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HbF

S

C

HbA

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Bio-Rad Variant NBS

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FAS

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Thal major

Cannot justify screening programme

No early mortality

Most B Thal major picked up by absent A

band

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Sickle cell disease is the most common genetic condition in England,

with higher prevalence than cystic fibrosis

Highest prevalence occurring inpeople of African and Afro-Caribbean origin, with birthprevalence as high as 1 in 300

in some areas (recessive)

Affects an estimated ~12,500individuals

Reported in more than 1 in2,000 live births over 300 new

births each year in England

Most common inherited disease

of Caucasians (recessivelyinherited)

Affects an estimated ~8,400individuals

Reported in more than 1 in

2,500 live births

Sickle Cell Disease1 Cystic Fibrosis2

In the UK, sickle cell disease is as prevalent as cystic fibrosis theonly difference is in the ethnic group most likely to be impacted

1. Source: Development of transcranial Doppler screening services in England, Dianne Addei, Nov 20072. Source: Specialist Services National Definitions Set (2nd Edition)

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Neonatal Screening for Sickle

Cell Disease Heel-prick blood spot taken by midwife at 5-7

days

Blood spot sent to centralised neonatal

screening laboratories 12-13 in England Spot analysed by HPLC or IEF

Hb variants confirmed by alternative method

Results sent out to Child Health, sickle cell

counsellors, named paediatricians, dependingon local arrangements

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Pitfalls

S/HPFH

Post transfusion

New mutations!!

Thal intermedia

Asylum seekers

Family blame

Other genetic disease

Anger if dont realise have been tested

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distribution

1% 7%

13%

45%

2%

8%

6%

6%

8%

4%North East

Yorkshire & TheHumber

West Midlands

London

SW

NW

E Mids

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Infection in sickle cell disease

600-700-fold increase in susceptibility to

pneumococcal sepsis in first 2 years

3 RCTs of penicillin prophylaxis show significant

reduction in pneumococcal sepsis in under 5s Penicillin resistance increasing

Increased susceptibility to other encapsulated

organisms - haemophilus, meningococcus Seek advice if child febrile

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Pneumococcal prophylaxis

Penicillin

Duration: lifelong

throughout childhood

Immunisation

Prevenar conjugate vaccine 7 valent covers 80% of

serotypes causing disease

Pneumovax 23 valent vaccine covers 90% of serotypes

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Severity of SCD

NEJM 2000

Dactylitis

Hb

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CVA in SCDEpidemiology

Childhood stroke in BaltimoreEarley 1998 overall incidence 1.3/100,000/y

SCD: 39% 285/100,000/y

CSSCD HbSS CVA 0.61/100 pt yrs

250 times more common than other children

25% of SS & 10% of SC stroke by 45

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Rates of infarctive and haemorrhagic stroke

in HbSS patients by age Ohene-Frempong 1998

10 20 30 40 50

0.0010

0.0040

0.0025

Ageyears

Hazard Function

HaemorrhagicStroke

IschaemicStroke

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TIAs, Stroke, Coma9y girl HbSS, previously well, Top of class

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Moyamoya

Severe stenosis or occlusion of the terminal

internal carotid artery / proximal middle

cerebral artery with collateral vesselsYoon 2000

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MRI findings

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Effects of Iron Chelators on

Liver Iron Concentration (LIC)

Deferasirox 5 10 20 30

Doses (mg/kg/d)

-10

-8

-6

-4

-2

0

2

46

8

10

MeanC

hangeinLIC

(mg

Fe/gdw)

SCD -thalassaemia, MDS,

other rare anaemias)

-thalassaemia

LIC: Good control with desferrioxamine or deferasirox;inconsistent effects with deferiprone

Deferasirox shown to maintain and reduce LIC in phase 2/3 clinical trialsin adult and paediatric patients (12-month efficacyLIC)

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STOP trial

Stroke Prevention Trial in Sickle CellAnaemia

No previous history of stroke Screened on 2 occasions for TCD velocity

>200cm/s 130 children randomly assigned to

transfusion / supportive care 10 cerebral infarctions in supportive care

vs 1 intransfusion group (median FU

21 months)Trial terminated early

Adams, MD et al, NEJM 1998

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STOP

Problems

Chronic transfusion regime

Sensitisation 10%

15% stopped transfusion unacceptable

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UK childhood stroke guidelinesPrimary prevention

Children with haemoglobin SS or So

thalassaemia should be screened yearly from

the age of 12 months for internal carotid artery

or middle cerebral artery velocity >200cm/susing appropriately trained personnel and

transcranial Doppler ultrasound (A)

Children with internal carotid artery/middle

cerebral artery velocity >200cm/s should beoffered long-term blood transfusion (A)

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There are a number of sites, particularly in London, where there arehigh numbers of children with sickle cell disease and no on-site TCD

facility

Milton Keynes

Cambridge

Luton

Sheffield

Nottingham

Leicester

Northampton & Kettering

Newcastle

Leeds

Manchester

Liverpool

Oxford

Portsmouth

Bristol

Birmingham

Reading

Southampton

Plymouth

Royal London

Great Ormond St

Whipps Cross

Central Middlesex

Whittington

University College

Royal Free

North Middlesex

St Marys

Ealing

Hillingdon

Kings College

Guys & St.Thomass

University Hospital, Lewisham

QE Hospital,Woolwich

St George

St Helier

River Thames

London

Site with 50-100 children with sickle cell and no TCD facility

Site with >100 children with sickle cell and no TCD facility

Correlation between # children with sickle cell and lack of TCD provision

YBHR

London.

MedwayMaritime Hosp

Mayday University Hospital

Source: Sickle Cell Anaemia Survey (May, 2008)

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Therapy available/drivers

Improved symptomatic care

Transfusion

Hydroxyurea

HSCT

Improved psychologic and social care

Drive from clients and health professionalsto improve standards

Various NHS initiatives ,NSF etc

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Increasing emphasis on pro-active

intervention

Identifying bad sickle looking for--

Abnormal TCD

Oxygen saturations

Early renal/lung disease Falling school performance

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?

?

?

UK Thalassaemia

Register

1999:807 patients / 164

doctors

71 only 1 attending

77 2 9 patients

8 10 30

4 > 50

11 doctors @ 9 sitessaw 20 ormore

patients

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The Process

Define population at risk demographics,numbers and disease

what exists at present

what do we aspire to ,define standards what is the gap

how to move from existing services to

new clinical units how to maintain /continually improve

services

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Conclusions

Services best described as patchy

Little organisation about who does what

Particular concern is links or not of smallunits

Urgent need for standards and agreed

networks of care

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What existed in 2004

No nationally organised network of care

for patients with Haemoglobin disorders

Ad hoc arrangements around centres with

interest and population

No data collection

No standards of care

Screening classic- chicken before egg !!

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Standards

Thalassaemia major completed 2006

sponsored by Thalassaemia society

multidisciplinary group backing of DH

main theme is promoting the

development of a patient and familycentred service .

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Sickle Standards

Again produced by multidisciplinary group

including patient representative group

Sickle cell society

Themes very similar to Thal

Define specialist units and relationship to

smaller units

Defines good /best practice

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Sickle (cont )

Specifies penicillin prophylaxis

Pneumococcal immunisation targets

TCD targets Failsafe arrangements

Again emphasis is on building on existing

resources to ensure all have equitableaccess to both local and specialist care

and that the role of each is defines

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Clinical network arrangements:

1)Annual review of all affected infants by the specialistcentre is recommended.

2)formalise existing informal networks is beingdeveloped with support from the DOH, BSH, the UK

Forum Haemoglobin Disorders, the RCPCH

3)Support services for timely FU &Rx.

4)Experience from the USA shows that the main reasonfor the failure of the screening programme is the failureto ensure that identified infants are enrolled in aprogramme of treatment and care, or having beenenrolled are subsequently lost to follow-up.

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Specialist centres

Local unit has designated centre

Annual review at specialist centre

Consideration of alternative treatment

options such as hydroxyurea, transfusion

programme, CBT, SCT

Links to specialist services

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Specialist services

ENT

Stroke screening, neurology

Psychology - educational, clinical, CBT

General surgery + anaesthetics

Orthopaedics

Endocrinology

Ophthalmology

HSCT

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Local Inpatient management

protocolsGeneral

Pain relief

Hydration

Antibiotics

Oxygen saturations

Blood transfusion

Specific

Acute chest syndrome

Stroke

Splenic sequestration + aplastic crises

Priapism

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Governance

need to move to a system of appraisal of

networks

Quality standards defined

Pilot appraisal undertaken proposed to undertake every 2 years

Who will be appraisers ? Must involve wide

group of health professionals Who will train ?

Who will pay ?

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Cancer parallels

In West Midlands 150 new cancers inchildren pa treatment lasts 1-3 years

6-8 consultants with nursing , psychology

and many other support services Organised levels of care and Appraisal,

high on public/managerial horizon

Haemoglobinopathy numbers on activetreatment not that much less but huge gulfin resources available

Th b f hi h i dd i i th h t

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There are a number of areas which require addressing in the short-

term in order to improve treatment of sickle cell disease

Enhance service

provision

Improve training& education

Raise the profile

Address gaps in TCD provision initially on Regional basis

Address shortages in nursing (both hospital and community)and trained TCD ultrasonographers

Formulate a plan for direct access to medical advice/care

Improve education particularly for non-haematologists:- GPs- A&E doctors- Anaesthetists

(we are already addressing education of doctors, scientists and nurses)

Build a comprehensive, national database for capturing andanalysing prevalence and treatment data and outcomes (NCEPOD)

(has been built but we need to encourage roll-out)Capture key data

Provide bettercoordination

Ensure full involvement of key stakeholder groups:- Royal Colleges- Royal College of Nursing- Royal College of Paediatricians

Biannual then annual meetings of clinicians with key stakeholders ?advertising campaign

Introduce regional and national roles for coordinating provision ofservices and best practice sharing

(initially using experience of DH (blood policy/clinical services) and then via exemplar sites)

Involve the SC society who have done much in involving and

informing patients

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Outstanding issues

Must move towards defining how an

appraisal/audit of the clinical networks

might work

Data collection probably should be inked

to above ,live adverse event reporting

Must engage with local service planners

and commissioners develop collaborativecommissioning pathways .