Haemolysis

Question 1

What is haemolysis?

Answer 1

Premature red cell destruction

Question 2

Why are red cells particularly susceptible to damage?

Answer 2

Need to have biconcave shape to transit the circulation successfully

They have limited metabolic reserve and rely exclusively on glucose metabolism for energy (no mitochondria)

Can’t generate new proteins once in circulation (no nucleus)

Question 3

What is compensated haemolysis?

Answer 3

Increased red cell destruction compensated by increased red cell production (Hb maintained)

Question 4

What is decompensated haemolysis (haemolytic anaemia)?

Answer 4

Increased rate of red cell destruction exceeding bone marrow capacity for red cell production (Hb falls)

Question 5

What are the two main consequences of hamolysis?

Answer 5

1. Erythroid hyperplasia (increased bone marrow red cell breakdown)
2. Excess red cell breakdown products e.g. bilirubin (clinical features differ by aetiology and site of red cell breakdown)

Question 6

What is the bone marrow response to haemolysis?

Answer 6

Erythroid hyperplasia
Reticulocytosis

Question 7

Are reticulocytes nucleated cells?

Answer 7

NO!!!!

Question 8

Reticulocytes are not diagnostic of haemolysis, they are also found when?

Answer 8

In response to bleeding
Iron therapy in iron deficiency anaemia

Question 9

A blood film with reticulocytes will be described as?

Answer 9

Polychromatic because there is ribosomal RNA in reticulocytes

Question 10

What stain can you use for reticulocytes?

Answer 10

Supravital stain staining ribosomal RNA (new methylene blue)

Question 11

What happens in extravascular haemolysis?

Answer 11

Hyperplasia at site of destruction (splenomegaly +/- hepatomegaly)

Taken up by reticuloendothelial system (spleen and liver predominantly)

Question 12

What is commoner - extravascular or intravascular haemolysis?

Answer 12

Extravascular haemolysis

Question 13

What happens to end products in extravascular haemolysis?

Answer 13

Release of protoporphyrin
- Unconjugated bilirubinaemiea (jaundice, gall stones)
- Urobilinogenuria

NORMAL PRODUCTS IN EXCESS

Question 14

What is intravascular haemolysis?

Answer 14

Red cells destroyed in circulation spilling their contents

ABNORMAL PRODUCTS

may be life threatening

Question 15

What 4 signs can be seen in intrasvascular haemolysis?

Answer 15

Haemoglobinaemia (Free Hb in circulation)
Methaemalbuminaemia
Haemoglobinuria (pink urine, turns black on standing)
Haemosiderinuria

Question 16

What are causes of intravascular haemolysis?

Answer 16

ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria (blackwater fever)
Rarer still PNH, PCH

Question 17

What tests should you do to confirm haemolytic state?

Answer 17

FBC (+ blood film)
Retiulocyte count
Serum unconjugated bilirubin
Serum haptoglobins
Urinary urobilinogen

Question 18

How do you identify cause of haemolysis?

Answer 18

History + exam (genetic / acquired)
Blood film
- Membrane damage (spherocytes)
- Mechanical damage (red cell fragments)
- Oxidative damage (Heinz bodies)
- Others e.g. HbS (sickle cells)

Specialist investigations (Direct Coombs test and others)

Question 19

If you classify haemolysis by site of red cell defect, what would be the 4 categories?

Answer 19

Premature destruction of normal red cells (immune or mechanical)
Abnormal cell membrane
Abnormal red cell metabolism
Abnormal haemoglobin

Congenital vs. acquired

Question 20

What are acquired immune causes of haemolysis?

Answer 20

Autoimmune haemolysis
Alloimmune haemolysis

Question 21

What are examples of autoimmune haemolysis?

Answer 21

Warm or cold autoantibody

Warm (IgG)
Cold (IgM)

Question 22

Warm autoimmune haemolysis has what antibody?

Answer 22

IgG

Question 23

Cold autoimmune haemolysis has what antibody?

Answer 23

IgM

Question 24

What are causes of warm autoimmune haemolysis?

Answer 24

Idiopathic (commonest)
Autoimmune disorders (SLE)
Lymphoproliferative disorders (CLL)
Drugs (penicillins, etc.)
Infections

Question 25

What are causes of cold autoimmune haemolysis?

Answer 25

Idiopathic Infections (EBV, mycoplasma) Lymphoproliferative disorders

Question 26

What does Direct Coombs test test for? How does it work?

Answer 26

Autoimmune haemolysis

Question 27

What are causes of alloimmune haemolysis?

Answer 27

Immune response (antibody produced) - Haemolytic transfusion reaction (immediate (IgM) predominantly intravascular; delayed (IgG) predominately extravascular) Passive transfer of antibody - Haemolytic disease of the newborn (RhD, ABO incompatibility, others e.g. Anti-Kell)

Question 28

What are causes of mechanical red cell destruction?

Answer 28

Disseminated intravascular coagulation (DIC) Haemolytic uraemic syndrome (e.g. E. coli 0157) TTP Leaking heart valve Infections e.g. Malaria

Question 29

What kind of haemolysis does a mechanical valve cause?

Answer 29

Microangiopathic haemolytic anaemia (MAHA) Red cell fragmentation as a result of mechanical (Extrinsic) damage

Question 30

What can be seen in burns related haemolysis?

Answer 30

Microspherocytes

Question 31

What are causes of acquired membrane defect causes of haemolysis?

Answer 31

ALL VERY RARE Liver disease (Zieve's syndrome) Vitamin E deficiency Paroxysmal nocturnal haemoglobinuria

Question 32

What is Zieve's syndrome and what is seen?

Answer 32

Question 33

What are genetic causes of abnormal cell membrane haemolysis?

Answer 33

Red cell membrane abnormalities - Reduced membrane deformability - Increased transit time through spleen - Oxidant environment in spleen causes extravascular red cell destruction - Hereditary spherocytosis

Question 34

What genetic causes exist for abnormal red cell metabolism haemolysis?

Answer 34

G6PD deficiency - Failure to cope with oxidant stress Failure to generate ATP: metabolic processes fail NB: even the metabolic pathways of normal cells if sufficiently stressed e.g. by dapsone or salazopyrin can get oxidative damage

Question 35

Dapsone therapy can cause what changes to blood cells?

Answer 35

Question 36

What genetic causes of haemolysis exist whereby the problem is abnormal haemoglobin?

Answer 36

Sickle cell disease (HbS) - affects physical properties of haemoglobin (abnormal polymerisation) resulting in shortened red cell survival - Caused by a point mutation in beta globin chain - Disease has variable clinical severity - Trait asymptomatic

Question 37

What bone marrow and blood changes would you see in beta thalassaemia major?

Answer 37

Question 38

What happens in HbH disease (a form of alpha thalassaemia) and what is seen on blood film?

Answer 38