 |
 |
|
Home |
Current Issue |
Past Issues |
In the Clinic |
ACP Journal Club |
CME |
Collections |
Audio/Video |
Mobile |
Subscribe |
Tools |
Help |
ACP Online
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
15 January 1997 | Volume 126 Issue 2 | Pages 133-136
Background: Loading doses of warfarin that are larger than those used for maintenance therapy are widely used in clinical practice, but they have never been prospectively evaluated.
Objective: To compare the effect of 5- and 10-mg loading doses of warfarin on laboratory markers of warfarin's anticoagulant effect.
Design: Randomized clinical trial.
Setting: Tertiary care teaching hospital.
Patients: 49 patients seen over a 5-month period with a target international normalized ratio (INR) of 2.0 to 3.0.
Intervention: Patients were randomly assigned to receive an initial dose of 5 or 10 mg of warfarin. Subsequent doses of warfarin were administered on the basis of dosing nomograms.
Measurements: INRs and levels of factors II, VII, IX, and X and protein C were measured daily for 5 days.
Results: 11 of 25 patients in the 10-mg group (44% [95% CI, 34% to 54%]) and 2 of 24 patients in the 5-mg group (8% [CI, 3% to 14%]) had INRs greater than 2.0 at 36 hours (P = 0.005), at which time the factor VII levels were 27% (CI, 18% to 36%) in the 10-mg group and 54% (CI, 43% to 65%) in the 5-mg group (P < 0.001). In contrast, factor II levels were 74% (CI, 67% to 81%) in the 10-mg group and 82% (CI, 73% to 93%) in the 5-mg group (P > 0.2). At 60 hours, 9 of 25 patients in the 10-mg group (36% [CI, 17% to 54%]) and no patients in the 5-mg group had INRs greater than 3.0. At 84 hours, 15 of 24 patients in the 10-mg group (63% [CI, 43% to 81%]) and 19 of 24 patients in the 5-mg group (79% [CI, 62% to 95%]) had INRs between 2.0 and 3.0. Four patients in the 10-mg group and 1 patient in the 5-mg group received vitamin K for excessive prolongation of the INR.
Conclusions: A 5-mg loading dose of warfarin produces less excess anticoagulation than does a 10-mg loading dose; the smaller dose also avoids the development of a potential hypercoagulable state caused by precipitous decreases in levels of protein C during the first 36 hours of warfarin therapy.
Author and Article Information
For author affiliations and current author addresses, see end of text.
BRIEF COMMUNICATION
Comparison of 5-mg and 10-mg Loading Doses in Initiation of Warfarin Therapy
Grant Support: In part by the Heart and Stroke Foundation of Canada, the Medical Research Council of Canada, and DuPont Pharmaceuticals, USA.
Requests for Reprints: Jack Hirsh, MD, The Hamilton Civic Hospitals Research Centre, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada.
Current Author Addresses: Ms. Harrison; Ms. Johnston; Drs. Massicotte, Crowther, and Hirsh; and Ms. Moffat: The Hamilton Civic Hospitals Research Centre, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada.
Related articles in Annals:
This article has been cited by other articles:
|
|
 |
|
  L. M Hynicka, W. D Cahoon Jr, and B. L Bukaveckas Genetic Testing for Warfarin Therapy Initiation Ann. Pharmacother., September 1, 2008; 42(9): 1298 - 1303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ansell, J. Hirsh, E. Hylek, A. Jacobson, M. Crowther, and G. Palareti Pharmacology and Management of the Vitamin K Antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 160S - 198S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Kearon, S. R. Kahn, G. Agnelli, S. Goldhaber, G. E. Raskob, and A. J. Comerota Antithrombotic Therapy for Venous Thromboembolic Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 454S - 545S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A Lenzini, G. R Grice, P. E Milligan, S. K Gatchel, E. Deych, C. S Eby, R S. J Burnett, J. C Clohisy, R. L Barrack, and B. F Gage Optimal Initial Dose Adjustment of Warfarin in Orthopedic Patients Ann. Pharmacother., November 1, 2007; 41(11): 1798 - 1804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Millican, P. A. Lenzini, P. E. Milligan, L. Grosso, C. Eby, E. Deych, G. Grice, J. C. Clohisy, R. L. Barrack, R. S. J. Burnett, et al. Genetic-based dosing in orthopedic patients beginning warfarin therapy Blood, September 1, 2007; 110(5): 1511 - 1515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. E. Dager and M. P. Gulseth Implementing anticoagulation management by pharmacists in the inpatient setting Am. J. Health Syst. Pharm., May 15, 2007; 64(10): 1071 - 1079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. F. Gage Pharmacogenetics-Based Coumarin Therapy Hematology, January 1, 2006; 2006(1): 467 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Hillman, R. A. Wilke, S. H. Yale, H. J. Vidaillet, M. D. Caldwell, I. Glurich, R. L. Berg, J. Schmelzer, and J. K. Burmester A Prospective, Randomized Pilot Trial of Model-Based Warfarin Dose Initiation using CYP2C9 Genotype and Clinical Data Clin. Med. Res., August 1, 2005; 3(3): 137 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. T. Haines and E. A. Nutescu Current and emerging treatment options for venous thrombosis: A case discussion Am. J. Health Syst. Pharm., March 15, 2005; 62(6): 593 - 605. [Full Text] [PDF]
|
|
|
|
|
|
B. J. G. Larson, M. S. Zumberg, and C. S. Kitchens A Feasibility Study of Continuing Dose-Reduced Warfarin for Invasive Procedures in Patients With High Thromboembolic Risk Chest, March 1, 2005; 127(3): 922 - 927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Bartholomew Transition to an Oral Anticoagulant in Patients With Heparin-Induced Thrombocytopenia Chest, February 1, 2005; 127(2_suppl): 27S - 34S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D Eckhoff, R. J DiDomenico, and N. L Shapiro Initiating Warfarin Therapy: 5 mg versus 10 mg Ann. Pharmacother., December 1, 2004; 38(12): 2115 - 2121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ansell, J. Hirsh, L. Poller, H. Bussey, A. Jacobson, and E. Hylek The Pharmacology and Management of the Vitamin K Antagonists: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 204S - 233S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. R. Buller, G. Agnelli, R. D. Hull, T. M. Hyers, M. H. Prins, and G. E. Raskob Antithrombotic Therapy for Venous Thromboembolic Disease: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 401S - 428S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Dowd Anticoagulation in the Elderly Journal of Pharmacy Practice, April 1, 2004; 17(2): 94 - 102. [Abstract] [PDF]
|
|
|
|
 |
|
 M. A. Crowther, L. Harrison, and J. Hirsh Randomized Trial of Warfarin Nomograms Ann Intern Med, March 16, 2004; 140(6): 490 - 490. [Full Text] [PDF]
|
|
|
|
|
|
K. L. McCall Randomized Trial of Warfarin Nomograms Ann Intern Med, March 16, 2004; 140(6): 491 - 491. [Full Text] [PDF]
|
|
|
|
|
|
B. F. Gage Randomized Trial of Warfarin Nomograms Ann Intern Med, March 16, 2004; 140(6): 489 - 489. [Full Text] [PDF]
|
|
|
|
|
|
R. J. DiDomenico Randomized Trial of Warfarin Nomograms Ann Intern Med, March 16, 2004; 140(6): 489 - 490. [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. Rich The Management of Venous Thromboembolic Disease in Older Adults J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2004; 59(1): M34 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-A. Linkins, P. T. Choi, and J. D. Douketis Clinical Impact of Bleeding in Patients Taking Oral Anticoagulant Therapy for Venous Thromboembolism: A Meta-Analysis Ann Intern Med, December 2, 2003; 139(11): 893 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Georgin, J. Pouchot, F. Raschilas, S. Barete, D. L. Lerolle, and P. Vinceneux Paradoxical Venous Limb Gangrene Complicating Oral Anticoagulation in a Patient With Cancer-Associated Deep Venous Thrombosis Arch Dermatol, September 1, 2003; 139(9): 1126 - 1128. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Schulman Care of Patients Receiving Long-Term Anticoagulant Therapy N. Engl. J. Med., August 14, 2003; 349(7): 675 - 683. [Full Text] [PDF]
|
|
|
|
|
|
G. W Roberts, T. Helboe, C. B. Nielsen, A. S Gallus, I. Jensen, D. G Cosh, and V. S Eaton Assessment of an Age-Adjusted Warfarin Initiation Protocol Ann. Pharmacother., June 1, 2003; 37(6): 799 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. E Dager Initiating Warfarin Therapy Ann. Pharmacother., June 1, 2003; 37(6): 905 - 908. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hirsh, V. Fuster, J. Ansell, and J. L. Halperin American Heart Association/American College of Cardiology Foundation guide to warfarin therapy J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1633 - 1652. [Full Text] [PDF]
|
|
|
|
|
|
M. J. Kovacs, M. Rodger, D. R. Anderson, B. Morrow, G. Kells, J. Kovacs, E. Boyle, and P. S. Wells Comparison of 10-mg and 5-mg Warfarin Initiation Nomograms Together with Low-Molecular-Weight Heparin for Outpatient Treatment of Acute Venous Thromboembolism: A Randomized, Double-Blind, Controlled Trial Ann Intern Med, May 6, 2003; 138(9): 714 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hirsh, V. Fuster, J. Ansell, and J. L. Halperin American Heart Association/American College of Cardiology Foundation Guide to Warfarin Therapy Circulation, April 1, 2003; 107(12): 1692 - 1711. [Full Text] [PDF]
|
|
|
|
|
|
A. I. Schafer, M. N. Levine, B. A. Konkle, and C. Kearon Thrombotic Disorders: Diagnosis and Treatment Hematology, January 1, 2003; 2003(1): 520 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Anderson, S. J.-A. Wilson, J. Blundell, D. Petrie, R. Leighton, W. Stanish, D. Alexander, K. S. Robinson, E. Burton, and M. Gross Comparison of a Nomogramand Physician-Adjusted Dosageof Warfarin for Prophylaxis Against Deep-Vein Thrombosis After Arthroplasty J. Bone Joint Surg. Am., November 12, 2002; 84(11): 1992 - 1997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. V Joffe and S. Z Goldhaber Laboratory thrombophilias and venous thromboembolism Vascular Medicine, May 1, 2002; 7(2): 93 - 102. [Abstract] [PDF]
|
|
|
|
|
|
J. Hirsh and A. Y. Y. Lee How we diagnose and treat deep vein thrombosis Blood, May 1, 2002; 99(9): 3102 - 3110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Higashi, D. L. Veenstra, L. M. Kondo, A. K. Wittkowsky, S. L. Srinouanprachanh, F. M. Farin, and A. E. Rettie Association Between CYP2C9 Genetic Variants and Anticoagulation-Related Outcomes During Warfarin Therapy JAMA, April 3, 2002; 287(13): 1690 - 1698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Warkentin Venous Limb Gangrene during Warfarin Treatment of Cancer-Associated Deep Venous Thrombosis Ann Intern Med, October 16, 2001; 135(8_Part_1): 589 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Schechter, H. P.G. Dave, and B. M. Alving Update in Hematology Ann Intern Med, January 2, 2001; 134(1): 38 - 46. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Ginsberg, M. A. Crowther, R. H. White, and T. L. Ortel Anticoagulation Therapy Hematology, January 1, 2001; 2001(1): 339 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hirsh, J. E. Dalen, D. R. Anderson, L. Poller, H. Bussey, J. Ansell, and D. Deykin Oral Anticoagulants: Mechanism of Action, Clinical Effectiveness, and Optimal Therapeutic Range Chest, January 1, 2001; 119(1_suppl): 8S - 21S. [Full Text] [PDF]
|
|
|
|
|
|
J. Ansell, J. Hirsh, J. Dalen, H. Bussey, D. Anderson, L. Poller, A. Jacobson, D. Deykin, and D. Matchar Managing Oral Anticoagulant Therapy Chest, January 1, 2001; 119(1_suppl): 22S - 38S. [Full Text] [PDF]
|
|
|
|
|
|
T. M. Hyers, G. Agnelli, R. D. Hull, T. A. Morris, M. Samama, V. Tapson, and J. G. Weg Antithrombotic Therapy for Venous Thromboembolic Disease Chest, January 1, 2001; 119(1_suppl): 176S - 193S. [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Kalafut, R. Gandhi, C. S. Kidwell, and J. L. Saver Safety and Cost of Low-Molecular-Weight Heparin as Bridging Anticoagulant Therapy in Subacute Cerebral Ischemia Stroke, November 1, 2000; 31(11): 2563 - 2568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Guidelines on diagnosis and management of acute pulmonary embolism Eur. Heart J., August 2, 2000; 21(16): 1301 - 1336. [PDF]
|
|
|
|
|
|
D. E. Wallis, R. Quintos, W. Wehrmacher, and H. Messmore Safety of Warfarin Anticoagulation in Patients With Heparin-Induced Thrombocytopenia Chest, November 1, 1999; 116(5): 1333 - 1338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Wallis, B. E. Lewis, H. L. Messmore, R. Pifarre, and J. M. Walenga Inadequacy of Current Prevention Strategies for Heparin-Induced Thrombocytopenia Clinical and Applied Thrombosis/Hemostasis, October 1, 1999; 5(1_suppl): S16 - S20. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Angelo, R. J. Nardino, and M. A. Crowther Comparing 5-mg and 10-mg Warfarin Loading Doses: Are the Groups Similar? Arch Intern Med, July 26, 1999; 159(14): 1624 - 1625. [Full Text] [PDF]
|
|
|
|
|
|
Mark. A. Crowther, J. B. Ginsberg, C. Kearon, L. Harrison, J. Johnson, M. P. Massicotte, and J. Hirsh A Randomized Trial Comparing 5-mg and 10-mg Warfarin Loading Doses Arch Intern Med, January 11, 1999; 159(1): 46 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Z. Goldhaber Pulmonary Embolism N. Engl. J. Med., July 9, 1998; 339(2): 93 - 104. [Full Text] [PDF]
|
|
|
|
|
|
R. H. White, H. Zhou, and P. S. Romano Length of Hospital Stay for Treatment of Deep Venous Thrombosis and the Incidence of Recurrent Thromboembolism Arch Intern Med, May 11, 1998; 158(9): 1005 - 1010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Z Goldhaber Clinical overview of venous thromboembolism Vascular Medicine, February 1, 1998; 3(1): 35 - 40. [Abstract] [PDF]
|
|
|
|
|
|
C. Kearon and J. Hirsh Management of Anticoagulation before and after Elective Surgery N. Engl. J. Med., May 22, 1997; 336(21): 1506 - 1511. [Full Text] [PDF]
|
|
Article
