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Management of Antithrombotic Therapy in Periprocedural, Regional Anesthesia and/or Pain Procedure Settings – Adult – Inpatient/Ambulatory

Management of Antithrombotic Therapy in Periprocedural, Regional Anesthesia and/or Pain Procedure Settings – Adult – Inpatient/Ambulatory - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Hematology and Coagulation


1
Management of Antithrombotic Therapy
in the Setting of Periprocedural,
Regional Anesthesia and/or Pain
Procedures – Adult –
Inpatient/Ambulatory
Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
EXECUTIVE SUMMARY ........................................................................................................... 3
SCOPE ................................................................................................................................... 3
METHODOLOGY .................................................................................................................... 4
DEFINITIONS.......................................................................................................................... 5
INTRODUCTION ..................................................................................................................... 5
RECOMMENDATIONS ............................................................................................................ 5
UW HEALTH IMPLEMENTATION ........................................................................................... 14
APPENDIX A. EVIDENCE GRADING SCHEME(S) ...................................................................... 16
REFERENCES ........................................................................................................................ 16
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Contact for Content:
Name: Anne Rose, PharmD ± Pharmacy
Phone Number: (608) 263-9738
Email Address: arose@uwhealth.org
Contact for Changes:
Name: Philip Trapskin, PharmD, BCPS ± Pharmacy
Phone Number: (608) 165-0341
Email Address: ptrapskin@uwhealth.org
Guideline Author(s):
Anne Rose, PharmD ± Anticoagulation Stewardship, Pharmacy
Coordinating Team Members:
Alaa Abd-Elsayed, MD ± Anesthesia and Director of UW Health Pain Services
David Ciske, MD ± Medical Director: Anticoagulation Clinic and Internal Medicine
Erin Robinson, PharmD, CACP ± Anticoagulation Clinic
Michael Ford, MD ± Anesthesia
$QQH�2¶&RQnor, MD ± Cardiology
Patrick Pfau, MD ± Gastroenterology
Kristopher Schroeder, MD ± Anesthesia
Scott Springman, MD ± Anesthesia
Krystal Weierstahl, MD ± Anesthesia
Review Individuals/Bodies:
Inpatient Anticoagulation Committee ± November 14, 2016
Ambulatory Anticoagulation Committee ± November 28, 2016
Committee Approvals/Dates:
Pharmacy & Therapeutics Committee (Last Periodic Review: August 2015)
ξ Interim revisions (December 15, 2016)
Release Date: December 2016 | Next Review Date: October 2017
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Executive Summary
Guideline Overview
The following guideline provides recommendations for patients receiving antithrombotic therapy
and who require surgery, other invasive procedures, neuraxial or peripheral nerve procedures
and spine pain procedures. Evaluating thromboembolic and bleeding risks are outlined, as well
as considerations for administering antithrombotic therapy in the periprocedural setting and prior
to regional anesthesia pain interventions.
Key Revisions (Interim Update November 2016)
1. Addition of recommendations for spinal pain procedures
2. Update to recommendations for antiplatelet agents when used for cardiac stents
Key Practice Recommendations
1. Recommendations for periprocedural antithrombotic management on the following:
ξTable_1 Procedural bleeding risk
ξTable_2 Evaluating individual thrombotic risk
ξTable_3 Endoscopic procedures
ξTable_4 Warfarin
ξTable_5 Creating a bridge plan for warfarin
ξTable_6 Direct oral anticoagulants
ξTable_8 Parenteral anticoagulants
ξTable_10 Antiplatelet agents
2. Recommendations for antithrombotic agents in neuraxial anesthesia and interventional
spine pain procedures:
ξTable_11 Antithrombotics and neuraxial anesthesia
ξTable_12 Antithrombotics and spine pain procedures
Companion Documents
1. UW Health Procoagulant Therapy for Bleeding Associated with Acquired Bleeding Disorders
- Adult - Guideline
2. Peri-operative Medication Management ± Adult ± Guideline
Scope
Disease/Condition(s): Any disease or condition that would necessitate the need for anticoagulant,
antiplatelet, or thrombolytic therapy. (ex. atrial fibrillation, cardiac disease, stroke)
Clinical Specialty:
Surgical services
Proceduralists
Anesthesia Pain Service
Primary care providers
Hospitalists
Anticoagulation clinic
Intended Users:
Physicians, Advanced Practice Providers, Pharmacists, Nurses
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Objective(s): To assist clinicians with providing recommendations for holding, bridging and
resuming antithrombotic therapy for procedures and holding, administering and resuming
antithrombotic therapy for neuraxial analgesia and spine pain procedures.

Target Population: Adult patients who have indication(s) for antithrombotic medications that
require either a surgical procedure and/or the need for neuraxial analgesia or spine pain
procedure.

Interventions and Practices Considered:
ξ Identification of high risk patients in need of periprocedural bridging
ξ Consideration of bleeding risks for procedures
ξ Recommendations for antithrombotic medications by drug class
ξ Recommendations for antithrombotic medications prior, during and after spinal/epidural
catheter placement
ξ Recommendations for antithrombotic medication prior and after spine pain procedures.

Major Outcomes Considered:
ξ Thromboembolic events in the absence of antithrombotic therapy in the periprocedural
setting
ξ Hemorrhagic events with antithrombotic therapy in the periprocedural setting
ξ Hemorrhagic events with antithrombotic therapy with epidural or spinal catheter placement
and removal
ξ Hemorrhagic events with antithrombotic therapy with spine pain procedures
Methodology
Methods Used to Collect/Select the Evidence:
Electronic database searches (e.g., PUBMED) were conducted by the guideline author(s) and
workgroup members to collect evidence for review. Expert opinion and clinical experience were
also considered during discussions of the evidence.

Methods Used to Formulate the Recommendations:
The workgroup members agreed to adopt recommendations developed by external
organizations and/or arrived at a consensus through discussion of the literature and expert
experience. All recommendations endorsed or developed by the guideline workgroup were
reviewed and approved by other stakeholders or committees (as appropriate).

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 in Appendix A).

Rating Scheme for the Strength of the Evidence/Recommendations:
See Appendix A for the rating scheme(s) used within this document.


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Recognition of Potential Health Care Disparities:
Under or uninsured patients may have difficulty acquiring low molecular weight heparin or other
agents commonly used for bridging in the periprocedural period due to cost. In some situations
direct oral anticoagulants may be considered. Thromboembolic risks while off anticoagulant
therapy should be discussed with the patient. The medication assistance program may be able
to assist with acquiring medications.
Definitions
1. 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 10-12 day period.1

2. Regional anesthesia ± includes techniques and administration of analgesics through the
epidural or intrathecal routes. Also referred to as neuraxial analgesia or spinal/epidural
analgesia.

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.34

The use of antithrombotics for venous thromboembolism (VTE) prevention, VTE treatment,
cardiac and vascular disease, and the use of thrombolytics can increase the risk of spinal
hematoma if these medications are not appropriately held prior to, during and after removal of
an epidural catheter or spinal pain procedure. Spinal hematoma, while rare, is a serious
complication that is closely associated with antithrombotic administration during spinal and
epidural analgesia.5

This guideline will be separated into 2 sections for antithrombotic management: Periprocedural
and Neuraxial Anesthesia/Spinal Pain Procedures.

Recommendations

Periprocedural Antithrombotic Management

1. Weigh the consequences of short-term risk for thromboembolism and bleeding for the
individual patient.1
1.1. Only high risk patients should be considered for periprocedural anticoagulation
or bridging therapy3-4 (UW Health moderate quality of evidence, weak/conditional
recommendation)
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
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effects than compared to consequences of major bleeding1-2. (UW Health low quality of
evidence, weak/conditional recommendation)
1.3. Use Table 1 to evaluate the bleeding risk of procedure or surgery1 (UW Health low
quality of evidence, weak/conditional recommendation)Use Table 2 to identify patients at
risk for systemic embolism if antithrombotic agent is discontinued1-4 (UW Health
moderate quality of evidence, weak/conditional recommendation)
1.3.1. It is recommended to use periprocedural (bridge) therapy for patients identified
in Table 2.1-4 (UW Health moderate quality of evidence, weak/conditional
recommendation)
1.3.2. There are specific recommendations provided for endoscopic and breast
biopsy procedures in section 2 and 3 of this guideline.

Table 1. Bleeding Risk for Surgery/Procedure1,7,8
Bleed Risk Surgery/Procedure Type
High ξ Aortic aneurysm repair
ξ Bladder surgery
ξ Bowel polypectomy
ξ Coronary artery bypass grafting (CABG)
ξ Heart valve replacement
ξ Intracranial surgery
ξ Major cancer surgery
ξ Major orthopedic surgery (hip or knee replacement)
ξ Peripheral artery bypass and other major vascular surgery
ξ Prostate surgery
ξ Reconstructive plastic surgery
ξ Spinal surgery/Epidural procedure
Moderate ξ Renal biopsy
ξ Resection of colon polyps
ξ Prostate biopsy
ξ Pacemaker or defibrillator implantation
ξ Major intraabdominal surgery
ξ Major intrathoracic surgery
ξ More invasive dental or ophthalmic procedures
Low ξ Cataract surgery
ξ Dental procedures
Dental hygiene
Simple extractions
Restorations
Endodontics
Prosthetics
ξ Cutaneous surgeries (most)
ξ Laparoscopic cholecystectomy or hernia repair
ξ Coronary angiography
ξ Endoscopy with or without biopsy
ξ Colonoscopy with or without biopsy


Table 2. Periprocedural Risk for Thromboembolism1,3,4,9
Risk High:
Periprocedural Anticoagulation advised
Mechanical Heart
Valve
ξ Any mechanical mitral valve
ξ Older mechanical valve model (caged ball or tilting disc) in mitral or
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aortic position
ξ Recently placed mechanical valve (< 3 months) in mitral or aortic
position
ξ Recent stroke or TIA (within 6 months) with mitral or aortic valve
Atrial Fibrillation

ξ With mechanical heart valve in mitral or aortic position
ξ With recent stroke or TIA (within 3 months)
Venous
Thromboembolism
ξ VTE within previous 3 months


2. Endoscopic procedures
2.1. For low thromboembolic risk patients1,6,7 (UW Health moderate quality of evidence,
weak/conditional recommendation)
2.1.1. Hold warfarin and proceed with endoscopic procedure when the INR < 1.5
2.1.2. Other anticoagulants see specific recommendations in Tables 5-8.
2.2. For high thromboembolic risk patients: see Table 3. Hold anticoagulation
based on specific recommendations for each drug listed in Tables 5-8. 16,7 (UW Health
moderate quality of evidence, weak/conditional recommendation)

Table 3. Anticoagulation Considerations for Endoscopic Procedures1,7,8
Endoscopic Procedure High Thromboembolic Risk
Diagnostic or Screening Hold anticoagulation*
Create bridge plan (see Table 5)
Low biopsy risk
Removal of < 10 mm polyps with cold
snare or forceps
Hold anticoagulation*
Create bridge plan (see Table 5)
Large polyp removal (> 10 mm) Hold anticoagulation*
Create bridge plan (see Table 5)
Sphincterotomy
Esophageal Dilation
Fine Needle Aspiration
Hold anticoagulation*
Create bridge plan (see Table 5)
*See individual anticoagulant recommendations for holding prior to procedure

3. Warfarin1,8-10
3.1. Assess INR at least 7 days before surgery or procedure to allow for planning of
perioperative management. (UW Health moderate quality of evidence, strong
recommendation)
3.2. Warfarin may be continued during procedures where bleed risk is low.1,8, (UW
Health moderate quality of evidence, weak/conditional recommendation)
3.2.1. Simple dental procedures (including extractions) if there is coadministration
of an oral prohemostatic agent. (If no oral prohemostatic agent is
coadministered, then warfarin should be held for 2-3 days before the
procedure)
3.2.2. Cataract surgery
3.2.3. Diagnostic or screening colonoscopies
3.2.4. Some cutaneous surgeries
3.2.5. For endoscopic procedures ± see Table 3
3.3. Check INR within 24 hours of surgical procedure to ensure that INR goal has been
attained.1 (UW Health low quality of evidence, weak/conditional recommendation)
3.4. If a bridge plan is needed see Table 6 for assistance
3.4.1. The most common bridge plan incorporates a 5 day warfarin hold
3.4.2. A 3 day warfarin hold or bridging in the post-procedural phase can also
be considered
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3.5. 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 if the procedure or surgery
cannot be delayed. (UW Health moderate quality of evidence, weak/conditional
recommendation)

Table 4 Periprocedural planning for warfarin1,8-10
Drug Pre-procedure
INR
Last Dose Prior to Procedure Post Procedure Plan
Warfarin 2.0 ± 3.0 5 days

Within 24 hours after surgical
procedure or on postoperative day 1
if hemostasis is achieved and if
approved by surgeon
3.0 ± 4.5 6 days

> 4.5 6-7 days
Recheck INR after 2-3 days of held doses
If indicated consider phytonadione

Table 5. Example of a warfarin 5 day hold with low molecular weight heparin (LMWH) peri-
procedural bridge plan


Date LMWH AM LMWH PM Warfarin
Day 5

Hold Hold Hold
Day 4

Hold Hold Hold
Day 3
Bridging Dose Bridging Dose Hold

Day 2
Bridging Dose Bridging Dose Hold

Day 1
Bridging Dose Hold Hold

Procedure Day
Hold Hold Warfarin Dose

Post Day 1
Bridging Dose Bridging Dose Warfarin Dose

Post Day 2 Bridging Dose Bridging Dose Warfarin Dose

Post Day 3 Bridging Dose Bridging Dose Warfarin Dose

Post Day 4 Bridging Dose Bridging Dose Warfarin Dose

Post Day 5
Bridging Dose Bridging Dose
Warfarin Dose

Recheck INR


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4. Direct Oral Anticoagulants1,2,11-14 – Listed Alphabetically
4.1 Assess renal function at least 7 days before surgery to allow for planning of
perioperative management. Pre-operative parenteral anticoagulation (bridging) is
not needed. (UW Health low quality of evidence, weak/conditional recommendation)
4.2 If timing does not allow for reversal of anticoagulant effect from withholding doses
alone, administration of procoagulant agents may be necessary if the procedure or
surgery cannot be delayed. (UW Health low quality of evidence, weak/conditional
recommendation)
4.3 Tables 6 and 7 provide recommendations for periprocedural management (UW
Health moderate quality of evidence, weak/conditional recommendation)

Table 6 Pre-procedural planning for the direct oral anticoagulants11-14
Drug Pre-procedure
renal function
Minor or standard bleed risk
surgery last dose prior to
procedure
Major or high bleed risk surgery
last dose prior to procedure
Apixaban Scr < 1.5 mg/dL 24 hours 48 hours

Scr > 1.5 mg/dL 48 hours 72 hours

Dabigatran CrCl • 50 mL/min 1 - 2 days 2 ± 4 days

CrCl < 50 mL/min 3 ± 5 days

> 5 days
Edoxaban CrCl • 50 mL/min 24 hours 48 hours

CrCl < 50 mL/min 48 hours 72 hours

Rivaroxaban CrCl > 30 mL/min 24 hours 48 hours

CrCl < 30 mL/min 48 hours 72 hours


Table 7 Post-procedural planning for the direct oral anticoagulants11-14
Drug Minor surgery or Standard
bleed risk surgery resume
Major surgery or high bleed
risk surgery resume
Onset of
anticoagulation
Apixaban Within 24 hours
if approved by surgeon
Within 72 hours
if approved by surgeon
3 ± 5 hours
Dabigatran Within 24 hours
if approved by surgeon
Within 72 hours
if approved by surgeon
2 hours
Edoxaban Within 24 hours
if approved by surgeon
Within 72 hours
if approved by surgeon
2 hours
Rivaroxaban Within 24 hours
if approved by surgeon
Within 72 hours if approved by
surgeon
2 ± 4 hours




5. Parenteral Anticoagulants1,8,10,15-19 ± Listed Alphabetically
5.1 Parenteral anticoagulation may be used for periprocedural anticoagulation
management or bridging therapy in certain high risk patients.
5.2 If timing does not allow for reversal of anticoagulant effect from withholding doses
alone, administration of reversal agents or procoagulant agents may be necessary
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if the procedure or surgery cannot be delayed. (UW Health low quality of evidence,
weak/conditional recommendation)
5.3 Tables 8 and 9 provide recommendations for periprocedural management (UW
Health moderate quality of evidence, weak/conditional recommendation)

Table 8 Pre-procedural planning for parenteral anticoagulants15-19
Drug Pre-procedure Last dose prior to procedure
Argatroban Normal hepatic function 3 hours
Child-Pugh Score > 6 9 hours

Bivalirudin CrCl • 30 mL/min 1.5 hours
CrCl < 30 mL/min 3 hours
Enoxaparin Prophylactic Dosing 12 hours
Therapeutic Dosing 24 hours
Fondaparinux CrCl • 50 mL/min 3 days
CrCl < 50 mL/min 5 days
Unfractionated Heparin Prophylactic Dosing 12 hours
Therapeutic Dosing 4-6 hours

Table 9 Post-procedural planning for parenteral anticoagulants15-19
Drug Minor or standard bleed risk
surgery resume
Major surgery or high bleed
risk surgery resume
Onset of
anticoagulation
Argatroban Within 12 hours
if approved by surgeon
Within 24 hours
if approved by surgeon
30 minutes
Bivalirudin Within 12 hours
if approved by surgeon
Within 24 hours
if approved by surgeon
15 minutes
Enoxaparin Within 12-24 hours
if approved by surgeon

Within 72 hours
if approved by surgeon

3 ± 5 hours
Fondaparinux Within 24 hours
if approved by surgeon
Within 72 hours if approved
by surgeon
3 hours
Unfractionated
Heparin
Within 12 hours is approved
by surgeon
Within 24 hours
if approved by surgeon
Immediate

6. Antiplatelet Therapy1,20-23 ± Listed Alphabetically
6.1 For periprocedural management of antiplatelet therapy, assess use at least 7 days
before surgery or procedure to allow for adequate hold time. (UW Health moderate
quality of evidence, strong recommendation)
6.1.1 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 low quality of evidence, strong recommendation)
6.2 For patients with cardiac stents any interruption in antiplatelet therapy should be
coordinated with the surgeon, anesthesiologist and the prescribing provider. (UW
Health strong recommendation, low quality evidence)
6.2.1 If the prescribing provider is a non-UW provider, every effort should be
made to engage this provider in the coordination of care. If unable to
connect with the non-UW provider, it is reasonable to contact UW
Cardiology for recommendations. (UW Health conditional recommendation,
low quality evidence)
6.3 Antiplatelet use with cardiac stents for elective (non-cardiac) surgery:23
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6.3.1 Bare metal stent (BMS): surgery should not be performed within 30 days
after placement (UW Health moderate quality of evidence, strong
recommendation)
6.3.2 Drug eluting stent (DES): surgery should not be performed within 3
months after placement and should ideally be delayed 6 months after
placement (UW Health moderate quality of evidence, strong recommendation)
6.3.3 If surgical procedure requires discontinuation of antiplatelet therapy, it is
recommended to continue aspirin (if possible). (UW Health low quality of
evidence, strong recommendation)
6.4 Table 10 provide recommendations for periprocedural management (UW Health
moderate quality of evidence, weak/conditional recommendation)

Table 10 Periprocedural management for antiplatelet drugs1,20-22
Drug Last Dose Prior to Procedure Post-Procedure Plan
Aspirin
(low cardiovascular event risk)
7 ± 10 days Within 24 hours
if approved by surgeon
Aspirin
(high cardiovascular event risk)
May continue aspirin Within 24 hours
if approved by surgeon
Clopidogrel* 5 days Within 24-48 hours
if approved by surgeon
Cilostazol

1 -2 days Within 24 hours
if approved by surgeon
Dipyridamole

1 -2 days Within 24 hours
if approved by surgeon
Prasugrel* 5 ± 7 days Within 24-48 hours
if approved by surgeon
Ticagrelor* 5 days Within 24-48 hours
if approved by surgeon
*If used for cardiac stent notify WKH�SDWLHQW¶V�FDUGLRORJLVW�SULRU�WR�VWRSSLQJ�WKHUDS\�

Neuraxial Anesthesia, Interventional Spine and Pain Procedures and Antithrombotic
Management
Regional anesthesia and interventional spine and pain procedures have a broad range of risk
for spinal hematoma and therefore recommendations should consider both procedural and
patient-specific risk factors for bleeding. Spinal hematoma, while rare, is a serious complication
of spinal or epidural anesthesia and spine and pain procedures. Risk factors for the
development of spinal hematoma include: advanced age, underlying coagulopathy, difficult
needle placement and administration of antithrombotic agents with an indwelling neuraxial
catheter. To reduce the risk of spinal hematoma related to antithrombotics, discontinuation of
these agents should be timed appropriately when either neuraxial anesthesia is initiated,
continued and/or removed or when a spine and pain procedure is planned.5,24

7. Anticoagulants±
7.1. Prior to neuraxial anesthesia or a spine and pain procedure, a review of the patient
medication list, both current and prior to admission, should be reviewed for use of
an antithrombotic. 5,24 (UW Health moderate quality of evidence, strong
recommendation)
7.2. Tables 11 and 12 provide recommendations on holding anticoagulants prior to
spinal/epidural catheter placement or spine and pain procedures, use of
anticoagulants during neuraxial therapy, and for resuming anticoagulation after
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spina/epidural catheters have been removed or spine and pain procedures are
complete in intermediate to high risk procedures.
7.2.1. For low risk procedures consider bleeding risks and individual patient risk
factors to determine hold and resumption plan. (UW Health moderate quality
of evidence, weak/conditional recommendation)
7.2.2. No anticoagulant may be administered unless approved by the Anesthesia
Pain Service (APS). (UW Health low quality of evidence, strong recommendation)
7.2.3. Unfractionated heparin (subcutaneously) up to doses of 5,000 units every
8-12 hours have been approved for use by the APS with epidural catheters
(UW Health low quality of evidence, weak/conditional recommendation)

8. Antiplatelets
8.1. Prior to neuraxial anesthesia or a spine and pain procedure a review of the patient
medication list, both current and prior to admission, should be reviewed for use of
an antiplatelet.5,24 (UW Health moderate quality of evidence, strong recommendation)
8.2. Antiplatelet use for coronary artery stents in elective (non-cardiac) procedure:23
8.2.1. Bare metal stent (BMS): procedure should not be performed within 30 days
after placement (UW Health moderate quality of evidence, strong
recommendation)
8.2.2. Drug eluting stent (DES): procedure should not be performed within 3
months after placement and should ideally be delayed 6 months after
placement (UW Health moderate quality of evidence, strong recommendation)
8.2.3. If procedure requires discontinuation of antiplatelet therapy, it is
recommended to continue aspirin (if SRVVLEOH��DQG�FRQWDFW�WKH�SDWLHQW¶V�
cardiologist prior to stopping therapy. (UW Health low quality of evidence,
strong recommendation)
8.3. Utilize Tables 11 and 12 for recommendations on holding antiplatelets prior to
spinal/epidural catheter placement or spine and pain procedures, use of
antiplatelets during neuraxial therapy, and for resuming antiplatelets after
spinal/epidural catheters have been removed or spine and pain procedures are
complete. (UW Health moderate quality of evidence, weak/conditional recommendation)
8.3.1. No antiplatelets may be administered unless approved by the APS (UW
Health low quality of evidence, strong recommendation)
8.3.2. Aspirin up to doses of 325 mg twice daily and other non-steroidal anti-
inflammatory medications have been approved for use by the APS with
epidural catheters (UW Health low quality of evidence, weak/conditional
recommendation)

9. Thrombolytics
9.1. Prior to neuraxial anesthesia or a spine and pain procedure a review of the patient
medication list, both current and prior to admission, should be reviewed for use of a
thrombolytic.5,24 (UW Health moderate quality of evidence, strong recommendation)
9.2. Utilize Tables 11 and 12 for recommendations on using thrombolytics prior to
spinal/epidural catheter placement or spine and pain procedures, use of
thrombolytics during neuraxial therapy, and for using thrombolytics after
spinal/epidural catheters have been removed or spine and pain procedures are
complete. (UW Health low quality of evidence, weak/conditional recommendation)
9.2.1. No therapeutic dose of thrombolytic may be administered unless
approved by the APS (UW Health low quality of evidence, strong
recommendation)
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9.2.2. When administered via a chest tube into the intrapleural space, alteplase
should have minimal systemic absorption26. Use during spinal/epidural
analgesia must be approved by APS prior to use. (UW Health low quality of
evidence, weak/conditional recommendation)

Table 11 Antithrombotic Recommendations for Spinal/Epidural Analgesia
Oral Anticoagulants
Drug Name Last Dose Prior to
Placement
Restart After
Placement
Last Dose Prior to
Removal
Time to Restart
After Removal
Apixaban 3 days Contraindicated Contraindicated 6 hours
Dabigatran 5 days Contraindicated Contraindicated 6 hours
Edoxaban 3 days Contraindicated Contraindicated 6 hours
Rivaroxaban 3 days Contraindicated Contraindicated 6 hours
Warfarin Hold 4-5 days AND
INR < 1.2
Contraindicated Contraindicated 6 hours
Parenteral Anticoagulants
Drug Name Last Dose Prior to
Placement
Restart After
Placement
Last Dose Prior to
Removal
Time to Restart
After Removal
Argatroban 3 hours or until
aPTT < 35 sec
Contraindicated Contraindicated 6 hours
Bivalirudin 3 hours or until
aPTT < 35 sec
Contraindicated Contraindicated 6 hours
Enoxaparin
CrCl > 30 mL/min
CrCl < 30 mL/min
Therapeutic dose

12 hours
24 hours
24 hours

Contraindicated

Contraindicated

6 hours
Fondaparinux 4 days Contraindicated Contraindicated 6 hours
Unfractionated Heparin
(IV)
6 hours or until Xa
< 0.1 IU/mL
1 hour 4 hours AND Xa
<0.1 IU/mL
1 hour
Unfractionated Heparin
(SQ) 5000 units BID or
TID
6 hours Can restart
immediately
6 hours Can restart
immediately
Antiplatelet Agents
Drug Name Last Dose Prior to
Placement
Restart After
Placement
Last Dose Prior to
Removal
Time to Restart
After Removal
Aspirin Doses up to 325 mg BID may be given prior, during and after removal without any
time restrictions
Cilostazol 2 days Contraindicated Contraindicated 6 hours
Clopidogrel 7 days Contraindicated Contraindicated 6 hours
Dipyridamole 2 days Contraindicated Contraindicated 6 hours
NSAIDs NSAIDs may be given prior, during and after removal without any time restrictions
Prasugrel 7-10 days Contraindicated Contraindicated 6 hours
Ticagrelor 5-7 days Contraindicated Contraindicated 6 hours
Thrombolytics
Drug Name Last Dose Prior to
Placement
Restart After
Placement
Last Dose Prior to
Removal
Time to Restart
After Removal
Alteplase (Full dose) 10 days Contraindicated Contraindicated 10 days
Alteplase
(CVAD clearance)
May be given prior, during and after removal without any time restrictions
*If traumatic puncture occurs may consider delaying administration of antithrombotic 24-48 hours after removal if appropriate
Table 12 Antithrombotic Recommendations for High Risk Spine Pain Procedures
Oral Anticoagulants
Drug Name Last Dose Prior to Procedure Time to Restart After Procedure
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14


Apixaban 3-5 days 24 hours
Dabigatran 4-5 days
*6 days if renal impairment
24 hours
Edoxaban 3-5 days 24 hours
Rivaroxaban 3 days 24 hours
Warfarin Hold 5 days AND
INR < 1.2
24 hours
Parenteral Anticoagulants
Drug Name Last Dose Prior to Procedure Time to Restart After Procedure
Argatroban 4 hours or until aPTT < 35 sec 2 hours
Bivalirudin 4 hours or until aPTT < 35 sec 2 hours
Enoxaparin
Prophylactic dose
Therapeutic dose

12 hours
24 hours

24 hours
Fondaparinux 4 days 24 hours
Unfractionated Heparin (IV) 6 hours or until Xa < 0.1 IU/mL 2 hours
Unfractionated Heparin (SQ) 8-10 hours 2 hours
Antiplatelet Agents
Drug Name Last Dose Prior to Procedure Time to Restart After Procedure
Aspirin Primary prevention: 6 days
Secondary prevention: risk stratify
24 hours
Cilostazol 2 days 24 hours
Clopidogrel 7 days 12 ± 24 hours
Diclofenac 1 day 24 hours
Dipyridamole 2 days 24 hours
Etodolac 2 days 24 hours
Ibuprofen 1 day 24 hours
Indomethacin 2 days 24 hours
Ketorolac 1 day 24 hours
Meloxicam 4 days 24 hours
Nabumetone 6 days 24 hours
Naproxen 4 days 24 hours
Piroxicam 10 days 24 hours
Prasugrel 7-10 days 12 - 24 hours
Ticagrelor 5 days 12 - 24 hours
Thrombolytics
Drug Name Last Dose Prior to Procedure Time to Restart After Procedure
Alteplase (Full dose) 48 hours 48 hours
Alteplase (CVAD clearance) May be given prior to or after procedure without any time restrictions




UW Health Implementation
Potential Benefits:
This guideline will provide a standardized approach for the management of antithrombotic
agents in the periprocedural and neuraxial analgesia settings. Through limited use of
periprocedural bridging and appropriate timing of holding and administering antithrombotic
agents it would be expected to see a decrease in the number of bleeding events related to
antithrombotic agents in these settings.

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15


Potential Harms:
There remain areas where there is limited literature and clear recommendations regarding
periprocedural bridging with mechanical heart valves and significant heart valve disease, as well
as, the use of alteplase for catheter clearance and intrapleural use during neuraxial anesthesia.
In these situations clinical judgement, risk for thrombosis and bleeding risks will be weighed to
determine the management strategy.

As with any antithrombotic agent, choosing therapy may result in an increased risk for bleeding,
while withholding antithrombotic agents may result in an increased risk for thromboembolic
event.

Pertinent UW Health Policies & Procedures
1. UW Health Administrative Policy 8.92: Epidural and Intrathecal (Neuraxial) Analgesia

Patient Resources
Health Facts For You #4322: Epidural Analgesia
Health Facts For You #5915: Spinal Analgesia for Chronic Pain
Health Facts For You #6115: Stopping Anticoagulation and Antiplatelet Therapy
Health Facts For You #6404: Medicines, Herbs, and Vitamins Which Affect Bleeding
Health Facts For You #6915: Heparin (Unfractionated and Low Molecular Weight)
Health Facts For You #6325: Going Home After Spinal or Epidural Anesthesia

Guideline Metrics
1. Metric #1: 30 day thromboembolic event following procedure
2. Metric #2: 30 day bleeding event following procedure
3. Metric #3: appropriate antithrombotic hold time in relation to individual patient risk,
procedure, neuraxial catheter placement or removal, or prior to/after spine pain procedure
and the inappropriate administration of antithrombotic medications during neuraxial catheter
placement

Implementation Plan/Clinical Tools
1. Guideline will be posted on uConnect in a dedicated location for Clinical Practice Guidelines.
2. Content and hyperlinks within clinical tools, documents, or Health Link related to the
guideline recommendations (such as the following) will be reviewed for consistency and
modified as appropriate.
3. Guideline will be posted externally on UW Health Anticoagulation website:
www.uwhealth.org/anticoagulation

Best Practice Alerts (BPA)
Name: Epidural catheter ± no unapproved anticoagulants

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 rHSODFH�D�FOLQLFLDQ¶V�MXGJPHQW�RU�WR�HVWDEOLVK�D�SURWRFRO�IRU�DOO�SDWLHQWV��,W�LV�
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.

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16


Appendix A. Evidence Grading Scheme(s)

Figure 1. GRADE Methodology adapted by UW Health


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 The net benefit of the treatment is clear, patient values and circumstances
are unlikely to affect the decision.
Weak/conditional
Recommendation may be conditional upon patient values and
preferences, the resources available, or the setting in which the
intervention will be implemented.

References
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e350S.
2. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: Antithrombotic therapy
and prevention of thrombosis: American College of Chest Physicians Evidence-Based Clinical
Practice Guidelines (9th edition). CHEST. 2012;141: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):823-33.
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Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 12/2016CCKM@uwhealth.org

17


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Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 12/2016CCKM@uwhealth.org