Haemolysis Lecture

Question 1

definition of haemolysis?

Answer 1

Premature red cell destruction

i.e. shortened red cell survival

Question 2

Why are red cells susceptible to damage?

Answer 2

need to have biconcave shape to transit in the circulation successfully
Have limited metabolic reserve and rely on glucose metabolism for energy
Can’t generate new proteins once in circulation

Question 3

Compensated haemolysis definition?

Answer 3

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

Question 4

What is haemolytic anaemia?

Answer 4

decompensated haemolysis
inc 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?

• to red cell production?
• products?

Answer 5

-erythroid hyperplasia (increased production of red cells by the BM)
Excess red cell breakdown products e.g. bilirubin

Question 6

How does the bone marrow respond to haemolysis? (2)

Answer 6

reticulocytosis & erythroid hyperplasia

Question 7

Reticulocytosis

• what is it?
• Blood film findings?
• stain used?

Answer 7

• increase in number of immature (non-nucleated) RBCs
• polychromasia (ribosomal RNA)
• Supravital stain

Question 8

Erythroid hyperplasia

-what is it?

Answer 8

excessive growth of immature RBCs

Question 9

give the 2 classifications of heamolysis?

• and the definition of each?
• give causes for each intra (4) and extra (1)

Answer 9

Extravascular Vs intravascular

-Extravascular
taken up by reticuloendothelial system
intravascular
red cells destroyed within the circulation

-intra 
ABO incompatibility
G6PD deficiency
severe falciparum malaria 
Rarer still PNH, PCH
Extra
everything else :/

Question 10

Extravascular haemolysis

• instance?
• location & effect?
• breakdown products? cause what?

Answer 10

• commoner
• hyperplasia in organs at site of destruction e.g. liver and spleen

-release of protoporphyrin
causes unconjugated bilirubinaemia and jaundice/gall stones/Urobilinogenuria

Question 11

Intravascular haemolysis

-pathophysiological events and consequences? i.e. products of breakdown and clinical impact

Answer 11

haemoglobinaemia 
(free Hb in circulation)
Methaemalbuminaemia
(Methaemalbumin in blood)
Haemoglobinuria: 
(urine pink, turns black on standing)
Haemosiderinuria
(brown urine)

Question 12

investigations in heamolysis
-to confirm the haemolytic state? (5)
-to identify cause? (2)
what should be looked for on blood film? (4)

Answer 12

-FBC (+Blood film)
reticulocyte count 
serum unconjugated bilirubin 
serum haptoglobins
urinary urobilinogen

-Hx & examination
(genetic vs acquired)
specialist inv e.g. Coombs test

-spherocytes, red cell fragments, heinz bodies, sickle cells

Question 13

Haemolysis can also be classified according to site of red cell defect, state the 4 site?s (4)

Answer 13

premature destruction of normal red cells (immune/mechanical)
abnormal cell membrane
abnormal red cell metabolism
abnormal Hb

Question 14

Give the two causes Of acquired, immune mediated haemolysis?

Answer 14

Autoimmune haemolysis

Alloimmune haemolysis

Question 15

Autoimmune haemolysis

• warm (what Ig involved and associated with what (5)?)
• cold (what Ig involved and associated with what (3)?)
• test used to diagnose?

Answer 15

-IgG
idiopathic 
autoimmune disorders e.g. SLE
Lymphoproliferative disorder (CLL)
Drugs e.e. penicillin
infection 

-IgM
idiopathic
infections
Lymphoproliferative disorders

-Direct Coombs’ test
this identifies antibody and complete bound to own red cells
patients RBCs + anti-human IgG = agglutination then +

Question 16

Alloimmune haemolysis 
-immune response 
(seen in what? what Ig involved (2)?)
-Passive transfer
(seen in what? what Ig involved?)

Answer 16

-haemolytic transfusion reaction
immediate- IgM (intravascular)
delayed- IgG (extravascular)

-antibody passively transferred across in haemolytic disease of the newborn
RhD/ABO incompatibility

Question 17

give causes of mechanical Red cell destruction? (5)

Answer 17

Disseminated intravascular coagulation 
Haemolytic Uraemia syndrome 
TTP
leaking heart valve 
infection

Question 18

What is seen on blood film in severe burns?

Answer 18

microspherocytes, the red cells are sheared as they pass through damaged capillaries

Question 19

name 3 acquired membrane defects that result in haemolysis?

Name 4 genetic membrane defects that result in haemolysis?

Answer 19

Liver disease- Zieve's syndrome
(Haemolysis, Alcoholic liver disease, hyperlilidaemia)
Vitamin E deficiency 
Paroxysmal Nocturnal haemoglobinuria 
all very rare 

-reduced membrane deformability
increased transit time though spleen
Oxidant environment in spleen causes extravascular red cell destruction
Hereditary spherocytosis

Question 20

name congenital causes off abnormal red cell metabolism? (2)

acquired causes? (1)

Answer 20

G6PD deficiency
(failure to cope with oxidative stress)
failure to generate ATP

some drugs that initiate oxidative stress
e.g. Dapsone

Question 21

give congenital causes for abnormal Hb?

Answer 21

sickle cell disease