Macrocytic anaemia

• ·       Megaloblastic causes of macrocytic anaemia result in an increased MCV due to impaired DNA synthesis.

  ·       Non-megaloblastic causes do not affect DNA synthesis but result in an increased MCV nonetheless.
• When trying to differentiate between megaloblastic and non-megaloblastic causes, serum homocysteine and methylmalonic acid levels are useful investigations.
• A homocysteine test is a blood test. It measures the amount of homocysteine, an amino acid in the body. The test is often used to diagnose vitamin B6, B9 or B12 deficiency.
• Methylmalonic acid is a substance that increases when vitamin B12 is low. The test is used to diagnose vitamin B12 deficiency in adults. The test is not a routine test, but it may be ordered to confirm a suspected B12 deficiency or to monitor the effectiveness of B12 supplements.
• Folate (B9) deficiency (megaloblastic)

  -          Poor diet

  -          Increased demand – pregnancy, haemolytic anaemia, cancer

  -          Folate antagonists

   

  Lab findings:

  ·       Increased MCV (>100)

  ·       Increased serum homocysteine

  ·       Normal serum methylmalonic acid
• Vitamin B12 deficiency is the less common megaloblastic anaemia as the liver has large hepatic stores of vitamin B12 that take a while to become depleted. Vitamin B12 absorption requires the cofactor known as intrinsic factor (from atrophic gastritis), manufactured by gastric parietal cells. In pernicious anaemia, the parietal cells are destroyed through an autoimmune process, impairing the absorption of vitamin B12.
• Causes of B12 deficiency:

  Pernicious anaemia is the most common cause of this deficiency but pancreatic insufficiency, damage to the terminal ileum or dietary insufficiency (e.g. vegan diet) are other potential causes.
• The main difference in clinical manifestation between folate and vitamin B12 deficiency are the neurological symptoms that occur in B12 deficiency, due to elevated levels of methylmalonic acid.
• Lab findings in B12 deficiency:

  ·       Increased MCV (>100)

  ·       Increased serum homocysteine

  ·       Increased serum methylmalonic acid
• Non-megaloblastic macrocytic anaemia causes:

  -          Alcoholism

  -          Hypothyroidism

  -          Reticulocytosis

  Drugs – fluorouracil
• Macrocytic anaemia is a condition in which red blood cells are too large. The enlarged red blood cells are not fully developed and do not function the way they should. This causes diminished oxygen delivery to all cells of the body, resulting in fatigue and low energy. When red blood cells are too large, there are fewer of them, and they contain less haemoglobin.
• Macrocytic – B12 deficiency

  For people with neurological involvement:

  ·       Seek urgent specialist advice from a neurologist and haematologist

  ·       Consider initially administering hydroxocobalamin 1mg intramuscularly on alternate days, until no further improvement then administer hydroxocobalamin 1mg intramuscularly every 2 months

  For people with no neurological involvement:

  Initially administer hydroxocobalamin 1 mg intramuscularly three times a week for 2 weeks.
• Give dietary advice about foods that are a good source of vitamin B12:

  ·       Eggs.

  ·       Foods which have been fortified with vitamin B12 (for example some soy products, and some breakfast cereals and breads) are good alternative sources to meat, eggs, and dairy products.

  ·       Meat.

  ·       Milk and other dairy products.

  ·       Salmon and cod.
• Give dietary advice about foods that are a good source of folic acid:

  ·       Asparagus.

  ·       Broccoli.

  ·       Brown rice.

  ·       Brussels sprouts.

  ·       Chickpeas.

  ·       Peas.
• Monitoring for B12/folate treatment

  FBC and reticulocyte count within 7–10 days of starting treatment.

  ·       A rise in the Hb level and an increase in the reticulocyte count to above the normal range indicates that treatment is having a positive effect.

  ·       If there is no improvement following initial B12 treatment, check serum folate level.

  And after 8 weeks of treatment.

  ·       Blood counts and mean cell volume should have normalised.

  ·       At this point, also measure iron and folate levels

  And on completion of folic acid treatment to confirm a response.
• Treatment of normocytic anaemia can include controlling blood loss, treatment of underlying disease, blood transfusion, and medication to promote your red blood cell production.