for prevention of venous thromboembolism after major abdominal surgery. The Thromboprophylaxis Collaborative Group. Lancet 1993; 341:259. 5. Jaffer AK. Perioperative management of warfarin and antiplatelet therapy. Cleve Clin J Med 2009; 76 Suppl 4:S37. 6. Gallego P, Apostolakis S, Lip GY. Bridging evidence-based practice and practice-based evidence in periprocedural anticoagulation. Circulation 2012; 126:1573. 7. Bell BR, Spyropoulos AC, Douketis JD. Perioperative Management of the Direct Oral Anticoagulants: A Case-Based Review. Hematol Oncol Clin North Am 2016; 30:1073. 8. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e326S. 9. Healey JS, Eikelboom J, Douketis J, et al. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial. Circulation 2012; 126:343. 10. Garcia D, Alexander JH, Wallentin L, et al. Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures. Blood 2014; 124:3692. 11. Sherwood MW, Douketis JD, Patel MR, et al. Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF). Circulation 2014; 129:1850. 12. Coon WW, Willis PW 3rd. Recurrence of venous thromboembolism. Surgery 1973; 73:823. 13. Douketis JD, Foster GA, Crowther MA, et al. Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy. Arch Intern Med 2000; 160:3431. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 35/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 14. Kearon C, Hirsh J. Management of anticoagulation before and after elective surgery. N Engl J Med 1997; 336:1506. 15. Levine MN, Hirsh J, Gent M, et al. Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis. Thromb Haemost 1995; 74:606. 16. Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary embolism. Research Committee of the British Thoracic Society. Lancet 1992; 340:873. 17. Cardiogenic brain embolism. Cerebral Embolism Task Force. Arch Neurol 1986; 43:71. 18. Lip GY. Intracardiac thrombus formation in cardiac impairment: the role of anticoagulant therapy. Postgrad Med J 1996; 72:731. 19. Loh E, Sutton MS, Wun CC, et al. Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med 1997; 336:251. 20. Nixon JV. Left ventricular mural thrombus. Arch Intern Med 1983; 143:1567. 21. Nieuwenhuis HK, Albada J, Banga JD, Sixma JJ. Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin. Blood 1991; 78:2337. 22. Levine MN, Raskob G, Landefeld S, Hirsh J. Hemorrhagic complications of anticoagulant treatment. Chest 1995; 108:276S. 23. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123:2736. 24. Omran H, Bauersachs R, R benacker S, et al. The HAS-BLED score predicts bleedings during bridging of chronic oral anticoagulation. Results from the national multicentre BNK Online bRiDging REgistRy (BORDER). Thromb Haemost 2012; 108:65. 25. Armstrong MJ, Gronseth G, Anderson DC, et al. Summary of evidence-based guideline: periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2013; 80:2065. 26. Collins LJ, Silverman DI, Douglas PS, Manning WJ. Cardioversion of nonrheumatic atrial fibrillation. Reduced thromboembolic complications with 4 weeks of precardioversion anticoagulation are related to atrial thrombus resolution. Circulation 1995; 92:160. 27. Singer DE, Albers GW, Dalen JE, et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:546S. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 36/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 28. Salem DN, O'Gara PT, Madias C, Pauker SG. Valvular and structural heart disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:593S. 29. McIntyre H. Management, during dental surgery, of patients on anticoagulants. Lancet 1966; 2:99. 30. Wahl MJ. Dental surgery in anticoagulated patients. Arch Intern Med 1998; 158:1610. 31. Malden N. Dental procedures can be undertaken without alteration of oral anticoagulant regimen. Evid Based Dent 2005; 6:11. 32. Blinder D, Manor Y, Martinowitz U, Taicher S. Dental extractions in patients maintained on oral anticoagulant therapy: comparison of INR value with occurrence of postoperative bleeding. Int J Oral Maxillofac Surg 2001; 30:518. 33. Garcia-Darennes F, Darennes J, Freidel M, Breton P. [Protocol for adapting treatment with vitamin K antagonists before dental extraction]. Rev Stomatol Chir Maxillofac 2003; 104:69. 34. Perry DJ, Noakes TJ, Helliwell PS, British Dental Society. Guidelines for the management of patients on oral anticoagulants requiring dental surgery. Br Dent J 2007; 203:389. 35. Svensson R, Hallmer F, Englesson CS, et al. Treatment with local hemostatic agents and primary closure after tooth extraction in warfarin treated patients. Swed Dent J 2013; 37:71. 36. Sindet-Pedersen S, Ramstr m G, Bernvil S, Blomb ck M. Hemostatic effect of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery. N Engl J Med 1989; 320:840. 37. Webster K, Wilde J. Management of anticoagulation in patients with prosthetic heart valves undergoing oral and maxillofacial operations. Br J Oral Maxillofac Surg 2000; 38:124. 38. Souto JC, Oliver A, Zuazu-Jausoro I, et al. Oral surgery in anticoagulated patients without reducing the dose of oral anticoagulant: a prospective randomized study. J Oral Maxillofac Surg 1996; 54:27. 39. Patatanian E, Fugate SE. Hemostatic mouthwashes in anticoagulated patients undergoing dental extraction. Ann Pharmacother 2006; 40:2205. 40. Sticherling C, Marin F, Birnie D, et al. Antithrombotic management in patients undergoing electrophysiological procedures: a European Heart Rhythm Association (EHRA) position document endorsed by the ESC Working Group Thrombosis, Heart Rhythm Society (HRS), and Asia Pacific Heart Rhythm Society (APHRS). Europace 2015; 17:1197. 41. Birnie DH, Healey JS, Wells GA, et al. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med 2013; 368:2084. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 37/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 42. Essebag V, Proietti R, Birnie DH, et al. Short-term dabigatran interruption before cardiac rhythm device implantation: multi-centre experience from the RE-LY trial. Europace 2017. 43. Shahi V, Brinjikji W, Murad MH, et al. Safety of Uninterrupted Warfarin Therapy in Patients Undergoing Cardiovascular Endovascular Procedures: A Systematic Review and Meta- Analysis. Radiology 2016; 278:383. 44. Di Biase L, Burkhardt JD, Santangeli P, et al. Periprocedural stroke and bleeding complications in patients undergoing catheter ablation of atrial fibrillation with different anticoagulation management: results from the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) randomized trial. Circulation 2014; 129:2638. 45. Godier A, Dincq AS, Martin AC, et al. Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study. Eur Heart J 2017; 38:2431. 46. White RH, McKittrick T, Hutchinson R, Twitchell J. Temporary discontinuation of warfarin therapy: changes in the international normalized ratio. Ann Intern Med 1995; 122:40. 47. Larson BJ, Zumberg MS, Kitchens CS. A feasibility study of continuing dose-reduced warfarin for invasive procedures in patients with high thromboembolic risk. Chest 2005; 127:922. 48. Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med 2015; 373:823. 49. Kovacs MJ, Wells PS, Anderson DR, et al. Postoperative low molecular weight heparin bridging treatment for patients at high risk of arterial thromboembolism (PERIOP2): double blind randomised controlled trial. BMJ 2021; 373:n1205. 50. Hylek EM, Regan S, Go AS, et al. Clinical predictors of prolonged delay in return of the international normalized ratio to within the therapeutic range after excessive anticoagulation with warfarin. Ann Intern Med 2001; 135:393. 51. Douketis JD, Berger PB, Dunn AS, et al. The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:299S. 52. Shaw JR, Li N, Vanassche T, et al. Predictors of preprocedural direct oral anticoagulant levels in patients having an elective surgery or procedure. Blood Adv 2020; 4:3520. 53. Stangier J, Rathgen K, St hle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet 2010; 49:259. 54. van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 38/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate activity. Thromb Haemost 2010; 103:1116. 55. Hankey GJ, Eikelboom JW. Dabigatran etexilate: a new oral thrombin inhibitor. Circulation 2011; 123:1436. 56. Schulman S, Carrier M, Lee AY, et al. Perioperative Management of Dabigatran: A Prospective Cohort Study. Circulation 2015; 132:167. 57. Warkentin TE, Margetts P, Connolly SJ, et al. Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran-associated postcardiac surgery bleeding. Blood 2012; 119:2172. 58. Wysokinski WE, McBane RD 2nd. Periprocedural bridging management of anticoagulation. Circulation 2012; 126:486. 59. Tafur A, Douketis J. Perioperative management of anticoagulant and antiplatelet therapy. Heart 2018; 104:1461. 60. Kuo HC, Liu FL, Chen JT, et al. Thromboembolic and bleeding risk of periprocedural bridging anticoagulation: A systematic review and meta-analysis. Clin Cardiol 2020; 43:441. 61. Douketis JD, Healey JS, Brueckmann M, et al. Perioperative bridging anticoagulation during dabigatran or warfarin interruption among patients who had an elective surgery or procedure. Substudy of the RE-LY trial. Thromb Haemost 2015; 113:625. 62. Steinberg BA, Peterson ED, Kim S, et al. Use and outcomes associated with bridging during anticoagulation interruptions in patients with atrial fibrillation: findings from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Circulation 2015; 131:488. 63. Beyer-Westendorf J, Gelbricht V, F rster K, et al. Peri-interventional management of novel oral anticoagulants in daily care: results from the prospective Dresden NOAC registry. Eur Heart J 2014; 35:1888. 64. Baumgartner C, de Kouchkovsky I, Whitaker E, Fang MC. Periprocedural Bridging in Patients with Venous Thromboembolism: A Systematic Review. Am J Med 2019; 132:722. 65. Siegal D, Yudin J, Kaatz S, et al. Periprocedural heparin bridging in patients receiving vitamin K antagonists: systematic review and meta-analysis of bleeding and thromboembolic rates. Circulation 2012; 126:1630. 66. Ansell J, Hirsh J, Poller L, et al. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126:204S. 67. Kearon C, Ginsberg JS, Julian JA, et al. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 39/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate thromboembolism. JAMA 2006; 296:935. 68. Jaffer AK, Brotman DJ, Bash LD, et al. Variations in perioperative warfarin management: outcomes and practice patterns at nine hospitals. Am J Med 2010; 123:141. 69. Tafur AJ, McBane R 2nd, Wysokinski WE, et al. Predictors of major bleeding in peri- procedural anticoagulation management. J Thromb Haemost 2012; 10:261. 70. Skeith L, Lazo-Langner A, Kovacs MJ. The equipoise of perioperative anticoagulation management: a Canadian cross-sectional survey. J Thromb Thrombolysis 2014; 37:411. 71. Skeith L, Taylor J, Lazo-Langner A, Kovacs MJ. Conservative perioperative anticoagulation management in patients with chronic venous thromboembolic disease: a cohort study. J Thromb Haemost 2012; 10:2298. 72. Clark NP, Witt DM, Davies LE, et al. Bleeding, Recurrent Venous Thromboembolism, and Mortality Risks During Warfarin Interruption for Invasive Procedures. JAMA Intern Med 2015; 175:1163. 73. Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:141S. 74. O'Donnell MJ, Kearon C, Johnson J, et al. Brief communication: Preoperative anticoagulant activity after bridging low-molecular-weight heparin for temporary interruption of warfarin. Ann Intern Med 2007; 146:184. 75. Douketis JD, Woods K, Foster GA, Crowther MA. Bridging anticoagulation with low- molecular-weight heparin after interruption of warfarin therapy is associated with a residual anticoagulant effect prior to surgery. Thromb Haemost 2005; 94:528. 76. Strebel N, Prins M, Agnelli G, B ller HR. Preoperative or postoperative start of prophylaxis for venous thromboembolism with low-molecular-weight heparin in elective hip surgery? Arch Intern Med 2002; 162:1451. 77. Dunn AS, Spyropoulos AC, Turpie AG. Bridging therapy in patients on long-term oral anticoagulants who require surgery: the Prospective Peri-operative Enoxaparin Cohort Trial (PROSPECT). J Thromb Haemost 2007; 5:2211. 78. Levy JH, Tanaka KA, Dietrich W. Perioperative hemostatic management of patients treated with vitamin K antagonists. Anesthesiology 2008; 109:918. 79. Sarode R, Milling TJ Jr, Refaai MA, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation 2013; 128:1234. 80. Pollack CV Jr, Reilly PA, van Ryn J, et al. Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. N Engl J Med 2017; 377:431. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 40/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 81. Horlocker TT. Regional anaesthesia in the patient receiving antithrombotic and antiplatelet therapy. Br J Anaesth 2011; 107 Suppl 1:i96. 82. Horlocker TT, Vandermeuelen E, Kopp SL, et al. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Fourth Edition). Reg Anesth Pain Med 2018; 43:263. Topic 1312 Version 84.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 41/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate GRAPHICS Perioperative thrombotic risk Indication for anticoagulant therapy Thrombotic risk Mechanical heart valve Atrial fibrillation VTE High thrombotic risk* Any mitral valve CHADS score 5-6 Recent (within 3 2 prosthesis months) VTE CHA DS -VASc 2 2 score 7-9 Any caged-ball or Severe thrombophilia tilting disc aortic valve prosthesis (eg, deficiency of protein C, protein S, or Recent (within 3 months) stroke or antithrombin; antiphospholipid antibodies; multiple abnormalities) Recent (within 6 months) stroke or transient ischemic attack transient ischemic attack Rheumatic valvular heart disease Moderate thrombotic risk Bileaflet aortic valve prosthesis and 1 or more of the of following risk factors: atrial fibrillation, prior CHADS score 3-4 VTE within the past 3 to 12 months 2 CHA DS -VASc 2 2 score 4-6 Nonsevere thrombophilia (eg, heterozygous factor V Leiden or prothrombin gene mutation) stroke or transient ischemic attack, hypertension, diabetes, congestive heart failure, age >75 years Recurrent VTE Active cancer (treated within 6 months or palliative) Low thrombotic risk Bileaflet aortic valve prosthesis without CHADS score 0-2 VTE >12 months previous and no other 2 CHA DS -VASc 2 2 atrial fibrillation and no risk factors score 0-3 (assuming no prior stroke or other risk factors for stroke transient ischemic attack) The risk classification is largely based on indirect evidence and is intended to be used as a starting point to estimate risk. Patient-specific factors and clinical judgment should also be incorporated into the risk estimate. The source guideline used CHADS scores for risk estimation; additional information from CHA DS -VASc scores may also inform risk, but these scores have not been directly 2 2 2 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 42/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate compared in a clinical trial. Refer to UpToDate topics on perioperative anticoagulation management for details. VTE: venous thromboembolism; CHADS : congestive heart failure, hypertension, age 75 years, diabetes mellitus, and stroke or transient ischemic attack; CHA DS -VASc: congestive heart failure, hypertension, age 75 years (2 points), diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism (2 points), vascular disease (peripheral artery disease, myocardial infarction, or aortic plaque), age 65 to 74 years, sex category female. 2 2 2 Very high-risk patients may also include those with a prior stroke or transient ischemic attack occurring <3 months before the planned surgery and a CHADS score >5 or CHA DS -VASc score >6 2 2 2 (those with prior thromboembolism during temporary interruption of anticoagulation, or those undergoing certain types of surgery associated with an increased risk for stroke or other thromboembolism [eg, cardiac valve replacement, carotid endarterectomy, major vascular surgery]). Modi ed from Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl):e326S. Copyright 2012. Reproduced with permission from the American College of Chest Physicians. Graphic 86930 Version 7.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 43/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Procedural bleeding risk High bleeding risk procedure (two-day risk of major bleed 2 to 4%) Any major operation of duration >45 minutes Abdominal aortic aneurysm repair Coronary artery bypass Endoscopically guided fine-needle aspiration Foot/hand/shoulder surgery Heart valve replacement Hip replacement Kidney biopsy Knee replacement Laminectomy Neurosurgical/urologic/head and neck/abdominal/breast cancer surgery Polypectomy, variceal treatment, biliary sphincterectomy, pneumatic dilatation Transurethral prostate resection Vascular and general surgery Low bleeding risk procedure (two-day risk of major bleed 0 to 2%) Abdominal hernia repair Abdominal hysterectomy Arthroscopic surgery lasting <45 minutes Axillary node dissection Bronchoscopy with or without biopsy Carpal tunnel repair Cataract and noncataract eye surgery Central venous catheter removal Cholecystectomy Cutaneous and bladder/prostate/thyroid/breast/lymph node biopsies Dilatation and curettage Gastrointestinal endoscopy biopsy, enteroscopy, biliary/pancreatic stent without sphincterotomy, endosonography without fine-needle aspiration Hemorrhoidal surgery https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 44/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Hydrocele repair Noncoronary angiography Pacemaker and cardiac defibrillator insertion and electrophysiologic testing Paracentesis Thoracentesis Tooth extractions (multiple tooth extractions is an exception that may be higher risk) This table is based on definitions derived from surgical/subspecialty societies in anticoagulant bridging or anticoagulant bridging management studies. Refer to UpToDate content on management of anticoagulants in patients undergoing gastrointestinal procedures for information on bleeding risks of additional gastrointestinal procedures. Adapted from research originally published in Blood. Spyropoulos AC, Douketis JD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood 2012; 120:2954. Copyright 2012 the American Society of Hematology. Graphic 86929 Version 7.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 45/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Clinical risk factors for stroke, transient ischemic attack, and systemic embolism in the CHA DS -VASc score 2 2 (A) The risk factor-based approach expressed as a point based scoring system, with the acronym CHA DS -VASc 2 2 (NOTE: maximum score is 9 since age may contribute 0, 1, or 2 points) CHA DS -VASc risk factor Points 2 2 Congestive heart failure +1 Signs/symptoms of heart failure or objective evidence of reduced left ventricular ejection fraction Hypertension +1 Resting blood pressure >140/90 mmHg on at least 2 occasions or current antihypertensive treatment Age 75 years or older +2 Diabetes mellitus +1 Fasting glucose >125 mg/dL (7 mmol/L) or treatment with oral hypoglycemic agent and/or insulin Previous stroke, transient ischemic attack, or thromboembolism +2 Vascular disease +1 Previous myocardial infarction, peripheral artery disease, or aortic plaque Age 65 to 74 years +1 Sex category (female) +1 (B) Adjusted stroke rate according to CHA DS -VASc score 2 2 CHA DS -VASc score Patients Stroke and 2 2 (n = 73,538) thromboembolism event rate at 1-year follow-up (%) 0 6369 0.78 1 8203 2.01 2 12,771 3.71 3 17,371 5.92 4 13,887 9.27 5 8942 15.26 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 46/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 6 4244 19.74 7 1420 21.50 8 285 22.38 9 46 23.64 CHA DS -VASc: Congestive heart failure, Hypertension, Age ( 75; doubled), Diabetes, Stroke (doubled), Vascular disease, Age (65 to 74), Sex. 2 2 Part A from: Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial brillation developed in collaboration with EACTS. Europace 2016; 18(11):1609-1678. By permission of Oxford University Press on behalf of the European Society of Cardiology. Copyright 2016 Oxford University Press. Available at: www.escardio.org/. Graphic 83272 Version 29.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 47/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Clinical characteristics comprising the HAS-BLED bleeding risk score Letter Clinical characteristic* Points H Hypertension (ie, uncontrolled blood pressure) 1 A Abnormal renal and liver function (1 point each) 1 or 2 S Stroke 1 B Bleeding tendency or predisposition 1 L Labile INRs (for patients taking warfarin) 1 E Elderly (age greater than 65 years) 1 D Drugs (concomitant aspirin or NSAIDs) or excess alcohol use (1 point each) 1 or 2 Maximum 9 points HAS-BLED score (total points) Bleeds per 100 patient-years 0 1.13 1 1.02 2 1.88 3 3.74 4 8.70 5 to 9 Insufficient data The HAS-BLED bleeding risk score has only been validated in patients with atrial fibrillation receiving warfarin. Refer to UpToDate topics on anticoagulation in patients with atrial fibrillation and on specific anticoagulants for further information and other bleeding risk scores and their performance relative to clinical judgment. INR: international normalized ratio; NSAIDs: nonsteroidal antiinflammatory drugs. Hypertension is defined as systolic blood pressure >160 mmHg. Abnormal renal function is defined as the presence of chronic dialysis, renal transplantation, or serum creatinine 200 micromol/L. Abnormal liver function is defined as chronic hepatic disease (eg, cirrhosis) or biochemical evidence of significant hepatic derangement (eg, bilirubin more than 2 times the upper limit of normal, plus 1 or more of aspartate transaminase, alanine transaminase, and/or alkaline phosphatase more than 3 times the upper limit of normal). Bleeding predisposition includes chronic bleeding disorder or https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 48/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate previous bleeding requiring hospitalization or transfusion. Labile INRs for a patient on warfarin include unstable INRs, excessively high INRs, or <60% time in therapeutic range. Based on initial validation cohort from Pisters R. A novel-user-friendly score (HAS-BLED) to assess 1- year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138:1093. Actual rates of bleeding in contemporary cohorts may vary from these estimates. Original gure modi ed for this publication. Lip GY. Implications of the CHA2DS2-VASc and HAS-BLED Scores for thromboprophylaxis in atrial brillation. Am J Med 2011; 124:111. Table used with the permission of Elsevier Inc. All rights reserved. Graphic 75259 Version 16.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 49/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Algorithm for anticoagulant discontinuation in individuals undergoing elective Refer to UpToDate for further information on the bleeding risk of common procedures and the thromboemb risk of common underlying conditions. High thromboembolic risk includes mechanical heart valve, high risk stroke, or recent venous thromboembolism (within the prior 3 months). DOAC: direct oral anticoagulant; VKA: vitamin K antagonist; CrCl: creatinine clearance; VTE: venous thromboembolism; IVC: inferior vena cava; LMW: low molecular weight. Anticoagulants: Direct oral anticoagulants (DOACs) include dabigatran, apixaban, edoxaban, and rivaroxaban. Vitamin K antagonists include warfarin, acenocoumarol, phenprocoumon, and fluindione. The following applies to DOAC interruption: These intervals are for individuals with normal kidney function and factor Xa inhibitors regardless of ki function. For individuals with CrCl 30 to 50 mL/min receiving dabigatran, longer intervals are used (omit from 2 before a low/moderate bleeding risk procedure; omit from 4 days before a high bleeding risk procedu The perioperative management from the PAUSE study (a population with atrial fibrillation) can be appl individuals who are receiving a DOAC for VTE that was >30 days prior. If the individual had a VTE within prior 30 days, DOAC interruption should be individualized and may include placement of a temporary filter or shorter periods of DOAC interruption. Bridging is not used for DOACs. The following applies to VKA interruption: For warfarin, discontinue 5 days before the procedure. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 50/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate If bridging is needed for a high thromboembolic risk patient, start LMW heparin at therapeutic dose approximately 3 days before surgery, with the last preoperative dose approximately 24 hours before s Resume warfarin postoperatively once hemostasis is assured (typically the evening of the day of surge the day after surgery). Resume LMW heparin approximately 2 to 3 days after surgery (determined by t bleeding risk of the procedure) and discontinue LMW heparin after stable warfarin anticoagulation. The overlap period between LMW heparin and warfarin depends on the patient's thromboembolic risk Based on guidance from A Tafur, J Douketis. Perioperative management of anticoagulant and antiplatelet therapy. Heart 2018; 104:14 Graphic 129999 Version 2.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 51/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Timing for interruption of a direct oral anticoagulant (DOAC) before and after elective surgery This strategy applies to all DOACs in individuals with normal kidney function (eg, CrCl >50 mL/min) and individuals taking apixaban, edoxaban, or rivaroxaban with CrCl 30 to 50 mL/min. For individuals taking dabigatran who have CrCl of 30 to 50 mL/min, omit an additional dose before the procedure. For any DOAC and a high bleeding risk procedure, it may be reasonable to omit the DOAC for an additional postoperative day (5 days total interruption). Refer to UpToDate for additional details. DOAC: direct oral anticoagulant; CrCl: creatinine clearance. Graphic 130000 Version 1.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 52/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Perioperative management of oral direct thrombin inhibitors and factor Xa inhibitors Interval between last dose and procedure Resumption after NOTE: No anticoagulant procedure Kidney is administered the day Anticoagulant function of the procedure and dose High Low High Low bleeding risk bleeding risk bleeding risk bleeding risk https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 53/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Dabigatran CrCl >50 mL/minute Give last dose 3 days before Give last dose 2 days before procedure (ie, skip 4 doses procedure (ie, skip 2 doses Dose 150 mg twice daily on the 2 days on the day before the procedure) before the procedure) CrCl 30 to 50 Give last dose Give last dose mL/minute 5 days before procedure (ie, 3 days before procedure (ie, Dose 150 mg skip 8 doses skip 4 doses twice daily on the 4 days before the procedure) on the 2 days before the procedure) Rivaroxaban CrCl >50 mL/minute Give last dose 3 days before procedure (ie, skip 2 doses on the 2 days before the procedure) Give last dose 2 days before procedure (ie, skip 1 dose on the day before the procedure) Dose 20 mg once daily Resume 48 to 72 hours after surgery (ie, postoperative day 2 to 3) Resume 24 hours after surgery (ie, postoperative day 1) CrCl 30 to 50 mL/minute Dose 15 mg once daily Apixaban CrCl >50 mL/minute Give last dose 3 days before procedure (ie, Give last dose 2 days before procedure (ie, Dose 5 mg twice daily skip 4 doses on the 2 days before the procedure) skip 2 doses on the day before the procedure) CrCl 50 mL/minute Dose 2.5 mg twice daily Edoxaban CrCl 51 to 95 Give the last Give the last mL/minute dose 3 days dose 2 days before the procedure (ie, before the procedure (ie, Dose 60 mg once daily skip 2 doses on the 2 days skip 2 dose on the day CrCl 50 mL/minute* before the before the procedure) procedure) Dose 30 mg once daily Bleeding risk is determined primarily by the type of surgery; patient comorbidities may also play a role. In patients undergoing neuraxial anesthesia or a very high bleeding risk procedure, a longer https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 54/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate period of interruption may be warranted. In many low bleeding risk procedures, the anticoagulant does not need to be interrupted. Bridging anticoagulation may be appropriate preoperatively in patients with a very high thromboembolic risk who require more prolonged interruption of the anticoagulant (eg, for renal insufficiency) and/or postoperatively in patients who are unable to resume the anticoagulant (eg, unable to take oral medication due to intestinal ileus). Refer to the UpToDate topics on perioperative management of patients receiving anticoagulants for further details. CrCl: creatinine clearance. Product information varies in different countries regarding a lower limit of CrCl below which the drug should not be used. As an example, product information in the United States specifies avoiding use with CrCl <15 mL/minute. Graphic 93260 Version 12.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 55/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Expected effects of anticoagulant drugs on commonly used coagulation tests Brand Anti-factor Drug class Drug PT aPTT name(s) Xa activity / * Vitamin K Warfarin Jantoven antagonists / * Acenocoumarol Sintrom Heparins Unfractionated heparin / LMW heparins Enoxaparin Lovenox Dalteparin Fragmin Nadroparin Fraxiparine / Fondaparinux Arixtra Direct thrombin inhibitors Argatroban Acova / Dabigatran Pradaxa / / Direct factor Xa inhibitors Rivaroxaban Xarelto / / Apixaban Eliquis Edoxaban Lixiana, Savaysa PT and aPTT are measured in seconds; anti-factor Xa activity is measured in units/mL. Upward arrow ( ) signifies an increase above normal due to the anticoagulant (prolongation of PT or aPTT; increase in anti-factor Xa activity). The effect magnitude will vary depending on the reagent formulation and instrument used. Dash ( ) signifies no appreciable effect. Normal ranges for the PT, aPTT, and anti-factor Xa activity vary among laboratories and should be reported from the testing laboratory along with the patient result. Refer to the UpToDate topic on coagulation testing for details. PT: prothrombin time; aPTT: activated partial thromboplastin time; LMW heparin: low molecular weight heparin. Warfarin has a weak effect on most aPTT reagents. However, warfarin use will increase the sensitivity of the aPTT to heparin effect. While heparin, LMW heparin, and fondaparinux should, in theory, prolong the PT as indirect thrombin inhibitors, in practice most PT reagents contain heparin-binding chemicals that block any heparin effect below a concentration of 1 unit/mL. Above concentrations of 1 unit/mL, heparin effect on the PT may be observed. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 56/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Anti-factor Xa activity testing must be calibrated for the specific anticoagulant; this information should be verified with the clinical laboratory. Some of the data are from: Samuelson BT, Cuker A, Crowther M, Garcia DA. Laboratory assessment of the anticoagulant activity of direct oral anticoagulants: A systematic review. Chest 2017; 151:127. Graphic 91267 Version 9.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 57/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Recommendations for preoperative and postoperative anticoagulation in patients on a vitamin K antagonist Indication Before surgery After surgery Venous thromboembolism Within first month IV heparin or SQ LMWH IV heparin or SQ LMWH Second/third month No change* IV heparin or SQ LMWH 3 months No change* SQ heparin or LWMH Arterial thromboembolism Recent, within one month IV heparin or SQ LMWH IV heparin or SQ LMWH Prophylaxis (eg, non-valvular AF, mechanical heart valve) No change* Resume oral anticoagulation NOTE: Warfarin should be withheld to allow the INR to fall spontaneously to 1.5 to 2 before surgery is performed. IV: intravenous; SQ: subcutaneous; LMWH: low molecular weight heparin; AF: atrial fibrillation; INR: international normalized ratio. If the patient is hospitalized, SQ heparin or LMWH should be administered, but hospitalization is not recommended solely for this purpose. Can use SQ heparin or SQ LMWH if the surgery carries a high risk of postoperative thromboembolism. Graphic 81389 Version 4.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 58/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Reversing anticoagulation in warfarin-associated bleeding Management Time to anticoagulation Comments and cautions option reversal Discontinuing 5 to 14 days Five days is typical for patients with an warfarin therapy INR in the therapeutic range Vitamin K* 6 to 24 hours to correct the INR, longer to fully reverse anticoagulation Recovery of factors X and II (prothrombin) takes longer than 24 hours Risk of anaphylaxis with intravenous injection Impaired response to warfarin lasting up to one week may occur after large doses (ie, >5 mg) Fresh frozen Depends on the time it takes to Effect is transient and concomitant plasma complete the infusion; typically 12 to 32 hours for complete reversal vitamin K must be administered Potential for volume overload (2 to 4 L to normalize INR) Potential for TRALI Potential for viral transmission Prothrombin complex 15 minutes after 10-minute to 1-hour infusion Effect is transient, and concomitant vitamin K must be administered; concentrate limited availability Cost