Information
Editors
MarjattaSinisalo
OutiLaine
Iron Deficiency Anaemia
Essentials
- Iron deficiency is the most common aetiology of anaemia. Bleeding is its most common cause in developed countries. Intestinal parasites cause a large share of iron deficiency anaemia cases in developing countries.
- Menstruation is in most cases the cause of iron deficiency anaemia in women of reproductive age. About 20% of them have iron deficiency at some stage.
- Iron deficiency in men and in women after reproductive age is always abnormal and caused in most cases by gastrointestinal bleeding Haematemesis and Melaena or absorptive disorder (coeliac disease) Coeliac Disease.
- The older the patient is, the higher the possibility that anaemia is caused by colon cancer.
- Basic blood count with platelets is the most important laboratory test, showing typically microcytic anaemia (MCV < 80 fl).
- Ferritin is a good indicator of body iron stores and its low concentration is always a sign of iron deficiency. High ferritin concentration does not necessarily, however, exclude anaemia (ferritin is also an acute-phase protein).
Causes
- Chronic haemorrhage
- Malabsorption (most commonly caused by coeliac disease)
- Defective nutrition (rarely)
Diagnostics
- There may be iron deficiency in the body already before anaemia develops. Iron deficiency is detected with plasma ferritin assay. Due to the high prevalence of iron deficiency, many individuals with ferritin concentration within the reference range have iron deficiency. In the literature a cut-off limit of 30 µg/l has been accepted as a sign of iron deficiency in adults, but in anaemic patients the value is usually < 15 µg/l. Iron deficiency without anaemia may cause unspecific symptoms such as fatigue, concentration difficulties and restless legs syndrome.
- Iron deficiency in association with a chronic disease is detected by determining, in addition to ferritin, transferrin saturation since ferritin concentration may be increased due to chronic inflammation. Transferrin saturation < 20% and concurrent ferritin concentration < 100 µg/l suggest iron deficiency. Serum soluble transferrin receptor assay (sTfR) exceeding the reference range also is a strong indicator of iron deficiency. The assay is not reliable in all situations, e.g. pregnancy, acute haemorrhage, haemolysis, sickle cell anaemia, thalassaemia and polycythaemia.
- Bone marrow examination Bone Marrow Examination is usually not needed in typical iron deficiency anaemia. If, however, the condition is associated with other deviations in the blood picture, a bone marrow examination should be performed. Mild thrombocytosis Thrombocytosis often accompanies iron deficiency and in this context does not necessitate bone marrow examination.
- With the development of biochemical assays, bone marrow examination has lost its role as a central investigation. In unclear cases and when suspecting an actual haematological disease, bone marrow examination is still indicated.
Determining the cause of iron deficiency
- Iron deficiency anaemia is only a symptom. The underlying pathogenic mechanisms must be uncovered.
- In fertile women the most likely cause is excessive menstrual bleeding. For anaemia during pregnancy, see article on antenatal care Antenatal Clinics: Care and Examinations. Menstrual bleeding that causes anaemia may sometimes be caused by a coagulation disorder Hereditary Coagulation Factor Deficiencies. Hence, family history should be discussed with the patient and sometimes it may be warranted to measure the activity of von Willebrand factor.
- Haemorrhages, especially gastrointestinal ones (gastric ulcer, intestinal tumours, also haemorrhoids) are common Haematemesis and Melaena. In all men and in women whose anaemia is not explained by menstrual bleeding, the cause of iron deficiency should be sought for by endoscopic examinations of the gastrointestinal tract. Faecal occult blood test is not useful because negative test result does not exclude gastrointestinal tumours as the cause of anaemia.
- The patient's age and past history together with current symptoms determine the order of investigations.
- It is advisable to investigate the colon in all patients over 50 years of age by colonoscopy Colonoscopy and Sigmoidoscopy. Gastroscopy is the first examination if the patient has (had) melena Haematemesis and Melaena or there are symptoms compatible with a gastric ulcer.
- With younger patients the examinations begin with gastroscopy, especially if there are gastric symptoms. If the symptoms point to a disease at the distal end of the gastrointestinal tract or if gastroscopy does not explain the anaemia, the colon should be examined. If the cause of iron deficiency is not revealed by the aforementioned investigations, the patient is referred to a specialist in gastroenterology.
- Nutritional factors and malabsorption are rarer causes.
- In suspected coeliac disease Coeliac Disease, the IgA tissue transglutaminase antibodies are determined, and if positive, the diagnosis is confirmed by endomysial antibodies or, as required, by small bowel biopsy.
- It is most important to prevent excess iron (blood) losses and to guarantee the sufficient iron content of the diet.
- Iron substitution is usually given orally. A sufficient daily amount is 100-200 mg, which can be given once daily or every second day, which may even improve its absorption.
- In moderate to severe iron deficiency anaemia there is a reticulocyte response usually seen 5-10 days after starting therapy.
- Normalization of haemoglobin and MCV values is expected in 2-4 months.
- Iron substitution should be maintained for 6 months after the normalization of haemoglobin concentration in order to fill body iron stores.
- Parenteral iron substitution may be needed if the patient does not tolerate oral treatment, as well as in iron absorption deficiency (postgastrectomy sequela or inflammatory bowel disease). Also patients with renal disease may need parenteral iron substitution in association with dialysis and/or erythropoietin therapy.
- Intravenous iron products are relatively well tolerated, but they may be associated with the possible risk of anaphylactic reactions and hypophosphataemia.
- Patients with iron deficiency anaemia are not treated by haematologists. If there are other deviations in the blood picture than low haemoglobin and thrombocytosis that is often associated to it, a haematologist should be consulted.
References
- Pasricha SR, Tye-Din J, Muckenthaler MU et al. Iron deficiency. Lancet 2021;397(10270):233-248 [PubMed]