Tranexamic acid and bleeding in patients treated with non-vitamin K oral anticoagulants undergoing dental extraction: The EXTRACT-NOAC randomized clinical trial

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.

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Tranexamic Acid to Reduce Bleeding in Patients Treated With Non-Vitamin K Oral Anticoagulants Undergoing Dental Extraction: The EXTRACT-NOAC Randomized Clinical Trial

SSRN Electronic Journal ◽

10.2139/ssrn.3769221 ◽

2021 ◽

Author(s):

Anna Ockerman ◽

Isabel Miclotte ◽

Maarten Vanhaverbeke ◽

Thomas Vanassche ◽

Ann Belmans ◽

...

Keyword(s):

Clinical Trial ◽

Tranexamic Acid ◽

Randomized Clinical Trial ◽

Vitamin K ◽

Oral Anticoagulants ◽

Dental Extraction

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Tranexamic acid to reduce bleeding after dental extraction in patients treated with non-vitamin K oral anticoagulants: design and rationale of the EXTRACT-NOAC trial

British Journal of Oral and Maxillofacial Surgery ◽

10.1016/j.bjoms.2019.10.297 ◽

2019 ◽

Vol 57 (10) ◽

pp. 1107-1112

Author(s):

A. Ockerman ◽

M. Vanhaverbeke ◽

I. Miclotte ◽

A. Belmans ◽

T. Vanassche ◽

...

Keyword(s):

Tranexamic Acid ◽

Vitamin K ◽

Oral Anticoagulants ◽

Dental Extraction

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Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial

Critical Care ◽

10.1186/s13054-020-03243-4 ◽

2020 ◽

Vol 24 (1) ◽

Cited By ~ 1

Author(s):

Amy Brenner ◽

◽

Antonio Belli ◽

Rizwana Chaudhri ◽

Timothy Coats ◽

...

Keyword(s):

Placebo Group ◽

Tranexamic Acid ◽

Randomised Trial ◽

Early Death ◽

Intracranial Bleeding ◽

Exploratory Analysis ◽

Pool Data ◽

Risk Of Death ◽

Link Type ◽

Gcs Score

Abstract Background The CRASH-3 trial hypothesised that timely tranexamic acid (TXA) treatment might reduce deaths from intracranial bleeding after traumatic brain injury (TBI). To explore the mechanism of action of TXA in TBI, we examined the timing of its effect on death. Methods The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with a GCS score of 3 or bilateral unreactive pupils, stratified by severity and country income. We pool data from the CRASH-2 and CRASH-3 trials in a one-step fixed effects individual patient data meta-analysis. Results There were 7637 patients for analysis after excluding patients with a GCS score of 3 or bilateral unreactive pupils. Of 1112 deaths, 23.3% were within 24 h of injury (early deaths). The risk of early death was reduced with TXA (112 (2.9%) TXA group vs 147 (3.9%) placebo group; risk ratio [RR] RR 0.74, 95% CI 0.58–0.94). There was no evidence of heterogeneity by severity (p = 0.64) or country income (p = 0.68). The risk of death beyond 24 h of injury was similar in the TXA and placebo groups (432 (11.5%) TXA group vs 421 (11.7%) placebo group; RR 0.98, 95% CI 0.69–1.12). The risk of death at 28 days was 14.0% in the TXA group versus 15.1% in the placebo group (544 vs 568 events; RR 0.93, 95% CI 0.83–1.03). When the CRASH-2 and CRASH-3 trial data were pooled, TXA reduced early death (RR 0.78, 95% CI 0.70–0.87) and death within 28 days (RR 0.88, 95% CI 0.82–0.94). Conclusions Tranexamic acid reduces early deaths in non-moribund TBI patients regardless of TBI severity or country income. The effect of tranexamic acid in patients with isolated TBI is similar to that in polytrauma. Treatment is safe and even severely injured patients appear to benefit when treated soon after injury. Trial registration ISRCTN15088122, registered on 19 July 2011; NCT01402882, registered on 26 July 2011.

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Correction to: First report of a comparative patient-oriented perspective on the use of non-vitamin-K oral anticoagulants or vitamin-K antagonists in atrial fibrillation: patients’ experiences, side-effects and practical problems leading to non-adherence

Netherlands Heart Journal ◽

10.1007/s12471-021-01577-4 ◽

2021 ◽

Vol 29 (5) ◽

pp. 297-298

Author(s):

N. Bennaghmouch ◽

A. J. W. M. de Veer ◽

C. Zivelonghi ◽

L. van Dijk ◽

J. M. ten Berg

Keyword(s):

Atrial Fibrillation ◽

Side Effects ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

First Report ◽

Link Type

A Correction to this paper has been published: 10.1007/s12471-019-01331-x

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A prospective comparative study to assess the risk of postoperative bleeding after dental surgery while on medication with direct oral anticoagulants, antiplatelet agents, or vitamin K antagonists

BMC Oral Health ◽

10.1186/s12903-021-01868-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mayte Buchbender ◽

Nicola Schlee ◽

Marco R. Kesting ◽

Jannik Grimm ◽

Jakob Fehlhofer ◽

...

Keyword(s):

Clinical Trial ◽

Vitamin K ◽

Surgical Intervention ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Postoperative Bleeding ◽

Anticoagulation Therapy ◽

The Other ◽

Detailed Instruction ◽

Significant Difference

Abstract Background The aim of this prospective study was to investigate the occurrence and severity of postoperative bleeding following dentoalveolar surgery in patients with uninterrupted anticoagulation therapy (AT). Methods Patients receiving AT (vitamin k antagonist (VK), direct oral anticoagulants (DOAC) or antiplatelet therapy (APT) and in need of surgical intervention classified as A, B or C (single or serial tooth extraction, osteotomy, or implant placement) were studied between 2019 and 2021. A healthy, non-anticoagulated cohort (CG) served as a control group. The main outcomes measured were the frequency of postoperative bleeding, the classification of the severity of postoperative bleeding (1a, 1b, 1c, 2, 3), and the correlation with the AT surgical intervention classification. Results In total, 195 patients were included in the study, with 95 patients in the AT group and 100 in the CG. Postoperative bleeding was significant in the AT group vs. the CG (p = 0.000), with a significant correlation with surgical intervention class C (p = 0.013) and the severity class of bleeding 1a (p = 0.044). There was no significant correlation with procedures of type A, B or C for the other postoperative bleeding gradations (1b, 1c, 2 and 3). There was a statistically significant difference in the occurrence of postoperative bleeding events between the DOAC/APT group and the VK group (p = 0.036), but there were no significant differences regarding the other AT agents. Conclusion The continuation of anticoagulation therapy for surgical interventions also seems reasonable for high-risk interventions. Although significantly more postoperative bleeding occurs, the severity of bleeding is low. The perioperative management of anticoagulated patients requires well-coordinated interdisciplinary teamwork and detailed instruction of patients. Clinical trial registration The study is registered (29.03.2021) at the German clinical trial registry (DRKS00024889).

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Efficacy of Topical Tranexamic Acid in Reducing Blood Loss after Laminectomy and Posterolateral Fusion of the Spine: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial

Journal of Orthopedic and Spine Trauma ◽

10.18502/jost.v7i1.5959 ◽

2021 ◽

Author(s):

Moslem Shakeri ◽

Mansour Valaie ◽

Farhad Mirzaei ◽

Ramyar Hariri ◽

Ehsan Jangholi ◽

...

Keyword(s):

Clinical Trial ◽

Tranexamic Acid ◽

Posterolateral Fusion ◽

Controlled Clinical Trial ◽

Bleeding Rate ◽

Intergroup Comparison ◽

Significant Difference ◽

The Mean ◽

Double Blinded ◽

Topical Tranexamic Acid

Background: Multi-level spine surgeries are associated with high bleeding during and after surgery. A majority of studies have previously evaluated the effect of tranexamic acid (TXA) in reducing bleeding with a focus on intravenous (IV) administration. The aim of the study was to evaluate the efficacy of topical TXA in decreasing bleeding after laminectomy and spinal fusion. Methods: In this randomized, double-blinded, placebo-controlled clinical trial, 80 patients were enrolled from January 2017 to January 2019. The patients were eligible for laminectomy (2 or more levels) and posterolateral fusion with a pedicle screw. Patients were randomly divided into two equal groups; single-dose TXA (1 g/50 ml) and normal saline. Intergroup comparison was performed for the amount of bleeding during and after surgery, received packed cells, and the number of hospitalization days. Results: The mean age of the patients was 55.51 ± 10.27 years, and 50 of them were women. 18 and 20 patients in control and TXA groups had intraoperative bleeding more than 400 ml, respectively (P ˃ 0.05). The only significant difference was observed in the first and second 12 hours, and total bleeding after surgery in patients who had bleeding above 400 ml (P = 0.011, P = 0.039, P = 0.015, respectively). Conclusion: The application of topical TXA was effective in patients with high amount of hemorrhage during spine surgery for reducing the bleeding rate in the first and second 12 hours, as well as the mean total bleeding rate after surgery. It had no significant effect on total intraoperative hemorrhage, total packed cells, and total hospitalization length.

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Spectrophotometric Assays of Prothrombin in Plasma of Patients Using Oral Anticoagulants

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657025 ◽

1979 ◽

Vol 42 (04) ◽

pp. 1296-1305 ◽

Cited By ~ 29

Author(s):

R M Bertina ◽

W van der Marel-van Nieuwkoop ◽

E A Loeliger

Keyword(s):

Prothrombin Time ◽

Vitamin K ◽

Oral Anticoagulation ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Factor Xa ◽

Factor V ◽

Anticoagulant Treatment ◽

Factor Ii ◽

K Deficiency

SummaryTwo spectrophotometric assays for prothrombin have been developed and compared with a one stage coagulant and an immunological assay. One of these assays (called the XAPC assay) uses a combination of factor Xa, phospholipid, Ca2+ and factor V as activator of prothrombin, and measures only normal prothrombin. The second (the ECAR assay) uses Echis carinatus venom as activator. This assay measures both normal prothrombin and PIVKA II (protein induced by vitamin K antagonists/absence). Combination of the results obtained by the XAPC and ECAR assays provides rapid and reliable information on the degree of “subcarboxylation” of prothrombin (oral anticoagulation, vitamin K deficiency).For patients on long term anticoagulant treatment the prothrombin time (Thrombotest) shows better correlation with the ratio prothrombin/prothrombin plus PIVKA II (XAPC/ ECAR) than with the factor II concentration. For patients starting the anticoagulant treatment there is no correlation between the Thrombotest time and the XAPC/ECAR ratio.It seems doubtful that (a) spectrophotometric factor II assay(s) will be as useful as the prothrombin time in the control of oral anticoagulation.

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