Abstract: We identified three new studies in this update of the review. In total seven studies were eligible for inclusion, three were ongoing RCTs and four were completed studies. The four completed studies were included in the original review and the three ongoing studies were included in this update. We did not identify any RCTs that compared TXA with EACA. Of the four completed studies, one cross-over TXA study (eight participants) was excluded from the outcome analysis because it had very flawed study methodology. 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 participants), one EACA (18 participants) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All three studies included adults with acute leukaemia receiving chemotherapy. One study (12 participants) only included participants with acute promyelocytic leukaemia. None of the studies included children. One of the three studies reported funding sources and this study was funded by a charity. We are uncertain whether antifibrinolytics reduce the risk of bleeding (three studies; 86 participants; very low-quality evidence). Only one study reported the number of bleeding events per participant and there was no difference in the number of bleeding events seen during induction or consolidation chemotherapy between TXA and placebo (induction; 38 participants; mean difference (MD) 1.70 bleeding events, 95% confidence interval (CI) -0.37 to 3.77: consolidation; 18 participants; MD -1.50 bleeding events, 95% CI -3.25 to 0.25; very low-quality evidence). The two other studies suggested bleeding was reduced in the antifibrinolytic study arm, but this was statistically significant in only one of these two studies. Two studies reported thromboembolism and no events occurred (68 participants, very low-quality evidence). All three studies reported a reduction in platelet transfusion usage (three studies, 86 participants; very low-quality evidence), but this was reported in different ways and no meta-analysis could be performed. No trials reported the number of platelet transfusions per participant. Only one study reported the number of platelet components per participant and there was a reduction in the number of platelet components per participant during consolidation chemotherapy but not during induction chemotherapy (consolidation; 18 participants; MD -5.60 platelet units, 95% CI -9.02 to -2.18: induction; 38 participants, MD -1.00 platelet units, 95% CI -9.11 to 7.11; very low-quality evidence). Only one study reported adverse events of TXA as an outcome measure and none occurred. One study stated side effects of EACA were minimal but no further information was provided (two studies, 74 participants, very low-quality evidence). None of the studies reported on the following pre-specified outcomes: overall mortality, adverse events of transfusion, disseminated intravascular coagulation (DIC) or quality of life (QoL). Our results indicate that the evidence available for the use of antifibrinolytics in haematology patients is very limited. The trials were too small to assess whether or not antifibrinolytics decrease bleeding. No trials reported the number of platelet transfusions per participant. The trials were too small to assess whether or not antifibrinolytics increased the risk of thromboembolic events or other adverse events. There are three ongoing RCTs (1276 participants) due to be completed in 2017 and 2020.

Plain-language summary: The evidence is current to March 2016. In this update, seven randomised controlled trials were identified. Three trials are either not yet recruiting or still recruiting participants and and have not been completed. Four randomised controlled trials with a total of 95 participants were reviewed. These trials were conducted between 1983 and 1995. Data from one of the trials (eight participants) was excluded from the outcome analysis because the conduct of the study was so flawed. All three trials (86 participants) included in the outcome analysis were of adults with acute leukaemia receiving chemotherapy. None of the studies included children. One of these three studies reported funding sources and this study was funded by a charity. In people with haematological disorders who have a low platelet count and would usually be treated with platelet transfusions, we are uncertain whether antifibrinolytics decrease the risk of bleeding and the use of platelet transfusions. We are uncertain whether antifibrinolytics increase the risk of developing a clot. We are uncertain whether antifibrinolytics increases the risk of adverse events. None of the studies reported several of this review's outcomes including overall mortality, adverse events of transfusion, and quality of life. The quality of the evidence was very low, making it difficult to draw conclusions or make recommendations regarding the usefulness and safety of antifibrinolytics. The only evidence available is for adults with acute leukaemia receiving chemotherapy. We await the results of the three ongoing trials that are expected to recruit 1276 participants in total by 2020.