The information gathered was entered into Microsoft Access, and 50 patients were randomly selected to be included in the evaluation. A computer-generated report of all patients receiving warfarin was generated daily from July 24, 2000, to August 20, 2000. May repeat if needed.Ĭriteria for warfarin administration were developed that were supported by the medical literature and approved by the Drug Utilization Evaluation Subcommittee of the Pharmacy and Therapeutics Committee. Replace with prothrombin complex concentrate and give 10 mg of vitamin K 1 by infusion. When appropriate, heparin can be given until the patient becomes responsive to warfarin. May repeat vitamin K 1 every 12 hours and give fresh plasma transfusion or prothrombin complex concentrate as needed. Stop warfarin give vitamin K 1 10 mg by slow IV infusion. Serious bleeding or major warfarin overdose Reassess need and dose of warfarin when INR approaches desirable range. Stop warfarin give vitamin K 1 3–5 mg orally follow INR closely repeat vitamin K 1 if needed. Vitamin K 1 2–4 mg orally (expected reversal within 24 hours) give additional1–2 mg if INR remains high at 24 hours. No bleeding but reversal needed for surgery or dental extraction within 24 hours Omit next 1–2 doses, monitor INR more frequently, and restart at lower dose when INR approaches target range or omit dose and give 1–2.5 mg vitamin K 1 orally (use this if patient has risk factor for bleeding). If the INR is only minimally above range, no dosage reduction may be required. Omit next few warfarin doses and/or restart at lower dose when INR approaches desired range. No bleeding or need for rapid reversal (i.e., no need for surgery) Lab error should also be considered for unexpected values. Unexpected fluctuations in the INR in an otherwise stable patient could be due to a change in diet, poor compliance, undisclosed drug use, alcohol consumption, or self-medication ( 2). When a patient is started on an oral anticoagulant, INR monitoring should be performed daily until the INR is within the therapeutic range for at least 2 consecutive days. The safety and efficacy of warfarin therapy are dependent on maintaining the INR within the target range for the indication (Table (Table1 1). Once the INR is therapeutic for at least 2 days, the supplemental anticoagulation treatment may be discontinued ( 1, 4, 5). If a rapid anticoagulant effect is required, an initial dose of heparin or a low molecular-weight heparin should be used and overlapped with warfarin for approximately 4 to 5 days. The administration of a loading dose is a possible source of prolonged hospitalization secondary to dramatic rises in the INR value that may necessitate the administration of vitamin K ( 5). Administration of loading doses may place a patient in a hypercoagulable state due to a severe depletion of protein C ( 2). In clinical practice, loading doses (e.g., 7.5 mg or more per day) of warfarin may increase the patient's risk of bleeding complications early in therapy by eliminating the production of functional factor VII ( 2, 5). Because prothrombin has a half-life of around 50 hours, loading doses of warfarin are of limited value ( 4). Initiation of warfarin therapy is challenging, since the pharmacodynamic response is delayed and difficult to predict. The antithrombotic effect of warfarin is not present until approximately the fifth day of therapy, which is dependent on the clearance of prothrombin ( 1, 2). The earliest changes in INR are typically seen 24 to 36 hours after administration of the dose. The anticoagulant and antithrombotic activity of warfarin depends on the clearance of functional clotting factors from the systemic circulation once the drug is administered ( 2, 3). Warfarin inhibits the synthesis of clotting factors II, VII, IX, and X, as well as the naturally occurring endogenous anticoagulant proteins C and S ( 2). Warfarin has also been used to prevent recurrent transient ischemic attacks and to reduce the risk of recurrent myocardial infarction, but data supporting these indications are inconclusive at this time ( 1). Warfarin, a vitamin K antagonist, is an oral anticoagulant indicated for the prevention and treatment of venous thrombosis and its extension and the prevention and treatment of the thromboembolic complications associated with atrial fibrillation. The goal of anticoagulant therapy with warfarin is to administer the lowest effective dose of the drug to maintain the target international normalized ratio (INR).
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