Tranexamic acid and bleeding in patients treated with non-vitamin K oral anticoagulants undergoing dental extraction: The EXTRACT-NOAC randomized clinical trial
PLoS medicine. 2021;18(5):e1003601
BACKGROUND Oral bleeding after dental extraction in patients on non-vitamin K oral anticoagulants (NOACs) is a frequent problem. We investigated whether 10% tranexamic acid (TXA) mouthwash decreases post-extraction bleeding in patients treated with NOACs. METHODS AND FINDINGS The EXTRACT-NOAC study is a randomized, double-blind, placebo-controlled, multicenter, clinical trial. Patients were randomly assigned to 10% TXA or placebo mouthwash and were instructed to use the mouthwash prior to dental extraction, for 3 times a day for 3 days thereafter. The primary outcome was the number of patients with any post-extraction oral bleeding up to day 7. Secondary outcomes included the periprocedural, early, and delayed bleeding, and the safety outcomes included all thrombotic events. The first patient was randomized on February 9, 2018 and the last patient on March 12, 2020. Of 222 randomized patients, 218 patients were included in the full analysis set, of which 106 patients were assigned to TXA (74.8 (±8.8) years; 81 men) and 112 to placebo (72.7 (±10.7) years; 64 men). Post-extraction bleeding occurred in 28 (26.4%) patients in the TXA group and in 32 (28.6%) patients in the placebo group (relative risk, 0.92; 95% confidence interval [CI], 0.60 to 1.42; P = 0.72). There were 46 bleeds in the TXA group and 85 bleeds in the placebo group (rate ratio, 0.57; 95% CI, 0.31 to 1.05; P = 0.07). TXA did not reduce the rate of periprocedural bleeding (bleeding score 4 ± 1.78 versus 4 ± 1.82, P = 0.80) and early bleeding (rate ratio, 0.76; 95% CI, 0.42 to 1.37). Delayed bleeding (rate ratio, 0.32; 95% CI, 0.12 to 0.89) and bleeding after multiple extractions (rate ratio, 0.40; 95% CI, 0.20 to 0.78) were lower in the TXA group. One patient in the placebo group had a transient ischemic attack while interrupting the NOAC therapy in preparation for the dental extraction. Two of the study limitations were the premature interruption of the trial following a futility analysis and the assessment of the patients' compliance that was based on self-reported information during follow-up. CONCLUSIONS In patients on NOACs undergoing dental extraction, TXA does not seem to reduce the rate of periprocedural or early postoperative oral bleeding compared to placebo. TXA appears to reduce delayed bleeds and postoperative oral bleeding if multiple teeth are extracted. TRIAL REGISTRATION ClinicalTrials.gov NCT03413891 EudraCT; EudraCT number:2017-001426-17; EudraCT Public website: eudract.ema.europa.eu.
Efficacy and Safety of Tranexamic Acid in Bimaxillary Orthognathic Surgery
Plast Surg (Oakv). 2020;28(2):94-104
Background: Tranexamic acid (TXA) has been widely used during craniofacial and orthognathic surgery (OS). However, results of the literature are inconsistent due to specific type of surgery and a small sample of studies. The purpose of this study was to evaluate the role of TXA in bimaxillary OS. Methods: We performed a comprehensive literature search of PubMed, Cochrane Central Register of Controlled Trials, and EMBASE to identify randomized controlled trials (RCTs) that compared effect of TXA on bimaxillary OS with placebo. Outcomes of interests included intraoperative blood loss, allogenic transfusion, operation time, and volume of irrigation fluid. Random effects models were chosen considering that heterogeneity between studies was anticipated, and I (2) statistics were used to test for the presence of heterogeneity. Results: Totally 6 RCTs were identified. Tranexamic acid resulted in significantly reduced intraoperative blood loss (weighted mean difference [WMD] = -264.82 mL; 95% CI: -380.60 to -149.04 mL) and decreased amounts of irrigation fluid (WMD = -229.23 mL; 95% CI: -399.63 to -58.83 mL). However, TXA had no remarkable impact on risk of allogenic blood transfusion (pooled risk ratio = 0.50; 95% CI: 0.20-1.23), operation time (WMD = -8.71 min; 95% CI: -20.98 to 3.57 min), and length of hospital stay (WMD = -0.24 day; 95% CI: -0.62 to 0.14 day). No TXA-associated severe adverse reactions or complications were observed. Conclusions: Currently available meta-analysis reveals that TXA is effective in decreasing intraoperative blood loss; however, it does not reduce the risk of allogenic blood transfusion in bimaxillary OS.
Tranexamic Acid in Aesthetic Facial Plastic Surgery: A Systematic Review of Evidence, Applications, and Outcomes
Aesthetic surgery journal. Open forum. 2020;2(3):ojaa029
BACKGROUND Tranexamic acid (TXA) is an antifibrinolytic that has become widely used in aesthetic facial plastic surgery, although its efficacy has not been well investigated. OBJECTIVES To evaluate the existing evidence for use of TXA in aesthetic facial plastic surgery, highlighting routes of administration, dosing, surgical applications, and clinical outcomes. METHODS Systematic review of primary literature evaluating TXA in aesthetic facial plastic surgery. RESULTS Eleven studies met inclusion criteria: 8 prospective randomized controlled trials, 2 retrospective case series/cohort studies, and 1 clinical opinion. Six studies evaluated TXA in rhinoplasty, 4 in rhytidectomy, and 1 in blepharoplasty. Significant reductions in intraoperative blood loss were found in 5 rhinoplasty studies. Three rhinoplasty and 2 rhytidectomy studies found significantly reduced postoperative edema and ecchymosis. One rhinoplasty and 1 rhytidectomy study reported reduced operative time and time to achieve hemostasis. One rhytidectomy study reported reduced postoperative drain output and faster time to drain removal. No studies reported an adverse outcome directly related to TXA. CONCLUSIONS Existing literature investigating TXA in aesthetic facial plastic surgery is sparse with varying levels of evidence and heterogeneous data. Literature suggests systemic TXA reduces intraoperative blood loss during rhinoplasty, although the clinical significance of this blood loss reduction is unclear. TXA may also reduce postoperative edema and/or ecchymosis in rhytidectomy and rhinoplasty, although the lack of validated grading scales yields insufficient evidence to support this claim. Topical and subcutaneously injected TXA are emerging administration routes in rhytidectomy, with evidence suggesting TXA mixed with tumescent may reduce postoperative drain output, thereby expediting drain removal.
Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions
The Cochrane database of systematic reviews. 2019;4:Cd011385
BACKGROUND Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease (VWD). The amount and severity of singular bleedings depend on disease-related factors, such as the severity of the haemophilia, both local and systemic patient factors (such as periodontal inflammation, vasculopathy or platelet dysfunction) and intervention-related factors (such as the type and number of teeth extracted or the dimension of the wound surface). Similar to local haemostatic measures and suturing, antifibrinolytic therapy is a cheap, safe and potentially effective treatment to prevent bleeding complications in individuals with bleeding disorders undergoing oral or dental procedures. However, a systematic review of trials reporting outcomes after oral surgery or a dental procedure in people with an inherited bleeding disorder, with or without, the use of antifibrinolytic agents has not been performed to date. This is an update of a previously published Cochrane Review. OBJECTIVES Primarily, we aim to assess the efficacy of antifibrinolytic agents to prevent bleeding complications in people with haemophilia or VWD undergoing oral or dental procedures.Secondary objectives are to assess if antifibrinolytic agents can replace or reduce the need for clotting factor concentrate therapy in people with haemophilia or VWD and to establish the effects of these agents on bleeding in oral or dental procedures for each of these patient populations. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches of the Cochrane Central Register of Controlled Trials (CENTRAL), of MEDLINE and from handsearching of journals and conference abstract books. We additionally searched the reference lists of relevant articles and reviews. We searched PubMed, Embase, Cinahl and the Cochrane Library. Additional searches were performed in ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP).Date of last search of the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 01 March 2019. SELECTION CRITERIA Randomised and quasi-randomised controlled trials in people with haemophilia or VWD undergoing oral or dental procedures using antifibrinolytic agents (tranexamic acid or epsilon aminocaproic acid (EACA)) 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 for potentially relevant abstracts and two authors independently assessed these for inclusion based on the selection criteria. A third author verified trial eligibility. Two authors independently performed data extraction and risk of bias assessments using standardised forms. MAIN RESULTS While there were no eligible trials in people with VWD identified, two randomised, double-blind, placebo-controlled trials (total of 59 participants) in people with haemophilia undergoing dental extraction were included. One trial of tranexamic acid published in 1972 included 28 participants with mild, moderate or severe haemophilia A and B and one of EACA published in 1971 included 31 people with haemophilia with factor VIII or factor IX levels less than 15%. Overall, the two included trials showed a beneficial effect of tranexamic acid and EACA, administered systemically, in reducing the number of bleedings, the amount of blood loss and the need for therapeutic clotting factor concentrates. Regarding postoperative bleeding, the tranexamic acid trial showed a risk difference (RD) of -0.64 (95% confidence interval (CI) -0.93 to - 0.36) and the EACA trial a RD of -0.50 (95% CI 0.77 to -0.22). The combined RD of both trials was -0.57 (95% CI -0.76 to -0.37), with the quality of the evidence (GRADE) for this outcome is rated as moderate. Side effects occurred once and required stopping EACA (combined RD of -0.03 (95% CI -0.08 to 0.13). There was heterogeneity between the two trials regarding the proportion of people with severe haemophilia included, the concomitant standard therapy and fibrinolytic agent treatment regimens used. We cannot exclude that a selection bias has occurred in the EACA trial, but overall the risk of bias appeared to be low for both trials. AUTHORS' CONCLUSIONS Despite the discovery of a beneficial effect of systemically administered tranexamic acid and EACA in preventing postoperative bleeding in people with haemophilia undergoing dental extraction, the limited number of randomised controlled trials identified, in combination with the small sample sizes and heterogeneity regarding standard therapy and treatment regimens between the two trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in oral or dental procedures in people with haemophilia. No trials were identified in people with VWD.
Efficacy of Feracrylum as Topical Hemostatic Agent in Therapeutically Anticoagulated Patients Undergoing Dental Extraction: A Comparative Study
Journal of maxillofacial and oral surgery. 2019;18(4):579-583
Aims and Objective: To compare the efficacy of feracrylum with tranexamic acid (TXA), following dental extraction in patients who are therapeutically anticoagulated with warfarin. Study Design: Sixty patients on warfarin were randomly divided into three groups. Groups 1 and 2 patients were given feracrylum (1%), and TXA (5%) solution pressure pack and a control group (Group 3) was given normal saline (NS) pressure pack after extraction. Postoperative bleeding was assessed and graded numerically and periodically (0, 1, 2, 5 and 7 days). The values were statistically analyzed. Results: Sixty patients (M:F::37:23) with a mean age of 56 years who were therapeutically anticoagulated for different medical conditions were included. The mean warfarin dosage was 3.5 mg, and the mean INR was 2.83. Out of 27 patients who showed bleeding on day of extraction, eight, ten and nine patients belonged to groups I, II and III, respectively, and the difference was nonsignificant. Out of 15 patients who showed bleeding on post-extraction day 1, one, five and nine patients belonged to groups I, II and III, respectively. The difference was statistically significant on day 1 and nonsignificant in the next follow-ups. Conclusion: Local hemostatic agents like TXA and feracrylum arrest bleeding without having any systemic action and without the necessity of altering the anticoagulant regimen. Feracrylum has an added advantage of a single application, formation of a mechanical barrier and an additional antimicrobial effect. These agents should be incorporated in the protocol for managing patients on oral anticoagulants.
Role of tranexamic acid in nasal surgery: A systemic review and meta-analysis of randomized control trial
OBJECTIVE Nasal surgeries (such as Functional Endoscopic Sinus Surgery, Rhinoplasty, and Septorhinoplasty) are popular procedures. But perioperative bleeding, eyelid edema, and periorbital ecchymosis remain problems. Tranexamic acid (TXA) is an antifibrinolytic, and it was used to reduce the perioperative bleeding. However, there is no enough evidence judging its safety and efficiency. Therefore, a meta-analysis is conducted by us to evaluate the role of TXA in patients undergoing nasal surgeries. METHOD A search of the literature was performed until June 2018; the PubMed, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar databases were searched for related articles using search strategy. Two authors independently assessed the methodological quality of the included studies and extracted data. Surgical information and postoperative outcomes were analyzed. Only randomized controlled trial (RCT) articles were included, and subgroup analysis was established to deal with heterogeneity. RevMan 5.3 software was selected to conduct the meta-analysis. RESULT Eleven RCTs were included in our meta-analysis. There were significant differences in blood loss (P < .001), surgical field quality (P < .001), edema rating of upper (P < .001) and lower (P < .001) eyelid, ecchymosis rating of upper (P < .001) and lower eyelid (P < .001) when comparing the TXA group to the placebo group. However, the difference in operation time (P = .57) was not significant between the two groups. CONCLUSION Perioperative TXA could reduce the blood loss and improve the quality of surgery field during nasal surgery, and it was helpful for reducing the edema and ecchymosis after nasal surgeries, but it has little influence in reducing the operation time.
Antifibrinolytic therapy for preventing oral bleeding in people on anticoagulants undergoing minor oral surgery or dental extractions
The Cochrane Database of Systematic Reviews. 2018;((7)):CD012293.
BACKGROUND 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. OBJECTIVES 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. 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 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. 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 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 co
Effects of Tranexamic Acid Based on its Population Pharmacokinetics in Pediatric Patients Undergoing Distraction Osteogenesis for Craniosynostosis: Rotational Thromboelastometry (ROTEM(TM)) Analysis
International Journal of Medical Sciences. 2018;15((8)):788-795.
Background: Distraction osteogenesis for craniosynostosis is associated with significant hemorrhage. Additionally, patients usually require several transfusions. Tranexamic acid (TXA) is effective for reducing blood loss and the need for transfusions during surgeries. However, the significance of TXA infusion has not been thoroughly described yet. Methods: Forty-eight children undergoing distraction osteogenesis for craniosynostosis were administered intraoperative TXA infusion (loading dose of 10 mg/kg for 15 min, followed by continuous infusion at 5 mg/kg/h throughout surgery; n = 23) or normal saline (control, n = 25). Rotational thromboelastometry (ROTEM(TM)) was conducted to monitor changes in coagulation perioperatively. Results: Blood loss during surgery was significantly lower in the TXA-treated group than it was in the control group (81 vs. 116 mL/kg, P = 0.003). Furthermore, significantly fewer transfusions of red blood cells and fresh frozen plasma were required in the TXA group. In the control group, clotting time during the postoperative period was longer than it was during the preoperative period. Similarly, clot strength was weaker during the postoperative period. D-dimer levels dramatically increased in the control group compared with the TXA group after surgery. The duration of mechanical ventilation and the number of postoperative respiratory-related complications were significantly greater in the control group than they were in the TXA group. Conclusions: TXA infusion based on population pharmacokinetic analysis is effective in reducing blood loss and the need for transfusions during the surgical treatment of craniosynostosis. It can also prevent the increase in D-dimer levels without affecting systemic hemostasis.
The antiplaque and bleeding control effects of a cetylpyridinium chloride and tranexamic acid mouth rinse in patients with gingivitis
Journal of Periodontal & Implant Science. 2017;47((3)):134-142.
PURPOSE This study aimed to evaluate the effects of a cetylpyridinium chloride (CPC) and tranexamic acid (TXA) mouth rinse on patients with gingivitis. METHODS This randomized, placebo-controlled, double-blind, parallel-group, clinical trial included 45 healthy adults with gingivitis, who were randomized into 2 groups. The experimental group used a 0.05% CPC and 0.05% TXA mouth rinse, and the control group used a placebo mouth rinse. The following clinical indices were assessed at baseline, at 3 weeks, and at 6 weeks: the Turesky-Quigley-Hein plaque index (QHI), the Loe-Silness gingival index (GI), and bleeding on marginal probing (BOMP). The subjects used the mouth rinse during the experimental period for 20 seconds, 4-5 times daily (10 mL each time). RESULTS There were no significant differences in the clinical indices between the groups at baseline. In the experimental group (CPC+TXA), a statistically significant improvement was evident in the QHI, GI, and BOMP at 3 and 6 weeks. These results were similar to those observed in the control group at 3 and 6 weeks, although the change in BOMP was not statistically significant in that group. At 6 weeks, the experimental group had a significantly lower mean score for the QHI than the control group. CONCLUSIONS This study demonstrated that a CPC and TXA mouth rinse exhibited significant antiplaque and anti-gingivitis efficacy, and had a positive effect on bleeding control when used daily for 6 weeks.
Impact of aprotinin - a proteolytic enzyme on postsurgical symptoms in patients undergoing third molar surgeries
Journal of Clinical and Diagnostic Research : Jcdr. 2016;10((1)):ZC18-22.
INTRODUCTION Dealing with postoperative pain and inflammation remains an arena for never ending research. Different agents have been the subject of many studies to prevent the occurrence of unpleasant postoperative sequel. Extraction of third molars is often associated with significant deterioration in oral health related quality of life (physical, social and psychological) in immediate postoperative period. The complaints of pain, swelling and limitation of mouth opening, which ensue as a result of acute inflammatory response, are frequent consequences of postsurgical procedures involving extraction of impacted 3(rd) molars. AIM: Aprotinin, a naturally occurring protease inhibitor was assessed for its effectiveness in plummeting postsurgical pain and swelling, after surgical removal of impacted 3(rd) molars. MATERIALS AND METHODS Thirty randomly selected adult patients age ranging from 16-35 years, who required simultaneous surgical removal of bilateral impacted mandibular third molars were recruited. Before the surgical procedure, randomly selected side of the patient was injected with 1 m of 10,000 Kallikrein Inactivator Units (KIU) of aprotinin sub-mucosally around the surgical site and the contra lateral side with 1ml of isotonic saline as a control following which adequate local anaesthesia was obtained. The surgical removal of impacted 3(rd) molars was conducted in a similar manner on both test and control sides on all patients. Postoperatively, the patients were evaluated for pain and swelling for one week i.e., 1(st), 2(nd) and 7(th) day. RESULTS It was observed that there was marked clinical reduction in postoperative pain and swelling. There were no adverse affects observed after using aprotinin. CONCLUSION Since, the current pharmacologic agents being used have adverse effects and associated morbidity which still pose a problem, aprotinin a naturally occurring agent could be efficiently used after surgical extraction of 3(rd) molars in management of postsurgical symptoms and improve patient comfort and quality of life. In future, further studies with use of aprotinin in a large number of patients and comparative studies with other drugs are required.