Iron deficiency anemia
"For a discussion of iron deficiency more broadly, see the Wikipedia article iron deficiency."
Iron deficiency anemia is the most common type of
anemia, and is also known as sideropenic anemia. It is the most common cause of microcytic anemia.
Iron deficiency anemia occurs when the dietary intake or absorption of
ironis insufficient, and hemoglobin, which contains iron, cannot be formed. [cite journal |author=Brady PG |title=Iron deficiency anemia: a call for aggressive diagnostic evaluation |journal=South. Med. J. |volume=100 |issue=10 |pages=966–7 |year=2007 |pmid=17943034 |doi=10.1097/SMJ.0b013e3181520699 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?doi=10.1097/SMJ.0b013e3181520699] In the United States, 20% 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 blood lost during menses. Iron deficiency anemia can be caused by parasitic infections, such as hookworms. Intestinal bleeding caused by hookworms can lead to fecal blood loss and heme/iron deficiency [cite journal |author=Calis JC, Phiri KS, Faragher EB, "et al" |title=Severe anemia in Malawian children |journal=N. Engl. J. Med. |volume=358 |issue=9 |pages=888–99 |year=2008 |pmid=18305266 |doi=10.1056/NEJMoa072727 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18305266&promo=ONFLNS19] . Chronic inflammation caused by parasitic infections contributes to anemia during pregnancy in most developing countries cite journal |author=Dreyfuss ML, Stoltzfus RJ, Shrestha JB, "et al" |title=Hookworms, malaria and vitamin A deficiency contribute to anemia and iron deficiency among pregnant women in the plains of Nepal |journal=J. Nutr. |volume=130 |issue=10 |pages=2527–36 |year=2000 |pmid=11015485 |doi=]
Iron deficiency anemia is an advanced 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 spleenas part of a finely tuned system of human iron metabolism. 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 and stored by the body is not adequate for growth and development or to replace the amount lost.
A disease believed to be iron deficiency anemia is described in about 1500 B.C. in the
Egyptian Ebers papyrus. It was termed "chlorosis" or "green sickness" in Medieval Europe, and iron salts were used for treatment in Franceby the mid-17th century. Thomas Sydenhamrecommended iron salts as treatment for chlorosis, but treatment with iron was controversial until the 20th century, when its mechanism of action was more fully elucidated.
Iron deficiency anemia is characterized by
pallor(reduced amount of oxyhemoglobin in skin or mucous membrane), fatigue and weakness. Because it tends to develop slowly, adaptation occurs and the disease often goes unrecognized for some time. In severe cases, dyspnea(trouble breathing) can occur. Unusual obsessive food cravings, known as pica, may develop. Pagophagia or Pica for ice is a very specific symptom and may disappear with correction of iron deficiency anemia. [cite journal |author=Cook JD |title=Iron-deficiency anaemia |journal=Baillieres Clin. Haematol. |volume=7 |issue=4 |pages=787–804 |year=1994 |pmid=7881154 |doi= |url=] Hair loss and lightheadedness can also be associated with iron deficiency anemia.
Other symptoms patients with iron deficiency anemia have reported are:
*Seeing bright colors
Faintingor feeling faint
Tingling, numbness, or burning sensations
*Missed menstrual cycle
*Heavy menstrual period
*Slow social development
*Sore or swollen tongue
Koilonychia(spoon-shaped nails) or nails that are weak or brittle
Iron deficiency anemia for infants in their earlier stages of development may have significantly greater consequences than it does for adults. An animal made severely iron deficient during its earlier life cannot recover to normal iron levels even with iron therapy. In contrast, iron deficiency during later stages of development can be compensated with sufficient
iron supplements. Iron deficiency anemia affects neurological development by decreasing learning ability, altering motor functions, and permanently reducing the number of dopaminereceptors and seratoninlevels. Iron deficiency during development can lead to reduced myelinationof the spinal cord, as well as a change in myelin composition. Additionally, iron decifiency anemia has a negative effect on physical growth. Growth hormonesecretion is related to serum transferrinlevels, suggesting a positive correlation between iron-transferrin levels and an increase in height and weight. cite journal | author=Ryan AS | title=Iron-Deficiency Anemia in Infant Development: Implications for Growth, Cognitive Development, Resistance to Infection, and Iron Supplementation | journal=Yearbook of Physical Anthropology | volume=40 | issue=10 | pages=25–59 | year=1997 | doi=10.1002/(SICI)1096-8644(1997)25 <25::AID-AJPA2>3.0.CO;2-6 | doi_brokendate=2008-06-21]
Anemia may be diagnosed from symptoms and signs, but when anemia is mild it may not be diagnosed from mild non-specific symptoms. Anemia is often first shown by routine blood tests, which generally include a
complete blood count(CBC). A sufficiently low hemoglobin(HGB) or hematocrit(HCT) value is characteristic of anemia, and further studies will be undertaken to determine its cause and the exact diagnosis. One of the first abnormal values to be noted on a CBC will be a high red blood cell distribution width(RDW), reflecting a varied size distribution of red blood cells. A low MCV, MCH or MCHC, and the appearance of the RBCs on visual examination of a peripheral blood smearwill narrow the diagnosis to a "microcytic anaemia". The blood smear of a patient with iron deficiency shows many hypochromatic and rather small RBCs, and may also show poikilocytosis(variation in shape) and anisocytosis(variation in size), and a few target cells. Microcytic anemia can also be the result of malabsorption phenomena associated with gluten-sensitive enteropathy/ coeliac disease. The diagnosis of iron deficiency anemia will be suggested by appropriate history (e.g., anemia in a menstruating woman), and by such diagnostic tests as a low serum ferritin, a low serum ironlevel, an elevated serum transferrinand a high total iron binding capacity(TIBC). Serum ferritin is the most sensitive lab test for iron deficiency anemia. [cite journal | author = Guyatt G, Patterson C, Ali M, Singer J, Levine M, Turpie I, Meyer R | title = Diagnosis of iron-deficiency anemia in the elderly | journal = Am J Med | volume = 88 | issue = 3 | pages = 205–9 | year = 1990 | pmid = 2178409 | doi = 10.1016/0002-9343(90)90143-2]
Iron deficient 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
hemachromatosis(accumulation of iron in the liver). A hemoglobin electrophoresis would provide useful evidence in distinguishing these two conditions, along with iron studies.
A definitive diagnosis requires a demonstration of depleted body iron stores by performing a
bone marrowaspiration, with the marrow stained for ironFact|date=March 2008. Because this is invasive and painful, while a clinical trialof iron supplementation is inexpensive and non-traumatic, patients are often treated without a definitive diagnosis.
Determination of etiology
The diagnosis of iron deficiency anemia requires further investigation as to its cause. It can be a sign of other disease, such as
colon cancer, which will cause the loss of blood in the stool. In adults, 60% of patients with iron deficiency anemia may have underlying gastrointestinal disorders leading to chronic blood loss.cite journal |author=Rockey D, Cello J |title=Evaluation of the gastrointestinal tract in patients with iron-deficiency anemia |journal=N Engl J Med |volume=329 |issue=23 |pages=1691–5 |year=1993 |pmid=8179652 |doi=10.1056/NEJM199312023292303] . In addition to dietary insufficiency, malabsorption, chronic blood loss, diversion of iron to fetal erythropoiesisduring pregnancy, intravascular haemolysisand haemoglobinuriaor other forms of chronic blood loss should all be considered.
If the cause is dietary iron deficiency,
iron supplements, usually with iron (II) sulfate, ferrous gluconate, or iron amino acid chelate NaFeEDTA, will usually correct the anemia.
Recent research suggests the replacement dose of iron, at least in the elderly with iron deficiency, may be as little as 15 mg per day of elemental iron cite journal |author=Rimon E, Kagansky N, Kagansky M, Mechnick L, Mashiah T, Namir M, Levy S |title=Are we giving too much iron? Low-dose iron therapy is effective in octogenarians |journal=Am J Med |volume=118 |issue=10 |pages=1142–7 |year=2005 |pmid=16194646 | doi = 10.1016/j.amjmed.2005.01.065] . An experiment done in a group of 130 anemia patients showed a 98% increase in iron count when using an iron supplement with an average of 100mg of Iron. [cite journal |author=Radtke H, Mayer B, Röcker L, Salama A, Kiesewetter H |title=Iron supplementation and 2-unit red blood cell apheresis: a randomized, double-blind, placebo-controlled study |journal=Transfusion |volume=44 |issue=10 |pages=1463–7 |year=2004 |pmid=15383019 |doi=10.1111/j.1537-2995.2004.04045.x |url=http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0041-1132&date=2004&volume=44&issue=10&spage=1463] .
Women who develop iron deficiency anemia in mid-pregnancy can be effctively treated with low doses of iron (20-40 mg per day).cite journal |author=Zhou SJ, Gibson RA, Crowther CA, Makrides M |title=Should we lower the dose of iron when treating anaemia in pregnancy? A randomized dose-response trial |journal=Eur J Clin Nutr |volume= |issue= |pages= |year=2007 |pmid=17928802 |doi=10.1038/sj.ejcn.1602926] The lower dose is effective and produces fewer gastrointestinal complaints.
Many tests have shown that iron supplementation can lead to an increase in
infectious diseasemorbidity in areas where bacterial infections are common. For example, children receiving iron-enriched foods have demonstrated an increased rate in diarrheaoverall and enteropathogen shedding [cite journal |author=Long K, Rosado J, Fawzi W |title=The Comparative Impact of Iron, the B-Complex Vitamins, Vitamins C and E, and Selenium on Diarrheal Pathogen Outcomes Relative to the Impact Produced by Vitamin A and Zinc |journal=Nutritional Reviews |volume=65 |issue=5 |pages=218–232 |year=2007 |doi=10.1301/nr.2007.may.218-232 ] . Iron deficiency protects against infection by creating an unfavorable environment for bacterial growth. Nevertheless, while iron deficiency might lessen infections by certain pathogenic diseases, it also leads to a reduction in resistance to other strains of viral or bacterial infections, such as Salmonella typhimuriumor Entamoeba histolytica. Overall, it may be concluded that iron supplementation can be both beneficial and harmful to an individual in an environment that is prone to many infectious diseases [cite journal |author=Ndyomugyenyi R, Kabatereine N, Olsen A, Magnussen P |title=Malaria and hookworm infections in relation to haemoglobin and serum ferritin levels in pregnancy in Masindi district, western Uganda |journal=Transaction of the Royal Society of Tropical Medicine and Hygiene |volume=102 |pages=130–136 |year=2008 |doi=10.1016/j.trstmh.2007.09.015]
There can be a great difference between iron intake and iron absorption, also known as
bioavailability. Scientific studies indicate iron absorption problems when iron is taken in conjunction with milk, tea, coffee and other substances. There are already a number of proven solutions for this problem, including:
* Fortification with
ascorbic acid, which increases bioavailability in both presence and absence of inhibiting substances, but which is subject to deterioration from moisture or heat. Ascorbic acidfortification is usually limited to sealed dried foods, but individuals can easily take ascorbic acidwith basic iron supplement for the same benefits.
* Microencapsulation with
lecithin, which binds and protects the iron particles from the action of inhibiting substances. The primary benefit over ascorbic acidis durability and shelf life, particularly for products like milk which undergo heat treatment.
* Using an iron amino acid chelate, such as NaFeEDTA, which similarly binds and protects the iron particles. A study performed by the Hematology Unit of the University of Chile indicates that chelated iron (ferrous bis-glycine chelate) can work with
ascorbic acidto achieve even higher absorption levels cite journal |author=Olivares M, Pizarro F, Pineda O, Name JJ, Hertrampf E, Walter T.
title=Milk inhibits and ascorbic acid favors ferrous bis-glycine chelate bioavailability in humans |journal=J Nutr |volume=127 |issue=7 |pages=1407–11 |year=1997 |month=Jul |pmid=9202099] .
* Separating intake of iron and inhibiting substances by a couple of hours.
* Using goats' milk instead of cows' milk.
* Gluten-free diet resolves some instances of iron-deficiency anemia.
* Some peoplewho believe that "heme iron”, found only in animal foods such as meat, fish and poultry, is more easily absorbed than "non-heme" iron, found in plant foods and supplements [cite journal |author=Scholl TO, Hediger ML, Fischer RL, Shearer JW |title=Anemia vs iron deficiency: increased risk of preterm delivery in a prospective study |journal=Am. J. Clin. Nutr. |volume=55 |issue=5 |pages=985–8 |year=1992 |pmid=1570808 |doi= |url=http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=1570808] .
Iron bioavailability comparisons require stringent controls, because the largest factor affecting bioavailability is the subject's existing iron levels. Informal studies on bioavailability usually do not take this factor into account, so exaggerated claims from health supplement companies based on this sort of evidence should be ignored. Scientific studies are still in progress to determine which approaches yield the best results and the lowest costs.
If anemia does not respond to oral treatments, it may be necessary to administer iron
parenterally (e.g., as iron dextran) using a drip or haemodialysis. Parenteral iron involves risks of fever, chills, backache, myalgia, dizziness, syncope, rash, anaphylactic shock[http://www.globalrph.com/irondextran.htm Iron dextran dosing calculator. Total dose infusion. Iron deficiency anemia ] ] and secondary iron overload. Epinephrineis used to counter anaphylactic shock, and Chelation therapyis used to manage secondary iron overload cite journal |author=Kushner JP, Porter JP, Olivieri NF |title=Secondary iron overload |journal=Hematology Am Soc Hematol Educ Program |volume= |issue= |pages=47–61 |year=2001 |pmid=11722978 |doi= |url=http://asheducationbook.hematologylibrary.org/cgi/content/full/2001/1/47] .
A follow up
blood testis essential to demonstrate whether the treatment has been effective.
Note that iron supplements must be kept out of the reach of children, as iron-containing supplements are a frequent cause of poisoning in the pediatric age group.
Effect of vitamin and mineral supplements
There is an observed correlation between serum
retinoland hemoglobinlevels. Women with a low serum retinol concentration are more likely to be iron-deficient and anemic, compared to those with normal to high levels of retinol. While vitamin A deficiencyhas an adverse effect on hemoglobin synthesis, even a slight increase in vitamin A intake can lead to a significant rise in hemoglobin levels. However, vitamin A is less effective in alleviating severe iron-deficiency anemia. Without a doubt, low levels of iron in the body cannot be relieved by vitamin A supplementation alone. Additionally, a low ascorbic acidstores in the body causes an impairment in the release of stored iron in the reticuloendothelial cells[cite journal |author=Villamor E, Mbise R, Spiegelman D, Ndossi G, Fawzi WW |title=Vitamin A supplementation and other predictors of anemia among children from Dar Es Salaam, Tanzania |journal=Am. J. Trop. Med. Hyg. |volume=62 |issue=5 |pages=590–7 |year=2000 |pmid=11289670 |doi= |url=http://www.ajtmh.org/cgi/pmidlookup?view=long&pmid=11289670] . Ascorbic acid plays an important role in modulating ferritinsynthesis and iron storage.
Copper is necessary for iron uptake, and a
copper deficiencycan result in iron deficiency. Copper deficiencycan sometimes be caused by excessive zincor vitamin Csupplementation.
Human iron metabolism
* [http://www.anaemiaworld.com/portal/eipf/pb/m/aw/establishing_the_cause_of_anemia| Establishing the cause of anemia] - AnaemiaWorld.com
* http://www.anemia.org/patients/information-handouts/iron-deficiency/ - National Anemia Action Council
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