MANAGEMENT PRE-PROCEDURE

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Page of 8 THROMBOTIC RISK BLEEDING RISK 5 MANAGEMENT PRE-PROCEDURE POST-PROCEDURE RE-INITIATION TIME Patient scheduled for procedure on anticoagulant [The primary care team will determine whether the procedure can be done safely while the patient is on an anticoagulant after discussion with the patient regarding the,, overall of.] High thrombotic Low thrombotic High 5 Low 5 High 5 Low 5 Hold anticoagulants per Appendix C If patient on warfarin, bridge and hold anticoagulation per Appendix D Consult IMPAC (if outpatient) Continue current anticoagulant Hold anticoagulants per Appendix C If patient on warfarin, bridging is not necessary Consult IMPAC, if needed Continue current anticoagulant Neurosurgery procedures: Anticoagulation restarted no sooner than 96 hours post-procedure Other procedures: Patients within 0 days of acute pulmonary embolism without overt or, restart anticoagulation within -6 hours post-procedure All other patients, restart warfarin or heparin within hours or DOACs within at least 8 hours post-procedure DOAC = direct oral anticoagulants For questions, call appropriate service depending on procedure (Anesthesia, Cardiology, Internal Medicine Perioperative Assessment Center [IMPAC]) See internal Coagulation Reversal Recommendations (click here) For patients on antiplatelet therapy, see Management of Antiplatelet Therapy in Patients with Cardiac Stents Undergoing Procedures Algorithm See Appendix A for Indications of Thrombotic Risk 5 See Appendix B for Procedural Bleeding Risks based on type of procedure Department of Clinical Effectiveness V Approved by the Executive Committee of the Medical Staff on 08/9/07

Page of 8 APPENDIX A: Thrombotic Risks High (require bridging if on warfarin) Risk Mechanical Heart Valve Atrial Fibrillation Venous Thromboembolism (VTE) Any mitral valve prosthesis Any caged-ball or tilting disc aortic valve prosthesis Stroke or transient ischemic attack (TIA) within 6 months CHA DS -VASc score of greater than or equal to 7 Stroke or TIA within months Rheumatic valvular heart disease VTE within months VTE of any duration with severe thrombophilia (e.g., deficiency of protein C, protein S, or antithrombin, antiphospholipid antibodies, homozygous factor V Leiden or prothrombin G00A, or multiple abnormalities) Low Bileaflet aortic valve prosthesis and one or more of the following factors: atrial fibrillation, prior stroke or TIA, hypertension, diabetes, congestive heart failure, age over 75 years Bileaflet aortic valve prosthesis without factors for stroke CHA DS -VASc score less than 7 VTE within the past - months VTE with non-severe thrombophilia (e.g., heterozygous factor V Leiden or prothrombin gene mutation) Recurrent idiopathic VTE Active cancer (treated within 6 months or palliative) VTE greater than months previous and no other factors CHA DS -VASc Score Criteria Points Male 0 Female Congestive heart failure history Diabetes mellitus history Hypertension history Vascular disease history Age 65-7 years Age greater than or equal to 75 years Stroke/TIA/thromboembolism history Department of Clinical Effectiveness V Approved by the Executive Committee of the Medical Staff on 08/9/07

Page of 8 APPENDIX B: Procedure Bleeding Risks Note: Clinical or laboratory suspicion (i.e., elevated PT/aPTT or INR) of an underlying coagulopathy unrelated to anticoagulation therapy should be evaluated prior to the procedure. Please contact Benign Hematology or General Internal Medicine for advice on management. Interventional Radiology High Bleeding Risk Transjugular intrahepatic porto-systemic shunt Lung interventions: biopsy, drainage (parenchymal) Solid organ biopsies Solid organ drainage: nephrostomy, biliary, cholecystostomy Ablations: solid organs, bone, soft tissues, lung Transjugular liver biopsy Tunneled central venous catheter placement Angiography, arterial intervention with access size up to 6 French Trans-arterial embolotherapy Venous interventions Portal vein embolization and stenting Non-organ biopsy (e.g., retroperitoneal, vertebral, intra-abdominal) Non-organ drainage (e.g., abdominal or retroperitoneal abscess) Drainage catheter exchange less than 6 weeks (biliary, nephrostomy, abscess) Gastrostomy tube placement Spine procedures: vertebroplasty, kyphoplasty Tunneled drainage catheter placement (e.g., Denver catheter) Central line removal (tunneled) All interventional procedures where heparin and bivalirudin are used Low Bleeding Risk Non-tunneled venous access Central line removal (non-tunneled) Drainage catheter exchange greater than 6 weeks (biliary, nephrostomy, abscess) Thoracentesis Non-tunneled chest tube placement (pleural space) Paracentesis Intraperitoneal catheter placement Superficial (e.g., lymph nodes) or palpable mass biopsies Superficial abscess drainage Inferior vena cava (IVC) filter placement IVC filter retrieval Left and right cardiac catheterization For patients on antiplatelet therapy, see Management of Antiplatelet Therapy in Patients with Cardiac Stents Undergoing Procedures Algorithm Appendix B continued on next page Department of Clinical Effectiveness V Approved by the Executive Committee of the Medical Staff on 08/9/07

Page of 8 APPENDIX B: Procedural Bleeding Risks - continued General Procedures High Bleeding Risk: Lumbar puncture Peripherally inserted central catheter (PICC) line placement All operating room procedures Low Bleeding Risk: Bone marrow aspiration and biopsy Ommaya reservoir puncture Subclavian or femoral vein catheter placement Pulmonary Procedures High Bleeding Risk: Diagnostic bronchoscopy with transbronchial biopsy Diagnostic bronchoscopy with endobronchial biopsy Therapeutic bronchoscopy with endobronchial tumor destruction, stenosis relief, or management of hemoptysis Pleuroscopy, pleural biopsy Diagnostic bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) Tunneled pleural catheter placement Tunneled pleural catheter removal Low Bleeding Risk: Diagnostic bronchoscopy airway exam Diagnostic bronchoscopy with bronchoalveolar lavage (BAL) Thoracentesis Gastroenterology Procedures High Bleeding Risk: Biliary or pancreatic sphincterotomy Polypectomy Cystogastrostomy Endoscopic hemostasis Endoscopic ultrasound (EUS) with FNA Tumor ablation by any technique Pneumatic or bougie dilation percutaneous endoscopic gastrostomy (PEG) placement Therapeutic balloon-assisted enteroscopy Treatment of varices Low Bleeding Risk: Capsule endoscopy Diagnostic (esophagogastroduodenoscopy (EGD), colonoscopy, flexible sigmoidoscopy) including biopsy Enteral stent deployment (without dilation) Enteroscopy and diagnostic balloon-assisted enteroscopy Endoscopic retrograde cholangiopancreatogram (ERCP) without sphincterotomy EUS without FNA Cardiology Procedures High Bleeding Risk Pacemaker or defibrillator placement Coronary intervention Endomyocardial biopsy Low Bleeding Risk Electrophysiology testing and/or ablation Diagnostic coronary angiography For patients on antiplatelet therapy, see Management of Antiplatelet Therapy in Patients with Cardiac Stents Undergoing Procedures Algorithm Department of Clinical Effectiveness V Approved by the Executive Committee of the Medical Staff on 08/9/07

APPENDIX C: Recommended Holding Time Prior to Procedure Page 5 of 8 These dates are approximate based on t½ (hour) of specific new oral anticoagulant in various degree of renal impairment. Note: Renal function should be considered when determining appropriate hold times for anticoagulants. Normal of needs drug half-lives between the last dose and surgery; aim for mild to moderate residual anticoagulant effect at surgery less than % to 5% High of needs drug half-lives between the last dose and surgery; aim for minimal residual anticoagulant effect at surgery less than % to 6% Attention: Expert panels DO NOT RECOMMEND use of DOACs in patients with cancer. A multidisciplinary consultation is strongly recommended with Benign Hematology, Cardiology, and/or General Internal Medicine. Each case needs to be individually assessed prior to use of DOACs. The following recommendations for hold strategy are based on estimated half-life of each anticoagulation and data for hold strategy in cancer patients is very limited. Clinicians should always consider of versus of thrombosis in cancer patients in determining the hold strat egy. Minimum hold days of DOAC according to Creatinine Clearance (CrCl) ml/minute and. days listed as a count down to day of procedure which is Day 0 Anticoagulant Hold Parameter Warfarin (Coumadin ) Day LMWH [enoxaparin (Lovenox ), Stop the dose hours before surgery or on Day - or dalteparin (Fragmin ), tinzaparin (Innohep ) ] longer in patients with renal impairment. CrCl (ml/minute) greater than 50 0-50 less than 0 Fondaparinux (Arixtra ) of -7 6-7 Contraindicated High of 6 CrCl (ml/minute) greater than 80 50-79 0-9 less than 0 Dabigatran (Pradaxa ) Rivaroxaban (Xarelto ) Apixaban (Eliquis ) Edoxaban (Savaysa ) of - High of -6 of High of Increased for death in elderly patients with renal insufficiency Full dose 8 hours (low ) and 96 hours (high ) prior to procedure (longer-half life) 5 - - - of - - Non-formulary High of Note: column is information for the patient and column is information for the provider. of - - High of Department of Clinical Effectiveness V Approved by the Executive Committee of the Medical Staff on 08/9/07

Page 6 of 8 APPENDIX D: Bridge Strategy for Patients on Warfarin (should be discussed with primary physician) Day - Heparin Last dose warfarin Continuous infusion Continuous infusion Continuous infusion Enoxaparin (Lovenox ) and Dalteparin (Fragmin ) Last dose warfarin Weight based dose Weight based dose Fondaparinux (Arixtra ) Last dose warfarin One dose if low of Example for a patient on warfarin who will bridge with heparin infusion for a procedure scheduled for Wednesday (Day 0) patient will hold warfarin on Friday (Day ), start continuous infusion heparin on Saturday (Day ), and continue until hours prior to procedure on Wednesday. Example for a patient on warfarin who will bridge with low molecular weight heparin (LMWH) for a procedure scheduled for Wednesday (Day 0) patient will hold warfarin on Friday (Day ), start full dose LMWH on Sunday (Day ) and Monday (Day -), and only take half dose LMWH on Tuesday morning (Day -). - Continuous infusion Take ½ dose at 8AM 0 Stop hours before procedure Bridging: Use of a short-acting anticoagulant to assist peri-procedure management of anticoagulation and the process for resuming the patient s appropriate therapeutic anticoagulant dosing regimen post-procedure. Consider an appointment with IMPAC prior to the procedure. Note: Renal function should be considered when determining appropriate hold times for anticoagulants Department of Clinical Effectiveness V Approved by the Executive Committee of the Medical Staff on 08/9/07

Page 7 of 8 SUGGESTED READINGS Doherty, J. U., Gluckman, T. J., Hucker, W. J., Januzzi, J. L., Ortel, T. L., Saxonhouse, S. J.,... & Periprocedural Management of Anticoagulation Writing Committee. (07). 07 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients With Nonvalvular Atrial Fibrillation: A Report of the American College of Cardiology Clinical Expert Consensus Document Task Force. Journal of the American College of Cardiology. Douketis, J. D., Spyropoulos, A. C., Kaatz, S., Becker, R. C., Caprini, J. A., Dunn, A. S.,... & Schulman, S. (05). Perioperative bridging anticoagulation in patients with atrial fibrillation. New England Journal of Medicine, 7(9), 8-8. Douketis, J. D., Spyropoulos, A. C., Spencer, F. A., Mayr, M., Jaffer, A. K., Eckman, M. H.,... & Kunz, R. (0). Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis: American College of Chest Physicians evidence-based clinical practice guidelines. Chest Journal, (_suppl), e6se50s. doi: 0.78/chest.-98 Garwood, C. L., Gortney, J. S., & Corbett, T. L. (0). Is there a role for fondaparinux in perioperative bridging? American Journal of Health-System Pharmacy, 68(). Hall, R., & Mazer, C. D. (0). Antiplatelet drugs: a review of their pharmacology and management in the perioperative period. Anesthesia & Analgesia, (), 98. Kearon, C., & Hirsh, J. (997). Management of anticoagulation before and after elective surgery. New England Journal of Medicine, 6(), 506. doi:0.056/nejm99705607 Mar, P. L., Familtsev, D., Ezekowitz, M. D., Lakkireddy, D., & Gopinathannair, R. (06). Periprocedural management of anticoagulation in patients taking novel oral anticoagulants: Review of the literature and recommendations for specific populations and procedures. International Journal of Cardiology, 0, 578 585. doi:0.06/j.ijcard.05.09.05 Nutescu, E. A. (0). Oral anticoagulant therapies: Balancing the s. American Journal of Health-System Pharmacy, 70(0 Supplement ), S S. doi:0.6/ajhp000 Ortel, T. L. (0). Perioperative management of patients on chronic antithrombotic therapy. Blood, 0(), 699 705. doi:0.8/blood-0-058 Patel, I. J., Davidson, J. C., Nikolic, B., Salazar, G. M., Schwartzberg, M. S., Walker, T. G., & Saad, W. A. (0). Consensus guidelines for Periprocedural management of Coagulation status and Hemostasis in Percutaneous image-guided interventions. Journal of Vascular and Interventional Radiology, (6), 77 76. doi:0.06/ j.jvir.0.0.0 Pudusseri, A., Spyropoulos, A.C. (0). Management of Anticoagulants in the Periprocedural Period for Patients With Cancer. Journal of the National Comprehensive Cancer Network, (), 7-70. Spyropoulos, A. C., & Douketis, J. D. (0). How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood, 0(5), 95 96. doi:0.8/blood-0-0659 Department of Clinical Effectiveness V Approved by the Executive Committee of the Medical Staff on 08/9/07

Page 8 of 8 DEVELOPMENT CREDITS This practice consensus algorithm is based on majority expert opinion of the Peri-procedure Anticoagulant Management work group at the University of Texas MD Anderson Cancer Center. It was developed using a multidisciplinary approach that included input from the following clinical staff: Kamran Ahrar, MD Ŧ Lara Bashoura, MD Thao Bui, MD David Crowther, PharmD Wendy Garcia, BS Amanda Hamlin, MS, PA Sandra Horowitz, PharmD Peter Hsu, MD Cezar Iliescu, MD Ŧ Michael Kroll, MD Ŧ Patrick Lynch, MD Elizabeth P. Ninan, MBA Amy Pai, PharmD Todd Pickard, PAC Sunil K. Sahai, MD Ŧ Ali Zalpour, PharmD Ŧ Ŧ Core Development Team Leads Clinical Effectiveness Development Team Department of Clinical Effectiveness V Approved by the Executive Committee of the Medical Staff on 08/9/07