Audience

• Highland HSCP

Ferritin less than 12 microgram/L indicates complete absence of stored iron and less than 30 microgram/L indicates iron depletion. Between 30 and 50 microgram/L can also be consistent with iron deficiency; especially in elderly patients and in inflammatory states where ferritin may be ‘falsely’ elevated to the ‘normal’ range. Less than 30 microgram/L has a 92% sensitivity and 98% specificity for diagnosing iron deficiency and a ferritin less than 40 microgram/L is 98% sensitivity and specific for iron deficiency. A ferritin above 50 microgram/L excludes iron deficiency unless there is inflammation.

Whilst a low MCV and MCH are often seen in iron deficiency they are not completely sensitive so a normal full blood count does not rule out iron deficiency. 50% of patients with iron deficiency will have a normal MCV but are likely to have had a fall in their MCV with time. When there are concerns of iron deficiency but the ferritin is normal due to co-existent inflammation further testing is not usually helpful.  In the vast majority of cases a ferritin is all that is required and we do not advise routine testing for ‘iron studies’. The serum iron is not a good test for iron deficiency as it varies depending on time of day, recent meals and does not reflect iron stores. Transferrin saturation is usually low in iron deficiency AND the anaemia of inflammation.

Causes

• Blood loss is by far the commonest cause
  • Gastrointestinal, gynaecological or urological blood losses
  • Blood donor, repeated phlebotomy
• Poor dietary intake of iron
• Malabsorption
• Increased requirements e.g. pregnancy, infancy, myeloproliferative neoplasms
• Paroxysmal nocturnal haemoglobinuria (very rare)

History and examination

Look for causes of blood loss. Ask about blood donation. Ask about malabsorption symptoms and diet. Enquire about travel history.

Suggested investigations

• Full blood count
• Coeliac screen
• Helicobacter pylori
• Stool parasite if relevant travel history and/or eosinophilia
• Urinalysis
• Ferritin (CRP if ferritin normal and suspect iron deficiency)
• Inflammatory markers
• As directed by gastroenterology or gynaecology or urology e.g. endoscopies etc.

Management

• We do not review patients with iron deficiency in haematology and we can not provide iron infusions.
• Iron deficiency should be managed as per local and national guidelines
• If further investigations are required patients should be referred to another specialty depending on the history and examination (e.g. gastroenterology, gynaecology, urology).
• If oral iron is required suggest that this is taken with vitamin C or orange juice and without acid suppressant
  • Repeat full blood count in four weeks to ensure responding – there should be a 20 g/L rise in haemoglobin after four weeks of therapy if not bleeding/failing to absorb
  • Carry on iron therapy for three months after anaemia resolved and MCV normalised to build stores and/or aim ferritin over 50 microgram/L
  • Ongoing monitoring g. every three months and then annually for those at risk of further iron deficiency
  • Continuous replacement may be required if ongoing losses e.g. heavy menstrual bleeding or Once daily or even alternate daily iron supplementation is usually all that is required when on long term prophylaxis. These patients should have their full blood count and ferritin monitored every six to 12 months.
• Please note that commercial preparations claiming to be better tolerated often have low amounts of elemental iron and may not be sufficient in someone with iron deficiency anaemia but may be considered as maintenance therapy
• Dietary changes are usually insufficient once patients are deficient in iron and supplementation is usually required
• For patients who do not tolerate oral iron:
  • Laxatives if constipation
  • Use alternative preparation (ferrous gluconate has less elemental iron than ferrous sulphate or ferrous fumarate and therefore may be better tolerated)
  • Use lower dose of elemental iron (e.g. alternate day dosing as in small trials this has been shown to improve haemoglobin as effectively as daily dosing but with less side effects)
  • Take with food (although this may impair absorption)
  • Use liquid paediatric formulation e.g. sodium feredetate
  • There is some evidence to suggest that alternate day oral iron is as effective as traditional three times daily regimes and may be better tolerated
• If oral iron does not work
  • Check compliance
  • Take on empty stomach with vitamin C
  • Take in the morning when hepcidin levels are usually lower
  • Avoid acid suppressants
  • Avoid taking with calcium-containing products and tannins (e.g. tea and wine)
  • Check coeliac serology, H pylori test and enquire about malabsorption
  • Avoid slow-release or enteric-coated preparations (these often release their iron late in the small bowel after the optimal sites of absorption)
  • Ensure no other nutritional deficiencies e.g. vitamin B12 or folate

• Intravenous preparations may be needed if inflammation as this reduces the amount of iron absorbed
• Patients should store iron supplements carefully to avoid accidental overdose

Intravenous iron is generally only considered when patients are truly intolerant of oral supplements, after a trial of at least two different oral agents. There is some limited evidence that intravenous iron may work slightly more quickly than oral iron and could be considered where a rapid rise in haemoglobin is required. In general some indications for intravenous iron are below:

• Iron deficiency anaemia with intolerance of oral iron, especially in inflammatory bowel disease, or where oral iron is ineffective.
• To support the use of erythropoiesis stimulating agents (including patients on renal dialysis).
• Persistent bleeding where taking oral iron is insufficient g. hereditary haemorrhagic telangiectasia
• Anaemia of chronic disease/inflammation where oral iron is poorly absorbed
• As an alternative to blood transfusion when a rapid increase in haemoglobin is required (e.g. perioperative anaemia, severe anaemia in late pregnancy or postpartum anaemia).

If intravenous iron is required urgently then this can be accessed via medical ambulatory care. In general speak to a specialist relevant to the underlying cause of the iron deficiency.

We cannot offer an IV iron infusion service in haematology.