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

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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Guidelines for mono, double and triple antithrombotic therapy

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2020-138938 ◽

2021 ◽

pp. postgradmedj-2020-138938

Author(s):

Renate C A E van Uden ◽

Ilse Houtenbos ◽

Anita Griffioen-Keijzer ◽

Diego A M Odekerken ◽

Patricia M L A van den Bemt ◽

...

Keyword(s):

Vitamin K ◽

Antithrombotic Therapy ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Duration Of Therapy ◽

European Guidelines ◽

Therapeutic Anticoagulation ◽

Triple Antithrombotic Therapy

Guidelines for antithrombotic therapy are complex, especially if a patient has several indications that require antithrombotic therapy. In general, no patient should receive lifelong double or triple antithrombotic therapy. In this overview, we outline the most common indications for mono, double and triple antithrombotic therapy; the preferred antithrombotic therapy and the recommended duration of therapy. Both antiplatelet therapy and therapeutic anticoagulation therapy with vitamin K antagonists or direct oral anticoagulants were included. European guidelines were used or, if no European guidelines were available, the Dutch guidelines were used.

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21 Direct oral anticoagulants vs. vitamin K antagonists in the treatment of left ventricular thrombosis: a systematic review and meta-analysis

European Heart Journal Supplements ◽

10.1093/eurheartj/suab131.003 ◽

2021 ◽

Vol 23 (Supplement_G) ◽

Author(s):

Francesco Condello ◽

Matteo Maurina ◽

Mauro Chiarito ◽

Matteo Sturla ◽

Riccardo Terzi ◽

...

Keyword(s):

Ischaemic Stroke ◽

Vitamin K ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Left Ventricular ◽

Clinical Effects ◽

Significant Difference ◽

Secondary Endpoints

Abstract Aims Evidence about the use of direct oral anticoagulants (DOACs) in patients with left ventricular thrombosis (LVT) are emerging. The aim of our study was to provide a comprehensive synthesis of the available evidence concerning the clinical effects of DOACs vs. vitamin K antagonists (VKAs) in LVT treatment. Methods Systematic search of studies evaluating DOACs vs. VKAs use in patients with LVT was performed on 11 May 2021. Data were pooled by meta-analysis using a random-effects model. Odds ratios (OR) with relative 95% confidence intervals (CI) were used as measures of effect estimates. The primary efficacy and safety endpoint were ischaemic stroke and any bleeding, respectively. Secondary endpoints were LVT resolution, systemic embolism, major bleeding, haemorrhagic stroke, and all cause death. Results Twenty studies were included in the meta-analysis: 1391 patients were treated with DOACs and 1534 with VKAs. A significant reduction in the risk of ischaemic stroke [OR 0.67, 95% CI 0.45–0.98, P = 0.048, number needed to treat to benefit (NNTB) 22 (95% CI 15–43)] and any bleeding [OR 0.64, 95% CI 0.46–0.89, P = 0.009, NNTB 26 (95% CI 16–80)] was observed with DOACs compared to VKAs. No statistically significant difference was observed among the two treatment arms for the secondary endpoints. Conclusion Compared to VKAs, DOACs are associated with a reduced risk of ischaemic stroke and bleeding. In light of these findings, and the practical advantages of DOACs, additional large scale randomized controlled trials are needed to confirm the benefits of DOACs in patients with LVT.

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Off-label Non-vitamin K Antagonist Oral Anticoagulants Does Not Decrease the Stroke Risk of Atrial Fibrillation Patients in East China

10.21203/rs.3.rs-141450/v1 ◽

2021 ◽

Author(s):

Peng Zhou ◽

Rongchen Liu ◽

Yangjie Yu ◽

Wei Chen ◽

Yunzhi Ma ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Vitamin K Antagonist ◽

East China ◽

Once Daily ◽

Off Label ◽

Significant Difference ◽

Label Dose

Abstract Background: For anticoagulation therapy of atrial fibrillation (AF) in east Asia, some off-label dose, so called “Asian Dose” of non-vitamin K antagonist oral anticoagulants (NOACs) was used concerning on the bleeding risks in these patients, such as low-dose rivaroxaban (10-15 mg once daily) or dabigatran (110-150 mg once daily). However, the efficacy of the off-label dose of NOACs remains controversial. Methods: We conducted a retrospective cohort study to compared the efficacy and safety among patients with AF in three groups: patients with the off-label dose of NOACs treatment (OFL group, dabigatran 110 mg once daily or rivaroxaban under 20 mg daily), patients with the standard dose of anti-coagulation therapy (SAG group, dabigatran 110 mg twice daily or rivaroxaban 20 mg once daily, or warfarin with international normalized ratio (INR) 2-3), and patients without non-coagulation treatment (NCG group) in east China. Results: A total of 296 patients were recruited in our study. Compared to patients in SAG group, patients in OFL group had higher risk in stroke and thromboembolism events (P=0.000). The risk of other events including major bleeding (P=0.597) was comparable in these two groups, while there was no significant difference in all-cause mortality, which were both dramatically lower than NAG group (0.52, P=0.000). Conclusions: Collectively, our results demonstrate that “Asian dose” of NOACs indeed can not bring much benefit for AF patients in east China.

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Delayed Time to Emergency Hip Surgery in Patients Taking Oral Anticoagulants

Blood ◽

10.1182/blood-2019-128849 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2445-2445

Author(s):

Teresa Cafaro ◽

Vicky Tagalakis ◽

Maral Koolian ◽

Simard Camille

Keyword(s):

Hip Fracture ◽

Vitamin K ◽

Action Plan ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Group Versus ◽

Hip Fracture Surgery ◽

Significant Difference ◽

Time Of Admission

Abstract Introduction Surgical intervention within 48 hours of admission in patients with acute hip fractures has been associated to lower morbidity and mortality. Patients anticoagulated with Vitamin K Antagonists (VKAs) have longer time to corrective surgery than those not anticoagulated. Sparse data exists on time to surgery (TTS) in patients taking direct oral anticoagulants (DOACs). The aim of this study is to establish TTS among non-anticoagulated and anticoagulated patients taking either VKA or DOAC. Materials and Methods We conducted a retrospective cohort study of consecutive patients admitted with acute hip fracture between July 1, 2016 and December 31, 2017. Patient-, anticoagulant- and surgery-related characteristics were collected. The primary outcome was TTS calculated from time of admission. Median TTS with interquartile range (IQR) was compared among 3 groups of patients: DOAC, VKA and No OAC. Results A total of 472 patients were included: 12.5% (59/472) were anticoagulated (28/472 on VKAs and 31/472 on DOACs). Median TTS was longer in the VKA group [64 hours (IQR: 50-84)] and in the DOAC group [(61 hours; IQR: 42 to 77)] versus the No OAC group [44 hours (IQR: 28-63), p =0.0006 and p=0.003 respectively]. There was no significant difference in median TTS in the VKA group versus the DOAC group (p =0.6396). Conclusion Patients taking either VKA or DOAC have significant delays to emergency hip fracture surgery compared to those not anticoagulated. An action plan aimed at early identification and cessation of anticoagulation is warranted in this vulnerable group of patients. Keywords: Direct Oral anticoagulants, Vitamin K antagonists, Anticoagulation, Acute hip fracture, Emergency surgery Disclosures Tagalakis: BMS-Pfizer: Other: participated on ad boards; Sanofi Aventis: Other: investigator initiated grant;participated on ad boards; Pfizer: Other: participated on ad boards; Bayer: Other: participated on ad boards; Servier: Other: participated on ad boards.

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Thrombotic events and rebleeding after hemorrhage in patients taking direct oral anticoagulants for non-valvular atrial fibrillation

PLoS ONE ◽

10.1371/journal.pone.0260585 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0260585

Author(s):

Daisuke Yanagisawa ◽

Koichiro Abe ◽

Hirohito Amano ◽

Shogo Komatsuda ◽

Taku Honda ◽

...

Keyword(s):

Atrial Fibrillation ◽

Gastrointestinal Bleeding ◽

Anticoagulant Therapy ◽

Oral Anticoagulant ◽

Clinical Course ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

The Other ◽

Direct Oral Anticoagulant

Several direct oral anticoagulants have been developed to prevent cardiogenic thrombosis in patients with atrial fibrillation, on the other hand, have the complication of bleeding. Since clinical course after bleeding with direct oral anticoagulant remains unclear, the present retrospective cohort study was to clarify the course after hemorrhage among patients receiving direct oral anticoagulants. Among all 2005 patients prescribed dabigatran, rivaroxaban, apixaban, or edoxaban between April 2011 and June 2017, subjects comprised 96 patients with non-valvular atrial fibrillation who experienced relevant bleeding during direct oral anticoagulant therapy (Bleeding Academic Research Consortium type 2 or above). The clinical course after hemorrhage was reviewed to examine whether rebleeding or thrombotic events occurred up to the end of December 2019. Gastrointestinal bleeding was the most frequent cause of initial bleeding (57 patients, 59%). Rebleeding occurred in 11 patients (4.5%/year), with gastrointestinal bleeding in 10 and subarachnoid hemorrhage in 1. All rebleeding occurred in patients who resumed anticoagulation therapy. Another significant factor related with rebleeding included past history of gastrointestinal bleeding. On the other hand, major adverse cardiac and cerebrovascular events occurred in 6 patients older than 75 years old or more (2.5%/year), with systemic thrombosis in 4 and cardiac death in 2. All 4 patients with systemic thrombosis withheld anticoagulants after index bleeding, although only 10 patients withheld anticoagulation therapy. Rebleeding should be taken care of when anticoagulants are resumed after bleeding, particularly among patients who initially experienced gastrointestinal bleeding. Systemic thrombosis occurred at a high rate when anticoagulant therapy was withheld after bleeding.

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Postoperative Bleeding Complications in Patients on Novel Oral Anticoagulants and Vitamin K Antagonist Following an Invasive Dental Procedure - A Review of Literature

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2021/621 ◽

2021 ◽

Vol 10 (35) ◽

pp. 3047-3052

Author(s):

Pavithra M ◽

Arvind Muthukrishnan

Keyword(s):

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Postoperative Bleeding ◽

New Drugs ◽

Current Evidence ◽

Bleeding Complications ◽

Novel Anticoagulants ◽

Increased Risk ◽

Significant Difference

The incidence of thromboembolic diseases is high. It is one of the leading causes of death and disability. Anticoagulants are used for preventing or reducing blood clot formation and treatment of other related thrombotic disorders. Vitamin K antagonists (VKA) were developed more than 60 years ago. Warfarin is the most commonly used VKA. The drawbacks of vitamin K antagonists were that it requires frequent monitoring and dose adjustments, food and drug interactions, narrow therapeutic range, diet restrictions. For the past 15 years, various new drugs have been introduced to overcome the disadvantages of vitamin K antagonists. In 2008, a new group of anticoagulants were introduced. They are known as novel anticoagulants (NOAC) or direct oral anticoagulants. They include dabigatran, apixaban, rivaroxaban and edoxaban. The major issue with NOAC is difficulty in monitoring the dose. A literature search was done on this topic. It is very important for the dentists to know the bleeding complications in patients under anticoagulant therapy. The dental treatment of patients who tend to have an increased risk of bleeding due to the use of anticoagulants and / or antiplatelet drugs raises a challenge in the daily practice of dental professionals. According to current evidence, there is no significant difference in postoperative bleeding between novel anticoagulants and vitamin K antagonists. The risk of thromboembolic events on stopping the anticoagulants should be assessed. Local haemostatic measures are shown to suffice to control possible bleeding secondary to dental treatments. KEY WORDS Anticoagulants; Apixaban; Dabigatran; Dentistry; Edoxaban; Rivaroxaban.

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Multi-Center Study of Thromboplastin Calibration Precision – Influence of Reagent Species, Composition, and International Sensitivity Index (ISI)

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651544 ◽

1993 ◽

Vol 69 (01) ◽

pp. 035-040 ◽

Cited By ~ 12

Author(s):

A M H P van den Besselaar ◽

R M Bertina

Keyword(s):

Oral Anticoagulants ◽

International Normalized Ratio ◽

The Other ◽

World Health ◽

Rabbit Brain ◽

Sensitivity Index ◽

Bovine Plasma ◽

Significant Difference ◽

The Mean ◽

International Sensitivity Index

SummaryFour thromboplastin reagents were tested by 18 laboratories in Europe, North-America, and Australasia, according to a detailed protocol. One thromboplastin was the International Reference Preparation for ox brain thromboplastin combined with adsorbed bovine plasma (coded OBT/79), and the second was a certified reference material for rabbit brain thromboplastin, plain (coded CRM 149R). The other two thromboplastin reagents were another rabbit plain brain thromboplastin (RP) with a lower ISI than CRM 149R and a rabbit brain thromboplastin combined with adsorbed bovine plasma (RC). Calibration of the latter two reagents was performed according to methods recommended by the World Health Organization (W. H. O.).The purpose of this study was to answer the following questions: 1) Is the calibration of the RC reagent more precise against the bovine/combined (OBT/79) than against the rabbit/plain reagent (CRM 149R)? 2) Is the precision of calibration influenced by the magnitude of the International Sensitivity Index (ISI)?The lowest inter-laboratory variation of ISI was observed in the calibration of the rabbit/plain reagent (RP) against the other rabbit/plain reagent (CRM 149R) (CV 1.6%). The highest interlaboratory variation was obtained in the calibration of rabbit/plain (RP) against bovine/combined (OBT/79) (CV 5.1%). In the calibration of the rabbit/combined (RC) reagent, there was no difference in precision between OBT/79 (CV 4.3%) and CRM 149R (CV 4.2%). Furthermore, there was no significant difference in the precision of the ISI of RC obtained with CRM 149R (ISI = 1.343) and the rabbit/plain (RP) reagent with ISI = 1.14. In conclusion, the calibration of RC could be performed with similar precision with either OBT/79 or CRM 149R, or RP.The mean ISI values calculated with OBT/79 and CRM 149R were practically identical, indicating that there is no bias in the ISI of these reference preparations and that these reference preparations have been stable since their original calibration studies in 1979 and 1987, respectively.International Normalized Ratio (INR) equivalents were calculated for a lyophilized control plasma derived from patients treated with oral anticoagulants. There were small but significant differences in the mean INR equivalents between the bovine and rabbit thromboplastins. There were no differences in the interlaboratory variation of the INR equivalents, when the four thromboplastins were compared.

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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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A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index

Journal of Clinical Medicine ◽

10.3390/jcm10132924 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2924

Author(s):

Domenico Acanfora ◽

Marco Matteo Ciccone ◽

Valentina Carlomagno ◽

Pietro Scicchitano ◽

Chiara Acanfora ◽

...

Keyword(s):

Diabetes Mellitus ◽

Atrial Fibrillation ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Risk Index ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Efficacy Rate ◽

Cochrane Central Register ◽

Efficacy And Safety

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.

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Safety and efficacy of direct oral anticoagulants (DOACs) vs low molecular weight heparin (LMWH) in malignancy induced venous thromboembolism-a systematic review and meta analysis

European Heart Journal Acute Cardiovascular Care ◽

10.1093/ehjacc/zuab020.199 ◽

2021 ◽

Vol 10 (Supplement_1) ◽

Author(s):

A Abdul Razzack ◽

N Hussain ◽

S Adeel Hassan ◽

S Mandava ◽

F Yasmin ◽

...

Keyword(s):

Molecular Weight ◽

Venous Thromboembolism ◽

Major Bleeding ◽

Low Molecular Weight Heparin ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Low Molecular Weight ◽

Efficacy And Safety ◽

Dichotomous Data ◽

Significant Difference

Abstract Funding Acknowledgements Type of funding sources: None. Background- Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) have been proven to be more effective in the management of venous thromboembolism (MVTE). The efficacy and safety of LMWH or DOACs in treatment of recurrent or malignancy induced VTE is not studied in literature. Objective To compare the efficacy and safety of LMWH and DOACs in the management of malignancy induced VTE Methods- Electronic databases ( PubMed, Embase, Scopus, Cochrane) were searched from inception to November 28th, 2020. Dichotomous data was extracted for prevention of VTE and risk of major bleeding in patients taking either LMWH or DOACs. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p < 0.05. Results- Three studies with 2607 patients (DOACs n = 1301 ; LMWH n = 1306) were included in analysis. All the study population had active cancer of any kind diagnosed within the past 6 months. Average follow-up period for each trial was 6 months. Patients receiving DOACs have a lower odds of recurrence of MVTE as compared to LMWH( OR 1.56; 95% CI 1.17-2.09; P = 0.003, I2 = 0). There was no significant difference in major bleeding among patients receiving LMWH or DOACs (OR-0.71, 95%CI 0.46-1.10, P = 0.13, I2 = 22%) (Figure 1). We had no publication bias in our results (Egger’s regression p > 0.05). Conclusion- DOACs are superior to LMWH in prevention of MVTE and have similar major bleeding risk as that of LMWH. Abstract Figure. A)VTE Recurrence B)Major Bleeding events

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