II. Mechanism

  1. Inhibits Vitamin K participation in factor synthesis
    1. Clotting Factors (both pro-coagulant and Anticoagulant) are Vitamin K Dependent
    2. Vitamin K is required for carboxylation of terminal ends of coagulation proteins
    3. Without carboxylation, Clotting Factors/proteins are not activated and Clotting Cascade does not occur
    4. Warfarin inhibits the cyclic interconversion of Vitamin K to a reduced form, thereby keeping it and dependent factors inactive
  2. Vitamin K dependent coagulation proteins
    1. Procoagulant Activity (1972)
      1. Factor 10 (36 hour half life)
      2. Factor 9 (24 hour half life)
      3. Factor 7 (8 hour half life)
      4. Factor 2 (50-72 hour half life)
    2. Anticoagulant Activity
      1. Protein C (8-14 hour half life)
      2. Protein S (30-42 hour half life)
  3. Coumadin has an initial paradoxical procoagulant effect
    1. Anticoagulant factors are depleted first
    2. Initially both Hypercoagulable and at increased risk for Warfarin skin necrosis
    3. Concurrently administer Heparin for first 4-5 days

III. Indications: Standard INR between 2.0 and 3.0

  1. Major orthopedic surgery
    1. Hip replacement or ORIF Fracture (for 28-35 days)
    2. Elective total knee arthroplasty (for 10-14 days)
  2. Atrial Fibrillation
    1. High CVA risk (CHADS Score 2 or higher)
    2. Persistent, paroxysmal Atrial Fibrillation, flutter
    3. Cardioversion (Warfarin for 3 weeks before, 4 weeks after)
    4. Mitral Stenosis
    5. Coronary Stent and high CVA risk (CHADS Score 2 or higher)
      1. Warfarin is continued indefinately AND
      2. Antiplatelet agents
        1. First - Immediately after stenting: Triple Therapy
          1. Clopidogrel AND Aspirin (and Warfarin)
          2. Continue triple therapy for 1 month following bare metal stent
          3. Continue triple therapy for 3-6 months following drug eluting stent
        2. Next - Following initial period of triple therapy: Dual Therapy
          1. Clopidogrel OR Aspirin (and Warfarin) until 12 months following stenting
        3. Next - Following first year of antiplatelet drugs
          1. Continue Warfarin alone
  3. Venous Thromboembolism (Deep Vein Thrombosis or Pulmonary Embolism)
    1. First episode with reversible risks: 3 months
    2. First episode and idiopathic: 6-12 months
    3. Cancer: LMWH x3-6 months, then Warfarin longterm
    4. Antiphospholipid Antibody (Lupus Anticoagulant): 12 months or longterm
    5. Two Thrombophilias: 12 months or longterm
    6. Clotting disorder related: 6-12 months or longterm
    7. Two or more episodes: Longterm
  4. Coronary Artery Disease
    1. High risk patients for Myocardial Infarction without stent
      1. Continue Warfarin for 3 months following Myocardial Infarction
      2. Continue with low dose Aspirin (e.g. 81 mg)
    2. High risk patients for Myocardial Infarction with bare metal stent
      1. First: Triple therapy (Warfarin AND Clopidogrel AND low dose Aspirin) for 1 month
      2. Next: Dual therapy (Warfarin AND Clopidogrel or low dose Aspirin) for 2 months
    3. High risk patients for Myocardial Infarction with drug eluting stent
      1. First: Triple therapy (Warfarin AND Clopidogrel AND low dose Aspirin) for 3-6 months
  5. Heart Valve Replacement
    1. Mechanical Aortic Valve Replacement with bileaflet or tilting disk valves
      1. Low dose Aspirin (e.g. 81 mg) is recommended with Warfarin if low bleeding risk
    2. Bioprosthetic Heart Valve in mitral position
      1. Warfarin for 3 months after insertion

IV. Indications: Target INR between 2.5 and 3.5

  1. Mechanical Heart Valves
    1. Ball and cage valve
    2. Comorbid Atrial Fibrillation, CHF, MI, LAE
    3. Mitral Valve Replacement

V. Dosing Protocol

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Cost: Medications

Warfarin (on 6/18/2017 at Walmart.com)
Warfarin 10mg #30 tablets for $4.00 $0.13 each
Warfarin 10mg #90 tablets for $10.00 $0.11 each
Warfarin 1mg #30 tablets for $4.00 $0.13 each
Warfarin 1mg #90 tablets for $10.00 $0.11 each
Warfarin 2.5mg #30 tablets for $4.00 $0.13 each
Warfarin 2.5mg #90 tablets for $10.00 $0.11 each
Warfarin 2mg #30 tablets for $4.00 $0.13 each
Warfarin 2mg #90 tablets for $10.00 $0.11 each
Warfarin 3mg #30 tablets for $4.00 $0.13 each
Warfarin 3mg #90 tablets for $10.00 $0.11 each
Warfarin 4mg #30 tablets for $4.00 $0.13 each
Warfarin 4mg #90 tablets for $10.00 $0.11 each
Warfarin 5mg #30 tablets for $4.00 $0.13 each
Warfarin 5mg #90 tablets for $10.00 $0.11 each
Warfarin 6mg #30 tablets for $4.00 $0.13 each
Warfarin 6mg #90 tablets for $10.00 $0.11 each
Warfarin 7.5mg #30 tablets for $4.00 $0.13 each
Warfarin 7.5mg #90 tablets for $10.00 $0.11 each
warfarin (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
WARFARIN SODIUM 1 MG TABLET Generic $0.13 each
WARFARIN SODIUM 10 MG TABLET Generic $0.19 each
WARFARIN SODIUM 2 MG TABLET Generic $0.13 each
WARFARIN SODIUM 2.5 MG TABLET Generic $0.14 each
WARFARIN SODIUM 3 MG TABLET Generic $0.14 each
WARFARIN SODIUM 4 MG TABLET Generic $0.13 each
WARFARIN SODIUM 5 MG TABLET Generic $0.13 each
WARFARIN SODIUM 6 MG TABLET Generic $0.21 each
WARFARIN SODIUM 7.5 MG TABLET Generic $0.18 each
coumadin (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
COUMADIN 1 MG TABLET Generic $0.13 each
COUMADIN 10 MG TABLET Generic $0.19 each
COUMADIN 2 MG TABLET Generic $0.13 each
COUMADIN 2.5 MG TABLET Generic $0.14 each
COUMADIN 3 MG TABLET Generic $0.14 each
COUMADIN 4 MG TABLET Generic $0.13 each
COUMADIN 5 MG TABLET Generic $0.13 each
COUMADIN 6 MG TABLET Generic $0.21 each
COUMADIN 7.5 MG TABLET Generic $0.18 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