Engelen Eveline T, Schutgens Roger Eg, Mauser-Bunschoten Evelien P, van Es Robert Jj, van Galen Karin Pm
University Medical Centre Utrecht, Poortstraat 95, Utrecht, Netherlands, 3572HG.
Cochrane Database Syst Rev. 2018 Jul 2;7(7):CD012293. doi: 10.1002/14651858.CD012293.pub2.
Individuals on continuous treatment with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) are at increased risk of bleeding complications during and after oral or dental procedures. Anticoagulant treatment is preferably continued at the same dose, since dose reduction or discontinuation of treatment is associated with an increased risk of thromboembolism. The use of haemostatic measures during or after the procedure (or both) could enable continuation of the oral anticoagulant treatment.
We aimed to assess the efficacy of antifibrinolytic agents for preventing bleeding complications in people on oral anticoagulants undergoing minor oral surgery or dental extractions.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. We searched PubMed, Embase and the Cochrane Library. Additional searches were performed using ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), the CINAHL database of nursing and allied health services, the open access ProQuest dissertation database, papers and reports from the American College of Clinical Pharmacy (ACCP) and abstract books from annual scientific conferences.Date of last search: 04 January 2018.
Randomised and quasi-randomised controlled trials in people on continuous treatment with VKAs or DOACs undergoing oral or dental procedures using antifibrinolytic agents (tranexamic acid (TXA) or epsilon aminocaproic acid) to prevent perioperative bleeding compared to no intervention or usual care with or without placebo.
Two authors independently screened the titles and abstracts of all identified articles. Full texts were obtained from potentially relevant abstracts and two authors independently assessed these for inclusion based of the selection criteria. A third author verified trial eligibility. Two authors independently performed data extraction and risk of bias assessments using standardized forms. The quality of the evidence was assessed using GRADE.
No eligible trials in people on continuous treatment with DOACs undergoing oral or dental procedures were identified.Three randomised trials and one quasi-randomised trial (follow-up in all was seven days) in people on continuous treatment with VKAs were included with a total of 253 participants (mean age 60 years). Two trials published in 1989 and 1993 compared the antifibrinolytic agent TXA with placebo in people using VKAs. Two other trials were published in 1999 and 2015 and compared TXA with gelatin sponge and sutures, and dry gauze compression, respectively. In all included trials, those who were treated with VKAs had international normalised ratio (INR) values within the therapeutic range and TXA was applied locally, not systemically.The two trials from 1989 and 1993 comparing TXA with placebo showed a statistically significant beneficial effect regarding the number of major postoperative bleeding episodes requiring intervention, with a pooled risk difference (RD) of -0.25 (95% confidence interval (CI) -0.36 to -0.14) (128 participants) (moderate-quality evidence). For the two trials that compared TXA with either gelatin sponge and sutures or with dry gauze compression, there was no difference between the TXA and the standard care group, RD 0.02 (95% CI -0.07 to 0.11) (125 participants) (moderate-quality evidence). The combined RD of all included trials was -0.13 (95% CI -0.30 to 0.05) (moderate-quality evidence). There were no side effects of antifibrinolytic therapy that required treatment withdrawal (128 participants) (moderate-quality evidence). Despite heterogeneity between trials with respect to the different haemostatic measures used in the control groups, the trials were comparable regarding design and baseline participant characteristics.Overall, we considered the risk of bias to be low in the trials comparing TXA with placebo and moderate in the trials comparing TXA with alternative haemostatic measures.
AUTHORS' CONCLUSIONS: Based on the results of this Cochrane Review, there seems to be a beneficial effect of locally applied TXA in preventing oral bleeding in people on continuous treatment with VKAs undergoing minor oral surgery or dental extractions. However, the small number of identified randomised controlled trials, the relatively small number of participants included in the trials and the differences in standard therapy and treatment regimens between trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in this population.We were unable to identify any eligible trials in people on continuous treatment with DOACs undergoing oral or dental procedures. Therefore, a beneficial effect of antifibrinolytic therapy can currently only be assumed based on data from the people using VKAs.
正在接受维生素K拮抗剂（VKA）或直接口服抗凝剂（DOAC）持续治疗的个体，在进行口腔或牙科手术期间及术后发生出血并发症的风险增加。抗凝治疗最好维持相同剂量，因为减少剂量或中断治疗会增加血栓栓塞风险。在手术期间或术后（或两者均采用）采取止血措施可使口服抗凝治疗得以继续。
我们旨在评估抗纤维蛋白溶解剂对接受小手术或拔牙的口服抗凝剂使用者预防出血并发症的疗效。
我们检索了Cochrane囊性纤维化和遗传性疾病凝血障碍试验注册库，该注册库通过电子数据库检索以及对期刊和会议摘要书籍的手工检索汇编而成。我们还检索了相关文章和综述的参考文献列表。我们检索了PubMed、Embase和Cochrane图书馆。另外还使用ClinicalTrials.gov、国际临床试验注册平台（ICTRP）、护理及相关健康服务领域的CINAHL数据库、开放获取的ProQuest学位论文数据库、美国临床药师学会（ACCP）的论文和报告以及年度科学会议的摘要书籍进行了检索。最后检索日期：2018年1月4日。
针对正在接受VKA或DOAC持续治疗、进行口腔或牙科手术并使用抗纤维蛋白溶解剂（氨甲环酸（TXA）或ε-氨基己酸）预防围手术期出血的人群开展的随机和半随机对照试验，与不干预或使用或不使用安慰剂的常规护理进行比较。
两位作者独立筛选所有已识别文章的标题和摘要。从可能相关的摘要中获取全文，两位作者根据选择标准独立评估这些全文是否纳入。第三位作者核实试验的合格性。两位作者使用标准化表格独立进行数据提取和偏倚风险评估。使用GRADE评估证据质量。
未识别到关于正在接受DOAC持续治疗、进行口腔或牙科手术的人群的合格试验。纳入了三项随机试验和一项半随机试验（所有试验的随访期均为7天），这些试验针对正在接受VKA持续治疗的人群，共有253名参与者（平均年龄60岁）。1989年和1993年发表的两项试验比较了使用VKA的人群中抗纤维蛋白溶解剂TXA与安慰剂的效果。另外两项试验分别于1999年和2015年发表，比较了TXA与明胶海绵及缝线以及干纱布压迫的效果。在所有纳入试验中，接受VKA治疗的患者国际标准化比值（INR）值在治疗范围内，且TXA是局部应用而非全身应用。1989年和1993年比较TXA与安慰剂的两项试验显示，在需要干预的术后大出血事件数量方面具有统计学显著的有益效果，合并风险差值（RD）为-0.25（95%置信区间（CI）-0.36至-0.14）（128名参与者）（中等质量证据）。对于比较TXA与明胶海绵及缝线或干纱布压迫的两项试验，TXA组与标准护理组之间无差异，RD为0.02（95%CI -0.07至0.11）（125名参与者）（中等质量证据）。所有纳入试验的合并RD为-0.13（95%CI -0.30至0.05）（中等质量证据）。抗纤维蛋白溶解治疗没有导致需要停药的副作用（128名参与者）（中等质量证据）。尽管各试验在对照组使用的不同止血措施方面存在异质性，但在设计和参与者基线特征方面各试验具有可比性。总体而言，我们认为在比较TXA与安慰剂的试验中偏倚风险较低，而在比较TXA与其他止血措施的试验中偏倚风险为中等。
基于本Cochrane系统评价的结果，对于正在接受VKA持续治疗、进行小手术或拔牙的人群，局部应用TXA在预防口腔出血方面似乎具有有益效果。然而，已识别的随机对照试验数量较少、试验纳入的参与者数量相对较少以及各试验之间标准治疗和治疗方案存在差异，使我们无法得出抗纤维蛋白溶解治疗在该人群中的确切疗效。我们未识别到任何关于正在接受DOAC持续治疗、进行口腔或牙科手术的人群的合格试验。因此，目前只能根据使用VKA人群的数据推测抗纤维蛋白溶解治疗的有益效果。
