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Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support
Estcourt LJ, Malouf R, Trivella M, Fergusson DA, Hopewell S, Murphy MF
The Cochrane Database of Systematic Reviews. 2017;((1)):CD011305.
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Abstract
BACKGROUND Many people diagnosed with haematological malignancies experience anaemia, and red blood cell (RBC) transfusion plays an essential supportive role in their management. Different strategies have been developed for RBC transfusions. A restrictive transfusion strategy seeks to maintain a lower haemoglobin level (usually between 70 g/L to 90 g/L) with a trigger for transfusion when the haemoglobin drops below 70 g/L), whereas a liberal transfusion strategy aims to maintain a higher haemoglobin (usually between 100 g/L to 120 g/L, with a threshold for transfusion when haemoglobin drops below 100 g/L). In people undergoing surgery or who have been admitted to intensive care a restrictive transfusion strategy has been shown to be safe and in some cases safer than a liberal transfusion strategy. However, it is not known whether it is safe in people with haematological malignancies. OBJECTIVES To determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (HSCT). SEARCH METHODS We searched for randomised controlled trials (RCTs) and non-randomised trials (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 6), and 10 other databases (including four trial registries) to 15 June 2016. We also searched grey literature and contacted experts in transfusion for additional trials. There was no restriction on language, date or publication status. SELECTION CRITERIA We included RCTs and prospective NRS that evaluated a restrictive compared with a liberal RBC transfusion strategy in children or adults with malignant haematological disorders or undergoing HSCT. DATA COLLECTION AND ANALYSIS We used the standard methodological procedures expected by Cochrane. MAIN RESULTS We identified six studies eligible for inclusion in this review; five RCTs and one NRS. Three completed RCTs (156 participants), one completed NRS (84 participants), and two ongoing RCTs. We identified one additional RCT awaiting classification. The completed studies were conducted between 1997 and 2015 and had a mean follow-up from 31 days to 2 years. One study included children receiving a HSCT (six participants), the other three studies only included adults: 218 participants with acute leukaemia receiving chemotherapy, and 16 with a haematological malignancy receiving a HSCT. The restrictive strategies varied from 70 g/L to 90 g/L. The liberal strategies also varied from 80 g/L to 120 g/L.Based on the GRADE rating methodology the overall quality of the included studies was very low to low across different outcomes. None of the included studies were free from bias for all 'Risk of bias' domains. One of the three RCTs was discontinued early for safety concerns after recruiting only six children, all three participants in the liberal group developed veno-occlusive disease (VOD). Evidence from RCTsA restrictive RBC transfusion policy may make little or no difference to: the number of participants who died within 100 days (two trials, 95 participants (RR: 0.25, 95% CI 0.02 to 2.69, low-quality evidence); the number of participants who experienced any bleeding (two studies, 149 participants; RR:0.93, 95% CI 0.73 to 1.18, low-quality evidence), or clinically significant bleeding (two studies, 149 participants, RR: 1.03, 95% CI 0.75 to 1.43, low-quality evidence); the number of participants who required RBC transfusions (three trials; 155 participants: RR: 0.97, 95% CI 0.90 to 1.05, low-quality evidence); or the length of hospital stay (restrictive median 35.5 days (interquartile range (IQR): 31.2 to 43.8); liberal 36 days (IQR: 29.2 to 44), low-quality evidence).We are uncertain whether the restrictive RBC transfusion strategy: decreases quality of life (one trial, 89 participants, fatigue score: restrictive median 4.8 (IQR 4 to 5.2); liberal m
PICO Summary
Population
Children or adults with malignant haematological disorders treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (6 studies).
Intervention
Restrictive red blood cell (RBC) transfusion strategy.
Comparison
Liberal RBC transfusion strategy.
Outcome
Evidence from randomised controlled trials showed that a restrictive RBC transfusion policy may make little or no difference to: the number of participants who died within 100 days (RR: 0.25); the number of participants who experienced any bleeding (RR: 0.93), or clinically significant bleeding (RR: 1.03); the number of participants who required RBC transfusions (RR: 0.97); or the length of hospital stay. It was uncertain whether the restrictive RBC transfusion strategy: decreases quality of life, or reduces the risk of developing any serious infection (RR: 1.23).
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Alternatives, and adjuncts, to prophylactic platelet transfusion for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation
Desborough M, Estcourt LJ, Doree C, Trivella M, Hopewell S, Stanworth SJ, Murphy MF
The Cochrane Database of Systematic Reviews. 2016;((8)):CD010982.
Abstract
BACKGROUND Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people with thrombocytopenia. Although considerable advances have been made in platelet transfusion therapy since the mid-1970s, some areas continue to provoke debate especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. OBJECTIVES To determine whether agents that can be used as alternatives, or adjuncts, to platelet transfusions for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation are safe and effective at preventing bleeding. SEARCH METHODS We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 4), MEDLINE (OvidSP, 1946 to 19 May 2016), Embase (OvidSP, 1974 to 19 May 2016), PubMed (e-publications only: searched 19 May 2016), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 19 May 2016). SELECTION CRITERIA We included randomised controlled trials in people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII, desmopressin (DDAVP), or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard care or platelet transfusion). We excluded studies of antifibrinolytic drugs, as they were the focus of another review. DATA COLLECTION AND ANALYSIS Two review authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two review authors assessed risk of bias in the included studies and extracted data independently. MAIN RESULTS We identified 16 eligible trials. Four trials are ongoing and two have been completed but the results have not yet been published (trial completion dates: April 2012 to February 2017). Therefore, the review included 10 trials in eight references with 554 participants. Six trials (336 participants) only included participants with acute myeloid leukaemia undergoing intensive chemotherapy, two trials (38 participants) included participants with lymphoma undergoing intensive chemotherapy and two trials (180 participants) reported participants undergoing allogeneic stem cell transplantation. Men and women were equally well represented in the trials. The age range of participants included in the trials was from 16 years to 81 years. All trials took place in high-income countries. The manufacturers of the agent sponsored eight trials that were under investigation, and two trials did not report their source of funding.No trials assessed artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin.Nine trials compared a TPO mimetic to placebo or standard care; seven of these used pegylated recombinant human megakaryocyte growth and differentiation factor (PEG-rHuMGDF) and two used recombinant human thrombopoietin (rhTPO).One trial compared platelet-poor plasma to platelet transfusion.We considered that all the trials included in this review were at high risk of bias and meta-analysis was not possible in seven trials due to problems with the way data were reported.We are very uncertain whether TPO mimetics reduce the number of participants with any bleeding episode (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.10 to 1.62, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce the risk of a life-threatening bleed after 30 days (OR 1.46, 95% CI 0.06 to 33.14, three trials, 209 participants, very low quality evidence); or after 90 days (OR 1.00, 95% CI 0.06 to 16.37, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce platelet transfusion requirements after 30 days (mean difference -3.00 units, 95% CI
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Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation
Estcourt LJ, Stanworth SJ, Doree C, Hopewell S, Trivella M, Murphy MF
Cochrane Database of Systematic Reviews.. 2015;((11)):CD010983.
Abstract
BACKGROUND Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to 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.This is an update of a Cochrane review first published in 2004, and previously updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews looking at these questions individually; this review compares prophylactic platelet transfusion thresholds. OBJECTIVES To determine whether different platelet transfusion thresholds for administration of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect the efficacy and safety of prophylactic platelet transfusions in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy or haematopoietic stem cell transplantation (HSCT). SEARCH METHODS We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6, 23 July 2015), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. SELECTION CRITERIA We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with haematological disorders (receiving myelosuppressive chemotherapy or undergoing HSCT) that compared different thresholds for administration of prophylactic platelet transfusions (low trigger (5 x 10(9)/L); standard trigger (10 x 10(9)/L); higher trigger (20 x 10(9)/L, 30 x 10(9)/L, 50 x 10(9)/L); or alternative platelet trigger (for example platelet mass)). DATA COLLECTION AND ANALYSIS We used the standard methodological procedures expected by Cochrane. MAIN RESULTS Three trials met our predefined inclusion criteria and were included for analysis in the review (499 participants). All three trials compared a standard trigger (10 x 10(9)/L) versus a higher trigger (20 x 10(9)/L or 30 x 10(9)/L). None of the trials compared a low trigger versus a standard trigger or an alternative platelet trigger. The trials were conducted between 1991 and 2001 and enrolled participants from fairly comparable patient populations.The original review contained four trials (658 participants); in the previous update of this review we excluded one trial (159 participants) because fewer than 80% of participants had a haematological disorder. We identified no new trials in this update of the review.Overall, the methodological quality of the studies was low across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity.Three studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no evidence of a difference in the number of participants with a clinically significant bleeding episode between the standard and higher trigger groups (three studies; 499 participants; risk ratio (RR) 1.35, 95% confidence interval (CI) 0.95 to 1.90; low-quality evidence).One study reported the number of days with a clinically significant bleeding event (adjusted for repeated measures). There was no evidence of a difference in the number of days of bleeding per participant between the standard and higher trigger groups (one study; 255 participants; relative proportion of days with World Health Organization
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Impact of prophylactic platelet transfusions on bleeding events in patients with hematologic malignancies: a subgroup analysis of a randomized trial
Stanworth SJ, Estcourt LJ, Llewelyn CA, Murphy MF, Wood EM, TOPPS Study Investigators
Transfusion. 2014;54((10):):2385-93.
Abstract
BACKGROUND A recent randomized trial compared a policy of no prophylaxis with a policy of prophylactic platelet (PLT) transfusions at counts of fewer than 10x10(9) /L in patients with hematologic malignancies. The results suggested the effectiveness of prophylactic PLT transfusions may vary according to patient diagnosis and treatment plan. STUDY DESIGN AND METHODS This article presents full subgroup analyses and compares treatment effects between autologous hematopoietic stem cell transplantation (autoHSCT; n=421) and chemotherapy/allogeneic HSCT (chemo/alloHSCT; n=179) patients. RESULTS Prespecified subgroup analysis found that the reduction in proportion of patients experiencing WHO Grade 2 to 4 bleeds (main trial outcome) seen in the prophylaxis arm was of greater magnitude in chemo/alloHSCT than autoHSCT patients (interaction p=0.04). Analysis of secondary outcomes showed a shorter time to first bleeding episode with no prophylaxis in the chemo/alloHSCT group (hazard ratio, 1.84; 95% confidence interval CI, 1.21-2.79; p=0.004) compared to the autoHSCT group (hazard ratio, 1.12; 95% CI, 0.85-1.48; p=0.4; interaction p=0.08). The increased number of days with Grade 2 to 4 bleeds with a no-prophylaxis policy was similar in chemo/alloHSCT (rate ratio, 1.89; 95% CI, 1.10-3.26) and in autoHSCT patients (rate ratio, 1.43; 95% CI, 1.04-1.97). Both subgroups showed significant reductions in PLT transfusions with a no-prophylaxis strategy. CONCLUSION There is evidence that the effectiveness of prophylactic PLT transfusions may differ between subgroups, with chemo/alloHSCT patients receiving prophylactic PLT transfusions appearing to show a greater reduction in bleeding outcomes compared to patients following a no-prophylaxis policy. 2014 Crown copyright. This article Impact of Prophylactic Platelet Transfusions on Bleeding Events in Patients with Hematologic Malignancies: A Sub-group Analysis of a Randomised Trial was written by Stanworth, Estcourt, Llewelyn, Murphy, & Wood. It is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.
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Antifibrinolytics (lysine analogues) for the prevention of bleeding in patients with haematological disorders
Wardrop D, Estcourt LJ, Brunskill SJ, Doree C, Trivella M, Stanworth S, Murphy MF
Cochrane Database of Systematic Reviews. 2013;((7):):CD009733.
Abstract
BACKGROUND Patients with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia. This is despite the routine use of prophylactic platelet transfusions (PlTx) to prevent bleeding once the platelet count falls below a certain threshold. PlTx are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic PlTxs is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). OBJECTIVES To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in patients with haematological disorders. SEARCH METHODS We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL Issue 12, 2012), MEDLINE (1948 to 10 January 2013), EMBASE (1980 to 10 January 2013), CINAHL (1982 to 10 January 2013), PubMed (e-publications only) and the Transfusion Evidence Library (1980 to January 2013). We also searched several international and ongoing trial databases to 10 January 2013 and citation-tracked relevant reference lists. SELECTION CRITERIA RCTs involving patients with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA. DATA COLLECTION AND ANALYSIS Two authors independently screened all electronically derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data. MAIN RESULTS Of 470 articles initially identified, 436 were excluded on the basis of the title and abstract. We reviewed 34 full-text articles from which four studies reported in five articles were eligible for inclusion. We did not identify any RCTs which compared TXA with EACA. We did not identify any ongoing RCTs.One cross-over TXA study (eight patients) was excluded from the outcome analysis because data from this study were at a high risk of bias. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology.Three studies (two TXA (12 to 56 patients), one EACA (18 patients)) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo.All studies reported bleeding, but it was reported in different ways. All three studies suggested antifibrinolytics reduced the risk of bleeding. The first study showed a difference in average bleeding score of 42 in placebo (P) versus three (TXA). The second study only showed a difference in bleeding episodes during consolidation chemotherapy, with a mean of 2.6 episodes/patient (standard deviation (SD) 2.2) (P) versus a mean of 1.1 episodes/patient (SD 1.4) (TXA). The third study reported bleeding on 50% of days at risk (P) versus bleeding on 31% of days at risk (EACA).Two studies (68 patients) reported thromboembolism and no events occurred.All three studies reported a reduction in PlTx usage. The first study reported a difference of 222 platelet units (P) versus 69 platelet units (TXA). The second study only showed a difference in total platelet usage during consolidation chemotherapy, with a mean of 9.3 units (SD 3.3) (P) versus 3.7 (SD 4.1) (TXA).The third study reported one PlTx every 10.5 days at risk (P) versus one PlTx every 13.3 days at risk (EACA).Two studies reported red cell transfusion requirements and one study found a reduction in red cell transfusion usage.One study reported death due to bleeding as an outcome measure and none occurred.Only one study repo
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A no-prophylaxis platelet-transfusion strategy for hematologic cancers
Stanworth SJ, Estcourt LJ, Powter G, Kahan BC, Dyer C, Choo L, Bakrania L, Llewelyn C, Littlewood T, Soutar R, et al
New England Journal of Medicine. 2013;368((19):):1771-80.
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Abstract
BACKGROUND The effectiveness of platelet transfusions to prevent bleeding in patients with hematologic cancers remains unclear. This trial assessed whether a policy of not giving prophylactic platelet transfusions was as effective and safe as a policy of providing prophylaxis. METHODS We conducted this randomized, open-label, noninferiority trial at 14 centers in the United Kingdom and Australia. Patients were randomly assigned to receive, or not to receive, prophylactic platelet transfusions when morning platelet counts were less than 10x10(9) per liter. Eligible patients were persons 16 years of age or older who were receiving chemotherapy or undergoing stem-cell transplantation and who had or were expected to have thrombocytopenia. The primary end point was bleeding of World Health Organization (WHO) grade 2, 3, or 4 up to 30 days after randomization. RESULTS A total of 600 patients (301 in the no-prophylaxis group and 299 in the prophylaxis group) underwent randomization between 2006 and 2011. Bleeding of WHO grade 2, 3, or 4 occurred in 151 of 300 patients (50%) in the no-prophylaxis group, as compared with 128 of 298 (43%) in the prophylaxis group (adjusted difference in proportions, 8.4 percentage points; 90% confidence interval, 1.7 to 15.2; P=0.06 for noninferiority). Patients in the no-prophylaxis group had more days with bleeding and a shorter time to the first bleeding episode than did patients in the prophylaxis group. Platelet use was markedly reduced in the no-prophylaxis group. A prespecified subgroup analysis identified similar rates of bleeding in the two study groups among patients undergoing autologous stem-cell transplantation. CONCLUSIONS The results of our study support the need for the continued use of prophylaxis with platelet transfusion and show the benefit of such prophylaxis for reducing bleeding, as compared with no prophylaxis. A significant number of patients had bleeding despite prophylaxis. (Funded by the National Health Service Blood and Transplant Research and Development Committee and the Australian Red Cross Blood Service; TOPPS Controlled-Trials.com number, ISRCTN08758735.).
PICO Summary
Population
Patients 16 years old or older, with hematologic cancers enrolled at 14 centres in the United Kingdom and Australia (n= 600).
Intervention
Prophylactic platelet transfusions (Prophylaxis group, n= 299).
Comparison
No prophylactic platelet transfusions (No-prophylaxis group, n= 301).
Outcome
Bleeding of WHO grade 2, 3, or 4 occurred in 151 of 300 patients (50%) in the no-prophylaxis group, as compared with 128 of 298 (43%) in the prophylaxis group (adjusted difference in proportions, 8.4 percentage points; 90% confidence interval, 1.7 to 15.2). Patients in the no-prophylaxis group had more days with bleeding and a shorter time to the first bleeding episode than did patients in the prophylaxis group. Platelet use was markedly reduced in the no-prophylaxis group. A prespecified subgroup analysis identified similar rates of bleeding in the two study groups among patients undergoing autologous stem-cell transplantation.
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The effect of a no-prophylactic versus prophylactic platelet transfusion strategy on bleeding in patients with hematological malignancies and severe thrombocytopenia (TOPPS trial): a randomized controlled, non-inferiority trial
Stanworth SJ, Estcourt L, Powter G, Kahan BC, Dyer C, Bakrania L, Llewelyn C, Choo L, Bielby L, Norfolk D, et al
Blood. 2012;120((21):): Abstract No. 1.
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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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Do all patients with hematologic malignancies and severe thrombocytopenia need prophylactic platelet transfusions? Background, rationale, and design of a clinical trial (trial of platelet prophylaxis) to assess the effectiveness of prophylactic platelet transfusions
Stanworth SJ, Dyer C, Choo L, Bakrania L, Copplestone A, Llewelyn C, Norfolk D, Powter G, Littlewood T, Wood EM, et al
Transfusion Medicine Reviews. 2010;24((3):):163-71.
Abstract
Although considerable advances have been made in many aspects of platelet transfusion therapy in the last 30 years, some areas continue to provoke debate, including the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding in patients with bone marrow failure. We have designed a randomized controlled trial to compare prophylactic platelet use with a threshold of a platelet count of 10 x 109/L with no prophylaxis in adult thrombocytopenic patients with hematologic malignancies. The trial question is whether a no-prophylactic policy for the use of platelet transfusions in patients with hematologic malignancies is not inferior to a threshold prophylactic policy at 10 x 109/L, for bleeding at World Health Organization (WHO) grade 2, 3, or 4, up to 30 days from randomization. The primary outcome measure is the proportion of patients who have a significant clinical bleed, defined as WHO grade 2 or higher up to 30 days from randomization. Subsidiary clinical outcome measures include time to first bleed and a descriptive analysis of all severe bleeds. A bleeding assessment form is completed daily for all study subjects until day 30 from randomization. Minor modifications were made to the definitions at WHO grades 1 and 2 for petechiae and duration of nose bleeds, after piloting of the bleeding assessment forms. This study has been designed as a 2-stage randomized trial with an interim analysis planned after a minimum of 100 patients had been randomized and had completed their period of observation. Patients have initially been enrolled through 3 United Kingdom hematology centers. The interim analysis has been completed, and the results have confirmed a final sample size of 600 patients. Recruitment is now being extended to other centers in United Kingdom and Australia. Local research nurses are not blinded to treatment allocation, but a number of measures to reduce risk of assessment bias include repeated education around standard operating procedures, common definitions, and duplication of assessments. The expected completion date for the 5-year study is December 2011. 2010 Elsevier Inc.