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Prophylactic versus selective blood transfusion for sickle cell disease in pregnancy

  1. Babasola O Okusanya1,*,
  2. Olufemi T Oladapo2

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 3 DEC 2013

Assessed as up-to-date: 31 OCT 2013

DOI: 10.1002/14651858.CD010378.pub2


How to Cite

Okusanya BO, Oladapo OT. Prophylactic versus selective blood transfusion for sickle cell disease in pregnancy. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD010378. DOI: 10.1002/14651858.CD010378.pub2.

Author Information

  1. 1

    Faculty of Clinical Sciences, College of Medicine, University of Lagos, Idi-Araba, Experimental and Maternal Medicine Unit, Department of Obstetrics and Gynaecology, Lagos, Nigeria

  2. 2

    Obafemi Awolowo College of Health Sciences, Olabisi Onabanjo University, Maternal and Fetal Health Research Unit, Department of Obstetrics and Gynaecology, Sagamu, Ogun State, Nigeria

*Babasola O Okusanya, Experimental and Maternal Medicine Unit, Department of Obstetrics and Gynaecology, Faculty of Clinical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria. babakusanya@yahoo.co.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 3 DEC 2013

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This is not the most recent version of the article. View current version (22 DEC 2016)

 
Characteristics of included studies [ordered by study ID]
Koshy 1987

MethodsRandomised controlled trial. 


Participants26 pregnant women with sickle cell anaemia (HbSS) presenting at less than 28 weeks and whose diagnosis was confirmed by Hb electrophoresis on cellulose acetate, citrate agar and solubility test. Exclusion criteria: Pregnant women with HbSC and HbSβ-Thalassaemia, religious belief against blood transfusion (i.e. Jehovah's witness), pregnancy > 28 weeks, women presenting with several medical complications or had several RBC antibodies.

Setting: Michael Reese Hospital and Medical Centre, Chicago, Illinois, USA.


InterventionsPartial exchange prophylactic transfusion on out-patient basis, beginning at early weeks of pregnancy to maintain HbS < 35% and Hb concentration at 11 g/dL (n = 13) versus emergency blood transfusion for medical or obstetric complications (i.e. Hb < 5 g%, hypoxaemia, septicaemia, splenic sequestration, and preparation for surgery and anaesthesia. n = 13.


OutcomesPain crisis and total units of blood transfused.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not stated. "Patients with sickle cell anaemia were randomized..."

Allocation concealment (selection bias)Unclear riskNo information about allocation concealment to permit judgement.

Blinding of participants and personnel (performance bias)
All outcomes
High riskAlthough it is impracticable to blind participants and key study personnel to intervention, the knowledge of the intervention by the study personnel makes performance bias a high possibility.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskUncertain whether outcome assessors were blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing data.

Selective reporting (reporting bias)High riskThe study emphasised pain (vaso-occlusive) crisis as the only outcome of interest without including results for many other recognised morbidities in pregnant women with sickle cell anaemia. It is unclear whether the reported 'total units of blood transfused' was pre-specified for the study as the "paper evaluates only the occurrence, frequency, and management of pain crisis during pregnancy".

Other biasLow riskThe study appears free of other bias.

Koshy 1988

MethodsRandomised controlled trial.


Participants72 pregnant women diagnosed with sickle cell anaemia presenting in early pregnancy without other medical disorders. Exclusion criteria: women previously on long-term prophylactic transfusion beginning before the study; pregnant women with other haemoglobinopathies such as HbSC and HbSβ-Thalassaemia.

Setting: Six hospitals in Chicago (secondary and university hospitals) and Johns Hopkins Hospital, Baltimore.


InterventionsIntervention: red cell transfusion at the beginning of the management of their pregnancy with the goal of maintaining Hb concentration at 10 and 11 g/dL, or the haematocrit near 0.33, and to reduce the HbS below 35% by simple transfusion or partial exchange transfusion. Immediately upon entry into the study, patients received 2 units of packed washed frozen red cells weekly for 3 weeks or until the above goals were reached. All blood transfused was obtained from volunteer donors and processed according to standard blood banking procedures (n = 36).

Control: blood transfusion only for medical or obstetric indications. Haematologic indication for blood transfusion were a Hb concentration below 6 g/dL, a haematocrit below 18% and a reticulocyte count below 3%. All blood transfused was obtained from volunteer donors and processed according to standard blood banking procedures (n = 36).


OutcomesMaternal death, severe maternal morbidity (acute chest syndrome, pulmonary embolism, congestive heart failure), perinatal death, pain crisis, total units of blood transfused, blood transfusion reaction.


NotesThe study was conducted over a period of 7 years and 2 months.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not stated. Study was described as "controlled randomized prospective study…". Patients were random assigned to one of two treatments.

Allocation concealment (selection bias)Unclear riskNo information about allocation concealment to permit judgement.

Blinding of participants and personnel (performance bias)
All outcomes
High riskAlthough it is impracticable to blind participants and key study personnel to intervention, the knowledge of the intervention by the study personnel makes performance bias a high possibility.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskUncertain whether outcome assessors were blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing data reported.

Selective reporting (reporting bias)Unclear riskComparison of outcome measure in the 'Methods' and 'Results; sections of the report indicated no evidence of selective outcome reporting although there was a reference to occurrence of maternal mortality in the 'Discussion' section.

Other biasUnclear riskThe significant difference in previous perinatal mortality (as one of the baseline characteristics) between intervention and control groups questions the effectiveness of the randomisation procedures.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Cerqueira 1999The report involved 34 pregnant women with SCD in a randomised control study published as a conference abstract in 1999 and the full publication of the completed study cannot be located. Trial authors' conclusion in the abstract is suggestive of an incomplete study ("These are still preliminary data and the small number of patients do not allow us to reach a definitive conclusion"). All attempts to contact trial authors for full publication of completed study was unsuccessful.

Koshy 1991This paper compared the findings of 2 studies on pregnant women with SCD:

1. Koshy 1988 (RCT comparing prophylactic versus selective transfusion for women with HbSS),

2. an observational study on pregnancy outcomes of women with HbSS, SC and Sβ-Thalassaemia delivering at the same centre over a specified period; with

3. findings in women without medical complications or haemoglobinopathy who delivered the same institution.

 
Comparison 1. Prophylactic versus selective blood transfusion

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

 1 Maternal death172Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Severe maternal morbidity (pulmonary embolism)172Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Severe maternal morbidity (congestive cardiac failure)172Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.07, 15.38]

 4 Severe maternal morbidity (acute chest syndrome)172Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.12, 3.75]

 5 Perinatal death176Risk Ratio (M-H, Fixed, 95% CI)2.85 [0.61, 13.22]

 6 Sickle cell crisis (pain crisis)298Risk Ratio (M-H, Random, 95% CI)0.42 [0.17, 0.99]

 7 Sickle cell crises (acute splenic sequestration)172Risk Ratio (M-H, Fixed, 95% CI)0.33 [0.01, 7.92]

 8 Sickle cell crisis (haemolysis)172Risk Ratio (M-H, Fixed, 95% CI)0.33 [0.04, 3.06]

 9 Blood transfusion reaction172Risk Ratio (M-H, Fixed, 95% CI)2.0 [0.54, 7.39]

 
Summary of findings for the main comparison. Prophylactic versus selective blood transfusion for sickle cell disease in pregnancy

Prophylactic versus selective blood transfusion for sickle cell disease in pregnancy

Patient or population: patients with sickle cell disease in pregnancy
Settings: Secondary or university hospitals in USA
Intervention: Prophylactic versus selective blood transfusion

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlProphylactic versus selective blood transfusion

Maternal deathSee commentSee commentNot estimable72
(1 study)
⊕⊝⊝⊝
very low1,2
0 participants died in this study.

Severe maternal morbidity (pulmonary embolism)See commentSee commentNot estimable72
(1 study)
⊕⊝⊝⊝
very low1,2
0 participants experienced pulmonary embolism in this study.

Severe maternal morbidity (congestive cardiac failure)28 per 100028 per 1000
(2 to 427)
RR 1
(0.07 to 15.38)
72
(1 study)
⊕⊝⊝⊝
very low1,2

Perinatal death54 per 1000154 per 1000
(33 to 715)
RR 2.85
(0.61 to 13.22)
76
(1 study)
⊕⊝⊝⊝
very low1,2

Sickle cell crisis (pain crisis)Study populationRR 0.42
(0.17 to 0.99)
98
(2 studies)
⊕⊕⊝⊝
low3,4

490 per 1000206 per 1000
(83 to 485)

Moderate

481 per 1000202 per 1000
(82 to 476)

Sickle cell crises (acute splenic sequestration)28 per 10009 per 1000
(0 to 220)
RR 0.33
(0.01 to 7.92)
72
(1 study)
⊕⊝⊝⊝
very low1,5

Blood transfusion reaction83 per 1000167 per 1000
(45 to 616)
RR 2
(0.54 to 7.39)
72
(1 study)
⊕⊝⊝⊝
very low1,5

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Study at moderate risk of bias due to unclear methods of random sequence generation and allocation concealment and use of unblinded interventions.
2 The number of events was zero and the total study population was small (n = 72). The confidence interval is likely to be very wide.
3 Studies at moderate risk of bias due to unclear methods of random sequence generation and allocation concealment and use of unblinded interventions.
4 Cumulative study population was relatively small (n = 98).
5 The number of events and total study population were very small. Confidence interval was very wide.
* Little variation in baseline risks.