Anaemia

Question 1

What is anaemia

Answer 1

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 in a FBC is reduced in anaemia

Answer 2

Hb

Usually RBC and Hct

Question 3

What may anaemia be a result of

Answer 3

Reduction in the absolute amount of haemoglobin in the blood stream
Occasionally due to an increase in volume plasma (cannot persist as excess fluid is excreted)

Question 4

What are the mechanisms of anaemia

Answer 4

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

Question 5

What are the causes of microcytic anaemia

Answer 5

Defect in haem synthesis

• iron deficiency
• anaemia of chronic disease

Defect in global synthesis (thalassaemia)

• Defect in α chain synthesis
• Defect in β chain synthesis

Question 6

Describe macrocytic anaemia

Answer 6

Average cell size is increased
Usually result from abnormal haemopoiesis
The red cell precursors continue to synthesise haemoglobin and other cellular proteins but fail to divide normally

May be due to premature release of cells from bone marrow (20% larger)

Question 7

What is megaloblastic erythropoiesis

Answer 7

A cause of macrocytic anaemia

Delay in maturation of the nucleus while the cytoplasm continues to mature and the cell continues to grow

Question 8

What is a megaloblast

Answer 8

Abnormal bone marrow erythroblast

Larger than normal and shows nuclei-cytoplasmic dissociation

Question 9

What are the common causes of macrocytic anaemia

Answer 9

Megaloblastic anaemia as a result of lack of vitamin B12 or folic acid
Use of drugs interfering with DNA synthesis
Liver disease and ethanol toxicity
Recent major blood loss with adequate iron stores (increased reticulocytes)
Haemolytic anaemia (increased reticulocytes)

Question 10

What are the mechanisms of normocytic anaemia

Answer 10

Recent blood loss
Failure of production of red cells
Pooling of red cells in the spleen

Question 11

What are the causes of normocytic normochromic anaemia

Answer 11

Peptic ulcer, oesophageal varices, trauma
Failure of production of red cells
Hypersplenism e.g. portal cirrhosis

Question 12

Describe haemolytic anaemia

Answer 12

Resulting from shortened survival of red cells in the circulation
May be due to intrinsic abnormality of the red cells or extrinsic factors acting on normal red cells

Question 13

What is the difference between inherited and acquired haemolytic anaemia

Answer 13

Inherited - can result from abnormalities in the cell membrane, haemoglobin or enzymes in the red cell

Acquired - usually results from extrinsic factors such as micro-organisms, chemicals or drugs that damage the red cell

Question 14

What is the difference between intravascular and extravascular haemolysis

Answer 14

Haemolysis is partly intravascular and partly extravascular

Intravascular - if there is very acute damage to the red cell

Extravascular - Defective red cells are removed by the spleen

Question 15

Give examples of causes of inherited haemolytic anaemia

Answer 15

Cell membrane - Hereditary spherocytosis

Haemoglobin - Sickle cell

Glycolytic pathway - pyruvate kinase deficiency

Enzymes of pentose shunt - G6PD deficiency

Question 16

Give examples of causes of acquired haemolytic anaemia

Answer 16

Cell membrane - Autoimmune haemolytic anaemia or snake bite
Whole cell - Microangiopathic haemolytic anaemia, malaria
Oxidant exposure - damson or primaquine

Question 17

How may acquire haemolytic anaemia cause inherited anaemia

Answer 17

Precipitation of episodic haemolysis in individuals with an enzyme deficiency (from oxidant exposure damage) can cause a defect in enzymes of the pentose shunt

Question 18

When should haemolytic anaemia be expected

Answer 18

Otherwise unexplained anaemia (normochromic and normocytic/macrocytic)
Evidence of morphologically abnormal red cells
Evidence of increased red cell breakdown
Evidence of increased bone marrow activity

Question 19

Describe hereditary spherocytosis

Answer 19

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

Question 20

How does hereditary spherocytosis lead to jaundice

Answer 20

Spherocytes are less flexible and are removed prematurely by the spleen (extravascular haemolysis)
The bone marrow responds nay increasing output of red cells, leading to polychromasia and reticulocytosis
Leads to increased bilirubin production, jaundice and gall stones

Question 21

What is the osmotic fragility test

Answer 21

Spherocytes are more prone to haemolyse when osmotic pressure is reduced

Question 22

How is hereditary spherocytosis treated

Answer 22

Splenectomy
Good diet so secondary folic acid deficiency does not occur
One folic acid tablet taken daily

Question 23

Describe glucose-6-phosphate dehydrogenase deficiency

Answer 23

G6PD is an important enzyme in the pentose phosphate shunt
Essential for the protection of the red cell from oxidant damage
Gene for G6PD is on the X chromosome so those affected are usually homozygous males (sometimes homozygous females)

Question 24

What causes oxidant damage

Answer 24

Oxidants may be generated in the blood stream e.g. during infection, or may be exogenous
extrinsic - broad beans
intrinsic - naphthalene in mothballs
Drugs - dapsone, primaquine

Question 25

What does G6PD deficiency cause

Answer 25

Intermittent severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant
Such episodes are associated with irregularly contracted cells
Haemoglobin is denatured and forms Heinz bodies (round inclusions)

Question 26

Describe autoimmune haemolytic anaemia

Answer 26

Results from production of autoantibodies directed at red cell antigens
Immunoglobulins bound to red cell membrane is recognised by splenic macrophages, which removes parts of the red cell membrane -> spherocytosis
Complements can be bound to the Ig molecule and recognised by splenic macrophages

Question 27

How does autoimmune haemolytic anaemia -

Answer 27

Spherocytes are less flexible
Combination of cell rigidity and recognition of antibody and complement on the red cell surface by splenic macrophages leads to removal of cells by the spleen

Question 28

How is autoimmune haemolytic anaemia diagnosed

Answer 28

Spherocytes found
Increased reticulocyte count
Immunoglobulin and complement on red cell surface detected
Antibodies to red cell antigens or other autoantibodies in the plasma detected

Question 29

How is autoimmune haemolytic anaemia treated

Answer 29

use of corticosteroids and other immunosuppressive agents

Splenectomy for severe cases

Question 30

How is microangiopathic haemolytic anaemia treated

Answer 30

Remove the cause e.g. treat 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

Question 31

What can cause failure of production of red cells

Answer 31

• Early stages of iron deficiency or anaemia of chronic disease
• renal failure
• bone marrow failure or suppression
• bone marrow infiltration