Related | Warfarin Management - Adult - Inpatient
Warfarin Management - Adult - Inpatient
Consensus Care Guideline
Population/Problem:
Warfarin is an anticoagulant used for the primary and secondary prevention of venous and
arterial thromboembolic events.1 The efficacy and safety of warfarin are dependent upon
achieving and maintaining a patient's INR within a target range. The complex pharmacokinetics,
pharmacodynamics, and pharmacogenomics of warfarin require regular monitoring and dosing
adjustments.
The guideline provides consensus recommendations for the initiation or continuation of warfarin
for hospitalized adults (e.g., target INR ranges, duration of therapy, dosing, monitoring).
Definitions
1. Baseline INR: (for patients not previously on warfarin)
• For scheduled surgical patients, the INR must be resulted within the electronic
medical record within the past 30 days
• 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: (for patients previously on warfarin)
• An INR reported on the same calendar date as the scheduled warfarin dose
Recommendations:
1. Indications for use, INR goals and duration of therapy are listed in Table 1
1.1. Alternative INR goals may be chosen when bleeding risk outweighs clotting risk as
determined by the individual’s provider (UW Health GRADE very low-quality evidence, C
recommendation)
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Table 1. Indications for use, INR Ranges, and Duration of Therapy
Table 1. Target INR Ranges and Duration of Therapy
Indication INR Goal
(Range)
Duration
Thrombophilia with Thromboembolic Event2-4
Antiphospholipid Syndrome 2.5 (2-3) Indefinite ACCP Grade 2B
Homozygous Factor V Leiden 2.5 (2-3) Indefinite
Protein C, S or Anti-Thrombin
deficiency
2.5 (2-3)
Indefinite
Atrial Fibrillation (AF)/Atrial Flutter5,6
Note: additional management information is available UW Health Atrial Fibrillation Guidelines
Prior stroke, transient ischemic
attack (TIA)
2.5 (2-3) Indefinite AHA/ACC/HRS Grade IA
For AF: CHA2DS2-VASc score of 2
or greater in men or 3 or greater in
women
2.5 (2-3) Indefinite AHA/ACC/HRS Grade IA
For AF: CHA2DS2-VASc score of 1
or greater in men or 2 or greater in
women
2.5 (2-3) Indefinite AHA/ACC/HRS Grade IIb, C-LD
Pre-cardioversion (AF or atrial flutter
>48 hours or unknown duration)
regardless of CHA2DS2VASc score
2.5 (2-3) At least 3-
weeks unless
the need for
immediate
cardioversion
AHA/ACC/HRS Grade IB
Post-cardioversion to normal sinus
rhythm
2.5 (2-3) At least 4-
weeks
AHA/ACC/HRS Grade IB
Cerebral Venous Thrombosis (CVT)7,8
Cerebral venous thrombosis (CVT) 2.5 (2-3) 3-6 months ACCP Grade 2B
Provoked CVT associated with a
transient risk factor (e.g., pregnancy,
dehydration, infection)
2.5 (2-3) 3-6 months AHA/ASA Grade IIb, C
Unprovoked CVT 2.5 (2-3) 6-12 months AHA/ASA Grade IIb, C
Recurrent CVT, VTE after CVT, or
first CVT with severe thrombophilia
2.5 (2-3) Indefinite AHA/ASA Grade IIb, C
Venous Thromboembolism (VTE)9,10
Note: additional management information is available UW Health VTE Diagnosis and Treatment
Guideline
Deep Vein Thrombosis (DVT) or
pulmonary embolism (PE)
2.5 (2-3) At least 3
months
Individualize the duration based
upon provoked events, risk
factors for thrombosis and
bleeding.
(Table continues on next page)
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Table 1. Target INR Ranges and Duration of Therapy (cont)
Indication INR Goal
(Range)
Duration
Valve Surgical Replacement – Bioprosthetic11,12
Aortic or Mitral Aspirin 75 mg to 100 mg per day is reasonable in all patients with a
bioprosthetic aortic or mitral valve. AHA/ACC IIa, B
Aortic or Mitral with low risk of
bleeding
2.5 (2-3) 3 to 6 months AHA/ACC IIa, B-NR
Valve Surgical Replacement – Mechanical11-13
Aortic bileaflet or current-generation
single-tilting disk and no risk factors
for thromboembolism
2.5 (2-3) Chronic AHA/ACC IB
Aortic with additional risk factors for
thromboembolic events (AF,
previous thromboembolism, LV
dysfunction, or hypercoagulable
conditions) or an older-generation
mechanical AVR (such as ball-in-
cage)
3 (2.5-3.5) Chronic AHA/ACC IB
Mitral 3 (2.5-3.5) Chronic AHA/ACC IB
Dual Aortic and Mitral Valve 3 (2.5 -3.5) Chronic AHA/ACC IB
On-X Aortic 2.5 (2-3) 3 months After 3 months consider
decrease the INR goal to 1.5-
2.0 (in conjunction with aspirin
81mg daily) AHA/ACC IIb, B-R
On-X Mitral 3 (2.5-3.5) Chronic AHA/ACC IB
Aspirin 75 mg to 100 mg daily is recommended in addition to anticoagulation with warfarin in patients with a
mechanical valve prosthesis. AHA/ACC IA
Anticoagulant therapy with oral direct thrombin inhibitors or anti-Xa agents should not be used in patients with
mechanical valve prostheses. AHA/ACC III:Harm
Transcatheter Aortic Valve Replacement (TAVR)12,14
Guideline
Pivotal Trials (Placement of
Aortic Transcatheter Valve
Trial [PARTNER] and US
CoreValve15-17
American College of
Cardiology/American
Heart Association
Guidelines 201712
European Society of
Cardiology/
European
Association for
Cardiothoracic
Surgery Guidelines
201718
First 3 to 6 months Aspirin plus clopidogrel for
first 3 or 6 months followed
by monotherapy
Clopidogrel 75mg daily
for the first 6 months in
addition to lifelong
aspirin 75-100mg
(AHA/ACC IIb, C)
Low-dose aspirin
plus P2Y12 inhibitor
for 3 to 6 months
followed by lifelong
single antiplatelet
therapy in patients
without indication for
oral anticoagulation
(ESC/EACTS IIb, C)
Lifelong treatment If vitamin K antagonist is
indicated, aspirin plus
warfarin (without clopidogrel)
Warfarin with an INR of
2.5 (2-3) for at least 3
months in patients with
low bleeding risk
(AHA/ACC IIb,B)
Lifelong oral
anticoagulants for
patients with
indication
(ESC/EACTS IC)
(Table continues on next page)
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Table 1. Target INR Ranges and Duration of Therapy (cont)
Indication INR Goal
(Range)
Duration
Orthopedic Surgery19
Total Knee or Hip Arthroplasty* 1.8-2.2 10-14 days INR goal per surgeon
Hip Fracture Surgery* 1.8-2.2 10-14 days INR goal per surgeon
Trauma Surgery* 1.8-2.2 35 days INR goal per surgeon
* If other indication for anticoagulation exist - INR goal should be clarified
Patient Assessment
2. Patients 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.1,2 (UW Health GRADE high quality
evidence, S recommendation) (see Table 2)
Table 2. Warfarin sensitivity factors
Increases sensitivity (usually require lower doses)
• Baseline (pre-warfarin) PT/INR (e.g., greater than 1.4)
• Advanced age (e.g., 60 years of age or older)20-29
• Underweight (e.g., BMI less than 18kg/m2)28,30,31
• Nutritional status (e.g., malnourished, low vitamin K intake/stores)
• Genetic factors (e.g., CYP2C9, VKORC1 phenotypes)
• Drug-drug interactions
• Hypoalbuminemia32,33
• Ethnicity (Asian)29,34,35
• Liver disease29,36
• Thyroid Disease (e.g., hyperthyroidism, Graves’ disease)37-40
• Heart Failure41,42
• Febrile illness
• Prolonged vomiting and diarrhea
• Surgery and blood loss
• Cannabinoids
• Alcohol
• Drug interactions
Decrease warfarin sensitivity (may require higher doses)
• Enteral feedings
• High-vitamin K intake
• Estrogens
• Chewing tobacco
Warfarin Dosing Considerations
3. Initial warfarin dosing should be tailored based on baseline INR, patient bleed risk, potential
sensitivity to warfarin (see Table 2), indication, goal INR range and if potential drug
interactions are present1 (UW Health GRADE high quality evidence, S recommendation)
4. 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 hours1,9 (UW Health GRADE
high quality evidence, S recommendation)
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5. Prior to making a dose adjustment, assess for any missed doses, drug interactions, dietary
intake or supplements, documentation of bleeding, change in medical condition or other
changes that may affect INR1,2 (UW Health GRADE moderate quality evidence, S
recommendation)(See Table 3)
5.1. Pregnant patients should not take warfarin and should be transitioned to an alternative
anticoagulant (e.g. low molecular weight heparin) (UW Health GRADE high quality
evidence, S recommendation)
6. Warfarin dosing should be based on current INR results and the dose should not be
administered until an INR has been resulted within the medical record. (UW Health GRADE
low quality evidence, C recommendation)
Table 3. Monitoring Considerations
• Signs and symptoms of thrombosis progression or bleeding
• PT/INR (daily during initiation or unstable, and at least weekly when stable)
• CBC without differential prior to warfarin initiation and then at least every 3 days
• Missed or held doses
• Drug-drug and drug-food interactions
• Nutrition
• Activity level
Table 4. Warfarin Dosing Protocol with INR Goal 2-3
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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Table 5. Warfarin Dosing Protocol with INR Goal 2.5-3.5
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
Laboratory Monitoring1,2 (UW Health GRADE low quality evidence, C recommendation)
Baseline
Within the past 30 days • Baseline INR
• Pregnancy test*
• CBC without diff
*Pregnancy test is not needed if:
1. Are postmenopausal (12 months of amenorrhea in a
woman > 45 years old in the absence of other biological
or physiological causes)
2. Had a hysterectomy or bilateral salpingo-oophorectomy
3. Have ovarian failure
4. Had a bilateral tubal ligation or other surgical
sterilization procedure
5. Are known to be pregnant
6. Have had a miscarriage or abortion in the last 7 days
7. Have given birth within the past 4 weeks
Within the past 90 days • ALT
• Creatinine
During Admission
Daily • INR If providing a daily warfarin dose
At least weekly • CBC without diff
• INR
If providing a weekly warfarin dose
After Discharge
Within 3-4 days • INR
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Drug Interactions
7. Most drug interactions with warfarin will start to have an effect within 3-5 days of
concomitant therapy. In general, it is recommended to check an INR 3-4 days after starting
a medication that has the potential to interact with warfarin. If the INR is affected at that
time, then a dose adjustment can be made. There are some notable exceptions to this:
Medication INR check after starting Adjustment
Amiodarone Every 7 days Target a 50% weekly dose reduction over 2 weeks
Rifampin Every 7 days Target a 50% weekly dose increase over 2 weeks
Fluconazole 2 – 3 days Target a 30% weekly dose decrease
Metronidazole 2 – 3 days Target a 30% weekly dose decrease
Sulfamethoxazole/
Trimethoprim
2 days
Should reduce dose prior to
starting medication to avoid
critical INR elevation
Target a 30% weekly dose decrease
(UW Health GRADE moderate quality evidence, S recommendation)
Table 6. Medications, dietary supplements, and food that INCREASE INR or bleeding risk.1,2,29,43
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
GI Drugs and
Food
Cimetidine
Mango
Omeprazole
Grapefruit Orlistat
Herbal
Supplement
Fenugreek
Feverfew
Dandelion
Danshen
Capsicum
Forskolin*
(Table continues on next page)
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Table 6. Medications, dietary supplements, and food that INCREASE INR or bleeding risk.,(cont)
Drug Class Known Interaction Probable Interaction Possible
Interaction
Unlikely
Interaction
Herbal
Supplement
Fish Oil
Ginkgo
Quilinggao
Don Quai
Lycium
PC-SPES
Red or Sweet Clover
Garlic
Ginger
Turmeric
Other Anabolic Steroids
Capecitabine
Zileuton
Fluorouracil
Gemcitabine
Levamisole
Paclitaxel
Tamoxifen
Tolterodine
Acarbose
Cyclophosphamide
Danazol
Iphosphamide
Trastuzumab
Etoposide
Carboplatin
Levonorgestrel
*Indicates significant interaction
Table 7. Medications, dietary supplements, and food that DECREASE INR.1,2,29,43
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
*Indicates significant interaction
Dietary Interactions
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.1,29,44-46
8. Promote consistent intake of dietary vitamin K and not avoidance1 (UW Health GRADE high
quality evidence, S recommendation)
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9. For enteral nutrition hold the tube feed 1 hour before and 1 hour after warfarin
administration44,46 (UW Health GRADE moderate quality evidence, S recommendation)
9.1 If unable to hold enteral nutrition, increase warfarin dose until a therapeutic INR is
achieved46(UW Health GRADE low quality evidence, C recommendation)
9.2 If on cycled tube feeding, administer warfarin at a time when tube feeds are off46,47
(UW Health GRADE moderate quality evidence, S recommendation)
10. A significant decrease (> 50%) in total dietary intake for >3 days may cause an increase in
INR.
Warfarin Reversal: see Antithrombotic Reversal- Adult- Inpatient guideline
Transitioning to Outpatient Management
Prior to discharge from the emergency department, urgent care, or hospital setting a follow up
care plan that includes contact with the provider or clinic who will manage warfarin, plan for a
follow up INR within 3-4 days of discharge, and education on compliance, dietary advice, follow
up monitoring and drug interactions and adverse drug reactions must be provided to the patient
and/or caregiver prior to ED discharge.1,2 If outpatient INR monitoring cannot be established at
the time of discharge then consider an alternative oral anticoagulant or parenteral anticoagulant.
Disclaimer
Consensus care models 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.
Communication to
the next provider of
care
Indication
Target INR range
Warfarin dose
Date for next INR check
Name of the clinic or provider assuming warfarin management
Length of therapy
Potential drug, herbal, or supplement interactions
Longitudinal record of inpatient INR values and warfarin doses
Bridging therapy if needed
Educational materials provided to the patient
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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 – Director, Pharmacy Policy, Safety, Compliance, and
Informatics
Phone Number: (608) 265-0341
Email Address: ptrapskin@uwhealth.org
Guideline Author(s):
Anne Rose, PharmD – Pharmacy
Workgroup Members:
John Hoch, MD- Dept. of Surgery- Vascular Surgery
Kraig Kumfer, MD- Dept. of Medicine- Hospitalists
Anne Rose, PharmD- Dept. of Pharmacy- Anticoagulation Stewardship
John Sheehan, MD – Dept. of Medicine- Oncology
Sara Shull, PharmD, MBA- Dept. of Pharmacy- Drug Policy Program
Eliot Williams, MD – Dept. of Medicine- Oncology
Luke Zurbriggen, MD- Dept. of Medicine Education (Hematology/Oncology)
Reviewer(s):
David Yang, MD – Lab
Committee Approval(s):
Inpatient Anticoagulation Committee: November 2012; September 2015; December 2019; May
2020; March 2021
Pharmacy & Therapeutics Committee: February 2013; July 2020; May 2021
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Table 1. 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.
Table 2. 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.)
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Strength of Recommendations Grading System (American College of Chest Physicians
2012)
Collateral Tools & Resources
The following collateral tools and resources support staff execution and performance of the
evidence-based model recommendations in everyday clinical practice.
Metrics
• Time within therapeutic INR range (%): goal > 70%
• % of patients with critical INR results
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)
Order Sets
1. IP – Warfarin Therapy – Adult – Supplemental [2441]
Protocols
Pharmacist Management of Warfarin – Adult - Inpatient [12]
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References:
1. 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.
2. Holbrook A, Schulman S, Witt DM, 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(2 Suppl):e152S-e184S.
3. Garcia D, Erkan D. Diagnosis and Management of the Antiphospholipid Syndrome. N
Engl J Med. 2018;379(13):1290.
4. Guyatt GH, Norris SL, Schulman S, et al. Methodology for the development of
antithrombotic therapy and prevention of thrombosis guidelines: Antithrombotic Therapy
and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-
Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):53S-70S.
5. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the
management of patients with atrial fibrillation: a report of the American College of
Cardiology/American Heart Association Task Force on practice guidelines and the Heart
Rhythm Society. Circulation. 2014;130(23):e199-267.
6. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the
2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A
Report of the American College of Cardiology/American Heart Association Task Force
on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol.
2019;74(1):104-132.
7. Lansberg MG, O'Donnell MJ, 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(2 Suppl):e601S-e636S.
8. Saposnik G, Barinagarrementeria F, Brown RD, et al. Diagnosis and management of
cerebral venous thrombosis: a statement for healthcare professionals from the American
Heart Association/American Stroke Association. Stroke. 2011;42(4):1158-1192.
9. Kearon C, Akl EA, Comerota AJ, 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(2
Suppl):e419S-e496S.
10. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST
Guideline and Expert Panel Report. Chest. 2016;149(2):315-352.
11. Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH. 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(2 Suppl):e576S-e600S.
12. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC Focused Update of the 2014
AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A
Report of the American College of Cardiology/American Heart Association Task Force
on Clinical Practice Guidelines. Circulation. 2017;135(25):CIR.000000000000.
13. Puskas JD, Gerdisch M, Nichols D, et al. Anticoagulation and Antiplatelet Strategies
After On-X Mechanical Aortic Valve Replacement. J Am Coll Cardiol. 2018;71(24):2717-
2726.
14. Saito Y, Nazif T, Baumbach A, et al. Adjunctive Antithrombotic Therapy for Patients With
Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement. JAMA Cardiol.
2019.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Effective 5-20-2021. Contact CCKM@uwhealth.org for previous versions.
15. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve
replacement in high-risk patients. N Engl J Med. 2011;364(23):2187-2198.
16. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic
stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363(17):1597-
1607.
17. Adams DH, Popma JJ, Reardon MJ, et al. Transcatheter aortic-valve replacement with a
self-expanding prosthesis. N Engl J Med. 2014;370(19):1790-1798.
18. Falk V, Baumgartner H, Bax JJ, et al. 2017 ESC/EACTS Guidelines for the management
of valvular heart disease. Eur J Cardiothorac Surg. 2017;52(4):616-664.
19. Johanson NA, Lachiewicz PF, Lieberman JR, et al. American academy of orthopaedic
surgeons clinical practice guideline on. Prevention of symptomatic pulmonary embolism
in patients undergoing total hip or knee arthroplasty. J Bone Joint Surg Am.
2009;91(7):1756-1757.
20. Britt RP, James AH, Raskino CL, Thompson SG. Factors affecting the precision of
warfarin treatment. J Clin Pathol. 1992;45(11):1003-1006.
21. Gurwitz JH, Avorn J, Ross-Degnan D, Choodnovskiy I, Ansell J. Aging and the
anticoagulant response to warfarin therapy. Ann Intern Med. 1992;116(11):901-904.
22. Shendre A, Parmar GM, Dillon C, Beasley TM, Limdi NA. Influence of Age on Warfarin
Dose, Anticoagulation Control, and Risk of Hemorrhage. Pharmacotherapy.
2018;38(6):588-596.
23. Shepherd AM, Hewick DS, Moreland TA, Stevenson IH. Age as a determinant of
sensitivity to warfarin. Br J Clin Pharmacol. 1977;4(3):315-320.
24. Kamali F, Khan TI, King BP, et al. Contribution of age, body size, and CYP2C9 genotype
to anticoagulant response to warfarin. Clin Pharmacol Ther. 2004;75(3):204-212.
25. Gladman JR, Dolan G. Effect of age upon the induction and maintenance of
anticoagulation with warfarin. Postgrad Med J. 1995;71(833):153-155.
26. Dobrzanski S, Duncan SE, Harkiss A, Wardlaw A. Age and weight as determinants of
warfarin requirements. J Clin Hosp Pharm. 1983;8(1):75-77.
27. Redwood M, Taylor C, Bain BJ, Matthews JH. The association of age with dosage
requirement for warfarin. Age Ageing. 1991;20(3):217-220.
28. Wilke RA, Berg RL, Vidaillet HJ, Caldwell MD, Burmester JK, Hillman MA. Impact of age,
CYP2C9 genotype and concomitant medication on the rate of rise for prothrombin time
during the first 30 days of warfarin therapy. Clin Med Res. 2005;3(4):207-213.
29. Warfarin (Coumadin®) [prescribing information]. Brisol-Meyers Squibb, Inc.; Princeton,
NJ. 2010.
30. Wallace JL, Reaves AB, Tolley EA, et al. Comparison of initial warfarin response in
obese patients versus non-obese patients. J Thromb Thrombolysis. 2013;36(1):96-101.
31. Mueller JA, Patel T, Halawa A, Dumitrascu A, Dawson NL. Warfarin dosing and body
mass index. Ann Pharmacother. 2014;48(5):584-588.
32. Abdelhafiz AH, Myint MP, Tayek JA, Wheeldon NM. Anemia, hypoalbuminemia, and
renal impairment as predictors of bleeding complications in patients receiving
anticoagulation therapy for nonvalvular atrial fibrillation: a secondary analysis. Clin Ther.
2009;31(7):1534-1539.
33. Yoshizawa M, Hayashi H, Tashiro Y, et al. Effect of VKORC1-1639 G>A polymorphism,
body weight, age, and serum albumin alterations on warfarin response in Japanese
patients. Thromb Res. 2009;124(2):161-166.
34. Dang MT, Hambleton J, Kayser SR. The influence of ethnicity on warfarin dosage
requirement. Ann Pharmacother. 2005;39(6):1008-1012.
35. Zhang H, De T, Zhong Y, Perera MA. The advantages and challenges of diversity in
Pharmacogenomics: Can minority populations bring us closer to implementation?
Clinical Pharmacology & Therapeutics. 2019.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Effective 5-20-2021. Contact CCKM@uwhealth.org for previous versions.
36. Qamar A, Vaduganathan M, Greenberger NJ, Giugliano RP. Oral Anticoagulation in
Patients With Liver Disease. J Am Coll Cardiol. 2018;71(19):2162-2175.
37. Howard-Thompson A, Luckey A, George C, Choby BA, Self TH. Graves’ Disease and
Treatment Effects on Warfarin Anticoagulation. Case Reports in Medicine. 2014;2014:1-
6.
38. Busenbark LA, Cushnie SA. Effect of Graves' disease and methimazole on warfarin
anticoagulation. Ann Pharmacother. 2006;40(6):1200-1203.
39. Kellett HA, Sawers JS, Boulton FE, Cholerton S, Park BK, Toft AD. Problems of
anticoagulation with warfarin in hyperthyroidism. Q J Med. 1986;58(225):43-51.
40. Self TH, Straughn AB, Weisburst MR. Effect of hyperthyroidism on hypoprothrombinemic
response to warfarin. Am J Hosp Pharm. 1976;33(4):387-389.
41. Self TH, Reaves AB, Oliphant CS, Sands C. Does heart failure exacerbation increase
response to warfarin? A critical review of the literature. Curr Med Res Opin.
2006;22(11):2089-2094.
42. del Campo M, Roberts G. Changes in Warfarin Sensitivity During Decompensated Heart
Failure and Chronic Obstructive Pulmonary Disease. Ann Pharmacother.
2015;49(9):962-968.
43. Nutescu EA, Shapiro NL, Ibrahim S, West P. Warfarin and its interactions with foods,
herbs and other dietary supplements. Expert Opin Drug Saf. 2006;5(3):433-451.
44. 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.
45. Klang M, Graham D, McLymont V. Warfarin bioavailability with feeding tubes and enteral
formula. JPEN J Parenter Enteral Nutr. 2010;34(3):300-304.
46. Dickerson RN. Warfarin Resistance and Enteral Tube Feeding: An Old Problem With a
New Solution. 2008;43(6):520-524. https://doi.org/10.1310/hpj4306-520.
47. Petretich DA. Reversal of osmolite-warfarin interaction by changing warfarin
administration time. Clin Pharm. 1990;9(2):93.
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Contact: CCKM@uwhealth.org Last Revised: 07/2021
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