Elsevier

The Lancet

Volume 387, Issue 10021, 27 February–4 March 2016, Pages 907-916
The Lancet

Seminar
Iron deficiency anaemia

https://doi.org/10.1016/S0140-6736(15)60865-0Get rights and content

Summary

Anaemia affects roughly a third of the world's population; half the cases are due to iron deficiency. It is a major and global public health problem that affects maternal and child mortality, physical performance, and referral to health-care professionals. Children aged 0–5 years, women of childbearing age, and pregnant women are particularly at risk. Several chronic diseases are frequently associated with iron deficiency anaemia—notably chronic kidney disease, chronic heart failure, cancer, and inflammatory bowel disease. Measurement of serum ferritin, transferrin saturation, serum soluble transferrin receptors, and the serum soluble transferrin receptors–ferritin index are more accurate than classic red cell indices in the diagnosis of iron deficiency anaemia. In addition to the search for and treatment of the cause of iron deficiency, treatment strategies encompass prevention, including food fortification and iron supplementation. Oral iron is usually recommended as first-line therapy, but the most recent intravenous iron formulations, which have been available for nearly a decade, seem to replenish iron stores safely and effectively. Hepcidin has a key role in iron homoeostasis and could be a future diagnostic and therapeutic target. In this Seminar, we discuss the clinical presentation, epidemiology, pathophysiology, diagnosis, and acute management of iron deficiency anaemia, and outstanding research questions for treatment.

Introduction

Iron deficiency occurs in two main forms: absolute or functional. Absolute iron deficiency arises when total body iron stores are low or exhausted; functional iron deficiency is a disorder in which total body iron stores are normal or increased, but the iron supply to the bone marrow is inadequate. Absolute and functional deficiencies can coexist. Functional iron deficiency can be present in many acute and chronic inflammatory states, and hepcidin—the master regulator of iron homoeostasis—has a key role in pathogenesis. In this Seminar, we focus mainly on absolute iron deficiency.

Section snippets

Clinical presentation

Patients with iron deficiency anaemia can present with symptoms that are associated with all anaemias, which are sometimes associated with specific signs due to iron deficiency (panel 1). Pallor of the skin, conjunctivae, and nail beds are common.1, 11 The diagnostic usefulness of these signs is increased when clinicians can ascertain whether their presence is a change from normal in the patient. Other symptoms and signs result from hypoxic functioning: fatigue,2 exertional dyspnoea progressing

Epidemiology

In 2010, global anaemia prevalence was 32·9% (ie, more than 2·2 billion people were affected); iron deficiency was the most common cause.20 WHO estimated that, between 1993 and 2005, worldwide prevalence of anaemia was 24·8% in the general population—from 12·7% in men to 47·4% in children aged 0–5 years. Prevalence was 30·2% in women, and 41·8% in pregnancy. 23·9% of people older than 60 years were anaemic.21 Between 1995 and 2011, worldwide prevalence of anaemia decreased by 4–5% in children

Pathophysiology

Iron is an essential component of haemoglobin in red blood cells and of myoglobin in muscles, which contain around 60% of total body iron (appendix). It is also necessary for the functioning of various cellular mechanisms, including enzymatic processes, DNA synthesis, and mitochondrial energy generation. In adults, the body contains 3–5 g of iron; 20–25 mg is needed daily for production of red blood cells and cellular metabolism.29 Because dietary intake is limited (1–2 mg per day), other

Risk factors

Physiological and pathological conditions can promote iron deficiency anaemia (panel 2). The maximum absorption of iron from the diet is less than the body's requirements for iron, resulting in a risk of iron deficiency. In infants and young children (aged 0–15 years), rapid growth consumes the iron stores that accumulate during gestation, which can, in turn, lead to an absolute deficiency.41 After childhood, adolescent girls are particularly at risk of iron deficiency anaemia, because of

Diagnostic investigations

The diagnosis of anaemia is made after confirmation of a reduced blood haemoglobin concentration as shown by a full blood count. Thresholds to define anaemia depend on age, sex, pregnancy, altitude, and smoking. An adult man is deemed anaemic when his haemoglobin concentration is less than 130 g/L, whereas an adult woman is judged anaemic when her haemoglobin concentration is less than 120 g/L. In pregnancy, this cutoff is lowered to 110 g/L (table 2).63

Diagnosis of iron deficiency is somewhat

Acute and long-term management

The aim of treatment is to supply enough iron to normalise haemoglobin concentrations and replenish iron stores, and thereby to improve quality of life, symptoms, and the prognosis of many chronic disorders. Two distinct approaches exist: prevention strategies targeted at populations at risk and active iron supplementation approaches in confirmed iron deficiency anaemia.

On a global level, food-based approaches—ie, promotion of access to, and consumption of, iron-rich foods such as meat and

Iron supplementation

Iron supplementation is used in two clinical scenarios: to prevent iron deficiency anaemia in at-risk populations, or to treat patients with proven disease. In 2011, WHO recommended daily iron supplementation with 60 mg of elemental iron to prevent iron deficiency in menstruating adolescent girls and women where the prevalence of anaemia is 20%.84, 85 Similar recommendations were made for children aged 0–5 years (2 mg/kg daily) and children aged 5–12 years (30 mg daily).86

For therapeutic iron

Follow-up

Once the cause of iron deficiency anaemia has been treated and haemoglobin concentrations are healthy, full blood count and markers of iron status should be measured regularly. The British Society of Gastroenterology recommends monthly measurements for 3 months, and then every 3 months for a year.45 If symptoms persist, further blood tests should be done every 3 months for another year, and iron supplements should be given. If haemoglobin or red cell indices cannot be maintained in this way,

Outstanding research questions

Because oral iron is associated with gastrointestinal side-effects, new formulations have been developed. In a trial107 of patients with inflammatory bowel disease and iron deficiency anaemia, ferric maltol was more effective than placebo at increasing haemoglobin at 12 weeks (p<0·001), and had a similar safety profile. In non-dialysis-dependent patients with chronic kidney disease, oral haem iron polypeptide had similar efficacy to intravenous iron sucrose in maintaining haemoglobin, with no

Search strategy and selection criteria

We searched the Cochrane Library, Medline, and Embase with the terms “anaemia”, “iron deficiency”, “epidemiology”, “pathophysiology”, “ferritin”, “serum soluble transferrin receptors”, “hepcidin”, “supplementation”, “fortification”, and “review”. We selected work published in any language, largely between Jan 1, 2010, and Dec 31, 2014, but did not exclude commonly referenced and highly regarded older publications. Our last search was on Jan 25, 2015. We also searched the reference lists of

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