Haematology: Anaemia (Macrocytic; Pernicious & Haemolytic)

Question 1

What are specific signs associated with anaemia of vit. B12 deficiency? [1]

Answer 1

Glossitis

Question 2

Define what is meant by pernicious anaemia [2]

Answer 2

Pernicious anaemia is an autoimmune condition involving antibodies against the parietal cells or intrinsic factor. Intrinsic factor is essential for B12 absoprtion

Specifically have:
- Antibodies to intrinsic factor: block vitamin B12 binding site
- Antibodies to gastric parietal cells: reduced acid production and atrophic gastritis. Therefore less B12 absorption

Question 3

Where is B12 absorped? [1]

Answer 3

Distal ileum

Question 4

Name two core uses of Vitamin B12 [2]

Answer 4

vitamin B12 is important in both the production of blood cells and the myelination of nerves → megaloblastic anaemia and neuropathy

Question 5

Describe the clinical features of pernicious anaemia

Answer 5

Peripheral neuropathy, with numbness or paraesthesia (pins and needles)
**Loss of vibration sense **
Loss of proprioception
Visual changes
Mood and cognitive changes

Question 6

TOM TIP: For your exams, remember to test for vitamin B12 deficiency and pernicious anaemia in patients presenting with []

Answer 6

TOM TIP: For your exams, remember to test for vitamin B12 deficiency and pernicious anaemia in patients presenting with peripheral neuropathy, particularly with pins and needles.

Question 7

Describe the treatment regime for pernicious anaemia

Answer 7

Intramuscular hydroxocobalamin is initially given to all patients with B12 deficiency, depending on symptoms:

No neurological symptoms
- 3 times weekly for two weeks

Neurological symptoms
- alternate days until there is no further improvement in symptoms

MAINTENANCE:

Pernicious anaemia
– 2-3 monthly injections for life of intramuscular hydroxocobalamin

Diet-related:
- oral cyanocobalamin or twice-yearly injections

Question 8

Describe why treating B12 deficiency before a folate deficiency is essential [1]

Answer 8

Where there is B12 and folate deficiency together, it is essential to treat the B12 deficiency first before correcting the folate deficiency.

Giving patients folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord, with demyelination in the spinal cord and severe neurological problems.

Question 9

Describe the presentation of subacute combined degeneration of the spinal cord [3]

Answer 9

progressive weakness
ataxia
paresthesias that may progress to spasticity and paraplegia

Question 10

How would a B12 deficiency appear on a blood film? [1]

Answer 10

hypersegmented neutrophils on blood film

Question 11

Pernicious anaemia has an increased risk of which cancer? [1]

Answer 11

Gastric cancer

Question 12

Which vitamin is folate? [1]

Answer 12

B9

Question 13

Describe causes of folate deficiency [6]

Answer 13

• Inadequate dietary intake
• Alcohol excess
• Malabsorption (e.g. coeliac disease, Crohn’s disease)
• Increased requirements (e.g. pregnancy, malignancy)
• Increased loss (e.g. Chronic liver disease)
• Other (e.g. anti-convulsants, ETOH abuse)

Question 14

Why is folate an essential part of diet? [1]

Answer 14

THF plays a key role in the transfer of 1-carbon units (e.g. methyl, methylene, and formyl groups) to the essential substrates involved in the synthesis of DNA & RNA

Question 15

Which investigations are used to diagnose folate deficiency? [1]

Answer 15

Red cell folate is a better measure of levels than serum folate, since levels are affected even with a short period of deficiency.

Question 16

How do you treat folate deficiency? [1]

Answer 16

**Folic acid **is usually given as a **once daily oral dose of 5 mg for up to four months. **

Question 17

[] is the most common cause of a non-megaloblastic anaemia

Explain your answer [1]

Answer 17

Chronic alcohol use is the most common cause of a non-megaloblastic anaemia.

It is thought to be due to the toxic effects of acetaldehyde on erythrocyte progenitors.

Question 18

What advice should you give pregnant women regarding folic acid intake? [1]

Folate deficiency causes an increased risk of which pathology? [1]

Answer 18

all women should take 400mcg of folic acid until the 12th week of pregnancy

Risk of neural tube defects

Question 19

Which heridatory diseases fall under umbrella of haemolytic anaemia? [5]

Answer 19

• Hereditary spherocytosis
• Hereditary elliptocytosis
• Thalassaemia
• Sickle cell anaemia
• G6PD deficiency

Question 20

What are the subdivisions of hereditary haemolytic anaemias? [3]

Answer 20

Hereditary causes:

membrane:
* hereditary spherocytosis/elliptocytosis

metabolism:
- G6PD deficiency

haemoglobinopathies:
- sickle cell
- thalassaemia

Question 21

What are the subdivisions of acquired haemolytic anaemias? [2]

Answer 21

Acquired: immune causes

autoimmune
-: warm/cold antibody type

alloimmune:
- transfusion reaction
- haemolytic disease newborn

drugs:
- methyldopa
- penicillin

Acquired: non-immune causes

microangiopathic haemolytic anaemia (MAHA):
- TTP/HUS
- DIC,
- malignanc
- pre-eclampsia

prosthetic cardiac valves

paroxysmal nocturnal haemoglobinuria

infections:
- malaria

drug:
- dapsone

Question 22

What are the classical features of haemolytic anaemia? [3]

Answer 22

The features are a result of the destruction of red blood cells:
* Anaemia
* Splenomegaly (the spleen becomes filled with destroyed red blood cells)
* Jaundice (bilirubin is released during the destruction of red blood cells)

Question 23

What are the key investigation results for haemolytic anaemia? [3]

Answer 23

Full blood count shows a normocytic anaemia

Blood film shows
schistocytes (fragments of red blood cells)

Direct Coombs test is positive in autoimmune haemolytic anaemia (not in other types)

Question 24

Define what is meant by: [3]

• Hereditary spherocytosis
• Hereditary elliptocytosis

Answer 24

Hereditary spherocytosis
- Autosomal dominant familial condition; autoantibodies produced against proteins in RBC membrane mean it causes a spherical shape when they pass through the spleen
- Can still perform adequately despite reduced SA
- Fragile and easily lysed

Hereditary elliptocytosis:
- Autosomal dominant familial condition; autoantibodies produced against proteins in RBC membrane mean it causes an ellipse shape
- Can still perform adequately despite reduced SA
- Fragile and easily lysed

Question 25

Describe a patient with hereditary spherocytosis may present [4]

Answer 25

• Jaundice at birth
• However the onset of jaundice can be delayed for many years and some
  patients may go through life with no symptoms and are detected only during
  family studies
• May eventually develop anaemia
• Splenomegaly
• Ulcers on the leg
• Chronic haemolysis leads to the formation of gall stones

Question 26

What investigations would indicate either hereditary spherocytosis or hereditary elliptocytosis? [3]

Answer 26

• Raised mean corpuscular haemoglobin concentration (MCHC) on a full blood count
• Raised reticulocyte count due to rapid turnover of red blood cells
• Spherocytes / elpitocytes on a blood film

Question 27

What is the treatment of hereditary spherocytosis or hereditary elliptocytosis? [4]

Answer 27

Folate supplementation
blood transfusions when required
Splenectomy.

Gallbladder removal (cholecystectomy) may be required if gallstones are a problem.

Question 28

Describe the pathophysiology of G6PD deficiency [1]

Answer 28

G6PD deficiency is caused by a defect in the gene coding for glucose-6-phosphate dehydrogenase (G6PD)

G6PD is responsible for protecting the cells from oxidative damage

Causes acute bouts of haemolytic anaemia

Question 29

Describe the presentation of G6PD deficiency patients [2]

Answer 29

Most are asymptomatic but may get oxidative crisis due to reduction in
glutathione production

In attacks:
* Rapid anaemia
* Jaundice

Question 30

Which drugs can trigger acute bouts of haemolytic anaemia in G6PD deficiency? [5]

Answer 30

Acute drug-induced haemolysis (dose-related):

• Aspirin
• Antimalarials such as; Primaquine, Quinine & Chloroquine
• Antibacterials such as; Most Sulphonamides, Nitrofurantoin and
  Chloramphenicol
• Dapsone
• Quinidine
• Sulfonylureas

Fava beans.

Question 31

Which drugs can trigger haemolytic anaemia in G6PD deficiency? [3]

Answer 31

Drugs:
- ciprofloxacin
- sulfonylureas
- sulfasalazine

Question 32

What is the inheritance of G6PD deficiency? [1]

Answer 32

It is an X-linked recessive genetic condition

Question 33

Describe the presentation of G6PD deficiency [4]

How can you diagnose this pathology? [1]

Answer 33

G6PD deficiency presents with:
- jaundice (often in the neonatal period)
- gallstones
- anaemia
- splenomegaly
- Heinz bodies on a blood film.

Diagnosis can be made by doing a G6PD enzyme assay.

Question 34

Treatment for which pathology often triggers haemolytic anaemia in G6PD deficent patients? [1]

Answer 34

anti-malarials

Question 35

Why might haemolytic present as macrocytic anaemia [as opposed to the normal presentation of normocytic]? [1]

Answer 35

if there are **many young RBC’s **(which are
larger) due to excessive destruction of old RBCs

Question 36

Describe what is meant by the term a compensated haemolytic disease [1]

Answer 36

If the red cell loss can be contained within the marrow’s capacity for
increased output, then a haemolytic state can exist without anaemia

The bone marrow can increase its output by 6-8 times by increasing the
proportion of cells committed to erythropoiesis (RBC production) (erythroid
hyperplasia) and by expanding the volume of active marrow

Question 37

Describe how you would treat a patient with hereditary spherocytosis in:

• neonates [2]
• infants (>28 days old), children, and adults [5]

Answer 37

Neonates:
- 1st line: supportive care +/- red blood cell transfusions
- 2nd line: folic acid supplementation

infants (>28 days old), children, and adults
- 1st line: supportive care +/- red blood cell transfusions
- 2nd line: folic acid supplementation
- 3rd line: splenectomy with pre-op vaccination regimen
- Consider: cholecystectomy or cholecystostomy
- Plus: post-splenectomy antibiotic pneumococcal prophylaxis