and irreversible cognitive problems in the baby.[41]
Iron deficiency affects maternal well-being by increasing risks for infections and complications during pregnancy.[42] Some of these complications include pre-eclampsia, bleeding problems, and perinatal infections.[42] Iron deficiency can lead to improper development of fetal tissues.[43] Oral iron supplementation during the early stages of pregnancy, specifically the first trimester, is suggested to decrease the adverse effects of iron-deficiency anemia throughout pregnancy and to decrease the negative impact that iron deficiency has on fetal growth.[42] Iron supplements may lead to a risk for gestational diabetes, so pregnant women with adequate hemoglobin levels are recommended not to take iron supplements.[44] Iron deficiency can lead to premature labor and to problems with neural functioning, including delays in language and motor development in the infant.[42]
Some studies show that women pregnant during their teenage years can be at greater risk of iron-deficiency anemia due to an already increased need for iron and other nutrients during adolescent growth spurts.[42]
Children
Babies are at increased risk of developing iron deficiency anemia due to their rapid growth.[25] Their need for iron is greater than they are getting in their diet.[25] Babies are born with iron stores; however, these iron stores typically run out by 4–6 months of age. In addition, infants who are given cow's milk too early can develop anemia due to gastrointestinal blood loss.[25]
Children who are at risk for iron-deficiency anemia include:[45]
- Preterm infants
- Low birth weight infants
- Infants fed with cow's milk under 12 months of age
- Breastfed infants who have not received iron supplementation after age 6 months, or those receiving non-iron-fortified formulas
- Children between the ages of 1 and 5 years old who receive more than 24 ounces (700 mL) of cow milk per day
- Children with low socioeconomic status
- Children with special health care needs
- Children of Hispanic ethnicity[46]
- Children who are overweight[46]
Blood donation
Frequent blood donors are also at risk for developing iron deficiency anemia.
Hepcidin
Decreased levels of serum and urine hepcidin are early indicators of iron deficiency.[48] Hepcidin concentrations are also connected to the complex relationship between malaria and iron deficiency.[49]
Mechanism
Anemia can result from significant iron deficiency.[37] When the body has sufficient iron to meet its needs (functional iron), the remainder is stored for later use in cells, mostly in the bone marrow and liver.[37] These stores are called ferritin complexes and are part of the human (and other animals) iron metabolism systems. Men store about 3.5 g of iron in their body, and women store about 2.5 g.[14]
Hepcidin is a peptide hormone produced in the liver that is responsible for regulating iron levels in the body. Hepcidin decreases the amount of iron available for erythropoesis (red blood cell production).[39] Hepcidin binds to and induces the degradation of ferroportin, which is responsible for exporting iron from cells and mobilizing it to the bloodstream.[39] Conditions such as high levels of erythropoesis, iron deficiency and tissue hypoxia inhibit hepcidin expression.[39] Whereas systemic infection or inflammation (especially involving the cytokine IL-6) or increased circulating iron levels stimulate hepcidin expression.[39]
Iron is a mineral that is important in the formation of red blood cells in the body, particularly as a critical component of hemoglobin.[23] About 70% of the iron found in the body is bound to hemoglobin.[14] Iron is primarily absorbed in the small intestine, in particular the duodenum and jejunum. Certain factors increase or decrease absorption of iron. For example, taking Vitamin C with a source of iron is known to increase absorption. Some medications such as tetracyclines and antacids can decrease absorption of iron.[14] After being absorbed in the small intestine, iron travels through blood, bound to transferrin, and eventually ends up in the bone marrow, where it is involved in red blood cell formation.[23] When red blood cells are degraded, the iron is recycled by the body and stored.[23]
When the amount of iron needed by the body exceeds the amount of iron that is readily available, the body can use iron stores (ferritin) for a period of time, and red blood cell formation continues normally.[37] However, as these stores continue to be used, iron is eventually depleted to the point that red blood cell formation is abnormal.[37] Ultimately, anemia ensues, which by definition is a hemoglobin lab value below normal limits.[3][37]
Diagnosis
Conventionally, a definitive diagnosis requires a demonstration of depleted body iron stores obtained by
A thorough medical history is important to the diagnosis of iron-deficiency anemia. The history can help to differentiate common causes of the condition such as a menstruation in woman or the presence of blood in the stool.[54] A travel history to areas in which hookworms and whipworms are endemic may also be helpful in guiding certain stool tests for parasites or their eggs.[55] Although symptoms can play a role in identifying iron-deficiency anemia, they are often vague, which may limit their contribution to determining the diagnosis.[citation needed]
Blood tests
Change | Parameter |
---|---|
↓ | ferritin, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin |
↑ | total iron-binding capacity, transferrin, red blood cell distribution width |
Anemia is often discovered by routine blood tests. A sufficiently low
A low
The blood smear of a person with iron-deficiency anemia shows many
Iron-deficiency anemia is confirmed by tests that include
Another finding that can be used is the level of red blood cell distribution width.[59] During haemoglobin synthesis, trace amounts of zinc will be incorporated into protoporphyrin in the place of iron which is lacking. Protoporphyrin can be separated from its zinc moiety and measured as free erythrocyte protoporphyrin, providing an indirect measurement of the zinc-protoporphyrin complex. The level of free erythrocyte protoporphyrin is expressed in either μg/dl of whole blood or μg/dl of red blood cells. An iron insufficiency in the bone marrow can be detected very early by a rise in free erythrocyte protoporphyrin.[citation needed]
Further testing may be necessary to differentiate iron-deficiency anemia from other disorders, such as
Screening
It is unclear if screening pregnant women for iron-deficiency anemia during pregnancy improves outcomes in the United States.
Treatment
Treatment should take into account the cause and severity of the condition.
For less severe cases, treatment of iron-deficiency anemia includes dietary changes to incorporate iron-rich foods into regular oral intake and oral iron supplementation.
Most forms of oral iron replacement therapy are absorbed well by the
The various forms of treatment are not without possible adverse side effects.
It can take six months to one year to get blood levels of iron up to a normal range and provide the body with iron stores.
As iron-deficiency anemia becomes more severe, if the anemia does not respond to oral treatments, or if the treated person does not tolerate oral iron supplementation, then other measures may become necessary.[5][65] Two options are intravenous iron injections and blood transfusion.[64] Intravenous can be for people who do not tolerate oral iron, who are unlikely to respond to oral iron, or who require iron on a long-term basis.[64] For example, people receiving dialysis treatment who are also getting erythropoietin or another erythropoiesis-stimulating agent are given parenteral iron, which helps the body respond to the erythropoietin agents to produce red blood cells.[65][66][39]
Low-certainty evidence suggests that IBD-related anemia treatment with
Ferric maltol, marketed as Accrufer and Ferracru, is available in oral and IV preparations. When used as a treatment for IBD-related anemia, very low certainty evidence suggests a marked benefit with oral ferric maltol compared with placebo. However it was unclear whether the IV preparation was more effective than oral ferric maltol. [69]
A Cochrane review of controlled trials comparing intravenous (IV) iron therapy with oral iron supplements in people with chronic kidney disease, found low-certainty evidence that people receiving IV-iron treatment were 1.71 times as likely to reach their target hemoglobin levels.[70] Overall, hemoglobin was 0.71g/dl higher than those treated with oral iron supplements. Iron stores in the liver, estimated by serum ferritin, were also 224.84 µg/L higher in those receiving IV-iron.[70] However there was also low-certainty evidence that allergic reactions were more likely following IV-iron therapy. It was unclear whether type of iron therapy administration affects the risk of death from any cause, including cardiovascular, nor whether it may alter the number of people who may require a blood transfusion or dialysis.[70]
Ferric derisomaltose (Monoferric) was approved in the United States in January 2020, for the treatment of iron deficiency anemia.[71][72]
Epidemiology
A moderate degree of iron-deficiency anemia affects approximately 610 million people worldwide or 8.8% of the population.[74] It is slightly more common in females (9.9%) than males (7.8%).[74] Up to 15% of children ages 1–3 years have iron deficiency anemia.[46] Mild iron deficiency anemia affects another 375 million.[74] Iron deficiency affects up to 52% of pregnant women worldwide.[42]
The prevalence of iron deficiency as a cause of anemia varies among countries; in the groups in which anemia is most common, including young children and a subset of non-pregnant women, iron deficiency accounts for a fraction of anemia cases in these groups (25% and 37%, respectively).[75] Iron deficiency is common in pregnant women.[76]
Within the United States, iron-deficiency anemia affects about 2% of adult males, 10.5% of White women, and 20% of African-American and Mexican-American women.[77]
A map provides a country-by-country listing of what nutrients are fortified into specified foods. Some of the Sub-Saharan countries shown in the deaths from iron-deficiency anemia map from 2012 are as of 2018 fortifying foods with iron.[31]
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External links
- The Importance of Iron – From IronTherapy.Org
- Interactive material on Iron Metabolism Archived 2016-05-29 at the Wayback Machine – From IronAtlas.com
- Approach to chronic anemia : https://ashpublications.org/hematology/article/2012/1/183/83845/How-to-approach-chronic-anemia
- Handout: Iron Deficiency Anemia – From the National Anemia Action Council
- NPS News 70: Iron deficiency anaemia: NPS – Better choices, Better health – From the National Prescribing Service