1. jshmay09 Laboratory Perspective of screening Joan Henthorn Central Middlesex Hospital London UK July 2009

2. jshmay09 Screening versus Diagnosis Screening – systematic testing of a whole or selected population Uses fast throughput technique Uses fast throughput technique Often used to target certain conditions 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

3. jshmay09 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

4. jshmay09 The aim of the programme is to detect the following: NEONATALSSSCSDSO-ARABSBETAANTENATALSCD-PunjabEO-Arab Beta thal trait Delta/beta thal trait Alpha 0 thal trait Lepore Antenatal and neonatal

5. jshmay09 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

6. jshmay09 Beta thalassaemia trait Some cases of beta thalassaemia intermedia Some rare variants HPFH What we cannot detect with Neonatal Screening Neonatal

7. jshmay09 Antenatal Screening Programme - England Areas are defined as high or low prevalence 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 High prevalence is defined as a foetal prevalence rate for sickle cell disease of 1.5 or more per 10000 pregnancies

8. jshmay09 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 alpha 0 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 alpha 0 thalassaemia

9. jshmay09 Family Origin Questionnaire

10. jshmay09 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. Probably normal, but a silent mutation cannot be excluded Reduced MCH Raised Hb A2 Beta Normal/low A2, raised F Delta/beta Normal A2 and F Possible Fe def Possible alpha thal Rare cases of beta thal Variant detected IEF, Cellulose acetate, Acid electrophoresis as appropriate. Sickle test. Antenatal

11. jshmay09 Outline of the investigation scheme for haemoglobin disorders HPLC/Electrophoresis Variant detected Antenatal

12. jshmay09 Risk assessment of using the algorithm ‘Silent’ or ‘near silent’  -thalassaemia trait Possibly some  -thalassaemias obscured by severe iron deficiency anaemia  0 thalassaemia 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, D Punjab, E, O Arab in the North-European ethnic group

13. jshmay09 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

14. jshmay09 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

15. jshmay09 Challenges - Antenatal A2 variants Alpha/beta interactions Silent beta thalassaemia trait Alpha thalassaemia B12/Folate/Iron deficiency Borderline raised A2 values HIV HIV Sporadic Sporadic Antenatal

16. jshmay09 What we aim to provide Agreed turnaround times Readable reports with explanations and recommended actions Advice if needed

17. jshmay09 Report elements (Antenatal) The numeric data FBC (Hb,MCV and MCH) FBC (Hb,MCV and MCH) The A2 The A2 Any Variants found Any Variants found Interpretation of the resultsInterpretation of the results The action recommendedThe action recommended

18. jshmay09 What we expect to receive Properly labelled samples and legible forms Partners correctly identified

19. jshmay09 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.