High Bleeding Risk Procedures Research Articles

Risk of Bleeding with Endoscopic Ultrasound-Guided Tissue Acquisition in Patients on Antithrombotic Therapy: A Systematic Review and Meta-Analysis.

The present guidelines stratify endoscopic ultrasound-guided tissue acquisition (EUS-TA) as a high-bleeding risk procedure in patients on antithrombotics. However, the data regarding the same are conflicting. Therefore, this meta-analysis aimed to analyze the bleeding event rates associated with EUS-TA in patients receiving antithrombotic therapy. A literature search from January 2000 to August 2022 was done for studies on EUS-guided TA in patients receiving antithrombotics. The primary outcome was incidence of overall and major bleeding. Pooled event rates across studies were expressed with summative statistics. A total of 12 studies were included in the meta-analysis. The pooled risk of overall bleeding and major bleeding in patients on antithrombotics was 2.0% (0.6-3.4) and 0.8% (0.0-1.6), respectively. In patients taking thienopyridine or anticoagulants, the pooled risk of overall bleeding and major bleeding was 2.4% (0.9-3.9) and 1.7% (0.4-3.1), respectively. Patients on antithrombotics had a higher odd of overall bleeding (OR 2.12, 1.20-3.83) and major bleeding (OR 3.58, 1.11-11.52) compared to controls. The odds of overall bleeding (OR 0.95, 95%CI 0.38-2.42) and major bleeding (OR 1.57, 95%CI 0.45-5.54) were comparable between patients on antithrombotics who continued and those who discontinued it preprocedural. Despite an increase risk of bleeding with EUS-TA in patients on antithrombotics, the pooled incidence remains low. Compared to the previous guidelines stating thienopyridine use as high risk for bleeding, the present analysis showed a bleeding rate of less than 1%. Discontinuing antithrombotics prior to EUS-TA does not reduce the bleeding risk significantly, requiring strict monitoring.

Perioperative Considerations for Antithrombotic Therapy in Oculofacial Surgery: A Review of Current Evidence and Practice Guidelines.

Purpose:Recent survey studies have demonstrated wide variability in practice patterns regarding the management of antithrombotic medications in oculofacial plastic surgery. Current evidence and consensus guidelines are reviewed to guide perioperative management of antithrombotic medications.Methods:Comprehensive literature review of PubMed database on perioperative use of antithrombotic medication.Results/Conclusions:Perioperative antithrombotic management is largely guided by retrospective studies, consensus recommendations, and trials in other surgical fields due to the limited number of studies in oculoplastic surgery. This review summarizes evidence-based recommendations from related medical specialties and provides context for surgeons to tailor antithrombotic medication management based on patient’s individual risk. The decision to continue or cease antithrombotic medications prior to surgery requires a careful understanding of risk: risk of intraoperative or postoperative bleeding versus risk of a perioperative thromboembolic event. Cessation and resumption of antithrombotic medications after surgery should always be individualized based on the patient’s thrombotic risk, surgical and postoperative risk of bleeding, and the particular drugs involved, in conjunction with the prescribing doctors. In general, we recommend that high thromboembolic risk patients undergoing high bleeding risk procedures (orbital or lacrimal surgery) may stop antiplatelet agents, direct oral anticoagulants, and warfarin including bridging warfarin with low-molecular weight heparin. Low-risk patients, regardless of type of procedure performed, may stop all agents. Decision on perioperative management of antithrombotic medications should be made in conjunction with patient’s internist, cardiologist, hematologist, or other involved physicians which may limit the role of guidelines depending on patient risk and should be used on a case-by-case basis. Further studies are needed to provide oculofacial-specific evidence-based guidelines.

MANAGEMENT OF TOOTH EXTRACTIONS IN PATIENTS RECEIVING THE NEW ORAL ANTICOAGULANTS

Introduction: High bleeding risk procedures pose a serious challenge for dental practitioners treating patients taking some of the novel oral anticoagulants. Aim: The aim of the present study was to assess clinically the bleeding risk in a typical tooth extraction in patients on monotherapy with one of the new oral anticoagulants rivaroxaban (Xarelto), apixaban (Eliquis), and dabigatran (Pradaxa). Materials and methods: The study included 30 patients on these anticoagulants who underwent a typical tooth extraction. Local hemostasis was achieved using Surgicel, Haemocollagen or Gelaspon, and suturing the edges of the wound. Clinical evaluation of the bleeding was performed at 10 and 30 minutes, and 24 hours after the extraction. Anticoagulants were discontinued for the day of extraction. Results: Post-extraction bleeding in the first 10 minutes was observed in 17 patients (56.66%). Bleeding within 30 minutes was observed in 11 patients (36.66%). Two (6.66%) patients reported having only mild oozing within 24 hours. No additional haemostasis was required for any of the patients. Bleeding in a typical tooth extraction is of capillary origin. Bleeding sites are easily accessible and local hemostatic agents are effective enough to control the bleeding. Discontinuation of the anticoagulant on the day of extraction is sufficient to prevent any adverse events. No abnormal post-extraction bleeding was observed in our study. Conclusions: If tooth extraction is required in patients taking the new oral anticoagulants rivaroxaban (Xarelto), apixaban (Eliquis) or dabigatran (Pradaxa), the patient can cease the reception of the drug only for the day of the procedure.

Tranexamic acid to reduce operative blood loss in brain tumor surgery: A meta-analysis.

Background: Major blood loss during neurosurgery may result in a variety of complications, such as potentially fatal hemodynamic instability. Brain tumor and skull base surgery is among the high bleeding risk procedures. Tranexamic acid (TXA) has been found to reduce bleeding events in various fields of medicine.Methods: We searched for all randomized controlled trials published in English or Bahasa which compared the use of TXA with placebo in brain tumor surgery. The studies should include adult patients with intracranial tumor who received TXA before skin incision. The primary and secondary outcomes are intraoperative blood loss and the need of transfusion.Results: This meta-analysis included a total of 200 patients from three studies. TXA resulted in less blood loss with pooled mean difference of −292.80 (95% CI, −431.63, −153.96, P<0.05). The need of transfusion was not significant between TXA and control group (pooled mean difference −85.36, 95% CI, −213.23 – (42.51), P=0.19).Conclusion: TXA reduced the volume of blood loss but did not reduce the need of blood transfusion.

Periprocedural edoxaban interruption is associated with low bleeding and thromboembolic risk: the Italian data of the EMIT-AF/VTE study

So far, the only available data for edoxaban periprocedural management come from the ENGAGE AF-TIMI 48 trial. The recently published EMIT-AF/VTE study showed low periprocedural bleeding and thromboembolic risks of edoxaban in a real-world setting in patients undergoing any diagnostic or therapeutic procedures. The aim of this study was to compare descriptively Italian and European data with regard to patient characteristics and outcomes in the EMIT-AF/VTE study. A total of 1155 patients treated with edoxaban for stroke prevention in non-valvular atrial fibrillation and with venous thromboembolism, and undergoing a wide range of diagnostic and therapeutic procedures were enrolled in 326 centers across Europe. Of these patients, 246 were from 43 Italian centers. The periprocedural interruption of edoxaban was at the physician's discretion. All the procedures were classified into minor, low, and high bleeding procedural risk according to the European Heart Rhythm Association (EHRA) definition. The primary outcome was the incidence of major bleeding. Secondary outcomes included thromboembolic events. Patients were older in Italy in comparison with the rest of Europe with a mean age of 74.2 vs 71.3 years. Also, the rate of comorbidities was higher in Italy (e.g. diagnosed cancer and vascular disease) than in Europe. In Italy, there was a higher rate of high bleeding risk procedures than in other European countries (37.8% vs 20.6%) and a more homogeneous distribution of all types of procedures (while in Europe 44.1% were vascular access and transcatheter diagnostic procedures and interventions). In Italy, a higher proportion of patients did not interrupt edoxaban (32.9% vs 29% in Europe). The number of major bleeding events (2 in Italy, 3 in Europe) as well as of thromboembolic events (4 in Italy, 3 in Europe) was overall low. In the EMIT-AF/VTE study, the number of bleeding and thromboembolic events in patients treated with edoxaban undergoing elective or unplanned procedures was low either in Italy or in the rest of Europe. The safety and efficacy of edoxaban was confirmed in Italy even if patients were older, presented more frequently with cancer, and there was a higher rate of high bleeding risk procedures by EHRA definition.

Endoscopy-Related Bleeding and Thromboembolic Events in Patients on Direct Oral Anticoagulants or Vitamin K Antagonists

Few prospective studies have assessed the safety of direct oral anticoagulants (DOACs) in elective endoscopy. Our primary aim was to compare the risks of endoscopy-related gastrointestinal bleeding and thromboembolic events in patients on DOACs or vitamin K antagonists (VKAs) in this setting. Secondarily, we examined the impact of the timing of anticoagulant resumption on the risk of delayed bleeding in high-risk therapeutic procedures. We conducted a multicenter, prospective, observational study from January 2018 to March 2020 of 1602 patients on oral anticoagulants (1004 on VKAs and 598 on DOACs) undergoing 1874 elective endoscopic procedures. Our primary outcomes were 90-day thromboembolic events and 30-day endoscopy-related gastrointestinal bleeding. The inverse probability of treatment weighting propensity score method was used for baseline covariate adjustment. The 2 groups had similar risks of endoscopy-related gastrointestinal bleeding (VKAs vs DOACs, 6.2% vs 6.7%; adjusted odds ratio [OR], 1.05; 95% CI, 0.67-1.65) and thromboembolic events (VKAs vs DOACs, 1.3% vs 1.5%; adjusted OR, 0.90; 95% CI, 0.34-2.38). In high bleeding risk procedures (n= 747), delayed anticoagulant resumption (> 48 hours or 24-48 hours vs < 24 hours) did not reduce the risk of postprocedural bleeding (10.3%, 9%, and 5.8%, respectively; adjusted P= .43). Hot and cold snare polypectomy were the most frequent high-risk interventions (41.8% and 39.8%, respectively). In a prospective study of patients on DOACs or VKAs undergoing elective endoscopy, endoscopy-related bleeding and thromboembolic events showed similar risk. Our study suggests that early anticoagulant resumption is safe in most patients, but more data are needed for advanced high-risk therapeutic procedures.

Kidney Biopsy

The introduction of renal biopsies has transformed practice in nephrology, particularly with regard to glomerular disease and the care of kidney transplant recipients. A biopsy can provide information about the diagnosis and prognosis of kidney disease while most importantly often leading to changes in therapy that can be life saving. Four groups of patients benefit most from renal biopsy: those with nephrotic syndrome, those with acute nephritic syndromes with rapid deterioration of renal function, those with unexplained acute kidney injury and renal transplant recipients. Non-nephrotic range proteinuria and/or hematuria or unexplained chronic kidney disease represent indications in selected cases. The evaluation of patients prior to undergoing a kidney biopsy requires a careful assessment that includes a detailed history to confirm the relative benefit of a biopsy in making an accurate diagnosis compared with individual’s risk of bleeding. The use of real-time ultrasound or CT-guidance with gun-mounted biopsy needles is paramount for the successful performance of the biopsy and reduction of risks. renal biopsies are mostly done as an inpatient but can be performed on an outpatient basis in selected cases. A renal biopsy has a bleeding risk of up to 5% and is considered a “high bleeding risk procedure”. For patients receiving -antithrombotic therapy, the approach to periprocedural use of antithrombotic agents needs to be individualized. Because it is a high-risk procedure, all efforts must be undertaken to minimize the risk including a careful assessment of the patient's specific situation, and only experienced operators at institutions that can care for post-biopsy complications should perform the procedure. This review contains 7 tables, 7 figures and 83 references Key words: kidney biopsy, native kidney, transplant kidney, indications, preparation, performing biopsy, ultrasound guidance, transjugular, CT-guided, complications

Kidney Biopsy

The introduction of renal biopsies has transformed practice in nephrology, particularly with regard to glomerular disease and the care of kidney transplant recipients. A biopsy can provide information about the diagnosis and prognosis of kidney disease while most importantly often leading to changes in therapy that can be life saving. Four groups of patients benefit most from renal biopsy: those with nephrotic syndrome, those with acute nephritic syndromes with rapid deterioration of renal function, those with unexplained acute kidney injury and renal transplant recipients. Non-nephrotic range proteinuria and/or hematuria or unexplained chronic kidney disease represent indications in selected cases. The evaluation of patients prior to undergoing a kidney biopsy requires a careful assessment that includes a detailed history to confirm the relative benefit of a biopsy in making an accurate diagnosis compared with individual’s risk of bleeding. The use of real-time ultrasound or CT-guidance with gun-mounted biopsy needles is paramount for the successful performance of the biopsy and reduction of risks. renal biopsies are mostly done as an inpatient but can be performed on an outpatient basis in selected cases. A renal biopsy has a bleeding risk of up to 5% and is considered a “high bleeding risk procedure”. For patients receiving -antithrombotic therapy, the approach to periprocedural use of antithrombotic agents needs to be individualized. Because it is a high-risk procedure, all efforts must be undertaken to minimize the risk including a careful assessment of the patient's specific situation, and only experienced operators at institutions that can care for post-biopsy complications should perform the procedure. This review contains 7 tables, 7 figures and 83 references Key words: kidney biopsy, native kidney, transplant kidney, indications, preparation, performing biopsy, ultrasound guidance, transjugular, CT-guided, complications

Periprocedural Interruption of Edoxaban in Real World Setting: Results from the Emit AF/VTE Study

Background: The optimal interruption schedule for NOACs in patients undergoing invasive procedures has not been determined. This analysis describes periprocedural interruption of edoxaban in real world EMIT AF/VTE study. Methods: EMIT AF/VTE was a prospective, non-interventional study conducted in 7 European countries that collected detailed information on periprocedural management of edoxaban from 5 days before to 30 days after procedure in patients with AF or VTE. Results: Among 1155 patients, pre-procedural interruption occurred in 781 (68%) patients (median 2 days, IQR 1.0-2.0) and post-procedural interruption in 308 (27%) patients (median 3 days, IQR 1.0-8.0); 279 (24.2%) patients had both pre- and post-procedural interruption. Edoxaban interruption in some patients differed from 2018 EHRA Recommendations for NOAC use in AF. Of 294 patients receiving minor risk procedures, for whom no interruption is recommended, 173 (58.8%) had preprocedural interruption (median 1 day). Of 581 patients with low bleeding risk procedures, for whom ≥24h preprocedural interruption is recommended, 188 (32.4%) had no interruption. Of 280 patients receiving high bleeding risk procedures, for whom ≥48h interruption is recommended, 46 (16.4%) had no interruption. Clinical events are shown in Table. Conclusion: Edoxaban interruption schedules in routine practice were not always consistent with EHRA guidelines; nevertheless, rates of clinically significant bleeding or acute thromboembolic events or coronary syndromes were low in the EMIT study. Table Disclosures Colonna: Boehringer Ingelheim: Honoraria; Daiichi Sankyo: Honoraria; BayerAG: Honoraria; Italian Cardiology Association: Other: Non-financial support; European Society of Cardiology: Other: Non-financial support; Pfizer/BMS: Honoraria. von Heymann:Daiichi Sankyo: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria; Bayer AG: Honoraria; Pfizer GmBH: Honoraria; CSL Behring: Honoraria; NovoNordisk Pharma: Honoraria; EACTA and EACTS: Other; DGGG: Other; Mitsubishi Pharma: Honoraria; Ferring GmbH: Honoraria; Biotest GmbH: Honoraria; Leo Pharma GmBH: Honoraria; German Society of Anaesthesiology and Intensive Care Medicine: Other. Saxena:Daiichi Sankyo: Honoraria, Research Funding. Vanassche:Boehringer Ingelheim: Honoraria; 367 Leo Pharma: Honoraria; Bayer: Honoraria; Daiichi Sankyo: Honoraria, Research Funding. Jin:Daiichi Sankyo: Current Employment. Wilkins:Daiichi Sankyo: Honoraria. Chen:Daiichi Sankyo: Current Employment. Unverdorben:Daiichi Sankyo: Current Employment.

Predictors of Bleeding in the Perioperative Anticoagulant Use for Surgery Evaluation Study.

BackgroundIn the PAUSE (Perioperative Anticoagulant Use for Surgery Evaluation) Study, a simple, standardized, perioperative interruption strategy was provided for patients with nonvalvular atrial fibrillation taking direct oral anticoagulants (DOACs). Our objective was to define the factors associated with perioperative bleeding.Methods and ResultsWe analyzed bleeding as the composite of major and clinically relevant nonmajor bleeding. Putative predictors of bleeding, and preoperative DOAC level were prospectively collected during recruitment. We used stratified logistic regression models for analysis. All statistical analyses were performed in R version 3.6.0. There were 3007 patients requiring perioperative DOAC interruption. More than one third of the included patients underwent a high bleeding risk procedure. The 30‐day rates of major and clinically relevant nonmajor bleeding were 3.02% in apixaban (n=1257), 2.84% in dabigatran (n=668), and 4.16% for rivaroxaban (n=1082). Multivariate analysis stratified by region found more bleeding for hypertension (odds ratio [OR], 1.79; 95% CI 1.07‐2.99; P=0.027), and prior bleeding (OR, 1.71; 95% CI, 1.08‐2.71; P=0.021). Surgical bleed risk classification (high‐ versus low‐risk) as a predictor of bleeding was only significant in the univariate analysis. The prediction model for major and clinically relevant nonmajor bleeding had an area under the curve of 0.71, and the preoperative DOAC level did not improve the area under the curve of the model.ConclusionsIn patients treated with DOACs who required an elective surgery/procedure and were managed with standardized DOAC interruption and resumption, there we did not find reversible risk factors for bleeding, suggesting that adjustment of the PAUSE management protocol to mitigate against bleeding is not needed.

Management of periprocedural anticoagulant therapy: a novel individualized approach-a transeusophageal echocardiographic study.

Patients with non-valvular atrial fibrillation who are under chronic oral anticoagulant therapy (OAC) treatment frequently require interruption of OAC treatment. By examining the presence of left atrial/left atrial appendage (LA/LAA) thrombus or dense spontaneous echo contrast (SEC) with transesophageal echocardiography (TEE) we aimed to develop an individualized strategy. To test the validity of CHA2DS2VASc score based recommendations was our secondary purpose. In this prospective study patients with non-valvular atrial fibrillation on OAC therapy were included. Patients' baseline characteristics, CHA2DS2VASc and HASBLED scores, medications, type of invasive procedures and clinical events were recorded.Each patient underwent to TEE examination prior to the invasive procedure. Bridging anticoagulation was recommended only to patients with LA/LAA thrombus. We included 155 patients and mean CHA2DS2VASc score of the study population was 3.4 ± 1.4. Seventy-one of them had LA/LAA thrombi or SEC on TEE examination and bridging anticoagulation was applied. OAC treatment was not bridged in 8 of 11 patients with prior cerebrovascular accident and 17 of 31 patients with CHA2DS2VASc score of > 4. 57 of 124 patients with CHA2DS2VASc score of ≤ 4 required bridging anticoagulation. There were 14 major bleedings decided according to ISTH bleeding classification. Major bleeding was observed only in patients underwent to high-risk bleeding procedure. In conclusion CHA2DS2VASc score by itself is not enough for decision-making regarding ischemic risk. Furthermore, since major bleedings occurred only in patients underwent to high-risk bleeding surgery, TEE-based individualisation may be a feasible approach particularly for those with high thromboembolic risk undergoing high-bleeding risk procedure.

The Peri-Operative Management of Anticoagulants: Systemic Review of Guidelines

Introduction Venous thromboembolism (VTE) and atrial fibrillation are thrombotic disorders resulting in significant morbidity and mortality, if left untreated. In Canada, 45,000 people, or 1-2 cases per 1000 people, per year will experience an acute VTE, and it is estimated that 200,000 Canadians have atrial fibrillation. The treatment of VTE and atrial fibrillation often includes the use of anticoagulants. Patients on anticoagulation may need interruption of treatment for surgeries and procedures. To evaluate differences in perioperative anticoagulation management strategies we conducted a systematic review of the peri-operative clinical practice guidelines for anticoagulants. Methods A protocol using the Preferred Reporting Items for Systematic review and Meta-analysis Protocols (PRISMA-P) was developed. Relevant primary clinical practice guidelines were identified using MEDLINE, EMBASE, and guideline-specific databases. All guidelines from the preceding 20 years up to January 11, 2019 were screened. Eligible manuscripts were reviewed by two independent reviewers. Data abstraction was independently completed in duplicate for included guidances and categorized according to thrombotic risks and bleeding risks. Guidances on emergency surgeries were not included for the purposes of this review. Information on anticoagulation interruption, bridging regimens, laboratory testing, and reversal strategies were collected. Results Eight guidelines met inclusion criteria and 6 contained sufficient information for peri-operative management of anticoagulants. One guideline focused on patients presenting with bleeding events and restated the same peri-operative guidelines as had been published a year prior by the same group, and was excluded. Another guideline only addressed emergency surgeries and was also excluded from this review. The majority of the guidelines had similar definitions of risk factors for venous and arterial thrombotic events (see table 1). There were no conflicting guidance recommendations identified, but there were differences in the component of peri-operative management addressed by each guideline, ie bridging, reversal agents, laboratory tests. The levels of evidence used to develop recommendations varied between guidelines. All guidelines provided recommendations on warfarin and low molecular weight heparins (LMWH) management and only one guideline provided suggestions for direct oral anticoagulants (DOACs). The findings for perioperative anticoagulation management for patients with atrial fibrillation and VTE are presented in Tables 2 and 3, respectively. For high bleeding risk surgeries, most guidelines cited similar studies resulting in similar recommendations for interruption of warfarin and bridging in high venous and arterial thrombotic risk patients. In high bleeding risk procedures and low thrombotic risk patients, no bridging is recommended. For low bleed risk procedures, regardless of thrombotic risk, guidelines recommended for continuation of anticoagulant therapy. Discussion This systematic review identified 6 guidelines of non-urgent peri-operative management recommendations of primarily warfarin and LMWH in patients with VTE and atrial fibrillation. While no major discrepancies in the guideline suggestions were noted, the scope of data examined (medication management, bridging, blood tests, reversal of agents) differed amongst the various agencies. The guidelines that were most consistent for recommendations of anticoagulant management and bridging tended to be from hematologic societies. The only guideline that addressed perioperative management of DOACs was the 2018 ASH guideline on management of VTE which was against measurement of DOAC levels prior to procedures. The lack of thorough guidance for DOACs is likely due to the year of publication of the guidelines examined and paucity of contributing studies. In terms of reversal agents, all clinical practice guidelines except for the ASH guidelines were prior to specific DOAC reversal agents such as idaracizumab. Future Directions We anticipate that there will be other guidelines developed that address specifically the use of DOACs in the perioperative setting, as well as their reversal agents. Disclosures Shivji: BMS-Pfizer Thrombosis Canada: Other: Fellowship award. Castellucci:BMS: Honoraria; Pfizer: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria; Sanofi: Honoraria; Aspen: Honoraria; Servier: Honoraria.

Predictors of Bleeding in the Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study

Introduction In the Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study a simplified, standardized, pharmacokinetic based perioperative interruption scheme was stablished for patients with non-valvular atrial fibrillation taking direct oral anticoagulants (DOACs). The rate of bleeding and thromboembolic outcomes was low, yet better awareness of bleeding predictors will aid the informed decision making for both clinicians and patients. Thus, we aimed to define the factors associated with perioperative bleeding events in the PAUSE cohorts. Methods The standardized interruption scheme is depicted in figure 1. We analyzed bleeding as the composite of major and clinically relevant non-major bleeding (MB/CRNM) according to the ISTH criteria. Putative predictors of bleeding were prospectively collected during the PAUSE recruitment. For patients taking dabigatran the dilute thrombin time was measured from a pre-operative blood sample. A DOAC-calibrated anti-factor Xa level was assessed preoperatively for patients taking factor Xa inhibitors. Continuous numeric variables were reported as means with SD; frequencies were reported when appropriate. We used stratified logistic regression models for analysis. All statistical analyses were performed in R version 3.6.0. Results There were 3007 patients requiring perioperative DOAC interruption, distributed in the apixaban (A) (N = 1,257), dabigatran (D) (N = 668), and rivaroxaban (R) (N = 1,082) cohorts. Characteristics of the patients who developed MB/CRNM are reported in table 1. More than one third of included patients underwent a high bleeding risk procedure. The rates of MB/CRNM were 3.02% in group A, 2.84% in group D, and 4.16% of group R patients from the point of DOAC interruption to 30 days after the procedure. In the univariate analysis, surgery bleeding risk was significantly associated with MB/CRNM (low vs high, OR 0.56, 95% CI 0.36-0.86; p=0.008). Multivariate analysis stratified by region found hypertension (OR 1.81, 95%CI 1.07-3.07; p=0.027), prior bleed or bleed predisposition (OR 1.62, 95% CI 1.02-2.58; p=0.043) were significantly associated with MB/CRNM (table 2); whereas surgery bleeding risk was not significant after adjusting other covariates. Female gender was associated with lower MB/CRNM risk (This result seems to be mainly driven by the rate of CRNM, 2.21% male had CRNM and 1.57% female had CRNM, and the signal disappeared in the model for MB). [Hypertension (OR 3.93, 95%CI 1.40-11.07; p=0.010), active cancer (OR 2.30, 95% CI 1.10-4.81; p=0.026) were significantly associated with MB (table 3)] Aspirin use was more prevalent among males (13.78%) than females (7.75%), but this did not fully explain the gender effect. The model for MB/CRNM had an area under the curve (AUC) of 0.65 (standard error 0.03). Drug level analysis was available for 2541 (84.5%) patients. In the stratified analysis with the DOAC level (&amp;gt;50ng/dL vs £50ng/dL) as a single predictor, there was no significant association with MB/CRNM observed (OR 1.07, 95% CI 0.38-2.96; p=0.902). In the multivariate model, adding DOAC level to the model did not improve the AUC. Discussion A standardized interruption scheme results in low risk of bleeding for patients with atrial fibrillation interrupting DOACs for surgery/invasive procedures. The protocol-defined surgical bleed risk in PAUSE was valid, and selected to numerically higher bleeding rates, but it was not independent predictor of bleeding when the interruption scheme and covariates are accounted for. Hypertension was the only potentially modifiable predictor of perioperative MB/CRNM bleeding. Likely selecting for a frail population, active cancer and hypertension were predictors of MB events. In the exploratory analyses, residual levels did not improve the predictive model. The multivariate model had a low performance and we do not advocate modification of the PAUSE-proposed interruption schema based on these results. The PAUSE trial is the first large scale study enabled to investigate the factors governing perioperative bleed among DOAC-Anticoagulated patients. Nonetheless, we did not have power to analyze DOAC cohorts independently due to the paucity outcomes. Overall, the results strengthen the validity of the PAUSE-proposed DOAC interruption scheme for atrial fibrillation patients who need surgery. Disclosures Tafur: Recovery Force: Consultancy; Janssen: Other: Educational Grants, Research Funding; BMS: Research Funding; Idorsia: Research Funding; Daichi Sanyo: Research Funding; Stago: Research Funding; Doasense: Research Funding. Spyropoulos:Bayer: Consultancy; Ingelheim: Consultancy; Portola: Consultancy; Janssen: Research Funding; Boehringer INgelheim: Research Funding; Janssen: Consultancy. Douketis:Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Portola: Other: Consultant ; Janssen: Other: Consultant ; The Merck Manual: Patents &amp; Royalties; Up-to-Date: Patents &amp; Royalties.

Thrombotic and Bleeding Outcomes Following Perioperative Interruption of Direct Oral Anticoagulants and Vitamin K Antagonists in Patients with Non-Valvular Atrial Fibrillation - a Comparative Analysis

Background: Atrial fibrillation (AF) is a common disorder that will affect up to 5.6 million patients in the U.S. by 2050. Both direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs), typically warfarin, are used for stroke prevention in AF and such patients frequently undergo invasive procedures requiring anticoagulant interruption. Temporary interruption of anticoagulants can be associated with significant morbidity and mortality in the form of thromboembolic and bleeding complications. DOACs have a short half-life and fast onset of action, thereby facilitating their perioperative management as compared to VKAs. Despite important differences in perioperative management and pharmacokinetics between DOACs and VKAs, there is a paucity of data comparing perioperative outcomes in DOAC and VKA-treated patients.Methods: We undertook a single-center, retrospective chart review that compared consecutive DOAC- or warfarin-treated patients with AF who underwent perioperative anticoagulant interruption for invasive procedures between January 2017 and March 2018. Perioperative warfarin interruption was done as per CHEST guidelines (Douketis et al. Chest 141,2 Suppl). Perioperative bridging with low-molecular-weight heparin was only used for patients with CHADS2 scores of 5-6 or in patients with stroke within the past 6 months. Perioperative interruption of DOACs was done as per Thrombosis Canada guidelines, with anticoagulation held for 3 half-lives prior to low bleeding risk procedures and 5 half-lives for high bleeding risk procedures. Primary outcomes included the 30-day post-operative thromboembolic and major bleeding rates. Secondary outcomes included the 30-day clinically relevant non-major bleeding (CRNMB) andl mortality rates. Major bleeding and CRNMB were defined according to ISTH definitions. Procedural bleeding risk was defined as per Schulman et al (Circulation 2015; 132(3)). Outcome events were independently adjudicated by two investigators. Outcomes from patients on DOACs and VKAs were compared. Demographic data was analyzed on a per-patient basis, p-values were calculated using independent T-Test, Chi-Square/Fisher's Exact Test where appropriate. Outcome data was analyzed on a per-interruption basis. P-values for unadjusted and adjusted comparisons were calculated using generalized estimating equations (GEE) to account for correlation between multiple procedures on the same patients.Results: 325 DOAC patients and 199 warfarin patients underwent 351 and 221 periprocedural interruptions, respectively. Warfarin patients had a significantly higher mean age, CHADS2 score, and proportion with renal dysfunction (Table 1). There was no statistically significant difference in 30-day post-operative rates of thromboembolism, CRNMB, and overall mortality, but warfarin patients had a significantly higher rate of major bleeding (Table 2). This latter result remained statistically significant following multivariate logistic regression correction for age, CHADS2 score and level of renal dysfunction. All bleeding events occurred post-procedure, with major bleeding events occurring from post-operative day 1 to post-operative day 25. None of the warfarin patients with major bleeding received perioperative bridging; the mean international normalized ratio (INR) at the time of major bleeding was 3.3. Most major bleeding events (7/8) in the VKA arm were surgical, with a single non-surgical major-bleed (spontaneous ICH on post-operative day 15 following urological surgery).Conclusions: The perioperative interruption of warfarin was associated with a higher 30-day rate of major bleeding as compared with DOAC interruption. Re-initiation of warfarin should be done judiciously following high bleeding risk procedures, and close INR monitoring may be warranted. [Display omitted] DisclosuresShaw:Portola Pharmaceuticals: Research Funding. Douketis:Janssen: Consultancy; Pfizer: Other: Advisory Board; Boehringer-Ingelheim: Consultancy, Other: Advisory Board, Research Funding; Portola: Other: Advisory Board; The Medicines Company: Other: Advisory Board; Daiichi-Sankyo: Other: Advisory Board; Biotie: Other: Advisory Board; Bayer: Other: Advisory Board; Sanofi: Consultancy, Other: Advisory Board; BMS: Other: Advisory Board; Astra-Zeneca: Other: Advisory Board. Carrier:Bayer: Honoraria; Pfizer: Honoraria; BMS: Honoraria, Research Funding; Leo Pharma: Research Funding.

Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study: A Perioperative Management Plan for Patients with Atrial Fibrillation Who Are Receiving a Direct Oral Anticoagulant

Introduction: The perioperative management of patients who are taking a direct oral anticoagulant (DOAC) for atrial fibrillation (AF) and require an elective surgery/procedure is uncertain. No studies have addressed the timing of perioperative DOAC interruption and resumption, and if perioperative heparin bridging and coagulation function testing are needed. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study hypothesized that a simple, standardized perioperative management strategy, based on DOAC-specific interruption and resumption intervals, that foregoes perioperative heparin bridging and coagulation function testing, is safe for patient care, with associated low rates of major bleeding (1%) and arterial thromboembolism (0.5%). We postulated that this management yields a high proportion of patients (>90%) with a minimal to no DOAC level at surgery/procedure. Methods: PAUSE is a prospective study with 3 parallel DOAC cohorts of patients with AF taking apixaban, dabigatran or rivaroxaban and requiring anticoagulant interruption for an elective surgery/procedure. Patients were managed using a standardized protocol based on DOAC pharmacokinetic properties, procedure-associated bleeding risk (Appendix 1) and creatinine clearance (CrCl). DOACs were interrupted for 1 day before and after surgery for a low bleed risk surgery and 2 days before and after a high bleed surgery; longer interruption was done in patients on dabigatran with a CrCl Results: We enrolled 3007 patients from 23 sites in Canada, the U.S. and Europe (Appendix 4). The patient characteristics were (Figure 2): mean age 72.5 years; 66.1% male; 33.5% high bleeding risk surgery/procedure, with 1257 patients in the apixaban cohort, 668 in the dabigatran cohort and 1082 in the rivaroxaban cohort (Table 1). DOAC interruption and resumption intervals are shown in Table 2. The 30-day postoperative rate (95% CI) of major bleeding was 1.35% (0-2.00) in the apixaban cohort, 0.90% (0-1.73) in the dabigatran cohort and 1.85% (0-2.65) in the rivaroxaban cohort; the rate (95% CI) of arterial thromboembolism was 0.16% (0-0.48) in the apixaban cohort, 0.6% (0-1.33) in the dabigatran cohort and 0.37% (0-0.82) in the rivaroxaban cohort (Table 3). There were 2541 (84.5%) patients with preoperative DOAC levels measured: a level Conclusions: In patients with AF who were taking a DOAC (apixaban, dabigatran, rivaroxaban) and required anticoagulant interruption for an elective surgery/procedure, using a standardized DOAC-specific perioperative management strategy was safe for patient care, with associated low rates of perioperative MB ( 90% overall; 98.8% at high bleeding risk) had a minimal or no residual DOAC level at the time of the surgery/procedure. PAUSE is the largest study, to date, that addresses how to manage the common problem of perioperative DOAC management. It is likely to have a practice-changing impact and will inform future practice guidelines in perioperative care. Study Funding: CIHR (313156) and the H&S Foundation of Canada (G-14-0006136). Aniara-Hyphen Biomed (assays). Acknowledgements: We thank Drs. Walter Ageno, David Garcia, Lehana Thabane, Wendt Lim, Lori Linkins, William Ristevski, and Demetrios J. Sahlas. Also, Kayla Lucier, Grace Wang, Tara McDougall, and HRLMP and CRLB. Supported by CanVector and REDCap. Disclosures Douketis:Bayer: Other: Advisory Board; Janssen: Consultancy; BMS: Other: Advisory Board; Biotie: Other: Advisory Board; Daiichi-Sankyo: Other: Advisory Board; Boehringer-Ingelheim: Consultancy, Other: Advisory Board, Research Funding; The Medicines Company: Other: Advisory Board; Sanofi: Consultancy, Other: Advisory Board; Astra-Zeneca: Other: Advisory Board; Portola: Other: Advisory Board; Pfizer: Other: Advisory Board. Spyropoulos:Janssen Scientific Affairs, LLC: Consultancy. Carrier:Bayer: Honoraria; Leo Pharma: Research Funding; Pfizer: Honoraria; BMS: Honoraria, Research Funding. Vanassche:Bayer: Consultancy; Boehringer Ingelheim: Consultancy; BMS/Pfizer: Consultancy. Verhamme:Bayer: Honoraria, Research Funding; Medtronic: Honoraria; Portola: Honoraria; Boehringer Ingelheim: Honoraria; Leo Pharma: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Shivakumar:Pfizer: Honoraria; Servier: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria. Gross:Pfizer: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria; Servier: Honoraria. Lee:Pfizer: Consultancy, Research Funding; BMS: Research Funding; Servier: Honoraria; LEO Pharma: Consultancy, Research Funding; Bayer: Consultancy, Honoraria. Le Templier:BMS-pfizer: Honoraria. Wu:Leo Pharma: Honoraria; Pfizer: Honoraria; BMS-Pfizer: Honoraria. Coppens:Bayer: Honoraria, Other: Non-financial support, Research Funding; CSL Behring: Honoraria, Other: non-financial support, Research Funding; Uniqure BV: Research Funding. Arnold:Bristol Myers Squibb: Research Funding; UCB: Consultancy; Amgen: Consultancy, Research Funding; UCB: Consultancy; Amgen: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Consultancy, Research Funding. Caprini:Alexion Pharmaceuticals: Membership on an entity9s Board of Directors or advisory committees; Recovery Force: Consultancy; BMS: Membership on an entity9s Board of Directors or advisory committees; Pfizor: Membership on an entity9s Board of Directors or advisory committees; Janssen RD Bayer: Honoraria; Sanofi: Honoraria; Boehringer-Ingelheim: Honoraria, Research Funding.

Periprocedural Interruption of Anticoagulation in Patients with Cancer-Associated VTE: An Analysis of Thrombotic and Bleeding Outcomes

Background: Approximately 10-20% of patients with venous thromboembolic events (VTE) have underlying malignancy. VTE is considered the second leading cause of death in patients with cancer, and patients with cancer-associated VTE are at higher risk of anticoagulant-related bleeding. Although patients with cancer often undergo diagnostic or therapeutic invasive procedures, there is a paucity of data on adverse outcomes following the periprocedural interruption of anticoagulation in this patient population.Methods: We did a single-center, retrospective chart review of consecutive patients with cancer-associated VTE who had periprocedural interruption of anticoagulation for invasive procedures between November 2015 and March 2018. Perioperative interruption of warfarin/low-molecular-weight heparin was done as per CHEST guidelines (Douketis et al. Chest 141(2 Suppl). Heparin bridging anticoagulation was used only for patients with recent (< 3 months) VTE. Perioperative interruption of direct oral anticoagulants (DOACs) was done as per Thrombosis Canada guidelines, with anticoagulation held for 3 half-lives prior to low bleeding risk procedures and 5 half-lives for high bleeding risk procedures. Active cancer was defined as per the HOKUSAI VTE CANCER trial (Raskob et al. NEJM 378(7)). Primary outcomes were 30-day post-operative rates of VTE and major bleeding. Secondary outcomes were 30-day post-operative rates of clinically relevant non-major bleeding (CRNMB) and mortality. Major bleeding and CRNMB were defined according to ISTH definitions. Data are reported on a per-interruption basis. Herein, we present an interim analysis of results.Results: To date, 82 perioperative interruptions are included, of whom 69.5% were receiving a DOAC. Mean age of the cohort was 65.8 years, 62.2% were male, 92.6% had active cancer and 41.5% had metastatic cancer. Thrombocytopenia (platelet count < 100 x 106/L) was present in 12.2% of interruptions. Procedures were stratified as high bleeding risk in 65.9% of cases. The 30-day rates of thromboembolism and major bleeding were both 3.70 % (95% confidence interval [CI] 1.25 to 10.2%), as was the 30-day rate of CRNMB. There were no deaths during the 30-day follow-up period.Conclusions: The periprocedural interruption of anticoagulation in patients with cancer-associated VTE appears to be associated with high rates of post-operative thrombotic and bleeding complications. Prospective studies are required to better quantify the risks of periprocedural anticoagulation interruption in this patient population. DisclosuresShaw:Portola Pharmaceuticals: Research Funding. Douketis:BMS: Other: Advisory Board; Janssen: Consultancy; Bayer: Other: Advisory Board; Pfizer: Other: Advisory Board; Daiichi-Sankyo: Other: Advisory Board; Portola: Other: Advisory Board; Astra-Zeneca: Other: Advisory Board; Sanofi: Consultancy, Other: Advisory Board; Biotie: Other: Advisory Board; Boehringer-Ingelheim: Consultancy, Other: Advisory Board, Research Funding; The Medicines Company: Other: Advisory Board. Carrier:Pfizer: Honoraria; Bayer: Honoraria; BMS: Honoraria, Research Funding; Leo Pharma: Research Funding.

Predictors of perioperative major bleeding in patients who interrupt warfarin for an elective surgery or procedure: Analysis of the BRIDGE trial

The use of low-molecular weight heparin bridge therapy during warfarin interruption for elective surgery/procedures increases bleeding. Other predictors of bleeding in this setting are not well described. BRIDGE was a randomized, double-blind, placebo-controlled trial of bridge therapy with dalteparin 100 IU/kg twice daily in patients with atrial fibrillation requiring warfarin interruption. Bleeding outcomes were documented from the time of warfarin interruption until up to 37 days postprocedure. Multiple logistic regression and time-dependent hazard models were used to identify major bleeding predictors. We analyzed 1,813 patients of whom 895 received bridging and 918 received placebo. Median patient age was 72.6 years, and 73.3% were male. Forty-one major bleeding events occurred at a median time of 7.0 days (interquartile range, 4.0-18.0 days) postprocedure. Bridge therapy was a baseline predictor of major bleeding (odds ratio [OR]=2.4, 95% CI: 1.2-4.8), as were a history of renal disease (OR=2.9, 95% CI: 1.4-6.0), and high-bleeding risk procedures (vs low-bleeding risk procedures) (OR=2.9, 95% CI: 1.4-5.9). Perioperative aspirin use (OR=3.6, 95% CI: 1.1-11.9) and postprocedure international normalized ratio >3.0 (OR=2.1, 95% CI: 1.5-3.1) were time-dependent predictors of major bleeding. Major bleeding was most common in the first 10 days compared with 11-37 days postprocedure (OR=3.5, 95% CI: 1.8-6.9). In addition to bridge therapy, perioperative aspirin use, postprocedure international normalized ratio >3.0, a history of renal failure, and having a high-bleeding risk procedure increase the risk of major bleeding around the time of an elective surgery/procedure requiring warfarin interruption.

Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study.

Patients receiving direct oral anticoagulants (DOACs) frequently undergo elective invasive procedures. Their management is challenging. We aimed to determine the optimal duration of DOAC discontinuation that ensures a minimal anticoagulant effect during the procedure. This prospective multicentre study included 422 DOAC-treated patients requiring an invasive procedure. Pre-procedural DOAC concentration ([DOAC]) and routine haemostasis assays were performed to determine i/the proportion of patients who achieved a minimal pre-procedural [DOAC] (≤30 ng/mL) according to the duration of DOAC discontinuation, ii/the predictors of minimal [DOAC] and, iii/the ability of routine assays to predict minimal [DOAC]. Lastly, we assessed the predictors of peri-procedural bleeding events. The duration of DOAC discontinuation ranged from 1 to 218 h and pre-procedural [DOAC] from ≤30 to 527 ng/mL. After a 49-72-h discontinuation, 95% of the [DOAC] were ≤30 ng/mL. A 72-h discontinuation predicted concentrations ≤30 ng/mL with 91% specificity. In multivariable analysis, duration of DOAC discontinuation, creatinine clearance <50 mL/min and antiarrhythmics were independent predictors of minimal pre-procedural [DOAC] (concordance statistic 0.869; 95% confidence interval: 0.829-0.912). Conversely, routine haemostasis assays were poor predictors. Last, creatinine clearance <50 mL/min, antiplatelets and high-bleeding risk procedures were predictors of bleeding events. A last DOAC intake 3 days before a procedure resulted in minimal pre-procedural anticoagulant effect for almost all patients. Moderate renal impairment, especially in dabigatran-treated patients, and antiarrhythmics in anti-Xa-treated patients should result in a longer DOAC interruption. In situations requiring testing, routine assays should not replace DOAC concentration measurement.

Bleeding and Thrombotic Outcomes Following Perioperative Interruption of Direct Oral Anticoagulants in Patients with Prior Venous Thromboembolic Disease

▪Introduction: The use of Direct Oral Anticoagulants (DOACs) for the prevention and treatment of Venous Thromboembolic Disease (VTE) is increasingly common. Patients on longstanding anticoagulation for the prevention of VTE frequently undergo invasive procedures that necessitate interruption of anticoagulation in order to avoid excessive bleeding during the procedure. There is little evidence surrounding the safety of perioperative DOAC interruption in patients with VTE.Methods: This study represents a retrospective analysis of adult patients on DOAC therapy for prior VTE, who underwent temporary interruption of anticoagulation therapy for inpatient or outpatient invasive procedures. The timing to hold and resume DOAC anticoagulation was based on the estimated half-life of the DOAC, as well as the bleeding risk of the procedure (Standard vs High). Our primary outcomes included the 30-day thromboembolic complication rate, as well as the 30-day major bleeding rate (ISTH non-surgical and surgical major bleeding criteria). Secondary outcomes included clinically relevant non-major bleeding (CRNMB) and overall mortality.Results: To date, a total of 87 patients have been included in the analysis, 68% of which were male. The mean age of the cohort was 58.3 years. All patients were on DOAC anticoagulation for acute treatment or secondary prevention of recurrent VTE. A large majority of patients (94%) were anticoagulated with rivaroxaban. Procedures were performed on an inpatient or outpatient basis in 24 and 63 patients, respectively. Forty six patients underwent procedures with standard bleeding risk. Mean time to anticoagulation discontinuation for standard and high bleeding risk procedures was 41.3 (SD = 20.8) and 49.3 (SD = 17.7) hours, respectively. The 30-day thromboembolic complication rate was 1.2% (95% CI: 0.2 to 6.2%), whereas the 30-day major bleeding rate was 0% (95% CI: 0 to 4.2%). The rate of CRNMB was 3.5% (95% CI: 1.2 to 9.7%). Overall mortality was 0% (95% CI: 0 to 4.2%).Conclusion: The perioperative interruption of direct oral anticoagulation for invasive procedures in patients with prior VTE appears to be associated with a relatively low risk of major bleeding, as well as recurrent VTE. Prospective studies are needed to evaluate the benefits and risks of perioperative interruption of direct oral anticoagulation in patients with prior VTE. DisclosuresCarrier:BMS: Research Funding; Leo Pharma: Research Funding.

Significant Differences between Vascular and Nonvascular Surgeons in the Perioperative Management of Antiplatelet Therapies in Patients with Coronary Stents

An increasing number of patients undergoing noncardiac surgery have coronary stents. Although guidelines regarding perioperative management of antiplatelet therapies in this patient population exist, practice patterns remain incompletely understood. This study evaluated these practice patterns, with particular attention to differences in management between vascular and nonvascular surgeons. A link to a 16-question survey was displayed in the American College of Surgeons (ACS) electronic newsletter NewsScope, which is posted on the ACS Web site. Questions were focused on perioperative management of antiplatelets (aspirin, clopidogrel) for bare-metal (BMS; placed within 2 months) and drug-eluting stents (DES; placed within the past year) during low- and high-risk bleeding procedures, assuming a patient with no other confounding medical issues. Primary stratification was by surgeon specialty. A total of 244 surgical providers responded to the survey, of which 40 (17%) were vascular surgeons. The majority of respondents were attending surgeons in practice for at least 10 years (79%, n = 190). A significantly higher percentage of vascular versus nonvascular surgeons would not stop aspirin preoperatively in low bleeding risk procedures (BMS: 90% vs. 54%, P = 0.001; DES: 88% vs. 58%, P = 0.009). A higher percentage of vascular surgeons would not stop aspirin preoperatively in high bleeding risk procedures as well (BMS: 70% vs. 28%, P < 0.001; DES: 78% vs. 32%, P < 0.001). Most vascular surgeons would not stop clopidogrel in a low-risk BMS patient (53% vs. 21% of nonvascular surgeons, P = 0.001). Similar findings with clopidogrel were observed in low- (would not stop: 65% vascular versus 30% nonvascular, P < 0.001) and high-risk DES patients (would not stop: 30% vascular versus 8% nonvascular, P = 0.001). The same trends were observed in resuming antiplatelets in the postoperative period. The majority of respondents were not familiar with professional guidelines regarding perioperative antiplatelet management (52%, n = 128), with no differences between vascular and nonvascular surgeons (45% vs. 54%, P = 0.30). This national survey demonstrates significant variation in perioperative antiplatelet management in patients with coronary stents, with marked differences between vascular and nonvascular surgeons. More effective communication of existing guidelines or the development of new specialty-specific professional guidelines appears prudent in reducing this variability in practice.