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Oral anticoagulation with warfarin

Warfarin orders for inpatients must be written daily (i.e., no standing
University of California San Francisco Medical Center
orders) If no dose is intended or the dose is to be withheld, write an order
Comprehensive Hemostasis and Antithrombotic Service (CHAS)
to this effect.
NOTE: These recommendations should be used in conjunction with the clinical
An INR increase of 0.2 - 0.3 units per day represents an optimal response to initiation of warfarin. Any increase in INR ≥ 0.4 units per day should result in The initial anticoagulant response to warfarin is dependent on the elimination warfarin dose reduction or holding warfarin dose. half-lives of clotting factors II (60 hr), VII (6 hr), IX (24 hr), and X (48 hr) as well INRs should not be assessed when aPTT is > 100 seconds, due to contribution as the accumulation of warfarin. The initial increase in INR is secondary to of UFH's effect to INR. Wait until aPTT is < 100 seconds before assessing depletion of factor VII. Therapeutic anticoagulation is usually achieved in 5 - 7 Warfarin is rated pregnancy category X. The drug is contraindicated in women For INRs significantly above therapeutic range, hold warfarin until INR falls within range prior to restarting warfarin, (see Reversal of warfarin Average dose required to maintain INR 2 - 3 is 3 - 5 mg Available warfarin dosages tablet and colors: Factors that may impact the INR: drug interactions, malnutrition, alcohol, concomitant disease (e.g., thyroid dysfunction, liver disease, fever), medication Factors to Consider When Initiating Warfarin Algorithm for initiating warfarin in hospitalized patients Baseline PT/INR, PTT and platelet count must be obtained prior to initiation of warfarin. Usual initiation dose = 5 mg (NOT 10 mg)
Consider higher initial dose (e.g., 7.5 mg) in the following populations:
4. Concomitant medications ("Drugs that Alter Anticoagulant Response to Decrease or hold dose*
Increase dose*
Consider lower initial dose (e.g., 2.5 mg) in the following populations:
Decrease dose*
Increase dose*
Daily increase 0.2 - 0.3 units Continue dose Daily increase 0.4 - 0.6 units Decrease dose*
°see “Factors to Consider When Initiating Warfarin” Concomitant medications ("Drugs that Alter Anticoagulant Response to *In general, with increased dosage adjustments do not exceed 2.5 mg or 50% of the
Recommended INR ranges for therapeutic anticoagulation (7th ACCP Consensus Conference on Antithrombotic Therapy, Chest 2004) Indication INR Range
Algorithm for managing warfarin in patients on warfarin prior to admission Prevention of systemic embolism (e.g. AMI, AF, valvular HD) Continue patient’s home warfarin regimen Mechanical prosthetic valves in the aortic position+ Adjust warfarin dose in the presence of factors which may alter INR (see Antiphospholipid antibody syndrome (without other risk factors)++ Recurrent thromboembolism on therapeutic warfarin Mechanical prosthetic valves in the mitral position or ball and cage If INR is out of range in the absence of factors which may alter INR, adjust dose by ± 5 - 10% of the weekly dose (see “Reversal of Warfarin Anticoagulant +Goal INR 2.5 - 3.5 if patients have additional risk factors (e.g., AF) Effects” for further recommendations on management of INR above UCSF GUIDELINE FOR DOSING WARFARIN
FFP, Bebulin®, and NovoSeven®
Give FFP and/or prothrombin complex concentrate (Bebulin®), or rhVIIa (NovoSeven®) in cases of bleeding or need immediate reversal of INR Reversal of anticoagulation in patients with supratherapeutic INRs and/or clinically o Call Hematology consult (443-4276) for dosing & monitoring recommendations o Usual initial doses: FFP, 4 units per treatment; Bebulin®, 35 units/kg x 1 IV Effects on INR are transient (FFP or Bebulin®, 4-6 hours, rhVIIa, 1-2 hours) Clinical
INR Recomme
This list is not all-inclusive; INR should be monitored after initiating or modifying any drug therapy • When INR falls to within therapeutic range, resume warfarin at lower dose. If initial INR was only slightly above range, may not be necessary to reduce dose (i.e., transient factors such as dietary variance or concurrent • Pts with high bleed risk: Give vitamin K *Moderate interaction **Significant interaction #May increase or decrease INR check INR in 24 hrs to assure response to therapy • Resume therapy at lower dose when INR falls within DISCHARGE PLANNING AND FOLLOW-UP
All patients should be scheduled for outpatient INR monitoring prior to discharge. • Give vitamin K1 5 - 10 mg po x 1 (may repeat in 24 hours 1. Criteria for enrollment into UCSF Anticoagulation Clinic. -PCP must practice in a UCSF clinic (ACC, Mt. Zion, Lakeshore)
• Check INR in 24 hrs to assure response to therapy -PCP must be notified and request warfarin monitoring in ACC
• Resume therapy at lower dose when INR within -Patient must attend clinic; telephone management is not available 2. Alternatives to UCSF Anticoagulation Clinic: prolongation in • Give FFP and/or prothrombin complex concentrate -Follow-up with other anticoagulation clinics (e.g., SFGH) (Bebulin®); use of rhVIIa (NovoSeven®) also may be Any patient who is being started on warfarin must receive warfarin teaching prior to discharge. You may contact the CHAS service with questions on warfarin teaching repeat in 12-24 hours, if INR not reduced and/or for educational materials (see below). • Initially, plan to follow INR frequently (every 2-4 hours), and at least twice daily as long as bleeding risk remains, IMPORTANT NUMBERS
• Arrange for admission (if not already admitted) Vitamin K1
CHAS attending – Patrick Fogarty, M.D. PO is the recommended route of administration; has predictable response and
Selected references: 1. 7th ACCP consensus conference on antithrombotic therapy. Chest 2004;126:163S-697S Oral vitamin K1 is available as 5 mg tablets. May split 5 mg tab, if 2.5 Harrison L et al. Comparison of 5 mg and 10 mg loading doses in initiation of warfarin therapy. Ann Intern Hirsh J et al. American Heart Association / American College of Cardiology Foundation guide to warfarin therapy. Circulation 2003;107:1692-1711. Higher doses of vitamin K1 (e.g., 10 mg) may lead to warfarin Crowther MA et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003;349:1133-8. IV is effective and recommended only in cases of serious bleeding due to its risk for Schulman S. Care of patients receiving long-term anticoagulant therapy. N Engl J Med 2003;349:675-83. anaphylaxis; requires slow IV infusion over at least 30 minutes Takahashi H and Echizen H. Pharmacogenetics of CYP2C9 and interindividual variability in anticoagulant response to warfarin. Pharmacogenomics J 2003;3:202-214. Subcutaneous dosing is not recommended due to unpredictable absorption
Holbrook AM, Pereira JA, Labiris R etal. Systematic overview of warfarin and its drug and food interactions. UCSF Medical Center - Comprehensive Hemostasis and Antithrombotic Service (CHAS) Lisa Tong, Pharm.D. ,CACP Steve Kayser, Pharm.D. Patrick Fogarty, M.D. Updated 01/2007

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