Iron Deficiency Anaemia

Anaemia is a condition where you either lack red blood cells or haemoglobin, or the red blood cells you do have are dysfunctional. It’s usually defined as <13.5g/dL in males and <11.5g/dL in females.

Iron deficiency anaemia (IDA) is the most common cause of anaemia. Iron is needed to form haemoglobin, which is the part of red blood cells that carry oxygen. When you are deficient in iron, you can get IDA.

Pathophysiology

1. Red blood cells carry oxygen around the body using haemoglobin.
    
2. Haemoglobin is made of two things – haem, and globin.
    
3. The globin bit refers to 4 polypeptide chains, with each globin chain containing one haem group. Haem is a complex of a porphyrin and a ferrous ion (Fe 2+). It's the iron ions (that's a tongue twister) that bind oxygen.
    
4. Haem is synthesised in red blood cells and you need Fe 2+ ions to form haem as mentioned.
    
5. Iron needs to be converted from its insoluble form of ferric (Fe 3+) to soluble ferrous (Fe 2+) to make haem. The acidity of the stomach is able to do this, so changing the acidity of stomach acid can alter iron absorption.
    
6. Iron is then absorbed in its ferrous state (Fe 2+) in the small bowel (duodenum and jejunum).
    
7. Iron that isn’t being used to form haemoglobin and subsequently in the formation of red blood cells is stored in the body using something called ferritin. Ferritin is basically an iron store (think of it like a ‘tin’ of iron).
    
8. If the iron requirements of the body exceed the iron intake, the body first depletes iron stores of the body. After time in a state of insufficient iron, you start to get iron deficiency anaemia.
    

Causes

• Insufficient dietary iron: Foods rich in iron include meat, poultry, broccoli and spinach
• Reduced iron absorption: Iron is absorbed in the small bowel (duodenum/jejunum) 
  • Coeliac Disease/Crohn’s Disease – due to malabsorption
  • Gastric bypass surgery: due to altered stomach acid
• Blood loss 
  • Menorrhagia
  • GI bleeding
    • Peptic Ulcer Disease
    • Inflammatory Bowel Disease (UC + Crohn’s)
    • Colorectal cancer
• Increased Iron Requirements
  • Pregnancy: The iron requirements in pregnancy goes up
  • Childhood/adolescence: Due to rapid growth of the body, iron requirements go up and dietary intake can sometimes be insufficient to keep up with this
• Medications  
  • NSAIDs: Peptic ulcer disease causing bleeding
  • Proton pump inhibitors: Altering the acidity of the stomach and thus absorption
  • Clopidogrel: Bleeding

Clinical Features

• Pallor
• Fatigue
• Koilonychia: spooning and thinning of the nails. They also become brittle.
• Angular stomatitis/chelitis: inflammation at the corners of the mouth
• Cold hands and feet
• Chest pain/palpitations
• Shortness of breath
• Tachycardia
• Lightheadedness
• Pica: abnormal dietary cravings e.g. craving dirt
• Headache
   

Investigations

Bedside

• ECG: For chest pain/palpitations to rule out a cardiac cause

Blood

• Full blood count: IDA is known as a hypochromic, microcytic anaemia. The microcytic bit means the red blood cells are small, and the hypochromic bit means they’re pale.
  • Mean Corpuscular Volume (MCV): Low: Microcytic i.e. the cells are small because they contain less haemoglobin
  • Mean cell haemoglobin concentration (MCHC): Low: As there isn’t as much haemoglobin, the red blood cells literally appear paler on a blood film because it’s the haemoglobin that gives red blood cells their colour – this is where the hypochromic part of IDA comes from
  • Total red blood cells (RBCs): Low: Reduced haemoglobin is usually accompanied by a fall in the total number of red cells
  • Haematocrit: Low: This is the volume percentage of packed red blood cells after a sample of blood is centrifuged. It is usually low in IDA as there are fewer RBCs
     
• Iron studies
  • Serum iron: Low
  • Transferrin: High: Iron travels in the blood bound to this. This goes up in IDA – the liver makes more transferrin to maximise whatever iron is available.
  • Transferrin Saturation: Low: Tells you the saturation of the transferrin. Goes down in IDA.
  • Total Iron Binding Capacity: High: This tells us the capacity of blood to bind iron with transferrin. Again, this goes up because you have more transferrin available to bind iron.
  • Ferritin: Low: This tells you the iron stores of the body (think of it like a ‘tin’ of iron). This is low in IDA.
     
• Haematinics: Folic Acid and B12 to rule out alternative causes of anaemia e.g. megaloblastic anaemia

Imaging

• CT CAP: If concerned about malignancy, as part of staging scan/work-up for carcinoma of unknown primary

Special Tests

• OGD/Colonoscopy
• Bone marrow aspiration / biopsy followed by iron staining (Prussian Blue Stain) – this is rarely used in practice these days
   

Differential Diagnosis

1. Thalassaemia: Having thalassaemia trait can result in a low MCV and MCHC
2. Sideroblastic anaemia
3. Anaemia of chronic disease: Usually causes a normocytic and normochromic anaemia
4. Lead poisoning: Rare but can cause microcytic, hypochromic anaemia

Management

Conservative

1. Iron rich diet - dark green vegetables, meat, apricots, prunes, raisins and iron-fortified bread.

Medical

1. Oral iron therapy

• Once daily tablet of oral tablet for 3 months usually to allow iron stores to be restored
  • Ferrous fumurate
  • Ferrous sulfate
  • Ferrous gluconate
• GI disturbance is a common side effect of iron tablets including constipation, black stools, decreased appetite and nausea.
• Taking iron with/after food or on alternate days can help with adverse effects

2. Iron infusion
   1. Usually used if oral iron isn’t tolerated or if the patient cannot absorb iron
   2. Examples include Ferinject, Cosmofer, Monofer etc.
3. Blood Transfusion: Will correct the anaemia but will not current its underlying cause – iron deficiency
4. Treat the underlying cause: If the underlying cause is a slow bleeding malignancy, giving iron tablets isn’t going to solve the problem,

References

https://cks.nice.org.uk/topics/anaemia-iron-deficiency/prescribing-information/adverse-effects/

https://www.msdmanuals.com/en-gb/professional/hematology-and-oncology/anemias-caused-by-deficient-erythropoiesis/iron-deficiency-anemia

https://www.ncbi.nlm.nih.gov/books/NBK470252/