Macrocytes and Macrocytic Anaemia

Question 1

What is macrocytic anaemia?

Answer 1

Anaemia in which the red cells have a larger than normal size = measured using MCV

Question 2

How is MCV measured?

Answer 2

Using analysers = use light scatter properties

Question 3

When would a cell be classed as a macrocyte?

Answer 3

MVC > 100fl

Question 4

What are the types of macrocytosis?

Answer 4

Genuine = true increase in MCV

Spurious (also known as false)

Question 5

What are the categories of genuine macrocytosis?

Answer 5

Megaloblastic and non-megaloblastic

Question 6

What are normal red cell precursors called?

Answer 6

Erythroblasts or normoblasts = have a nucleus and are marrow-based

Question 7

What happens to normoblasts once they contain an adequate amount of Hb?

Answer 7

They stop dividing and lose their nucleus

Question 8

What characterises macrocytic anaemia?

Answer 8

Lack of red cells due to predominant defects in DNA synthesis and nuclear maturation in precursors

Question 9

What is a megaloblast?

Answer 9

Abnormally large nucleated red cell precursor with an immature nucleus

Question 10

What is abnormal about megaloblast maturation?

Answer 10

Division is reduced and apoptosis increases

Question 11

Why do megaloblasts end up bigger?

Answer 11

Immature nucleus prevents division plus cytoplasmic development and Hb accumulation are normal

Question 12

What happens once the Hb level in the megaloblast is optimal?

Answer 12

The nucleus is extruded to leave behind a macrocyte

Question 13

Why does macrocytosis cause anaemia?

Answer 13

Overall there are fewer cells despite the fact that they are bigger

Question 14

What are the cause of megaloblastic macrocytic anaemia?

Answer 14

B12 deficiency, folate deficiency, drugs, rare inherited abnormalities

Question 15

What processes do B12 and folate regulate?

Answer 15

DNA synthesis and nuclear maturation

DNA modification and gene activity

Question 16

How does B12 enter the body?

Answer 16

Enters in food and is released in the stomach by acid = binds to rapid binder protein from saliva as protection

Question 17

Where is intrinsic factor secreted from?

Answer 17

Gastric parietal cells = occurs in response to food in stomach

Question 18

What happens to intrinsic factor and B12-rapid binder complex once they leave the stomach?

Answer 18

Travel to duodenum = B12 is released from complex and binds to intrinsic factor

Question 19

Where does the intrinsic factor-B12 complex travel to once it leaves the small bowel?

Answer 19

Travels to distal small bowel where it attaches to receptors and enters the bloodstream = occurs in ileum

Question 20

What does the intrinsic factor-B12 complex bind to once it is in the bloodstream?

Answer 20

Transcohalamin receptors

Question 21

What are some causes of B12 deficiency?

Answer 21

Vegan diet, pernicious anaemia, atrophic gastritis, Coeliac, Crohn’s, bacterial overgrowth

Question 22

What is pernicious anaemia?

Answer 22

Autoimmune condition causing destruction of gastric parietal cells

Question 23

What does pernicious anaemia result in?

Answer 23

Intrinsic factor deficiency plus B12 malabsorption and deficiency

Question 24

How are folates absorbed?

Answer 24

Dietary folates converted to monoglutamate

Absorbed in jejunum

Question 25

What are the causes of folate deficiency?

Answer 25

Malabsorption = Crohn's, Coeliac Excess utilisation = haemolysis, exfoliating dermatitis, pregnancy, malignancy Dietary insufficiency

Question 26

Why does folate deficiency present earlier than B12 deficiency?

Answer 26

Stores of folate

Question 27

What are some symptoms that occur in both folate and B12 deficiency?

Answer 27

Weight loss, diarrhoea, infertility, sore tongue, jaundice, developmental problems, signs of anaemia (e.g fatigue)

Question 28

What are some of the neurological conditions that occur in B12 deficiency?

Answer 28

Dorsal column abnormalities, neuropathy, dementia, psychiatric issues

Question 29

What is pancocytopenia?

Answer 29

Low number of all cells = can occur in some patients with B12 or folate deficiency

Question 30

How can B12 or folate deficiency be diagnosed?

Answer 30

Low red cell count = macrocytic anaemia Blood film Assay B12 and folate levels in serum

Question 31

What are the auto-antibodies associated with B12 and folate deficiency?

Answer 31

Anti-GPC and anti-IF auto-antibodies

Question 32

What does the blood film of a patient with B12 or folate deficiency show?

Answer 32

Macroovalocytes and hypersegmented neutrophils (more the 3-5 segments)

Question 33

How is megaloblastic macrocytic anaemia treated?

Answer 33

Vitamin B12 injections for life for pernicious anaemia Folic acid 5mg oral tablets Red cell transplant only if life threatening anaemia

Question 34

What are the causes of non-megaloblastic macrocytic anaemia?

Answer 34

Alcohol, liver disease and hypothyroidism = may not be associated with anaemia Marrow failure = myelodysplasia, myeloma, aplastic anaemia (all cause anaemia)

Question 35

What is spurious macrocytosis?

Answer 35

Volume of mature red cell is normal but MCV is still measured as high

Question 36

What are the causes of spurious macrocytosis?

Answer 36

Reticulocytosis and cold-agglutinins

Question 37

What causes reticulocytosis?

Answer 37

Increase in reticulocyte numbers occurs as marrow response to acute blood or haemolysis

Question 38

Why does reticulocytosis cause a falsely high MCV and result in spurious macrocytosis?

Answer 38

Reticulocytes are bigger than mature red cells and are analysed alongside red cells for MCV measurement

Question 39

What are cold-agglutinins?

Answer 39

Proteins produced by cancers and infection

Question 40

How do cold-agglutinins cause spurious macrocytosis?

Answer 40

Cause clumping of red cells in samples at temperature <37 = falsely measured as one giant cell

Question 41

How can falsely high MCV measurements due to cold agglutinins be prevented?

Answer 41

Warm blood samples to 37 degrees

Question 42

What causes patients with pernicious anaemia to appear mildly jaundiced?

Answer 42

Intramedullary haemolysis = causes ineffective erythropoiesis

Question 43

How does ineffective erythropoiesis cause jaundice?

Answer 43

Red cells die prematurely in marrow HB and LDH are released from dead red cells Hb is converted to bilirubin

Question 44

How can pancytopenia complicate megaloblastic macrocytic anaemia?

Answer 44

Nuclear maturation defects can affect multiple lineages