Perioperative Thromboembolic Risk Low/Low-Moderate (< 2%/ year) Moderate (2-10%/ year) High (> 10%/ year)  Non-valvular atrial fibrillation without  Non-valvular atrial fibrillation with history of  Non-valvular atrial fibrillation with a stroke/TIA within 12 months history of stroke/TIA stroke/TIA > 12 months prior  Acute VTE or arterial embolism within 3 months (Recommend delaying elective surgery  VTE occurring >12 months ago  Unprovoked VTE within the past 3 to 12 for ≥ 3 months)  Mechanical aortic valve prosthesis months  Mechanical aortic valve prosthesis and history of CVA/TIA/AFIB/low EF without atrial fibrillation (AFIB) or other  Cancer-associated VTE within 6 months (if  Mechanical mitral valve prosthesis major risk factors for stroke (low EF, cancer is high TE risk, may consider bridge)*  2 or more prosthetic heart valves hypercoag state)  Mechanical aortic valve prosthesis with one or  Caged ball or tilting disk aortic valve prosthesis A REFERENCE FOR more of the following: hypertension, diabetes,  Valvular atrial fibrillation PERIOPERATIVE MANAGEMENT age >75 yr  History of recurrent VTE while on anticoagulation or during brief interruption OF PATIENTS ON WARFARIN  Severe thrombophilia (deficiency of protein C, protein S or antithrombin, antiphospholipid BRIDGING NOT RECOMMENDED (For DOAC periop and guidance for antibodies, or multiple thrombophilic abnormalities) BRIDGING NO LONGER RECOMMENDED  VTE within 6 months in setting of cancer with a very high thrombotic risk neuraxial procedures, refer to separate IN GENERAL DUE TO UNCLEAR BENEFIT documents§) AND INCREASED RISK OF POST- BRIDGING STRONGLY CONSIDERED, BUT RISK / BENEFIT UNCLEAR. OPERATIVE BLEEDING* CONSULT ANTICOAGULATION SERVICE¥ Very Low Bleeding Risk - Cataract eye surgery Procedure can generally be performed on therapeutic anticoagulation. Discuss first with proceduralist - ICD or pacemaker placement - Simple dental procedures Low Bleeding Risk ** Some procedures can be performed on anticoagulants; discuss with proceduralist** Examples: If anticoagulation must be interrupted: If anticoagulation must be interrupted: - Gastrointestinal endoscopy +/- biopsy, enteroscopy, biliary/pancreatic stent without Before procedure: Before procedure: sphincterotomy, endonosonography without fine-  Stop warfarin 5 days prior to procedure (last dose 6 days prior to procedure)  Stop warfarin 5 days prior to procedure (last dose 6 days prior to procedure) needle aspiration ⱡ - Carpal tunnel repair  No bridging necessary  If bridging, use full-dose enoxaparin adjusted for renal function - Shoulder/foot/hand surgery and arthroscopy   INR day of procedure to document value. Perform procedure when INR below  Start bridge therapy no sooner than 36 hours after last warfarin dose - Dilatation and curettage threshold for procedure - Skin cancer excision  Last dose of enoxaparin should be given no sooner than 24 hours prior to - Abdominal hernia repair procedure - Hemorrhoidal surgery After procedure:   INR day of procedure to document value. Perform procedure when INR below - Axillary node dissection - Hydrocele repair  Resume/continue previous warfarin dose on the evening of surgery or when deemed threshold for procedure. - Noncoronary angiography safe After procedure: - Bronchoscopy +/- biopsy  No full-dose bridging - Central venous catheter removal  Resume/continue previous warfarin dose on POD #0 or when deemed safe - Cutaneous/bladder/prostate/thyroid/breast/  If the intervention increases the risk of thrombosis, administer prophylactic dose of  If bridging, start full-dose parenteral anticoagulation on POD #1 or when deemed lymph node biopsies enoxaparin or heparin safe. Continue until INR is in therapeutic range. High Bleeding Risk Before procedure: Perform procedure when INR below threshold for procedure  Stop warfarin 5 days prior to procedure (last dose 6 days prior to procedure) Examples:  If bridging, use full-dose enoxaparin adjusted for renal functionⱡ Before procedure: - Most cardiothoracic and vascular surgeries,  Start bridge therapy no sooner than 36 hours after last warfarin dose  Stop warfarin 5 days prior to procedure (take last dose 6 days prior to procedure) such as heart valve replacement/CABG, AAA  Last dose of enoxaparin should be given no sooner than 24 hours prior to repair, major vascular surgery  No bridging necessary procedure - Major abdominal surgery   INR day of procedure to document value - Neurosurgical / urologic / head and neck/   INR day of procedure to document value. Perform procedure when INR below /breast cancer surgery threshold for procedure (INR < 1.5) - Knee/hip replacement After procedure: - Kidney biopsy After procedure: - Polypectomy, variceal treatment, biliary  Resume previous warfarin dose on the evening of surgery or when deemed safe  Resume previous warfarin dose when deemed safe sphincterectomy, pneumatic dilatation of  No full-dose bridging strictures  Check renal function to guide choice of post-op anticoagulant  If the intervention increases the risk of thrombosis, administer prophylactic dose of - PEG placement  Resume full-dose bridging NO SOONER THAN 48-72 hours after surgery when - Endoscopically guided fine-needle aspiration enoxaparin or heparin hemostasis achieved. Enoxaparin should be adjusted for renal function. May opt

for heparin drip if high bleed risk. Dose may be also be “stepped up” from a prophylactic dose of heparin or enoxaparin. Continue until INR is in target range.

Note: Risk of full-dose bridging may outweigh benefits in certain situations

ⱡFull-intensity bridging dose of enoxaparin Est CrCl (ml/min) or eGFR Fraction of usual daily dose 30-39 0.5 mg/kg q12h 40-49 0.6-0.8 mg/kg q12h ≥ 50 1 mg/kg q12h -If full-dose once-daily LMWH (enoxaparin 1.5 mg/kg or dalteparin 150-200 units/kg) is used for bridging, last dose should be given no sooner than 36 hours pre-op. Alternatively, patient can be transitioned to twice-daily dosing and receive last dose 24 hours pre-op.

Notes:  Perioperative anticoagulation management will be provided by the Anticoagulation Service with input from Primary Care and specialists as needed. However, timing of resumption of anticoagulation post-procedure should be determined by proceduralist.  *Recent data have shown that bridge therapy is associated with increased risk of bleeding without a reduction in risk of thromboembolism (TE) in low/mod risk AFIB and VTE patients. While 9th ACCP (2012) recommends bridge therapy for moderate and high TE risk patients, more recent consensus recommendations are moving away from bridging. Generally, bridging will be reserved for those patients who are at highest thromboembolic risk and may be avoided in high risk TE patients who are also at high bleeding risk.  ¥UCSF: Hematology Consult (415-443-4276) or Anticoagulation Clinic. SFGH: Anticoagulation Pharmacist (415-327-0339). VA: Anticoagulation Service  For patients with decreased CrCl or who may require the need for immediate reversal of anticoagulant effect, consider IV unfractionated heparin (UFH) instead of enoxaparin.

 Do not bolus IV heparin in the post-op period. §Please refer to SFGH / UCSF / VASF Intranet site for most updated version of this guideline.

References Spyropoulos et al. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood.2012;120(15):2954-2962 Barras MA, Duffull SB, Atherton JJ, Green B. Individualized dosing of enoxaparin for subjects with renal impairment is superior to conventional dosing at achieving therapeutic concentrations. Ther Drug Monit. 2010 Aug;32(4):482-8. Douketis J 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–e350S. Douketis J et al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med. 2015; 373: 823-833 Clark N. et al. Bleeding, Recurrent Venous Thromboembolism, and Mortality Risks During Warfarin Interruption for Invasive Procedures. JAMA Intern Med. 2015 Jul 1;175(7):1163-8 Witt, DM. et al. Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism. J Thromb Thrombolysis. 2016; 41: 187-205.

Version 2.0 developed by: UCSF: Margaret Fang, MD and Ashley Thompson, PharmD; VASF Anticoagulation & Thrombosis Service: Lisa Tong, PharmD, Joyce Lin, PharmD, Tracy Minichiello, MD; ZSFGH: Christina S. Wang, PharmD; Approved February 2016