MacrocytosisandMacrocytic Anaemia Flashcards
what is a megaloblast?
Megaloblast: An abnormally large nucleated red cell precursor with an immature nucleus.
What causes megaloblasts?
defects in DNA synthesis and nuclear maturation
Cell has enough haemoglobin in cytosol but the nucleus is to immature to divide
What causes megaloblastic aneamias?
B12 deficiency Folate deficiency Others Drugs Rare inherited abnormalities
How do folate and B12 deficiencys cause megaloblastic aneamia?
B12 and folate are essential co-factors for nuclear maturation.
Enable chemical reactions that provide enough nucleosides for DNA synthesis
what sources do B12 and folate come from
B12 Meat,
Folate green leafy veg and yeast
Where are B12 and Folate absorbed
B12 Ileum
Folate Jejunum and Duodenum
list causes of folate deficiency
Inadequate intake
Dietary cause more likely than B12 due to lesser stores
Malabsorption
Coeliac disease, Crohn’s disease
Excess utilisation Haemolysis Exfoliating dermatitis Pregnancy Malignancy
Drugs
anticonvulsants
what are the clinical features of folate/B12 deficiency?
Common to both B12 and folate Symptoms/signs of anaemia weight loss, diarrhoea, infertility Sore tongue, jaundice Developmental problems
Vitamin B12 deficiency only (myelin sheath*)
Neurological problems** – posterior/dorsal column abnormalities, neuropathy, dementia, psychiatric manifestations
what is pernicious anaemia
What is it associated with
Autoimmune condition with resulting destruction of gastric parietal cells
Associated with atrophic gastritis and personal or family history of other autoimmune disorders (eg. Hypothyroidism, vitiligo, Addison’s disease)
what is the lab diagnosis of pernicious anaemia?
Macrocytic anaemia
Pancytopenia in some patients
Blood film shows macrovalocytes and hypersegmented neutrophils (normally 3-5 nuclear segments)
Assay B12 and folate levels in serum
FLAWS: low levels may not indicate deficiency and normal levels may not indicate normalcy!
Check for auto-antibodies (anti gastric-parietal cell (GPC) and anti-intrinsic factor (IF) (FLAWS: anti-GPC sensitive, not specific; anti-IF: more specific, not sensitive)
what is treatment of megaloblastic anaemia
Treat the cause where possible
Vitamin B12 (hydroxycobalamin in Europe) injections for life in pernicious anaemia, but high dose oral hydroxycobalamin may be effective
Folic acid tablets (5mg per day) orally
Only if potentially life-threatening anaemia, transfuse red cells
what are causes of non-megaloblastic anaemia?
Alcohol
Liver disease
Hypothyroidism
Marrow failure
what are causes of spurious macrocytosis
Reticulocytosis
Cold agglutinins
why might patients with pernicious anaemia be slightly jaundiced
intramedullary haemolysis
raises bilirubin and LDH
