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1.
Prophylactic platelet transfusions prior to surgery for people with a low platelet count
Estcourt LJ, Malouf R, Doree C, Trivella M, Hopewell S, Birchall J
The Cochrane Database of Systematic Reviews. 2018;((9)):CD012779.
Abstract
BACKGROUND People with thrombocytopenia often require a surgical procedure. A low platelet count is a relative contraindication to surgery due to the risk of bleeding. Platelet transfusions are used in clinical practice to prevent and treat bleeding in people with thrombocytopenia. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to surgery. Alternatives to platelet transfusion are also used prior surgery. OBJECTIVES To determine the clinical effectiveness and safety of prophylactic platelet transfusions prior to surgery for people with a low platelet count. SEARCH METHODS We searched the following major data bases: Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), PubMed (e-publications only), Ovid MEDLINE, Ovid Embase, the Transfusion Evidence Library and ongoing trial databases to 11 December 2017. SELECTION CRITERIA We included all randomised controlled trials (RCTs), as well as non-RCTs and controlled before-and-after studies (CBAs), that met Cochrane EPOC (Effective Practice and Organisation of Care) criteria, that involved the transfusion of platelets prior to surgery (any dose, at any time, single or multiple) in people with low platelet counts. We excluded studies on people with a low platelet count who were actively bleeding. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane for data collection. We were only able to combine data for two outcomes and we presented the rest of the findings in a narrative form. MAIN RESULTS We identified five RCTs, all conducted in adults; there were no eligible non-randomised studies. Three completed trials enrolled 180 adults and two ongoing trials aim to include 627 participants. The completed trials were conducted between 2005 and 2009. The two ongoing trials are scheduled to complete recruitment by October 2019. One trial compared prophylactic platelet transfusions to no transfusion in people with thrombocytopenia in an intensive care unit (ICU). Two small trials, 108 participants, compared prophylactic platelet transfusions to other alternative treatments in people with liver disease. One trial compared desmopressin to fresh frozen plasma or one unit of platelet transfusion or both prior to surgery. The second trial compared platelet transfusion prior to surgery with two types of thrombopoietin mimetics: romiplostim and eltrombopag. None of the included trials were free from methodological bias. No included trials compared different platelet count thresholds for administering a prophylactic platelet transfusion prior to surgery. None of the included trials reported on all the review outcomes and the overall quality per reported outcome was very low.None of the three completed trials reported: all-cause mortality at 90 days post surgery; mortality secondary to bleeding, thromboembolism or infection; number of red cell or platelet transfusions per participant; length of hospital stay; or quality of life.None of the trials included children or people who needed major surgery or emergency surgical procedures.Platelet transfusion versus no platelet transfusion (1 trial, 72 participants)We were very uncertain whether giving a platelet transfusion prior to surgery had any effect on all-cause mortality within 30 days (1 trial, 72 participants; risk ratio (RR) 0.78, 95% confidence interval (CI) 0.41 to 1.45; very-low quality evidence). We were very uncertain whether giving a platelet transfusion prior to surgery had any effect on the risk of major (1 trial, 64 participants; RR 1.60, 95% CI 0.29 to 8.92; very low-quality evidence), or minor bleeding (1 trial, 64 participants; RR 1.29, 95% CI 0.90 to 1.85; very-low quality evidence). No serious adverse events occurred in either study arm (1 trial, 72 participants, very low-quality evidence).Platelet transfusion versus alternative to platelet transfusion (2 trials, 108 participants)We were very uncertain whether giving a platelet transfusion prior to surgery compared to an alternative has any effect on the ri
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Pathogen-reduced platelets for the prevention of bleeding
Estcourt LJ, Malouf R, Hopewell S, Trivella M, Doree C, Stanworth SJ, Murphy MF
The Cochrane Database of Systematic Reviews. 2017;((7)):CD009072.
Abstract
BACKGROUND Platelet transfusions are used to prevent and treat bleeding in people who are thrombocytopenic. Despite improvements in donor screening and laboratory testing, a small risk of viral, bacterial, or protozoal contamination of platelets remains. There is also an ongoing risk from newly emerging blood transfusion-transmitted infections for which laboratory tests may not be available at the time of initial outbreak.One solution to reduce the risk of blood transfusion-transmitted infections from platelet transfusion is photochemical pathogen reduction, in which pathogens are either inactivated or significantly depleted in number, thereby reducing the chance of transmission. This process might offer additional benefits, including platelet shelf-life extension, and negate the requirement for gamma-irradiation of platelets. Although current pathogen-reduction technologies have been proven to reduce pathogen load in platelet concentrates, a number of published clinical studies have raised concerns about the effectiveness of pathogen-reduced platelets for post-transfusion platelet count recovery and the prevention of bleeding when compared with standard platelets.This is an update of a Cochrane review first published in 2013. OBJECTIVES To assess the effectiveness of pathogen-reduced platelets for the prevention of bleeding in people of any age requiring platelet transfusions. SEARCH METHODS We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 9), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 24 October 2016. SELECTION CRITERIA We included RCTs comparing the transfusion of pathogen-reduced platelets with standard platelets, or comparing different types of pathogen-reduced platelets. DATA COLLECTION AND ANALYSIS We used the standard methodological procedures expected by Cochrane. MAIN RESULTS We identified five new trials in this update of the review. A total of 15 trials were eligible for inclusion in this review, 12 completed trials (2075 participants) and three ongoing trials. Ten of the 12 completed trials were included in the original review. We did not identify any RCTs comparing the transfusion of one type of pathogen-reduced platelets with another.Nine trials compared Intercept(R) pathogen-reduced platelets to standard platelets, two trials compared Mirasol(R) pathogen-reduced platelets to standard platelets; and one trial compared both pathogen-reduced platelets types to standard platelets. Three RCTs were randomised cross-over trials, and nine were parallel-group trials. Of the 2075 participants enrolled in the trials, 1981 participants received at least one platelet transfusion (1662 participants in Intercept(R) platelet trials and 319 in Mirasol(R) platelet trials).One trial included children requiring cardiac surgery (16 participants) or adults requiring a liver transplant (28 participants). All of the other participants were thrombocytopenic individuals who had a haematological or oncological diagnosis. Eight trials included only adults.Four of the included studies were at low risk of bias in every domain, while the remaining eight included studies had some threats to validity.Overall, the quality of the evidence was low to high across different outcomes according to GRADE methodology.We are very uncertain as to whether pathogen-reduced platelets increase the risk of any bleeding (World Health Organization (WHO) Grade 1 to 4) (5 trials, 1085 participants; fixed-effect risk ratio (RR) 1.09, 95% confidence interval (CI) 1.02 to 1.15; I2 = 59%, random-effect RR 1.14, 95% CI 0.93 to 1.38; I2 = 59%; low-quality evidence).There was no evidence of a difference between pathogen-reduced platelets and standard platelets in the incidence of clinically significant bleeding complications (WHO Grade 2 or higher) (5 trials, 1392 participants; RR 1.10, 95% CI 0.97 to 1.25; I2 = 0%; moderate-quality evidence), and there
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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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Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: a meta-analysis and systematic review
Desborough M, Hadjinicolaou AV, Chaimani A, Trivella M, Vyas P, Doree C, Hopewell S, Stanworth SJ, Estcourt LJ
The Cochrane Database of Systematic Reviews. 2016;((10)):CD012055.
Abstract
People with thrombocytopenia due to bone marrow failure are vulnerable to bleeding. Platelet transfusions have limited efficacy in this setting and alternative agents that could replace, or reduce platelet transfusion, and are effective at reducing bleeding are needed. To compare the relative efficacy of different interventions for patients with thrombocytopenia due to chronic bone marrow failure and to derive a hierarchy of potential alternative treatments to platelet transfusions. We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (the Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 27 April 2016. We included randomised controlled trials in people with thrombocytopenia due to chronic bone marrow failure who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII (rFVIIa), desmopressin (DDAVP), recombinant factor XIII (rFXIII), recombinant interleukin (rIL)6 or rIL11, or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard of care or platelet transfusion). We excluded people undergoing intensive chemotherapy or stem cell transfusion. Two review authors independently screened search results, extracted data and assessed trial quality. We estimated summary risk ratios (RR) for dichotomous outcomes. We planned to use summary mean differences (MD) for continuous outcomes. All summary measures are presented with 95% confidence intervals (CI).We could not perform a network meta-analysis because the included studies had important differences in the baseline severity of disease for the participants and in the number of participants undergoing chemotherapy. This raised important concerns about the plausibility of the transitivity assumption in the final dataset and we could not evaluate transitivity statistically because of the small number of trials per comparison. Therefore, we could only perform direct pairwise meta-analyses of included interventions.We employed a random-effects model for all analyses. We assessed statistical heterogeneity using the I2 statistic and its 95% CI. The risk of bias of each study included was assessed using the Cochrane 'Risk of bias' tool. The quality of the evidence was assessed using GRADE methods. We identified seven completed trials (472 participants), and four ongoing trials (recruiting 837 participants) which are due to be completed by December 2020. Of the seven completed trials, five trials (456 participants) compared a TPO mimetic versus placebo (four romiplostim trials, and one eltrombopag trial), one trial (eight participants) compared DDAVP with placebo and one trial (eight participants) compared tranexamic acid with placebo. In the DDAVP trial, the only outcome reported was the bleeding time. In the tranexamic acid trial there were methodological flaws and bleeding definitions were subject to significant bias. Consequently, these trials could not be incorporated into the quantitative synthesis. No randomised trial of artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII, rIL6 or rIL11 was identified.We assessed all five trials of TPO mimetics included in this review to be at high risk of bias because the trials were funded by the manufacturers of the TPO mimetics and the authors had financial stakes in the sponsoring companies.The GRADE quality of the evidence was very low to moderate across the different outcomes.There was insufficient evidence to detect a difference in the number of participants with at least one bleeding episode between TPO mimetics and placebo (RR 0.86, 95% CI 0.56 to 1.31, four trials, 206 participants, low-quality evidence).There was insufficient evidence to detect a difference in the risk of a life-threatening bleed between those treated with a TPO mimetic and placebo (RR 0.31, 95% CI 0.04 to 2.26, one tri
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Use of platelet transfusions prior to lumbar punctures or epidural anaesthesia for the prevention of complications in people with thrombocytopenia
Estcourt LJ, Ingram C, Doree C, Trivella M, Stanworth SJ
The Cochrane Database of Systematic Reviews. 2016;((5)):CD011980.
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Abstract
BACKGROUND People with a low platelet count (thrombocytopenia) often require lumbar punctures or an epidural anaesthetic. Lumbar punctures can be diagnostic (haematological malignancies, epidural haematoma, meningitis) or therapeutic (spinal anaesthetic, administration of chemotherapy). Epidural catheters are placed for administration of epidural anaesthetic. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to lumbar punctures and epidural anaesthesia, in order to mitigate the risk of serious procedure-related bleeding. However, the platelet count threshold recommended prior to these procedures varies significantly from country to country. This indicates significant uncertainty among clinicians of the correct management of these patients. The risk of bleeding appears to be low but if bleeding occurs it can be very serious (spinal haematoma). Therefore, people may be exposed to the risks of a platelet transfusion without any obvious clinical benefit. OBJECTIVES To assess the effects of different platelet transfusion thresholds prior to a lumbar puncture or epidural anaesthesia in people with thrombocytopenia (low platelet count). SEARCH METHODS We searched for randomised controlled trials (RCTs) in CENTRAL (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), EMBASE (from 1974), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 3 March 2016. 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 of any age with thrombocytopenia requiring insertion of a lumbar puncture needle or epidural catheter. We only included RCTs published in English. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS We identified no completed or ongoing RCTs in English. We did not exclude any completed or ongoing RCTs because they were published in another language. AUTHORS' CONCLUSIONS There is no evidence from RCTs to determine what is the correct platelet transfusion threshold prior to insertion of a lumbar puncture needle or epidural catheter. There are no ongoing registered RCTs assessing the effects of different platelet transfusion thresholds prior to the insertion of a lumbar puncture or epidural anaesthesia in people with thrombocytopenia. Any future RCT would need to be very large to detect a difference in the risk of bleeding. We would need to design a study with at least 47,030 participants to be able to detect an increase in the number of people who had major procedure-related bleeding from 1 in 1000 to 2 in 1000.
Clinical Commentary
Richard Kaufman MD, Brigham and Women’s Hospital, Boston
What is known?
In rare cases, bleeding complicates lumbar punctures and epidural anesthesia. The clinical consequences of bleeding in this setting range from trivial (traumatic tap detectable by cerebrospinal fluid cell count only) to devastating (spinal hematoma/paralysis). Most cases of spinal hematoma following lumbar puncture have been reported in patients with platelet counts below 50 X 109 cells/Lalthough other risk factors for bleeding were present in nearly all of these cases.1 Platelet transfusions are often administered prophylactically to thrombocytopenic patients having a lumbar puncture or epidural anesthesia. But what constitutes a safe minimum platelet count to perform these procedures is unclear, and clinical practices and published practice guidelines vary widely. This is an important topic because: (1) lumbar punctures and epidural anesthesia are performed commonly; (2) these procedures have rare but serious risks; (3) platelet transfusions carry a range of infectious and noninfectious risks; and (4) platelet units are expensive and limited in availability.
What did this paper set out to examine?
The authors conducted a systematic review of the literature aimed at evaluating the risks and benefits of different platelet transfusion thresholds before a lumbar puncture or epidural anesthesia in thrombocytopenic patients. This was an update of a 2016 Cochrane Review.
What did they show?
The authors found that the published literature on this topic remains extremely limited. They identified no high-quality studies. After rigorously screening 999 published reports, the authors included in their analysis only three retrospective cohort studies describing participants who received or did not receive lumbar puncture. One study was in adults; the other two were in children. No study compared different platelet count thresholds before a procedure. No major bleeding complications occurred in the two studies reporting this outcome (150 participants). There was no difference in minor bleeding (traumatic taps) among pediatric or adult patients who received or did not receive platelet transfusion pre-procedure. The authors concluded that no clinical study evidence exists on which to base a correct platelet transfusion threshold before lumbar puncture or epidural anesthesia.
At this time, it is impossible to make firm recommendations on whether platelet transfusions should be administered before lumbar puncture or epidural anesthesia in thrombocytopenic children or adults. A safe minimum platelet count for performing these procedures cannot be identified based on the existing data. Until stronger data allow us to better understand the risks and benefits of platelet transfusion before lumbar puncture or epidural anesthesia, practices will vary among clinicians and will remain a matter of clinical judgment.
What are the implications for practice and for future work?
What are the implications for future research?Because bleeding complication rates are so low in the setting of lumbar puncture and epidural anesthesia, the authors estimate that performing a randomized trial would require more than 47,000 participants. Utilizing large electronic patient registries/databases thus appears to be the only realistic way that our understanding in this area could be improved moving forward.
Predicting bleeding in the setting of any invasive procedure has proven to be remarkably difficult. Hemostasis is complex; bleeding from most procedures is rare; and the tools that we have to assess bleeding risk are crude. Platelet counts tell us nothing about platelet hemostatic function. Other variables, including medications, coagulation factor activity, tissue integrity, and disease state may predominate in determining a patient’s bleeding risk. Platelet counts are easy to measure, but hopefully in the future we will discover better ways to determine whether a platelet transfusion should be given.
What are the implications for future practice? At this time, it is impossible to make firm recommendations on whether platelet transfusions should be administered before lumbar puncture or epidural anesthesia in thrombocytopenic children or adults. A safe minimum platelet count for performing these procedures cannot be identified based on the existing data. Until stronger data allow us to better understand the risks and benefits of platelet transfusion before lumbar puncture or epidural anesthesia, practices will vary among clinicians and will remain a matter of clinical judgment.
References
1. Van Veen JJ, Nokes TJ, Makris M. The risk of spinal haematoma following neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals. Br J Haematol. 148(1):15-25.
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A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation
Crighton GL, Estcourt LJ, Wood EM, Trivella M, Doree C, Stanworth S
Cochrane Database of Systematic Reviews.. 2015;((9)):CD010981.
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.This is an update of a Cochrane review first published in 2004 and updated in 2012 that addressed four separate questions: therapeutic-only versus prophylactic platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. We have now split this review into four smaller reviews looking at these questions individually; this review is the first part of the original review. OBJECTIVES To determine whether a therapeutic-only platelet transfusion policy (platelet transfusions given when patient bleeds) is as effective and safe as a prophylactic platelet transfusion policy (platelet transfusions given to prevent bleeding, usually when the platelet count falls below a given trigger level) in patients with haematological disorders undergoing myelosuppressive chemotherapy or stem cell transplantation. SEARCH METHODS We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (Cochrane Library 2015, Issue 6), 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 RCTs involving transfusions of platelet concentrates prepared either from individual units of whole blood or by apheresis, and given to prevent or treat bleeding in patients with malignant haematological disorders receiving myelosuppressive chemotherapy or undergoing HSCT. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS We identified seven RCTs that compared therapeutic platelet transfusions to prophylactic platelet transfusions in haematology patients undergoing myelosuppressive chemotherapy or HSCT. One trial is still ongoing, leaving six trials eligible with a total of 1195 participants. These trials were conducted between 1978 and 2013 and enrolled participants from fairly comparable patient populations. We were able to critically appraise five of these studies, which contained separate data for each arm, and were unable to perform quantitative analysis on one study that did not report the numbers of participants in each treatment arm.Overall the quality of evidence per outcome was low to moderate according to the GRADE approach. None of the included studies were at low risk of bias in every domain, and all the studies identified had some threats to validity. We deemed only one study to be at low risk of bias in all domains other than blinding.Two RCTs (801 participants) reported at least one bleeding episode within 30 days of the start of the study. We were unable to perform a meta-analysis due to considerable statistical heterogeneity between studies. The statistical heterogeneity seen may relate to the different methods used in studies for the assessment and grading of bleeding. The underlying patient diagnostic and treatment categories also appeared to have some effect on bleeding risk. Individually these studies showed a similar effect, that a therapeutic-only platelet transfusion strategy was associated with an increased risk of clinically significant bleeding compared with a prophylactic platelet transfusion policy. Number of days with a clinically significant bleeding event per participant was higher in the therapeutic-only group than in the prophylactic group (one RCT; 600 participants; mean difference 0.50, 95% confidence interval (CI) 0.10 to 0.90; moderate-quality evidence). There was insufficient evidence to determine whether there was any difference in the number of participants with severe or
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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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Different doses of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation
Estcourt LJ, Stanworth S, Doree C, Trivella M, Hopewell S, Blanco P, Murphy MF
Cochrane Database of Systematic Reviews.. 2015;((10)):CD010984.
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 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; this review compares different platelet transfusion doses. OBJECTIVES To determine whether different doses of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect their efficacy and safety in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy with or without haematopoietic stem cell transplantation (HSCT). SEARCH METHODS We searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6), 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 Randomised controlled trials involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with malignant haematological disorders or undergoing HSCT that compared different platelet component doses (low dose 1.1 x 10(11)/m(2) +/- 25%, standard dose 2.2 x 10(11)/m(2) +/- 25%, high dose 4.4 x 10(11)/m(2) +/- 25%). DATA COLLECTION AND ANALYSIS We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS We included seven trials (1814 participants) in this review; six were conducted during one course of treatment (chemotherapy or HSCT).Overall the methodological quality of studies was low to moderate 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.Five 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 difference in the number of participants with a clinically significant bleeding episode between the low-dose and standard-dose groups (four studies; 1170 participants; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.13; moderate-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence); or high-dose and standard-dose groups (two studies; 951 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence).Three studies reported the number of days with a clinically significant bleeding event per participant. There was no difference in the number of days of bleeding per participant between the low-dose and standard-dose groups (two studies; 230 participants; mean difference -0.17, 95% CI -0.51 to 0.17; low quality evidence). One study (855 participants) showed no difference in the number of days of bleeding per participant between high-dose and standard-dose groups, or between low-dose and high-dose groups (849 participants).Three studies reported the number of participants with severe or life-threatening bleeding. There was no difference in the number of participants with severe or life-threatening bleeding between a low-dose and a standard-dose platelet transfusion policy (three studies; 1059 participants; RR 1.33, 95% CI 0.91 to 1.92; low-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.20, 95% C
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Pathogen-reduced platelets for the prevention of bleeding
Butler C, Doree C, Estcourt LJ, Trivella M, Hopewell S, Brunskill SJ, Stanworth S, Murphy MF
Cochrane Database of Systematic Reviews.. 2013;3:CD009072.
Abstract
BACKGROUND Platelet transfusions are used to prevent and treat bleeding in patients who are thrombocytopenic. Despite improvements in donor screening and laboratory testing, a small risk of viral, bacterial or protozoal contamination of platelets remains. There is also an ongoing risk from newly emerging blood transfusion-transmitted infections (TTIs) for which laboratory tests may not be available at the time of initial outbreak.One solution to reduce further the risk of TTIs from platelet transfusion is photochemical pathogen reduction, a process by which pathogens are either inactivated or significantly depleted in number, thereby reducing the chance of transmission. This process might offer additional benefits, including platelet shelf-life extension, and negate the requirement for gamma-irradiation of platelets. Although current pathogen-reduction technologies have been proven significantly to reduce pathogen load in platelet concentrates, a number of published clinical studies have raised concerns about the effectiveness of pathogen-reduced platelets for post-transfusion platelet recovery and the prevention of bleeding when compared with standard platelets. OBJECTIVES To assess the effectiveness of pathogen-reduced platelets for the prevention of bleeding in patients requiring platelet transfusions. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library2013, Issue 1), MEDLINE (1950 to 18 February 2013), EMBASE (1980 to 18 February 2013), CINAHL (1982 to 18 February 2013) and the Transfusion Evidence Library (1980 to 18 February 2013). We also searched several international and ongoing trial databases and citation-tracked relevant reference lists. We requested information on possible unpublished trials from known investigators in the field. SELECTION CRITERIA We included randomised controlled trials (RCTs) comparing the transfusion of pathogen-reduced platelets with standard platelets. We did not identify any RCTs which compared the transfusion of one type of pathogen-reduced platelets with another. DATA COLLECTION AND ANALYSIS One author screened all references, excluding duplicates and those clearly irrelevant. Two authors then screened the remaining references, confirmed eligibility, extracted data and analysed trial quality independently. We requested and obtained a significant amount of missing data from trial authors. We performed meta-analyses where appropriate using the fixed-effect model for risk ratios (RR) or mean differences (MD), with 95% confidence intervals (95% CI), and used the I2 statistic to explore heterogeneity, employing the random-effects model when I2 was greater than 30%. MAIN RESULTS We included 10 trials comparing pathogen-reduced platelets with standard platelets. Nine trials assessed Intercept pathogen-reduced platelets and one trial Mirasol pathogen-reduced platelets. Two were randomised cross-over trials and the remaining eight were parallel-group RCTs. In total, 1422 participants were available for analysis across the 10 trials, of which 675 participants received Intercept and 56 Mirasol platelet transfusions. Four trials assessed the response to a single study platelet transfusion (all Intercept) and six to multiple study transfusions (Intercept (N = 5), Mirasol (N = 1)) compared with standard platelets.We found the trials to be generally at low risk of bias but heterogeneous regarding the nature of the interventions (platelet preparation), protocols for platelet transfusion, definitions of outcomes, methods of outcome assessment and duration of follow-up.Our primary outcomes were mortality, 'any bleeding', 'clinically significant bleeding' and 'severe bleeding', and were grouped by duration of follow-up: short (up to 48 hours), medium (48 hours to seven days) or long (more than seven days). Meta-analysis of data from five trials of multiple platelet transfusions reporting 'any bleeding' over a long follow-up period found an increase in bleeding in those receiving pathogen-reduced platelets compared with standard platele