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Warfarin Management - Adult - Inpatient

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Warfarin Management - Adult - Inpatient
Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
Table of Contents
EXECUTIVE SUMMARY ........................................................................................................... 3
SCOPE ...................................................................................................................................... 4
METHODOLOGY ...................................................................................................................... 5
DEFINITIONS ............................................................................................................................ 5
INTRODUCTION ....................................................................................................................... 5
RECOMMENDATIONS .............................................................................................................. 5
UW HEALTH IMPLEMENTATION ............................................................................................12
REFERENCES .........................................................................................................................13
APPENDIX A: QUALITY OF EVIDENCE AND STRENGTH OF RECOMMENDATION
GRADING MATRIX ..................................................................................................................14
Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
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2
CPG Contact for Content:
Name: Anne Rose, PharmD - Pharmacy
Phone Number: (608) 263-9738
Email Address: arose@uwhealth.org
CPG Contact for Changes:
Name: Philip Trapskin, PharmD, BCPS – Drug Policy
Phone Number: (608) 265-0341
Email Address: ptrapskin@uwhealth.org
Guideline Author(s):
Anne Rose, PharmD – Anticoagulation Stewardship
Coordinating Team Members:
Jennifer Lai, PharmD, BCPS – Pharmacy
Nikki Lubcke, PharmD – Pharmacy
Rebecca Schuman, PharmD – Pharmacy
Ashley Stromich, PharmD – Pharmacy
Katie Willenborg, PharmD – Pharmacy
Review Individuals/Bodies:
Teresa Darcy, MD – Clinical Pathology
Inpatient Anticoagulation Committee
Committee Approvals/Dates:
Anticoagulation Committees: November 2012; September 2015
Pharmacy and Therapeutics: February 2013; October
Release Date: October 2015 | Next Review Date: October 2018
Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
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3
Executive Summary
Guideline Overview
This guideline outlines the evidence for managing anticoagulation therapy with oral
vitamin K antagonist (warfarin). Evidence is based on recommendations from the
Antithrombotic Therapy and Prevention of Thrombosis, 9th edition: American College of
Chest Physicians Clinical Practice Guidelines. It provides recommendations for how to
initiate, dose adjust and monitor warfarin therapy.
Key Practice Recommendations
1. Initial warfarin dosing should be tailored based on patient bleed risk, potential
sensitivity to warfarin, indication, goal INR range, and if potential drug interactions
are present.
2. Daily warfarin dose adjustments should be based on current INR measurements and
prior to making a dose adjustment assess for any missed doses, drug interactions,
dietary intake or supplements, documentation of bleeding, or other changes that
may affect the INR.
3. Table 4 and 5 provide recommendations for warfarin dosing for INR goals of 2-3 and
2.5 -3.5.
Companion Documents
1. Warfarin Management – Adult – Ambulatory Clinical Practice Guideline
2. Atrial Fibrillation – Adult – Inpatient/Ambulatory Clinical Practice Guideline
3. Antithrombotics in Non-Valvular Atrial Fibrillation – Adult – Inpatient/Ambulatory
Clinical Practice Guideline
4. HealthDecisionTM Atrial Fibrillation Risk Stratification Tool
5. Mechanical Circulatory Device (MCD) – Adult – Inpatient/Ambulatory Clinical
Practice Guideline
6. Indications for Blood Product Transfusion – Adult – Inpatient/Ambulatory
Pertinent UW Health Policies & Procedures
1. UWHC Policy #2.3 Anticoagulation Monitoring by UW Anticoagulation Clinic
Pharmacists
Patient Resources
1. Health Facts For You #6900: Warfarin (Coumadin, Jantoven)
2. Health Facts For You #322: Food-Drug Interactions: Coumadin & Warfarin Diet
Interactions
3. Health Facts For You #6915: Heparin (Unfractionated and Low Molecular Weight)
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Scope
Disease/Condition(s):
This guideline will apply to any disease or condition requiring anticoagulation with oral vitamin K
antagonist (warfarin) therapy
Clinical Specialty:
General Medicine/Hospitalist
Cardiology
Pharmacy
Intended Users:
Physicians
Advanced Practice Providers
Pharmacists
Nurses
Objective(s):
To provide a strategy for the management of warfarin therapy in adult hospitalized patients
using a standardized process while offering an individualized assessment.
Target Population:
Adult inpatients either being initiated on warfarin or continued on home warfarin therapy during
hospitalization.
Interventions and Practices Considered:
This guideline provides strategies and recommendations designed to assist clinicians in
developing warfarin management plans. It begins with providing recommendations for target
INR ranges based on indication for use. It focuses on how to dose warfarin based on individual
patient risk factors, INR response, drug interactions, and dietary interactions.
Major Outcomes Considered:
Thromboembolic events while initiating and maintaining warfarin therapy
Hemorrhagic events while initiating and maintaining warfarin therapy
Need for reversal agents in the event of a bleeding event or emergent surgery/procedure.
Guideline Metrics:
Metrics will include time to target INR range, sub and supratherapeutic INR values, critical INR
values, appropriate dose adjustments based on drug and dietary interactions while receiving
warfarin therapy.
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5
Methodology
Methods Used to Collect/Select the Evidence:
(1) completing a comprehensive literature search of electronic databases; (2) conducting an in-
depth review of relevant abstracts and articles; (3) conducting thoughtful discussion and
interpretation of findings; (4) ranking strength of evidence underlying the current
recommendations that are made.
Methods Used to Assess the Quality and Strength of the Evidence:
A similar grading system for the recommendations from the American College of Chest
Physicians was utilized.
Rating Scheme for the Strength of the Evidence:
For all other recommendations a modified Grading of Recommendations Assessment,
Development and Evaluation (GRADE) developed by the American Heart Association and
American College of Cardiology (Figure 1.) has been used to assess the Quality and Strength of
the Evidence in this Clinical Practice Guideline.1
Definitions
1. Baseline INR: For scheduled surgical patients the INR must be resulted within the
electronic medical record and within the past 30 days and for all other patients the INR
must be within 72 hours of warfarin order and prior to verification of the warfarin dose.
2. Current INR: an INR reported on the same calendar date as the scheduled warfarin dose
Introduction
Warfarin is a medication with a narrow therapeutic index that relies on a targeted range for
efficacy and reduction of complications.2 With this narrow therapeutic range, warfarin is
associated with bleeding complications, longer lengths of stays, adverse drug reactions, and
higher hospitalization costs.2,3 It is recommended to use standardized and validated dosing and
monitoring tools for most patients on warfarin therapy.4
Warfarin inhibits the reduction of vitamin K epoxide which limits the activation of vitamin K
dependant clotting factors II, VII, IX and X. Warfarin is highly protein bound with a half-life of
36-42 hours. It is metabolized by the cytochrome P450 enzymes: 2C9, 1A2, and 3A4.2
This guideline provides recommendations that are based on the evidence outlined from the
Antithrombotic Therapy and Prevention of Thrombosis 9th edition: American College of Chest
Physicians Clinical Practice Guidelines (CHEST).2,4-8
Recommendations
1. INR goals and duration of therapy listed in Table 1 are recommended by the CHEST
guidelines.2,4-8 (Class I, Level B)
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1.1. Exceptions include orthopedic surgery INR goals which are recommendations provided
by UW Health Orthopedic surgeon consensus and based on the American Association
of Orthopedic Surgeons clinical guideline on Prevention of Symptomatic Pulmonary
Embolism in Patients Undergoing Total Hip or Knee Arthroplasty9 (Class IIb, Level C)
1.2. Alternative INR goals may be chosen for specific patients when bleeding risk outweighs
clotting risk and will be determined by the individual’s provider (Class IIb, Level C)
Table 1. Indications for Antithrombotics, INR Ranges, and Duration of Therapy2,4-9
Indication INR
(Range)
Duration Comments
Thrombophilia with Thromboembolic Event4
Antiphospholipid Syndrome 2.5 (2-3) Chronic
Homozygous Factor V Leiden 2.5 (2-3) Chronic
Deficiency of Protein C, S or Anti-
Thrombin
2.5 (2-3) Chronic
Atrial Fibrillation (AF)/ Atrial Flutter5
CHA2DS2VASc = 0; Low stroke
risk
None May choose aspirin 75-325 mg
daily
CHA2DS2 VASc ≥ 1;
Intermediate/High stroke risk
2.5 (2-3) Chronic Anticoagulation CI: aspirin 75-325
mg and clopidogrel 75 mg daily
Pre-cardioversion (AF or flutter
>48 hours)
2.5 (2-3) 3 weeks
Post-cardioversion (in NSR) 2.5 (2-3) 4 weeks
Ischemic Stroke6
Non-cardioembolic stroke or TIA None Chronic Use antiplatelet therapy
Cardioembolic stroke or TIA
-With warfarin CI None Chronic Aspirin 81-325 mg daily
-With cerebral venous sinus
thrombosis
2.5 (2-3) 3-6 months
- With patent foramen ovale None Chronic Use antiplatelet therapy
Thromboembolism (DVT, PE) symptomatic or asymptomatic7
Provoked VTE event 2.5 (2-3) 3 months
Unprovoked: 1st VTE event
- Proximal or Distal DVT 2.5 (2-3) 3 months After 3 months evaluate risk-
benefit for extended therapy
- PE 2.5 (2-3) > 3 months After 3 months evaluate risk-
benefit for extended therapy
Unprovoked: 2nd VTE event
- DVT or PE 2.5 (2-3) > 3 months Consider chronic
With malignancy 2.5 (2-3) > 3 months LMWH preferred over warfarin
Consider chronic
Acute Upper Extremity DVT
- Associated with central
venous catheter that was
removed
2.5 (2-3) 3 months
- Associated with central
venous catheter that was
NOT removed
2.5 (2-3) Extended Continue anticoagulation until
catheter removed
- Not associated with a central
venous catheter
2.5 (2-3) 3 months
Spontaneous superficial vein
thrombosis
None 45 days Prophylaxis LMWH or
Fondaparinux
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Valvular Disease8
Rheumatic mitral valve disease
- Left atrial diameter < 55 mm None
- With AF, left atrial thrombus,
or left atrial diameter > 55 mm
2.5 (2-3) Chronic
Valve Repair
Aortic None Aspirin 81 mg daily
Mitral None 3 months Antiplatelet therapy
Valve Replacement - Bioprosthetic
Aortic or TAVI* None Antiplatelet therapy
Mitral 2.5 (2-3) 3 months Followed by aspirin 81 mg daily
* If other indication for anticoagulation exist – see specific indication for therapy recommendations
Valve Replacement - Mechanical
Aortic 2.5 (2-3) Chronic Low bleed risk: add aspirin 81 mg
Mitral 3 (2.5-3.5) Chronic Low bleed risk: add aspirin 81 mg
Dual Aortic and Mitral Valve 3 (2.5 -3.5) Chronic Low bleed risk: add aspirin 81 mg
Orthopedic Surgery9
Total Knee or Hip Arthroplasty* 1.8-2.2 10-14 days INR goal per UWHC Orthopedics
Hip Fracture Surgery* 1.8-2.2 10-14 days INR goal per UWHC Orthopedics
Trauma Surgery* 1.8-2.2 35 days INR goal per UWHC Orthopedics
* If other indication for anticoagulation exist - INR goal should be clarified
AF- atrial fibrillation; CAD – coronary artery disease; CI- contraindications; DVT- deep vein thrombosis; LMWH- low molecular
weight heparin; NSR- normal sinus rhythm; PE- pulmonary embolism; TIA- transient ischemic attack; TAVI - transcatether aortic
valve transplantation; VTE – venous thromboembolism
Patient Assessment
2. Patients newly started on warfarin should be assessed for risk factors that may make them
more sensitive to the effects of warfarin. If multiple high sensitivity risk factors are present
then a lower initiation dose or reduced maintenance dose may be needed.2,4(Class IIb,
Level C)
2.1. Table 2 identifies risk factors that may increase either INR response or bleeding risks.
Table 2. Factors for Identifying Warfarin Sensitive Patients2,4,10
Increased Warfarin Sensitivity
Increased INR Response Increased Bleeding Risk
Baseline INR ≥ 1.5 Current antiplatelet therapy
Age > 65 Thrombocytopenia: platelet <75 K/uL
Actual body weight < 45 kg or actual <
ideal
Significant hepatic disease:
cirrhosis or total bilirubin.>2.4 mg/dL
Malnourished/ NPO >3 days Alcohol abuse history
Hypoalbuminemia <2 g/dL End stage renal disease
Chronic diarrhea GI bleed within past 30 days
Significant drug interactions Surgery within past 2 weeks
Decompensated heart failure Intracranial bleed within past 30 days
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Initial Warfarin Dosing
3. Initial warfarin dosing should be tailored based on patient bleed risk, potential sensitivity to
warfarin, indication, goal INR range and if potential drug interactions are present2 (Class I,
Level C)
4. Warfarin should not be administered until a baseline INR has been resulted within the
medical record. (Class IIb, Level C)
5. A dose larger than the anticipated maintenance dose (loading dose) is inappropriate and
should not be used in most patients4 (Class IIb, Level C)
5.1 In healthy patients with acute VTE warfarin 10 mg for the first 2 days may be considered
followed by dosing based on INR measurements4,11,12(Class IIb, Level C)
6. Daily warfarin dose adjustments should be based on current INR measurements2,4 (Class I,
Level A))
7. Prior to making a dose adjustment assess for any missed doses, drug interactions, dietary
intake or supplements, documentation of bleeding, or other changes that may affect INR2,4
(Class I, Level C))
7.1 Tables 3 and 4 provide recommendations for warfarin dosing in the first 5 days of
therapy for INR goals of 2-3 or 2.5-3.5.
8. If appropriate, patients should receive another form of anticoagulation such as LMWH for at
least 5 days and until they are therapeutic on warfarin for 24-48 hours2,7 (Class I, Level B))
Table 4. Warfarin Dosing Protocol with INR Goal 2-3 (Class IIb, Level C)
High Sensitivity to Warfarin Low Sensitivity to Warfarin
INR Value Dose INR Value Dose
Day 1 <1.5 2.5 - 5 mg <1.5 5 - 7.5 mg
Day 2 <1.5
≥1.5
2.5 - 5 mg
0 - 2.5 mg
<1.5
≥1.5
5 - 7.5 mg
0 - 5 mg
Day 3 <1.5
1.5-1.9
2-2.5
≥2.6
5 mg
2.5 mg
1 mg
0 (no dose)
<1.5
1.5-1.9
2-2.5
≥2.6
7.5 mg
5 mg
2.5 mg
0 (no dose)
Day 4 <1.5
1.5-1.9
2-3
> 3
7.5 mg
5 mg
2.5 mg
0 - 1 mg
<1.5
1.5-1.9
2-3
>3
10 mg
7.5 mg
5 mg
0-2.5 mg
Day 5 <1.5
1.5-1.9
2-3
3-3.5
>3.5
10 mg
yesterday’s dose + 1 mg
yesterday’s dose
yesterday’s dose – 1 mg
0 (no dose)
<1.5
1.5-1.9
2-3
3-3.5
>3.5
12.5 mg
yesterday’s dose + 2.5 mg
yesterday’s dose
yesterday’s dose – 2.5 mg
0 (no dose)


If at any time INR increases > 0.5 consider reducing dose or if > 1 point consider holding dose
If holding for a high INR, restart warfarin at a reduced dose when INR is trending downward
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9
Table 5. Warfarin Dosing Protocol with INR Goal 2.5-3.5 (Class IIb, Level C)
High Sensitivity to Warfarin Low Sensitivity to Warfarin
INR Value Dose INR Value Dose
Day 1 < 1.5 2.5 - 5 mg < 1.5 5 - 7.5 mg
Day 2 < 1.5
≥ 1.5
2.5 - 5 mg
0 - 2.5 mg
< 1.5
≥ 1.5
5 - 7.5 mg
0 - 5 mg
Day 3 < 1.5
1.5-1.9
2.0-2.5
≥ 2.5
5 - 7.5 mg
5 mg
2.5 mg
0 ( no dose)
< 1.5
1.5-1.9
2.0-2.5
≥ 2.5
7.5 - 10 mg
7.5 mg
5 mg
0 (no dose)
Day 4 < 1.9
2.0-2.4
2.5-3.5
≥ 3.6
7.5 mg
5 mg
2.5 mg
0 - 1 mg
< 1.9
2.0-2.4
2.5-3.5
≥ 3.6
10 mg
7.5 mg
5 mg
0-2.5 mg
Day 5 < 1.9
2.0-2.4
2.5-3.5
3.6-4.0
≥ 4.0
10 mg
yesterday’s dose + 2.5 mg
yesterday’s dose
yesterday’s dose – 2.5 mg
0 (no dose)
< 1.9
2.0-2.4
2.5-3.5
3.6-4.0
≥ 4.0
12.5 mg
yesterday’s dose + 2.5 mg
yesterday’s dose
yesterday’s dose – 2.5 mg
0 (no dose)
If at any time INR increases > 0.5 consider reducing dose or if > 1 point consider holding dose
If holding for a high INR, restart warfarin at a reduced dose when INR is trending downward
Maintenance Warfarin Dosing
9. For patients on warfarin prior to admission and if there are no changes to medications or
medical condition that would affect the INR, their home dose may be resumed. (Class I,
Level C)
10. Warfarin should be adjusted based on current INR measurements2,4(Class I, Level A)
11. Prior to making a dose adjustment assess for any missed doses, drug interactions, dietary
intake or supplements, documentation of bleeding, or other changes that may affect the INR
level.2,4 (Class I, Level C)
Laboratory Monitoring
12. INR
12.1 A baseline INR must be resulted in the EMR prior to verification of the first dose of
warfarin (Class IIb, Level C)
12.2 A current INR must be resulted in the EMR prior to verification of the warfarin dose
adjustment (Class IIb, Level C)
12.3 Obtain daily INR for patients with daily warfarin dosing (Class IIb, Level C)
12.4 Obtain a weekly INR (at minimum) for patients who have been maintained on a
consistent warfarin dose with no changes in medications or medical condition that
would affect the INR. (Class IIb, Level C)
12.5 Upon discharge from the hospital an INR should be obtained within 3-4 days or at the
next scheduled INR visit if there are no changes in medications or medical conditions
that would affect the INR (Class IIb, Level C)
13. CBC should be obtained prior to initiating warfarin (baseline) and a minimum of every 3 days
thereafter (Class IIb, Level C)
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10
14. Urine HCG (pregnancy test) should be obtained for women of child bearing age before
initiating warfarin.2,4 (Class IIb, Level C)
Drug Interactions
Most drug interactions with warfarin will start to have an effect within 3-5 days of
concomitant therapy. There are some notable exceptions which include amiodarone,
carbamazepine, and rifampin which have a delayed effect after 7-14 days of dual
therapy.2,4,13,14 Tables 6 and 7 outlines potential drug-drug, drug-food, and drug-herb
interactions. Bolded medications are considered significant interactions. This table is
not all inclusive.
15. For most drug interactions with warfarin it is recommended to either increase or
decrease (based on expected INR response) the weekly dose by 30% (Class IIb,
Level C)
15.1 For amiodarone target a 50% reduction in weekly maintenance dose for
warfarin after 7-14 days of dual therapy13 or if initiating warfarin start at 2.5
mg dose. (Class IIb, Level C)
15.2 For rifampin target a 50% increase in weekly maintenance dose for warfarin
after 7-14 days of dual therapy.13 (Class IIb, Level C)
Table 6. Medications, dietary supplements and food that INCREASE INR or bleeding risk.2,4,13,14
Drug Class Known Interaction Probable Interaction Possible
Interaction
Unlikely
Interaction
Anti-Infective Ciprofloxacin
Erythromycin
Fluconazole
Isoniazid
Metronidazole
Miconazole
Miconazole Vaginal
Suppository
Moxifloxacin
Sulfamethoxazole
Voriconazole
Amoxicillin/clavulanate
Azithromycin
Clarithromycin
Itraconazole
Ketoconazole
Levofloxacin
Ritonavir
Tetracycline
Amoxicillin
Chloramphenicol
Darunavir
Daptomycin
Etravirine
Ivermectin
Nitrofurantoin
Norfloxacin
Ofloxacin
Saquinavir
Telithromycin
Terbinafine
Cefotetan
Cefazolin
Tigecycline
Cardiovascular Amiodarone*
Clofibrate
Diltiazem
Fenofibrate
Propafenone
Propranolol
Aspirin
Fluvastatin
Quinidine
Ropinirole
Simvastatin
Disopyramide
Gemfibrozil
Metolazone
Analgesics,
Anti-
Inflammatory
Piroxicam Acetaminophen
Aspririn
Celecoxib
Tramadol
Indomethacin
Propoxyphene
Sulindac
Tolmentin
Topical Salicylates
Methylprednisolo
ne
Nabumetone
CNS Drugs Alcohol
Citalopram
Entacapone
Sertraline
Disulfiram
Chloral hydrate
Fluvoxamine
Phenytoin
Felbamate Diazepam
Fluoxetine
Quetiapine
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GI Drugs and
Food
Cimetidine
Mango
Omeprazole
Grapefruit Orlistat
Herbal
Supplement
Fenugreek
Feverfew
Fish Oil
Ginkgo
Quilinggao
Dandelion
Danshen
Don Quai
Lycium
PC-SPES
Red or Sweet Clover
Capsicum
Forskolin
Garlic
Ginger
Turmeric
Other Anabolic Steroids
Capecitabine
Zileuton
Fluorouracil
Gemcitabine
Levamisole
Paclitaxel
Tamoxifen
Tolterodine
Acarbose
Cyclophosphamide
Danazol
Iphosphamide
Trastuzumab
Etoposide
Carboplatin
Levonorgestrel
Table 7. Medications, dietary supplements and food that DECREASE INR.2,4,13,14
Drug Class Known
Interaction
Probable Interaction Possible
Interaction
Unlikely
Interaction
Anti-Infective Griseofulvin
Nafcillin
Ribavirin
Rifampin*
Dicloxacillin
Ritonovir
Rifapentine
Terbinafine
Nelfinavir
Nevirapine
Cloxacillin
Rifaximin
Teicoplanin
Cardiovascular Cholestyramine Bosentan Telmisartan Furosemide
Analgesics, Anti-
Inflammatory
Mesalamine Azathioprine Sulfasalazine
CNS Drugs Barbiturates
Carbamazepine
Chlordiazepoxide Propofol
GI Drugs and
Food
High content
vitamin K food
Avocado
Soy milk
Sucralfate
Sushi containing
seaweed
Herbal
Supplement
Alfalfa Ginseng
Multivitamin
St. John’s Wort
Parsley
Chewing Tobacco
Co-Enzyme Q10
Yarrow
Licorice
Green Tea
Other Mercaptopurine
Chewing Tobacco
Chelation Therapy
Influenza vaccine
Raloxifene
Cyclosporine
Etretinate
Ubidecarenone
Dietary Interactions
Patients on long term warfarin therapy can be sensitive to the fluctuating levels of vitamin K
from both external dietary sources and internal gastrointestinal sources. Increased dietary
intake of vitamin K from either food sources or nutritional supplement sources can reduce the
effectiveness of warfarin and decrease the INR. Since warfarin is a high protein bound drug
with up to 99% of the drug bound to plasma proteins, patients who are malnourished with low
albumin levels will have higher concentrations of unbound drug and may experience faster INR
response. Conversely, patients receiving enteral nutrition will have more bound drug due to the
high protein concentration in these products.2,13,15-17
16. Promote consistent intake of dietary vitamin K and not avoidance2 (Class I, Level C)
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12
17. For enteral nutrition hold the tube feed 1 hour before and 1 hour after warfarin
administration15,17 (Class IIa, Level B)
17.1 If unable to hold enteral nutrition, increase warfarin dose until a therapeutic INR is
achieved17(Class IIb, Level B)
17.2 If on cycled tube feeding, administer warfarin at a time when tube feeds are off17,18
(Class IIa, Level B)
Warfarin Reversal
The treatment for warfarin reversal should be based on the indication for use, location of bleed,
severity of bleed and the extent of INR elevation. Guidelines for reversal of warfarin are available
within the UW Health Adult Procoagulant Therapy for Treatment of Non-Hemophiliac Bleeding
Clinical Practice Guideline.2,4
Transitioning to Outpatient Management
18. Communication describing either warfarin initiation and/or management during the inpatient
stay, along with the expected next INR check, should be communicated to the next provider
of care.(Class IIb, Level C)
18.1 Communication may occur electronically for patients who are managed in a UW
Health clinic or by phone/fax for a patient who is managed in a non-UW Health clinic.
UW Health Implementation
Potential Benefits:
This guideline will provide a resource for standardizing the approach to warfarin management
for an individual patient. Individualization of a warfarin management plan should result in lower
incidence of supra-therapeutic and critical INR results, minimize the risk for bleeding events and
provide guidance for managing drug and dietary interactions.
Potential Harms:
Warfarin is a complex medication that requires close monitoring to prevent adverse events.
While significant bleeding more commonly occurs when the INR is above the therapeutic range,
it, may also occur when the INR is within or slightly below target INR range. Bleeding is the
most common adverse event of warfarin for which to monitor. Additionally, if the INR remains
sub-therapeutic for an extended time there is the risk for thromboembolic events.
Qualifying Statements
Despite providing recommendations to manage many common scenarios, there may be
external factors that can influence the INR and dosing of warfarin that are not provided in this
guideline. Since standardization of warfarin management is unrealistic, clinical judgement
should be used when indicated to prevent unwanted adverse events
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Implementation Plan/Tools
Recommendations provided in this guideline will be disseminated to inpatient staff through a
variety of venues including newsletters, pharmacy inservice and additional tools as described
below:
1. Guideline will be housed on U-Connect in a dedicated folder for CPGs.
2. Guideline will also be posted on UW Health Anticoagulation Website:
www.uwhealth.org/anticoagulation
3. Release of the guideline will be advertised in the Pharmacy Department weekly newsletter.
4. Links to this guideline will included in the Warfarin – Adult – Supplemental Order Set and
included in the Warfarin Management protocol
Disclaimer
CPGs are described to assist clinicians by providing a framework for the evaluation and
treatment of patients. This Clinical Practice 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.
References
1. Tricoci P, Allen J, Kramer J, et al. Scientific evidence underlying the ACC/AHA Clinical Practice
Guidelines. JAMA. 2009;301(8):831-841.
2. Ageno W, Gallus AS, Wittkowsky A, et al. Oral Anticoagulant Therapy: Antithrombotic Therapy
and Prevention of Thrombosis, 9th ed. American College of Chest Physicians Evidence Based
Clinical Practice Guidelines. CHEST. 2012;141:e44s-88s.
3. Fanikos J, Stapinski C, Koo S, et al. Medications errors associated with anticoagulant therapy in
the hospital. Am J Cardiol. 2004; 94:532-535
4. Holbrook A, Schulman S, Witt D, et al. Evidence Based Management of Anticoagulant Therapy:
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed. American College of Chest
Physicians Evidence Based Clinical Practice Guidelines. CHEST. 2012;141:e152s-184s.
5. You J, Singer D, Howard P, et al. Antithrombotic Therapy for Atrial Fibrillation: Antithrombotic
Therapy and Prevention of Thrombosis, 9th ed. American College of Chest Physicians Evidence
Based Clinical Practice Guidelines. CHEST. 2012;141:e531s-575s.
6. Lansberg M, O’Donnell M, Khatri P, et al. Antithrombotic and Thrombolytic Therapy for Ischemic
Stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed. American College of Chest
Physicians Evidence Based Clinical Practice Guidelines. CHEST. 2012;141:601s-636s.
7. Kearon C, Akl E, Comerota A, et al. Antithrombotic Therapy for VTE Disease : Antithrombotic
Therapy and Prevention of Thrombosis, 9th ed. American College of Chest Physicians Evidence
Based Clinical Practice Guidelines. CHEST. 2012;141: 419s-494s.
8. Whitlock R, Sun J, Fremes S, et al. Antithrombotic and Thrombolytic Therapy for Valvular
Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed. American College of
Chest Physicians Evidence Based Clinical Practice Guidelines. CHEST. 2012;141:576s-600s.
9. American Academy of Orthopaedic Surgeons Clinical Practice Guideline of prevention of
symptomatic pulmonary embolism in patients undergoing total hip of knee arthroplasty.
Rosemont (IL): American Academy of Orthopaedic Surgeons (AAOS); 2007.63 p.
10. Pisters R, Lane DA, Nieuwlaat R, et al. A novel user friendly score (HAS-BLED) to assess 1 –
year risk of major bleeding in patients with atrial fibrillation : the Euro Heart Survey. CHEST.
2010 ;138 :1093-1100.
11. Harrison L, Johnston M, Massicotte MP, et al. Comparison of 5-mg and 10-mg loading doses in
initiation of warfarin therapy. Ann Intern Med. 1997; 126(2):133-6.
Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 10/2015CCKM@uwhealth.org

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12. Quiroz R, Gerhard-Herman M, Kosowsky JM, et al Comparison of a single end point to determine
optimal initial warfarin dosing (5 mg versus 10 mg) for venous thromboembolism. Am J Cardiol.
2006; 98(4):535-7.
13. Product Information: COUMADIN(R) oral tablets, intravenous injection, warfarin sodium oral
tablets, intravenous injection. Bristol-Myers Squibb Company, Princeton, NJ, 2010
14. Nutescu EA, Shapiro NL, Ibrahim S, et al (2006) Warfarin and its interactions with food, herbs
and other dietary supplements. Expert Opin Drug Saf 5(3):433-51.
15. Dickerson RN, Garmon WM, Kuhl DA, Minard G, Brown RO. Vitamin K-independent warfarin
resistance after concurrent administration of warfarin and continuous enteral nutrition.
Pharmacotherapy. 2008;28(3):308-313.
16. Klang M, Graham D, McLymont V. Warfarin bioavailability with feeding tubes and enteral
nutrition. JPEN J Parenter Enteral Nutr. 2010;34(3):300-304
17. Dickerson, RN. Warfarin resistance and enteral tube feeding: an old problem with a new solution.
Hosp Pharm. 2008;43(6): 520-524
18. Petretich DA. Reversal of osmolite warfarin interaction by changing warfarin administration time.
Clin Pharm. 1990;9(2):93
Appendix A: Quality of Evidence and Strength of Recommendation Grading Matrix
Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 10/2015CCKM@uwhealth.org