Comparison of 5-mg and 10-mg loading doses in initiation of warfarin therapy.
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.


METHODS
Randomized clinical trial.


METHODS
Tertiary care teaching hospital.


METHODS
49 patients seen over a 5-month period with a target international normalized ratio (INR) of 2.0 to 3.0.


METHODS
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.


METHODS
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.
Harrison
L
L
Hamilton Civic Hospital, McMaster University, Ontario, Canada.
Johnston
M
M
Massicotte
M P
MP
Crowther
M
M
Moffat
K
K
Hirsh
J
J
D000925:Anticoagulants / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005164:Factor IX / Q000378:metabolism; D005167:Factor VII / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D006801:Humans; D008991:Monitoring, Physiologic; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D011486:Protein C; D014859:Warfarin; D005167:Factor VII; D011516:Prothrombin; D005164:Factor IX; D005170:Factor X