Macrocytotic Anaemia

Question 1

What is INR?

Answer 1

International Normalised Ratio
Prothrombin time
Coagulation speed through the extrinsic pathway

Question 2

What is the coagulation speed through the intrinsic pathway called?

Answer 2

APTT (Activated Partial Thromboplastin Time)

Question 3

What is the normal range for INR?

Answer 3

0.8-1.2

Question 4

What is the normal INR on warfarin?

Answer 4

2-3

Question 5

What is warfarin?

Answer 5

Anticoagulant (blood thinner), inhibiting the action of vitamin K, reducing production of clotting factors

Question 6

What is the normal range for APTT?

Answer 6

35-45 seconds

Question 7

What is the normal range for APTT if on heparin?

Answer 7

60-80 seconds

Question 8

What is heparin?

Answer 8

Anticoagulant (blood thinner), enhances activity of antithrombin III which inhibits blood clotting

Question 9

What is the bleeding time or thrombin time?

Answer 9

Time for for fibrinogen to convert to fibrin in presence of thrombin

Question 10

What is a normal thrombin time?

Answer 10

12-14 seconds

Question 11

What is the order of factors involved in the intrinsic cascade ?

Answer 11

12, 11, 9, 8,

Question 12

What does MCV stand for?

Answer 12

Mean Corpuscular Volume (of a RBC)

Question 13

What does MCV of >95 mean?

Answer 13

Macrocytosis (can be megaloblastic or non-megaloblastic)

Question 14

What is the difference between megaloblastic or non-megaloblastic anemia?

Answer 14

Both anaemias occur in presence of macrocytosis.
Megaloblastic anaemia is when the RBCs also have hyper-segmented nucleated neutrophils.
Non-megaloblastic anaemia is when there aren’t hyper-segmented nucleated neutrophils.

Question 15

What causes megaloblastic anaemia? (macrocytosis and hyper-segmented neutrophils)

Answer 15

B12 deficiency
Folate deficiency

Question 16

What is B12?

Answer 16

Water soluble vitamin, needed for RBC formation, involved in DNA synthesis, has role in health of nervous system, involved in metabolism of fatty acids and amino acids.
Found in meat, fish, dairy and fortified cereals. Vegans should take supplement.

Question 17

How long does the body store B12 for?

Answer 17

3 years

Question 18

B12 is absorbed in the…

Answer 18

terminal ileum

Question 19

What must B12 bind to?

Answer 19

Intrinsic factor

Question 20

Where is intrinsic factor made?

Answer 20

The parietal cells in the gastric body and fundus

Question 21

What is the type of megaloblastic anaemia caused by vitamin B12 deficiency?

Answer 21

Pernicious anaemia

Question 22

How exactly is there a B12 deficiency in pernicious anaemia?

Answer 22

Body attacks parietal cells resulting in reduction in intrinsic factor production. Therefore, little B12 can bind as be absorbed. This leads to megaloblast formation.

Question 23

What are effects of pernicious anaemia

Answer 23

Pallor or in sever cases Lemon yellow skin (jaundice),
Angular stomatitis,
Glossitis
Fatigue,
SOB,
Neurological symptoms due to demyelination:
Symmetrical paraesthesia (tingling/numbness in hands and feet)
Muscle weakness
Altered mental status

Question 24

How is pernicious anaemia treated?

Answer 24

Hydroxycolbamin (B12 tablets)
Potentially B12 injections
Dietary advice to eat salmon and eggs

Question 25

What are causes other than pernicious anaemia of B12 deficiency?

Answer 25

Malnutrition Pregnancy Crohn's disease (affects ileum) Gastrectomy Bariatric surgery

Question 26

Before binding to IF in duodenum and being absorbed in the ileum, what does B12 bind with in the saliva?

Answer 26

transcobalamin (B12 is also called cobalamin)

Question 27

What are common symptoms in deficiency of B12, folate or Fe?

Answer 27

Angular stomatitis (cracked sores at corner of mouth) Glossitis (inflammation of tongue)

Question 28

What is the differential between folate deficiency and B12 deficiency?

Answer 28

B12 deficiency causes demyelination so shows neurological symptoms and can cause jaundice, whereas folate deficiency doesn't

Question 29

What investigations would you take in suspected pernicious anaemia?

Answer 29

FBC Blood film To look for serum B12 and presence of anti-parietal antibodies or anti-IF antibodies and to see macrocytic, hyper-segmented nucleated neutrophils.

Question 30

More lobes in a neutrophils means it is less mature because...

Answer 30

As DNA matures, it becomes more compacted and highly wound round histones.

Question 31

What are the 2 types of deficiencies that cause megaloblastic anaemia?

Answer 31

B12 and folate

Question 32

How long does it take for pernicious anaemia to develop?

Answer 32

Years (because B12 is stored for 3 years)

Question 33

How long does it take for folate deficiency anaemia to develop?

Answer 33

Months

Question 34

What is the role of folate in the body?

Answer 34

Essential for synthesis and repair of DNA including for RBC precursors, amino acid metabolism, neural tube formation in pregnancy, cell division and growth (children and teens growing)

Question 35

What are causes of folate deficiency?

Answer 35

Malnutrition Malabsorption Pregnancy Alcohol Dihydrofolate reductase inhibitors which reduce the levels of biologically active folate: The antibiotic Trimethoprim (in co-trimoxazole) The immunosuppressant Methotrexate

Question 36

What are good sources of folate?

Answer 36

Leafy greens and legumes

Question 37

What are symptoms of folate deficiency anaemia?

Answer 37

Fatigue Pallor SOB Weakness Angular stomatitis Glossitis

Question 38

What investigations would be carried out for potential folate deficiency anaemia?

Answer 38

FBC Blood film To see megaloblasts and hyper-segmented nucleated neutrophils and decreased serum folate

Question 39

What are megaloblasts?

Answer 39

Large immature precursors to RBCs found in bone marrow

Question 40

What is macrocytosis?

Answer 40

Large RBCs

Question 41

What treatment is given for folate deficiency anaemia?

Answer 41

Folate supplements - However, always check B12 levels first. Often also deficient. Then replace B12 first otherwise the B12 will be depleted more due to complex DNA synthesis pathway. Dietary advice = leafy greens and brown rice

Question 42

Even if not deficient, what should pregnant women be taking in first 12 weeks?

Answer 42

400mg prophylactic folate (for neural tube development)

Question 43

What are non-megaloblastic causes of macrocytic anaemia?

Answer 43

Alcohol Hypothyroidism NALD (Neonatal Adrenoleukodystrophy - rare genetic disorder) Liver disease

Question 44

What does 'non-megaloblastic' mean

Answer 44

No hyper-nucleated neutrophils present. These types of anaemias are not primarily associated with impaired DNA synthesis.

Question 45

How does alcohol cause non-megaloblastic anaemia?

Answer 45

Toxic to RBCs and depletes folate and B12.

Question 46

How can hypothyroidism cause non-megaloblastic anaemia?

Answer 46

Multifactorial - thyroid hormones influence the proliferation and differentiation of red blood cell precursors.

Question 47

How can liver disease cause non-megaloblastic anaemia?

Answer 47

The liver is involved with making proteins needed for RBC synthesis. Inflammatory cytokines released can also impact RBC synthesis.