Antithrombotic therapy and oral surgery - PowerPoint Presentation

Antithrombotic therapy and oral surgery Michael B Streiff, MD FACP Professor of Medicine and Pathology Medical Director, Johns Hopkins Anticoagulation Service Chairman, VTE Guideline Committee ,National Comprehensive Cancer Network President, Medical and Scientific Advisory Board, National Blood Clot Alliance

Disclosures- Michael B. Streiff, MD Research support AHRQ Boehringer-IngelheimJanssenNIH/NHLBI PCORIPortolaRoche Consulting Bayer CSL Behring Daiichi-Sankyo Janssen Pfizer Portola Educational Grants Covidien

Scope of the Problem In 2009 548 million dental procedures performed annually Over 50% of Americans take daily aspirin Over 2 million MI and stroke annually in USMore than 30 million warfarin prescriptions each year Manski , R.J. and Brown, E. AHRQ Statistical Brief #368. April 2012.. Williams CD et al Am J Prev Med 2015; AHA/ASA Annual stats 2018; Wysowski DK et al Arch Intern Med 2007

Plan for Procedures: Thromboembolism Risk Stratification Thromboembolism Risk Mechanical Heart Valve Atrial Fibrillation Venous Thromboembolism High (> 10% per year ATE or 10% per month VTE) Mitral valve, Caged-ball or tilting disk valve, recent stroke, systemic embolism CHADS2 score 5 or 6, Recent stroke, systemic embolism, rheumatic valve diseaseRecent VTE (< 3 months)High risk thrombophilia (protein C,S, AT deficiency, APS, etc.)Intermediate (4-10%)Bileaflet aortic valve with stroke risk factorsCHADS2 score 3 or 4VTE within past 3-12 months, recurrent VTE, active cancer, Low risk thrombophiliaLow (< 4%)Bileaflet aortic valve without stroke risk factorsCHADS2 score of 0-2 (no prior stroke or systemic embolism)VTE > 12 months ago Spyropoulos AC et al. J Thromb Haemost 2016

Perioperative Bleeding Risk Surgery/ProcedureVery highNeurosurgery (intracranial/spinal) Urologic or cardiac surgery High Major cancer surgery Renal biopsy Large polyp resection Orthopedic surgeryHead and neck surgeryMajor intra-abdominal or thoracic surgeryLowLaparoscopic cholecystectomyCoronary angiographyArthroscopyBronchoscopy with biopsyVery LowMinor dermatologic procedureCataract removalPlan for Procedures: Procedural Bleeding Risk StratificationNCCN Guidelines 2018

A Systematic Review of Peri-procedural Anticoagulation Review of 34 studies (21 prospective, 1 RCT) Therapeutic AC in 20 studies (57%) Last pre-op LMWH dose 24+ hrs. before surgery (36%), 12-23 hrs. (36%)LMWH restart within 24 hrs (55%), > 24 hrs (16%) Bridging increases bleeding complications Siegal D et al. Circulation 2012

The Bridge Trial (Standard Risk AF) Dalteparin 100 units/kg q12h N=950 Placebo N=934 R Procedure Pre-op Bridge Day -3 Warfarin Warfarin- restart POD 1 Day - 5 Low risk-within 24 hrs. High Risk-with 48-72 hrs. Follow up 30 days Randomized double-blind placebo controlled trial 6445 AF pts screened, 1884 (29%) enrolled Mean age 72 yrs. , Male 1382 (73%) Mean CHADS 2 score 2.35 Low bleeding risk procedures N=1539 (81.7%) Douketis JD et al. NEJM 2015

Bridging did not improve outcomes Douketis JD et al. NEJM 2015

Perioperative Management of AC for VTE Retrospective cohort of 1178 pts. a nd 1812 proceduresVTE risk: Low 79%, Med 18%, High 3%Therapeutic bridge 73%Conclusion: Bridge therapy associated with excess bleed risk, no benefit Outcome Bridge (N=555) No Bridge (N=1257) P Value Recurrent VTE High 0/360/211.0 Med0/1091/215 (0.5%)0.48 Low 0/410 2/1021 (0.2%) 0.37 Bleed High 2/36 (5.6%) 1/21 (4.8%) 0.90 Med 5/109 (4.6%) 0/215 0.004 Low8/410 (2.0%)1/1021 (0.1%)< 0.001 Clark NP et al. JAMA Internal Med 2015

Who should be considered for perioperative bridging? Mechanical mitral valve Afib with stroke (especially within 3 months)Afib with CHADS2 score 5 or 6Venous thromboembolism with 3 months Active cancer with unprovoked VTE Recurrent unprovoked VTE Previous thromboembolism with therapy interruption or subtherapeutic AC High risk thrombophilia (Antiphospholipid syndrome, protein C or S or antithrombin deficiency)

When to stop warfarin and apixaban Warfarin (INR 2-3): at least 5 days prior to procedureApixaban (Half-life): CrCl > 80 ml/min (12 hrs.)CrCl 50-79 ml/min ( 15 hrs.) CrCl 30-49 ml/min (18 hrs.) Low risk surgery (4 half-lives = 6.3% drug left) Stop 2-3 days before surgery CrCl > 80 = 48 h, CrCl 50-79 = 60 h, CrCl 30-49 = 72 hHigh risk surgery (6 half-lives = 1.6% drug left)Stop 3-4.5 days before surgeryCrCl > 80 = 72 h, CrCl 50-79 = 90 h, CrCl = 30-49 = 108 hUniversity of Washington Anticoagulation Service; NCCN Guideline 2018

When to stop dabigatran Half-life CrCl > 80 ml/min (14 h) CrCl 50-79 ml/min (17 h)CrCl 30-49 ml/min (19 h)Low risk surgery (4 half-lives = 6.3% drug left)Stop 2.5-3 days before surgeryCrCl > 80 = 56 h, CrCl 50-79 = 68 h, CrCl 30-49 = 76 h High risk surgery (6 half-lives = 1.6% drug left) Stop 4-5 days before surgeryCrCl > 80 = 84 h, CrCl 50-79 = 102 h, CrCl = 30-49 = 114 hVan Ryn J et al. Thromb Haemost 2010; NCCN Guideline 2018;

When to stop edoxaban Half-life 10-14 hours Low risk surgery (4 half-lives = 6.3% drug left)Stop 2 days before surgeryHigh risk surgery (6 half-lives = 1.6% drug left)Stop 4 days before surgery NCCN Guideline 2018; Edoxaban PI

When to stop rivaroxaban Half Life CrCl > 80 ml/min (8 hrs.)CrCl 50-79 ml/min (9 hrs.)CrCl 30-49 ml/min (9 hrs.) Age 60+ (11-13 hrs.) Low risk surgery (4 half-lives = 6.3% drug left ) (about 2 days) Stop 2 days before surgery CrCl > 80 = 32 h, CrCl 50-79 = 36 h, CrCl 30-49 = 36 h, Age 60+ = 52 hoursHigh risk surgery (6 half-lives = 1.6% drug left)(about 2-3 days)Stop 3 days before surgeryCrCl > 80 = 48 h, CrCl 50-79 = 54 h, CrCl = 30-49 = 54 h), Age 60+ = 78 hoursUniversity of Washington Anticoagulation Service; NCCN Guideline 2018; Rivaroxaban PI

When to restart AC Tentative based upon post-op course Collaborative decision with surgeon VTE prophylaxis dosing prior to therapeuticLow risk surgeryRestart no sooner than 24-48 hoursHigh risk surgeryRestart no sooner than 72 hours Very high risk surgery Restart no sooner than 5-7 days

Perioperative Management of AC Step 1: Assess the bleeding risk of the procedure Step 2: Assess the risk of recurrent thromboembolism Step 3: Determine the elimination half-life of the anticoagulants and review the list of medication and supplements Step 4: Review the pre-op labs (CBC, CMP, PT)Step 5: Design a tentative perioperative AC management plan and discuss with surgeon

Pre-operative AC Time line Pre-op day 10-14 CBC, CMP (Calculate creatinine clearance!), PT/INR Assess thromboembolic and bleeding riskDiscuss tentative bridging plan with patient and surgeon and disseminate planPre-op day 5-6 stop warfarin and start enoxaparin 1mg/kg q12h 36-48 hrs. after last dose of warfarinPre-op day 3-5 stop DOAC and start enoxaparin 12-24 hours after last dose of DOACLast dose of enoxaparin 24-48 hours pre-operation Very high thrombotic risk consider UFH IV

Warfarin and Oral Surgery Literature review ( Wahl MJ JADA 2000) 950 pts. with >2400 surgeries (extractions, alveolar or gingival surgery) Only 12 pts. (1.3%) required more than local measures for hemostasis Nine (75%) had supra-therapeutic INR; 5 of 526 pts (0.95%) who held AC had thrombotic event,4 diedSingle-center Retrospective study (Eichhorn W et al. Clin Oral Invest 2012) 637 pts., 934 procedures (osteotomy, extractions) continued warfarin (INR 2.44) Local hemostasis with collagen fleece, suture, compression, fibrin glue 47 pts. (7.4%) had bleeding treated with local measures vs. 2 of 285 (0.7%) control pts.

Warfarin and Oral Surgery Prospective single center study of warfarin (INR 2-3) plus aspirin (N=71) versus warfarin (N=71) or aspirin alone (N=71) ( Bajkin BV JADA 2012)Risk of bleeding tended to be more with combined warfarin INR 2-3 and aspirin therapy (4.2%) than warfarin INR 2-3 (2.8%) or aspirin (0 %) Bleeding manageable with local measures Prospective open randomized study of warfarin (N=109) v. warfarin-LMWH bridge (N=105) ( Bajkin B J Oral Maxillofac Surg 67:990-995, 2009)No difference in bleeding (7.3% v. 4.8%) , all treated with local measures, No thromboembolism

Warfarin and LMWH bridging Prospective randomized study of simple extractions with or without LMWH bridgingWarfarin INR 2.45 (N=109) vs. LMWH bridging (INR 1.26)Post-op bleeding: 8 warfarin (7.3%) vs. 5 LMWH (4.8%). Treated with local measures, no transfusionsConclusion- Bridging unnecessary for simple extractions Bajkin BV et al J Oral Maxilofac Surg 2009

DOACs and Dental Surgery Prospective observational study of 367 pts. (119 DOACs, 248 warfarin) DOAC held morning of the procedure; warfarin continued Bleeding: 4 DOAC (3.1%) vs. 23 warfarin (8.8%). Bleeding controlled with local measures or holding AC dose Yoshikawa H et al. J Oral Maxillofac Surg 2019

Estimated Bleeding Risk Low Bleeding Risk Moderate Bleeding Risk High Bleeding Risk Procedure Supragingival scaling (standard cleaning) Simple restorations Anesthetic injectionsSubgingival scalingRestorations with subgingival prepStandard root canalSimple extractionRegional injection of anesthesticsMultiple extractionsApicoectomy (root removal)Alveolar surgery (bone removal)ManagementContinue ACUse local hemostatic measuresMay continue ACConsult dentistUse local hemostatic measuresMay need to interrupt ACUse local hemostatic measuresPlan for Procedures: Procedural Bleeding Risk Stratification for Oral Surgery University of Washington Anticoagulation Service

Oral Surgery Recommendations Discussion between oral surgeon, physician and patient prior to procedure to outline management For routine oral surgery (simple extractions < 3, 3 implants, etc.) warfarin (INR < 3.5 on day prior to surgery), single or dual APA or DOAC may be continued with local hemostatic measures (collagen, TXA rinse, topical fibrin, sutures)For DOACs do not take daily dose morning of surgery For AC + dual APA or warfarin INR >3.5 or more extensive surgery individualized management Aframian DJ, et al Oral Surg Oral Med 2007; van Diermen DE et al. Oral Surg Oral Med 2013

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