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Hemostatic efficacy of pathogen-inactivated- versus untreated- platelets: a randomized controlled trial
van der Meer P F, Ypma P F, van Geloven N, van Hilten J A, van Wordragen-Vlaswinkel R J, Eissen O, Zwaginga J J, Trus M, Beckers E A M, Te Boekhorst P, et al
Blood. 2018;132((2):):223-231
Abstract
Pathogen inactivation of platelet concentrates reduces the risk of blood-borne infections. However, its effect on platelet function and hemostatic efficacy of transfusion is unclear. We conducted a randomized noninferiority trial comparing the efficacy of pathogen inactivated platelets using riboflavin and ultraviolet B illumination technology (intervention) compared to standard plasma-stored platelets (control) for the prevention of bleeding in patients with hematologic malignancies and thrombocytopenia. The primary outcome parameter was the proportion of transfusion treatment periods in which the patient had grade 2 or higher bleeding as defined by World Health Organization (WHO) criteria. Between November 2010 and April 2016, 469 unique patients were randomized to 567 transfusion treatment periods (283 in the control arm, 284 in the intervention arm). There was a 3% absolute difference in grade ≥ 2 bleeding in the intention-to-treat analysis: 51% of the transfusion treatment periods in the control arm and 54% in the intervention arm (95% CI -6 to 11, p-value for noninferiority 0.012). In the per-protocol analysis, however, difference in grade ≥ 2 bleeding was 8%: 44% in the control arm and 52% in the intervention arm (95% CI -2 to 18, p-value for noninferiority 0.19). Transfusion increment parameters were about 50% lower in the intervention arm. There was no difference in the proportion of patients developing HLA class I alloantibodies. In conclusion, the noninferiority criterion for pathogen inactivated platelets was met in the intention-to-treat analysis. This finding was not demonstrated in the per protocol analysis. (The Netherlands National Trial Registry number: NTR2106).
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2.
Prophylactic platelet transfusion for prevention of bleeding in patients with haematological disorders after chemotherapy and stem cell transplantation
Estcourt L, Stanworth S, Doree C, Hopewell S, Murphy MF, Tinmouth A, Heddle N
Cochrane Database of Systematic Reviews. 2012;5:CD004269
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
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3.
A randomized controlled trial comparing standard- and low-dose strategies for transfusion of platelets (SToP) to patients with thrombocytopenia
Heddle NM, Cook RJ, Tinmouth A, Kouroukis CT, Hervig T, Klapper E, Brandwein JM, Szczepiorkowski ZM, AuBuchon JP, Barty RL, et al
Blood. 2009;113((7):):1564-73.
Abstract
A noninferiority study was performed comparing low-dose and standard-dose prophylactic platelet transfusions. A double-blind randomized controlled trial (RCT) was performed in 6 sites in 3 countries. Thrombocytopenic adults requiring prophylactic platelet transfusion were randomly allocated to standard-dose (300-600 x 10(9) platelets/product) or low-dose (150- < 300 x 10(9) platelets/product) platelets. The primary outcome (World Health Organization [WHO] bleeding > or = grade 2) was assessed daily through clinical examination, patient interview, and chart review. A WHO grade was assigned through adjudication. The Data Safety Monitoring Board stopped the study because the difference in the grade 4 bleeding reached the prespecified threshold of 5%. At this time, 129 patients had been randomized and 119 patients were included in the analysis (58 low dose; 61 standard dose). Three patients in the low-dose arm (5. 2%) had grade 4 bleeds compared with none in the standard-dose arm. WHO bleeding grade 2 or higher was 49. 2% (30/61) in the standard-dose arm and 51. 7% (30/58) in the low-dose group (relative risk [RR], 1. 052; 95% confidence interval [CI], 0. 737-1. 502). A higher rate of grade 4 bleeding in patients receiving low-dose prophylactic platelet transfusions resulted in this RCT being stopped. Whether this finding was due to chance or represents a real difference requires further investigation. These clinical studies are registered on (http://www. clinicaltrials. gov) as NCT00420914.
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4.
ABO-identical vs. non-identical platelet transfusion. A systematic review
Shehata N, Tinmouth A, Naglie G, Freedman J, Wilson K
Transfusion. 2009;49((11):):2442-53.
Abstract
BACKGROUND The significance of ABO matching for platelet (PLT) transfusion has not been clearly defined. The primary objective of this report is to assess whether ABO-identical PLT transfusion is associated with improved mortality and/or morbidity for patients with hematologic/oncologic disorders. STUDY DESIGN AND METHODS A systematic review to January 2009 was conducted. Data on mortality, morbidity, PLT refractoriness, and PLT increment after transfusion were abstracted. RESULTS A total of 100 citations were identified. Nineteen studies were included in the systematic review. A total of 1502 patients from three randomized controlled trials and 16 observational studies were included. Survival, bleeding events, and transfusion reactions were only considered as secondary outcomes in the reports reviewed. The PLT count increment was the primary outcome of several studies and was consistently higher with ABO-identical PLT transfusion. The largest difference in increment between ABO-identical and nonidentical PLT transfusion was 4 x 10(9)/L. No consistent benefit in clinical outcomes was noted. Survival was assessed in three reports with conflicting results. Although two studies described bleeding as an outcome, the assessment of hemorrhage was considered inadequate. In six studies, ABO-nonidentical PLT transfusion was not associated with transfusion reactions, and the results from four studies addressing the impact of ABO-identical PLT transfusion on PLT and red blood cell utilization were conflicting. CONCLUSION ABO-identical PLT transfusion results in a higher PLT increment. Randomized controlled trials are required to definitely determine the effect of ABO-identical PLT transfusion on survival, bleeding events, or transfusion reactions.
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5.
Low-dose prophylactic platelet transfusions in recipients of an autologous peripheral blood progenitor cell transplant and patients with acute leukemia: a randomized controlled trial with a sequential Bayesian design
Tinmouth A, Tannock IF, Crump M, Tomlinson G, Brandwein J, Minden M, Sutton D
Transfusion. 2004;44((12):):1711-9.
Abstract
BACKGROUND Prophylactic platelet (PLT) transfusions are standard treatment for patients receiving high-dose chemotherapy, but the optimal dose is not known. A randomized controlled trial was undertaken to examine the effectiveness of low-dose PLT transfusions and to determine the need for further studies. STUDY DESIGN AND METHODS Patients (n = 111) with acute leukemia or undergoing autologous peripheral blood progenitor cell (PBPC) transplantation were randomly assigned to receive low-dose (3 PLT units) or standard-dose (5 PLT units) prophylactic PLT transfusions and were monitored daily for bleeding. Using a sequential Bayesian design, the difference in major bleeding events was determined. RESULTS The percentage of patients with major bleeding events was 10. 7 percent (95% credible region, 5. 1%-21. 2%) in the low-dose PLT group and 7. 3 percent (95% credible region, 2. 9%-17. 2%) in the standard-dose PLT group. The two additional events in the low-dose group occurred when the PLT count exceeded 100 x 10(9) per L. There is an 89 percent probability that the absolute increase in major bleeds is less than 10 percent with low-dose PLT transfusions. The number of minor bleeding events was higher in the standard-dose group. Patients receiving low-dose PLT transfusions received 25 percent fewer PLT units. There was an 89 percent probability that low-dose transfusions reduced PLT utilization in patients with acute leukemia and a 60 percent probability in patients undergoing PBPC transplantation. CONCLUSION Low-dose PLT transfusions appear to be safe and effective and reduce PLT utilization. They should be further evaluated in clinical trials designed to evaluate equivalency.
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6.
A randomized phase II trial of low dose and standard dose platelet transfusions during induction therapy for acute leukemia or autologous stem cell transplantation
Tinmouth A, Kotchetkova N, Tomlinson G, Crump M, Brandwein J, Tannock I, Sutton D
Vox Sanguinis. 2002;83((Suppl 1):):8. Abstract No. 021.