Laboratory Perspective of screening

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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
• 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
• Cascade family screening
• To target at risk families and offer future
  genetic choice
• To allow better Health Service resource planning

• ANTENATAL
• To target at risk couples and offer genetic
  choice
• To offer family screening
• To detect individuals with sickle cell syndromes
  who will benefit from diagnosis and treatment,
  thus reducing morbidity and mortality

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
• S
• C
• D-Punjab
• E
• O-Arab
• Beta thal trait
• Delta/beta thal trait
• Alpha0 thal trait
• Lepore

Antenatal and neonatal
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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

• Areas are defined as high or low prevalence
• 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
• All samples tested for thalassaemia and Hb
  variants by laboratory methods
• Family origin question used to assess the need
  for partner testing in cases of possible alpha0
  thalassaemia

• Low prevalence
• All samples screened for thalassaemia using red
  cell indices
• 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
Antenatal
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Outline of the investigation scheme for
haemoglobin disorders
Antenatal
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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 dont know exactly
  what it is?
• How should we convey what we cant 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 childs 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
• HIV
• Sporadic

Antenatal
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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
• 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.