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

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 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.

Do Antiplatelet Drugs Increase the Risk of Bleeding After Dental Implant Surgery? A Case-and-Crossover Study.

PURPOSE: Cessation versus continuation of antiplatelet drugs in patients undergoing dental implant surgery is a controversial issue. The present study evaluated postoperative bleeding during and after dental implant surgery in patients taking aspirin (ASA) or clopidogrel. MATERIAL AND METHODS: The present study is a case-and-crossover study. Patients who were using antiplatelet drugs and receiving 2 bilateral dental implants in the posterior region of the mandible were studied. During session 1, dental implants were placed without stopping the intake of antiplatelet drugs. During session 2, antiplatelet drugs were stopped for 5 days. In group 1, platelet activity was measured by an assay based on flow cytometry and represented the platelet reactivity index. In group 2, platelet function analysis was used to monitor the antiplatelet effect of ASA. Bleeding severity was assessed using a visual analog scale for 72 hours after dental implant placement during sessions 1 and 2. Use of antiplatelet drugs was the predictive factor of the study and bleeding severity and platelet function were the outcomes of the study. RESULTS: Twenty-two patients composed group 1 (clopidogrel 75 mg) and 20 composed group 2 (ASA 80 mg). In group 1, bleeding severity was 4.86 ± 0.77 during session 1 and 4.59 ± 0.66 during session 2. Data analysis showed no difference in bleeding severity between sessions 1 and 2 in group 1 (P = .72). In group 2, bleeding severity was 4.05 ± 0.94 during session 1 and 3.9 ± 0.85 during session 2. There was no difference in bleeding severity between sessions 1 and 2 in patients taking ASA (P = .19). CONCLUSION: The results suggest that continuing the intake of antiplatelet drugs did not increase bleeding after placement of dental implants.

Management of Patients With Left Ventricular Assist Devices Requiring Teeth Extraction: Is Halting Anticoagulation Appropriate?

PURPOSE: An increasing number of patients with end-stage heart failure are supported with left ventricular assist device (LVAD) implantation and must be maintained on a consistent anticoagulation regimen. Pre-emptive extraction of carious teeth in these patients is necessary to prevent seeding of the implanted device and endocarditis. Thus, the objective of this study was to evaluate bleeding complications after minor oral surgery, specifically teeth extractions, in this unique patient population requiring long-term anticoagulation. MATERIALS AND METHODS: This study was a retrospective single-center review. Adult patients supported on an implanted continuous-flow LVAD from January 1, 2007 to December 31, 2016 were included. Baseline characteristics were collected by retrospective chart review and the institutional LVAD registry. All extractions were performed in the operating room under local anesthesia with moderate sedation or general anesthesia with nasal intubation, and LVAD settings were monitored by a trained perfusionist. Preoperative and postoperative hematology laboratory values, such as hemoglobin and international normalized ratio (INR), were collected by chart review. Continuous variables were presented as mean ± standard deviation and compared using the Student t test. Categorical variables were presented as proportion and percentage and compared using the χ2 test or Fisher exact test as appropriate. Statistical significance was established at a P value less than .05. RESULTS: After screening 798 patients, 32 (4%) were found to have undergone dental extractions after LVAD implantation. The sample was composed of 32 patients with a mean age of 60.13 years and 81.25% were men. The average time from LVAD implantation to extraction was 445.19 ± 1,108.53 days. Average preoperative INR was 1.76 ± 0.47. Preoperative fresh frozen plasma was not administered to any patients. Twenty-eight patients (87.5%) were on Coumadin (warfarin) preoperatively. In 11 of these 28 patients (39.3%), Coumadin was held preoperatively. The average postoperative change in hemoglobin level was -0.79 ± 1.45. Only 1 patient (3%) required postoperative blood transfusion for a hemoglobin level of 7.6 that responded appropriately. There were no reoperations for bleeding. CONCLUSIONS: Minor oral surgical procedures can be performed safely for patients being supported on LVAD therapy. With primary closure of the gingiva at the site of extraction, dental extractions can be performed without the full reversal of anticoagulation.

The risk factors associated with postoperative hemorrhage after tooth extraction: a multi-center retrospective study of patients receiving oral antithrombotic therapy.

The purpose of this study was to retrospectively investigate the multivariate relationships between specific risk factors and postoperative hemorrhage after tooth extraction in patients who were prescribed oral antithrombotic therapy. Risk factors for postoperative hemorrhage after tooth extraction were evaluated using univariate and multivariate analyses. Patient characteristics such as age and gender; the presence or absence of known comorbidities such as diabetes mellitus, hypertension, cerebral infarction, and alcohol consumption; and perioperative diarrhea were assessed. The drug used for antithrombotic therapy, preoperative blood test results, the presence or absence of preoperative antibiotics or nonsteroidal anti-inflammatory drug (NSAID) administration, the total number of extracted teeth, and the type of surgical procedures were also evaluated. We found that the preoperative administration of antibiotics (odds ratio (OR) = 2.52), an increased prothrombin time international normalized ratio (PT-INR) value (OR = 1.94), and the extraction of multiple teeth (OR = 2.10) were significantly associated with postoperative hemorrhage. There was no significant association between postoperative hemorrhage and any other demographic factors or comorbidities, including concomitant alcohol use. We demonstrated the multivariate relationship between the risk factors and postoperative hemorrhage after tooth extraction in patients receiving oral antithrombotic therapy. Surgeons should be aware of these risks and monitor the PT-INR of anticoagulated patients.

Do antiplatelet drugs increase the risk of bleeding after tooth extraction? A case-crossover study.

The aim of this study was to assess the risk of bleeding after tooth extraction in patients taking aspirin or clopidogrel. This case-crossover study evaluated patients taking aspirin (80mg/day) or clopidogrel (75mg/day) and undergoing tooth extraction. In the first session, extraction was performed without discontinuing aspirin (group 1) or clopidogrel (group 2). In the second session, patients ceased using antiplatelet drugs 5days prior to tooth extraction. Bleeding was evaluated using a visual analogue scale (VAS) for 72h after tooth extraction. The platelet function assay (PFA) was performed for group 1 and flow cytometry assessment of vasodilator-stimulated phosphoprotein (VASP) was performed for group 2, in both sessions. Thirty-eight patients were studied: 20 in group 1 and 18 in group 2. Analysis of the data did not demonstrate any difference in bleeding severity between sessions 1 and 2 in either group (P>0.05). There was a significant difference between sessions 1 and 2 in group 1 for the mean collagen/epinephrine membrane closure time (PFA) (P=0.001). A significant difference in platelet reactivity index (flow cytometry for VASP) was noted between sessions 1 and 2 in group 2 (P=0.001). According to this case-crossover study, dental extraction can be performed safely without withdrawal of aspirin or clopidogrel.

Prevention of post-operative bleeding in hemostatic compromised patients using native porcine collagen fleeces-retrospective study of a consecutive case series.

INTRODUCTION: Various anticoagulant therapy regimes bear the risk of postsurgical bleeding events after dental extractions. Local hemostyptic measures, e.g., collagen fleeces, are applied by surgeons to prevent such bleedings. No standard protocol in prevention of bleeding events has met general acceptance among surgeons yet. PURPOSE: The purpose of this retrospective study was to determine if post-operative bleeding can be prevented by suturing native collagen fleeces into extraction wounds immediately after teeth removal, regardless what anticoagulant regime is performed. METHODS: A total of 741 extraction units were removed from 200 consecutive in-ward patients with or without alternation of different anticoagulant therapy regimes. Anti-vitamin K agents were the most prescribed drugs (n = 104, 52 %), followed by Acetylsalicylate (ASS) (n = 78, 39 %). Nineteen (9.5 %) patients received a dual anti-platelet therapy. Out of 104 patients receiving an anti-vitamin K agent (phenprocoumon), 84 patients were bridged, 20 patients continued to their anticoagulant therapy without alterations. Following careful tooth extraction, extraction sockets were filled using a native type I and III porcine collagen sponge (Collacone, Botiss Biomaterials, Berlin), supported by single and mattress sutures for local hemostasis. Post-operative bleeding events were rated according to their clinical relevance. RESULTS: In the post-operative phase, 8 out of 200 consecutively treated patients experienced a post-operative bleeding event. All of them had been designated for a long-term anti-vitamin K therapy (p ≤ 0.05), and extractions were performed under a heparin bridging regime (n = 6) or an uninterrupted anti-vitamin K agent therapy (n = 2). No bleeding events occurred in patients with ASS 100 therapy or low-dose LMWH therapy (p ≤ 0.05), or in patients with dual anti-platelet therapy (0 out of 24). None of the bleeding events put patients' health at risk or required systemic intervention. CONCLUSION: Sufficiently performed local hemostyptic measures, like the application of collagen fleeces in combination with atraumatic surgery, bears a great potential for preventing heavy bleeding events in hemostatic compromised patients, regardless of their anticoagulant therapy.

Bleeding after tooth extraction in patients taking aspirin and clopidogrel (Plavix®) compared with healthy controls.

The risk of perioperative bleeding is high in patients who take aspirin and clopidogrel after a percutaneous coronary intervention, and whether to stop the drugs is a matter of concern for dentists. The aim of this study was to answer the specific question: should aspirin and clopidogrel bisulphate (Plavix®) be discontinued during a conventional forceps extraction? We studied 64 patients during the first year after percutaneous insertion of coronary stents who were taking aspirin (ASA) 80mg and clopidogrel (Plavix(®)) 75mg, and 50 healthy patients who were to have a conventional forceps extraction at this polyclinic in 2013-2014 and acted as controls. Clinical details (underlying diseases; number of roots; type of tooth; type of haemostasis; and bleeding immediately, 30minutes, and 48hours after intervention) were compared. We evaluated 114 patients with the mean (range) age of 56 (43-76) years, and there were no significant differences in demographic data, underlying diseases, type of tooth, number of roots, and dose of anaesthetic between the groups. There were also no significant differences in the number of bleeds immediately and 30minutes after intervention (P=0.310 and 0.205). The time that the last dose of aspirin had been taken correlated with 30-minute haemostasis (20 compared with 12hours, p=0.037). During the 48hours after the intervention, there were no uncontrolled bleeds or emergency referrals. We conclude that using aspirin and Plavix® simultaneously has no considerable effect on the risk of bleeding in patients having conventional forceps extraction of a single tooth.

Postoperative bleeding risk for oral surgery under continued rivaroxaban anticoagulant therapy.

OBJECTIVES: The purpose of this study was to assess the risk of postoperative bleeding complications after oral procedures performed under continued mono or dual anticoagulation therapy with rivaroxaban (and aspirin). METHODS: This retrospective single-center observational study included 52 oral procedures performed under continued oral anticoagulant therapy with rivaroxaban (20 mg/day). Among them, two procedures were performed under continued dual therapy with aspirin (100 mg/day) added to the regimen. Postoperative bleeding events were compared with 285 oral procedures in patients without any anticoagulation/antiplatelet therapy. RESULTS: Postoperative bleeding complications after oral surgery occurred significantly more often in patients under continued rivaroxaban therapy (11.5 %) than in the control cases without anticoagulation/antiplatelet medication (0.7 %). All of the bleeding events were manageable: Two of them were treated with local compression, three by applying new fibrin glue with (one case) or without (two cases) secondary sutures, one occurred during a weekend and was therefore treated under inpatient conditions with suture replacement. All postoperative bleeding episodes occurred during the first postoperative week. CONCLUSIONS: According to our data, continued anticoagulation therapy with rivaroxaban significantly increases postoperative bleeding risk for oral surgical procedures, although the bleeding events were manageable. CLINICAL RELEVANCE: Oral surgeons, cardiologists, general physicians, and patients should be aware of the increased bleeding risk after oral surgical procedures. Close observation up to 1 week postoperatively is advisable to prevent excessive bleeding.

Managing dentoalveolar surgical procedures in patients taking new oral anticoagulants.

The development of new orally administered anticoagulants, such as dabigatran, rivaroxaban, and apixaban, in the past few years has focused on avoiding some of the drawbacks associated with warfarin. This work aims to illustrate the main features of the most commonly used new oral anticoagulants, reviewing the current literature on the management of patients taking these drugs and needing oral and implant surgery, and discussing the currently proposed related guidelines.

Healing acceleration in hamsters of oral mucositis induced by 5-fluorouracil with topical Calendula officinalis.

OBJECTIVE: This study assessed the potential of topical Calendula officinalis extract on the healing of oral mucositis induced by 5-fluorouracil (5-FU) in hamsters. STUDY DESIGN: Oral mucositis was induced in 60 male hamsters by 5-FU (60 mg/kg) on days 0, 5, and 10 of the study. The cheek pouch was scratched with a sterile needle on days 1 and 2. On days 12-17, 5% and 10% C. officinalis gel and gel base groups were treated and then compared with a control group. Macroscopic and microscopic scores and weights were evaluated. RESULTS: Microscopic and macroscopic scores of mucositis were lower in the 5% and 10% C. officinalis gel groups than in the gel base and control groups (P < .05). Weight gain was noted in the treatment groups compared with the gel base and control groups (P < .05). CONCLUSIONS: Calendula officinalis extract accelerated the healing of oral mucositis in hamsters.

Study on incidence of bleeding in hospitalized patients after antithrombotic therapy at a tertiary care hospital.

OBJECTIVES: To monitor the different antithrombotic drug combinations, determine the incidence, magnitude of bleeding and the association of HAS-BLED risk scoring schema with the magnitude of bleeding as defined using TIMI bleeding criteria. METHODS: A prospective observational study in a cohort of patients for a period of 8 months, at one of the tertiary care center-Krishna Institute of Medical Sciences, Hyderabad, was conducted. Consecutive patients were enrolled and followed from the date of admission till the adverse events are perceived/date of discharge. Pearson Correlation Statistics (Fisher's z Transformation) is applied to assess the association between HAS-BLED risk factors and the total risk score with bleeding criteria. RESULTS: A total of 400 cases were collected during the 8-month study period, of which 372 satisfied the inclusion criteria. Among them 34 (9.1%) bleeding cases were reported with mean (+/- SD) age of 57.8 (+/- 14.19) years. Bleeding occurred mostly in males 79.4% and a HAS-BLED Score of > or = 3 has been observed in 67.6% (n = 23) patients out of 34 bled patients. Two antiplatelets + One anticoagulant is the most common combination which caused bleeding in 41.2% (n = 14). Stroke history, bleeding predisposition, labile INR's are the HAS-BLED risk factors which are significant (< 0.05) with the TIMI Bleeding Criteria. CONCLUSION: There was a linear correlation between the HAS-BLED risk score and the TIMI bleeding criteria-higher the risk score the more frequent is the incidence of major bleeding. A HAS-BLED risk score of > or = 3 is associated with TIMI major bleeding.

Injection of sodium hypochlorite beyond the apical foramen--a case report.

The aim of this study was to report a clinical case of extravasation of 1% sodium hypochlorite into the periapical tissues during endodontic treatment. During apical debridement, absence of reflux of the irrigating solution was observed, followed by root canal hemorrhage. The patient immediately complained of intense pain, and a profuse edema and hyperemia was observed on the left side of her face compatible with extravasation of hypochlorite to the periapex. The patient was treated with ibuprofen 600 mg three times per day for three days, a single dose of dexamethasone 4 mg, amoxicillin 500 mg three times per day for seven days, and a cold compress for two days. Regression of the condition began on the fourth day, and normal tissue aspect and absence of sequelae were observed on the 14th day.

[Minor dentoalveolar surgery in patients ungergoing antithrombotic therapy]. / Mindre dentoalveolaer kirurgi på patienter i antitrombotisk behandling.

Minor oral dentoalveolar surgery can be performed safely without interrupting treatment with vitamin K antagonists provided the INR is within therapeutic range. Platelet inhibitors such as aspirin and clopidogrel may increase the risk of bleeding, but the risk of disabling or fatal sequelae is generally higher if the treatment is stopped. Application of local haemostatic agents and postoperative mouthwashes with tranexamic acid are recommended. Any changes in antithrombotic therapy must be undertaken in collaboration with the patient's prescribing physician.

[Dental surgery in patients receiving anticoagulant therapy]. / Zahnärztliche Eingriffe bei antikoagulierten Patienten.

It has long been a standard procedure to replace coumarin by heparin if a patient using this oral anticoagulant had to undergo dental surgery. The Quick-Value had then to exceed a certain limit before surgery could be safely performed. Today this procedure has changed in that a switch to heparin is only made for invasive and large area surgery. Simple dental extractions, small biopsies and periodontal treatments are performed under continuous oral anticoagulation and local hemostyptic measures are applied. It has been shown that the likelihood of postoperative bleeding complications after adequate local hemostasis during dental surgery is much lower than is the risk of thrombosis or embolic complication following cessation of anticoagulant medication before surgery.

Dentoalveolar procedures for the anticoagulated patient: literature recommendations versus current practice.

PURPOSE: To evaluate the current practice of oral and maxillofacial surgeons in Michigan regarding perioperative warfarin therapy and dentoalveolar surgery in defined procedure risk groups. MATERIALS AND METHODS: Surveys were distributed to all surgeons (n = 188) registered with the Michigan Society of Oral and Maxillofacial Surgeons. Low/moderate/high surgery risk groups were defined based on retrospective data accumulated for procedures on pretransplant liver failure patients. We requested the surgeon's maximum tolerated International Normalized Ratio (INR) for each risk group. In addition, surgeons were asked if their routine practice for each group included continuation or discontinuation of therapeutic warfarin perioperatively. RESULTS: A 72.6% response rate was achieved. The average maximum INR cutoff values for the various risk groups were: low, 2.68; moderate, 2.28; and high, 2.01. Routine discontinuation of warfarin occurred in these groups 23.6%, 48.8%, and 70.5%, respectively. Using a paired t test, these results showed statistically significant differences in patient management practices (P < .001) between the low, moderate, and high risk groupings. CONCLUSION: Lack of uniformity exists regarding warfarin therapy and dentoalveolar surgery. No studies to date involve significant numbers of moderate/high risk procedures to provide evidence-based support of safety with maintenance of therapeutic INR. For moderate or high risk procedures, the majority of surgeons prefer warfarin discontinuation with minimally therapeutic or subtherapeutic levels, a practice that secondarily increases risk for thromboembolism. Based on these preliminary data, we believe a prospective trial to elucidate stronger management guidelines for both the moderate and high risk surgery population is indicated.