Anaemia

Question 1

What is anaemia?

Answer 1

A reduction in the amount of haemoglobin in a given volume of blood below what would be expected in comparison with a healthy subject of the same age and gender.

Question 2

What is normally reduced in anaemia (in WBC)?

Answer 2

Hb
RBC
PCV/Hct

Question 3

What usually happens to Hb in anaemia?

Answer 3

The absolute amount of Hb decreases but it can also result from an increase in volume of plasma rather than a decrease in amount of Hb (short term as body can adjust)

Question 4

Describe some mechanisms of anaemia

Answer 4

1. Reduced production of RBCs/Hb in the bone marrow. Could be a condition causing:
   i. Reduced synthesis of haem – i.e. iron deficiency
   ii. Reduced synthesis of globin – i.e. beta-thalassaemia
2. Loss of blood from the body
3. Reduced survival of RBCs in the body
4. Pooling of RBCs in the spleen (splenomegaly)

Question 5

What can anaemia be classified on if a cause or mechanism is too hard to establish?

Answer 5

Cell size:

Microcytic – usually also hypochromic

Normocytic – usually also normochromic

Macrocytic – usually also normochromic

Question 6

What are some causes of microcytic anaemia?

Answer 6

Defect in haem synthesis; iron deficiency or anaemia of chronic disease

Defect in globin synthesis; thalassaemia (alpha chain or beta chain)

Question 7

What happens in macrocytic anaemia?

Answer 7

Usually a result of abnormal haemopoiesis – RBC precursors continue to synthesise Hb and other cellular proteins but fail to divide properly -> end up larger than usual

Question 8

What are the mechanisms of macrocytic anaemia?

Answer 8

Megablastic erythropoiesis – delay in maturation of the nucleus while the cytoplasm continues to mature and the cell continues to grow
Megaloblast – abnormal bone marrow erythroblast. It is larger than normal and shows nucleocytoplasmic dissociation. Possible to suspect from peripheral blood features but does require bone marrow examination.

Premature release of cells from the bone marrow. Young red cells are 20% larger than normal RBCs so more young cells mean the MCV will be increased in the blood stream.

Question 9

What are the causes of macrocytic anaemia?

Answer 9

1. Megaloblastic anaemia – as a result of lack of vitamin B12 or Folic acid
2. DNA synthesis interfering drugs
3. Liver disease and ethanol toxicity
4. Recent major blood loss with adequate iron stores (reticulocyte numbers increase) – body pumps more out.
5. Haemolytic anaemia (reticulocyte numbers increase) – RBCs lyse in blood stream

Question 10

What are the mechanisms of normocytic anaemia?

Answer 10

Recent blood loss – i.e. peptic ulcer, trauma

Failure of production of red cells – i.e. beginning of iron deficiency, renal failure, bone marrow failure or suppression, bone marrow infiltration

Pooling of red blood cells in the spleen – i.e. hypersplenism from portal cirrhosis

Question 11

What is haemolytic anaemia?

Answer 11

Shortened survival of RBCs in circulation

Question 12

What are the classes if haemolytic anaemia?

Answer 12

• Inherited – abnormalities in cell membrane, Hb or in enzymes of the RBC
• Acquired – extrinsic factors such as micro-organisms, drugs or chemicals
• Intravascular – occurs due to acute damage to RBC
• Extravascular – defective RBCs removed by spleen

Question 13

What are the two factors that can cause haemolytic anaemia?

Answer 13

• Intrinsic abnormality of red cells

- Extrinsic factors acting on normal red cells

Question 14

When should you suspect a patient has HA?

Answer 14

• There is an otherwise unexplainable anaemia, which is normochromic (MCHC is normal) and usually either normocytic or macrocytic
• Evidence of morphologically abnormal cells
• Evidence of increased RBC breakdown
• Evidence of increased bone marrow activity
• Iregularly contracted cells, hereditary elliptocytosis, poikilocytosis or sickle cell
• If a patient has gall stones (chronic HA means high excretion of bilirubin so they get higher incidence of gall stones) or jaundice (sickle cell – RBCs are breaking down quickly)
• If a patient has polychromic anaemia – antibodies remove membranes of Spherocytes and lyse cells

Question 15

Give examples of inherited haemolytic anaemia and the site of defect

Answer 15

herditary spherocytosis - membrane

sickle cell anaemia - Hb

pyruvate kinase def - glycolytic pathway

glucose-6-phosphate dehydrogenase def - pentose shunt

Question 16

Give examples of acquired haemolytic anaemia and the site of defect

Answer 16

autoimmune haemolytic anaemia - membrane (immune)

micrangiopathic haemolytic anaemia - whole red cell (mechanical)

drugs and chemicals - whole red cell (oxidant)

malaria - whole red cells (microbiological)

Question 17

Hereditary spherocytosis - describe the defect, the response, the effects?

Answer 17

• Results from an inherited intrinsic defect in the RBC membrane
• Red cells become less flexible and so are removed by the spleen prematurely causing extravascular haemolysis
• The bone marrow then responds to haemolysis with increased output leading to polychromasia (immature red cells in blood) and reticulocytosis (premature cells)
• The haemolysis leads to increased bilirubin, jaundice and gall stones.
• Spherocytes are more prone to haemolyse when osmotic pressure is reduced

Question 18

What is the treatment for hereditary spherocytosis?

Answer 18

Splenectomy – the only effective treatment

Good diet or folic acid tablets – so folic acid deficiency does not occur

Question 19

G6P Dehdrogenase deficiency - what is it, inheritance pattern, effect?

Answer 19

• G6PD is an important enzyme in the pentose-phosphate shunt and is essential for protection of RBCs from oxidant damage
• Oxidants may be generated in the blood stream and so a G6PDD may intrinsically affect the RBCs tending the system to HA
• The G6PD gene is on the X-chromosome usually affects males but can affect homozygous females
• G6PDD usually causes intermittent severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant

Question 20

Give examples of extrinsic oxidants

Answer 20

• Foodstuffs (e.g. broad beans) and chemicals (e.g. mothballs/naphthalene) or drugs (e.g. dapsone or primaquine).

Question 21

What are heinz bodies?

How are they removed by the body, how can they be detected and what is the treatment?

Answer 21

G6P Dehydrogenase Deficiency

• Usually these episodes of intravascular haemolysis are associated with appearance of considerable numbers of irregularly contracted cells
• Haemoglobin becomes denatured and forms round-balls known as Heinz bodies which are detected by a test
• Heinz bodies are removed by the spleen that leaves a defect in the cell
• As these haemolysis events can be acute and fast, blood transfusions are sometimes required so prevention is important

Question 22

What is autoimmune haemolytic anaemia?

Answer 22

Results from production of autoantibodies directed at RBC antigens -> splenic macrophage recognises antibody and removes parts of the RBC membrane leading to spherocytosis
- The Spherocytes are less flexible and so this combined with antigen recognition on RBC leads to removal of RBCs from circulation

Question 23

How is autoimmune haemolytic anaemia diagnosed?

Answer 23

• Spherocytes and increased reticulocyte count on film
• Detecting immunoglobulin on red cell surface
• Detecting antibodies to RBC antigens

Question 24

How is autoimmune haemolytic anaemia treated?

Answer 24

• Corticosteroids (or other immunosuppressive).

- Splenectomy for severe cases

Question 25

What is a microcytic anaemia likely to be caused by?

Answer 25

iron deficiency

Question 26

Polycythaemia in a person with red urine is likely to have what condition?

Answer 26

renal carcinoma

have to know whether it is due to red cells in urine or Hb in the urine