How does iron deficiency contribute to overall burden of disease globally?
Iron deficiency is in the top 20 risk factors for the global distribution of burden of disease1. It is frequently under-diagnosed resulting in increased hospitalisation, reduced quality of life and higher mortality rates in patients with comorbid conditions1–7. The WHO has estimated that iron deficiency causes the loss of 48,225 disability-adjusted life-years (DALYs) worldwide, more than is seen with lung cancer1. If iron deficiency is left to advance to anaemia it is harder to treat and associated with even worse outcomes4,6; however, recent research indicates that treating iron deficiency early on, before progression to anaemia, reduces mortality in comorbid conditions6,7.
For further information on the global burden of iron deficiency, please click here.
How do iron deficiency, iron deficiency anaemia and anaemia (without iron deficiency) differ?
What are the common symptoms of iron deficiency?
Common symptoms of iron deficiency are presented in the table below8–12. However, symptoms can vary depending on the type of iron deficiency and the severity, as well as with the presence of comorbid diseases8. The commonality between symptoms of iron deficiency, with or without anaemia, and those of concomitant diseases may complicate diagnosis and reliance upon symptoms alone is not appropriate9. Comprehensive screening of multiple blood iron parameters is the only method of accurately diagnosing iron deficiency.
Each therapeutic area has its own guidelines detailing the common presentation of iron deficiency within specific patient populations. More information can be found in the ‘Clinical guidelines’ section of the Iron Essentials page.
How do I diagnose iron deficiency versus other causes of anaemia?
Haematological and biological tests are the main source of information for a diagnosis of iron deficiency (see table below)10. As each test represents a different aspect of iron metabolism, care must be taken when interpreting the results and selecting threshold values of the measurements. The appropriate guidelines should always be adhered to when determining specific diagnostic cut offs. For more information on guidelines, please click here.
In addition, most types of anaemia that are not due to iron deficiency do not cause microcytosis, which means that a low mean corpuscular volume (MCV) can often be a marker of iron deficiency. There is an increasing body of literature suggesting that the percentage of hypochromic reticulocytes is a reliable indicator, but this test is not yet widely available10.
What is the difference between functional and absolute iron deficiency?
Absolute iron deficiency, which is commonly caused by blood loss, arises from depleted iron stores and often results in occurrence of anaemia. It is characterised by a low serum ferritin, low percentage saturation of transferrin and high total iron binding capacity8–10.
Functional iron deficiency, better described as iron restricted erythropoiesis, may occur in patients with upregulation of the iron regulatory protein hepcidin, which blocks iron absorption and release from circulating macrophages8. As a result, iron is present but unavailable, serum ferritin levels are normal to high, the percentage saturation is still low due to iron availability, and the total iron binding capacity is normal8–10. It also occurs when the bone marrow erythropoietic activity is significantly increased above baseline, as with the use of erythropoiesis stimulating agents (ESAs), and otherwise normal iron stores are unable to sustain an increased iron demand8–10.
For further information on distinguishing between different forms of iron deficiency, please click here.
How does prevalence of iron deficiency differ in different patient populations?
Prevalence of iron deficiency varies greatly across different patient populations due to differences in underlying causes. It occurs frequently in patients with chronic diseases such as inflammatory bowel disease, heart failure and chronic kidney disease13. This may be due to the body’s inflammatory response which leads to reduced iron uptake4–6. Iron deficiency is also common in pregnancy, in women with heavy menstrual bleeding and in cancer patients. In these patient groups iron deficiency is often a consequence of increased blood loss14,15.
How can iron deficiency affect patient outcomes in comorbid conditions?
Anaemia and iron deficiency are associated with poorer outcomes and increased morbidity across a range of comorbid conditions, some of which are listed below.
Chronic heart failure
Iron deficiency is linked to both disease severity and mortality in patients with chronic heart disease, and its correction has been shown to lead to a significant improvement in cognitive function, symptoms and exercise performance16,4.
Chronic kidney disease
Iron therapy provides clinical benefits in patients with chronic kidney disease and iron deficiency anaemia, including significant increases in haemoglobin levels and improvements in physical performance, immune function, thermoregulation and cognition17,18.
Iron deficiency is common in patients with gastrointestinal diseases. It is associated with reduced quality of life, and increased time away from work and frequency of hospitalisation19. It is common amongst patients with inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis.
Pregnancy and gynaecological patients
Iron deficiency in pregnancy is associated with multiple maternal and neonatal complications, including (but not limited to) premature birth, reduced birth weight, perinatal mortality, increased risk of maternal infections and decreased tolerance of infections or bleeding20.
Iron deficiency can have a significant, deleterious effect on quality of life in patients with specific types of cancer. Evidence suggests a correlation between iron deficiency and poor Eastern Cooperative Oncology Group (ECOG) performance status in patients with solid tumours15.
How do oral and intravenous iron therapies differ?
Treatment with oral iron offers a relatively simple and cost-effective option for iron replacement. For patients with no contraindications to oral iron or in those who do not experience adverse events, oral iron therapy can be effective21. However, it is unsuitable in certain patient populations21, and its use is frequently associated with gastrointestinal side effects including nausea, gastric cramping, constipation and diarrhoea. Significant toxicity is often reported with oral iron treatment and adherence is low21.
Intravenous iron avoids the need for oral intake, which is beneficial in patients with absorption problems. The iron is delivered directly into the blood and is, therefore, often effective when oral iron is unsuccessful or inappropriate. The currently used formulations offer the benefit of a relatively quick correction of iron deficiency (15-60 minute total-dose infusions). In addition, severity of side effects may be decreased with intravenous iron therapy. Intravenous iron is often under-used as a result of misinformation concerning minor reactions to administration22. However, serious adverse events are rare and intravenous administration often leads to better patient adherence and outcomes22.
Both intravenous and oral iron are currently recommended in several guidelines for the treatment of iron deficiency and iron deficiency anaemia23–29.
When is oral iron therapy not indicated?
Oral iron is unsuitable in certain patient populations, such as in those where it cannot work effectively, including patients who have undergone gastric bypass, have heavy uterine bleeding, and have ongoing blood loss such as in hereditary haemorrhagic telangiectasia and angiodysplasia30,31. It is also often ineffective in inflammatory disorders, such as in inflammatory bowel disease, where iron absorption through the gut is reduced31.
Another major clinical scenario where oral iron therapy is not indicated is in haemodialysis patients. Oral iron is not absorbed due to an increase in the iron regulatory hormone hepcidin in this patient group. Clinical practice guidelines suggest that only intravenous iron is useful in this population31.
For information on prescribing iron therapy, please refer to the ‘dosing and treatment’ section of the Iron Essentials page.