3) Anaemia and Polycythaemia

Question 1

Define 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?

Answer 2

An increase in the plasma volume can decrease the haemoglobin concentration

Question 3

Why would this type of anaemia only be transient in a healthy individual?

Answer 3

The excess fluid would be excreted in a healthy individual

Question 4

Broadly speaking, state four mechanisms of anaemia.

Answer 4

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

Question 5

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

Answer 5

Microcytic – hypochromic
Normocytic – normochromic
Macrocytic - normochromic

Question 6

State the common causes of microcytic anaemia.

Answer 6

Problem with Haem synthesis 
-  Iron deficiency
-  Anaemic of chronic disease
Problem with globin synthesis 
-  Alpha thalassemia 
-  Beta thalassemia

Question 7

What mechanism usually causes macrocytic anaemia?

Answer 7

It usually results from abnormal haemopoiesis

The cells fail to divide properly

Question 8

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

Answer 8

Megaloblastic erythropoiesis refers to a delay in the maturation of the nucleus while the cytoplasm continued to mature and the cell continues to grow
A megaloblast is an abnormal bone marrow erythroblast
They are large and show nucleo-cytoplasmic dissociation

Question 9

What is an alternative mechanism of macrocytosis?

Answer 9

You can get premature release of cells from the bone marrow
Reticulocytes are about 20% larger than mature red cells so reticulocytosis would increase the MCV

Question 10

State the two most common causes of megaloblastic anaemia.

Answer 10

B12 deficiency

Folate deficiency

Question 11

State some other common causes of macrocytic anaemia.

Answer 11

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

Question 12

State three mechanisms of normocytic normochromic anaemia.

Answer 12

Recent blood loss
Failure to produce red blood cells
Pooling of red blood cells in the spleen

Question 13

State five causes of normocytic normochromic anaemia.

Answer 13

Loss of Blood

• Peptic ulcer
• Oesophageal varices
• Trauma

Failure of production of red blood cells
- Early stages of iron deficiency and ACD
- Renal failure
- Bone marrow failure
- Bone marrow infiltration

Pooling of RBCs in spleen
- Hypersplenism e.g. portal cirrhosis

Question 14

Define haemolytic anaemia.

Answer 14

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

Question 15

State two different classifications of haemolytic anaemia.

Answer 15

Haemolysis can be inherited (resulting from abnormalities of the cell membrane, haemoglobin or the enzymes in the red blood cell)
It can be acquired usually resulting from extrinsic factors such as micro-organisms, chemicals or drugs
Haemolytic anaemia can also be described as intravascular if there is very acute damage to the red cell
It can also be classified as extravascular when the spleen removes defective red cells

Question 16

Explain how G6PD Deficiency can cause haemolytic anaemia.

Answer 16

G6PD is part of the pentose phosphate pathway =
the only source of reduced glutathione in RBCs.
Because of the oxygen-carrying role of red blood cells, they are at constant risk of oxidant damage
So people with G6PD deficiency are at risk of haemolytic anaemia in states of oxidative stress
G6PD-Deficiency usually causes intermittent severe intravascular haemolysis - associated with the presence irregularly contracted cells.
Also Heinz bodies

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

• hereditary elliptocytosis
• irregularly contracted cells

Evidence of increased red blood cell turnover

• gall stones
• jaundice
• splenomegaly

Evidence of increased bone marrow activity
- reticulocytosis

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 circulation (in the small circulation)

Question 19

What condition causes breakdown of red blood cells in small blood vessels?

Answer 19

Microangiopathic haemolytic anaemia

Question 20

State examples of inherited diseases causing haemolytic anaemia that have defects at the following sites:

a. Membrane
b. Haemoglobin
c. Glycolytic Pathway
d. Pentose Shunt

Answer 20

a. Membrane 
Hereditary spherocytosis 
b. Haemoglobin 
Sickle cell anaemia 
c. Glycolytic Pathway 
Pyruvate kinase deficiency
d. Pentose Shunt 
G6PD deficiency

Question 21

State examples of acquires disease causing haemolytic anaemia that have defects at the following sites:

a. Membrane - immune
b. Whole red cell - mechanical
c. Whole red cell - oxidant
d. Whole red cell - microbiological

Answer 21

a. Membrane – immune 
Autoimmune haemolytic anaemia
b. Whole red cell –mechanical 
Microangiopathic haemolytic anaemia
c. Whole red cell – oxidant 
Drugs and chemicals
d. Whole red cell – microbiological 
Malaria

Question 22

What is hereditary spherocytosis?

Answer 22

This is haemolytic anaemia or chronic compensated haemolysis resulting from an intrinsic inherited defect of the red cell membrane
After entering the circulation, the cells lose membrane in the cell and become spherocytic - they are removed prematurely by the spleen - extravascular haemolysis

Question 23

What are the features of red cells in hereditary spherocytosis?

Answer 23

They are LARGE and ROUND and have an increased MCHC

Question 24

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

Answer 24

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

Question 25

What is an effective treatment for hereditary spherocytosis?

Answer 25

Splenectomy

Question 26

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

Answer 26

They have increased bone marrow activity and erythropoiesis so they need a supply of B12, folate and iron to keep producing red blood cells

Question 27

Describe the pattern of inheritance of G6PD deficiency.

Answer 27

X linked recessive

Question 28

What can G6PD deficiency cause?

Answer 28

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

Question 29

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

Answer 29

Irregularly contracted cells

Question 30

What happens to the haemoglobin during these episodes?

Answer 30

It becomes denatured and forms round inclusions called Heinz bodies
NOTE: you can get more than one Heinz body per cell unlike Howell-Jolly bodies

Question 31

What causes autoimmune haemolytic anaemia?

Answer 31

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

Question 32

Describe how autoimmune haemolytic anaemia can lead to spherocytosis.

Answer 32

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

Question 33

State two causes of spherocytosis.

Answer 33

Hereditary spherocytosis

Autoimmune haemolytic anaemia

Question 34

Describe the diagnosis of acute haemolytic anaemia.

Answer 34

Finding spherocytes
Increased reticulocyte count
Detecting immunoglobulin on the red cell surface Detecting antibodies to red cell antigens or other antibodies in the plasma

Question 35

What is the treatment for acute haemolytic anaemia?

Answer 35

Corticosteroids or other immunosuppressive agents Splenectomy in severe cases

Question 36

Which red blood cell parameters are increased in polycythaemia?

Answer 36

RBC count
Hct
Hb

Question 37

What is the term given to a condition where these parameters are increased but the absolute amount of haemoglobin is not increased?

Answer 37

Pseudopolycythaemia (or apparent polycythaemia)

This is due to a decrease in plasma volume

Question 38

State some causes of polycythaemia.

Answer 38

Blood doping
Elevation of EPO when at altitude
Tumour (renal or other tumour that can secrete high amounts of EPO)
Abnormal function of bone marrow – it can result from inappropriately increased erythropoiesis that is independent of EPO, this is an intrinsic bone marrow disorder called polycythaemia vera
It is a chronic myeloproliferative neoplasm

Question 39

What are the consequences of polycythaemia?

Answer 39

Hyperviscosity of the blood

This can lead to vascular obstruction

Question 40

How can Haemolytic Anaemia be classified

Answer 40

inherited versus acquired

intravascular versus extravascular

Question 41

When does Intravascular Haemolysis occur

Answer 41

Occurs if there’s very acute damage to the RBC

Question 42

When does extravascular Haemolysis occur

Answer 42

when defective RBCs are removed by the spleen

Question 43

consequences of extravascular haemolysis in hereditary spherocytosis

Answer 43

jaundice
gallstones
increased bilirubin production

Question 44

what is true polycythaemia

Answer 44

if abnormally high RBC, Hct and Hb is due to increased number of circulating RBCs

Question 45

what is splenomegaly a sign of

Answer 45

polycythaemia vera