Macrocytosis and Macrocytic anaemia

Question 1

Describe the difference between a macrocytosis and a macrocytic anaemia

Answer 1

Macrocytosis - cells are larger than normal but no anaemia

Macrocytic anaemia - MCV larger and RBC and Hb count low

Question 2

What other cell on a blood film can be used as a reference point for the normal size of a mature RBC?

Answer 2

Nucleus of a small lymphocyte = same size as RBC

=> if RBCs are larger than this, suspect macrocytosis

Question 3

What are the genuine causes of macrocytosis?

Answer 3

Megaloblastic
- nucleus is immature and stops as much cell division as would normally take place
=> cells end lineage larger than normal
=> macrocytosis with overall fewer macrocytes => anaemia

Non-Megaloblastic

• Alcohol/Liver disease
• Hypothyroidism
• Marrow failure (assoc. with anaemia unlike above)
  e. g. Myelodysplasia, Myeloma, Aplastic anaemia

Question 4

WHat can cause megaloblastic anaemias?

Answer 4

B12 deficiency
Folate deficiency
Others - Drugs, inherited abnormalities

Question 5

Why are B12 and folate important in blood cell production?

Answer 5

For:
DNA synthesis / nuclear maturation
DNA modification and gene activity – (e.g. nervous system)

Question 6

Explain the physiology of how B12 is absorbed in the body

Answer 6

• comes from meat/eggs/ meat products
• stomach acid causes B12 to dissociate from meat and bind to haptocorrin protein
• in response to food gastric parietal cells make Intrinsic Factor (IF)
• all 3 travel into duodenum and pancreatic secretions cause increase in pH (more alkaline)
• Haptocorrin dissociates from B12 allowing IF to bind
• this complex binds to receptors in distal small bowel
• B12 absorbed into bloodstream and attaches to transcobalamin

Question 7

What problems can therefore cause patients to be deficient in B12?

Answer 7

STOMACH

• PPI/H2RA causes decreased stomach acid for dissociation of B12 from meat
• gastrectomy/bypass
• pernicious anaemia

GUT

• bacterial overgrowth
• crohns
• coeliac disease
• resection

PANCREAS
- chronic pancreatitis stops secretions being produced

Question 8

What is pernicious anaemia?

Answer 8

Autoimmune condition (anti-IF, anti-GPC)
- destruction of gastric parietal cells
- intrinsic factor deficiency 
=> B12 malabsorption and deficiency

Associated with other autoimmune disorders (eg. hypothyroidism, Addison’s)

Question 9

Where in the small bowel are iron, B12 and folate each absorbed?

Answer 9

Iron - proximal small bowel
Folate - jejunum
B12 distal small bowel

Question 10

How long do the body’s folate stores last in comparison to the B12 stores?

Answer 10

Folate 4 months
B12 - 2-4 years
=> if deficient, may take this long for symptoms to show

Question 11

What can cause folate deficiency?

Answer 11

Inadequate intake in diet
- more likely in alcoholics as poor diet

Malabsorption
- Coeliac /Crohn’s

Excess utilisation

• Haemolysis
• Pregnancy
• Malignancy

Drugs

• anticonvulsants
• methotrexate

Question 12

What symptoms are common in both B12 and folate deficiency?

Answer 12

• Symptoms/signs of anaemia
• weight loss, diarrhoea, infertility
• Sore tongue, jaundice
• Developmental problems

Question 13

Neurological problems are more commonly associated with what anaemia causing deficiency?

Answer 13

B12

- causes dorsal column abnormalities, neuropathy, dementia, psychiatric manifestations

Question 14

What would show up on a macrocytic anaemia blood film?

Answer 14

macrovalocytes and hypersegmented neutrophils (normally 3-5 nuclear segments, but more in this case)

some pts can be - Pancytopenic (all cells low)

Question 15

How can you attempt to confirm a cause of macrocytic anaemia?

Answer 15

• serum B12 and folate levels

- autoantibody testing (anti-IF and anti-GPC)

Question 16

How should B12 deficient patients be treated?

Answer 16

hydroxycobalamin IM injections

• lifelong
• high dose oral B12 may also be effective if dietary intake problem alone?

Question 17

How are folate deficient patients treated?

Answer 17

Folic acid tablets (5mg per day)

different from routine pregnancy recommendation

Question 18

When in macrocytic anaemia would a blood transfusion be considered?

Answer 18

Only if anaemia is potentially life-threatening

Question 19

What is meant by a spurious or false macrocytosis?

Answer 19

volume of MATURE red cell is NORMAL

But the MCV is measured as high

Question 20

What can cause a false macrocytosis?

Answer 20

• reticulocytosis
  => Reticulocytes bigger than mature red cells but analysed along with them for MCV => not accurate
• cold agglutinins
  => clumps of ‘agglutinated’ red cells are registered as 1 ‘giant’ cell by machine => MCV not accurate

Question 21

Why may patients with pernicious anaemia appear mildly jaundiced?

Answer 21

due to intramedullary haemolysis of RBCs as erythropoiesis is ineffective

=> Hb broken down to bilirubin

Question 22

Why can a megaloblastic anaemia appear as pancytopenia?

Answer 22

As problems with nuclear maturation defects can affect multiple lineages of blood cells