II. Definitions
- Vitamin K Antagonist
- Agents that inhibit the intrahepatic intercoversion of Vitamin K to its reduced form
- In the absence of Vitamin K, Clotting Factors/Proteins are not activated and Clotting Cascade does not occur
- Warfarin is the most commonly used Vitamin K Antagonist
- Other Vitamin K Antagonists include Dicoumarol, phenprocoumon and acenocoumarol
- Dicoumarol and coumarin are naturally occurring compounds found in plants
III. Mechanism
- Inhibits Vitamin K participation in factor synthesis (Vitamin K Antagonist)
- Clotting Factors (both pro-coagulant and Anticoagulant) are Vitamin K Dependent
- Vitamin K is required for carboxylation of terminal ends of coagulation Proteins
- Without carboxylation, Clotting Factors/Proteins are not activated and Clotting Cascade does not occur
- Warfarin inhibits the intrahepatic cyclic interconversion of Vitamin K to a reduced form
- Keeps Vitamin K and dependent factors inactive
-
Vitamin K dependent coagulation Proteins
- Procoagulant Activity (Mnemonic: "1972")
- Factor 10 (36 hour half life)
- Factor 9 (24 hour half life)
- Factor 7 (8 hour half life)
- Factor 2 (50-72 hour half life)
- Anticoagulant Activity
- Procoagulant Activity (Mnemonic: "1972")
- Coumadin has an initial paradoxical procoagulant effect
- Anticoagulant factors are depleted first
- Initially both Hypercoagulable and at increased risk for Warfarin skin necrosis
- Concurrently administer Heparin for first 4-5 days
IV. Indications: General
- DOACs are often preferred over Warfarin for most Anticoagulation indications (esp. Atrial Fibrillation, Venous Thromboembolism)
- However, Warfarin is preferred over DOACs in a few specific conditions
- Mechanical Heart Valve
- Moderate to severe Mitral Stenosis and Atrial Fibrillation
- Higher mortality and stroke risk with Rivaroxaban compared with Warfarin
- Left Ventricular Assist Device (LVAD)
- Antiphospholipid Antibody Syndrome and Thrombosis history
- Breakthough stroke on DOAC
- Chronic Kidney Disease Stage 4-5 (most DOACs contraindicated in severe renal disease)
- DOAC Drug Interactions that decrease Anticoagulation efficacy
- References
- (2022) Presc Lett 29(11): 62
V. Indications: Standard INR between 2.0 and 3.0
- Precautions
- INR 2.2 to 2.3 associated with lowest overall mortality
- Major orthopedic surgery
- Hip replacement or ORIF Fracture (for 28-35 days)
- Elective total knee arthroplasty (for 10-14 days)
-
Atrial Fibrillation
- High CVA risk (CHADS Score 2 or higher)
- Persistent, paroxysmal Atrial Fibrillation, flutter
- Cardioversion (Warfarin for 3 weeks before, 4 weeks after)
- Mitral Stenosis
- Coronary Stent and high CVA risk (CHADS Score 2 or higher)
- Warfarin is continued indefinately AND
- Antiplatelet agents
- First - Immediately after stenting: Triple Therapy
- Clopidogrel AND Aspirin (and Warfarin)
- Continue triple therapy for 1 month following bare metal stent
- Continue triple therapy for 3-6 months following drug eluting stent
- Next - Following initial period of triple therapy: Dual Therapy
- Clopidogrel OR Aspirin (and Warfarin) until 12 months following stenting
- Next - Following first year of antiplatelet drugs
- Continue Warfarin alone
- First - Immediately after stenting: Triple Therapy
-
Venous Thromboembolism (Deep Vein Thrombosis or Pulmonary Embolism)
- First episode with reversible risks: 3 months
- First episode and idiopathic: 6-12 months
- Cancer: LMWH x3-6 months, then Warfarin longterm
- Antiphospholipid Antibody (Lupus Anticoagulant): 12 months or longterm
- Two Thrombophilias: 12 months or longterm
- Clotting disorder related: 6-12 months or longterm
- Two or more episodes: Longterm
-
Coronary Artery Disease
- High risk patients for Myocardial Infarction without stent
- Continue Warfarin for 3 months following Myocardial Infarction
- Continue with low dose Aspirin (e.g. 81 mg)
- High risk patients for Myocardial Infarction with bare metal stent
- First: Triple therapy (Warfarin AND Clopidogrel AND low dose Aspirin) for 1 month
- Next: Dual therapy (Warfarin AND Clopidogrel or low dose Aspirin) for 2 months
- High risk patients for Myocardial Infarction with drug eluting stent
- First: Triple therapy (Warfarin AND Clopidogrel AND low dose Aspirin) for 3-6 months
- High risk patients for Myocardial Infarction without stent
-
Heart Valve Replacement
- Mechanical Aortic Valve Replacement with bileaflet or tilting disk valves
- Low dose Aspirin (e.g. 81 mg) is recommended with Warfarin if low bleeding risk
-
Bioprosthetic Heart Valve in mitral position
- Warfarin for 3 months after insertion
- Mechanical Aortic Valve Replacement with bileaflet or tilting disk valves
VI. Indications: Target INR between 2.5 and 3.5
-
Mechanical Heart Valves
- Ball and cage valve
- Comorbid Atrial Fibrillation, CHF, MI, LAE
- Mitral Valve Replacement
VII. Dosing
VIII. Drug Interactions
IX. Safety
- Pregnancy Category X in all trimesters (except if Mechanical Heart Valves)
- Considered safe in Lactation
X. Adverse Effects
- Major Bleeding (including gastrointestinal Hemorrhage)
- Highest risk on initiation and when INR elevated
- Other risks
- Variable INR
- Age over 65 years
- Gastrointestinal Bleeding history
- Hypertension
- Cerebrovascular Disease
- Malignancy
- Renal Insufficiency (Apixaban is preferred instead of GFR <30 ml/min)
- Warfarin Skin Necrosis
- Rare complication
- Gastrointestinal symptoms
- Nausea, Vomiting, Abdominal Pain and distention, Flatulence and Dysgeusia
XI. Resources
Images: Related links to external sites (from Bing)
Related Studies
warfarin (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
WARFARIN SODIUM 1 MG TABLET | Generic | $0.09 each |
WARFARIN SODIUM 10 MG TABLET | Generic | $0.12 each |
WARFARIN SODIUM 2 MG TABLET | Generic | $0.09 each |
WARFARIN SODIUM 2.5 MG TABLET | Generic | $0.09 each |
WARFARIN SODIUM 3 MG TABLET | Generic | $0.11 each |
WARFARIN SODIUM 4 MG TABLET | Generic | $0.09 each |
WARFARIN SODIUM 5 MG TABLET | Generic | $0.11 each |
WARFARIN SODIUM 6 MG TABLET | Generic | $0.12 each |
WARFARIN SODIUM 7.5 MG TABLET | Generic | $0.12 each |
Ontology: Warfarin (C0043031)
Definition (CHV) | a blood thinner |
Definition (NCI_NCI-GLOSS) | A drug that prevents blood from clotting. It belongs to the family of drugs called anticoagulants (blood thinners). |
Definition (NCI) | A synthetic anticoagulant. Warfarin inhibits the regeneration of vitamin K1 epoxide and so the synthesis of vitamin K dependent clotting factors, which include Factors II, VII, IX and X, and the anticoagulant proteins C and S. This inhibition results in a sequential depression of Factors VII, IX, X and II activities. Vitamin K is an essential cofactor for the post ribosomal synthesis of the vitamin K dependent clotting factors. The vitamin promotes the biosynthesis of gamma-carboxyglutamic acid residues in these proteins which are essential for biological activity. |
Definition (CSP) | synthetic coumarin anticoagulant. |
Definition (MSH) | An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. |
Definition (PDQ) | A synthetic anticoagulant. Warfarin appears to inhibit the regeneration of vitamin K1 epoxide and so the synthesis of vitamin K dependent clotting factors, which include Factors II, VII, IX and X, and the anticoagulant proteins C and S. This inhibition results in a sequential depression of Factors VII, IX, X and II activities. Vitamin K is an essential cofactor for the post ribosomal synthesis of the vitamin K dependent clotting factors. The vitamin promotes the biosynthesis of gamma-carboxyglutamic acid residues in these proteins which are essential for biological activity. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39740&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39740&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C945" NCI Thesaurus) |
Concepts | Pharmacologic Substance (T121) , Hazardous or Poisonous Substance (T131) , Organic Chemical (T109) |
MSH | D014859 |
SnomedCT | 372756006, 48603004 |
LNC | LP16309-4, MTHU003212 |
English | Warfarin, 2H-1-Benzopyran-2-one, 4-hydroxy-3-(3-oxo-1-phenylbutyl)-, 4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one, 3-(Alpha-acetonylbenzyl)-4-hydroxycoumarin, 3-Alpha-phenyl-beta-acetylethyl-4-hydroxycoumarin, 1-(4'-Hydroxy-3'-coumarinyl)-1-phenyl-3-butanone, Warfarin [Chemical/Ingredient], WARFARIN, 3-(.alpha.-Acetonylbenzyl)-4-hydroxycoumarin, 3-(.alpha.-Phenyl-.beta.-acetylethyl)-4-hydroxycoumarin, warfarin (medication), anticoagulants warfarin, warfarin, Warfarin (product), Warfarin (substance), WARF |
Swedish | Warfarin |
Czech | warfarin |
Finnish | Varfariini |
Russian | VARFARIN, ВАРФАРИН |
Croatian | VARFARIN |
Polish | Warfaryna |
Japanese | ワルファリン, ワーファリン |
Spanish | warfarina (producto), warfarina (sustancia), warfarina, Warfarina |
French | Warfarine |
German | Warfarin |
Italian | Warfarina |
Portuguese | Varfarina |
Ontology: Coumadin (C0699129)
Definition (CHV) | a kind of blood thinner |
Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
MSH | D014859 |
English | marevan, coumadin, Coumadin, Marevan, Boots Brand of Warfarin Sodium, Bristol-Myers Squibb Brand of Warfarin Sodium, Goldshield Brand of Warfarin Sodium |
Ontology: Vitamin K antagonists (C3653316)
Concepts | Pharmacologic Substance (T121) |
English | Vitamin K antagonists |