Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders.
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RATIONALE: People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review last published in 2016 (with database searches conducted on 7 March 2016). OBJECTIVES: To determine the benefits and harms of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Transfusion Evidence Library, and ongoing trial databases on 21 January 2025. We handsearched the reference lists of all identified randomised controlled trials (RCTs). We contacted the authors of relevant studies, study groups, and experts worldwide known to be active in the field to request information about unpublished material or further information on ongoing studies. ELIGIBILITY CRITERIA: We included RCTs in people with haematological disorders who required prophylactic platelet transfusions to prevent bleeding. We only included RCTs in which the interventions were the lysine analogues TXA or EACA. OUTCOMES: We assessed bleeding severity using the World Health Organization (WHO) bleeding scale (ordinal grades 0 to 4, with higher grades indicating more severe bleeding), which has been widely applied in thrombocytopenia studies. The outcomes prioritised for the summary of findings tables were: number of participants with grade 2 bleeding or higher; number of participants with grade 3 bleeding or higher; number of participants with any thromboembolism; all-cause mortality; and adverse events attributable to antifibrinolytic drugs. We provide results only for these outcomes below. RISK OF BIAS: We used Cochrane's risk of bias 2 (RoB 2) tool. We used this tool to re-assess the previously included trials. SYNTHESIS METHODS: For this update, two review authors independently selected trials for inclusion, assessed methodological quality and risk of bias, and extracted data. We used fixed-effect models for the meta-analysis. We analysed dichotomous outcomes using risk ratios (RRs) with 95% confidence intervals (CIs), and the Peto odds ratio (Peto OR) for outcomes with very low event rates (< 3% in both arms). We assessed the certainty of the evidence using the GRADE approach. INCLUDED STUDIES: We included eight RCTs (four newly included studies plus four from the previous versions) with a total of 1041 participants in this review update. Six trials compared TXA to placebo, one trial compared EACA to no EACA, and one trial compared EACA to standard platelet transfusion. We found no trials comparing TXA to EACA. Seven trials recruited adults, while one enroled children. SYNTHESIS OF RESULTS: Tranexamic acid (TXA) versus placebo There may be no difference between TXA and placebo in the risk of experiencing grade 2 bleeding or higher, grade 3 bleeding or higher, thromboembolism, death, and drug-related adverse events, although the certainty of the evidence varied from very low to moderate for these outcomes: grade 2 bleeding or higher: RR 0.89, 95% CI 0.75 to 1.05; I² = 7%; 3 studies, 894 participants; moderate-certainty evidence; grade 3 bleeding or higher: RR 1.07, 95% CI 0.51 to 2.22; I² = 6%; 3 studies, 894 participants; low-certainty evidence; any thromboembolism: Peto OR 0.85, 95% CI 0.39 to 1.86; I² = 0%; 5 studies, 984 participants; low-certainty evidence; all-cause mortality: Peto OR 1.50, 95% CI 0.62 to 3.63; I² = 37%; 3 studies, 930 participants; very low-certainty evidence; and number of adverse events attributable to antifibrinolytic drugs: Peto OR 2.24, 95% CI 0.64 to 7.78; I² = 0%; 3 studies, 949 participants; very low-certainty evidence. Epsilon aminocaproic acid (EACA) versus no EACA The single study addressing this comparison did not report bleeding severity in a form suitable for analysis, and did not report on the number of participants with any thromboembolism or all-cause mortality. The study reported that no patient died of thrombosis. There was insufficient evidence to analyse adverse events attributable to antifibrinolytic drugs. AUTHORS' CONCLUSIONS: For people with thrombocytopenia and haematological malignancies, TXA probably makes little to no difference to clinically significant bleeding (i.e. grade 2 or higher), and may make little to no difference to severe or life-threatening bleeding (i.e. grade 3 or higher) or any thromboembolism. The evidence is of very low certainty for all-cause mortality and serious adverse events attributable to antifibrinolytic drugs. For EACA compared to no EACA, there are insufficient data to assess clinically significant bleeding, life-threatening bleeding, any thromboembolism, all-cause mortality, and serious adverse events. Those making decisions about administration of prophylactic TXA to people with thrombocytopenia and haematological malignancies should consider that current evidence does not show a benefit or harm for TXA for preventing clinically significant or life-threatening bleeding. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol (2012): DOI: 10.1002/14651858.CD009733. Original review (2013): DOI: 10.1002/14651858.CD009733.pub2. Review update (2016): DOI: 10.1002/14651858.CD009733.pub3.kljkj.