Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders
Estcourt LJ, Desborough M, Brunskill SJ, Doree C, Hopewell S, Murphy MF, Stanworth SJ
The Cochrane Database of Systematic Reviews. 2016;((3)):CD009733.
BACKGROUND 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 first published in 2013. OBJECTIVES To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders. SEARCH METHODS 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 1950) and ongoing trial databases to 07 March 2016. SELECTION CRITERIA We included RCTs involving participants 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 review authors independently screened all electronically-derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review 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 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;
Efficacy of tranexamic acid mouthwash as an alternative for factor replacement in gingival bleeding during dental scaling in cases of hemophilia: A randomized clinical trial
Nuvvula S, Gaddam KR, Kamatham R
Contemporary Clinical Dentistry. 2014;5((1):):49-53.
OBJECTIVE The objective of the following study is to evaluate freshly prepared tranexamic acid mouth wash (FTAMW) as an alternative to factor replacement therapy (FRT) in controlling gingival bleeding in hemophiliacs during dental scaling. MATERIALS AND METHODS Experimental treatment regime (ETR) involved saline transfusion followed by FTAMW and the control treatment regime (CTR) involved FRT followed by placebo mouthwash. A total of 22 hemophiliacs randomly received dental scaling under either CTR or ETR at two different visits, following a split mouth design. They were instructed to use the rendered mouthwash 4 times a day for 5 days and record the mouthwash usage and bleeding episodes in a logbook. The difference in the bleeding episodes was analyzed using Chi-square test with the level of significance predetermined at 0.05. RESULTS Totally 19 patients completed the study. Seven patients reported no bleeding either in ETR or CTR; five patients noticed bleeding in CTR, but not in ETR. Three patients noticed bleeding in ETR, but not in CTR. Patients reported ease in usage and cost-effectiveness of ETR. CONCLUSION FTAMW was found to be an effective alternative to FRT in controlling gingival hemorrhage in hemophiliacs during dental scaling.
Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study
Geisthoff UW, Seyfert UT, Kubler M, Bieg B, Plinkert PK, Konig J
Thrombosis Research. 2014;134((3):):565-71.
INTRODUCTION Epistaxis is the most frequent manifestation in hereditary hemorrhagic telangiectasia, in which no optimal treatment exists. It can lead to severe anemia and reduced quality of life. Positive effects of tranexamic acid, an antifibrinolytic drug, have been reported on epistaxis related to this disorder. We sought to evaluate the efficacy of treating nosebleeds in hereditary hemorrhagic telangiectasia with tranexamic acid. MATERIALS AND METHODS In a randomized, double-blind, placebo controlled, cross-over phase IIIB study, 1 gram of tranexamic acid or placebo was given orally 3 times daily for 3months for a total of 6months. RESULTS 22 patients were included in the intention-to-treat analysis. Hemoglobin levels, the primary outcome measure, did not change significantly (p=0.33). The secondary outcome measure was epistaxis score and patients reported a statistically significant reduction in nosebleeds, equaling a clinically relevant 54% diminution (p=0.0031), as compared to the placebo period. No severe side effects were observed. CONCLUSION Tranexamic acid reduces epistaxis in patients with hereditary hemorrhagic telangiectasia. (Clinical trial registration numbers: BfArM 141 CHC 9008-001 and ClinicalTrials.gov NCT01031992). Copyright 2014 Elsevier Ltd. All rights reserved.
Effectiveness in controlling haemorrhage after dental scaling in people with haemophilia by using tranexamic acid mouthwash
Lee AP, Boyle CA, Savidge GF, Fiske J
British Dental Journal. 2005;198((1):):33-8; discussion 26.
AIMS: To compare the effectiveness of tranexamic acid mouthwash (TAMW) in controlling gingival haemorrhage after dental scaling with that of using factor replacement therapy (FRT) prior to dental scaling in people with haemophilia. DESIGN Double-blind cross-over randomised control trial. SETTING Dedicated hospital dental practice for patients with inherited bleeding disorders. METHOD Sixteen patients with haemophilia who required dental scaling participated in this pilot study. The experimental treatment regime (ETR) involved transfusing each patient with saline before scaling both quadrants on one side of the mouth followed by oral rinsing with TAMW four times daily for up to eight days. The control regime (CR) involved giving each patient FRT before scaling the opposite side of the mouth followed by use of a placebo TAMW. Each patient underwent both treatments in a random-ised sequence. Both the operator and the patients were unaware of which were the ETR and CR episodes. On both occasions the patient kept a log book of the rinsing regime and any post-operative bleeding. Additionally, a structured post-treatment telephone interview was conducted to assess the effectiveness and the patient acceptability of the ETR. RESULTS Thirteen patients completed the study. No statistically significant difference was found in gingival bleeding and mouthwashing frequencies between the ETR and the CR (p > 0. 05). Five patients reported no gingival bleeding with either the ETR or the CR. No patient, using either regime, required extra FRT due to gingival haemorrhage. All subjects found the ETR acceptable and easy and reported feeling safe in using TAMW alone to control gingival bleeding after dental scaling. CONCLUSION TAMW use after dental scaling was as effective as using FRT beforehand in controlling gingival haemorrhage for people with haemophilia.
Lack of efficacy of tranexamic acid in thrombocytopenic bleeding
Fricke W, Alling D, Kimball J, Griffith P, Klein H
A controlled, randomized, double-blind study was performed to assess the effect of the oral antifibrinolytic agent tranexamic acid in patients with amegakaryocytic thrombocytopenia as regards their need for platelet transfusions and the number of bleeding episodes experienced. Each patient served as his or her own control and received sequential, randomized courses of either tranexamic acid or an identical placebo. The need for platelet transfusions due to bleeding and the total number of bleeding episodes were compared for tranexamic acid and placebo courses. Patients received platelet transfusions at the discretion of their personal physician and kept detailed records of bleeding episodes. Of three patients who completed the full study, none had a reduction in the need for platelet transfusions. Moreover, in the eight patients who participated in the study, there was no reduction in number of bleeding episodes during tranexamic acid treatment as compared to the number with placebo. Our data indicate that the prophylactic administration of tranexamic acid does not decrease dependence on platelet transfusions or decrease bleeding episodes in patients with bleeding due to amegakaryocytic thrombocytopenia.
Antifibrinolytic treatment in haemophilia: a controlled trial of prophylaxis with tranexamic acid
Bennett AE, Ingram GI, Inglish PJ
British Journal of Haematology. 1973;24((1):):83-8.
Tranexamic acid in the control of spontaneous bleeding in severe haemophilia
Rainsford SG, Jouhar AJ, Hall A
Thrombosis et Diathesis Haemorrhagica. 1973;30((2):):272-9.
Tranexamic acid for prophylaxis in haemophilia
Ingram GI, Inglish PJ, Bennett AE
Journal of Clinical Pathology. 1972;25((7):):629.
Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease
Forbes CD, Barr RD, Reid G, Thomson C, Prentice CR, McNicol GP, Douglas AS
British Medical Journal. 1972;2((5809):):311-3.
In a double-blind trial tranexamic acid (AMCA, Cyclokapron), 1 g three times a day for five days, significantly reduced blood loss and transfusion requirements after dental extraction in patients with haemophilia and Christmas disease. No side effects were seen in either group of patients. Screening tests showed no toxic action of tranexamic acid on the liver, kidney, or heart.