periprocedural management with antithrombotic therapy

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Periprocedural Management with Antithrombotic Therapy - Adult - Inpatient/Ambulatory

Clinical Practice Guideline

Note: Active Table of Contents – Click each header below to jump to the section of interest

Table of Contents

INTRODUCTION .................................................................................................................................3

SCOPE ................................................................................................................................................3

DEFINITIONS ......................................................................................................................................3

RECOMMENDATIONS .........................................................................................................................3

METHODOLOGY .................................................................................................................................9

COLLATERAL TOOLS & RESOURCES ................................................................................................... 10

APPENDIX A. EXAMPLE 5-DAY HOLD BRIDGING PLAN ....................................................................... 11

APPENDIX B. DOSING OF PARENTERAL ANTICOAGULANTS FOR PERIPROCEDURAL MANAGEMENT .... 12

REFERENCES .................................................................................................................................... 13

Effective 10-17-2019. Contact [email protected] for previous versions.

Copyright © 2020 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission.Contact: Lee Vermeulen, [email protected] Last Revised: 01/[email protected]

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Content Expert(s):Name: Anne Rose, PharmD – Pharmacy Phone Number: (608)-263-9738 Email Address: [email protected]

Contact for Changes: Name: Philip Trapskin, PharmD – Drug Policy Program Phone Number: (608) 263-1328 Email Address: [email protected]

Guideline Author(s):Jennifer Fever, PharmD – Pharmacy Anne Rose, PharmD – Pharmacy

Reviewer(s):David Ciske, MD – Medical Director: Anticoagulation Clinic and Internal Medicine Erin Robinson, PharmD, CACP – Anticoagulation Clinic Patrick Pfau, MD – Gastroenterology David Yang, MD – Laboratory

Committee Approval(s): Inpatient Anticoagulation Committee: June 2019 Ambulatory Anticoagulation Committee: July 2019 Pharmacy & Therapeutics Committee

• Original: 2011• Revisions: 2013; 2015; October 2019


Copyright © 2020 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission.Contact: Lee Vermeulen, [email protected] Last Revised: 01/[email protected]

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Introduction

Patients receiving long term antithrombotic therapy who require surgery, or an invasive procedure present a difficult therapeutic dilemma for clinicians. In this periprocedural interval when antithrombotic therapy is halted, periprocedural anticoagulation (bridging therapy) with a heparin product may be recommended for some patients.1,2 There is new evidence to support the use of bridging therapy in a small group of high-risk patients which has been outlined in this guideline. Studies have shown an increase in bleeding events when bridging therapy with a heparin agent was used both before and after procedures, with no difference in the incidence of thromboembolic events, compared to patients who did not receive bridging therapy around the time of procedures.3,4

Scope

Intended User(s): • Physicians • Advanced Practice Providers • Pharmacists • Nurses

Objective(s):

• To provide guidance on holding, bridging and resuming antithrombotic therapy for planned procedures

Target Population: Inpatient and ambulatory adult patients who have indication(s) for antithrombotic medications and require antithrombotic therapy held for a planned surgical procedure Clinical Questions Considered:

• What patient population requires bridging of antithrombotic therapy for procedures? • When should antithrombotic therapy be resumed post procedure?

Definitions

1. Periprocedural or Bridging Anticoagulation – administration of a short acting anticoagulant

during the interruption of long-term antithrombotic therapy for major/minor surgery or procedures. Usually administered for a 10 to 12-day period.1

2. Periprocedural – the period of time prior to, during and following an invasive procedure

3. Antithrombotic therapy – includes any anticoagulant or antiplatelet medication

Recommendations

Periprocedural Antithrombotic Management 1. Weigh the consequences of short-term risk for thromboembolism and bleeding for the

individual patient.1 1.1. Very few patients will need periprocedural anticoagulation or bridging therapy3,4

(UW Health GRADE moderate quality evidence, strong recommendation).


Copyright © 2020 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission.Contact: Lee Vermeulen, [email protected] Last Revised:

01/[email protected]

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1.2. Overall risk stratification should focus on the patient's risk of thromboembolism since the consequences of a thromboembolic event are more likely to have serious, lasting effects than compared to consequences of major bleeding.1,2 (UW Health low quality evidence, weak/conditional recommendation)

1.3. Use Table 1 to evaluate the bleeding risk of procedure or surgery1 (UW Health GRADE moderate quality evidence, weak/conditional recommendation)

1.4. Use Table 2 to identify patients at risk for systemic embolism if antithrombotic agent is discontinued1-4 (UW Health GRADE moderate quality evidence, strong recommendation) 1.4.1. It is recommended to use periprocedural (bridge) therapy for patients identified in

Table 2.1-4 (UW Health GRADE moderate quality evidence, strong recommendation)

1.5. Endoscopic procedures 1.5.1. For low thromboembolic risk patients: hold warfarin and proceed with endoscopic

procedure when the INR < 1.5 and for other anticoagulants see specific recommendations in Tables 4-8.1,5,6 (UW Health low quality evidence, weak/conditional recommendation)

1.5.2. For high thromboembolic risk patients: see Table 3. Hold anticoagulation based on specific recommendations for each drug listed in Tables 4-8.1,5,6 (UW Health low quality evidence, weak/conditional recommendation)

Table 1. Bleeding Risk for Surgery/Procedure1,6,7 (UW Health moderate quality evidence; weak/conditional recommendation)

High Bleed Risk Moderate Bleed Risk Low Bleed Risk

• Any procedure using cardiopulmonary bypass or mechanical assist device

• Ablation (abdominal) • Bladder surgery • Bowel polypectomy • Fine needle aspiration of deep

tissue or peritoneal space • Interventional radiology

procedures: -Transjugular intrahepatic

portosystemic shunt (TIPS) -New biliary tube -Transjugular liver biopsy -Nephrostomy tube placement -Radiofrequency ablation

• Intracranial surgery • Major cancer surgery • Major orthopedic surgery (hip or

knee replacement) • Paracentesis • Peripheral artery bypass and

other major vascular surgery • Prostate surgery • Reconstructive plastic surgery • Spinal surgery/Epidural procedure

• Ablation (musculoskeletal) • Breast procedures (biopsy) • Epidural injection • Facet injection • Fine needle aspiration of a solid

organ • Interventional radiology

procedures: -Angio up to 7 french -Venous interventions -Chemo/radioembolizations -Uterine fibroid embolization

-Tunneled venous catheter placement

-Port -Abscess drain -Percutaneous cholecystectomy -Feeding tube insertion

• Renal or lung biopsy • Resection of colon polyps • Prostate biopsy • Pacemaker or defibrillator

implantation • Outpatient neurology procedures • Major intraabdominal surgery • Major intrathoracic surgery • More invasive dental or ophthalmic

procedures • Thoracentesis • Vertebroplasty

• Cataract surgery • Dental procedures:

-Dental hygiene - Simple extractions - Restorations - Endodontics - Prosthetics • Cutaneous surgeries (most) • Laparoscopic

cholecystectomy or hernia repair

• Coronary angiography • Endoscopy with or without

biopsy • Colonoscopy with or without

biopsy • Joint aspirations and

injections • Interventional radiology

procedures: -Catheter exchanges -Central line removal -Dialysis access intervention -IVC filter placement -Non-tunneled catheter placement -Superficial aspirations

• Venography




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Table 2. Periprocedural Risk for Thromboembolism1,3,4,8 (UW Health moderate quality evidence; strong recommendation)

Risk High: Periprocedural Anticoagulation advised

Mechanical Heart Valve

• Any mechanical mitral valve • Older mechanical valve model (caged ball or tilting disc) in mitral or

aortic position • Recently placed mechanical valve (< 3 months) in mitral or aortic

position • Recent stroke or TIA (within 6 months) with mitral or aortic valve

Atrial Fibrillation

• With mechanical heart valve in mitral or aortic position • With recent stroke or TIA (within 3 months)

Venous Thromboembolism

• VTE within previous 3 months

Coagulopathies • Deficiency of protein C, protein S, or antithrombin • Antiphospholipid antibody syndrome • Multiple thrombophilic abnormalities

Table 3. Anticoagulation Considerations for Endoscopic Procedures1,6,7 (UW Health low quality evidence; weak/conditional recommendation)

Endoscopic Procedure High Thromboembolic Risk

Diagnostic or Screening Hold anticoagulation* Determine if peri-procedural bridging is needed

Low biopsy risk Removal of < 10 mm polyps with cold snare or forceps

Hold anticoagulation* Determine if peri-procedural bridging is needed

Large polyp removal (> 10 mm) Hold anticoagulation* Determine if peri-procedural bridging is needed

Sphincterotomy Esophageal Dilation Fine Needle Aspiration

Hold anticoagulation* Determine if peri-procedural bridging is needed

*See individual anticoagulant recommendations for holding prior to procedure

2. Warfarin1,7,8,9

2.1. Evaluate the INR at least 7 days before surgery or procedure to allow for planning of perioperative management. Confirm target INR for specific procedure. (UW Health moderate quality evidence, strong recommendation)

2.2. Warfarin may be continued during procedures where bleed risk is low.1,7 (UW Health low quality evidence, weak/conditional recommendation) 2.2.1. Simple dental procedures (including extractions)

• If no oral prohemostatic agent is co-administered, then warfarin should be held for 2-3 days before the procedure)

2.2.2. Cataract surgery 2.2.3. Diagnostic or screening colonoscopies 2.2.4. Some cutaneous surgeries 2.2.5. For endoscopic procedures – see Table 3 2.2.6. Low risk abdominal procedures 2.2.7. Joint aspirations or injections




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2.3. Check INR within 24 hours of surgical procedure to ensure that INR goal has been attained.1 (UW Health low quality evidence, strong recommendation)

2.4. If timing does not allow for gradual reduction of INR from withholding warfarin alone, administration of phytonadione (vitamin K), fresh frozen plasma, or prothrombin complex concentrates may be necessary. (UW Health moderate quality evidence, strong recommendation)

2.5. Appendix A is an example of a bridging plan for warfarin

Table 4 Periprocedural planning for warfarin1,7,8,9 (UW Health low quality evidence, weak/conditional recommendation)

Drug Pre-procedure INR

Pre-Procedure Plan Post Procedure Plan

Warfarin 2.0 – 3.0 Stop 5 days before procedure

Start within 24 hours if approved by proceduralist

3.0 – 4.5 Stop 6 days before procedure

> 4.5 Stop 6-7 days before procedure Consider rechecking INR after 2-3 days of held doses If indicated, consider phytonadione

3. Direct Oral Anticoagulants (DOACs)1,2,10,11,12,13 – Listed Alphabetically 3.1 Pre-operative parenteral anticoagulation (bridging) is not needed. 3.2 Evaluate renal function at least 7 days before surgery to allow for planning of

perioperative management. (UW Health low quality evidence, weak/conditional recommendation)

3.3 DOACs may be continued during procedures where bleeding risk is low: 3.3.1 Low risk interventional radiology procedures (UW Health low quality

evidence, weak/conditional recommendation) 3.4 If timing does not allow for reversal of anticoagulant effect from withholding doses

alone, administration of procoagulant agents may be necessary. (UW Health low quality evidence, weak/conditional recommendation)

3.5 Tables 5 and 6 provide recommendations for periprocedural management. The PAUSE study was a prospective, cohort study evaluating the safety of a standardized perioperative DOAC strategy in AF patients. The standardized approach omitted DOACs 1 day prior to a low-bleeding risk procedure and 2 days prior to a high-bleeding risk procedure. DOACs were resumed 1 day after a low-bleeding risk procedure and 2 days after a high-bleeding risk procedure. Major bleeding and arterial thromboembolism were tracked for 30 days post procedure. Overall, major bleeding 30-day post-procedure for all was 1.35% for apixaban, 0.9% for dabigatran and 1.85% for rivaroxaban. Arterial thromboembolism was 0.16% for apixaban, 0.6% for dabigatran and 0.4% for rivaroxaban. There were 33.5% of patients with a high-bleed risk procedure, Major bleeding rates were 3% for apixaban and 3% for rivaroxaban. The PAUSE trial offers a standardized approach to periprocedural planning for DOACs.14




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Table 5 Periprocedural planning for direct oral anticoagulants14 (UW Health low quality evidence; weak/conditional recommendation)

Drug Minor Surgery of Standard Bleed Risk Surgery

Major Surgery or High Bleed Risk Surgery

Apixaban Stop 1 day before procedure Stop 2 days before procedure Dabigatran (CrCl > 50 mL/min) Stop 1 day before procedure Stop 2 days before procedure Dabigatran (CrCl ≤ 50 mL/min) Stop 2 days before procedure Stop 4 days before procedure Edoxaban Stop 1 day before procedure Stop 2 days before procedure Rivaroxaban Stop 1 day before procedure Stop 2 days before procedure

Table 6 Post-procedural planning for the direct oral anticoagulants10,11,12,13 (UW Health low quality evidence,

weak/conditional recommendation) Drug Minor surgery or Standard

bleed risk surgery Major surgery or high bleed risk surgery

Onset of anticoagulation

Apixaban Start within 24 hours if approved by proceduralist


3 – 5 hours

Dabigatran Start within 24 hours if approved by proceduralist


2 hours

Edoxaban Start within 24 hours if approved by proceduralist


2 hours

Rivaroxaban Start within 24 hours if approved by proceduralist


2 – 4 hours

4. Parenteral Anticoagulants1,7,9,15,16,17,18,19

4.1 Parenteral anticoagulation may be used for periprocedural anticoagulation management (bridging) in certain high-risk patients.

4.2 If timing does not allow for reversal of anticoagulant effect from withholding doses alone, administration of reversal agents or procoagulant agents may be necessary. (UW Health low quality evidence, weak/conditional recommendation)

4.3 Tables 7 and 8 provide recommendations for periprocedural management 4.4 Appendix B provides dosing recommendations for parenteral anticoagulants when

used for bridging

Table 7 Periprocedural planning for parenteral anticoagulants15,16,17,18,19 (UW Health low quality evidence, weak/conditional recommendation)

Drug Pre-procedure Any bleed risk surgery Argatroban Normal hepatic function Stop 3 hours before procedure

Child-Pugh Score > 6 Stop 9 hours before procedure

Bivalirudin CrCl ≥ 30 mL/min Stop 1.5 hours before procedure CrCl < 30 mL/min Stop 3 hours before procedure

Enoxaparin Prophylactic Dosing Stop 12 hours before procedure Therapeutic Dosing Stop 24 hours before procedure

Fondaparinux CrCl ≥ 50 mL/min Stop 3 days before procedure

CrCl < 50 mL/min Stop 5 days before procedure

Unfractionated Heparin Prophylactic Dosing May give the morning before procedure Therapeutic Dosing Stop 4-6 hours before procedure




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Table 8 Post-procedural planning for parenteral anticoagulants15,16,17,18,19 (UW Health low quality evidence, weak/conditional recommendation)

Drug Minor surgery or Standard bleed risk surgery

Major surgery or high bleed risk surgery

Onset of anticoagulation

Argatroban Start within 12 hours if approved by surgeon


30 minutes

Bivalirudin Start within 12 hours if approved by surgeon


15 minutes

Enoxaparin Start within 24 hours if approved by surgeon


3 – 5 hours

Fondaparinux Start within 24 hours if approved by surgeon

Start within 72 hours if approved by surgeon

3 hours

Unfractionated Heparin

Start within 12 hours if approved by surgeon


Immediate

5. Antiplatelet Therapy1,20,21,22 – Listed Alphabetically

5.1 For periprocedural management of antiplatelet therapy, assess use at least 7 days before surgery or procedure to allow for adequate hold time. (UW Health low quality evidence, weak/conditional recommendation)

5.2 If timing does not allow for reversal of antiplatelet effect from withholding doses alone, the surgeon may still elect to proceed with surgical procedure. (UW Health very low quality evidence, weak/conditional recommendation) 5.2.1 Patients with coronary artery stent requiring surgery it is recommended to defer

surgery for at least 6 weeks after stent placement.1 (UW Health moderate quality evidence, strong recommendation)

5.2.2 For inpatients the VerifyNow Platelet Reactivity laboratory tests may be used for aspirin or clopidogrel to determine the level of platelet inhibition (UW Health low quality evidence, weak/conditional recommendation

5.3 Table 9 provide recommendations for periprocedural management

Table 9 Periprocedural management for antiplatelet drugs1,20,21,22 (UW Health low quality evidence, weak/conditional recommendation)

Drug Pre-Procedure Plan Post-Procedure Plan Aspirin (low cardiovascular event risk)

Stop 7-10 days before procedure Start within 24 hours if approved by proceduralist

Aspirin (high cardiovascular event risk)

May continue aspirin Start within 24 hours if approved by proceduralist

Cangrelor Stop 1-6 hours before procedure Start within 24 hours if approved by proceduralist

Clopidogrel Stop 5-7 days before procedure Start within 24-48 hours if approved by proceduralist

Cilostazol

Stop 1 -2 days before procedure Start within 24 hours if approved by proceduralist

Dipyridamole

Stop 1 -2 days before procedure Start within 24 hours if approved by proceduralist

Prasugrel Stop 5-7 days before procedure Start within 24-48 hours if approved by proceduralist

Ticagrelor Stop 5 days before procedure Start within 24-48 hours if approved by proceduralist




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Disclaimer Clinical practice guidelines assist clinicians by providing a framework for the evaluation and treatment of patients. This guideline outlines the preferred approach for most patients. It is not intended to replace a clinician’s judgment or to establish a protocol for all patients. It is understood that some patients will not fit the clinical condition contemplated by a guideline and that a guideline will rarely establish the only appropriate approach to a problem.

Methodology

Development Process Each guideline is reviewed and updated a minimum of every 3 years. All guidelines are developed using the guiding principles, standard processes, and styling outlined in the UW Health Clinical Practice Guideline Resource Guide. This includes expectations for workgroup composition and recruitment strategies, disclosure and management of conflict of interest for participating workgroup members, literature review techniques, evidence grading resources, required approval bodies, and suggestions for communication and implementation. Methods Used to Collect the Evidence: The following criteria were used by the guideline author(s) and workgroup members to conduct electronic database searches in the collection of evidence for review. Literature Sources:

• Electronic database search (e.g., PubMed) • Hand-searching journals, external guidelines, and conference publications

Time Period: 2000 to 2019 Search Terms:

• Term 1: Periprocedural AND anticoagulant • Term 2: Periprocedural AND antiplatelet

Methods to Select the Evidence: Original research, meta-analysis, reviews and guidance papers were included in the review. Findings and recommendations derived from the included articles were discussed with guideline authors when developing recommendations. Methods Used to Formulate the Recommendations: The workgroup members agreed to adopt recommendations developed by external organizations and/or created recommendations internally via a consensus process using discussion of the literature and expert experience/opinion. If issues or controversies arose where consensus could not be reached, the topic was escalated appropriately per the guiding principles outlined in the UW Health Clinical Practice Guideline Resource Guide. Methods Used to Assess the Quality of the Evidence/Strength of the Recommendations: Recommendations developed by external organizations maintained the evidence grade assigned within the original source document and were adopted for use at UW Health. Internally developed recommendations, or those adopted from external sources without an assigned evidence grade, were evaluated by the guideline workgroup using an algorithm adapted from the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology (see Figure 1).




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Figure 1. GRADE Methodology adapted by UW Health

Rating Scheme for the Strength of the Evidence/Recommendations: GRADE Ranking of Evidence

High We are confident that the effect in the study reflects the actual effect.

Moderate We are quite confident that the effect in the study is close to the true effect, but it is also possible it is substantially different.

Low The true effect may differ significantly from the estimate.

Very Low The true effect is likely to be substantially different from the estimated effect. GRADE Ratings for Recommendations For or Against Practice

Strong (S) Generally should be performed (i.e., the net benefit of the treatment is clear, patient values and circumstances are unlikely to affect the decision.)

Conditional (C) May be reasonable to perform (i.e., may be conditional upon patient values and preferences, the resources available, or the setting in which the intervention will be implemented.)

Recognition of Potential Health Care Disparities: use of the guideline is not expected to result in health care disparities.

Collateral Tools & Resources

Not applicable Metrics

1. Metrics include appropriate patient selection for “bridge” therapy, thromboembolic event up to 30 days after procedure, bleeding event up to 30 days after procedure, appropriate hold time of antithrombotic in relation to procedure or neuraxial catheter placement or removal and inappropriate administration of antithrombotic medications during neuraxial catheter placement.

2. Thromboembolic events in the absence of antithrombotic therapy in the periprocedural setting 3. Hemorrhagic events with antithrombotic therapy in the periprocedural setting 4. Hemorrhagic events with antithrombotic therapy with epidural or spinal catheter placement and

removal




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Appendix A. Example 5-day hold bridging plan

Date

Bridging

Medication

Bridging

Medication Warfarin Labs/

Appointments AM PM

Pre-Procedure

Day -5 Hold Hold Hold

Pre-Procedure

Day -4 Hold Hold Hold

Pre-Procedure

Day -3 Bridging Dose Bridging Dose Hold

Pre-Procedure Bridging Dose Bridging Dose Hold

Day - 2

Pre-Procedure

Day -1 Bridging Dose Hold Hold

Procedure Day

Hold Hold mg

( tablets)

Post Procedure

Day 1 Bridging Dose Bridging Dose mg

( tablets)

Post Procedure


( tablets)

Post Procedure


( tablets)

Post Procedure


( tablets)

Post Procedure


INR

( tablets)

KEY Shaded cells: no doses administered Unshaded cells: doses administered




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Appendix B. Dosing of parenteral anticoagulants for periprocedural management

Drug Therapeutic Dose Prophylactic Dose

Enoxaparin (Lovenox®)

1 mg/kg SQ every 12 hours (Round to nearest prefilled syringe size)

40 mg SQ every 24 hours

Fondaparinux (Arixtra®)

Weight based < 50 kg: 5 mg SQ every 24 hours

50-100 kg: 7.5 mg SQ every 24 hours >100 kg: 10 mg SQ every 24 hours

2.5 mg SQ every 24 hours

UFH Refer to UWHC Guidelines for therapeutic dosing of IV heparin

5000 units SQ every 12 hours OR

5000 units SQ every 8 hours




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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(2 Suppl):e326S-e350S.

2. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S-e88S.

3. Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med. 2015;373(9):823-833.

4. Steinberg BA, Peterson ED, Kim S, et al. Use and outcomes associated with bridging during anticoagulation interruptions in patients with atrial fibrillation: findings from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Circulation. 2015;131(5):488-494.

5. Committee ASoP, Anderson MA, Ben-Menachem T, et al. Management of antithrombotic agents for endoscopic procedures. Gastrointest Endosc. 2009;70(6):1060-1070.

6. Witt DM, Delate T, McCool KH, et al. Incidence and predictors of bleeding or thrombosis after polypectomy in patients receiving and not receiving anticoagulation therapy. J Thromb Haemost. 2009;7(12):1982-1989.

7. Bahl V, Hu HM, Henke PK, Wakefield TW, Campbell DA, Jr., Caprini JA. A validation study of a retrospective venous thromboembolism risk scoring method. Ann Surg. 2010;251(2):344-350.

8. Garcia DA, Regan S, Henault LE, et al. Risk of thromboembolism with short-term interruption of warfarin therapy. Arch Intern Med. 2008;168(1):63-69.

9. Douketis JD. Perioperative anticoagulation management in patients who are receiving oral anticoagulant therapy: a practical guide for clinicians. Thromb Res. 2002;108(1):3-13.

10. Dabigatran (Pradaxa®) [prescribing information]. Boehringer Ingelheim Pharmaceuticals; Ridgefield, CT. In:2012.

11. Rivaroxaban (Xarelto®) [prescribing information]. Janssen Pharmaceuticals, Inc.; Gurabo, PR. In:2012.

12. Apixaban (Eliquis®) [prescribing information]. Brisol-Meyers Squibb, Inc.; Princeton, NJ. In:2012.

13. Edoxaban (Savaysa®) [prescribing information]. Daiichi Sankyo, Inc.; Parsippany, NJ. In:2015.

14. Douketis JD, Spyropoulos AC, Duncan J, et al. Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant. JAMA Intern Med. 2019.

15. O'Donnell MJ, Kearon C, Johnson J, et al. Brief communication: Preoperative anticoagulant activity after bridging low-molecular-weight heparin for temporary interruption of warfarin. Ann Intern Med. 2007;146(3):184-187.

16. Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):141S-159S.

17. Fondaparinux (Arixtra®) [prescribing information]. Organon Sanofi-Synthelabo; West Orange, CT. In:2002.

18. Bivalirudin (Angiomax®) [prescribing information]. The Medicines Company; Parsippany, NJ. In:2005.




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19. Argatoban [prescribing information]. GlaxoSmithKline; Research Triangle Park, NC. In:2014.

20. Eikelboom JW, Hirsh J, Spencer FA, Baglin TP, Weitz JI. Antiplatelet drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e89S-e119S.

21. Writing Committee M, Jneid H, Anderson JL, et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/Non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2012;126(7):875-910.

22. Hall R, Mazer CD. Antiplatelet drugs: a review of their pharmacology and management in the perioperative period. Anesth Analg. 2011;112(2):292-318.




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