Transcript NEONATAL SCREENING FOR HAEMOGLOBINOPATHY

Laboratory Perspective of
screening
Joan Henthorn
Central Middlesex Hospital
London UK
July 2009
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Screening versus Diagnosis
Screening – systematic testing of a whole
or selected population
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Uses fast throughput technique
Often used to target certain conditions
Diagnosis – the intensive investigation of a
individual or family using many different
techniques to arrive at a conclusion
All screening
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AIMS OF SCREENING
NEONATAL
To detect individuals who will
benefit from early diagnosis
and treatment, thus reducing
morbidity and mortality
ANTENATAL
To target at risk couples and
offer genetic choice
Cascade family screening
To offer family screening
To target at risk families and
offer future genetic choice
To detect individuals with
sickle cell syndromes who will
benefit from diagnosis and
treatment, thus reducing
morbidity and mortality
To allow better Health Service
resource planning
Antenatal and neonatal
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The aim of the programme is to detect
the following:
NEONATAL
SS
SC
SD
SO-ARAB
SBETA
Antenatal and neonatal
ANTENATAL
S
C
D-Punjab
E
O-Arab
Beta thal trait
Delta/beta thal trait
Alpha0 thal trait
Lepore
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Neonatal Screening Programme England
Universal
Use dried blood spots
Contemporaneously with PKU and Thyroid
First line screen to be either HPLC or IEF
Second line confirmation to be either IEF or HPLC
Neonatal
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What we cannot detect with Neonatal
Screening
Beta thalassaemia trait
Some cases of beta thalassaemia intermedia
Some rare variants
HPFH
Neonatal
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Antenatal Screening Programme England
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Areas are defined as high or low
prevalence
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High prevalence is defined as a foetal
prevalence rate for sickle cell disease of
1.5 or more per 10000 pregnancies
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Testing regimes for high and low prevalence
areas
High prevalence
Low prevalence
All samples tested for
thalassaemia and Hb variants by
laboratory methods
All samples screened for
thalassaemia using red cell
indices
Family origin question used to
assess the need for partner
testing in cases of possible alpha0
thalassaemia
All women assessed for
laboratory testing for variants
by use of the family origin
question
Family origin question used to
assess the need for partner
testing in cases of possible
alpha0 thalassaemia
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Family Origin Questionnaire
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Outline of the investigation scheme for haemoglobin
disorders
FBC,
HPLC/Electrophoresis
MCH,A2,F normal,
No structural variant seen,
no evidence of erthyrocytosis
or haemolytic anaemia.
Reduced MCH
Raised Hb A2
Normal/low A2,
raised F
Probably normal,
but a silent
mutation
cannot be excluded
Beta
Antenatal
Delta/beta
Variant detected
Normal A2 and F
Possible
Fe def
IEF,
Cellulose acetate,
Acid electrophoresis
as appropriate.
Sickle test.
Possible
alpha thal
Rare cases
of beta thal
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Outline of the investigation scheme for haemoglobin
disorders
FBC
and information from FOQ
MCH normal,
No structural variant seen,
or test not indicated by FOQ
no evidence of erthyrocytosis
or haemolytic anaemia.
Raised Hb A2
Probably normal,
but a silent
mutation
cannot be excluded
Antenatal
Beta
Reduced MCH
HPLC/Electrophoresis
indicated by FOQ
HPLC/Electrophoresis
Variant detected
Normal/low A2,
raised F
Delta/beta
Normal A2 and F
IEF,
Cellulose acetate,
Acid electrophoresis
as appropriate.
Sickle test.
Possible Possible Rare cases
Fe def alpha thal of beta thal
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Risk assessment of using the algorithm
‘Silent’ or ‘near silent’ -thalassaemia trait
Possibly some -thalassaemias obscured by severe
iron deficiency anaemia
0thalassaemia occurring outside the defined at risk
groups
Dominant haemoglobinopathies in the partner when
the woman is AA, - very rare and should be suggested
by the family history
Some women may not be tested if the ethnic group is
incorrectly stated or hidden.
-thalassaemia obscured by B12/folate deficiency or
liver disease
Hb S, C, DPunjab, E, OArab in the North-European ethnic
group
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Challenges - General
What should we report?
How should we report it?
How should we report it if we don’t know
exactly what it is?
How should we convey what we can’t
detect?
All screening
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Challenges - Neonatal
Transfused babies
Premature babies
Older babies/ Old samples
Gamma chain variants
Variants on HPLC and not IEF
Variants on IEF and not on HPLC
Conflicts between child’s result and parental
results
Neonatal
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Challenges - Antenatal
A2 variants
Alpha/beta interactions
Silent beta thalassaemia trait
Alpha thalassaemia
B12/Folate/Iron deficiency
Borderline raised A2 values
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Antenatal
HIV
Sporadic
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What we aim to provide
Agreed turnaround times
Readable reports with explanations and
recommended actions
Advice if needed
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Report elements (Antenatal)
The numeric data
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FBC (Hb,MCV and MCH)
The A2
Any Variants found
• Interpretation of the results
• The action recommended
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What we expect to receive
Properly labelled samples and legible
forms
Partners correctly identified
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LINKAGE – the final frontier
The antenatal and neonatal screening in
England are intended to be linked programmes
For each baby, the antenatal results should be
available at the time of the neonatal screen.
The neonatal result should be used to
crosscheck that each couple had the appropriate
antenatal screening offered and carried out.
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