Haemoglobinopathies
J Hall
Haemoglobinopathy Counsellor
There are approximately 1200
different types of Haemoglobin
Normal Haemoglobin:
consists of
• Four Globin chains each holding a molecule
that contains iron
• Globin A complex protein containing a
precise number of amino acids
Adult Haemoglobin
• (Hb AA) = 4 Globin Chains
• 2 Alpha
• 2 Beta Globin Chains
Fetus and New Born Infant
Mainly fetal haemoglobin (Hb F)
• 2 Alpha
• 2 Gamma Globin Chains
Production of the three types of
Globin Chains
• Controlled by three different pairs of genes
• Alpha Genes are active in fetal and adult
life
• Gamma Genes active in fetal life then
replaced by Beta Genes about the time of
birth
Abnormalities or Variations within the
Globin Chains
In Thalassaemia leads to an
• Absence of production or
• Diminished production of Haemoglobin
Thalassaemia
• Reduced production of Beta Globin
chains
• The blood cells are small Microcytic
• Do not contain as much iron Hypochromic
Haemoglobinopathies
• Thalassaemia is an inherited blood disorder
affecting the production of normal adult
Haemoglobin. It mainly, but not exclusively
affects people from black and minority ethnic
groups.
• The frequency of many Haemoglobinopathies
including Thalassaemia relates to the geographic
distribution of MALARIA.
• Estimated that over 6% of the population of
England and 11% of births are in groups at risk
of Haemoglobin disorders.
Thalassaemia Trait
Carrier state for the Disorder often confused
with Iron deficiency due to reduced MCV and
MCH
• Check serum Ferritin
• Normal Hb A2 1.5-3.5
• Hb A2 above 3.3-Diagnostic
Most Common
Haemoglobinopathy Traits
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Beta Thalassaemia Trait
Haemoglobin E Trait
Haemoglobin D
Haemoglobin C
Haemoglobin S
• Alpha-Zero Thalassaemia Trait
• Alpha-Plus Thalassaemia Trait
Mode of Inheritence
Known as Autosomal Recessive
disorders
When one parent carries the trait
• In each Pregnancy
• There is a 1 in 2 chance that the child will
be a carrier
• There is a 1 in 2 chance that the child will
be normal
Where both parents are
carriers of the disorder
• In each Pregnancy
• There is a 1 in 4 chance the child will have
the disorder
• There is a 1 in 4 chance that the child will
be normal
• There is a 1 in 2 chance that the child will
be a carrier of the trait
Major Haemoglobin Disorders
• Beta Thalassaemia Major
• Haemoglobin E/Beta Thalassaemia
• Alpha Zero Thalassaemia
(Hydrops Fatalis)
• Haemoglobin H Disease
• Sickle Cell disorders
Major Haemoglobin Disorders
The major Haemoglobin disorders are life
long illnesses. Most are forms of anaemia
and some more severe than others, they fall
in to two groups:
• Thalassaemias
• Sickle Cell Disorders
Thalassaemia
• Most common single gene disorder
• First recognised in 1925 by Thomas Cooley
• Also known as Cooley’s Anaemia
Later it was noticed that many patients with
the disorder came from the mediterranean
region hence the Greek word “Thalassa”
meaning from the sea.
Prevalence
• Mainly found in people with origins from
Pakistan, India, Bangladesh, Sri-Lanka and
countries from around the mediterranean.
• In the UK 78% of babies with the
disorder are Asian
Beta Thalassaemia
• Most Common type of Thalassaemia
• A disorder of the Beta Globin genes,
affecting adult Haemoglobin.
• Beta Thalassaemia trait in the carrier form
has no affect upon the individuals general
health
Beta Thalassaemia Major
• Symptoms arise from about 3-6 months of
age
• Children with Thalassaemia Major are
healthy at birth due to the presence of fetal
haemoglobin
• They become severely anaemic
(Typical Haemoglobin level below 7gm/dl)
before they reach 2 years of age
Untreated children with
Thalassaemia Major
are
• severely anaemic
• failure to thrive
• Irritable
• Stunted growth
• Enlarged liver and spleen
17 year old girl with Beta
Thalassaemia Major
• Showing reduced stature Height 134cms
and delayed pubertal development.
• Since circulating growth hormone levels
are usually normal, the lack of growth is
due to endocrine organ failure.
Skeletal Changes
• The Bone Marrow expands greatly as it tries
(uselessly) to make red cells. This weakens
and distends the bones, particularly the
bones of the face and skull.
• This is why the children with Thalassaemia
Major develop a characteristic facial
appearance.
Splenic Changes
• During the course of the disease the spleen,
which normally destroys the old red blood
cells begins to destroy young red blood cells
worsening the anaemia.
Mortality
• Most untreated children die from anaemia
or infections before 2 and at most 5 years of
age.
Treatment
• The current treatment for Thalassaemia
Major is blood transfusions every 4 weeks
for life.
• This results in good health mainly in the
short term.
Side effects of this treatment
• Blood contains a great deal of iron which
gradually accumulates in the body.
• Iron can damage the liver, heart and other
major organs. Unless it is removed it can
cause premature death through organ
failure. The most common being Heart
failure, this occurs between 16-30 years of
age.
Drug Treatment
• Iron can be removed by a drug called
Desferrioxamine, it is infused
subcutaneously through a fine needle
attached to a small pump or syringe driver.
• Its action is to bind with the iron and then
be excreted in the urine.
• This procedure takes 8-12 hours and has to
be carried out 5-6 times a week.
Compliance
• Having the treatment regularly patients with
Thalassaemia Major can live up to 50 years
plus leading a reasonably normal life.
• However this form of treatment is very hard
to comply with and as no ill effects are
experienced until organ damage is sustained
the main factor contributing to premature
death particularly in young people is
• Organ failure due to Non-compliance.
Innovations in current
Drug Therapy
• Oral chelator’s _ L1 Deferiprone and the latest
Exjade Deferasirox.
• (L1 has been on the market for 10 years initially
on a named patient basis only but is now available
and commonly used in combination therapy with
Desferioxamine
• Exjade has recently been developed and trialled,
relatively free of side effects, the iron is
excreted predominately in the faeces.
Innovations in Current Treatment
• Combination drug therapy specific to the
individuals need.
• T2* MRI and more recently the Ferriscan
technique specific in identifying organs
which are affected by iron overload
• Baxter Pumps
• Home delivery of equipment and
preparations ready to use
Bone Marrow Transplant
• This procedure is available to children
preferably below 7 years of age who have a
• Matching HLA (Human Leucocyte
Antigen).
• Genotypically matched sibling only
• About 30% of patients will have a sibling
match
Complications
• Arise due to Graft V Host Disease, which may be
acute or chronic.
• A life threatening disorder affecting the skin,
gastro-intestinal tract, liver and with rejection of
the bone marrow.
• The mortality and morbidity rate is between 93%
and 91% transplant related mortality of 7%
• At risk factor ( Liver disease) & poor chelation
history, disease free survival 79% & 58% with
10% risk of death during proceedure
Alpha Plus Thalassaemia
(Otherwise known as Alpha Thalassaemia Trait)
• A carrier state of one or two gene deletion
• This is a mild form of Alpha Thalassaemia
• It can be difficult to identify as the
haemoglobin is only minimally lowered and
electrophoresis is normal
• Definitive diagnosis requires DNA analysis
• At present all our DNA tests are carried out
at a specialist laboratory in Oxford.
Alpha Zero Thalassaemia Major
• Otherwise known as Hydrops Fetalis or
Bart’s Hydrops Fatalis
• This occurs when the fetus inherits
Alpha zero Thalassaemia from both parents
• The fetus has no Alpha genes and can not
make an alpha chains
• This means that it cannot make any fetal
haemoglobin.
Alpha Zero Thalassaemia
• This is a fatal anaemia
The Fetus
• Develops normally for the first 5 months of
pregnancy, sometimes longer then growth
slows, its heart begins to fail and its body
and the placenta becomes swollen with
fluid.
The Mother
• Can develop Pre-Eclampsia or even
Eclampsia
• The baby may be born at any time between
the 28th and 42nd week of pregnancy
Complications at delivery
• Include obstructed labour and excessive
bleeding, if the baby has not died in the
womb it will die shortly after birth.
Alpha Zero Thalassaemia Major.
• There is no treatment
• For couples at risk of having a baby with
this disorder, there is a 1 in 4 chance of a
still birth or neonatal death in every
pregnancy
PREGNANCY
Beta Thalassaemia Major
• Early booking with joint management by
the Obstetrician and Haemotologist
• Correction and prevention of anaemia
• Serial scans for fetal growth
• Prompt treatment of infection
The Fetus
The fetus is not directly affected in Utero
by Beta Thalassaemia as it is protected by
fetal haemoglobin.
Symptoms start to arise when the infant
is unable to produce normal adult
haemoglobin from six months of age
Ante- Natal Diagnosis
• If both partners are Carriers
• Pregnancy identified as “At Risk”
• Chorionic villus sampling carried out
between 10-12 weeks
• Amniocentesis from 15 weeks
• Fetal blood sampling some times carried out
in late pregnancy for rapid DNA analysis
Chorionic Villus Sampling
• Has the advantage of being carried out in
the 1st trimester of pregnancy.
• The timing falls within the limits set for a
(Therapeutic Abortion) in many religons
and reduces the emotional stresses of PreNatal diagnosis.
LABORATORY SCREENING
• All Antenatal women identified or known to have
• Haemoglobinopathy should be treated as urgent
The midwife informed by the paper copy stating
the disorder or carrier status.
• The counsellor by telephone in the first instance
and followed with a paper copy .
• Time is of an essence to allow for partner
testing and PND if required.
Pre-Natal Diagnosis
• It is well documented that the most
important factors influencing a couples
choice for or against PND
• Severity of the disorder
• Stage of pregnancy at counselling
Counselling
Preferably before Pregnancy
• Sensitive to the Needs of the couple
Issues such as
• Level of Risk
• Pre -natal diagnosis and in the case of an
affected child informed choice and
support
Points to remember
• If it is a subsequent pregnancy we cannot assume
that the husband/partner is the same.
• That they are aware of their carrier status or if they
are, have communicated it to the midwife
• That they have booked with the midwife early or
in plenty of time for PND
• Ideally the women should have been booked,
counselled, partner tested and referred for
Prenatal Diagnosis by week 11-13
Issues
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Communication
Ethical
Economic
Stigmatisation
Culture