CH3

Question 1

How long do red blood cells normally survive?

Answer 1

120 days

Question 2

How long do red blood cells normally survive in a patient with haemolytic anaemia?

Answer 2

The red cell survival time is considerably shortened

Question 3

Where does the breakdown of normal red cells occur?

Answer 3

In the macrophages of the bone marrow, liver & spleen

Question 4

What can excessive destruction of red cells cause?

Answer 4

Haemolytic anaemias

Question 5

Does the shortening of red cell lifespan always result in anaemia?

Answer 5

No, shortening of red cell survival does not always cause anaemia.
There is a compensatory increase in red cell production in the bone marrow
If red cell loss can be contained, a haemolytic state without anaemia can exist
- compensated haemolytic disease

Question 6

What are the consequences of haemolysis?

Answer 6

Shortening of red cell lifespan
Marrow output increased 6-8x by
- increasing the proportion of cells committed to erythropoiesis (erythroid hyperplasia)
- expanding the volume of active marrow

Immature red cells (reticulocytes) are released prematurely

• larger than mature cells
• stain blue on peripheral blood film (polychromasia)

Question 7

What are the two mechanisms whereby red blood cells are destroyed in haemolytic anaemia?

Answer 7

Extravascular haemolysis

Intravascular haemolysis

Question 8

What is extravascular haemolysis?

Answer 8

Excessive removal of RBC from the circulation by the macrophages of the reticuloendothelial system (spleen)

Question 9

What is intravascular haemolysis?

Answer 9

RBCs are broken down directly in the circulation .

• Haemoglobin is liberated. This is initially bound to plasma haptoglobins which become saturated

Question 10

Name some of the causes of intravascular haemolysis

Answer 10

Mismatched blood transfusion
G6PD deficiency with oxidant stress
Red cell fragmentation syndromes
Some autoimmune haemolytic anaemias
Some drug- and infection- induced haemolytic anaemias
Paroxysmal nocturnal haemoglobinuria
March haemoglobinuria
Unstable haemoglobin

Question 11

When a red blood cell breaks down extravascularly, it breaks down into 3 components. What are they?

Answer 11

Globin
Haem
Protoporphyrin

Question 12

When a red blood cell breaks down extravascularly, it breaks down into 3 components. What happens to the haem component?

Answer 12

The haem group breaks down into Fe3+ and biliverdin. The iron then binds to transferrin, which then recirculates.

The biliverdin is reduced to bilirubin, which is then released into the plasma, where it is bound to albumin, and then recirculated to the liver.

Question 13

What happens to excess free plasma Hb?

Answer 13

It is filtered by the renal glomerulus.

It enters the urine and small amounts will be reabsorbed by renal tubules

Hb is broken down deposited in cells as haemosiderin

Some free plasma Hb is oxidised to methaemoglobin, which dissociates into ferrihaem & globin

Plasma haemopexin binds ferrihaem

If its binding capacity is exceeded ferrihaem becomes attached to albumin forming methaemalbumin

Question 14

How can excess free plasma Hb be detected?

Answer 14

Detected in spun sediment of urine - Perls’ reaction

Question 15

What organ removes Hb?

Answer 15

The liver removes Hb bound to haptoglobin, haemopexin and free Hb.

When the red blood cells break down, haemoglobin and haptoglobin complex forms, and will be removed by the liver.

Question 16

When red blood cells break down, what happens to the globin chains?

Answer 16

Globin chains broken down to Amino acids, and reutilised for general protein synthesis

Haptoglobins bind to haemoglobin to form a Haptoglobin/ Haemoglobin complex, which is removed from plasma by reticuloendothelial system

Question 17

What are laboratory findings of intravascular haemolysis?

Answer 17

Raised levels of plasma Hb
Very low or absent haptoglobins
Haemoglobinaemia, Haemoglobinuria
Haemosidinuria (Fe storage protein in the spun deposit of urine)
+ve Schumm’ test - shows methaemalbuminaemia detected spectrophotometrically

Question 18

What evidence of haemolysis would be shown in a patient?

Answer 18

Increased red cell breakdown leads to:

• elevated serum bilirubin (unconjugated)
• excess urinary urobilinogen (bilirubin breakdown in intestine)
• reduced plasma haptoglobin
• raised serum lactic dehydrogenase (LDH)

Increased red cell production (compensatory mechanism) leads to

• Reticulocytosis
• Erythroid hyperplasia of the bone marrow

Abnormal red cells in some haemolytic anaemias:

• spherocytes
• sickle cells
• red cell fragments

Question 19

What are the causes of haemolytic anaemias?

Answer 19

Inherited

• Red cells membrane defect
• Haemoglobin abnormalities
• Metabolic effects

Acquired

• Immune (autoimmune, alloimmune, drug induced)
• Non-immune

Miscellaneous

Question 20

Describe the features of Autoimmune Haemolytic Anaemias

Answer 20

AIHAs are caused by antibody production by the body against its own red cells
They are characterised by a positive direct antiglobulin test (DAT) or Coombs’ test
AIHAs are divided into ‘warm’ and ‘cold’ types according to whether the antibody reacts more strongly with red cells at 37C or 4C