Download Haemolytic anaemias2

Inherited and acquired
haemolytic anaemias
Dr. Suhair Abbas Ahmed
Hereditary haemolytic anaemias
• Membrane defects – congenital
spherocytosis
• Metabolic defects – G6PD enzyme
deficiency
• Haemoglobin defects
– Qualitative defects – sickle cell anaemia
– Quantitative defects – Thalassaemia
Membrane defects
Hereditary spherocytosis
South East Asian ovalocytosis
Hereditary spherocytosis (HS)
• It is the most common hereditary
haemolytic anaemia in North
Europeans.
Pathogenesis of HS
• It is caused by a defect in the proteins
involved in the interactions between the
membrane cytoskeleton and the lipid
bilayer of the red cell. ( ankyrin,
spectrin and pallidin).
Clinical features
• The inheritance is autosomal dominant.
• Rarely it may be autosomal recessive.
• The anaemia may present at any age
from infancy to old age.
• Jaundice is fluctuating.
• Splenomegaly occurs in most of the
patients.
• Pigment gall stones are frequent.
Haematological findings in HS
• Anaemia is usual.
• Reticulocytosis 5-20%
• Microsherocytes are seen in the blood
film. (densely staining with smaller
diameters than normal red cells).
Reticulocytosis
• Reticulocytosis is a
feature of increased
red cell production.
• New methylene blue
is used to stain the
reticulocytes
Other investigations
• The classic finding is that the osmotic
fragility is increased.
• Autohaemolysis is increased and
corrected by glucose.
• Direct antiglobulin test is normal.
Autohaemolysis test in HS
There is increased
haemolysis in the
patient in
comparison with the
control. Glucose has
given partial
correction.
Treatment
• The principal form of treatment is
splenectomy although this should not
be performed unless clinically indicated
because of the risk of post-splenectomy
sepsis, particularly in early childhood.
• Folic acid is given in severe cases.
South-East Asian ovalocytosis
• This is common in Malaysia, Indonesia
and the Philippines.
• It is due to Band 3 protein abnormality.
• The cells are rigid and resist invasion by
malaria parasite.
• Most cases are asymptomatic.
Blood film in hereditary
stomato-ovalocytosis
• basophilic stippling
and numerous
stomatocytes.
Defective red cell metabolism
G6PD enzyme deficiency
Pyruvate kinase deficiency
• G6PD functions to
reduce nicotinamide
adenine dinucleotide
phosphate (NADPH)
while oxidizing
glucose-6phosphate.
• NADPH is needed for
the production of
reduced glutathione
(GSH) which is
important to defend
the red cells against
oxidant stress.
G6PD deficiency
• More than 400 variants due to point
mutations or deletions of the enzyme
G6PD have been characterized which
show less activity than normal.
• Worldwide over 400 million people are
G6PD deficient in enzyme activity.
Clinical features
• G6PD deficiency is usually
asymptomatic.
• Neonatal jaundice.
• Acute haemolytic anaemia in response
to oxidant stress: drugs, fava beans or
infections.
G6PD deficiency
• The inheritance is sex-linked, affecting
males, and carried by females.
• The main races affected are in West
Africa, the Mediteranean, the Middle
East, and South East Asia.
Diagnosis
• Between crises blood count is normal.
• The enzyme deficiency is detected by
– One of a number of screening tests or
– By direct enzyme assay on red cells.
• During the crisis, the blood film may show
contracted and fragmented cells, bite and
blister cells.
• Enzyme assay may give a false normal level
in the phase of acute haemolysis.
• There are feaures of intravascular haemolysis.
G6PD deficiency
• The blood film shows
irregularly contracted
cells [deep red arrows]
and sometimes
hemighosts [deep blue
arrow] in which all the
haemoglobin appears to
have retracted to one
side of the erythrocyte.
Treatment
• The offending drug is stopped.
• Any underlying infection is treated.
• Blood transfusion, if necessary, for
severe anaemia.
Defective haemoglbin
Sickle cell anaemia
Defective haemoglobin
Sickle cell anaemia
• It results from single base change in
the DNA coding for the amino acid in
the sixth position in the b-globin chain.
• This leads to an amino acid change
from glutamic acid to valine HbS will
be formed instead of the normal Hb.
Sickle cell anaemia
• Hb S is insoluble and forms crystals when
exposed to low oxygen tension.
• Deoxygenated sickle Hb polymerizes into long
fibrils.
• The red cells sickle and may block the
different areas of the microcirculation or large
vessels causing infarcts of various organs.
• It is widespread in Africa.
Laboratory findings
• Hb is usually 6-9 g/dl.
• Sickle cells and target cells occur in the
blood.
• Screening tests for sickling are positive.
• Hb electrophoresis in Hb SS, no Hb A is
detected. The amount of Hb F is
variable 5-15%.
Sickle cell anaemia
• Sickle cells in sickle
cell disease.