This is the current release of the guideline.

This guideline updates a previous version: Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004 Sep;126(3 Suppl):204S-33S.

The grades of recommendation (1A, 1B, 1C, 2A, 2B, 2C) are defined at the end of the "Major Recommendations" field.

Please refer to the original full-length guideline document for a detailed description of the pharmacology and monitoring of vitamin K antagonists (VKAs), the pharmacokinetics and pharmacodynamics of warfarin (including genetic and environmental factors), the antithrombotics effect of VKAs, monitoring anticoagulation intensity, and clinical applications of VKA therapy.

Initiation and Maintenance Dosing

In patients beginning vitamin K antagonist (VKA), therapy, we recommend the initiation of oral anticoagulation with doses between 5 mg and 10 mg for the first 1 or 2 days for most individuals, with subsequent dosing based on the international normalized ratio (INR) response (Grade 1B). At the present time, for patients beginning VKA therapy, without evidence from randomized trials, we suggest against the use of pharmacogenetic-based initial dosing to individualize warfarin dosing (Grade 2C)

Initiation of Anticoagulation in the Elderly or Other Populations

In elderly patients or patients who are debilitated, are malnourished, have congestive heart failure, have liver disease, have had recent major surgery, or are taking medications known to increase the sensitivity to warfarin (e.g., amiodarone), we recommend the use of a starting dose of <5 mg (Grade 1C) with subsequent dosing based on the international normalized ratio (INR) response.

Frequency of Monitoring

1. In patients beginning VKA therapy, we suggest that INR monitoring should be started after the initial two or three doses of oral anticoagulation therapy (Grade 2C).
2. For patients who are receiving a stable dose of oral anticoagulants, we suggest monitoring at an interval of no longer than every 4 weeks (Grade 2C).

Management of Nontherapeutic INRs

1. For patients with INRs above the therapeutic range, but < 5.0 and with no significant bleeding, we recommend lowering the dose or omitting a dose, monitoring more frequently, and resuming therapy at an appropriately adjusted dose when the INR is at a therapeutic level. If only minimally above therapeutic range, or associated with a transient causative factor, no dose reduction may be required (all Grade 1C).
2. For patients with INRs >5.0 but <9.0 and no significant bleeding, we recommend omitting the next one or two doses, monitoring more frequently, and resuming therapy at an appropriately adjusted dose when the INR is at a therapeutic level (Grade 1C). Alternatively, we suggest omitting a dose and administering vitamin K (1 to 2.5 mg) orally, particularly if the patient is at increased risk of bleeding (Grade 2A). If more rapid reversal is required because the patient requires urgent surgery, we suggest vitamin K (<5 mg) orally, with the expectation that a reduction of the INR will occur in 24 hours. If the INR is still high, we suggest additional vitamin K (1 to 2 mg) orally (Grade 2C).
3. For patients with INRs of ≥ 9.0 and no significant bleeding, we recommend holding warfarin therapy and administering a higher dose of vitamin K (2.5 to 5 mg) orally, with the expectation that the INR will be reduced substantially in 24 to 48 hours (Grade 1B). Clinicians should monitor the INR more frequently, administer additional vitamin K if necessary, and resume therapy at an appropriately adjusted dose when the INR reaches the therapeutic range.
4. In patients with serious bleeding and elevated INR, regardless of the magnitude of the elevation, we recommend holding warfarin therapy and giving vitamin K (10 mg) by slow IV infusion supplemented with fresh frozen plasma, prothrombin complex concentrate, or recombinant factor VIIa, depending on the urgency of the situation. We recommend repeating vitamin K administration every 12 hours for persistent INR elevation (All Grade 1C).
5. In patients with life-threatening bleeding (e.g., intracranial hemorrhage) and elevated INR, regardless of the magnitude of the elevation, we recommend holding warfarin therapy and administering fresh frozen plasma, prothrombin complex concentrate (PCC), or recombinant factor VIIa supplemented with vitamin K, 10 mg by slow IV infusion, repeated, if necessary, depending on the INR (Grade 1C).
6. In patients with mild-to-moderately elevated INRs without major bleeding, we recommend that when vitamin K is to be given, it be administered orally rather than subcutaneously (Grade 1A).

Management of Variable INRs

For patients receiving long-term warfarin therapy with a variable INR response not attributable to any of the usual known causes for instability, we suggest a trial of daily low-dose oral vitamin K (100 to 200 microgram) with close monitoring of the INR and warfarin dose adjustment to counter an initial lowering of the INR in response to vitamin K (Grade 2B).

Management of INRs in Antiphospholipid Syndrome

In patients who have a lupus inhibitor, who have no additional risk factors, and no lack of response to therapy, we recommend a therapeutic target INR of 2.5 (INR range, 2.0 to 3.0) (Grade 1A). In patients who have recurrent thromboembolic events with a therapeutic INR or other additional risk factors for thromboembolic events, we suggest a target INR of 3.0 (INR range, 2.5 to 3.5) (Grade 2C).

Optimal Management of VKA Therapy

For health-care providers who manage oral anticoagulation therapy, we recommend that they do so in a systematic and coordinated fashion, incorporating patient education, systematic INR testing, tracking, follow-up, and good patient communication of results and dosing decisions as occurs in an anticoagulation management service (Grade 1B).

Patient Self-Testing and Patient Self-Management

Patient self-management is a choice made by patients and health-care providers that depends on many factors. In patients who are suitably selected and trained, patient self-testing and patient self-management is an effective alternative treatment model. We suggest that such therapeutic management be implemented where suitable (Grade 2B).

Definitions:

*The guideline developers use the wording recommend for strong (Grade 1) recommendations and suggest for weak (Grade 2) recommendations.

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Not applicable: The guideline was not adapted from another source.

2004 Sep (revised 2008 Jun)

American College of Chest Physicians - Medical Specialty Society

American College of Chest Physicians

American College of Chest Physicians (ACCP) Expert Panel on Antithrombotic and Thrombolytic Therapy

Primary Authors: Jack Ansell, MD; Jack Hirsh, MD; Elaine Hylek, MD, MPH; Alan Jacobson, MD; Mark Crowther, MD; Gualtiero Palareti, MD

Committee Co-Chairs: Jack Hirsh, MD, FCCP (Chair); Gordon H. Guyatt, MD, FCCP; Gregory W. Albers, MD; Robert A. Harrington, MD, FCCP; Holger J. Schünemann, MD, PhD, FCCP

Participants: Giancarlo Agnelli, MD; Pierre Amarenco, MD; Jack E. Ansell, MD; Collin Baigent; Shannon M. Bates, MD; Kenneth A. Bauer, MD; Richard C. Becker, MD; Peter B. Berger, MD; David Bergqvist, MD, PhD; Rebecca J. Beyth, MD; Christopher P. Cannon, MD; Elizabeth A. Chalmers, MB, ChB, MD; Anthony K.C. Chan, MBBS; Clifford W. Colwell, Jr., MD; Anthony J. Comerota, MD; Deborah Cook, MD; Mark A. Crowther, MD; James E. Dalen, MD; Gabrielle deVeber, MD, MHSc; Maria Benedetta Donati, MD, PhD; James D. Douketis, MD; Andrew Dunn, MD; J. Donald Easton, MD; Michael Ezekowitz, MD; Margaret Fang; William H. Geerts, MD, FCCP; Alan S. Go, MD; Samuel Z. Goldhaber, MD, FCCP; Shaun D. Goodman, MD; Michael Gould, MD, FCCP; Ian A. Greer, MD; Andreas Greinacher, MD; David Gutterman, MD, FCCP, HSP; Jonathan L. Halperin, MD; John A. Heit, MD; Elaine M. Hylek, MD; Alan Jacobson, MD; Roman Jaeschke, MD, PhD; Amir K. Jaffer, MD; Susan Kahn; Clive Kearon, MBBCh, PhD; Fenella Kirkham, MBBC; Andreas Koster, MD, PhD; Michael R. Lassen, MD; Mark N. Levine, MD, MSc; Sandra Zelman Lewis, PhD; A. Michael Lincoff, MD; Gregory YH Lip, MD; Christopher Madias, MD; Warren J. Manning, MD; Daniel B. Mark, MD; M. Patricia Massicotte, MD, MSc; David Matchar, MD; Thomas W. Meade, DM, FCCP; Venu Menon, MD; Tracy Minichiello, MD; Paul Monagle, MBBS, MSc, MD, FCCP; Christopher M. O'Connor, MD; Patrick O'Gara, MD; E. Magnus Ohman, MD; Ingrid Pabinger, MD; Gualtiero Palareti, MD; Carlo Patrono, MD; Stephen G. Pauker, MD; Graham F. Pineo, MD; Jeffrey J. Popma, MD; Gary Raskob, PhD; Gerald Roth, MD; Ralph L. Sacco, MD; Deeb N. Salem, MD, FCCP; Charles-Marc Samama, MD, FCCP; Meyer Michel Samama, MD; Sam Schulman, MD, PhD; Daniel Singer, MD; Michael Sobel, MD; Shoshanna Sofaer, DrPH; Alex C. Spyropoulos, MD FCCP; Ph. Gabriel Steg, MD; Philip Teal, MD; Raymond Verhaeghe, MD; David A. Vorchheimer, MD; Theodore E. Warkentin, MD; Jeffrey Weitz, MD

Dr. Ansell discloses that he has received consultant fees from Bristol-Myers Squibb, Roche Diagnostics, and International Technidyne Corporation. He is also on the speakers bureau for Roche Diagnostic Corporation and Sanofi-Aventis, and is the past president of the Anticoagulation Forum.

Dr. Hirsh discloses that he has received partial support for writing two books, one on fondaparinux and one on low-molecular-weight heparin.

Dr. Jacobson discloses that he has received grant monies from the National Institutes of Health, the Department of Veterans Affairs, Sanofi, Boehringer Ingelheim, and Roche Diagnostics. He is on the speakers bureau for Bristol-Myers Squibb and GlaxoSmithKline. Dr. Jacobson has served on advisory committees for Roche Diagnostics and Sanofi. He has served in fiduciary positions for the Loma Linda Veterans Association for Research and Education, the Loma Linda University School of Medicine Alumni Association, and the Anticoagulation Forum.

Dr. Hylek discloses that she has received grant monies from AstraZeneca and Bristol-Myers Squibb, and that she has also served on an advisory committee for Bristol-Myers Squibb.

Dr. Crowther discloses that he received grant monies from the Heart and Stroke Foundation, the Canadian Institutes for Health Research, Leo Laboratories, Pfizer, and Sanofi-Aventis. He also received consultant fees from Leo Laboratories, Sanofi-Aventis, Bayer, and Pfizer. Dr. Crowther has served on the speakers bureau for Leo Laboratories, Pfizer, Bayer, and Organon, and is on an advisory committee for Bayer.

Dr. Palareti discloses that he serves on the speakers bureau of Sanofi-Aventis, GlaxoSmithKline, Instrumentation Laboratory of Roche Diagnostics, and Dade-Behring. He is a member of the Executive Committee of the Italian Federation of Anticoagulation Clinics and the Italian Society of Hematology and Thrombosis (ISTH), and is Co-chair of the Subcommittee on Control of Anticoagulation of the ISTH.

American College of Clinical Pharmacy - Medical Specialty Society
American Society of Health-System Pharmacists - Professional Association

This is the current release of the guideline.

This guideline updates a previous version: Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004 Sep;126(3 Suppl):204S-33S.

None available

This NGC summary was completed by ECRI on November 19, 2004. The information was verified by the guideline developer on January 12, 2005. This summary was updated by ECRI on December 7, 2005 following the U.S. Food and Drug Administration (FDA) advisory on NovoSeven. This summary was updated by ECRI on March 6, 2007 following the U.S. Food and Drug Administration (FDA) advisory on Coumadin (warfarin sodium). This summary was updated by ECRI Institute on June 22, 2007 following the U.S. Food and Drug Administration (FDA) advisory on heparin sodium injection. This summary was updated by ECRI Institute on September 7, 2007 following the revised U.S. Food and Drug Administration (FDA) advisory on Coumadin (warfarin). This summary was updated by ECRI Institute on March 14, 2008 following the updated FDA advisory on heparin sodium injection. This NGC summary was updated by ECRI Institute on November 24, 2008. The updated information was verified by the guideline developer on January 7, 2009.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.