Haemolysis

Question 1

What is haemolysis?

Answer 1

Premature red cell destruction i.e. shortened red cell survival

Question 2

Why are RBCs susceptible to damage?

Answer 2

1. They need to have a biconcave shape to circulate successfully 2. They have limited metabolic reserve and rely solely on glycolysis for energy 3. Can’t generate new proteins once in the circulation (no nucleus)

Question 3

What is compensated haemolysis?

Answer 3

Increased red cell destruction compensated by increased red cell production i.e. Hb is maintained

Question 4

What is haemolytic anaemia?

Answer 4

Decompensated haemolysis - increased 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

It’s not possible to directly measure red cell survival routinely so how is haemolysis identified?

Answer 6

Rely on detecting the consequences of haemolysis and then investigating the cause - increased red cell production, detection of breakdown products

Question 7

What is the bone marrow response to haemolysis?

Answer 7

Reticulocytosis and erythroid hyperplasia i.e. making lots of new immature RBCs

Question 8

What would the blood film of a patient with haemolysis feature?

Answer 8

Polychromasia due to ribosomal RNA

Question 9

What is automated reticulocyte counting?

Answer 9

Ribosomal RNA is labelled with a fluorochrome and fluorescent cells are counted

Question 10

How is haemolysis classified?

Answer 10

Extravascular and intravascular

Question 11

What is the basic pathology behind extravascular and intravascular haemolysis respectively?

Answer 11

Extravascular - RBCs taken up by reticuloendothelial system (spleen and liver) Intravascular - RBCs destroyed within the circulation

Question 12

Where does hyperplasia occur in extravascular haemolysis and what happens as a result of EV haemolysis?

Answer 12

More common than intravascular. Hyperplasia at site of destruction (e.g. splenomegaly). Release of protoporphyrin - unconjugated bilirubinaemia (jaundice and gall stones), urobilinogenuria NORMAL products but in excess

Question 13

What is the underlying mechanism of intravascular haemolysis and what happens as a result of intravascular haemolysis?

Answer 13

Red cells are destroyed in the circulation spilling their contents causing haemoglobinaemia (free Hb in circulation), methaemalbuminaemia, haemoglobinuria (pink urine, turns black on standing) and haemosiderinuria. ABNORMAL products - intravasuclar haemolysis may be life threatening

Question 14

What are some of the intravascular causes of haemolysis?

Answer 14

ABO incompatible blood transfusion, G6PD deficiency, severe falciparum malaria (blackwater fever)

Question 15

How is haemolysis investigated?

Answer 15

Confirm haemolytic state - FBC, reticulocyte count, serum unconjugated bilirubin, serum haptoglobins, urinary urobilinogen Identify cause - history and examination, blood film (spherocytes, red cell fragments, Heinz bodies, sickle cells), direct Coombs’ test

Question 16

What is another way of classifying haemolysis (other than intra vs extravascular)?

Answer 16

By site of red cell defect - congenital vs acquired

Question 17

What are the causes of acquired immune haemolysis?

Answer 17

Autoimmune haemolysis or alloimmune haemolysis

Question 18

There are 2 types of autoantibody possible in autoimmune haemolysis, what are these?

Answer 18

Warm - IgG Cold - IgM

Question 19

What conditions is the warm (IgG) autoantibody for autoimmune haemolysis seen in?

Answer 19

Autoimmune disorders e.g. SLE, lymphoproliferative disorders e.g. CLL, drugs e.g. penicillins, infections

Question 20

What conditions is the cold (IgM) autoantibody for autoimmune haemolysis seen in?

Answer 20

Infections e.g. EBV, mycoplasma Lymphoproliferative disorders e.g. CLL

Question 21

What does a direct Coombs’ test do?

Answer 21

Identifies antibody (and complement) bound to own red cells

Question 22

What can cause alloimmune haemolysis?

Answer 22

Immune response (antibody produced) - haemolytic transfusion reaction; immediate (IgM) predominantly intravascular or delayed (IgG) predominantly extravascular Passive transfer of antibody - haemolytic disease of the newborn; RhD, ABO incompatibility

Question 23

What are the causes of acquired mechanical haemolysis?

Answer 23

Disseminated intravascular coagulation, haemolytic uraemic syndrome (e.g. E.coli 0157), TTP, leaking heart valve, infections e.g. malaria

Question 24

What would appear on blood film in a patient with burns related haemolysis?

Answer 24

Microspherocytes, red cells are sheared as they pass through the damaged capillaries. Only seen therefore in severe burns

Question 25

What would cause acquired haemolysis due to abnormal cell membrane?

Answer 25

Very rare cause of acquired haemolysis. Liver disease (Zieve’s syndrome), vitamin E deficiency, paroxysmal nocturnal haemoglobinuria

Question 26

What are the features of Zieve’s syndrome?

Answer 26

Haemolysis, alcoholic liver disease and hyperlipidaemia are the main features Anaemia, polychromatic macrocytes and irregularly contracted cells

Question 27

What is the most common genetic cause of haemolysis?

Answer 27

Hereditary spherocytosis - abnormal red cell membrane

Question 28

What is the mechanism behind abnormal red cell metabolism as a genetic cause of haemolysis?

Answer 28

Failure to cope with oxidant stress (G6PD deficiency) -> failure to generate ATP (metabolic processes fail)

Question 29

What is the main cause of abnormal haemoglobin causing genetic haemolysis?

Answer 29

Sickle cell disease - affects physical properties of haemoglobin resulting in shortened red cell survival

Question 30

What causes sickle cell disease?

Answer 30

A point mutation in beta globin chain