Antifibrinolytic therapy for preventing oral bleeding in people on anticoagulants undergoing minor oral surgery or dental extractions



Individuals on continuous treatment with vitamin K antagonists (VKAs) or direct oralanticoagulants (DOACs) are at increased risk of bleeding complications during and after oralor 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 bleedingcomplications in people on oral anticoagulants undergoing minor oral surgery or dentalextractions.

Search methods

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, 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.

Selection criteria

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.

Data collection and analysis

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.

Main results

No eligible trials in people on continuous treatment with DOACs undergoing oral or dentalprocedures were identified.

Three randomised trials and one quasi‐randomised trial (follow‐up in all was seven days) inpeople 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 antifibrinolyticagent 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 ofantifibrinolytic 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 VKAsundergoing 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 DOACsundergoing oral or dental procedures. Therefore, a beneficial effect of antifibrinolytic therapycan currently only be assumed based on data from the people using VKAs.

Plain language summary

Drugs that prevent oral bleeding in people using oral anticoagulants undergoing minororal surgery or dental extractions

Review question

We reviewed the evidence about whether antifibrinolytic medicine (drugs that preventbreakdown of a blood clot), such as tranexamic acid or epsilon aminocaproic acid, canprevent oral bleeding after minor oral surgery or dental extractions in people using oralanticoagulants (blood thinners that are taken by mouth) without interruption during the procedure.


People on continuous oral anticoagulant treatment are at an increased risk of bleedingcomplications during and after oral surgery or dental extractions. There are two types of oralanticoagulant treatment: vitamin K antagonists (VKAs) (e.g. warfarin and coumarin) and direct oral anticoagulants (DOACs) (e.g. dabigatran, rivaroxaban, apixaban, edoxaban). DOACs are becoming an increasingly popular alternative for VKAs, traditionally used for preventingblood clotting in people at risk of thrombosis. The number of bleeds and the severity of eachbleed depend on medication‐related factors (such as the degree of anticoagulation, measured by the international normalised ratio (INR)), surgery‐related factors (such as the size of the wound or the number of roots extracted), as well as patient‐related factors (such as inflammation of the gums or blood vessel diseases). The INR level is important to determine how well the anticoagulant treatment is preventing blood clots. Within the desired range of the INR level, a person has both the least risk of blood clotting complications and the least risk of excessive bleeding. In routine practice antifibrinolytic medicine is often used before, during and after minor oral surgery or dental extractions for people using oral anticoagulants. The question is whether there is reliable scientific evidence for this practice.

Search date

The evidence is current to: 04 January 2018.

Study characteristics

We did not find any trials of antifibrinolytic medicine for preventing bleeding after minor oralsurgery or dental extractions in people using DOACs. This review includes four trials (253 participants) in people continuously treated with VKAs during minor oral surgery or dentalextractions. The earliest included trial was published in 1989 and the most recent one in 2015. The mean age of all participants was 60 years. The follow‐up time in all trials was seven days.

Key results

Overall, the included trials showed a reduction in the number of bleeds after dental extraction when using tranexamic acid solution in the mouth. Combining the results of the separate trials it appeared that antifibrinolytic medication reduces the bleeding rate after dentalextractions by 25% when compared to placebo (‘dummy’ treatment). However, there was no difference in bleeding rate between people treated with tranexamic acid and those treated with standard care (e.g. gauze compression or stitches). Side effects of the antifibrinolyticmedication rarely occurred and did not lead to individuals discontinuing tranexamic acid treatment.

No evidence was found for people being treated with DOACs. It could, however, be argued that, if antifibrinolytic medicine is effective in people on continuous treatment with VKAs, it might also work for people receiving other comparable anticoagulant drugs.

Quality of evidence

In relation to the review’s two primary outcomes of number of postoperative bleeds and side effects of therapy, we judged there to be moderate‐quality evidence.

In the two trials comparing tranexamic acid with placebo, the risk of bias, in relation to trial design, was considered to be low, in the two trials comparing tranexamic acid to standard care (gelatin sponge and sutures; or dry gauze compression) the risk of bias was considered to be moderate. This was mainly due to the lack of blinding (a way of making sure that thepeople involved in the trial do not know which trial arm they are assigned to) and inadequate allocation concealment (using the play of chance to assign participants to comparison groups to prevent selection bias) in two of these trials. There were differences between the trials with regards to different standard care treatments.

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