Intervention Review

You have free access to this content

Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease

  1. Winfred C Wang1,*,
  2. Kerry Dwan2

Editorial Group: Cochrane Cystic Fibrosis and Genetic Disorders Group

Published Online: 14 NOV 2013

Assessed as up-to-date: 1 NOV 2013

DOI: 10.1002/14651858.CD003146.pub2


How to Cite

Wang WC, Dwan K. Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD003146. DOI: 10.1002/14651858.CD003146.pub2.

Author Information

  1. 1

    St Jude Children's Research Hospital, Department of Hematology, Memphis, Tennessee 38105, USA

  2. 2

    University of Liverpool, Department of Biostatistics, Liverpool, England, UK

*Winfred C Wang, Department of Hematology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 800, Memphis, Tennessee 38105, USA. Winfred.Wang@stjude.org.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 14 NOV 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
STOP 1998

MethodsParallel RCT.


Participants130 children with HbSS or HbSβ0Thal, at high risk of stroke as predicted by TCD.

Transfusion: 63

Standard care: 67


InterventionsTransfusion (HbS < 30%) or standard care.


OutcomesDeath, stroke (intracranial haemorrhage or cerebral infarction).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation by permuted blocks.

Allocation concealment (selection bias)High riskIt was not possible to conceal whether the patient was randomised to receive transfusion or not.

Blinding (performance bias and detection bias)
Suspected stroke
High riskIt was not possible to blind the treating physicians, the centre coordinators or the participants.

Blinding (performance bias and detection bias)
All other outcomes
Low riskA blinded panel of neurologist adjudicators made the decision of whether an event should be classified as a stroke (cerebral infarction or intracranial haemorrhage).

Incomplete outcome data (attrition bias)
All outcomes
Low riskAn intention-to-treat analysis was used, despite 12 participants crossing over between groups (2) or withdrawing from the trial (10). Reasons were provided. 10 participants from the transfusion group withdrew from the trial because of problems with compliance (n = 4), multiple alloantibodies (n = 1), ineligibility (n = 1) or other unspecified reasons (n = 4). 2 participants from the standard care group crossed over to the transfusion group, one on the second day due to diagnosis of subacute intracerebral hematoma and the other after 12 months for treatment of leg ulcers.

Selective reporting (reporting bias)Low riskAll review primary outcomes fully reported (see  Table 1).

STOP 2 2005

MethodsParallel RCT.


Participants79 children with HbSS or HbSβ0Thal at high risk of stroke, who had received regular blood transfusions for at least 30 months.

Transfusion continued: 38.

Tansfusion halted: 41.


InterventionsTransfusion or discontinuation of transfusion (standard care).


OutcomesDeath, stroke, high risk of stroke judged by abnormal TCD velocity.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation by permuted blocks. Participants were stratified according to the presence of ischaemic lesions on MRI.

Allocation concealment (selection bias)High riskIt was not possible to conceal whether the patient was randomised to receive transfusion or not.

Blinding (performance bias and detection bias)
Suspected stroke
Low riskExperts who adjudicated suspected strokes were blinded to treatment allocation.

Blinding (performance bias and detection bias)
All other outcomes
Unclear riskNo information provided.

Incomplete outcome data (attrition bias)
All outcomes
High riskIt was not stated whether intention-to-treat analysis was used. Some reasons were provided for the 25 that dropped out.

Selective reporting (reporting bias)Low riskAll review primary outcomes fully reported (see  Table 1).

SWiTCH 2012

MethodsParallel RCT.


Participants133 children with HbSS and a history of stroke, chronic transfusion treatment and iron overload.


Interventions66 received transfusion and iron chelation; 67 received hydroxyurea and phlebotomy.


OutcomesComposite primary endpoint of secondary stroke recurrence rate and quantitative liver iron concentration.

Secondary trial endpoints included non-stroke neurological events, non-neurological sickle cell clinical events, quality of life evaluation, and measures of organ function.


NotesClinicalTrials.gov NCT00122980.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation.

Allocation concealment (selection bias)Low riskInvestigators were unaware of allocation determination process.

Blinding (performance bias and detection bias)
Suspected stroke
Low riskSingle blind. The stroke adjudication panel was blinded to the patient's intervention.

Blinding (performance bias and detection bias)
All other outcomes
Low riskOther part of primary outcome (iron overload) based on quantitative measurement, so bias unlikely.

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe SWiTCH trial states that they conducted an analysis in the "Intent to Treat Population, which consists of all participants who were randomised to a study treatment and for whom outcome data are available". Reasons were provided in each group for drop out.

Selective reporting (reporting bias)Low riskAll review primary outcomes fully reported (see  Table 1).

 
Characteristics of ongoing studies [ordered by study ID]
SCATE Trial

Trial name or titleSparing Conversion to Abnormal TCD Elevation (SCATE Trial)

MethodsPhase III randomised trial comparing 30 months of alternative therapy (hydroxyurea) to standard care (observation)

ParticipantsApproximately 115 children with sickle cell anaemia, 2 - 10 years old, with conditional TCD velocities

InterventionsHydroxyurea x 30 months

OutcomesPrimary outcome: Conversion to abnormal TCD. Secondary outcomes: neurologic and non-neurologic events, TCD velocities, quality of life.

Starting dateMay 2012

Contact informationRussell E Ware

NotesClinicalTrials.gov identifier: NCT01531387

SIT Trial

Trial name or title'Silent Cerebral Infarct Multi-Center Trial' (SIT Trial)

Methods

ParticipantsApproximately 3020 children with sickle cell disease, 6 - 13 years from 24 sites in USA will be screened (MRI), and approximately 204 who already have neurologic morbidity will be eligible for participation.

InterventionsProphylactic blood transfusion

OutcomesStroke, new cerebral infarcts, neurological damage and intellectual ability, risk benefit analysis of transfusion

Starting dateOngoing (36 month duration for individual patient follow up)

Contact informationMichael R DeBaun, Washington University School of Medicine

NotesClinicalTrials.gov identifier NCT00072761

TWiTCH Trial

Trial name or titleTranscranial Doppler with Transfusions Changing to Hydroxyurea (TWiTCH Trial)

MethodsPhase III randomised trial comparing 24 months of alternative therapy (hydroxyurea) to standard care (chronic transfusion)

ParticipantsChildren with sickle cell disease and abnormal TCD velocity

InterventionsContinued prophylactic blood transfusion compared to hydroxyurea

OutcomesPrevention of recurrence of abnormal TCD velocity

Starting dateOngoing

Contact informationRussell E Ware

NotesClinicalTrials.gov identifier: NCT01425307

 
Comparison 1. Blood transfusion versus standard care

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality2Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Clinical stroke2Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Other neurological events1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

    3.1 New silent infarcts
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Other sickle cell related complications1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

    4.1 Acute chest syndrome
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 Painful crises
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. Hydroxyurea and phlebotomy versus standard treatment (transfusions/chelation)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Clinical stroke1133Odds Ratio (M-H, Fixed, 95% CI)16.49 [0.92, 294.84]

 3 Other neurological event1Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 Transient ischaemic attack
1133Odds Ratio (M-H, Fixed, 95% CI)0.62 [0.21, 1.86]

 
Table 1. Outcome Table

TrialMortalityIncidence of clinical strokeTransfusion related complications (relating only to transfusion group)Incidence of TIA or silent infarctionMeasures of neurological impairmentIncidence of other sickle cell complicationsQuality of life, inpatient stay, immobility and disabilityMeasures of organ damageHaemoglobin level and haemoglobin S percentage

STOP 1998fully reportedfully reportedfully reportedfully reportedpartially reportedfully reportednot reportednot reportednot reported

STOP 2 2005fully reportedfully reportedfully reportednot reportednot reportedpartially reportednot reportednot reportedfully reported

SWiTCH 2012fully reportedfully reportedfully reportedfully reportednot reportednot reportednot reportednot reportedfully reported

 TIA: transient ischaemic attack