1.
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
2.
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
3.
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