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

Other than a reduction in the absolute amount of haemoglobin in the blood stream, what else could cause anaemia? Why would this type of anaemia only be transient in a healthy individual?

Answer 2

An increase in the plasma volume can decrease the haemoglobin concentration.

The excess fluid would be excreted in a healthy individual

Question 3

State four mechanisms of anaemia

Answer 3

1. Reduced production of red cells/haemoglobin in the bone marrow
2. Loss of blood from the body
3. Reduced survival of red cells in the circulation
4. Pooling of red cells in a very large spleen

Question 4

For each type of anaemia, state whether they are usually hypochromic, normochromic or hyperchromic.

Answer 4

Microcytic - hypochromic
Normocytic - normochromic
Macrocytic - normochromic

Question 5

State the common causes of microcytic anaemia.

Answer 5

Problem with Haem synthesis:

• Iron deficiency
• Anaemia of chronic disease

Problem with globin synthesis:

• Alpha thalassemia (defective alpha chain)
• Beta thalassemia (defective beta chain)

Question 6

What mechanism usually causes macrocytic anaemia?

Answer 6

Macrocytic anaemias usually result from abnormal haemopoiesis so that the red cell precursors continue to synthesize haemoglobin and other cellular proteins but fail to divide normally

Question 7

What is megaloblastic erythropoiesis? Describe the appearance of a megaloblast.

Answer 7

Megaloblastic erythropoiesis refers to a delay in the maturation of the nucleus while the cytoplasm continues to mature and the cell continues to grow => macrocytic anaemia

• A megaloblast is an abnormal bone marrow erythroblast
• They are large and show nucleo-cytoplasmic dissociation; detection requires bone marrow examination

Question 8

What is an alternative mechanism of macrocytosis?

Answer 8

Premature release of cells from the bone marrow

- Reticulocytes are about 20% larger than mature red cells so reticulocytosis would increase the MCV

Question 9

State the two most common causes of megaloblastic anaemia.

Answer 9

Lack of vitamin B12 or folic acid

Question 10

List some other common causes of macrocytic anaemia.

Answer 10

• Drugs that interfere with DNA synthesis
• Liver disease
• Ethanol toxicity
• Recent major blood loss with adequate iron stores (if you’ve lost blood, the bone marrow will start releasing reticulocytes to compensate)
• Haemolytic anaemia (reticulocytosis due to the loss of red cells)

Question 11

State three mechanisms of normocytic normochromic anaemia

Answer 11

1. Recent blood loss
2. Failure to produce red blood cells
3. Pooling of red blood cells in the spleen

Question 12

State five causes of normocytic normochromic anaemia

Answer 12

1. Peptic ulcer
2. Oesophageal varices
3. Trauma
4. Failure of production of red blood cells due to:
   - Early stages of iron deficiency and ACD
   - Renal failure
   - Bone marrow failure
   - Bone marrow infiltration
5. Hypersplenism, e.g. cirrhosis

Question 13

Define haemolytic anaemia.

Answer 13

Anaemia resulting from shortened survival of red blood cells in the circulation

Question 14

Summarise the classification of haemolytic anaemia

Answer 14

1. Haemolysis can result from an intrinsic abnormality of the red cells, or from extrinsic factors acting on normal red cells.
2. Can also be classified as inherited or acquired
3. Can also be classified as intravascular or extravascular:
   - Intravascular haemolysis occurs if there is very acute damage to the red cell
   - Extravascular haemolysis occurs when defective red cells are removed by the spleen
   (Often haemolysis is partly intravascular and partly extravascular)

Question 15

State some inherited abnormalities that can cause haemolytic anaemia. Give an example for each

Answer 15

• Abnormal red cell membrane e.g. hereditary spherocytosis
• Abnormal haemoglobin e.g. sickle cell
• Defect in the glycolytic pathway e.g. pyruvate kinase def.
• Defect in the enzymes of the pentose shuttle e.g. G6PD deficiency

Question 16

State some acquired abnormalities that cause haemolytic anaemia. Give examples for each

Answer 16

• Damage to the red cell membrane e.g. Autoimmune haemolytic anaemia or snake bite
• Damage to the whole red cell e.g. Microangiopathic haemolytic anaemia, Malaria
• Oxidant exposure to membrane/Hb e.g. dapsone or primaquine

Question 17

When would you suspect haemolytic anaemia?

Answer 17

• Otherwise unexplained anaemia that is normochromic and usually either normocytic or macrocytic
• Evidence of morphologically abnormal red cells
• Evidence of increased red blood cell turnover
• Evidence of increased bone marrow activity

Question 18

What does the presence of fragments in the blood film suggest?

Answer 18

This suggests that red blood cells are being broken down within the small circulation

Question 19

State and explain some important clinical signs of haemolytic anaemia.

Answer 19

Jaundice because of the increased break down of red blood cells there is an increase in bilirubin => increased risk of getting gallstones

Question 20

What is hereditary spherocytosis?

Answer 20

Haemolytic anaemia or chronic compensated haemolysis resulting from an inherited intrinsic defect of the red cell membrane
After entering the circulation the cells lose membrane in the spleen and thus become spherocytic - become less flexible and are removed prematurely by the spleen (extravascular haemolysis)

Question 21

How does the bone marrow respond to the increased extravascular haemolysis in hereditary spherocytosis?

Answer 21

It increases the output of red cells leading to polychromasia and reticulocytosis

Question 22

What key fact underlies the osmotic fragility test?

Answer 22

Spherocytes are more prone to haemolyse when osmotic pressure is reduced

Question 23

What is an effective treatment for hereditary spherocytosis?

Answer 23

Splenectomy (only done in severe cases)

Question 24

Why is a good diet important in patients with hereditary spherocytosis?

Answer 24

They need a supply of Vit B12, folic acid and iron to keep up with the demands of the bone marrow

Question 25

Describe the pattern of inheritance of G6PD deficiency.

Answer 25

X linked recessive (affected individuals are usually hemizygous males, but occasionally homozygous females)

Question 26

What can G6PD deficiency cause? How does the deficiency arise?

Answer 26

Intermittent, severe intravascular haemolysis as a result of infection or exposure to an *exogenous oxidant

*Extrinsic oxidants may be foodstuffs (e.g. broad beans), chemicals (e.g. naphthalene) or drugs (e.g. dapsone, primaquine)

Question 27

What tends to appear in blood films during these episodes of severe intravascular haemolysis?

Answer 27

Irregularly contracted cells

Question 28

What happens to the haemoglobin during these episodes of severe intravascular haemolysis?

Answer 28

• Haemoglobin is denatured and forms round inclusions known as Heinz bodies (can get more than one in cell)
• Heinz bodies are removed by the spleen, leaving a defect in the cell

Question 29

What causes acute haemolytic anaemia?

Answer 29

Results from the production of antibodies against red cell antigens - very sudden and dramatic

Question 30

Describe how acute haemolytic anaemia can lead to spherocytosis.

Answer 30

The immunoglobulin bound to the red cell is recognised by splenic macrophages, which remove parts of the cell membrane leading to spherocytosis

Question 31

State two causes of spherocytosis.

Answer 31

Hereditary spherocytosis

Autoimmune haemolytic anaemia

Question 32

What other components are recognised by splenic macrophages?

Answer 32

Complement components bound to the immunoglobulin molecule

Question 33

The combination of cell rigidity and recognition of antibody and complement on the red cell surface by splenic macrophages leads to what?

Answer 33

Removal of cells from the circulation by the spleen

Question 34

Describe the diagnosis of acute/autoimmune haemolytic anaemia.

Answer 34

Diagnosis is by:

• Finding spherocytes and an increased reticulocyte count
• Detecting immunoglobulin ± complement on the red cell surface
• Detecting antibodies to red cell antigens or other autoantibodies in the plasma

Question 35

What is the treatment for acute/autoimmune haemolytic anaemia?

Answer 35

• Use of corticosteroids and other immunosuppressive agents
• Splenectomy for severe cases

Question 36

What condition is characterised by physical damage to the red cells following the occlusion of arterioles and capillaries as a result of fibrin deposition or platelet aggregation. Describe the treatment.

Answer 36

Microangiopathic haemolytic anaemia

Treatment:

• Removing the cause, e.g. treating severe hypertension or stopping a causative drug
• Plasma exchange when it is caused by an antibody in the plasma that is leading indirectly to fibrin deposition