HAEMOLYSIS:

extravascular and
intravascular
Presenter; Gudila V.Shirima
Facilitator: Dr. BL Mtinangi
 contents
Overview
Causes of haemolysis
Extravascular haemolysis
Intravascular haemolysis
Clinical features of hemolysis
Investigations
Treatment
Conclusion
References
 overview
haemolysis means destruction of rbcs
occurs mainly extravascularly but can also
occur intravascularly when it is pathological.
A normal rbcs have a life span of 120 days.
When the rate of rbcs increases the bone marrow
is stimulated through the erythropoietin
mechanisms and the red cells concentrations are
maintained.
Suboptimal response is seen when there is:
1. lack of iron, B12 or folic acid
2. Red cell precusors are damaged
3. The marrow is infiltrated by the malignant cells
eg CLL
 Causes of rbcs destruction
After Rbc life span, haemolysis is
usually due to:
Cell membrane rigidity
Decreased cell enzyme activity
Decreased cell metabolism
Cell membrane damage
Apart from normal breakdown of aged
red blood cells, hemolysis is abnormal
in the living when it is due to:
blood transfusion reaction
 Causes of rbcs
destruction.
Hereditary disorders of Rbcs eg
SCD, Thalasemias, congenital
spherocytosis
Acquired haemolytic disorders
e.g. malaria ., by chemicals, venoms,
the toxic products of microorganisms
Haemolytic disease of the new
born ie , or Rh incompatibility of fetal
and maternal blood, a condition called
erythroblastosis fetalis
Autoimmune haemolytic diseases
 Extravascular haemolysis
The macrophages in the spleen, liver and
bone marrow remove the abnormal rbcs
from the circulation by phagocytosis.
Extravascular hemolysis is the most
common form of hemolytic anemia in
animals
Accounts for 80-90% of rbcs destruction
Reticuloendothelial system is responsible
for haemolysis
Extravascular haemolysis.
Hb is degraded into haem and globin
Globin is reutilized as a.a
Haem is degraded to pophyrin ring which
then is converted to choleglobin
Choleglobin is converted to biliverdin in
the presence of haem-oxygenase
enzyme
In the presence of biliverdin reductase,
biliverdin is converted to bilirubin, which
is released into the plasma.
 Cont
Bilirubin is bound to albumin in plasma and
transported to the liver where it is conjugated
with glucoronic acid to form conjugated
bilirubin (ie bilirubin glucoronide in presence
of an enzyme called glucoronile transferase.
When the rate of glucoronide formation by the
liver is exceeded , the conc. Of unconjugated
bilirubin rises in plasma ie
hyperbilirubinaemia.
Thro the bile duct, conjugated bilirubin is
transported to the intestines where further
conjugation by bacteria forms stercobilinogen.
 Extravascular
haemolysis.
Stercobilinogen is exposed to air in the
feaces and is oxidised to stercobilin

About 5% bilirubin is reabsorbed from

the intestine, transported to the kidney
as urobilinogen.
Urobilinogen is oxidised, when exposed
to air in the urine, to urobilin.
 Extravascular.

only a small amount of Hb escape to

plasma and can cause reduced serum
haptoglobin levels. Haptoglobin is a
glycoprotein which specifically binds
to Hb to prevent it from being filtered
by the renal glomerulus ie it become
larger when it is a Hb-haptoglobin
complex.
Extravascular..
 Intravascular haemolysis
Destruction of rbcs occurs in plasma
Accounts for 10-20% of rbcs destruction
The Hb realesed from intravascular
haemolysis of rbcs binds to haptoglobin
Hb haptoglobin is rapidly taken by
hepatoctes, therefore haptoglobin level
is reduced in plasma (normal level is 0.3
to 2.0g/l
When Hb binding capacity of
haptoglobin is exceeded, free Hb is
found in plasma ie haemoglobinaemia
 Intravascular
Some of the free Hb forms dimers which
passes thro the glomerulus causing
haemoglobinuria
Other dimers are taken by renal tubular
cells and are converted to haemosiderins ie
this is a form in which Fe is stored in cells.
When haptoglobin capacity to bind Hb is
exceeded, free Hb is converted to
methaemoglobin which breaks down to
ferrihaem and globin.
 Cont
Ferrihaem +haemopexin to form
ferrihaem-haemopexin complex,
preventing the glomerular filtration of the
small ferrihaem molecule, hence lowering
the plasma haemopexin levels.
NB: haemopexin is a glycoprotein,
synthesized in the liver and specifically
binds to free haem.
Some ferrihaem binds albumin forming
methaemalbuminaemia.
 Clinical features
General clinical features includes:
Features of anaemia
Jaundice
Splenomegaly
Bone defomities
 investigations
Extravascular haemolysis
Hyperbilirubinaemia
Low levels of haptoglobin

Intravascular haemolysis
Peripheral blood smear microscopy:
Reticulocytes, spherocytes , schizocytes may
be seen
Methaemalbuminaemia (imparts golden
to brown colour in plasma)
Haemoglobinaemia
 Haptoglobin levels are decreased
Direct coombs test is positive
haemosiderin in the urine indicates
chronic intravascular hemolysis.
 treatment
Symtomatic
Definitive Rx depends on the cause:
Blood transfusion
Splenoctomy
steroids
 conclusion
Haemolysis is the rbcs breakdown
It takes place mainly extravasculary,
while the minority occurs
intravascularly
It is normal when the aged rbcs are
destroyed but may be harmful when
it exceeds the usual rates .
 References

Lecture notes on haematology,by N.

C.Hughes-Jones and S. N. Wickramasinghe
Guyton 11th edition
Lecture notes by DR. BL Mtinangi
cause of anemia (in anemia (disease))
place in blood metabolism (in blood
(biochemistry): Red blood cells
(erythrocytes); in blood group: Hemolysis
Clinical haematology in medical
practce.5th edition