Manejo perioperatorio de la terapia antitrombótica, chest, 2012

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Manejo perioperatorio de la terapia antitrombótica, chest, 2012

  1. 1. Perioperative Management of Antithrombotic Therapy : Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines James D. Douketis, Alex C. Spyropoulos, Frederick A. Spencer, Michael Mayr, Amir K. Jaffer, Mark H. Eckman, Andrew S. Dunn and Regina Kunz Chest 2012;141;e326S-e350S DOI 10.1378/chest.11-2298 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/141/2_suppl/e326S.full.html Supplemental material related to this article is available at: http://chestjournal.chestpubs.org/content/suppl/2012/02/03/141.2_suppl. e326S.DC1.html Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright2012by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692Downloaded from chestjournal.chestpubs.org at McMaster University on March 14, 2012 © 2012 American College of Chest Physicians
  2. 2. CHEST Supplement ANTITHROMBOTIC THERAPY AND PREVENTION OF THROMBOSIS, 9TH ED: ACCP GUIDELINES Perioperative Management of Antithrombotic Therapy Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines James D. Douketis, MD, FCCP; Alex C. Spyropoulos, MD, FCCP; Frederick A. Spencer, MD; Michael Mayr, MD; Amir K. Jaffer, MD, FHM; Mark H. Eckman, MD; Andrew S. Dunn, MD; and Regina Kunz, MD, MSc (Epi) Background: This guideline addresses the management of patients who are receiving anticoagu- lant or antiplatelet therapy and require an elective surgery or procedure. Methods: The methods herein follow those discussed in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: In patients requiring vitamin K antagonist (VKA) interruption before surgery, we recom- mend stopping VKAs 5 days before surgery instead of a shorter time before surgery (Grade 1B). In patients with a mechanical heart valve, atrial fibrillation, or VTE at high risk for thromboem- bolism, we suggest bridging anticoagulation instead of no bridging during VKA interruption (Grade 2C); in patients at low risk, we suggest no bridging instead of bridging (Grade 2C). In patients who require a dental procedure, we suggest continuing VKAs with an oral prohemostatic agent or stopping VKAs 2 to 3 days before the procedure instead of alternative strategies (Grade 2C). In moderate- to high-risk patients who are receiving acetylsalicylic acid (ASA) and require non- cardiac surgery, we suggest continuing ASA around the time of surgery instead of stopping ASA 7 to 10 days before surgery (Grade 2C). In patients with a coronary stent who require surgery, we recommend deferring surgery . 6 weeks after bare-metal stent placement and . 6 months after drug-eluting stent placement instead of undertaking surgery within these time periods (Grade 1C); in patients requiring surgery within 6 weeks of bare-metal stent placement or within 6 months of drug-eluting stent placement, we suggest continuing antiplatelet therapy perioperatively instead of stopping therapy 7 to 10 days before surgery (Grade 2C). Conclusions: Perioperative antithrombotic management is based on risk assessment for thrombo- embolism and bleeding, and recommended approaches aim to simplify patient management and minimize adverse clinical outcomes. CHEST 2012; 141(2)(Suppl):e326S–e350S Abbreviations: aPTT 5 activated partial thromboplastin time; ASA 5 acetylsalicylic acid; AT8 5 Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition); AT9 5 Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines; ATE 5 arterial thromboembolism; CABG 5 coronary artery bypass graft; CHADS2 5 congestive heart failure, hypertension, age Ն 75 years, diabetes mellitus, prior stroke or transient ischemic attack; INR 5 international normalized ratio; LMWH 5 low-molecular-weight heparin; PICO 5 population, intervention, comparator, and outcome; SC 5 subcutaneous; UFH 5 unfractionated heparin; VKA 5 vitamin K antagonist newly added or have been changed since the publica- Summary of Recommendations tion of Antithrombotic and Thrombolytic Therapy: Note on Shaded Text: Throughout this guideline, American College of Chest Physicians Evidence-Basedshading is used within the summary of recommenda- Clinical Practice Guidelines (8th Edition). Recom-tions sections to indicate recommendations that are mendations that remain unchanged are not shaded.e326S Perioperative Management of Antithrombotic Therapy Downloaded from chestjournal.chestpubs.org at McMaster University on March 14, 2012 © 2012 American College of Chest Physicians
  3. 3. 2.1. In patients who require temporary inter- In patients with a mechanical heart valve,ruption of a VKA before surgery, we recom- atrial fibrillation, or VTE at moderate risk formend stopping VKAs approximately 5 days thromboembolism, the bridging or no-bridgingbefore surgery instead of stopping VKAs a approach chosen is, as in the higher- and lower-shorter time before surgery (Grade 1C). risk patients, based on an assessment of indi- vidual patient- and surgery-related factors.2.2. In patients who require temporary interrup-tion of a VKA before surgery, we recommend 2.5. In patients who require a minor dental pro-resuming VKAs approximately 12 to 24 h after cedure, we suggest continuing VKAs with coad-surgery (evening of or next morning) and when ministration of an oral prohemostatic agent orthere is adequate hemostasis instead of later stopping VKAs 2 to 3 days before the procedureresumption of VKAs (Grade 2C). instead of alternative strategies (Grade 2C). In patients who require minor dermatologic pro-2.4. In patients with a mechanical heart valve, cedures and are receiving VKA therapy, weatrial fibrillation, or VTE at high risk for throm- suggest continuing VKAs around the time ofboembolism, we suggest bridging anticoagula- the procedure and optimizing local hemostasistion instead of no bridging during interruption instead of other strategies (Grade 2C). In patientsof VKA therapy (Grade 2C). who require cataract surgery and are receiving VKA therapy, we suggest continuing VKAsRemarks: Patients who place a higher value on avoiding around the time of the surgery instead of otherperioperative bleeding than on avoiding periopera- strategies (Grade 2C).tive thromboembolism are likely to decline heparinbridging. 3.4. In patients who are receiving ASA for the secondary prevention of cardiovascular diseaseIn patients with a mechanical heart valve, atrial and are having minor dental or dermatologicfibrillation, or VTE at low risk for thromboem- procedures or cataract surgery, we suggest con-bolism, we suggest no bridging instead of tinuing ASA around the time of the procedurebridging anticoagulation during interruption instead of stopping ASA 7 to 10 days before theof VKA therapy (Grade 2C). procedure (Grade 2C).Revision accepted August 31, 2011.Affiliations: From the Department of Medicine (Drs Douketis 3.5. In patients at moderate to high risk forand Spencer), McMaster University, Hamilton, ON, Canada; cardiovascular events who are receiving ASADepartment of Medicine (Dr Spyropoulos), University of therapy and require noncardiac surgery, weRochester, Rochester, NY; Medical Outpatient Department(Dr Mayr), University Hospital Basel, Basel, Switzerland; Divi- suggest continuing ASA around the time of sur-sion of Hospital Medicine (Dr Jaffer), Department of Medicine, gery instead of stopping ASA 7 to 10 days beforeUniversity of Miami Miller School of Medicine, Miami, FL; Divi- surgery (Grade 2C) . In patients at low risk forsion of General Internal Medicine and Center for Clinical Effec-tiveness (Dr Eckman), University of Cincinnati Medical Center, cardiovascular events who are receiving ASACincinnati, OH; Department of Medicine (Dr Dunn), Mount therapy, we suggest stopping ASA 7 to 10 daysSinai School of Medicine, New York, NY; and Academy of Swiss before surgery instead of continuation of ASAInsurance Medicine (Dr Kunz), Department of Medicine, Uni-versity Hospital Basel, Basel, Switzerland. (Grade 2C).Funding/Support: The Antithrombotic Therapy and Preventionof Thrombosis, 9th ed: American College of Chest Physicians 3.6. In patients who are receiving ASA andEvidence-Based Clinical Practice Guidelines received support from require CABG surgery, we suggest continuing ASAthe National Heart, Lung, and Blood Institute [R13 HL104758]and Bayer Schering Pharma AG. Support in the form of educa- around the time of surgery instead of stoppingtional grants was also provided by Bristol-Myers Squibb; Pfizer, Inc; ASA 7 to 10 days before surgery (Grade 2C). InCanyon Pharmaceuticals; and sanofi-aventis US. patients who are receiving dual antiplatelet drugDisclaimer: American College of Chest Physician guidelines areintended for general information only, are not medical advice, and therapy and require CABG surgery, we suggestdo not replace professional medical care and physician advice, continuing ASA around the time of surgery andwhich always should be sought for any medical condition. The stopping clopidogrel/prasugrel 5 days beforecomplete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S. surgery instead of continuing dual antiplateletCorrespondence to: Regina Kunz, MD, MSc (Epi), Academy of therapy around the time of surgery (Grade 2C).Swiss Insurance Medicine, Department of Medicine, UniversityHospital Basel, Petersgraben 4, 4031, Basel, Switzerland; e-mail: 3.7. In patients with a coronary stent who areRKunz@uhbs.ch© 2012 American College of Chest Physicians. Reproduction receiving dual antiplatelet therapy and requireof this article is prohibited without written permission from the surgery, we recommend deferring surgery forAmerican College of Chest Physicians (http://www.chestpubs.org/ at least 6 weeks after placement of a bare-metalsite/misc/reprints.xhtml).DOI: 10.1378/chest.11-2298 stent and for at least 6 months after placementwww.chestpubs.org CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT e327S Downloaded from chestjournal.chestpubs.org at McMaster University on March 14, 2012 © 2012 American College of Chest Physicians
  4. 4. of a drug-eluting stent instead of undertaking Physicians Evidence-Based Clinical Practice Guide-surgery within these time periods (Grade 1C). In lines (8th Edition) (AT8), in the following ways:patients who require surgery within 6 weeksof placement of a bare-metal stent or within • There is a downgrading of several recommen-6 months of placement of a drug-eluting stent, dations. This reflects the emergence of additionalwe suggest continuing dual antiplatelet therapy evidence and, in general, a higher threshold foraround the time of surgery instead of stopping conferring strong (level 1) recommendations,dual antiplatelet therapy 7 to 10 days before which has been adopted across the Antithrom-surgery (Grade 2C). botic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians4.2. In patients who are receiving bridging anti- Evidence-Based Clinical Practice Guidelines (AT9).coagulation with therapeutic-dose IV UFH, we • There are fewer recommendations in AT9. Wesuggest stopping UFH 4 to 6 h before surgery aimed to make evidence-based recommenda-instead of closer to surgery (Grade 2C). tions on areas where studies exist that are directly pertinent to the clinical questions weRemarks: Patients who are more concerned about avoid- developed, which were based on the population,ing the unknown, but potentially large increase in intervention, comparator, and outcome (PICO)bleeding risk associated with the perioperative con- format. Whenever possible, we relied less ontinuation of dual antiplatelet therapy than avoiding indirect evidence from studies in the nonperi-the risk for coronary stent thrombosis are unlikely to operative setting.choose continuation of dual antiplatelet therapy. • For areas in which a PICO question was not developed but are, nonetheless, considered rel-4.3. In patients who are receiving bridging anti- evant for everyday practice, we have providedcoagulation with therapeutic-dose SC LMWH, narrative comments in the text without specificwe suggest administering the last preoperative recommendations.dose of LMWH approximately 24 h before sur- • The antithrombotic management of patientsgery instead of 12 h before surgery (Grade 2C). requiring urgent surgery is now addressed in the article by Falck-Ytter et al9 in this guideline.4.4. In patients who are receiving bridging anti-coagulation with therapeutic-dose SC LMWH The following definitions and qualifying remarksand are undergoing high-bleeding-risk surgery, are aimed to facilitate an understanding of this articlewe suggest resuming therapeutic-dose LMWH and its accompanying recommendations:48 to 72 h after surgery instead of resumingLMWH within 24 h after surgery (Grade 2C). • Bridging anticoagulation. In the absence of a universally accepted definition,6,10,11 we define bridging anticoagulation as the administrationThe perioperative management of patients who are receiving vitamin K antagonists (VKAs) or of a short-acting anticoagulant, consisting of subcutaneous (SC) low-molecular-weight hep-antiplatelet drugs and require a surgical or invasive arin (LMWH) or IV unfractionated heparinprocedure presents a dilemma for practicing clini- (UFH), for an ‫ -01ف‬to 12-day period duringcians. This clinical problem affects an estimated interruption of VKA therapy when the inter-250,000 patients annually in North America alone national normalized ratio (INR) is not within aand is of interest to a wide spectrum of clinicians, therapeutic range.including internists, surgeons, anesthetists, family • Therapeutic intent of heparin bridging and dosephysicians, and dentists.1-3 However, there is a rela- regimens. Bridging anticoagulation aims to min-tive paucity of well-designed clinical trials to inform imize the risk for arterial thromboembolismbest practices and a disproportionately large number (ATE), such as stroke and systemic embolism, inof methodologically weak observational studies.4-8 patients with a mechanical heart valve or atrialThe aims of this article are to (1) provide guidelines fibrillation and to minimize the risk for recur-for perioperative antithrombotic management that rent thrombosis in patients with prior VTE. Thereflect the quality of the available evidence and argument for using a high-dose (or therapeutic-(2) provide guidance for clinicians as to the practical dose) heparin regimen to prevent ATE is basedaspects of antithrombotic management in the peri- on two considerations. First, this dose regimenoperative setting. with LMWH or UFH is comparable to a thera- The current iteration of this article differs from peutic-dose VKA regimen when used for thethat of Douketis et al6 in the Antithrombotic and prevention of ATE in patients with a mechan-Thrombolytic Therapy: American College of Chest ical heart valve and the treatment of acutee328S Perioperative Management of Antithrombotic Therapy Downloaded from chestjournal.chestpubs.org at McMaster University on March 14, 2012 © 2012 American College of Chest Physicians
  5. 5. VTE.12,13 Second, a therapeutic-dose regimen of est therapeutic benefit and the greatest harm. idraparinux, a factor Xa antagonist with LMWH- (We acknowledge that different bridging regi- like anticoagulant properties, is as efficacious mens may be used and that such regimens may as a VKA to prevent ATE in patients with atrial have potential advantages or drawbacks com- fibrillation.14 However, its efficacy to prevent pared with a therapeutic-dose regimen.) perioperative ATE is not established. A low- • VKAs. Although several VKAs are available for dose (or prophylactic-dose) heparin regimen is clinical use, including warfarin, acenocoumarol, known to prevent postoperative VTE, but its phenprocoumon, and anisindione,16 our recom- efficacy to prevent ATE is also not established, mendations will refer to warfarin because perti- and the biological plausibility to support its effi- nent studies are dominated by warfarin use, cacy for this therapeutic aim may be questioned.15 with little or no study of other VKAs. Finally, the use of LMWH or UFH as periop- erative bridging is considered an off-label use of these drugs because their use is not approved Practical Aspects of Perioperative by regulatory authorities or drug manufacturers Antithrombotic Therapy Management in this clinical setting as a bridging agent. The perioperative management of patients who • Bridging dose regimens. Three dose regimens are receiving antithrombotic therapy is based on have been studied: (1) an assessment of patient risk for thromboembo- lism and (2) an assessment of risk for perioperative 1. A high-dose (therapeutic-dose) heparin bleeding. Addressing these issues will determine bridging regimen involves administering an whether antithrombotic therapy is interrupted around anticoagulant dose that is similar to that the time of the surgery or procedure and, if so, used for the treatment of acute VTE or whether bridging anticoagulation is considered. This an acute coronary syndrome (eg, enoxaparin article focuses on the three dominant clinical indi- 1 mg/kg bid or 1.5 mg/kg daily, dalteparin cations for VKA therapy: mechanical heart valves, 100 International Units/kg bid or 200 Inter- chronic atrial fibrillation, and VTE. national Units/kg daily, tinzaparin 175 Inter- To date, there are no validated risk stratification national Units/kg daily, IV UFH to attain schemes to reliably separate VKA-treated patients an activated partial thromboplastin time into risk strata for thromboembolism and bleeding. [aPTT] 1.5 to 2 times the control aPTT). Of necessity, our recommendations are based largely 2. A low-dose (prophylactic-dose) heparin reg- on indirect evidence and clinical experience.17-20 These imen involves administering a dose that risk stratification schemes are meant to provide gen- is used, typically, to prevent postoperative eral guidance; however, patient management may VTE (eg, enoxaparin 30 mg bid or 40 mg vary depending on individual patient characteristics, daily, dalteparin 5,000 International Units the surgery or procedure type, and patient values and daily, UFH 5,000-7,500 International Units preferences. bid). 3. An intermediate-dose regimen has recently Assessing Risk for Thromboembolism been studied for bridging and is interme- diate in anticoagulant intensity between Assessing patient risk for thromboembolism dur- high- and low-dose regimens (eg, enox- ing the perioperative interruption of antithrombotic aparin 40 mg bid). therapy is distinguished from assessing patient risk for postoperative VTE. In the former setting, patients • Our recommendations relating to the need for are already receiving antithrombotic therapy, and the bridging anticoagulation (section 2.4) will not aim is mainly to prevent ATE, in some instances, refer to a specific bridging dose regimen and with heparin bridging, whereas in the latter setting, will deal with the issue of whether bridging is the focus is on preventing postoperative VTE with needed in a more generic sense. de novo use of antithrombotic drugs. • Our recommendations relating to the periop- The suggested thromboembolic risk stratification erative management of patients who are receiving shown in Table 1 is based largely on indirect evidence bridging (section 4.0) will refer to a therapeutic- from studies outside of the perioperative setting dose bridging regimen because it is the most involving patients with a mechanical heart valve,21-23 widely studied and most widely used in clinical chronic atrial fibrillation,2,24-27 or VTE28-30 who either practice. It is also the dose regimen that we were not receiving anticoagulation (ie, placebo instead consider most important for practice guidelines of a VKA in patients with chronic atrial fibrillation) or because it has the potential to confer the great- were receiving less-effective treatment (eg, ASA insteadwww.chestpubs.org CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT e329S Downloaded from chestjournal.chestpubs.org at McMaster University on March 14, 2012 © 2012 American College of Chest Physicians
  6. 6. or antithrombin; antiphospholipid antibodies; multiple abnormalities) aHigh-risk patients may also include those with a prior stroke or transient ischemic attack occurring . 3 mo before the planned surgery and a CHADS score , 5, those with prior thromboembolism during temporary interruption of VKAs, or those undergoing certain types of surgery associated with an increased risk for stroke or other thromboembolism (eg, cardiac valve replacement, carotid endarterectomy, of a VKA in patients with a mechanical heart valve). In this suggested risk classification, patients classi- fied as high risk have a . 10% annual risk for throm- • Severe thrombophilia (eg, deficiency of protein C, protein S, • Nonsevere thrombophilia (eg, heterozygous factor V Leiden boembolism, patients classified as moderate risk have a 5% to 10% annual risk for thromboembolism, and patients classified as low risk have a , 5% annual risk for thromboembolism. Estimates as to the periop- • VTE . 12 mo previous and no other risk factors • Active cancer (treated within 6 mo or palliative) erative risk for thromboembolism in specific patient groups that do not receive heparin bridging during VKA therapy interruption are limited and pertain mainly VTE to patients with chronic atrial fibrillation or VTE.3,31 or prothrombin gene mutation) One limitation of the suggested risk stratification • VTE within the past 3-12 mo • Recent (within 3 mo) VTE is that individual patient factors may trump this Table 1—[Introduction] Suggested Risk Stratification for Perioperative Thromboembolism classification. For example, a perceived high-risk CHADS2 5 congestive heart failure, hypertension, age Ն 75 years, diabetes mellitus, and stroke or transient ischemic attack; VKA 5 vitamin K antagonist. patient group may also include those with atrial fibril- 2 • Recurrent VTE lation and prior stroke and one additional stroke risk factor (ie, congestive heart failure, hypertension, age Ն 75 years, diabetes mellitus, prior stroke or transient ischemic attack [CHADS2] score of 3), even though such patients would be classified as being in the moderate-risk group in the classification shown in Table 1. In addition, patients with remote • CHADS2 score of 0 to 2 (assuming no prior Indication for VKA Therapy • Recent (within 3 mo) stroke or transient (. 1 year ago), but severe VTE associated with pul- monary hypertension may be perceived as high risk, stroke or transient ischemic attack) • Rheumatic valvular heart disease even though they would be classified as low risk. Atrial Fibrillation Another general consideration in estimating peri- operative risk for thromboembolism is the surgery • CHADS2 score of 5 or 6 • CHADS2 score of 3 or 4 type. Although it is established that patients having coronary artery bypass, heart valve replacement, or ischemic attack carotid endarterectomy are at increased risk for stroke compared with patients having other types of surgery, emerging evidence also suggests that among patients undergoing noncardiovascular sur- gery, the risk for stroke may vary depending on the type of surgery.3 Taken together, an estimate of indi- • Recent (within 6 mo) stroke or transient ischemic attack vidual patient risk for perioperative thromboembolism • Bileaflet aortic valve prosthesis and one or more of the of following risk factors: atrial fibrillation, prior stroke or transient ischemic attack, hypertension, diabetes, is subjective but should consider both the estimated • Any caged-ball or tilting disc aortic valve prosthesis baseline risk and the individual factors related to the fibrillation and no other risk factors for stroke • Bileaflet aortic valve prosthesis without atrial patient and the surgery or procedure type. Mechanical Heart Valve congestive heart failure, age . 75 y Assessing Risk for Bleeding The assessment of perioperative bleeding risk • Any mitral valve prosthesis should consider two broad issues. First, for this article, we consider perioperative bleeding risk in the context of perioperative anticoagulant and anti- platelet drug administration and, in particular, when such drugs are administered in proximity to surgery. This distinction is important because whereas certain procedures may not typically result in postoperative major vascular surgery). bleeding, the administration of antithrombotic drugs may induce bleeding complications. For example, seem- ingly minor procedures, such as bowel polypectomy Risk Stratum Moderate or pacemaker insertion, are not, in isolation, associ- ated with increased bleeding but may be if anticoag- Higha Low ulants are administered in proximity to the procedure.e330S Perioperative Management of Antithrombotic Therapy Downloaded from chestjournal.chestpubs.org at McMaster University on March 14, 2012 © 2012 American College of Chest Physicians
  7. 7. Second, a distinction should be made as to bleed- • Cardiac, intracranial, or spinal surgery, especiallying risk when anticoagulants are used as heparin as small pericardial, intracerebral, or epiduralbridging and when these agents are used to prevent bleeds can have serious clinical consequences42-44postoperative venous thrombosis. In the former clin-ical setting, high-dose (or therapeutic-dose) bridging Standardized Perioperativeanticoagulation is administered, whereas in the latter Anticoagulant Therapy Protocolssetting, low-dose anticoagulants are used. The impor-tance of surgical bleeding risk, therefore, is height- Patients who are receiving warfarin and otherened in the setting of heparin bridging because of antithrombotic drugs and require elective surgerythe potential to induce bleeding complications. or procedures may benefit from management accord- Providing an evidence-based scheme that strat- ing to standardized, institution-specific protocols.ifies surgeries and procedures according to the risk Although there are no randomized trials showing thatfor bleeding in the context of perioperative anti- a standard management approach improves clinicalthrombotic drug use and, in particular, periopera- outcomes and minimizes health-care resource use,tive heparin bridging administration is problematic observational studies that incorporated standardizedbecause the available evidence on such bleeding risk perioperative anticoagulant therapy protocols andis based mainly on case series involving selected types heparin bridging regimens had low rates of throm-of surgery. Furthermore, although there are schemes boembolic and bleeding outcomes and appearedthat stratify patients according to the expected intra- to allow efficient use of health-care resources.31,45-51operative blood loss, these classifications have not Institutions and practitioners may consider incorpo-been prospectively validated and do not account for rating the following components into a standardizedthe effects of perioperative use of antithrombotic perioperative management protocol:drugs. Consequently, rather than propose a multi- • Assessing patients at least 7 days before surgerytiered scheme that encompasses most surgery or to allow planning of perioperative anticoagulantprocedure types that would be entirely subjective, we management, especially before major surgeryhave identified a group of surgeries and procedures • Providing patients and providers with a calendarthat appear to be associated with a high risk for outlining the perioperative timing of warfarin andbleeding in the context of perioperative anticoagulant antiplatelet drug discontinuation and resump-and antiplatelet drug use. tion, dose and timing of LMWH bridging, and Surgeries and procedures associated with an INR measurement scheduleincreased bleeding risk during perioperative anti- • Ensuring that the perioperative managementthrombotic drug administration include the following: strategy (including timing of VKA and antiplate- let drug interruption and initiation and resump- • Urologic surgery and procedures consisting of tion of LWMH bridging) accounts for the drugs’ transurethral prostate resection, bladder resec- pharmacokinetic profile and patients’ thrombo- tion, or tumor ablation; nephrectomy; or kidney embolic and bleeding risks biopsy in part due to untreated tissue damage • Ensuring patient and caregiver education on (after prostatectomy) and endogenous urokinase injection technique when outpatient LMWH release32-34 bridging is administered • Pacemaker or implantable cardioverter- • INR testing on the day before surgery, where defibrillator device implantation in which sepa- appropriate and feasible, to identify patients ration of infraclavicular fascial layers and lack with elevated INRs and permit timely use of of suturing of unopposed tissues within the corrective oral vitamin K (1.0-2.5 mg), thereby device pocket may predispose to hematoma avoiding blood product administration or sur- development35-38 gery deferral52 • Colonic polyp resection, typically of large • Assessing postoperative hemostasis, preferably (ie, . 1-2 cm long) sessile polyps, in which on the day of surgery and on the first postop- bleeding may occur at the transected stalk fol- erative day, to facilitate safe resumption of anti- lowing hemostatic plug release39 coagulant drugs • Surgery and procedures in highly vascular organs, such as the kidney, liver, and spleen Cost-effectiveness of Perioperative • Bowel resection in which bleeding may occur Management Strategies at the bowel anastomosis site • Major surgery with extensive tissue injury The cost-effectiveness of bridging anticoagula- (eg, cancer surgery, joint arthroplasty, recon- tion has been assessed using various decision analysis structive plastic surgery)40,41 models.53-55 These studies suggest that for patientswww.chestpubs.org CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT e331S Downloaded from chestjournal.chestpubs.org at McMaster University on March 14, 2012 © 2012 American College of Chest Physicians
  8. 8. other than those at highest risk for stroke and ATE, AT8 supplemented by additional searches of more recent studies;bridging anticoagulation is unnecessary. In patients (3) developing provisional recommendations and parallel devel- opment of a draft manuscript and revision of original PICO ques-undergoing minor dental procedures, decision analy- tions; and (4) developing final recommendations by nonconflictedses have suggested that continuation of VKA therapy panelists. The development of article recommendations wasis less expensive than VKA interruption with bridg- guided by the topic editor (R. K.), whereas the development ofing therapy.56 Studies of GI endoscopy have been the article narrative was overseen by the deputy editor (J. D.).consistent with American Society of GastroenterologyGuidelines, suggesting that continuing VKA therapy 1.3 Development of Evidence Profiles, Summary of Findings Tables, and Recommendationsin patients having procedures associated with a lowbleeding risk (eg, diagnostic endoscopy without biopsy) The recommendations in this article were developed in accor-is less expensive than bridging, whereas discontinua- dance with the methodologic changes in AT9 based on evidence profiles and summary of findings tables that followed the Gradestion of VKA therapy without bridging is more cost- of Recommendations, Assessment, Development, and Evaluationeffective in patients at low thromboembolic risk who system format.62,63are undergoing high-bleeding-risk procedures.57 Pro- For the section on the perioperative management of VKAspective cohort studies have compared the costs of therapy, we developed evidence profiles to formulate recommen-bridging anticoagulation with either in-hospital IV dations for the prespecified PICO questions. These evidence profiles include studies directly pertinent to our PICO questions.UFH or out-of-hospital SC LMWH.58-61 In one study Our recommendations were based on studies in the evidencecomparing patient-administered SC LMWH, nurse- profile that provided data specific to the perioperative clinicaladministered SC LWMH, and in-hospital IV UFH, setting. In cases where there also were relevant studies fromthe anticoagulant-related costs for patients having the nonperioperative setting, which were not part of the evi-surgery with an overnight hospital stay were esti- dence profile because they provided indirect data, these studies also had a bearing on the recommendations.mated at US $672, $933, and $3,916, respectively.59 For the section on the perioperative management of anti-Another cohort study comparing costs in 26 patients platelet therapy, evidence profiles were not produced in partwho received in-hospital IV UFH and 40 patients because there were insufficient studies to develop profiles spe-who received out-of-hospital SC LMWH and had cific to the prespecified PICO questions. We produced summaryelective surgery found a significantly lower mean of findings tables of all pertinent (but often indirect) data. The recommendations provided were based on the studies in thesetotal health-care cost (by $13,114) in patients who summary of findings tables, which are available in the online datareceived perioperative LMWH.60 Taken together, supplement. As with the perioperative VKA management sec-these findings lead to questions about the need for tions, additional studies may have been referenced in the nar-bridging therapy in patients not considered at high rative, but the recommendations were based entirely on studiesrisk for ATE. Furthermore, these studies confirm in the summary of findings tables.considerable cost savings with the use of SC LMWHsinstead of IV UFH, which can be given in an out- 2.0 Perioperative Management of Patientspatient setting by the patient or a family member Who Are Receiving VKA Therapyin . 90% of cases.45,46 2.1 Interruption of VKAs Before Surgery 1.0 Methods In patients undergoing major surgery or proce- dures, interruption of VKAs, in general, is required1.1 Data Sources to minimize perioperative bleeding,64-68 whereas The Medline English-language database was searched from VKA interruption may not be required in minorJanuary 1970 to January 2010 using multiple keywords and procedures as discussed in subsequent sections ofstandardized terminology, where applicable, as outlined in this article. Interruption of VKAs before surgeryAppendix S1. This search was done in two parts. The first was with the intent of achieving normal or near-normala systematic review of the literature from 1970 to January 2007, hemostasis at the time of surgery is based on thewhich was used in AT8.6 The second search updated this searchstrategy to include studies up until January 2010. We supple- residual pharmacodynamic effects of VKAs and themented these literature searches by conducting Internet-based associated time required for the regeneration ofsearches of ClinicalTrials.gov, meeting abstracts, and conference vitamin K-dependent coagulation factors. This canproceedings. In addition, reference lists of studies that satisfied be estimated by the elimination half-life of a VKA69-72:inclusion criteria were manually reviewed. Finally, content experts 8 to 11 h for acenocoumarol, 36 to 42 h for warfa-were contacted to identify additional studies that were not identi-fied by these search strategies. rin, and 96 to 104 h for phenprocoumon. Assuming first-order pharmacokinetics, each half-life elapsed1.2 Development of Chapter Recommendations and Narrative corresponds to an ‫ %05ف‬reduction in residual anti- coagulant effect: 50% after one half-life, 25% after The development of recommendations followed a prespeci-fied process based on the following four steps: (1) developing two half-lives, 12.5% after three half-lives, 6.25%PICO questions for clinical topics deemed important, which are after four half-lives, and 3.125% after five half-lives.summarized in Table 2; (2) identifying pertinent studies from For patients in whom the intent is to normalize thee332S Perioperative Management of Antithrombotic Therapy Downloaded from chestjournal.chestpubs.org at McMaster University on March 14, 2012 © 2012 American College of Chest Physicians
  9. 9. Table 2—[Section 1.2] Structured Clinical Questions Available Section Population Intervention and Comparator Outcomes Methodology www.chestpubs.org Patients receiving warfarin therapy 2.1 Patients receiving warfarin therapy In patients who require warfarin interruption before surgery Hemostasis at time of Observational who require an elective surgery to attain normal or near-normal INR at surgery, stopping surgery (INR) studies or invasive procedure warfarin 5-6 d before surgery vs stopping warfarin , 5 d before surgery 2.2 In patients with warfarin interruption before surgery, resuming Hemostasis at time Observational warfarin 12-24 h after surgery (evening of or next day) and of surgery studies when there is hemostasis vs resuming warfarin . 24 h from surgery 2.3 INR testing to monitor anticoagulant effect of warfarin Hemostasis at time of surgery (aPTT, Observational before and after surgery vs no testing antifactor Xa) studies 2.4 Need for bridging anticoagulation during perioperative warfarin interruption Patients considered at high risk for Bridging anticoagulation with heparin/LMWH Stroke, other systemic embolism, major Observational perioperative thromboembolism vs no bridging hemorrhage studies Patients considered at moderate risk for Bridging anticoagulation with heparin/LMWH Stroke, other systemic embolism, major Observational perioperative thromboembolism vs no bridging hemorrhage studies Patients considered at low risk for Bridging anticoagulation with heparin/LMWH Stroke, other systemic embolism, major Observational perioperative thromboembolism vs no bridging hemorrhage studies 2.5 Patients having minor dental, skin, or eye procedures Patients receiving warfarin therapy Continuing warfarin and coadministering an oral ATE or VTE, major hemorrhage RCTs, observational and having a minor dental procedure prohemostatic drug vs stopping warfarin 5-6 d studies before the procedure without administering a prohemostatic drug Patients receiving warfarin therapy and Continuing warfarin around the time of the procedure ATE or VTE, major hemorrhage RCTs, observational © 2012 American College of Chest Physicians having a minor skin procedure vs stopping warfarin 5-6 d before the procedure studies Patients receiving warfarin therapy and Continuing warfarin around the time of the procedure ATE or VTE, postoperative bleeding RCTs, observational having cataract procedure vs stopping warfarin 5-6 d before the procedure studies Patients receiving antiplatelet therapy 3.4 Patients receiving antiplatelet therapy Continuing antiplatelet drugs around the time of the Myocardial ischemia, postoperative Observational and having minor dental, skin, or eye procedure vs stopping antiplatelet drugs 7-10 d bleeding procedure before procedure 3.5 Patients receiving antiplatelet therapy and Continuing antiplatelet drugs around the time of the Myocardial ischemia, postoperative RCTs, observationalDownloaded from chestjournal.chestpubs.org at McMaster University on March 14, 2012 having elective noncardiac surgery procedure vs stopping antiplatelet drugs 7-10 d bleeding studies before noncardiac surgery 3.6 Patients receiving antiplatelet therapy Continue antiplatelet drugs around the time of surgery Myocardial ischemia, postoperative Observational CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT and having elective CABG surgery vs stopping antiplatelet drugs 7-10 d before CABG bleeding studies (Continued) e333S

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