7.

Haemolytic
anaemia
Learning
Objectives
By the end of this lecture you
should be able to
Define what a haemolytic anaemia is
Understand the concept of compensated
haemolytic anaemia
Discuss in detail the difference between
intravascular and extravascular
haemolysis and how these can be
differentiated in the laboratory setting
Outline the clinical feature of haemolysis
Name several specific causes/types of
haemolytic anaemia
 Describe the structure of the red blood
cell membrane with particular reference
to the vertical and horizontal protein
interaction
Discuss the pathophysiology of hereditary
spherocytosis (HE) and elliptocytosis
(including the molecular defects)
Discuss the diagnosis of HS
Discuss the pathophysiology of red cell
metabolic defects such as G6PD
deficiency and include its mode of
inheritance, geographical distribution,
clinical symptoms, diagnosis and
management
Haemolytic anaemia
An increase in rate of red blood cell
destruction
Red cell production can be increased to 6-8
times the normal rate before patient shows signs
of anaemia Why?
Erythropoietic hyperplasia
Expansion of marrow cavity
Marked reticulocytosis
Rbc lifespan < 30 days signs of anaemia

Compensated haemolytic anaemia

Haemolysis
 Laboratory analysis
What features are characteristic are
increased red cell breakdown?

Serum bilirubin increased (bound to albumin and

unconjugated)
Faecal stercobilinogen increased
Urine urobilinogen increased
Serum haptoglobins absent (saturated with Hb and
removed from circulation)
 Features of increased red cell production
Reticulocytosis (due to premature release of rbcs from the BM)
Marrow hyperplasia

Features if damaged cells are present

Microspherocytes, schistocytes (rbc fragments) and some
elliptocytes
Increased osmotic fragility due to spherocytes
Shortened rbc survival
 Sometimes red cells are broken
down in the circulation
intravascular haemolysis
Free haemoglobin is released
Bound to haptoglobins
Excess resorbed by kidney glomerulus
Once kidney is saturated then free Hb enters
the urine haemoglobinuria
Breakdown of Hb in kidney leads to release
of iron complexed as haemosiderin - also
appears in urine haemosiderinuria
Diagram Extravascular haemolysis v
intravascular haemolysis
Clinical features of
haemolysis
Pallor of mucous membranes
Mild jaundice
Splenomegaly
Urine may turn dark on standing due to
urobilinogen
Ulcers around the leg (sickle cell disease)
Aplastic crisis erythropoiesis shuts
down increased anaemia
Lab findings
Features of increased red cell
destruction
Raised serum bilirubin (unconjugated and
bound to albumin)
Increase urobilinogen
Absent haptoglobins
Increased red cell production
Increased reticulocyte count
Erythroid hyperplasia of the bone marrow
Damaged red cells
Morphology cell fragments
Osmotic Fragility (OF) test
Enzyme, protein, DNA test (if due
to genetic abnormality)
 Intravascular
haemolysis

Sickle cell
disease
Membrane Defects
Hereditary Spherocytosis (HS)
Hereditary Elliptocytosis (HE)

You must know about the

structure of the red cell
membrane (Ch. 2)
Hereditary
Spherocytosis (HS)
Diagnosis
Often asymptomatic
Mild anaemia
Reticulocytosis (5-20%)
Microspherocytes present on film
Lab test see next slide
Lab test look
these up!
Osmotic fragility (OF) test
Dye binding assay rapid
fluorescent flow analysis
Eosin-5-maleimide
HS reduced mean channel
fluorescence due to membrane
bound band 3 protein
Does not detect ankyrin deficiency
HS Deficiencies
Spectrin
Band 4.2
Band 3
Ankyrin
 Clinical picture
Autosomal dominant (rarely
autosomal recessive)
Anaemia may or may not be
present
Jaundice may or may not be present
Splenomegaly often occurs
Look up on OMIM
Treatment for HS
Splenectomy
Reduces red cell destruction
Only if clinically indicated
(particularly in children)
anaemia
gallstones
leg ulcers
Hereditary
Elliptocytosis (HE)
Similar to HS except elliptocytes are
found on blood film
 Clinically mild usually
asymptomatic
Splenectomy rarely needed
Spectrin heterodimers dont
form heterotetramers
 Metabolic defects
eg. Glucose 6-phosphate
dehydrogenase (G6PD)
deficiency
G6PD reduces NADP to
NADPH
NADPH is needed for
glutathione production
Without G6PD cells are
vulnerable to oxidative stress
 Usually asymptomatic
400 million people world-wide
have G6PD def.
X-linked inheritance
Female carriers have increased
resistance to Falciparum
malaria (selective advantage)
 Symptoms
Acute haemolytic anaemia
Due to oxidative stress
Fava beans
Infection
Side effect of drug use (antimalarials, aspirin,
chloramphenicol)
These cause a haemolytic crisis in patients
Neonatal jaundice
Treatment and
diagnosis
Diagnosis involving G6PD assay
(also note Heinz bodies on blood
film)
Remove the cause of the crisis (eg.
stop drug treatment/no more Fava
beans/treat infection)
Transfusion if haemolysis is severe
Phototherapy for neonatal jaundice
and possibly exchange transfusion
Summary
See learning objective at
start of lecture