HNY Policy and Pathway Repository - North Yorkshire

The most common cause of anaemia will be iron deficiency presenting with a low MCV/MCH and low serum ferritin (see "Iron deficiency"). There are however many other possible causes of anaemia so co-morbidities, medication, diet, ethnicity and family history are all potentially relevant.

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Initially consider the MCV as this can help narrow down the cause of anaemia:

• Low MCV - iron deficiency, some anaemia of chronic disease (otherwise MCV normal) or haemoglobinopathy. Rare sideroblastic anaemia or lead poisoning.
• Normal MCV - some anaemia of chronic disease, acute bleeding, mixed iron and B12/folate deficiency and most non-haematinic causes of anaemia.
• High MCV - B12/folate deficiency, liver disease, hypothyroidism, some bone marrow disorders (e.g. myelodysplastic syndrome) or increased red cell destruction. A mildly increased MCV can also be seen in pregnancy (~4fl above baseline).

Differential Diagnosis:

• Iron deficiency - usually low MCV/MCH. Low serum ferritin, although this can be masked by inflammation. Usually due to chronic blood loss, but consider diet and malabsorption (e.g. coeliac disease). NICE CKS on iron deficiency.
• Acute bleeding - may have normal MCV if not yet iron deficient. May have increased reticulocytes. Most commonly gastrointestinal if no obvious source.
• Anaemia of chronic disease - normal or low MCV/MCH (often normal MCV, low MCH). Normal or increased ferritin with low serum iron, transferrin & transferrin saturation. True iron deficiency should have a low ferritin and increased transferrin. Raised inflammatory markers due to underling infection, inflammation, malignancy or autoimmune disease. Treat underlying cause.
• Megaloblastic anaemia (B12, folate or anti-metabolite drugs) - high MCV and megaloblastic features on blood film. Low serum B12 or folate. See NICE Clinical Knowledge Summary for B12 & folate deficiency.
• Increased red cell destruction - inherited or acquired haemolytic anaemia with raised reticulocytes, bilirubin and LDH. Positive Direct Coombs test if autoimmune. Blood film may show spherocytes. Needs Haematology referral.
• Bone marrow disorder - blood film appearances may be suggestive. May also have low WCC and PLT. Many possibilities - needs Haematology referral.
• Medications - e.g. GI bleeding with NSAIDs; bone marrow suppression with chemotherapy, azathioprine or methotrexate; red cell haemolysis with dapsone or sulphasalazine. Many other possibilities.
• Renal impairment - often with normal MCV. Incidence increases as renal function declines, although the cause of renal impairment is also relevant (e.g. diabetic nephropathy tends to be more anaemic than expected from the eGFR alone). If suspected then refer to renal team to consider erythropoietin.
• Liver disease - often with high MCV, although could be normal, or low if concurrent iron deficiency, e.g. GI bleeding due to varicies. Endocrine- thyroid, parathyroid, pituitary or adrenal dysfunction.
• Physiological - a mild drop in haemoglobin is normal in pregnancy and with increasing age (e.g. if age 70+ then the lower end of the normal range drops to 105g/L in females and 115g/L in males).

Examination:

• Depends on suspected cause.
• Include abdominal examination and rectal exam if considering iron deficiency anaemia or occult bleeding (rectal exam if tenesmus or history of fresh bleeding).
• Include examination for lymphadenopathy, splenomegaly and hepatomegaly if considering a haematological disorder.

Baseline investigations:

• Depending on suspected cause, additional investigation may include:
  • Low MCV: blood film, U+E, LFT, ferritin / iron studies, CRP. Screening for a haemoglobinopathy is normally carried out automatically by the laboratory if the red cell indices and ethnic origin are suggestive.
  • Normal MCV: blood film, reticulocytes, U&E, LFT, ferritin, B12/folate, CRP.
  • High MCV: blood film, reticulocytes, U+E, LFT, TSH, B12/folate.
• Serum immunoglobulins and serum free light chains (more sensitive than urine Bence-Jones protein) if myeloma is being considered.
• Consider HIV serology in patients with any unexplained cytopenia.

Consider Haematology referral if:

• Suspected primary haematological disorder (bone marrow disorder, haemolytic anaemia).
• Unexplained anaemia with haemoglobin <100g/L (female) / <110g/L (male), especially if progressive or symptomatic.
• We do not routinely see haemoglobinopathy carriers, however an information sheet is sent from the laboratory for all new cases.
• Other specialty referrals based on suspected cause. If anaemia of chronic disease but no obvious explanation for the inflammatory process then consider referral to General Medicine.

Haematology Handbook - South Tees Hospitals NHS Foundation Trust

• South Tees Hospitals