Macrocytic anaemia Flashcards
Define
• Anaemia associated with a high MCV of erythrocytes (> 100 fl in adults)
What’s the aetiology?
Megalobastic
Non-megalobastic
Megaloblast -
Nuclear maturation is delayed compared to cytoplasm.
What are the causes of megalobastic anaemia?
Vit B12 deficiency
Folate deficiency
Drugs
What are the causes of vit B12 deficiency?
- Reduced absorption (e.g. post-gastrectomy, pernicious anaemia, terminal ileal resection or disease)
- Reduced intake (vegans)
- Abnormal metabolism (congenital transcobalamin II deficiency, nitrous oxide)
How is Vit B12 absorbed?
Animal products (meat and dairy products).
Liberated from food by gastric enzymes and pepsin and binds to R protein.
Pancreatic enzymes release free B12.
Binds to intrinsic factor (produced by gastric parietal cells)
Absorbed in terminal ileum
Transported to tissues by transcobalamin II
What are the causes of folate deficiency?
- Reduced intake (alcoholics, elderly, anorexia)
- Increased demand (Physiological: pregnancy, lactation, prematurity. Pathological: malignancy, chronic inflammation)
- Reduced absorption
- Jejunal disease (e.g. coeliac disease)
- Drugs (e.g. phenytoin)
What drugs can cause megaloblastic anaemia?
- Methotrexate (dihydrofolate reductase inhibitor)
- Hydroxyurea
- Azathioprine
- Zidovudine
What are the causes of non-megalobalstic anaemia?
o Alcohol excess o Liver disease o Myelodysplasia o Multiple myeloma o Hypothyroidism o Pregnancy o Haemolysis (shift to immature red cell form - reticulocytosis) o Drugs (e.g. tyrosine kinase inhibitor)
What is pernicious anaemia?
autoimmune condition in which there is atrophic gastritis (plasma and lymphoid cell infiltration in the fundus) with loss of parietal cells and hence failure of intrinsic factor production and vitamin B12 malabsorption. There is also achlorhydria. It is the most common cause of vitamin B12 deficiency in adults in Western countries.
Epidemiology
- More common in ELDERLY FEMALES
- The most common cause of macrocytosis in the UK is alcohol excess
- Pernicious anaemia is the MOST COMMON cause of B12 deficiency in the West. Common in elderly people and women and people with blue eyes and fair hair
- Higher incidence of gastric carcinoma with pernicious anaemia
What are the presenting symptoms?
• Non-specific symptoms of anaemia: o Tiredness o Lethargy o Dyspnoea • Family history of autoimmune disease • Previous GI surgery • Symptoms of the CAUSE (e.g. weight loss, diarrhoea)
What are the signs?
• Signs of Anaemia o Pallor o Tachycardia o Breathlessness • Signs of Pernicious Anaemia o Mild jaundice o Glossitis o Angular stomatitis o Weight loss o progressive weakness, ataxia and eventually paraplegia if untreated o Insidious onset • Signs of B12 Deficiency o Peripheral neuropathy o Ataxia o Subacute combined degeneration of the spinal cord o Optic atrophy o Dementia
What are the appropriate investigations?
• Bloods
o FBC
• High MCV
• Pancytopaenia in megaloblastic anaemia
• Different degrees of cytopaenia in myelodysplasia
• Exclude reticulocytosis
o LFT
• High bilirubin (due to ineffective erythropoiesis or haemolysis)
o ESR
o TFT
o Serum vitamin B12 (<50ng/l)
o Red cell folate (more accurate than serum folate)
o Anti-parietal cell and anti-intrinsic (specific) factor antibodies
o Serum protein electrophoresis - looking for a dense band in myeloma
• Blood Film
o Large erythrocytes
o In megaloblastic anaemia:
• Megaloblasts
• Hypersegmented neutrophil nuclei
• Schilling Test
o Method of testing for pernicious anaemia
o B12 will only be absorbed when given with intrinsic factor
• Bone Marrow Biopsy (rarely needed)
• Investigations for the cause
How would you manage?
• Pernicious Anaemia o IM hydroxycobalamin for life • Folate Deficiency o Oral folic acid o If B12 deficiency is present, it must be treated before the folic acid deficiency
What are the possible complications?
- Pernicious anaemia –> increased risk of gastric cancer
* Pregnancy - folate deficiency increases the risk of neural tube defects
