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Meta-Analysis
. 2012 May 16;2012(5):CD004269.
doi: 10.1002/14651858.CD004269.pub3.

Prophylactic platelet transfusion for prevention of bleeding in patients with haematological disorders after chemotherapy and stem cell transplantation

Lise Estcourt  1 , Simon Stanworth, Carolyn Doree, Sally Hopewell, Michael F Murphy, Alan Tinmouth, Nancy Heddle
Affiliations
Meta-Analysis

Prophylactic platelet transfusion for prevention of bleeding in patients with haematological disorders after chemotherapy and stem cell transplantation

Lise Estcourt et al. Cochrane Database Syst Rev. .

Abstract

Background: Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in thrombocytopenic patients with bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding.

Objectives: To determine the most effective use of platelet transfusion for the prevention of bleeding in patients with haematological disorders undergoing chemotherapy or stem cell transplantation.

Search methods: This is an update of a Cochrane review first published in 2004. We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4, 2011), MEDLINE (1950 to Nov 2011), EMBASE (1980 to Nov 2011) and CINAHL (1982 to Nov 2011), using adaptations of the Cochrane RCT search filter, the UKBTS/SRI Transfusion Evidence Library, and ongoing trial databases to 10 November 2011.

Selection criteria: RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in patients with haematological disorders. Four different types of prophylactic platelet transfusion trial were included.

Data collection and analysis: In the original review one author initially screened all electronically derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two authors performed this task in the updated review. Two authors independently assessed the full text of all potentially relevant trials for eligibility. Two authors completed data extraction independently. We requested missing data from the original investigators as appropriate.

Main results: There were 18 trials that were eligible for inclusion, five of these were still ongoing.Thirteen completed published trials (2331 participants) were included for analysis in the review. The original review contained nine trials (718 participants). This updated review includes six new trials (1818 participants).Two trials (205 participants) in the original review are now excluded because fewer than 80% of participants had a haematological disorder.The four different types of prophylactic platelet transfusion trial, that were the focus of this review, were included within these thirteen trials.Three trials compared prophylactic platelet transfusions versus therapeutic-only platelet transfusions. There was no statistical difference between the number of participants with clinically significant bleeding in the therapeutic and prophylactic arms but the confidence interval was wide (RR 1.66; 95% CI 0.9 to 3.04).The time taken for a clinically significant bleed to occur was longer in the prophylactic platelet transfusion arm. There was a clear reduction in platelet transfusion usage in the therapeutic arm. There was no statistical difference between the number of participants in the therapeutic and prophylactic arms with platelet refractoriness, the only adverse event reported.Three trials compared different platelet count thresholds to trigger administration of prophylactic platelet transfusions. No statistical difference was seen in the number of participants with clinically significant bleeding (RR 1.35; 95% CI 0.95 to 1.9), however, this type of bleeding occurred on fewer days in the group of patients transfused at a higher platelet count threshold (RR 1.72; 95% CI 1.33 to 2.22).The lack of a difference seen for the number of participants with clinically significant bleeding may be due to the studies, in combination, having insufficient power to demonstrate a difference, or due to masking of the effect by a higher number of protocol violations in the groups of patients with a lower platelet count threshold. Using a lower platelet count threshold led to a significant reduction in the number of platelet transfusions used. There were no statistical differences in the number of adverse events reported between the two groups.Six trials compared different doses of prophylactic platelet transfusions. There was no evidence to suggest that using a lower platelet transfusion dose increased: the number of participants with clinically significant (WHO grade 2 or above) (RR 1.02; 95% CI 0.93 to 1.11), or life-threatening (WHO grade 4) bleeding (RR 1.87; 95% CI 0.86 to 4.08). A higher platelet transfusion dose led to a reduction in the number of platelet transfusion episodes, but an increase in total platelet utilisation. Only one adverse event, wheezing after transfusion, had a significantly higher incidence when standard and high dose transfusions were compared but this difference was not seen when low dose and high dose transfusions were compared. It is therefore likely to be a type I error (false positive).One small trial compared prophylactic platelet transfusions versus platelet-poor plasma. The risk of a significant bleed was decreased in the prophylactic platelet transfusion arm (RR 0.47; 95% CI 0.23 to 0.95) and this was statistically significant.All studies had threats to validity; the majority of these were due to methodology of the studies not being described in adequate detail.Although it was not the main focus of the review, it was interesting to note that in one of the pre-specified sub-group analyses (treatment type) two studies showed that patients receiving an autologous transplant have a lower risk of bleeding than patients receiving intensive chemotherapy or an allogeneic transplant (RR 0.73, 95% CI 0.65 to 0.82).

Authors' conclusions: These conclusions refer to the four different types of platelet transfusion trial separately. Firstly, there is no evidence that a prophylactic platelet transfusion policy prevents bleeding. Two large trials comparing a therapeutic versus prophylactic platelet transfusion strategy, that have not yet been published, should provide important new data on this comparison. Secondly, there is no evidence, at the moment, to suggest a change from the current practice of using a platelet count of 10 x 10(9)/L. However, the evidence for a platelet count threshold of 10 x 10(9)/L being equivalent to 20 x 10(9)/L is not as definitive as it would first appear and further research is required. Thirdly, platelet dose does not affect the number of patients with significant bleeding, but whether it affects number of days each patient bleeds for is as yet undetermined. There is no evidence that platelet dose affects the incidence of WHO grade 4 bleeding.Prophylactic platelet transfusions were more effective than platelet-poor plasma at preventing bleeding.

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Conflict of interest statement

Lise Estcourt: none declared

Simon Stanworth: none declared

Carolyn Doree: none declared

Sally Hopewell: none declared

Mike Murphy: none declared

Alan Tinmouth: none declared

Nancy Heddle:none declared

Figures

1
1
PRISMA Flow Diagram
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot of comparison: 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, outcome: 2.2 Numbers of participants with a significant bleeding event.
4
4
Forest plot of comparison: 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, outcome: 2.4 Number of days with a significant bleed.
5
5
Forest plot of comparison: 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, outcome: 2.8 Mean number of platelet transfusions per patient.
6
6
Forest plot of comparison: 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, outcome: 2.9 Mean number of red cell transfusions per patient.
7
7
Forest plot of comparison: 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, outcome: 2.10 Remission rates.
8
8
Forest plot of comparison: 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, outcome: 3.2 Number of participants with a significant bleeding event.
9
9
Forest plot of comparison: 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, outcome: 3.3 Number of days with significant bleeding.
10
10
Forest plot of comparison: 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, outcome: 3.6 Number of participants with WHO grade 4 bleeding.
1.1
1.1. Analysis
Comparison 1 Prophylactic platelet transfusion versus non prophylactic or therapeutic transfusion, Outcome 1 Numbers of participants with a significant bleeding event.
1.2
1.2. Analysis
Comparison 1 Prophylactic platelet transfusion versus non prophylactic or therapeutic transfusion, Outcome 2 Number of days with significant bleeding.
1.3
1.3. Analysis
Comparison 1 Prophylactic platelet transfusion versus non prophylactic or therapeutic transfusion, Outcome 3 Mortality from all causes.
1.4
1.4. Analysis
Comparison 1 Prophylactic platelet transfusion versus non prophylactic or therapeutic transfusion, Outcome 4 Mortality from bleeding.
1.5
1.5. Analysis
Comparison 1 Prophylactic platelet transfusion versus non prophylactic or therapeutic transfusion, Outcome 5 Mean number of platelet transfusions per course of chemotherapy.
1.6
1.6. Analysis
Comparison 1 Prophylactic platelet transfusion versus non prophylactic or therapeutic transfusion, Outcome 6 Mean number of red cell transfusions per patient.
1.7
1.7. Analysis
Comparison 1 Prophylactic platelet transfusion versus non prophylactic or therapeutic transfusion, Outcome 7 Remission rates.
1.8
1.8. Analysis
Comparison 1 Prophylactic platelet transfusion versus non prophylactic or therapeutic transfusion, Outcome 8 Number of participants with platelet refractoriness.
2.1
2.1. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 1 Number of participants with any bleeding event.
2.2
2.2. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 2 Numbers of participants with a significant bleeding event.
2.3
2.3. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 3 Number of participants with WHO Grade 3 or 4 bleeding.
2.4
2.4. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 4 Number of participants with bleeding requiring a red cell transfusion.
2.5
2.5. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 5 Number of days with any bleeding.
2.6
2.6. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 6 Number of days with a significant bleed.
2.7
2.7. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 7 Mortality from all causes.
2.8
2.8. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 8 Mortality from bleeding.
2.9
2.9. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 9 Mean number of platelet transfusions per patient.
2.10
2.10. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 10 Mean number of red cell transfusions per patient.
2.11
2.11. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 11 Remission rates.
2.12
2.12. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 12 Numbers of participants with platelet transfusion reactions.
2.13
2.13. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 13 Number of participants with thromboembolic disease.
2.14
2.14. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 14 Number of participants requiring HLA‐matched platelets.
2.15
2.15. Analysis
Comparison 2 Prophylactic platelet transfusion at one trigger level versus another trigger level, Outcome 15 Number of participants with platelet refractoriness.
3.1
3.1. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 1 Number of participants with any bleeding event.
3.2
3.2. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 2 Number of participants with a significant bleeding event.
3.3
3.3. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 3 Number of participants with WHO Grade 3 or 4 bleeding.
3.4
3.4. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 4 Number of participants with WHO grade 4 bleeding.
3.5
3.5. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 5 Number of participants with bleeding requiring a red cell transfusion.
3.6
3.6. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 6 Number of participants with bleeding causing cardiovascular compromise.
3.7
3.7. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 7 Number of days with significant bleeding.
3.8
3.8. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 8 Mortality from all causes.
3.9
3.9. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 9 Mortality from bleeding.
3.10
3.10. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 10 Number of participants with platelet transfusion reactions.
3.11
3.11. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 11 Thromboembolic disease.
3.12
3.12. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 12 Number of participants with a significant bleeding episode.
3.13
3.13. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 13 Time to first significant bleeding event.
3.14
3.14. Analysis
Comparison 3 Prophylactic platelet transfusion with one dose schedule versus another dose schedule, Outcome 14 Number of days with WHO grade 2 or above bleeding per patient.
4.1
4.1. Analysis
Comparison 4 Prophylactic platelet transfusion versus platelet‐poor plasma, Outcome 1 Number of participants with a significant bleeding event.
4.2
4.2. Analysis
Comparison 4 Prophylactic platelet transfusion versus platelet‐poor plasma, Outcome 2 Time to first bleed.
4.3
4.3. Analysis
Comparison 4 Prophylactic platelet transfusion versus platelet‐poor plasma, Outcome 3 Number of participants with bleeding requiring a red cell transfusion.
4.4
4.4. Analysis
Comparison 4 Prophylactic platelet transfusion versus platelet‐poor plasma, Outcome 4 Number of participants with bleeding causing cardiovascular compromise.
4.5
4.5. Analysis
Comparison 4 Prophylactic platelet transfusion versus platelet‐poor plasma, Outcome 5 Mortality from bleeding.
4.6
4.6. Analysis
Comparison 4 Prophylactic platelet transfusion versus platelet‐poor plasma, Outcome 6 Complete remission.
4.7
4.7. Analysis
Comparison 4 Prophylactic platelet transfusion versus platelet‐poor plasma, Outcome 7 Development of HLA Antibodies.
See this image and copyright information in PMC

Update of

References

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Gmur 1991 {published data only}
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Heddle 1999 {published data only}
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    1. Heddle NM, Blajchman MA, Meyer RM, Lipton JH, Walker IR, Sher GD, et al. A randomized controlled trial comparing the frequency of acute reactions to plasma‐removed platelets and prestorage WBC‐reduced platelets. Transfusion 2002;42(5):556‐566. - PubMed
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Hilbom 2008 {published data only}
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    1. ISRCTN49080246. Platelet Process Improvement Project. http://www.controlled‐trials.com/ISRCTN49080246.
Johansson 2007 {published data only}
    1. Johansson PI, Stensballe J, Rosenberg I, Hisløv TL, Jørgensen L, Secher NH. Proactive administration of platelets and plasma for patients with a ruptured abdominal aortic aneurysm: evaluating a change in transfusion practice. Transfusion 2007;47(4):593‐8. - PubMed
Julmy 2009 {published data only}
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Kakaiya 1981 {published data only}
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Kerkhoffs 2010 {published data only}
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Lawrence 2001 {published data only}
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Lozano 2011 {published data only}
    1. Lozano M, Knutson F, Tardivel R, Cid J, Maymó RM, Löf H, et al. A multi‐centre study of therapeutic efficacy and safety of platelet components treated with amotsalen and ultraviolet A pathogen inactivation stored for 6 or 7 d prior to transfusion. British Journal of Haematology 2011;153(3):393‐401. - PubMed
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Messerschmidt 1988 {published data only}
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Mirasol 2010 {published data only}
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Navarro 1998 {published data only}
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Nevo 2007 {published data only}
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Oksanen 1991 {published data only}
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Oksanen 1994 {published data only}
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Paananen 2009 {published data only}
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Qureshi 2007 {published data only}
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Rabinowitz 2010 {published data only}
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Reed 1986 {published data only}
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Sagmeister 1999 {published data only}
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Samama 2005 {published data only}
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Schiffer 1983 {published data only}
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Shanwell 1992 {published data only}
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Shehata 2009 {published data only}
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Singer 1988 {published data only}
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Sintnicolaas 1995 {published data only}
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Slichter 2006 {published data only}
    1. Slichter SJ, Raife TJ, Davis K, Rheinschmidt M, Buchholz DH, Corash L, et al. Platelets photochemically treated with amotsalen HCl and ultraviolet A light correct prolonged bleeding times in patients with thrombocytopenia. Transfusion 2006;46(5):731‐40. - PubMed
Speiss 2004 {published data only}
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van Rhenen 2003 {published data only}
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Wandt 2005 {published data only}
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Wandt 2006 {published data only}
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Zumberg 2002 {published and unpublished data}
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References to ongoing studies

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