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

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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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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Non-vitamin K antagonist oral anticoagulants and sport

Minerva Cardioangiologica ◽

10.23736/s0026-4725.20.05177-4 ◽

2020 ◽

Vol 68 (2) ◽

Author(s):

Silvio Romano ◽

Elisa Salustri ◽

Antonio G. Robles ◽

Leonardo Calò ◽

Maria Penco ◽

...

Keyword(s):

Vitamin K ◽

Oral Anticoagulants ◽

Vitamin K Antagonist

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Perioperative Management of Patients Receiving New Anticoagulants

Current Pharmaceutical Design ◽

10.2174/1381612825666190709220449 ◽

2019 ◽

Vol 25 (19) ◽

pp. 2149-2157 ◽

Cited By ~ 1

Author(s):

Massimo Lamperti ◽

Andrey Khozenko ◽

Arun Kumar

Keyword(s):

Vitamin K ◽

Elective Surgery ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Oral Intake ◽

Bleeding Risk ◽

Dietary Vitamin ◽

Reversal Agent ◽

Onset Of Action ◽

Reversal Agents

There is an increased use of oral anticoagulants for the prevention of venous and arterial thrombosis. Vitamin-K antagonists have been used for decades as the main oral anticoagulants but they have the draback a complex therapeutic management, slow onset of action and by a different oral intake caused by dietary vitamin K intake. New non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. Their management is easier as it requires a fixed daily dose without coagulation monitoring. Although their therapeutic profile is safe, proper attention should be paid in case of unexpected need for the reversal of their coagulation effect and in case a patient needs to have a scheduled surgery. For non-acute cardiac surgery, discontinuation of NOACs should start at least 48 hours prior surgery. Intracranial bleedings associated with NOACs are less dangerous comparing to those warfarin-induced. NOACs need to be stopped ≥24 hours in case of elective surgery for low bleeding-risk procedures and ≥48 hours for high bleeding-risk surgery in patients with normal renal function and 72 hours in case of reduced CrCl < 80. The therapy with NOACs should be resumed from 48 to 72 hours after the procedure depending on the perceived bleeding, type of surgery and thrombotic risks. There are some available NOAC reversal agents acting within 5 to 20 minutes. In case of lack of reversal agent, adequate diuresis, renal replacement therapy and activated charcoal in case of recent ingestion should be considered.

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Non-Vitamin K Antagonist Oral Anticoagulants in Pulmonary Embolism: An Overview of Systematic Reviews

Current Pharmaceutical Design ◽

10.2174/1381612826666200506114450 ◽

2020 ◽

Vol 26 (23) ◽

pp. 2686-2691 ◽

Cited By ~ 1

Author(s):

Ioannis Doundoulakis ◽

Christina Antza ◽

Haralambos Karvounis ◽

George Giannakoulas

Keyword(s):

Pulmonary Embolism ◽

Vitamin K ◽

Systematic Reviews ◽

Methodological Quality ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Language Restriction ◽

Overview Of Systematic Reviews

Background: Anticoagulation in patients with pulmonary embolism. Objective: To identify how non-vitamin K antagonist oral anticoagulants are associated with multiple outcomes in patients with pulmonary embolism. Methods: We performed a systematic search of systematic reviews via multiple electronic databases from inception to August 19th, 2019, without language restriction. Two authors independently extracted data and assessed the methodological quality of the included systematic reviews using the ROBIS tool. Results: We found twelve systematic reviews. Eleven SRs collected their data from randomized clinical trials and one from observational studies. All the included studies were published between 2014 and 2019 in English. The methodological quality of the 12 systematic reviews was low to high. None of the systematic reviews, which are included in our overview of systematic reviews, has evaluated the overall quality of evidence outcome using the Grading of Recommendations Assessments, Development and Evaluation (GRADE) approach. Conclusion: This is the first effort to summarize evidence about non-vitamin K antagonist oral anticoagulants in an overview of systematic reviews focusing exclusively on patients with pulmonary embolism. The evidence suggests that the non-vitamin K antagonist oral anticoagulants seem to be more effective and safer than a dualdrug approach with LMWH- VKA.

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Is Anticoagulation with Novel Oral Anticoagulants an Effective Treatment for Tuberculosis Patients not Achieving a Therapeutic Range with Vitamin K Antagonists? A Systematic Review

Cardiovascular & Haematological Disorders - Drug Targets ◽

10.2174/1871529x17666170703115545 ◽

2017 ◽

Vol 17 (2) ◽

Author(s):

Marco Fiore ◽

Alberto Enrico Maraolo ◽

Paolo Chiodini ◽

Claudio Cerchione ◽

Ivan Gentile ◽

...

Keyword(s):

Systematic Review ◽

Effective Treatment ◽

Vitamin K ◽

Therapeutic Range ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Novel Oral Anticoagulants ◽

Tuberculosis Patients

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Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and End-Stage Renal Disease

The American Journal of Cardiology ◽

10.1016/j.amjcard.2017.09.030 ◽

2018 ◽

Vol 121 (1) ◽

pp. 131-140 ◽

Cited By ~ 14

Author(s):

Marin Nishimura ◽

Jonathan C. Hsu

Keyword(s):

Atrial Fibrillation ◽

Renal Disease ◽

Vitamin K ◽

End Stage Renal Disease ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Stage Renal Disease ◽

End Stage

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Anticoagulation in Atrial Fibrillation Cardioversion: What Is Crucial to Take into Account

Journal of Clinical Medicine ◽

10.3390/jcm10153212 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3212

Author(s):

Fabiana Lucà ◽

Simona Giubilato ◽

Stefania Angela Di Fusco ◽

Laura Piccioni ◽

Carmelo Massimiliano Rao ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Thrombus Formation ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Significant Advance ◽

Thromboembolic Events ◽

Thromboembolic Risk ◽

Pharmacological Cardioversion

The therapeutic dilemma between rhythm and rate control in the management of atrial fibrillation (AF) is still unresolved and electrical or pharmacological cardioversion (CV) frequently represents a useful strategy. The most recent guidelines recommend anticoagulation according to individual thromboembolic risk. Vitamin K antagonists (VKAs) have been routinely used to prevent thromboembolic events. Non-vitamin K antagonist oral anticoagulants (NOACs) represent a significant advance due to their more predictable therapeutic effect and more favorable hemorrhagic risk profile. In hemodynamically unstable patients, an emergency electrical cardioversion (ECV) must be performed. In this situation, intravenous heparin or low molecular weight heparin (LMWH) should be administered before CV. In patients with AF occurring within less than 48 h, synchronized direct ECV should be the elective procedure, as it restores sinus rhythm quicker and more successfully than pharmacological cardioversion (PCV) and is associated with shorter length of hospitalization. Patients with acute onset AF were traditionally considered at lower risk of thromboembolic events due to the shorter time for atrial thrombus formation. In patients with hemodynamic stability and AF for more than 48 h, an ECV should be planned after at least 3 weeks of anticoagulation therapy. Alternatively, transesophageal echocardiography (TEE) to rule out left atrial appendage thrombus (LAAT) should be performed, followed by ECV and anticoagulation for at least 4 weeks. Theoretically, the standardized use of TEE before CV allows a better stratification of thromboembolic risk, although data available to date are not univocal.

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