Iron deficiency anemia
Encyclopedia
Iron-deficiency anemia is a common anemia that occurs when iron loss (often from intestinal bleeding or menses) occurs, and/or the dietary intake or absorption of iron
is insufficient. In iron deficiency, hemoglobin, which contains iron, cannot be formed.
Iron deficiency is the most common single cause of anemia worldwide, accounting for about half of all anemia cases. It is more common in women than men. Estimates of iron deficiency worldwide range very widely, but the number almost certainly exceeds one billion persons globally. Worldwide, the most important cause of iron-deficiency anemia is parasitic infection caused by hookworms, whipworm
s, and roundworms, in which intestinal bleeding caused by the worms may lead to undetected blood loss in the stool. These are especially important problems in growing children. Malaria infections that destroy red blood cells (although the iron is recycled) and chronic blood loss caused by hookworms (where the iron is lost) contribute to anemia during pregnancy in most developing countries. In adults of post-menopausal age (over 50 years old) the most common cause of iron-deficiency anemia is chronic gastrointestinal bleeding from nonparasitic causes, such as from gastric ulcer, duodenal ulcer or a gastrointestinal cancer
.
In the developed world, where intestinal worm parasite burden is less than in many undeveloped countries, about 20% of all women of childbearing age have iron-deficiency anemia, compared with only 3% of adult men. The principal cause of iron-deficiency anemia in these countries is blood lost during menses
in premenopausal women and not compensated by intake from food and supplements.
Iron-deficiency anemia is one result of advanced-stage iron deficiency
, which is even more common. When the body has sufficient iron to meet its needs (functional iron), the remainder is stored for later use, mostly in the bone marrow
, liver
, and spleen
(although all cells store some iron) as part of a finely tuned system of human iron metabolism
. The store of iron present in all animal cells is deposited mostly in ferritin
complexes. In humans each of these are made up of 24 subunit protein molecules of two different types, with each ferritin complex carrying about 4500 iron atoms, as ferrous
ions.
Iron deficiency ranges from iron depletion, which produces 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 enters a state in which it requires more iron than is being absorbed from the diet.
(reduced oxyhemoglobin in skin or mucous membranes), 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.
Hair loss and lightheadedness can also be associated with iron-deficiency anemia.
Other symptoms and signs of iron-deficiency anemia include:
. Iron-deficiency anemia affects neurological development by decreasing learning ability, altering motor functions, and permanently reducing the number of dopamine
receptors and serotonin
levels. Iron deficiency during development can lead to reduced myelination of the spinal cord
, as well as a change in myelin composition. Additionally, iron-deficiency anemia has a negative effect on physical growth. Growth hormone
secretion is related to serum transferrin
levels, suggesting a positive correlation between iron-transferrin levels and an increase in height and weight. This is also linked to pica
as it can be a cause.
The most important cause of iron deficiency worldwide is infestation with parasitic worms (hookworms, whipworms, roundworms). Estimates of infection in the world population vary from a minimum of a billion humans to as many as 5 of 6 billion. In addition to parasitosis, dietary insufficiency, malabsorption, chronic blood loss, diversion of iron to fetal erythropoiesis
during pregnancy, intravascular hemolysis
and hemoglobinuria
or other forms of chronic blood loss should all be considered, according to the patient's sex, age, and history. Other common causes include gastrointestinal blood loss due to drug therapy (often in the case of NSAIDs or aspirin
), and hypochlorhydria/achlorhydria
(often due to long-term proton pump inhibitor
therapy). In babies and adolescents, rapid growth may outpace dietary intake of iron, and result in deficiency without disease or grossly abnormal diet. In women of childbearing age, heavy or long menstrual periods can also cause mild iron-deficiency anemia.
Especially in adults over the age of 50, iron deficiency is often a sign of other disease in the gastrointestinal tract, such as chronic bleeding from any cause (for example, a colon cancer) that causes loss of blood in the stool
. Such loss is often undetectable, except with special testing. In adults, 60% of patients with iron-deficiency anemia have underlying gastrointestinal disorders leading to chronic blood loss, and this percentage increases with patient age. Iron deficiency in adult men from purely dietary causes is quite rare, and in such cases other causes of iron loss must be vigorously sought until found.
, an abnormal craving for dirt, ice, or other "odd" foods occurs variably in iron and zinc deficiency, but is neither sensitive or specific to the problem so is of little diagnostic help.
Anemia is often first shown by routine blood tests, which generally include a complete blood count
(CBC) which is performed by an instrument which gives an output as a series of index numbers. A sufficiently low hemoglobin
(HGB) by definition makes the diagnosis of anemia, and a low hematocrit
(HCT) value is also characteristic of anemia. Further studies will be undertaken to determine the anemia's cause. If the anemia is due to iron deficiency, one of the first abnormal values to be noted on a CBC, as the body's iron stores begin to be depleted, will be a high red blood cell distribution width
(RDW), reflecting an increased variability in the size of red blood cells (RBCs). In the course of slowly depleted iron status, an increasing RDW normally appears even before anemia appears.
A low mean corpuscular volume
(abbreviated MCV) often appears next during the course of body iron depletion. It corresponds to a high number of abnormally small red blood cells. A low MCV, a low mean corpuscular hemoglobin
(MCH) and/or Mean corpuscular hemoglobin concentration
(MCHC), and the appearance of the RBCs on visual examination of a peripheral blood smear narrows the problem to a microcytic anemia
(literally, a "small red blood cell" anemia). The numerical values for red blood count, blood hemoglobin, MCV, MCH, MCHC are all calculated by modern laboratory equipment.
The blood smear of a patient with iron deficiency shows many hypochromic
(pale and relatively colorless) and rather small RBCs, and may also show poikilocytosis
(variation in shape) and anisocytosis
(variation in size). With more severe iron-deficiency anemia the peripheral blood smear may show target cells, hypochromic pencil-shaped cells, and occasionally small numbers of nucleated red blood cells. Very commonly, the platelet count is slightly above the high limit of normal in iron deficiency anemia (this is mild thrombocytosis
). This effect was classically postulated to be due to high erythropoietin
levels in the body as a result of anemia, cross-reacting to activate thrombopoietin
receptors in the precursor cells that make platelets; however, this mechanistic effect has been searched for and not corroborated. Such slightly increased platelet counts present no danger, but remain valuable as an indicator even if their mechanistic origin is not yet known.
The diagnosis of iron-deficiency anemia will be suggested by appropriate history (e.g., anemia in a menstruating woman or an athlete engaged in long distance running), the presence of occult blood
(i.e., hidden blood) in the stool, and often by other history. For example, known celiac disease
can cause malabsorption of iron. A travel history to areas in which hookworm and whipworm are endemic may be helpful in guiding certain stool tests for parasites or their eggs.
Body-store iron deficiency is diagnosed by diagnostic tests as a low serum ferritin
, a low serum iron
level, an elevated serum transferrin
and a high total iron binding capacity (TIBC). A low serum
ferritin is the most sensitive lab test for iron deficiency anemia. However, serum ferritin can be elevated by any type of chronic inflammation and so is not always a reliable test of iron status if it is within normal limits (i.e., this test is meaningful if abnormally low, but less meaningful if normal).
Serum iron levels (i.e., iron not part of the hemoglobin in red cells) may be measured directly in the blood, but these levels increase immediately with iron supplementation (the patient must stop supplements for 24 hours), and pure blood-serum iron concentration in any case is not as sensitive as a combination of total serum iron, along with a measure of the serum iron-binding protein levels (total iron binding capacity or TIBC). The ratio of serum iron to TIBC (called iron saturation or transferrin saturation
index or percent) is the most specific indicator of iron deficiency, when it is sufficiently low. The iron saturation (or transferrin saturation) of < 5% almost always indicates iron deficiency, while levels from 5% to 10% make the diagnosis of iron deficiency possible but not definitive. Saturations over 12% (taken alone) make the diagnosis unlikely. Normal saturations are usually slightly higher for women (>12%) than for men (>15%), but this may indicate simply an overall slightly poorer iron status for women in the "normal" population.
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 various organs, especially the liver). A hemoglobin electrophoresis
provides useful evidence for distinguishing these two conditions, along with iron studies.
of iron supplementation is inexpensive and non-traumatic, patients are often treated based on clinical history and serum ferritin levels without a bone marrow biopsy. Furthermore, a study published April 2009 questions the value of stainable bone marrow iron following parenteral iron therapy.
, usually with iron(II) sulfate
, ferrous gluconate, or iron amino acid chelate ferrous bisglycinate, synthetic chelate NaFerredetate EDTA
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. 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 100 mg of iron.
Women who develop iron deficiency anemia in mid-pregnancy can be effectively treated with low doses of iron (20–40 mg per day). The lower dose is effective and produces fewer gastrointestinal complaints. There is evidence that the body adapts to oral iron supplementation, so that iron is often effectively started at a comparatively low dose, then slowly increased.
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:
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 parenteral
ly (e.g., as iron dextran
) using a drip or hemodialysis. Parenteral iron involves risks of fever, chills, backache, myalgia, dizziness, syncope, rash and anaphylactic shock. A follow up blood test
is essential to demonstrate whether the treatment has been effective.
(an acute phase reaction protein) in acute infections is thought to be to sequester iron from bacteria, it is generally thought that iron supplementation (which circumvents this mechanism) should be avoided in patients who have active bacterial infections. Replacement of iron stores is seldom such an emergency situation that it cannot wait for such infections to be treated.
Some studies have found that iron supplementation can lead to an increase in infectious disease
morbidity in areas where bacterial infections are common. For example, children receiving iron-enriched foods have demonstrated an increased rate in diarrhea
overall and enteropathogen shedding. 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 typhimurium or Entamoeba histolytica
. Overall, it is sometimes difficult to decide whether iron supplementation will be beneficial or harmful to an individual in an environment that is prone to many infectious diseases; however this is a different question than the question of supplementation in individuals who are already ill with a bacterial infection.
and hemoglobin
levels. 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 deficiency
has 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. Low levels of iron in the body cannot be relieved by vitamin A supplementation alone. Additionally, a low ascorbic acid
stores in the body causes an impairment in the release of stored iron in the reticuloendothelial cells. Copper is necessary for iron uptake, and a copper deficiency
can result in iron deficiency. Copper deficiency can sometimes be caused by excessive zinc
or vitamin C
supplementation.
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
is insufficient. In iron deficiency, hemoglobin, which contains iron, cannot be formed.
Iron deficiency is the most common single cause of anemia worldwide, accounting for about half of all anemia cases. It is more common in women than men. Estimates of iron deficiency worldwide range very widely, but the number almost certainly exceeds one billion persons globally. Worldwide, the most important cause of iron-deficiency anemia is parasitic infection caused by hookworms, whipworm
Whipworm
The human tapworm is a roundworm, which causes trichuriasis when it infects a human large intestine. The name whipworm refers to the shape of the worm; they look like whips with wider "handles" at the posterior end.-Life cycle:The female T. trichiura produces 2,000–10,000 single celled eggs per day...
s, and roundworms, in which intestinal bleeding caused by the worms may lead to undetected blood loss in the stool. These are especially important problems in growing children. Malaria infections that destroy red blood cells (although the iron is recycled) and chronic blood loss caused by hookworms (where the iron is lost) contribute to anemia during pregnancy in most developing countries. In adults of post-menopausal age (over 50 years old) the most common cause of iron-deficiency anemia is chronic gastrointestinal bleeding from nonparasitic causes, such as from gastric ulcer, duodenal ulcer or a gastrointestinal cancer
Gastrointestinal cancer
Gastrointestinal cancer refers to malignant conditions of the gastrointestinal tract, including the esophagus, stomach, biliary system, pancreas, bowels, and anus. The symptoms relate to the organ affected, and can include obstruction , abnormal bleeding, or other associated problems...
.
In the developed world, where intestinal worm parasite burden is less than in many undeveloped countries, about 20% of all women of childbearing age have iron-deficiency anemia, compared with only 3% of adult men. The principal cause of iron-deficiency anemia in these countries is blood lost during menses
Menstruation
Menstruation is the shedding of the uterine lining . It occurs on a regular basis in sexually reproductive-age females of certain mammal species. This article focuses on human menstruation.-Overview:...
in premenopausal women and not compensated by intake from food and supplements.
Iron-deficiency anemia is one result of advanced-stage iron deficiency
Iron deficiency (medicine)
Iron deficiency is one of the most common of the nutritional deficiencies. Iron is present in all cells in the human body, and has several vital functions...
, which is even more common. When the body has sufficient iron to meet its needs (functional iron), the remainder is stored for later use, mostly in the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, and spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
(although all cells store some iron) as part of a finely tuned system of human iron metabolism
Human iron metabolism
Human iron metabolism is the set of chemical reactions maintaining human homeostasis of iron. Iron is an essential element for most life on Earth, including human beings. The control of this necessary but potentially toxic substance is an important part of many aspects of human health and disease...
. The store of iron present in all animal cells is deposited mostly in ferritin
Ferritin
Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...
complexes. In humans each of these are made up of 24 subunit protein molecules of two different types, with each ferritin complex carrying about 4500 iron atoms, as ferrous
Ferrous
Ferrous , in chemistry, indicates a divalent iron compound , as opposed to ferric, which indicates a trivalent iron compound ....
ions.
Iron deficiency ranges from iron depletion, which produces 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 enters a state in which it requires more iron than is being absorbed from the diet.
Symptoms and signs
Iron-deficiency anemia is characterized by pallorPallor
Pallor is a reduced amount of oxyhaemoglobin in skin or mucous membrane, a pale color which can be caused by illness, emotional shock or stress, stimulant use, lack of exposure to sunlight, anaemia or genetics....
(reduced oxyhemoglobin in skin or mucous membranes), fatigue and weakness. Because it tends to develop slowly, adaptation occurs and the disease often goes unrecognized for some time. In severe cases, dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
(trouble breathing) can occur. Unusual obsessive food cravings, known as pica
Pica (disorder)
Pica is characterized by an appetite for substances largely non-nutritive . For these actions to be considered pica, they must persist for more than one month at an age where eating such objects is considered developmentally inappropriate...
, may develop. Pagophagia
Pagophagia
-Pagophagia:The compulsive eating of ice that is a common symptom of a lack of iron is also a form of the disorder Pica, the ingestion of unusual foods or substances. More often Pagophagia is related to women who may be pregnant or people who have iron deficiency anemia...
or pica for ice is a very specific symptom and may disappear with correction of iron-deficiency anemia.
Hair loss and lightheadedness can also be associated with iron-deficiency anemia.
Other symptoms and signs of iron-deficiency anemia include:
- AnxietyAnxietyAnxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
often resulting in OCD type compulsions and obsessions - IrritabilityIrritabilityIrritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....
or a low feeling - AnginaAnginaAngina pectoris, commonly known as angina, is chest pain due to ischemia of the heart muscle, generally due to obstruction or spasm of the coronary arteries . Coronary artery disease, the main cause of angina, is due to atherosclerosis of the cardiac arteries...
- ConstipationConstipationConstipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
- Sleepiness
- TinnitusTinnitusTinnitus |ringing]]") is the perception of sound within the human ear in the absence of corresponding external sound.Tinnitus is not a disease, but a symptom that can result from a wide range of underlying causes: abnormally loud sounds in the ear canal for even the briefest period , ear...
- Mouth ulcerMouth ulcerA mouth or oral ulcer is an open sore in the mouth, or rarely a break in the mucous membrane or the epithelium on the lips or surrounding the mouth. The types of mouth ulcers are diverse, with a multitude of associated causes including: physical abrasion, acidic fruit, infection, other medical...
s - Palpitations
- Hair loss
- Fainting or feeling faint
- DepressionDepression (mood)Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
- Breathlessness on exertion.
- TwitchingMuscle contractionMuscle fiber generates tension through the action of actin and myosin cross-bridge cycling. While under tension, the muscle may lengthen, shorten, or remain the same...
muscles - Tingling, numbness, or burning sensations
- Missed menstrual cycle
- Heavy menstrual periodMenorrhagiaMenorrhagia is an abnormally heavy and prolonged menstrual period at regular intervals. Causes may be due to abnormal blood clotting, disruption of normal hormonal regulation of periods or disorders of the endometrial lining of the uterus...
- Slow social development
- GlossitisGlossitisGlossitis is inflammation of the tongue. It causes the tongue to swell and change color. Finger-like projections on the surface of the tongue may be lost, causing the tongue to appear smooth....
(inflammation or infection of the tongue) - Angular cheilitisAngular cheilitisAngular cheilitis is an inflammatory lesion at the labial commissure, or corner of the mouth, and often occurs bilaterally. The condition manifests as deep cracks or splits...
(inflammatory lesions at the mouth's corners) - KoilonychiaKoilonychiaKoilonychia is a nail disease that can be a sign of hypochromic anemia, especially iron-deficiency anemia. Koilonychia literally means "spoon nails." It refers to abnormally thin nails which have lost their convexity, becoming flat or even concave in shape...
(spoon-shaped nails) or nails that are weak or brittle - Poor appetiteAnorexia (symptom)Anorexia is the decreased sensation of appetite...
- Pruritus (Itchiness)
- DysphagiaDysphagiaDysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....
due to formation of esophageal webEsophageal web-Presentation:Its main symptoms are pain and difficulty in swallowing .Esophageal webs are thin membranes of normal esophageal tissue consisting of mucosa and submucosa. They can be congenital or acquired. Congenital webs commonly appear in the middle and inferior third of the esophagus, and they...
s (Plummer-vinson syndromePlummer-Vinson syndromePlummer–Vinson syndrome , also called Paterson–Brown–Kelly syndrome or sideropenic dysphagia presents as a triad of dysphagia , glossitis, and iron deficiency anemia...
). - Restless Legs SyndromeRestless legs syndromeRestless legs syndrome or Willis-Ekbom disease is a neurological disorder characterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. It most commonly affects the legs, but can affect the arms, torso, and even phantom limbs...
Infant development
Iron-deficiency anemia for infants in their earlier stages of development may have 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 supplementsIron supplements
Iron supplements are supplements that can be prescribed by a doctor for a medical reason. Iron can also be a dietary supplement, which can be purchased in supermarkets etc. These two categories should not be confused....
. Iron-deficiency anemia affects neurological development by decreasing learning ability, altering motor functions, and permanently reducing the number of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
receptors and serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
levels. Iron deficiency during development can lead to reduced myelination of the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
, as well as a change in myelin composition. Additionally, iron-deficiency anemia has a negative effect on physical growth. Growth hormone
Growth hormone
Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
secretion is related to serum transferrin
Transferrin
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...
levels, suggesting a positive correlation between iron-transferrin levels and an increase in height and weight. This is also linked to pica
Pica (disorder)
Pica is characterized by an appetite for substances largely non-nutritive . For these actions to be considered pica, they must persist for more than one month at an age where eating such objects is considered developmentally inappropriate...
as it can be a cause.
Cause
The diagnosis of iron-deficiency anemia requires further investigation as to its cause. Iron deficiency can be caused by increased iron demand or decreased iron intake, and can occur in both children and adults.The most important cause of iron deficiency worldwide is infestation with parasitic worms (hookworms, whipworms, roundworms). Estimates of infection in the world population vary from a minimum of a billion humans to as many as 5 of 6 billion. In addition to parasitosis, dietary insufficiency, malabsorption, chronic blood loss, diversion of iron to fetal erythropoiesis
Erythropoiesis
Erythropoiesis is the process by which red blood cells are produced. It is stimulated by decreased O2 in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin...
during pregnancy, intravascular hemolysis
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
and hemoglobinuria
Hemoglobinuria
In medicine, hemoglobinuria or haemoglobinuria is a condition in which the oxygen transport protein hemoglobin is found in abnormally high concentrations in the urine. The condition is often associated with hemolytic anemia, in which red blood cells are destroyed, thereby increasing levels of free...
or other forms of chronic blood loss should all be considered, according to the patient's sex, age, and history. Other common causes include gastrointestinal blood loss due to drug therapy (often in the case of NSAIDs or aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
), and hypochlorhydria/achlorhydria
Achlorhydria
Achlorhydria or hypochlorhydria refers to states where the production of gastric acid in the stomach is absent or low, respectively. It is associated with various other medical problems.-Signs and symptoms:...
(often due to long-term proton pump inhibitor
Proton pump inhibitor
Proton-pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar...
therapy). In babies and adolescents, rapid growth may outpace dietary intake of iron, and result in deficiency without disease or grossly abnormal diet. In women of childbearing age, heavy or long menstrual periods can also cause mild iron-deficiency anemia.
Especially in adults over the age of 50, iron deficiency is often a sign of other disease in the gastrointestinal tract, such as chronic bleeding from any cause (for example, a colon cancer) that causes loss of blood in the stool
Human feces
Human feces , also known as a stool, is the waste product of the human digestive system including bacteria. It varies significantly in appearance, according to the state of the digestive system, diet and general health....
. Such loss is often undetectable, except with special testing. In adults, 60% of patients with iron-deficiency anemia have underlying gastrointestinal disorders leading to chronic blood loss, and this percentage increases with patient age. Iron deficiency in adult men from purely dietary causes is quite rare, and in such cases other causes of iron loss must be vigorously sought until found.
Diagnosis
Anemia may be diagnosed from symptoms and signs, but when anemia is mild it may not be diagnosed from mild non-specific symptoms. PicaPica (disorder)
Pica is characterized by an appetite for substances largely non-nutritive . For these actions to be considered pica, they must persist for more than one month at an age where eating such objects is considered developmentally inappropriate...
, an abnormal craving for dirt, ice, or other "odd" foods occurs variably in iron and zinc deficiency, but is neither sensitive or specific to the problem so is of little diagnostic help.
Anemia is often first shown by routine blood tests, which generally include a complete blood count
Complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
(CBC) which is performed by an instrument which gives an output as a series of index numbers. A sufficiently low hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
(HGB) by definition makes the diagnosis of anemia, and a low hematocrit
Hematocrit
The hematocrit or packed cell volume or erythrocyte volume fraction is the percentage of the concentration of red blood cells in blood. It is normally about 45% for men and 40% for women...
(HCT) value is also characteristic of anemia. Further studies will be undertaken to determine the anemia's cause. If the anemia is due to iron deficiency, one of the first abnormal values to be noted on a CBC, as the body's iron stores begin to be depleted, will be a high red blood cell distribution width
Red blood cell distribution width
The red blood cell distribution width is a measure of the variation of red blood cell width that is reported as part of a standard complete blood count. Usually red blood cells are a standard size of about 6–8 μm. Certain disorders, however, cause a significant variation in cell size. Higher...
(RDW), reflecting an increased variability in the size of red blood cells (RBCs). In the course of slowly depleted iron status, an increasing RDW normally appears even before anemia appears.
A low mean corpuscular volume
Mean corpuscular volume
The mean corpuscular volume, or "mean cell volume" , is a measure of the average red blood cell size that is reported as part of a standard complete blood count....
(abbreviated MCV) often appears next during the course of body iron depletion. It corresponds to a high number of abnormally small red blood cells. A low MCV, a low mean corpuscular hemoglobin
Mean corpuscular hemoglobin
The mean corpuscular hemoglobin, or "mean cell hemoglobin" , is the average mass of hemoglobin per red blood cell in a sample of blood. It is reported as part of a standard complete blood count...
(MCH) and/or Mean corpuscular hemoglobin concentration
Mean corpuscular hemoglobin concentration
The mean corpuscular hemoglobin concentration, or MCHC, is a measure of the concentration of hemoglobin in a given volume of packed red blood cells. It is reported as part of a standard complete blood count....
(MCHC), and the appearance of the RBCs on visual examination of a peripheral blood smear narrows the problem to a microcytic anemia
Microcytic anemia
Microcytic anemia is a generic term for any type of anemia characterized by small red blood cells. The normal mean corpuscular volume is 76-100 fL, with smaller cells as macrocytic....
(literally, a "small red blood cell" anemia). The numerical values for red blood count, blood hemoglobin, MCV, MCH, MCHC are all calculated by modern laboratory equipment.
The blood smear of a patient with iron deficiency shows many hypochromic
Hypochromic anemia
Hypochromic anemia is a generic term for any type of anemia in which the red blood cells are paler than normal. A normal red blood cell will have an area of pallor in the center of it; in hypochromic cells, this area of central pallor is increased...
(pale and relatively colorless) and rather small RBCs, and may also show poikilocytosis
Poikilocytosis
Poikilocytosis refers to the presence of poikilocytes in the blood. Poikilocytes are abnormally shaped red blood cells as seen on a blood film in humans and many wild and domestic species of animals, though they are common in some clinically normal small ruminants, particularly goats.Normal red...
(variation in shape) and anisocytosis
Anisocytosis
Anisocytosis is a medical term meaning that a patient's red blood cells are of unequal size. This is found in anemia and other blood conditions...
(variation in size). With more severe iron-deficiency anemia the peripheral blood smear may show target cells, hypochromic pencil-shaped cells, and occasionally small numbers of nucleated red blood cells. Very commonly, the platelet count is slightly above the high limit of normal in iron deficiency anemia (this is mild thrombocytosis
Thrombocytosis
Thrombocytosis is the presence of high platelet counts in the blood, and can be either primary or reactive...
). This effect was classically postulated to be due to high erythropoietin
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
levels in the body as a result of anemia, cross-reacting to activate thrombopoietin
Thrombopoietin
Thrombopoietin also known as megakaryocyte growth and development factor is a protein that in humans is encoded by the THPO gene....
receptors in the precursor cells that make platelets; however, this mechanistic effect has been searched for and not corroborated. Such slightly increased platelet counts present no danger, but remain valuable as an indicator even if their mechanistic origin is not yet known.
The diagnosis of iron-deficiency anemia will be suggested by appropriate history (e.g., anemia in a menstruating woman or an athlete engaged in long distance running), the presence of occult blood
Fecal occult blood
Fecal occult blood refers to blood in the feces that is not visibly apparent. A fecal occult blood test checks for hidden blood in the stool...
(i.e., hidden blood) in the stool, and often by other history. For example, known celiac disease
Coeliac disease
Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
can cause malabsorption of iron. A travel history to areas in which hookworm and whipworm are endemic may be helpful in guiding certain stool tests for parasites or their eggs.
Body-store iron deficiency is diagnosed by diagnostic tests as a low serum ferritin
Ferritin
Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...
, a low serum iron
Serum iron
Serum iron is a medical laboratory test that measures the amount of circulating iron that is bound to transferrin. Clinicians order this laboratory test when they are concerned about iron deficiency, which can cause anemia and other problems....
level, an elevated serum transferrin
Transferrin
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...
and a high total iron binding capacity (TIBC). A low serum
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
ferritin is the most sensitive lab test for iron deficiency anemia. However, serum ferritin can be elevated by any type of chronic inflammation and so is not always a reliable test of iron status if it is within normal limits (i.e., this test is meaningful if abnormally low, but less meaningful if normal).
Serum iron levels (i.e., iron not part of the hemoglobin in red cells) may be measured directly in the blood, but these levels increase immediately with iron supplementation (the patient must stop supplements for 24 hours), and pure blood-serum iron concentration in any case is not as sensitive as a combination of total serum iron, along with a measure of the serum iron-binding protein levels (total iron binding capacity or TIBC). The ratio of serum iron to TIBC (called iron saturation or transferrin saturation
Transferrin saturation
Transferrin saturation, abbreviated as TSAT and measured as a percentage, is a medical laboratory value. It is the ratio of serum iron and total iron-binding capacity, multiplied by 100. Of the transferrin that is available to bind iron, this value tells a clinician how much serum iron is actually...
index or percent) is the most specific indicator of iron deficiency, when it is sufficiently low. The iron saturation (or transferrin saturation) of < 5% almost always indicates iron deficiency, while levels from 5% to 10% make the diagnosis of iron deficiency possible but not definitive. Saturations over 12% (taken alone) make the diagnosis unlikely. Normal saturations are usually slightly higher for women (>12%) than for men (>15%), but this may indicate simply an overall slightly poorer iron status for women in the "normal" population.
| Change | Parameter |
|---|---|
| Decrease | ferritin, hemoglobin, MCV |
| Increase | TIBC, transferrin, RDW |
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 various organs, especially the liver). A hemoglobin electrophoresis
Hemoglobin electrophoresis
Hemoglobin electrophoresis is a blood test that can detect different types of hemoglobin. It uses the principles of gel electrophoresis to separate out the various types of hemoglobin and is a type of native gel electrophoresis...
provides useful evidence for distinguishing these two conditions, along with iron studies.
Gold standard
Conventionally, a definitive diagnosis requires a demonstration of depleted body iron stores obtained by bone marrow aspiration, with the marrow stained for iron. Because this is invasive and painful, while a clinical trialClinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
of iron supplementation is inexpensive and non-traumatic, patients are often treated based on clinical history and serum ferritin levels without a bone marrow biopsy. Furthermore, a study published April 2009 questions the value of stainable bone marrow iron following parenteral iron therapy.
Treatment
If the cause is dietary iron deficiency, eating more iron-rich foods such as beans and lentils or taking iron supplementsIron supplements
Iron supplements are supplements that can be prescribed by a doctor for a medical reason. Iron can also be a dietary supplement, which can be purchased in supermarkets etc. These two categories should not be confused....
, usually with iron(II) sulfate
Iron(II) sulfate
Iron sulfate or ferrous sulfate is the chemical compound with the formula FeSO4. Known since ancient times as copperas and as green vitriol, the blue-green heptahydrate is the most common form of this material...
, ferrous gluconate, or iron amino acid chelate ferrous bisglycinate, synthetic chelate NaFerredetate EDTA
EDTA
Ethylenediaminetetraacetic acid, widely abbreviated as EDTA , is a polyamino carboxylic acid and a colourless, water-soluble solid. Its conjugate base is named ethylenediaminetetraacetate. It is widely used to dissolve limescale. Its usefulness arises because of its role as a hexadentate ligand...
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. 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 100 mg of iron.
Women who develop iron deficiency anemia in mid-pregnancy can be effectively treated with low doses of iron (20–40 mg per day). The lower dose is effective and produces fewer gastrointestinal complaints. There is evidence that the body adapts to oral iron supplementation, so that iron is often effectively started at a comparatively low dose, then slowly increased.
There can be a great difference between iron intake and iron absorption, also known as bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
. 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 acidAscorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
, which increases bioavailability in both presence and absence of inhibiting substances, but which is subject to deterioration from moisture or heat. Ascorbic acid fortification is usually limited to sealed dried foods, but individuals can easily take ascorbic acid with basic iron supplementIron supplementsIron supplements are supplements that can be prescribed by a doctor for a medical reason. Iron can also be a dietary supplement, which can be purchased in supermarkets etc. These two categories should not be confused....
for the same benefits. - Microencapsulation with lecithinLecithinLecithin is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues, and in egg yolk, composed of phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides, and phospholipids .The word lecithin was originally coined in 1847 by...
, which binds and protects the iron particles from the action of inhibiting substances. The primary benefit over ascorbic acid is durability and shelf life, particularly for products like milk which undergo heat treatment. - Using an iron amino acid chelate, such as NaFeEDTAEDTAEthylenediaminetetraacetic acid, widely abbreviated as EDTA , is a polyamino carboxylic acid and a colourless, water-soluble solid. Its conjugate base is named ethylenediaminetetraacetate. It is widely used to dissolve limescale. Its usefulness arises because of its role as a hexadentate ligand...
, 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 acid to achieve even higher absorption levels - Separating intake of iron and inhibiting substances by a couple of hours.
- Using non-dairy milk (such as soy, rice, or almond milk) or goats' milk instead of cows' milk.
- Gluten-free diet resolves some instances of iron-deficiency anemia, especially if the anemia is a result of celiac diseaseCoeliac diseaseCoeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
. - It is believed 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.
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 parenteral
Parenteral
Parenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...
ly (e.g., as iron dextran
Dextran
Dextran is a complex, branched glucan composed of chains of varying lengths...
) using a drip or hemodialysis. Parenteral iron involves risks of fever, chills, backache, myalgia, dizziness, syncope, rash and anaphylactic shock. A follow up blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
is essential to demonstrate whether the treatment has been effective.
Iron supplementation and infection risk
Because one of the functions of elevated ferritinFerritin
Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...
(an acute phase reaction protein) in acute infections is thought to be to sequester iron from bacteria, it is generally thought that iron supplementation (which circumvents this mechanism) should be avoided in patients who have active bacterial infections. Replacement of iron stores is seldom such an emergency situation that it cannot wait for such infections to be treated.
Some studies have found that iron supplementation can lead to an increase in infectious disease
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
morbidity in areas where bacterial infections are common. For example, children receiving iron-enriched foods have demonstrated an increased rate in diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
overall and enteropathogen shedding. 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 typhimurium or Entamoeba histolytica
Entamoeba histolytica
Entamoeba histolytica is an anaerobic parasitic protozoan, part of the genus Entamoeba. Predominantly infecting humans and other primates, E. histolytica is estimated to infect about 50 million people worldwide...
. Overall, it is sometimes difficult to decide whether iron supplementation will be beneficial or harmful to an individual in an environment that is prone to many infectious diseases; however this is a different question than the question of supplementation in individuals who are already ill with a bacterial infection.
Effect of vitamin and mineral supplements
There is an observed correlation between serum retinolRetinol
Retinol is one of the animal forms of vitamin A. It is a diterpenoid and an alcohol. It is convertible to other forms of vitamin A, and the retinyl ester derivative of the alcohol serves as the storage form of the vitamin in animals....
and hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
levels. 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 deficiency
Vitamin A deficiency
Vitamin A deficiency is a lack of vitamin A in humans. It is common in developing countries but rarely seen in developed countries. Night blindness is one of the first signs of vitamin A deficiency. Xerophthalmia and complete blindness can also occur since Vitamin A has a major role in...
has 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. Low levels of iron in the body cannot be relieved by vitamin A supplementation alone. Additionally, a low ascorbic acid
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
stores in the body causes an impairment in the release of stored iron in the reticuloendothelial cells. Copper is necessary for iron uptake, and a copper deficiency
Copper deficiency
Copper deficiency is a very rare hematological and neurological disorder. The neurodegenerative syndrome of copper deficiency has been recognized for some time in ruminant animals, in which it is commonly known as "swayback" The disease involves a nutritional deficiency in the trace element copper...
can result in iron deficiency. Copper deficiency can sometimes be caused by excessive zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
or vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
supplementation.
Epidemiology
See also
- Human iron metabolismHuman iron metabolismHuman iron metabolism is the set of chemical reactions maintaining human homeostasis of iron. Iron is an essential element for most life on Earth, including human beings. The control of this necessary but potentially toxic substance is an important part of many aspects of human health and disease...
- Iron supplementsIron supplementsIron supplements are supplements that can be prescribed by a doctor for a medical reason. Iron can also be a dietary supplement, which can be purchased in supermarkets etc. These two categories should not be confused....
- HematogenHematogenHematogen is a Russian fudge candy bar, which is notable in that one of its main ingredients is processed cow's blood. It is often considered to be a medicinal product, and is used to treat anemia ....
- Iron deficiency
External links
- Iron deficiency textbook IronTherapy.Org
- Establishing the cause of anemia – AnaemiaWorld.com
- Handout: Iron Deficiency Anemia – National Anemia Action Council
- Simplified decision guide for treating iron deficiency anemia – Section: Iron Therapy at Monofer.com
- NPS News 70: Iron deficiency anaemia: NPS – Better choices, Better health – 2011 National Prescribing Service Limited
- Simple Guide to Iron Deficiency Anemia