1. PreOp Anticoagulation Decision Support Click here to begin Click here for references

2. Oral Anticoagulants What oral anticoagulant does the patient take? Warfarin (Coumadin®, others) Dabigatran (Pradaxa®) Rivaroxaban (Xarelto®)

3. Is the surgery or procedure elective or emergent? ElectiveEmergent

4. Thromboembolism Risk This risk classification is an initial guide for decision-making that should be adapted to individual patient circumstances. If you are unsure of your patient’s risk of thromboembolism, continue with decision support here. here If you already know your patient’s risk of thromboembolism, choose a management plan below: – High Thromboembolic Risk High Thromboembolic Risk – Moderate Thromboembolic Risk Moderate Thromboembolic Risk – Low Thromboembolic Risk Low Thromboembolic Risk

5. Is the Patient having a Low Bleeding Risk Procedure? Low risk bleeding procedures Cutaneous procedures: Mohs, excisions and biopsies GI procedures: Diagnostic upper endoscopy, enteroscopy and colonoscopy (including biopsies), endosonography and capsule endoscopy Dental extraction Cataract extraction/IOL Procedures that are not low risk Closure after Mohs procedure GI procedures: Screening colonoscopy, polypectomy, sphincterotomy, dilatation, ablation, fine needle biopsies, PEG tube placement, therapeutic balloon-assisted enteroscopy, treatment of varices No Yes

6. HIGH RISK: Does patient have any of the following? 1) Any mitral valve prosthesis? 2) Caged-ball or tilting disc valve prosthesis? (Types of Mechanical Valves) 3) Stroke, TIA, or VTE in last 3 months? 4) Stroke or TIA with mechanical valve in last 6 months? 5) Severe thrombophilia? (examples) 6) Rheumatic valvular heart disease with atrial fibrillation?Types of Mechanical Valvesexamples Yes No

7. MODERATE RISK: Does patient have any of the following? 1) Bileaflet aortic valve prosthesis with at least one risk factor? (risk factors) 2) Atrial fibrillation? (Chad 2 Score) 3) VTE within past 3-12 months? 4) Recurrent VTE? 5) Active cancer (treated within 6 months or palliative)? 6) Non-severe thrombophilia? (examples)risk factorsChad 2 Scoreexamples Yes No

8. Patient does not meet criteria for moderate or high risk of thromboembolism. Recommend no bridging therapy during interruption of warfarin based on patient’s history. Click here for suggested management plan.Click here for suggested management plan. Exit

9. No need to stop warfarin before surgery, but adjust warfarin for INR<3.0 on day of procedure (Plan 1). Exit Exit

10. Types of Mechanical Valves Valve TypeValve Name(s) Bileaflet St. Jude; CarboMedics; ATS Open Pivot; On-X; Conform-X Tilting Disc (single leaflet) Bjork-Shiley (now discontinued); Medtronic Hall; Omnicarbon; Monostrut Caged-BallStarr-Edwards (only one FDA approved) Bioprosthetic (does not require anticoagulation) Carpentier-Edwards (porcine); Hancock II and Mosaic (both by Medtronic, porcine); Edwards Prima Plus, Medtronic Freestyle, and Toronto SPV (by St. Jude) are pericardial porcine valves. Prosthetic Heart Valves. Author: Eric M Kardon, MD, FACEP, Attending Emergency Physician, Georgia Emergency Medicine Specialists; Physician, Division of Emergency Medicine, Athens Regional Medical Center. Return to previous slide

11. CHADS 2 Scoring Tool CharacteristicPoints Symptoms due to CHF1 Hypertension (treated or untreated)1 Age > 75 years1 Diabetes1 Prior Stroke or TIA2 Return to previous slide

12. Examples of Severe Thrombophilia Protein C Deficiency Protein S Deficiency Antithrombin Deficiency Antiphospholipid Syndrome Multiple abnormalities Return to previous slide

13. Risk Factors Atrial fibrillation Prior stroke or TIA Hypertension Diabetes Congestive heart failure Age > 75 Return to previous slide

14. Examples of Non-severe Thrombophilia Heterozygous factor V Leiden mutation Factor II (prothrombin) mutation Return to previous slide

15. Patient is at HIGH risk for thromboembolism Recommend bridging patient with therapeutic enoxaparin if bleeding risk acceptable. Click here for suggested bridging plan. Click here for suggested bridging plan. Consider use of heparin infusion for patients with a mechanical valve.

16. Patient is at LOW risk of thromboembolism Recommend no bridging therapy during interruption of warfarin based on patient’s history. Click here for suggested management plan. Exit Click here for suggested management plan. Exit

17. High Thromboembolism Risk Use therapeutic enoxaparin perioperative bridging. (Plan 4) DayAnticoagulation Plan Pre-op Day 5Stop warfarin (last dose on Pre-op Day 6). Pre-op Day 3Start therapeutic enoxaparin bridging (1 mg/kg SC q12h) when INR < goal range. Pre-op Day 1Consider checking INR, give vitamin K 2.5 mg orally if INR > 1.5. Last dose of therapeutic enoxaparin (if using) must be > 24 hours prior to surgery. Day of SurgeryCheck INR, consider additional vitamin K if INR > 1.5. Stop heparin infusion (if using) 4-6 hours prior to surgery. Post-op Day 1May resume warfarin this evening if hemostasis achieved. Standard bleeding risk: Resume therapeutic enoxaparin (1 mg/kg SC q12h) or heparin infusion this AM if hemostasis achieved. High bleeding riskHigh bleeding risk: Consider no bridging or low-dose enoxaparin (40 mg SC daily) this AM if hemostasis achieved. Post-op Day 2High bleeding risk: Resume therapeutic enoxaparin (1 mg/kg SC q12h) or heparin infusion 48-72 hours after surgery if hemostasis achieved. Post-op Day 4+Discontinue bridging when INR has been > 2 for 48 hours. Exit

18. Moderate Thromboembolism Risk Use low dose enoxaparin perioperative bridging. (Plan3) DayAnticoagulation Plan Pre-op Day 5Stop warfarin (last dose on Pre-op Day 6). Pre-op Day 3Start low-dose enoxaparin (40mg SC daily) Pre-op Day 1Consider checking INR, give vitamin K 2.5 mg orally if INR > 1.5. Last dose of any enoxaparin must be > 24 hours prior to surgery. Day of SurgeryCheck INR, consider additional vitamin K if INR > 1.5. Assess hemostasis postoperatively. Post-op Day 1Resume warfarin this evening if hemostasis achieved. Standard bleeding risk: Resume low-dose enoxaparin (40mg SC daily) or heparin infusion 24 hours after surgery if hemostasis achieved. High bleeding riskHigh bleeding risk: Consider no bridging or low-dose enoxaparin (40 mg SC daily) 24 hours after surgery if hemostasis achieved. Post-op Day 2High bleeding risk: Continue (or begin) low-dose enoxaparin (if started post-op day 1) or heparin infusion 48-72 hours after surgery if hemostasis achieved. Post-op Day 4+Discontinue bridging when INR has been >2 for 48 hours. Exit

19. Emergency Surgery When rapid reversal is required for any INR: 1)Discontinue warfarin temporarily 2)Administer vitamin K 1 2-5mg PO or by slow IV infusion** 3)Supplement with fresh frozen plasma (at least 15ml/kg) 4)Recheck INR and administer additional vitamin K 1 in 4-8 hrs, if necessary ** Intravenous vitamin K should be diluted in 50mL Dextrose 5% and administered over 20-60 minutes to decrease risk of anaphylaxis. RN should be present during and for 15 minutes after administration to observe for infusion reactions. Exit Return to Anticoagulation Bridging Decision Support

20. High Bleeding Risk Examples Urologic surgery and procedures consisting of TURP, bladder resection, or tumor ablation; nephrectomy; or kidney biopsy Pacemaker or implantable cardioverter-defibrillator device implantation Colonic polyp resection, typically of large (1-2 cm long) sessile polyps Surgery and procedures in highly vascular organs (kidney, liver, spleen) Bowel resection Major surgery with extensive tissue injury (cancer surgery, joint arthroplasty, reconstructive plastic surgery) Cardiac, intracranial, or spinal surgery Return to High Thromboembolism Risk Perioperative Bridging Return to Moderate Thromboembolism Risk Perioperative Bridging Exit

21. Dabigatran “Bridging” (Plan 5) Emergent Surgery: – Stop dabigatran. If appropriate, consider delaying surgery until aPTT is normal or appropriate amount of time has passed for drug to have cleared (see table below). INR is not a reliable indicator. – There is no reversal agent for dabigatran. Transfuse FFP, PRBC and platelets as indicated. Consider use of recombinant factor VIIa or hemodialysis. PCC is not available at St. Mary’s Hospital. – Consider Hematology Consult. Elective Surgery: * dabigatran is contraindicated when CrCl ≤ 30 mL/min Click for a description of High bleeding risk:High bleeding risk Restart dabigatran post-operatively when hemostasis achieved and wound is stable. Bridging anticoagulation is not necessary due to rapid onset of dabigatran, but use of an alternate route anticoagulant (e.g. LMWH) may be appropriate if the patient cannot take medications by mouth. Creatinine Clearance (mL/min) Dabigatran Half-life (hours) Last dose of dabigatran prior to surgery Standard Bleeding RiskHigh Bleeding Risk > 8013 (11-22)24 hours2-4 days > 50 to ≤ 8015 (12-34)24 hours2-4 days > 30 to ≤ 5018 (13-23)At least 2 days (48 hours)4 days ≤ 30*27 (22-35)2-5 days> 5 days Exit

22. Rivaroxaban “Bridging” (Plan 6) Emergent Surgery: – Stop rivaroxaban. If appropriate, consider delaying surgery until PT (not INR) is normal or appropriate amount of time has passed for drug to have cleared (see below). – There is no reversal agent for rivaroxaban. Transfuse FFP, PRBC and platelets as indicated. Consider use of recombinant factor VIIa. Rivaroxaban is not dialyzable. PCC is not available at St. Mary’s Hospital. – Consider Hematology consult. Elective Surgery: Hold rivaroxaban for 1-2 days prior to surgery based on elimination half-life (5-9 hours in healthy adults, 11-13 hours in elderly adults). Restart rivaroxaban post-operatively when hemostasis achieved, at least 6-10 hours. Bridging anticoagulation is not necessary due to rapid onset or rivaroxaban, but use of an alternate route anticoagulant (e.g. LMWH) may be appropriate if the patient cannot take medications by mouth. Exit

23. References Return to Anticoagulation Bridging Decision Support Return to Anticoagulation Bridging Decision Support Douketis JD, Spyropoulos AC, Spencer FA, Mayr M, Jaffer AK, Eckman MH, et al. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9 th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141:e326S-e350S. Douketis JD. Perioperative management of patients who are receiving warfarin therapy: an evidence-based and practical approach. Blood. 2011;117(19):5044-5049. Garcia DA. Update in bridging anticoagulation. J Thromb Thrombolysis. 2011;31(3):259-264. Lexi-comp Online TM, Lexi-Drugs Online TM, Hudson, Ohio: Lexi-Comp, Inc.; September 20, 2011. Guidelines for testing and perioperative management of dabigatran. New Zealand Government PHARMAC. DeLoughery TG. Practical aspects of the oral new anticoagulants. Am J Hematol. 2011;86:586-590. Updated Feb 15, 2013 Katherine Rotzenberg, PharmD; Roy Kim, MD; Dave Pauly, RPh

24. Patient is at MODERATE risk of thromboembolism For patients with moderate risk bridging is not routinely recommended. – If not bridging then use this planthis plan – If due to unique patient preferences bridging is to be done then use this planthis plan

25. Low to Moderate Thromboembolism Risk Adjust warfarin for INR < 1.5 but no pre or postoperative bridging. (Plan 2) DayAnticoagulation Plan Pre-op day 5Stop warfarin (last dose on Pre-op Day 6). Pre-op day 1Consider checking INR, give vitamin K 2.5 mg orally if INR > 1.5. Day of SurgeryCheck INR, consider additional vitamin K if INR > 1.5. May resume warfarin the evening of surgery if hemostasis achieved. Exit

26. Dabigatran “Bridging” (Plan 5) Emergent Surgery: – Stop dabigatran. If appropriate, consider delaying surgery until aPTT is normal or appropriate amount of time has passed for drug to have cleared (see table below). INR is not a reliable indicator. – There is no reversal agent for dabigatran. Transfuse FFP, PRBC and platelets as indicated. Consider use of recombinant factor VIIa or hemodialysis. PCC is not available at St. Mary’s Hospital. – Consider Hematology Consult. Elective Surgery: * dabigatran is contraindicated when CrCl ≤ 30 mL/min Restart dabigatran post-operatively when hemostasis achieved and wound is stable. Bridging anticoagulation is not necessary due to rapid onset of dabigatran, but use of an alternate route anticoagulant (e.g. LMWH) may be appropriate if the patient cannot take medications by mouth. Creatinine Clearance (mL/min) Dabigatran Half-life (hours) Last dose of dabigatran prior to surgery Standard Bleeding RiskHigh Bleeding Risk > 8013 (11-22)24 hours2-4 days > 50 to ≤ 8015 (12-34)24 hours2-4 days > 30 to ≤ 5018 (13-23)At least 2 days (48 hours)4 days ≤ 30*27 (22-35)2-5 days> 5 days

27. Dabigatran “Bridging” (Plan 5) Emergent Surgery: – Stop dabigatran. If appropriate, consider delaying surgery until aPTT is normal or appropriate amount of time has passed for drug to have cleared (see table below). INR is not a reliable indicator. – There is no reversal agent for dabigatran. Transfuse FFP, PRBC and platelets as indicated. Consider use of recombinant factor VIIa or hemodialysis. PCC is not available at St. Mary’s Hospital. – Consider Hematology Consult. Elective Surgery: Creatinine Clearance (mL/min) Dabigatran Half-life (hrs) Last dose of dabigatran prior to surgery Standard Bleeding Risk High Bleeding Risk > 80 13 (11-22) 24 hours 2-4 days > 50 to ≤ 80 15 (12-34)24 hours 2-4 days > 30 to ≤ 50 18 (13-23) At least 2 days (48 hours) 4 days ≤ 30* 27 (22-35) 2-5 days > 5 days * dabigatran is contraindicated when CrCl ≤ 30 mL/min Restart dabigatran post-operatively when hemostasis achieved and wound is stable. Bridging anticoagulation is not necessary due to rapid onset of dabigatran, but use of an alternate route anticoagulant (e.g. LMWH) may be appropriate if the patient cannot take medications by mouth.