Anaemia

Question 1

what is anaemia?

Answer 1

Anaemia is 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
By definition, the Hb is reduced
The RBC and the Hct/PCV are usually also reduced
Anaemia is usually due to a reduction of the absolute amount of haemoglobin in the blood stream

Question 2

what is the other possible cause of anaemia?

Answer 2

Occasionally it results from an increase in the volume of plasma rather than a decrease in the amount of haemoglobin
In a healthy person, anaemia resulting from an increase in plasma volume cannot persist because the excess fluid in the circulation is excreted
For practical purposes, anaemia can therefore be regarded as a resulting from a decrease of the absolute amount of haemoglobin in the circulation

Question 3

what are the mechanisms of anaemia?

Answer 3

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 4

what is the difference between the mechanism and causes of anaemia?

Answer 4

We need to distinguish the mechanism of anaemia from the cause
The mechanism of the anaemia might be reduced synthesis of haemoglobin in the bone marrow
The cause of this could be either a condition causing reduced synthesis of haem or one causing reduced synthesis of globin

Question 5

what is the classification of anaemia on the basis of cell size?

Answer 5

Microcytic (usually also hypochromic)
Normocytic (usually also normochromic)
Macrocytic (usually also normochromic)

Question 6

what are the common causes of a microcytic anaemia?

Answer 6

Common causes of a microcytic anaemia

Defect in haem synthesis

• Iron deficiency
• Anaemia of chronic disease

Defect in globin synthesis (thalassaemia)

• Defect in α chain synthesis (α thalassaemia)
• Defect in β chain synthesis (β thalassaemia)

Question 7

what is the mechanism behind macrocytic anaemia?

Answer 7

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
As a result, the red cells end up larger than normal

Question 8

what is one cause of macrocytic anaemia?

Answer 8

A macrocytic anaemia is one in which average cell size is increased
One cause of this is megaloblastic erythropoiesis
This refers specifically to a delay in maturation of the nucleus while the cytoplasm continues to mature and the cell continues to grow

Question 9

what is a megaloblast?

Answer 9

A megaloblast is an abnormal bone marrow erythroblast
It is larger than normal and shows nucleo-cytoplasmic dissociation
It is possible to suspect megaloblastic anaemia from the peripheral blood features but to be sure requires bone marrow examination

Question 10

what is an alternative mechanism of macrocytosis?

Answer 10

An alternative mechanism of macrocytosis is premature release of cells from the bone marrow
Young red cells are about 20% larger than mature red cells so if there is an increased proportion of young red cells (reticulocytes) in the circulation, the average cell size (MCV) will be increased

Question 11

what are the common causes of macrocytic anaemia?

Answer 11

• 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 (reticulocytes increased)
• Haemolytic anaemia (reticulocytes increased)

Question 12

what might be the mechanism behind normocytic normochromic anaemia?

Answer 12

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

Question 13

what are the causes behind normocytic normochromic anaemia?

Answer 13

-Peptic ulcer, oesophageal varices, trauma
-Failure of production of red cells
Early stages of iron deficiency or anaemia of chronic disease
Renal failure
Bone marrow failure or suppression
Bone marrow infiltration
Hypersplenism, e.g. portal cirrhosis

Question 14

what is haemolytic anaemia?

Answer 14

Haemolytic anaemia is anaemia resulting from shortened survival of red cells in the circulation
Haemolysis can result from an intrinsic abnormality of the red cells
Haemolysis can result from extrinsic factors acting on normal red cells

Question 15

haemolytic anaemia can be further divided into inherited or acquired- what does this mean?

what can extrinsic factors do?

Answer 15

Haemolytic anaemia can also be classified as inherited or acquired

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

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

Extrinsic factors can interact with red cells that have an intrinsic abnormality

Question 16

Haemolytic anaemia can also be classified into intravascular haemolysis and extravascular haemolysis- what does this mean?

Answer 16

Haemolytic anaemia 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 17

give examples of inherited anaemia

Answer 17

• abnormal red cell membrane eg hereditary spherocytosis
• abnormal Hb eg in sickle cell anaemia
• defect in glycolytic pathway eg pyruvate kinase deficiency
• defect in enzymes of pentose shunt eg G6PD deficiency

Question 18

give examples of acquired anaemia

Answer 18

-damage to red cell membrane eg snake bite or autoimmune haemolytic anaemia
-damage to whole red cell eg malaria
-oxidant exposure damage to red cell membrane and Hb eg dapsone
(this can then lead to precipitation of episodic haemolysis in individuals with enzyme deficiency)

Question 19

when would you suspect haemolytic anaemia?

Answer 19

Otherwise unexplained anaemia, which is normochromic and usually either normocytic or macrocytic
Evidence of morphologically abnormal red cells
Evidence of increased red cell breakdown
Evidence of increased bone marrow activity

Question 20

what is hereditary spherocytosis? and what happens?

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
Red cells become less flexible and are removed prematurely by the spleen – extravascular haemolysis
The bone marrow responds to haemolysis by an increased output of red cells leading to polychromasia and reticulocytosis
Haemolysis leads to increased bilirubin production, jaundice and gallstones

Question 21

what are spherocytes more prone to?

Answer 21

Spherocytes are also more prone to haemolyse when osmotic pressure is reduced

Question 22

name some treatment options for hereditary spherocytosis?

Answer 22

The only effective treatment is splenectomy, but this has its own risks so is only done in severe cases
A good diet is important so that a secondary folic acid deficiency does not occur
Alternatively, one folic acid tablet can be taken daily

Question 23

what occurs in glucose-6-phosphate dehydrogenase deficiency?

Answer 23

G6PD is an important enzyme in the pentose phosphate shunt
It is essential for the protection of the red cell from oxidant damage
Oxidants may be generated in the blood stream, e.g. during infection, or may be exogenous (Extrinsic oxidants may be foodstuffs (e.g. broad beans), chemicals (e.g. naphthalene) or drugs (e.g. dapsone, primaquine))

Question 24

where is the gene for G6PD?

Answer 24

The gene for G6PD is on the X chromosome so affected individuals are usually hemizygous males (but occasionally homozygous females)

Question 25

what type of haemolysis does G6PD deficiency cause?

Answer 25

G6PD deficiency usually causes intermittent, severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant

These episodes of intravascular haemolysis are associated with the appearance of considerable numbers of irregularly contracted cells
Haemoglobin is denatured and forms round inclusions known as Heinz bodies, which can be detected by a specific test

Question 26

what structures can you lookout for in G6PD deficiency?

Answer 26

irregularly contracted cells
Heinz bodies
Heinz bodies are removed by the spleen, leaving a defect in the cell

Question 27

what is the treatment for G6PD deficiency?

Answer 27

Acute haemolysis sometimes requires blood transfusion

Thereafter, prevention is important

Question 28

what does autoimmune haemolytic anaemia result from?

Answer 28

Autoimmune haemolytic anaemia results from production of autoantibodies directed at red cell antigens
The immunoglobulin bound to the red cell membrane is recognized by splenic macrophages, which remove parts of the red cell membrane, leading to spherocytosis
Complement components can also be bound to the immunoglobulin molecule, and they are also recognised by receptors on splenic macrophages

Question 29

why are spherocytes more prone to being removed from circulation?

Answer 29

The spherocytes are less flexible than normal red cells
The combination of cell rigidity and recognition of antibody and complement on the red cell surface by splenic macrophages leads to removal of cells from the circulation by the spleen

Question 30

how can you diagnose autoimmune haemolytic anaemia?

Answer 30

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 31

what is the treatment for autoimmune haemolytic anaemia?

Answer 31

Treatment is by
Use of corticosteroids and other immunosuppressive agents
Splenectomy for severe cases

Question 32

what is the treatment for microangiopathic haemolytic anaemia?

Answer 32

Treatment may be by
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

Question 33

what is Microangiopathic hemolytic anemia (MAHA)?

Answer 33

Microangiopathic hemolytic anemia (MAHA) is a microangiopathic subgroup of hemolytic anemia (loss of red blood cells through destruction) caused by factors in the small blood vessels. It is identified by the finding of anemia and schistocytes on microscopy of the blood film.