Macrocytic Anaemia

Question 1

What is common MCV cut off for macrocytic anaemia?

Answer 1

MCV >100fl

Question 2

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

Answer 2

B12 deficiency

Question 3

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

Answer 3

Life-style

Question 4

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

Answer 4

Pregnancy

Question 5

Causes of macrocytosis? (true and false)

Answer 5

megaloblastic,

non-megaloblastic

Question 6

What triggers erthryoblast to stop dividing and lose their nucleus?

Answer 6

Critical Hb Content

Question 7

Megaloblast definition

Answer 7

abnormally large nucleated red cell precursor with an immature nucleus

Question 8

Megaloblastic anaemias characterised by

Answer 8

lack of red cells due to issues with DNA synthesis and nuclear maturation in the precursor cells in marrows

Question 9

In maturing megaloblasts, division is increased/reduced and apoptosis increased/reduces

Answer 9

division reduced and apoptosis increases

Question 10

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?

Answer 10

True

Question 11

The larger cell size in megaloblastic anaemia is due to the increase in the size of the developing cell. T/F?

Answer 11

False - is due to a failure to become smaller

Question 12

List 5 causes of megaloblastic anaemia

Answer 12

pernicious anaemia most common -> B12 deficiency,
folate deficiency,
drugs e.g. PPis/H2-receptor antagonists,
rare inherited abnormalities e.g. cubulin receptor deficiency

Question 13

Role of B12 and folate in haem system and nervous system?

Answer 13

DNA synthesis and nuclear maturation - haem system,

DNA modification and gene activity - nervous system

Question 14

Causes of B12 deficiency?

Answer 14

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

Question 15

What is macrocytosis?

Answer 15

Normal Hb but high MCV so before macrocytic anaemia

Question 16

Which is more common and more commonly causes megaloblastic anaemia- vitamin B12 or folate deficiency?

Answer 16

B12 deficiency

Question 17

What is pernicious anaemia?

Answer 17

autoimmune condition with destruction of gastric parietal cells

Question 18

What is deficient in pernicious anaemia that causes B12 malabsorption and deficiency?

Answer 18

Intrinsic factor

Question 19

What conditions are pernicious anaemia associated with?

Answer 19

Atrophic gastritis,

personal/FH of autoimmune disorders e.g. hypothyrdoisim, vitiligo or Addison’s disease

Question 20

Where are folates absorbed?

Answer 20

In jejunum & duodenum

Question 21

What are dietary folates converted to?

Answer 21

Monoglutamate

Question 22

Causes of folate deficiency?

Answer 22

inadequate intake e.g. alcoholics
malabsorption e.g. Coeliac, Crohn’s,
excess utilisation e.g. Haemolysis, exfoliating dermatitis, pregnancy, malignancy,
drugs e.g. anticonvulsants

Question 23

Why are dietary causes of folate deficiency more likely than dietary causes of B12 deficiency?

Answer 23

Because folate stores are only 4 months whereas B12 stores are 2-4years

Question 24

Source of B12?

Answer 24

Animal

Question 25

Source of folates? (3)

Answer 25

liver, leafy veg, fortified cereals

Question 26

Where is B12 absorbed?

Answer 26

ileum

Question 27

What is daily requirement of B12?

Answer 27

1.5ug/day

Question 28

What is daily requirement of folate?

Answer 28

200ug/day

Question 29

7 clinical features common to both B12 and folate deficiency?

Answer 29

``` anaemia signs & symptoms, weight loss, diarrhoea, infertility, sore tongue, jaundice, developmental problems ```

Question 30

What symptoms are more associated with vit B12 deficiency?

Answer 30

neurological problems - posterior/dorsal column abnormalities, neuropathy, dementia or psychiatric manifestations

Question 31

How can B12/folate deficiencies present on lab diagnosis? (6)

Answer 31

``` 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, ```

Question 32

What does blood film in B12/folate deficiency show?

Answer 32

macrovalocytes and hyperhsegmented neutrophils normally 3-5 nuclear segments)

Question 33

anti gastric parietal cell auto-antibodies are flawed how?

Answer 33

are sensitive but not specific

Question 34

anti intrinsic factor antibodies are flawed how?

Answer 34

are specific but not sensitive

Question 35

Where is intrinsic factor normally absorbed?

Answer 35

terminal ileum

Question 36

B12 and folic acid role?

Answer 36

involved in converting folic acid into its active form

Question 37

Megaloblastic anaemia treatment?

Answer 37

Vit B12 injections for life in pernicious anaemia, folic acid orally 5mg, ONLY if potentially life-threatening transfuse red cells

Question 38

Causes of non-megaloblastic macrocytosis? Which associated with anaemia and which may not be?

Answer 38

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

Question 39

Causes of spurious macrocytosis?

Answer 39

reticulocytosis, | cold-agglutinins,

Question 40

What can cause reticulocytosis leading to a spurious macrocytosis?

Answer 40

reticulocytosis occurs as a marrow response to acute blood loss or haemolysis

Question 41

Why might patients with pernicious anaemia appear mildly jaundiced?

Answer 41

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

Question 42

How can pancytopenia complicate megaloblastic anaemia?

Answer 42

Because nuclear maturation defects can affect multiple lineages

Question 43

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?

Answer 43

non-megaloblastic e.g. alcoholism, hypothyroidism or liver cause