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Signs and symptoms

How to Treat – Iron deficiency

from page 20
Adults In the developed world, adult dietary iron intake is usually adequate to maintain iron stores, therefore the most common cause of iron deficiency is blood loss. 2, 3
Menstrual blood loss is the likely cause of iron deficiency in premenopausal women, who typically lose 10-15mg of iron per cycle. However, iron deficiency in adult men and post-menopausal women is always pathological and needs to be investigated. The most common causes in this population are non-parasitic, gastrointestinal bleeding due to peptic ulcer disease, oesophagitis or gastritis, angiodysplasia or portal gastropathy, oesophageal varices, inflammatory bowel disease, premalignant or malignant lesions. 2-4, 7 These lesions are often occult, as they only need to lose 5-10mL of blood per day to render the patient iron deficient.
Iron deficiency due to malabsorption can occur in patients with coeliac disease, infiltrative process involving the proximal small bowel or inflammatory bowel disease, including Crohn’ s disease and ulcerative colitis( see figure 2).
Box 1. Adolescents at risk of developing iron deficiency
• Girls from menarche, especially with heavy menstrual losses
• Those with eating disorders
• Those who are under weight or malnourished
• Those who consume alternative diets such as vegetarians and vegans
• Athletes, especially endurance athletes, from elevated hepcidin levels and increased losses in sweat
• Chronic illnesses
• Lower socioeconomic backgrounds
• Obese children, due to subclinical inflammation resulting in increased hepcidin release
An increasingly recognised cause of iron deficiency( often in combination with vitamin B12 deficiency) occurs after gastric bypass surgery or partial gastrectomy, either for the management of obesity or malignancy. In these cases, the reduced intestinal absorption of iron occurs because of lower gastric acid content in the gastric pouch, or from surgical bypass of the duodenum and proximal jejunum. The surgery reduces the surface area available for maximal iron absorption.
Helicobacter pylori infections affect both serum iron and ferritin levels, as the outer membrane of the bacteria have receptors that sequester serum iron. Eradication of H. pylori organisms results in an appropriate response to oral iron replacement.
Pregnancy and lactation increase iron demand threefold due to the expansion of maternal red cell volume, diversion of maternal iron stores to the fetus, blood loss during delivery, and the secretion of iron into the breastmilk( up to 1mg per day).
It has been estimated that around 1200mg of iron is required prior to pregnancy to prevent the development of pregnancy-related iron deficiency.
Table 2. Recommended iron requirements for adolescents
Age
Iron requirement
14-18-year-old boys 11mg / day, maximal requirements occur at 13 years of age
14-18-year-old girls 15mg / day, maximal requirements occur at 11 years of age
Source: Pasricha, et al. Medical Journal of Australia 2010; 193:525-32.
Figure 2. Endoscopic image of ulcerative colitis showing diffuse mucosal inflammation.

Signs and symptoms

IN developed countries, mild iron deficiency in well-nourished individuals is often asymptomatic. However, multiple studies have described myriad neurocognitive manifestations of iron deficiency that appear to affect all age groups.
Severe iron deficiency anaemia during pregnancy has been associated with an increased risk of low birth weight, preterm labour, newborn and maternal morbidity. 2, 5 An association has been described between iron deficiency and impaired psychomotor and cognitive development( verbal learning and memory formation) in infants, young children and adolescents. 2, 5, 6 This appears to be reversible with iron supplementation.
Untreated iron deficiency during infancy appears to be associated with subtle, but persistent, abnormal auditory and visual acuity later in life. Finally, reversible neurocognitive impairments are also well described in adults who report diminished work productivity together with cognitive and behavioural problems. 2, 3
If the iron deficiency is not corrected, iron deficiency anaemia
Figure 3. A hand demonstrating pallor due to anaemia( left, wearing ring). Source: James Heilman http:// bit. ly / 2u29df1
can develop. Infants and young children can present with lethargy, irritability, poor feeding, failure to thrive, pallor( see figure 3) and even cardiac failure due to severe anaemia. Adult patients often present
with non-specific symptoms, including headaches, fatigue and weakness, reduced exercise tolerance attributed to low delivery of oxygen, and decreased activity of iron-containing enzymes. Iron
Figure 4. Pagophagia.
deficiency may also predispose to infections, precipitate heart failure and cause restless leg syndrome. 2
Iron deficiency can also present with unusual eating behaviours known as pagophagia or pica( see
figure 4). Patients describe specific, abnormal cravings for sometimes bizarre substances such as dirt, clay or ice. These behaviours promptly resolve with iron supplementation.

Diagnosis
Iron studies BODY iron stores can be assessed with fasting iron studies, especially the serum ferritin. Very low serum ferritin levels( below 15 µ g / L) are diagnostic of iron deficiency with a 95 % sensitivity and a 99 % specificity; ferritin levels of 15-30 µ g / L are highly suggestive of iron deficiency with a 92 % sensitivity and 98 % specificity. As iron deficiency progresses, the total iron binding capacity( TIBC) will increase while the transferrin saturation
falls; once it is under 16 %, there is inadequate iron for erythropoiesis.
However, it should be remembered that ferritin is an acute phase reactant and can increase severalfold due to infection, inflammation, liver disease or malignancy, making the diagnosis of iron deficiency challenging. Despite this, it is rare for a patient with iron deficiency to have a ferritin of more than 100 µ g / L. Screening biochemistry, including liver function tests, renal function and inflammatory
markers such as CRP / ESR, are useful adjuncts in this situation.
The serum iron should not be used to diagnose iron deficiency as it is a poor indicator of the body’ s total iron stores. This is because it is subject to diurnal variations, with higher levels later in the day, and it can also be low or normal in iron-deficient patients.
Soluble serum transferrin receptor Unlike serum ferritin, the soluble
serum transferrin receptor( sTfR) concentration is not affected by inflammation. Therefore, this test can be used to help differentiate between iron deficiency and anaemia of chronic disease. The latter is a multifactorial anaemia associated with increased cytokine production, upregulation of hepcidin and abnormal iron haemostasis. The sTfR is elevated in iron deficiency but normal in anaemia of chronic disease. Furthermore, the sTfR / log ferritin ratio appears to
better correlate with the patient’ s true iron stores. However, the sTfR assay still needs national validation due to wide variations in inter-assay cut-offs. Limited numbers of laboratories perform this test, and with specimen batching, turnaround times may be slow.
Blood film and red cell indices Iron deficient red cells are microcytic and hypochromic due to cont’ d page 24
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