Iron is an important part of the haemoglobin molecule. Iron deficiency leads to anaemia (a low concentration of haemoglobin). Iron deficiency causes microcytic hypochromic anaemia. Microcytic refers to small red blood cells with a low mean cell volume (MCV). Hypochromic refers to pale cells due to a reduced haemoglobin concentration.
Causes
Several scenarios can lead to iron deficiency:
- Insufficient dietary iron (e.g., restrictive diets)
- Reduced iron absorption (e.g., coeliac disease)
- Increased iron requirements (e.g., pregnancy)
- Loss of iron through bleeding (e.g., from a peptic ulcer or bowel cancer)
The most common cause in adults is blood loss. There is a clear source of blood loss in menstruating women, particularly in women with heavy periods (menorrhagia). In women not menstruating and men, the most common source of blood loss is the gastrointestinal tract. This bleeding might be from:
- Cancer (e.g., stomach or bowel cancer)
- Oesophagitis and gastritis
- Peptic ulcers
- Inflammatory bowel disease
- Angiodysplasia (abnormal vessels in the wall)
Dietary insufficiency is the most common cause in children. During growth, iron requirements often exceed the dietary intake. Pica (e.g., eating dirt or soil) is a common exam presentation for iron deficiency anaemia in children.
Iron is mainly absorbed in the duodenum and jejunum. It requires the acid from the stomach to keep the iron in the soluble ferrous (Fe2+) form. When the stomach contents are less acidic, it changes to the insoluble ferric (Fe3+) form. Medications that reduce stomach acid, such as proton pump inhibitors (e.g., omeprazole), can interfere with iron absorption. Inflammation of the duodenum or jejunum (e.g., from coeliac disease or Crohn’s disease) can also reduce iron absorption.
Testing
Iron travels around in the blood bound to a carrier protein called transferrin. Total iron-binding capacity (TIBC) is the space for iron to attach to on all the transferrin molecules combined. Total iron-binding capacity is directly related to the amount of transferrin in the blood. Transferrin saturation refers to the proportion of the transferrin molecules bound to iron, expressed as a percentage. The formula for transferrin saturation is:
Transferrin saturation = serum iron / total iron-binding capacity
Ferritin is a protein that stores iron inside cells. Ferritin is an acute-phase protein released with inflammation (e.g., in infection or cancer). Low ferritin is highly suggestive of iron deficiency. Normal ferritin does not exclude iron deficiency. Raised ferritin is difficult to interpret and may be caused by:
- Inflammation (e.g., infection or cancer)
- Liver disease
- Iron supplements
- Haemochromatosis
Serum iron varies significantly throughout the day, with higher levels in the morning and after eating iron-containing meals. On its own, serum iron is not a very useful measure.
Total iron-binding capacity is a marker for how much transferrin is in the blood. TIBC and transferrin increase with iron deficiency and decrease with iron overload.
Transferrin saturation indicates the total iron in the body. With less iron in the body, transferrin will be less saturated. With increased iron in the body, transferrin will be more saturated. It can temporarily increase after eating a meal rich in iron or taking iron supplements. Therefore, a fasting sample gives the most accurate results.
|
Normal Range |
|
|
Serum Ferritin |
41 – 400 ug/L |
|
Serum Iron |
12 – 30 μmol/L |
|
Total Iron-Binding Capacity |
45 – 80 μmol/L |
|
Transferrin Saturation |
15 – 50% |
Iron overload results in high values of all of these markers (except TIBC) and may be caused by:
- Haemochromatosis
- Iron supplements
- Acute liver damage (the liver contains lots of iron)
Management
New iron deficiency in an adult without a clear underlying cause (e.g., heavy menstruation or pregnancy) should be investigated further, including a colonoscopy and oesophagogastroduodenoscopy (OGD) for malignancy.
There are three options for treating iron deficiency anaemia:
- Oral iron (e.g., ferrous sulphate or ferrous fumarate)
- Iron infusion (e.g., IV CosmoFer)
- Blood transfusion (in severe anaemia)
Oral iron works slowly. A rise in haemoglobin of 20 grams/litre is expected in the first month. Common side effects are constipation and black stools. Prophylactic supplementation may be required in recurrent cases.
Iron infusions provide a rapid boost in iron. There is a small risk of allergic reactions and anaphylaxis. It should be avoided during infections, as there is potential for it to “feed” the bacteria.
Last updated August 2023