Perioperative Management of the Anticoagulated Patient Citywide Resident Perioperative Medical Consultation Conference 5/5/17 Matthew Eisen, MD Director, Anticoagulation Services MetroHealth Medical Center Overview Surgery, thrombosis, bleeding Review of the literature Practical approach to patient management Newer oral anticoagulants Cases! 1
General Considerations Surgery markedly increases thrombosis risk immobilization, vascular injury, alterations in blood flow? hypercoagulability when anticoagulation stopped abruptly (in vitro data) Venous risk increased 50-100x Arterial risk also appears to be increased VTE after Major Orthopedic Surgery Total venographic DVT: 40-60% mostly distal, asymptomatic, resolves without tx Proximal venographic DVT: 10-30% Symptomatic VTE: 1-5% Fatal PE: 0.1-2.0% Risk decreased ~ 50% with VTE prophylaxis 2
Timing of Post-Operative VTE Sweetland, et al. BMJ 2009;339:b4583 This talk is about This talk is not about VTE prophylaxis but rather the patient who is already on therapeutic anticoagulation and facing a surgical procedure or intervention 3
Thromboembolic Risk Thromboembolic risk depends on: indication for anticoagulation time since previous TE event (if any) patient co-morbidities (eg, cancer) type of surgery or procedure highest VTE risk with neurosurgery, major vascular surgery, lower extremity orthopedic surgery ¹ ¹White. Thromb Haemost 2003;90:446-55 Thromboembolic Risk Indication for AC Rate without AC (per month) Acute VTE - 1 st mo 40% Acute VTE - 2 nd, 3 rd mo 5-10% Rate without AC (per year) VTE - after 3 rd mo 5-10% Acute stroke - 1 st mo 15% A fib 4% A fib with prior stroke 12% Mitral valve 22% Aortic valve 8% Kearon. N Engl J Med 1997;336:1506-11 4
Bleeding Risk Risk of anticoagulation pre-op is minimal appropriate timing of last dose (renal fxn) Risk of anticoagulation post-op: type of surgery (major vs minor, location) patient factors (prior bleeding, low plt) quality of intra-op and post-op hemostasis intensity and timing of post-op anticoagulation (4-5x if < 24 h) 1 1 Jaffer. Am J Med 2010;123:141-150 Bridging Literature Older studies mostly observational with small sample sizes 1 More recent studies systematic review/meta-analysis (Siegal, Circulation 2012) substudy of RE-LY trial (Douketis, Thromb and Haemost 2015) outcomes registry (ORBIT-AF Steinberg, Circulation 2015) retrospective cohort of VTE pts (Clark, JAMA Intern Med 2015) randomized controlled trial (BRIDGE Douketis, NEJM 2015) 1 Chest 2008;133 no. 6 (suppl):299s-339s 5
Thromboembolic Events 1.1% 0.9% Siegal, et al. Circulation. 2012;126:1630-1639 Overall Bleeding Events 11.2% 2.0% Siegal, et al. Circulation. 2012;126:1630-1639 6
Major Bleeding Events 3.7% 0.7% Siegal, et al. Circulation. 2012;126:1630-1639 Clinical Outcome Bridging Status Warfarin (%) Warfarin (OR) Dabigatran (%) Dabigatran (OR) Major Bleeding Bridged Not Bridged 6.8 (26/383) 1.6 (16/1032) 4.62 (2.45 8.72), P < 0.001 6.5 (27/417) 1.8 (42/2,274) 3.68 (2.24 6.04), P < 0.001 Stroke or Systemic Embolism Bridged Not Bridged 0.5 (2/383) 0.2 (2/1,032) 2.70 (0.38 19.3), P = 0.321 0.5 (2/417) 0.3 (6/2,274) 1.82 (0.37 9.06), P = 0.463 Any Thromboembolism Bridged Not Bridged 1.8 (7/383) 0.3 (3/1,032) 6.39 (1.64 24.8), P =0.007 1.2 (13/417) 0.6 (5/2,274) 2.11 (0.75 5.95), P = 0.158 Douketis, et al. Thromb Haemost 2015; 113: 625 632 7
Steinberg, et al. Circulation. 2015 Feb 3; 131(5): 488 494 Clark, et al. JAMA Intern Med. 2015;175:1163-1168 8
Randomized Controlled Trials BRIDGE NHLBI (NIH) 1884 patients with AF (CHADS 2 1) published 2015 (NEJM) PERIOP-2 CIHR patients with AF (CHADS 2 1) or mechanical valve estimated completion 2017 BRIDGE Trial Douketis, et al. N Engl J Med 2015; 373:823-833 9
BRIDGE Trial Douketis, et al. N Engl J Med 2015; 373:823-833 BRIDGE Trial Douketis, et al. N Engl J Med 2015; 373:823-833 10
BRIDGE Trial Definitive study consistent with recent non-randomized data has changed practice Small numbers of pts with very high CHADS 2 scores (5, 6) leaves some uncertainty about these pts Small numbers of pts who underwent major procedures could lead to underestimate of bleeding as well as thrombotic events PERIOP-2 trial is ongoing will provide further randomized data including pts with mechanical valves No randomized VTE trials study by Clark, et al, supports more restrictive use of bridging UpToDate Suggest bridging in pts with: Embolic stroke or systemic embolism within previous 12 wks Mechanical mitral valve Mechanical aortic valve with additional stroke risk factors AF and very high risk of stroke (CHADS 2 5 or 6, stroke or systemic embolism within previous 12 wks) VTE within previous 12 wks Previous thromboembolism during interruption of chronic AC For most other patients on warfarin with AF, we suggest not using bridging. We feel more strongly about avoiding bridging the lower the pt s baseline thromboembolic risk and the higher the risk of bleeding. This practice is supported by the BRIDGE trial Lip, Douketis. Perioperative Management of Patients Receiving Anticoagulants. UpToDate 11
Management Strategies Assess thromboembolic/bleeding risk: indication for anticoagulation, time since last TE event (if any), pt co-morbidities, type of surgery Management options: continue anticoagulation without interruption (minor procedures) hold anticoagulation with or without bridging? IVC filter (in rare circumstances) Interruption Not Necessary Procedures with low bleeding risk: minor dental minor dermatologic cataract surgery arthrocentesis, joint/soft tissue injections endoscopies (without polypectomy) Check INR before procedure Chest 2012 141:2 suppl e326s-e350s 12
Low Management Strategies Thromboembolic Risk No interruption High Bleeding Risk Hold Bridge High? IVC filter Bridging Protocol Stop warfarin 5 d prior to surgery Begin full-dose LMWH 4 d prior to surgery avoid if CrCl <30, wt <45 kg or >150 kg, h/o HIT Give last dose LMWH 24 h pre-op 50% total daily dose consider checking INR prior to surgery Restart warfarin day of surgery (in pm) Restart LMWH POD#1-2 if bleeding risk high: delay full-dose until POD#2-3 (consider prophylactic dose initially) continue LMWH until INR therapeutic 13
Decrease in INR after Stopping Warfarin 36 hours 4 days 5 days Older age White. Ann Intern Med 1995;122:40 2 Anticoagulant Half-Lives Argatroban Heparin Enoxaparin Rivaroxaban Apixaban Dabigatran Fondaparinux Warfarin 40-50 min 1-2 hr 4-5 hr 7-11 hr 9-14 hr 12-17 hr 17-21 hr 20-60 hr caution if impaired renal function 14
New Oral Anticoagulants EHRA Practical Guide for use of the new oral anticoagulants. Europace 2013;15:625 651 (www.noacforaf.eu) Case #1 70 yo man with a mechanical mitral valve - scheduled for a screening colonoscopy The best management strategy is: A. hold warfarin - no bridging B. hold warfarin - use bridging C. continue warfarin without interruption consider if bileaflet aortic valve and no other stroke risk factors patient preference 15
Case #2 60 yo man with A fib, HTN - scheduled for laparoscopic cholecystectomy The best management strategy is: A. hold warfarin - no bridging - if CHADS 2 not very high B. hold warfarin - use bridging - if CHADS 2 very high, prior CVA C. continue warfarin without interruption Case #3 55 yo woman 2 wk s/p DVT - scheduled for resection of colon cancer The best management strategy is: if post-op bleeding risk low A. hold warfarin - use bridging B. stop warfarin - place IVC filter - if post-op bleeding risk high C. postpone procedure for 3 mo may not be appropriate to delay 16
Case #4 64 yo woman with HTN, DM, creat 1.5 (CrCl = 43) and A fib on dabigatran - scheduled for ventral hernia repair The best management strategy is: A. hold dabigatran 1 day B. hold dabigatran 2 days C. hold dabigatran 4 days insufficient hold given renal fxn if low bleeding risk if high bleeding risk 17