Haemolysis

Question 1

Define haemolysis

Answer 1

Premature red cell destruction

i.e. shortened red cell survival

Question 2

What makes RBCs susceptible to damage?

Answer 2

1. Biconcave shape
2. Limited metabolic reserve - rely exclusively on glucose metabolism
3. Enucleated in circulation - no new protein generation

Question 3

What is compensated haemolysis?

Answer 3

Increased red cell destruction compensated by increased red cell production

i.e. Hb Maintained

Question 4

What is decompensated haemolysis?

Answer 4

Increased rate of red cell destruction exceeding bone marrow capacity for red cell production

aka HAEMOLYTIC ANAEMIA

i.e. Hb Falls

Question 5

What are the consequences of haemolysis?

Answer 5

• erythroid hyperplasia (ncreased BM activity on biopsy)

- excess red cell break down products (ex. bilirubin)

Question 6

How is haemolysis detected?

Answer 6

Rely on detecting the consequence of haemolysis and then investigate the cause

• increased red cell prod
• detection of breakdown products
• look for signs of erythroid hyperplasia (ex. retic)

Question 7

What is the bone marrow response to haemolysis?

Answer 7

1. reticulocytosis

2. erythroid hyperplasia

Question 8

What is seen on the blood films of patient with haemolysis?

Answer 8

Polychromasia

Question 9

Retics are diagnostic of haemolysis - T/F?

Answer 9

F

Only shows the bone marrow is responding to the anaemia

Question 10

Name the special stain for reticulocytes. What is the feature it stains?

Answer 10

New methylene blue stains ribosomal RNA

Question 11

How is haemolysis classified?

Answer 11

Depending on site where it occurs:

a) extravascular - taken up by reticuloendothelial system (mainly liver and spleen)
b) intravascular - destroyed within circulation

Different mechanisms therefore different breakdown products detected

Question 12

Which classification of haemolysis is more common?

Answer 12

EXTRA vascular

Question 13

What are the features of extravascular haemolysis?

Answer 13

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

Release of protoporphyrin:
Unconjugated bilrubinaemia
  Jaundice
  Gall stones
Urobilinogenuria

**Normal products in excess

Question 14

What are the features of intravascular red cell destruction?

Answer 14

Red cells are destroyed in the circulation spilling their contents. This explains the pathophysiology

Haemoglobinaemia (free Hb in circulation)

Methaemalbuminaemia

Haemoglobinuria: pink urine, turns black on standing

Haemosiderinuria: iron containing protein which stains the urine

**Abnormal products

Question 15

What are the causes of intravascular haemolysis?

Answer 15

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

All other causes of haemolysis leads to EXTRAVASCULAR haemolysis

Question 16

List the investigations to confirm haemolytic state

Answer 16

FBC (+blood film)
Reticulocyte count
Serum unconjugated bilirubin
Serum haptoglobins (binds to Hb)
Urinary urobilinogen

Question 17

Which investigations identify the cause of haemolysis?

Answer 17

History and examination

Blood film 
Membrane damage (spherocytes)
Mechanical damage (red cell fragments)
Oxidative damage (Heinz bodies)
 Others e.g.. HbS (sickle cells

Specialist investigations - ex. direct coomb’s test

Question 18

How is haemolysis classified based on site of red cell defect?

Answer 18

1. Premature destruction of normal red cells (immune or mechanical)
2. Abnormal cell membrane
3. Abnormal red cell metabolism
4. Abnormal Hb

Question 19

What are the acquired immune causes of haemolysis?

Answer 19

Autoimmune haemolysis

Alloimmune haemolysis

Question 20

List the autoimmune conditions producing warm (IgG) autoantibodies?

Answer 20

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

Question 21

What does direct Coomb’s test detect?

Answer 21

Autoimmune haemolysis

Question 22

When does alloimmune haemolysis occur?

Answer 22

Immune response (production of Abs)
Haemolytic transfusion reaction
Immediate (IgM) - predominantly intravascular
Delayed (IgG) -predominantly extravascular

Passive transfer of antibody
Haemolytic disease of the newborn
Rh D
ABO incompatibility
Others eg anti-Kell

Question 23

What are the mechanical causes of red cell destruction?

Answer 23

Disseminated intravascular coagulation

Haemolytic uraemic syndrome (eg E. coli O157)

TTP

Leaking heart valve

Infections e.g. Malaria

Question 24

What are the acquired causes of membrane defects leading to haemolysis?

Answer 24

Liver Disease (Zieve’s Syndrome) 
Vitamin E deficiency
Paroxysmal Nocturnal Haemoglobinuria

(ALL VERY RARE)

Question 25

Zieve’s syndrome in context of haematology

Answer 25

Anaemia
Polychromatic macrocytes
Irregularly contracted cells

Question 26

What are the congenital causes of red cell abnormalities leading to hameolysis?

Answer 26

Reduced membrane deformability
Increased transit time through spleen
Oxidant environment in spleen causes extravascular red cell destruction
Hereditary Spherocytosis

Question 27

What are the genetic causes of abnormal red cell metabolism?

Answer 27

failure to cope with oxidant stress (G6PD deficiency)

failure to generate ATP: metabolic processes fail

Question 28

What are the genetic causes of abnormal Hb?

Answer 28

Sickle cell disease (Hb S): 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