Guide to Perioperative Medication Bleed and Thromboembolism Management Considerations Start Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 7 10 days prior to Perform Medication Reconciliation Table 1: Risk Assessment 1,2 Assess risk for ATE or VTE Instructions 1. Perform patient anticoagulation assessment 7+ days prior to s. 2. Categorize -related bleeding risk using columns to the right. 3. Categorize underlying thrombosis risk using rows below. 4. View suggestions for anticoagulant interruption and bridging in cell where row and column intersect. 5. View specific guidance for novel oral anticoagulant (NOAC) users in Table 2. 6. View specific guidance for warfarin users in Table 3. 7. View specific guidance for antiplatelet users in Table 4. Assess risk for bleeding If on anticoagulant determine whether interruption and/or bridging is suggested Assess for Meds to hold/timing Anticoagulants Anti-platelets NSAIDs Others Determine timing for resumption of held meds Table 1 Table 1 Tables 1 and 3 Tables 2 5 Tables 2 and 3 High Bleeding Risk Procedures (2 day risk of major bleeds 2%) Major surgery with extensive tissue injury Cancer surgery Major orthopedic surgery Reconstructive plastic surgery Urologic or Gastrointestinal surgery Transurethral prostate resection, bladder resection or tumor ablation Nephrectomy, kidney biopsy Colonic polyp resection Bowel resection Percutaneous endoscopic gastrotomy (PEG) placement, endoscopic retrograde cholangiopancreatography (ERCP) Other Cardiac, intracranial, or spinal surgery Surgery in highly vascular organs (kidneys, liver, spleen) Multiple tooth extractions Any major operation ( duration >45 minutes) Pacemaker or cardioverter-defibrillator device implantation* Low Bleeding Risk Procedures (2 day risk of major bleeds 0% - 2%) Minor dental s (simple dental extractions, restorations, prosthetic, endodontics) Cutaneous/lymph node biopsies Shoulder/foot/hand surgery Coronary angiography Gastrointestinal endoscopy +/- biopsy Colonscopy +/- biopsy Abdominal hysterectomy Laparoscopic cholecystectomy Abdominal hernia repair Hemorrhoidal surgery Bronchoscopy +/- biopsy Epidural injections with INR <1.2 Pacemaker battery change Arthroscopy Monitor post up to at least 7 10 days post Minimal Bleeding Risk Procedures Minor dermatologic s (excision of basal and squamous cell skin cancers, actinic keratosis, and premalignant or cancerous skin nevi) Cataract s Dental cleanings, fillings Underlying Thromboembolic Risk A B C HIGH ( > 10%/yr. risk of arterial thromboembolism [ATE] or >10%/month risk of venous thromboembolism [VTE]) Bridging with low molecular weight heparin (LMWH) NOT suggested for NOACs (see table Consider interrupting NOAC using clinical judgment. Bridging with LMWH NOT suggested 2); for NOACs (see table 2); Any mechanical mitral valve Caged ball or tilting disk valve in mitral/aortic position Stroke or transient ischemic attack (TIA) within last 6 months in patients with a mechanical valve Atrial fibrillation (AF) with CHADS2 score of 5 or 6 Stroke or TIA within past 3 months in patients with AF Rheumatic valvular heart disease VTE within past 3 months Severe thrombophilia Deficiency of protein C, protein S or antithrombin Antiphospholipid antibodies Multiple thrombophilias MEDIUM (4 10%/yr. risk of ATE or 4 10%/month risk of VTE) Bileaflet aortic valve replacement (AVR) WITH major risk factors for stroke AF with CHADS2 score of 3 or 4 VTE within past 3 12 months Recurrent VTE Non-severe thrombophilia Active cancer LOW (<4%/yr. risk of ATE or <4%/month risk of VTE) Bileaflet AVR WITHOUT major risk factors for stroke AF with CHADS2 score of 0-2 (and no prior stroke or TIA) VTE more than 12 months ago 1 2 3 Warfarin (Coumadin, Jantoven) users: Interrupt warfarin and bridge with LMWH suggested (see table 3) Bridging with LMWH NOT suggested for NOACs (see table 2); Interrupt warfarin and consider bridging with LMWH suggested (see table 3) Warfarin (Coumadin, Jantoven) users: Consider interrupting warfarin using clinical judgment. Bridging with LMWH suggested if warfarin interrupted (see table 3) Consider interrupting NOAC using clinical judgment. Bridging with LMWH NOT suggested for NOACs (see table 2); Do NOT interrupt anticoagulants Do NOT interrupt anticoagulants A2 B2 C2 Consider interrupting warfarin with or without LMWH bridging based on clinician judgment (see table 3) Bridging with LMWH NOT suggested for NOACs (see table 2); Bridging with LMWH NOT suggested for NOACs (see table 2); A1 B1 C1 Do NOT interrupt anticoagulants A3 B2 C3 Interrupt warfarin. Bridging with LMWH NOT necessary (see table 3) Interrupt warfarin. Bridging with LMWH NOT necessary (see table 3)
Table 2: Novel Oral Anticoagulant (NOAC) Interruption Suggestions. Note: Bridging with LMWH NOT suggested 1,4 Drug Patient Low Bleeding Risk ** High Bleeding Risk Resumption of Therapy Renal Function Surgery (2 or 3 drug half-lives between last dose and surgery) Surgery (4 or 5 drug half-lives between last dose and surgery) Low Bleeding Risk Surgery High Bleeding Risk Surgery Dabigatran (Pradaxa) t½ = 14 17 hours CrCl > 50 ml/min Last dose: 2 days t½ = 16 18 hours CrCl 30 50 ml/min Rivaroxaban (Xarelto) CrCl > 50 ml/min Last dose: 2 days t½ = 8 9 hours t½ = 9 hours CrCl 30 50 ml/min Last dose: 2 days t½ = 9 hours CrCl 15 29.9 ml/min Apixaban (Eliquis) CrCl > 50 ml/min Last dose: 2 days t½ = 7 8 hours t½ = 17 18 hours CrCl 30 50 ml/min Edoxaban (Savaysa) CrCl > 50 ml/min Last dose: 2 days t½ = 6 11 hours Last dose: 4 5 days Last dose: 4 days Last dose: 4 days Table 3: Warfarin (Coumadin, Jantoven) Interruption and Bridging Suggestions use table 1 to determine if bridging is suggested 1,2 Day Warfarin Dose LMWH Bridge INR Monitoring -7 to -10 Maintenance Dose Assess for perioperative bridging anticoagulation; classify as undergoing high or low bleeding risk s Check baseline labs (hemoglobin, platelet count, serum creatinine, INR) -6 or -5 Begin to hold warfarin day 5 or 6 No LMWH None -4 No Warfarin No LMWH None -3 No Warfarin Start LMWH None -2 No Warfarin Continue LMWH None -1 No Warfarin ½ total day dose at least 24 hours prior to If INR < 1.5, proceed with surgery If INR >1.5 and <1.8, consider low dose vitamin K (1-2.5 mg) 0 or +1 Resume maintenance dose of None None warfarin on evening of or morning after +1 Maintenance Dose Low Bleed Risk: restart LMWH Per clinical judgment High Bleed Risk: none +2 or +3 Maintenance Dose Low Bleed Risk: continue LMWH Per clinical judgment High Bleed Risk: restart LMWH +4 Maintenance Dose Low Bleed Risk: INR testing (discontinue if INR > 1.9) INR High Bleed Risk: INR testing (discontinue if INR > 1.9) +7 to +10 Maintenance Dose INR Table 4: Peri-Procedural Use of Antiplatelets 3 Patient Population on Antiplatelet On aspirin for secondary prevention of cerebrovascular disease (CVD) and is having minor dental or dermatologic, or cataract surgery On aspirin with moderate to high risk for cardiovascular events and requires non-cardiac surgery On aspirin with low risk for cardiovascular events and requires noncardiac surgery On aspirin and requires coronary artery bypass grafting (CABG) surgery On dual antiplatelet (aspirin plus another agent) drug therapy and requires CABG surgery On dual antiplatelet drug therapy and requires surgery within 6 weeks of bare-metal stent or within 6 months of drug-eluting stent and cannot wait the suggested time periods before surgery. Action Continue aspirin Continue aspirin Stop aspirin 7 to 10 days Continue aspirin Continue aspirin; Stop clopidogrel (Plavix) or ticagrelor (Brilinta) 5 days before surgery; Stop prasugrel (Effient) 7 days before surgery Stop ticlodipine (Ticlid) 10 days before to surgery Stop cilostazol (Pletal) 4 days before surgery Stop dipyridamole (Persantine) 2 days before surgery [Note: Aggrenox contains aspirin/dipyridamole] Continue dual antiplatelet drug therapy if surgery cannot be deferred until after those time periods (6 weeks for bare-metal stent/6 months for drug-eluting stent)
All Non-steroidal Anti-inflammatory Drugs (NSAIDs) can inhibit platelet aggregation and may prolong bleeding time. However, unlike aspirin, NSAIDs reversibly inhibit platelet aggregation with the effect lasting only as long as the drug remains in the circulation. As a rule of thumb NSAIDs are considered to be cleared from the body within five (5) half-lives; although, it should be noted that extendedreleased products may pose a prolonged bleeding risk due to their drug delivery system. Therefore, prior to surgery or an invasive patients should stop taking a medication appearing on this list for a period of time equivalent to five (5) half-lives. While an effort has been made to comprehensively identify medications in each of these drug classes, this list should not be a substitute for good clinical judgment. Additionally, other drugs not appearing on this list that are known to pose a potential bleeding risk should be considered in this same regard. Table 5: Recommendations for Holding NSAIDS Before Surgery or Invasive Procedure 5-12 Drug Brand name Half life Five Half-lives Approximate Notes Days Prior Celecoxib Celebrex No antiplatelet activity Consider Continuation, may provide postoperative pain relief Diclofenac (delayed-release, extended-release, topical gel/cream) Arthrotec, Cambia, Cataflam, Voltaren, and others 2 hours 10 hours Half day Diclofenac patch Flector 12 hours 60 hours 2 3 days Prolonged action may result from depot formed in skin due to drug delivery system Diflunisal Dolobid 8 12 hours 40 60 hours 2 3 days Half-life in anephric patients reported to range from 68 138 hours Etodolac Lodine 5 8 hours 25 40 hours 1 2 days Half-life is extended to ~12 hours in children under 16 yrs Fenoprofen Nalfon 2.5 3 12.5 15 Half 1 day hours hours Flurbiprofen Ansaid 5.7 hours 28.5 hours 1 day Ibuprofen Motrin, Advil, 2 4 hours 10 20 hours Half 1 day Caldolor, Vicoprofen, and others Indomethacin Indocin 4.5 hours 22.5 hours 1 day Half-life may be prolonged and highly variable in neonates Ketoprofen (immediaterelease) Orudis, Actron, and others 2 4 hours 10 20 hours Half 1 day Half-life is 5 9 hours for a CrCl <30 ml/min; half-life is prolonged 26% in geriatrics Ketoprofen (extended-release) Oruvail 3 7.5 hours 15 37.5 hours) 1 2 days No studies connected to renal impairment; half-life prolonged 54% in geriatrics Ketorolac Toradol 4 6 hours 20 30 hours 1 2 days Half-life may be prolonged to 10 hours in renal impairment (SCr >1.9) Meclofenamate Meclomen 1 2 hours 5 10 hours Half day Lesser active metabolite has half-live of 12 15 hours Mefenamic acid Ponstel 2 hours 10 hours Half day Meloxicam Mobic 15 20 75 100 3 4 days hours hours Nabumetone Relafen 24 hours 120 hours 4 days Half-life increased by ~50% in patients with CrCl <50 ml/min Naproxen Aleve, Anaprox, Naprosyn, Naprelan, Treximet, and others 12 17 hours 60 85 hours 3 days Oxaprozin Daypro 41 55 205 275 10 11 days hours hours Piroxicam Feldene 50 hours 250 hours 10 days Half-life reported to range from 14 158 hours in health adults Sulindac Clinoril 7.8 hours 39 hours 2 days Half-life of active metabolites Tolmetin Tolectin 1 5 hours 5 25 hours Half 1 day This tool was adapted from IPRO s Management of Anticoagulation in the Peri-Procedural Period: A Tool For Clinicians 5/1/2014 and a tool from The Pharmacist s Letter. Full references and notes are below:
DISCLAIMER: Anticoagulation prescribing is highly complex, and should be conducted with the greatest care on a case by case basis, considering the complete patient medical profile. The information presented is for general guidance only. Prescribers are encouraged to consult the most current medical evidence and organizational policies and s. References: 1. 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. 2. Spyropoulus AC, Douketis JD. How I Treat Anticoagulated Patients Undergoing an Elective Procedure or Surgery. Blood. 2012; DOI 10.1182/blood-2012-06-415943. 3. Baron TH, Kamath PS, McBane RD. Management of Antithrombotic Therapy in Patients Undergoing Invasive Procedures. NEJM. 2013; 368:2113-24. 4. Tun NM, Oo TH. Prevention and Treatment of Venous Thromboembolism with New Orgal Anticoagulants: A Practical Update for Clinicians. Thrombosis. 2013; 2013:183616. 5. AHFS Drug Information, 2012 6. DailyMed Product Labeling (http://www.dailymed.nlm.nih.gov) Accessed: 10/15/12 7. LexiComp Online 8. Micromedex DrugDex 9. Drug Facts Comparisons, 2011 10. Wilner KD, Rushing M, Walden C, Adler R, Eskra J, Noveck R, Vargas R. Celecoxib does not affect the antiplatelet activity of aspirin in healthy volunteers. J Clin Pharmacol. 2002;42(9):1027-30. 11. Leese PT, Hubbard RC, Karim A, Isakson PC, Yu SS, Geis GS. Effects of Celecoxib, a Novel Cyclooxygenase-2 Inhibitor, on Platelet Function in Healthy Adults: A Randomized, Controlled Trial. The Journal of Clinical Pharmacology. 2000. 40(2);124 132. 12. Roswell Park Cancer Institute. Anesthesia Perioperative Evaluation Center. Perioperative Medication Management: Analgesics. Viewed Dec 2015. Notes: * Recent evidence suggests that interruption of anticoagulation for ICD and pacemaker-related s is not necessary. See Birnie DH et al. NEJM 368(22):2084-2093. Also: Weitz JI, Healey MD, Skanes AC, Verma AV. Periprocedural Management of Oral Anticoagulants in Patients Undergoing Atrial Fibrillation Ablation. Circulation. 2014;129:1688-1694. Therapeutic LMWH regimens include enoxaparin 1.5 mg/kg once daily or 1.0 mg/kg twice daily subcutaneously; dalteparin 200 IU/kg once daily or 100 IU/kg twice daily subcutaneously. Intermediate dose LMWH (i.e., enoxaparin 40 mg twice daily subq) has been less studied in this situation. Estimated t1/2 based on renal clearance. CrCl calculated using Cockcroft-Gault method. ** Aiming for mild to moderate residual anticoagulant effect at surgery (12%-25%). Aiming for no or minimal residual anticoagulant effect (3% - 6%) at surgery. For patients at high risk for thromboembolism and high bleeding risk after surgery, consider administering a reduced dose of dabigatran (75 mg twice daily), rivaroxaban (10 mg once daily), or apixaban (2.5 mg twice daily) on the evening after surgery and on the following day (first postoperative day) after surgery. Value for patients receiving rivaroxaban, 15 mg once daily.
Case Example: How to Use the Tool Start Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 7 10 days prior to Perform Medication Reconciliation Assess risk for ATE or VTE Assess risk for bleeding If on anticoagulant determine whether interruption and/or bridging is suggested Assess for Meds to hold/timing Anticoagulants Anti-platelets NSAIDs Others Determine timing for resumption of held meds Table 1 Table 1 Tables 1 and 3 Tables 2 5 Tables 2 and 3 Monitor post up to at least 7 10 days post Patient AZ 67 yr old male with chronic afib and a CHADS2 score of 4, currently managed with Xarelto (rivaroxaban) 20 mg once daily. He is to undergo a total knee replacement 2 weeks from today. 1. Begin assessment 7 10 days before the anticipated 2. Perform medication reconciliation. Upon med history review and reconciliation it is also discovered that the patient takes ASA 81 mg every morning over-the-counter (OTC). 3. Use table 1 to assess VTE/ATE risk, a. Here because he has AF with CHADS2 score of 4 his risk is considered medium. 4. Use table 1 to assess bleed risk level from anticipated a. Here because he is undergoing total knee (considered major orthopedic surgery) his bleed risk is considered high 5. Since on anticoagulant, here Xarelto (rivaroxaban), determine whether interruption and/or bridging is needed using table 1. a. Here we see that the thromboembolic risk and bleed risk intersect at box A2, which states that interruption of the NOAC (Xarelto[rivaroxaban]) is suggested and to refer to table 2. b. It is also noted that bridging is NOT suggested for NOACs, stated on table 2 as well. 6. Assess for meds to hold. Using table 2 you see that Xarelto (rivaroxaban) has different recommendations based upon high or low bleed risk as well as renal function status. If current serum creatinine (SCr) has not already been obtained it is recommended to obtain one for appropriate assessment. This patient s SCr was obtained and is current and using cockroft-gault method the creatinine clearance (CrCl) is estimated at 75 ml/min. We have determined above that that patient is having a high bleed risk. a. Here, the guide recommends giving the last dose of Xarelto (rivaroxaban) 3 days before the
b. Based on your updated med reconciliation, you also noted that the patient is taking aspirin. Using table 4 you note that based on your patient s past medical history they have not had a cardiac event such as MI or stent placement and thus consider the patient low risk (always room for clinical judgment) for a cardiovascular event at present. c. The rationale for aspirin use likely requires further investigation, nevertheless, here you note it is recommended that the patient stop aspirin 7 to 10 days prior to the. 7. When to resume the held meds? Use table 2 for Xarelto (rivaroxaban) and for aspirin generally using clinical judgment to be resumed when hemodynamically stable. a. Here, guide recommends resuming Xarelto (rivaroxaban) 2 to 3 days after the because it was a high bleed risk. b. Using clinical judgment the aspirin could be resumed when hemodynamically stable or 2 to 3 days after as well. 8. Monitor post up to at least 7 10 days.