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Iron deficiency

Author: Vanessa Ngan, Staff Writer, 2005. Updated by Dr Sara deMenezes,Basic Physician Trainee, Alfred Health, Melbourne, Australia;Chief Editor, Dr Amanda Oakley, Hamilton, New Zealand, July 2016.


Iron deficiency — codes and concepts
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What isanaemia?

Anaemia (American spelling, anemia) is a deficiency of red blood cells. It can occur either through the reduced production or an increased loss of red blood cells.

Three essential elements must be present to produce red blood cells: iron, vitamin B12 and folic acid. The most common cause of anaemia is iron deficiency, affecting more than 2 billion people worldwide.

What is iron-deficiency anaemia?

The estimatedprevalenceof iron deficiency worldwide is double that of iron deficiency anaemia. Iron deficiency anaemia occurs when there is insufficient iron to create red blood cells

Who gets iron deficiency?

The main groups at risk of iron deficiency and iron-deficiency anaemia are pre-school children, adolescents, pregnant and young women, which are times of increasedphysiologicalneed for iron.

What causes iron deficiency?

In people living indevelopingcountries, iron deficiency tends to be due to insufficient dietary iron intake or to blood loss from intestinal worm colonisation. In high-income countries, iron deficiency may result from a vegetarian diet,chronicblood loss, or malabsorption.

  • 与饮食相关缺铁
    • Malnutrition— poverty, premature babies (milk is a poor source of iron), young children who are picky eaters
    • Strict vegetarian and vegan diets
    • Cereal-based diets — decreases ironbioavailability, as phytates in grains reduce iron absorption
  • Blood loss
    • Heavy menstruation (periods)
    • 消化道出血——从消化性ulcer, polyps orcancer, may occur over a long period
    • Excessive blood donation
  • Gastrointestinal iron deficiency
    • Malabsorption
    • Crohn disease
    • Helicobacterinfectionoratrophicgastritis, which may also lead to B12 deficiency
    • Intestinalparasiticinfections, such ashookwormor tapeworm
  • Other conditions
    • Pregnancy
    • Bleeding disorders, such as von Willebrand disease
    • End-stagerenalfailure — a combination of blood loss fromdialysisand low erythropoietin levels (a hormone that stimulates red blood cell production)
    • Congestive cardiac failure — possibly due to subclinicalinflammationand impaired iron absorption
    • Myelodysplasia — bone marrow disease which can present with anaemia
    • Intravascularhaemolysis(rare) as inparoxysmalnocturnal haemoglobinuria

What are the clinical features of iron deficiency?

The signs and symptoms of an iron deficiency depend on whether the patient isanaemic, and if so, how fast the anaemia develops. In cases where anaemia develops slowly, the patient can often tolerate extremely low concentrations of red blood cells (< 100 g/L) for some weeks before developing any symptoms. The first symptoms to appear are due to low delivery of oxygen to tissues, and may include:

  • Lethargy
  • Weakness
  • Poor concentration
  • Shortness of breath
  • Palpitations.

Skin signs of iron deficiency anaemia

Skin signs of anaemia are often subtle and may include:

Cutaneous signs of iron deficiency

Systemicsymptoms of iron deficiency anaemia

Other characteristicmanifestationsof iron deficiency anaemia may include:

  • Pica — an appetite for clay, dirt, paper or starch
  • Pagophagia — a pica for ice, considered quite specific for iron deficiency. Responds rapidly to iron replacement.
  • Beeturia — excretion of red urine with the consumption of beets. In people with normal iron levels, ferric ions decolourise betalain (the redpigmentin beets). In iron-deficient states, there are inadequate amounts of iron to decolourise this pigment.
  • Restless legssyndrome— marked discomfort in the legs occurring at rest that is relieved by movement.

Iron deficiency may alsopredisposetobacterialandfungal infectionssuch asimpetigo,boilsandcandidiasis.

What tests should be done?

Full blood count

A full, or complete, blood count (FBC, CBC) is essential to detect anaemia. Iron deficiency can be present when blood count indices are normal.

If anaemia is due to iron deficiency, the cells are smaller and contain lesshaemoglobinresulting in lowered red blood cell count orhaematocrit,meancorpuscular volume (MCV) and mean cell haemoglobin concentration (MCH). Reticulocyte haemoglobin content (Ret-Hb), which tends to be low in iron deficiency anaemia, can be used to monitor response to iron replacement. Red celldistributionwidth (RDW) can reveal mixed iron and vitamin B12 deficiency as this results in red cells of variable size.

Ferritin

Ferritin is a measure of iron stores and is the most sensitive and specific test for iron deficiency. Low levels of ferritin less than 15 μg/ml are diagnostic of iron deficiency. Levels higher than 40 μg/ml in a healthy person are considered optimal.

Normal or high levels of ferritin do not exclude iron deficiency, because ferritin acts as anacutephase reactant. Levels are higher in the presence of chronic inflammation (eg,rheumatoidarthritis) whenerythrocytesedimentation rate (ESR) orC-reactiveprotein(CRP) are elevated. In the context of inflammation, significantly higher cut-off values for ferritin are used (eg, 100 μg/ml) and are more predictive of iron deficiency. Ferritin is also more elevated in patients with chronic kidney disease and heart failure.

Other iron tests

In iron deficiency:

  • Serumiron is reduced — be aware that serum iron can be very variable, fluctuating through the day, and serum iron is not useful in assessing iron stores
  • Iron binding capacity is increased — a measure of the capacity of iron to bind with transferrin (an iron transporter)
  • Transferrin saturation is reduced
  • Soluble transferrinreceptor(sTfR) is reduced – this reflects total body stores, except if there is a disease of the bone marrow. sTfR is an expensive test. It is useful at discriminating iron deficiency in difficult cases, for instance, in patients with chronic renal failure or chronic inflammation like rheumatoid arthritis. It is unchanged in anaemia of chronic disease.

Retest iron status after three months of iron supplementation.

老年患者铁def有时原因不明iciency anaemia. If bowel investigation is negative, bone marrow examination may be considered in undifferentiated cases.

What is the treatment for iron deficiency?

Once iron deficiency has been established, the underlying cause should be investigated and managed (correct/controlGI bleeding or menstrual blood loss, eg, with the levonorgestrel-releasingintrauterinedevice ortranexamic acid一个女人有着沉重的时间)。大多数人与iron deficiency anaemia will need iron replacement therapy to correct the anaemia and replenish iron stores. The benefit of treating iron deficiency without anaemia is still uncertain. Specific groups of patients like those with cardiovascular disease (with heart failure orangina) should receive red blood cell transfusions which will correct bothhypoxia(low oxygen) and the iron deficiency.

Increase dietary iron

Red meat contains haem iron, which is readily absorbed. Non-haem iron sources may need the help of vitamin C in the form of fresh fruit or tablets.

Many manufactured foods contain iron, so it is essential to read the labels.

Calcium (in milk products) and tannin in tea, coffee and red wine, reduce the absorption of non-haem iron, so these should be taken several hours before a meal. Conversely, vitamin C (ascorbic acid) enhances the absorption of iron when they are taken together.

Oral iron

Iron supplementation is safe in pregnancy, infants, children and adults. It can be used in iron deficiency anaemia and anaemia of chronic disease.

Iron preparations come in the form of tablets, oral liquids and injection. Oral preparations are most commonly used.

Oral iron preparations from reputable sources include:

  • Ferrous fumarate 33% elemental iron
  • Ferrous sulfate 20% elemental iron
  • 亚铁gluconate 12% elemental iron

Enteric-coated and slow-releaseformulationsare less well absorbed, but better tolerated. Taking iron with vitamin C (ascorbic acid) may increase its absorption and help replenish iron stores more quickly. Lower dose preparations are less effective.

In anaemic patients, once haemoglobin levels are corrected to within the normal range, iron replacement should be continued for a further three months to replenish iron stores. Aim for serum ferritin levels over 50 μg/ml.

Iron absorption is reduced in the presence of gastrointestinal disease (atrophic gastritis, infection withHelicobacter pylori,coeliac disease,inflammatory bowel disease), chronic kidney disease and inflammatory conditions.

Interactions with iron

Iron may interfere with the absorption of some medications, including:

Iron absorption is decreased by calcium, tannins (in tea and red wine) and plant phytates (in cereals). Iron should be taken at a different time of day.

Iron infusions

Intravenous infusions are used in patients that cannot tolerate oral supplementation, or where iron losses exceed the daily amount that can be absorbed orally. Intravenous iron is also essential in the management of anaemia in patients with chronic kidney disease that are receiving dialysis and treatment with erythropoiesis-stimulating agents (agents to stimulate red blood cell production). Parenteral iron in patients with heart failure has led to improvements in physical performance, symptoms and quality of life.

The most commonly used intravenous preparation is iron polymaltose, which is infused over several hours. Other intravenous preparations include lowmolecularweight iron dextran, iron carboxymaltose, iron sucrose and ferric gluconate complex.

Side effects of iron replacement

Adherence to recommended oral iron replacement therapy may be poor with some patients as iron preparations are associated with a highincidenceof side effects. These include nausea, constipation, diarrhoea and black stools. To reduce this:

  • Take the iron preparation after meals — but iron absorption is reduced
  • Wait 30 minutes before lying down
  • Divide the dose and take it twice daily
  • Take it alternate days, which is better tolerated
  • If treatment is not urgent, start with one tablet twice weekly and gradually increase the dose as tolerated
  • Start with doses containing under 30 mg of elemental iron.

Intravenous iron polymaltose may cause infusion reactions such as headache, nausea and muscle pains. Severeallergic reactionsincludinganaphylaxishave been reported. Delayed reactions includefeverand joint pain.Extravasationis rare but may lead topersistentbrown discolouration of affected skin.

Intramuscularinjections of iron are now rarely used. They may result in long-lasting brown staining (siderosis), pain,haematomaand sterileabscesses. Improvement in iron staining has been reported following treatment withQ-switchedrubyandNd:YAGlaser.

Siderosis from iron injection

What is the outcome for iron deficiency anaemia?

Most patients with uncomplicated iron deficiency anaemia should experience:

  • Rapid resolution of pagophagia
  • Improved feeling of well-being within the first few days of treatment
  • Increase in reticulocyte count (red blood cell precursors) and haemoglobin concentration within a week
  • Slow recovery of tongue papillae, skin,nailsand hair.

In those who do not respond to treatment, alternative diagnoses need to be considered, for example, B12 or folate deficiencies, myelodysplastic syndrome (bone marrowabnormalities) and inherited anaemias.

References

  • Book: Textbook of Dermatology. Ed Rook A, Wilkinson DS, Ebling FJB, Champion RH, Burton JL. Fourth edition. Blackwell Scientific Publications.
  • Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015 May 07; 372(19):1832-43.
  • Schrier SL. Causes and diagnosis of iron deficiency anemia in the adult. In: UpToDate, Post TW(Ed),UpToDate, Waltham, MA. (Accessed on June 30, 2016).
  • Schrier SL, Auerbach M. Treatment of iron deficiency anemia in adults. In: UpToDate, Post TW(Ed),UpToDate, Waltham, MA. (Accessed on June 30, 2016).
  • Stoffel NU, Cercamondi CI, Brittenham G, et al. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematol 2017.PubMed.

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