Macrocytic Anaemia Flashcards
What is common MCV cut off for macrocytic anaemia?
MCV >100fl
Presentation: tired, tingling in hands & feet.
FBC shows low Hb, low RBC and high MCV.
Which of the following is the most likely explanation for the results?
A. Iron deficiency
B. B12 deficiency
C. Aplastic anaemia
D. Acute myeloid leukaemia
B12 deficiency
Presentation: collapsed at home, alcohol excess.
FBC shows only high MCV, everything else normal.
Which of the following is the most likely explanation for the results?
A. Iron deficiency
B. B12 deficiency
C. Life-style
D. Acute myeloid leukaemia
Life-style
Presentation: pregnant but low B12, everything else normal. Which of the following is the most likely explanation for the results?
A. Iron deficiency
B. B12 deficiency
C. Pregnancy
D. Folate deficiency
Pregnancy
Causes of macrocytosis? (true and false)
megaloblastic,
non-megaloblastic
What triggers erthryoblast to stop dividing and lose their nucleus?
Critical Hb Content
Megaloblast definition
abnormally large nucleated red cell precursor with an immature nucleus
Megaloblastic anaemias characterised by
lack of red cells due to issues with DNA synthesis and nuclear maturation in the precursor cells in marrows
In maturing megaloblasts, division is increased/reduced and apoptosis increased/reduces
division reduced and apoptosis increases
In megaloblastic anaemia, cytoplasmic development and Hb accumulation are normal. When Hb level reached the nucleus is kicked out and so bigger than normal red cell left - macrocyte. T/F?
True
The larger cell size in megaloblastic anaemia is due to the increase in the size of the developing cell. T/F?
False - is due to a failure to become smaller
List 5 causes of megaloblastic anaemia
pernicious anaemia most common -> B12 deficiency,
folate deficiency,
drugs e.g. PPis/H2-receptor antagonists,
rare inherited abnormalities e.g. cubulin receptor deficiency
Role of B12 and folate in haem system and nervous system?
DNA synthesis and nuclear maturation - haem system,
DNA modification and gene activity - nervous system
Causes of B12 deficiency?
insufficient dietary intake e.g. vegans, vegetarians,
malabsorption e.g. pernicious anaemia, coeliac disease, surgery so lack of intrinsic factor, PPIs, atrophic gastritis, jejunum: bacterial overgrowth, duodenum: Crohn’s, chronic pancreatitis
HIV
What is macrocytosis?
Normal Hb but high MCV so before macrocytic anaemia
Which is more common and more commonly causes megaloblastic anaemia- vitamin B12 or folate deficiency?
B12 deficiency
What is pernicious anaemia?
autoimmune condition with destruction of gastric parietal cells
What is deficient in pernicious anaemia that causes B12 malabsorption and deficiency?
Intrinsic factor
What conditions are pernicious anaemia associated with?
Atrophic gastritis,
personal/FH of autoimmune disorders e.g. hypothyrdoisim, vitiligo or Addison’s disease
Where are folates absorbed?
In jejunum & duodenum
What are dietary folates converted to?
Monoglutamate
Causes of folate deficiency?
inadequate intake e.g. alcoholics
malabsorption e.g. Coeliac, Crohn’s,
excess utilisation e.g. Haemolysis, exfoliating dermatitis, pregnancy, malignancy,
drugs e.g. anticonvulsants
Why are dietary causes of folate deficiency more likely than dietary causes of B12 deficiency?
Because folate stores are only 4 months whereas B12 stores are 2-4years
Source of B12?
Animal
Source of folates? (3)
liver,
leafy veg,
fortified cereals
Where is B12 absorbed?
ileum
What is daily requirement of B12?
1.5ug/day
What is daily requirement of folate?
200ug/day
7 clinical features common to both B12 and folate deficiency?
anaemia signs & symptoms, weight loss, diarrhoea, infertility, sore tongue, jaundice, developmental problems
What symptoms are more associated with vit B12 deficiency?
neurological problems - posterior/dorsal column abnormalities, neuropathy, dementia or psychiatric manifestations
How can B12/folate deficiencies present on lab diagnosis? (6)
macrocytic anaemia, pancytopenia in some patients, serum B12/folate (not very useful), autoantibodies anti GPC or anti IF, Schilling's test in past, bone marrow exam rarely,
What does blood film in B12/folate deficiency show?
macrovalocytes and hyperhsegmented neutrophils normally 3-5 nuclear segments)
anti gastric parietal cell auto-antibodies are flawed how?
are sensitive but not specific
anti intrinsic factor antibodies are flawed how?
are specific but not sensitive
Where is intrinsic factor normally absorbed?
terminal ileum
B12 and folic acid role?
involved in converting folic acid into its active form
Megaloblastic anaemia treatment?
Vit B12 injections for life in pernicious anaemia,
folic acid orally 5mg,
ONLY if potentially life-threatening transfuse red cells
Causes of non-megaloblastic macrocytosis? Which associated with anaemia and which may not be?
alchohol - may not be assoc. with anaemia,
liver disease - may not be assoc. with anaemia,
hypothyroidism - may not be assoc. with anaemia,
marrow failure e.g. myelodysplasia, myeloma, aplastic anaemia - associated with anaemia
Causes of spurious macrocytosis?
reticulocytosis,
cold-agglutinins,
What can cause reticulocytosis leading to a spurious macrocytosis?
reticulocytosis occurs as a marrow response to acute blood loss or haemolysis
Why might patients with pernicious anaemia appear mildly jaundiced?
Due to intramedullary haemolysis due to ineffective erythropoiesis. red cells die prematurely in the marrow, haemoglobin and lactate dehydrogenase are released from dead red cells and Hb is converted to bilirubin
How can pancytopenia complicate megaloblastic anaemia?
Because nuclear maturation defects can affect multiple lineages
After macrocytosis confirmed, a blood film should be carried out to investigate cause. If reticulocytes are absent, this suggests what type of cause of macrocytosis?
non-megaloblastic e.g. alcoholism, hypothyroidism or liver cause
