Haemolysis

Question 1

What is haemolysis?

Answer 1

Premature red cell destruction i.e. shortened red cell survival in the circulation

Question 2

Why are red cells particularly susceptible to damage?

Answer 2

• They need to have a biconcave shape to transit the circulation successfully
• They have limited metabolic reserve and rely exclusively on glucose metabolism for energy (no mitochondria)
• Cannot generate new proteins once in circulation as they do not have a nucleus

Question 3

What is compensated haemolysis?

Answer 3

Increased destruction of red cells coupled with an increased production of red cells i.e. Hb is maintained

Question 4

What is haemolytic anaemia (decompensated haemolysis)?

Answer 4

Increase rate of red cell destruction exceeding bone marrow capacity for red cell production i.e. Hb falls

Question 5

What are the consequences of haemolysis?

Answer 5

Erythroid hyperplasia (increased bone marrow red cell production)
Excess red cell breakdown products e.g. bilirubin

Question 6

What is the bone marrow response to haemolysis?

Answer 6

Reticulocytosis

Erythroid hyperplasia

Question 7

What is important to remember about reticulocytes?

Answer 7

They do not have a nucleus! (do have RNA remnants etc but no nucleus)

Question 8

What is the appearance of reticulocytosis on blood film

Answer 8

Polychromasia ( due to rRNA)

Large cells

Question 9

What are the two broad classifications of haemolysis?

Answer 9

Extravascular= taken up by reticuloendothelial system eg spleen and liver
Intravascular= red cells destroyed within the circulation 

Different classification- therefore different breakdown products detected
Knowing whether it is intra/extra helps determine cause of haemolysis

Question 10

Which is more common; intra or extravascular red cell destruction?

Answer 10

Extravascular

Question 11

What are the feautres of an extravascular red cell destruction

Answer 11

Hypeplasia of site of destruction - splenomegaly, hepatomegaly
Release of protoporphyrin
-unconjugated biliribinaemia resulting in jaundice or gallstone
-urobilinogenuria

Normal products are in excess.

Question 12

What are the features of intravascular red cell destruction?

Answer 12

Red cells are destroyed in the circulation therefore spilling their contents.

• Haemoglobinaiemia (free Hb in circulation)
• Methaemalbuminaemia
• Haemoglobinuria (pink urine, turns black on standing)
• Haemosiderinuria

Abnormal products

This type of haemolysis can be life threatening!

Question 13

What are the causes of intravascular haemolysis

Answer 13

ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria (blackwater fever)
PNH, PCH (paroxysmal nocturnal haemoglobinuria, paroxysmal cold haemoglobinurea)- v. rare

Question 14

What investigations are done to confirm a haemolytic state?

Answer 14

FBC and blood film
Reticulocyte count
Serun unconjugated bilirubin
Serum haptoglobins
Urinary urobilinogen

Question 15

What tests are done to try determine the cause of haemolysis

Answer 15

Membrane damage - spherocytes
Mechanical damage- red cell fragments
Oxidative damage - Heinz bodies
Others eg HbS - sickle cell

Direct coombs test

Question 16

what are the possible sites of a red cell defect

Answer 16

1/ premature destruction of normal cells
2. abnormal cell membrane
3. abdnormal red cell metabolism
4 abnormal haemoglobin

Question 17

What causes premature destruction of red cells

Answer 17

Autoimmune or alloimmune haemolysis

Question 18

What are the forms of autoimmune haemolysis?

Answer 18

Warm or cold auto-antibody

Warm(IgG) - Idiopathic (commonest)

• Autoimmune (SLE)
• Lymphoprofiferative disorders (CLL)
• Drugs (penicillins etc)
• Infections

Cold (IgM) -Idiopathic

• Infections (EBV, mycoplasma)
• Lymphoproliferative disorders

Question 19

what is direct coombs test?

Answer 19

Used to identify antibody and compliment bound to own red cells.
if agglutination occurs = positive

Question 20

What are the causes of alloimmune haemolyis?

Answer 20

Immune response (antibody produced) - haemolytic transfusion reaction either delayed (IgG) or immediate (IgM)

Passive transfer of antibody - haemolytic disease of the newborn

Question 21

name some acquired causes of haemolysis

Answer 21

Mechanical red cell destruction eg

• disseminated intravascular coagulation
• Haemolytic uraemic syndrome (E. colli 0157)
• Thrombotic thrombocytopenic purpura
• Leaking hear valve
• Infections eg malaria

Question 22

WHy does a valvular problem result in haemolytic anaemia

Answer 22

Microangiopathic haemolytic anaemia occurs because the red cells fragment as a result of mechanical damage due to a diseased valve.

Question 23

How does burns cause haemolysis

Answer 23

red cells are sheared as they pass through damages capillaries so only seen in sever burns

Microspherocytes

Question 24

What acquire membrane defects can cause haemolyis

Answer 24

Liver disease (sieve's syndrome)
Vitamin E deficiency
Paroxysmal nocturnal haemoglobinuria