Summary
A prospective, randomized trial was conducted to compare the effectiveness and safety
of warfarin given in two regimens in prevention of venous thrombosis after total knee
replacement. Adult patients scheduled for primary or revision total knee replacement
were randomly assigned to receive either a “two-step” warfarin regimen beginning 10-14
days pre-operatively or, alternatively, to begin warfarin the night before surgery.
Post-operatively, the dose was adjusted in both groups to achieve a target International
Normalized Ratio (INR) of 2.2 and prophylaxis was continued until venography on post-operative
days five through nine. Bleeding was assessed by surgical blood loss, transfusion
requirements, changes in hematocrit, and clinically identified bleeding complications.
The occurrence of deep vein thrombosis was nearly the same in the two treatment groups,
39% in patients randomized to the two-step regimen as compared to 38% in those beginning
the night before surgery. The occurrence of proximal vein thrombosis was also similar,
5% versus 7% (p = NS). Patients in the two-step group received 1.33 ± 1.26 transfusions
compared to 0.95 ± 1.22 in the night before group (p <0.05) and also had a lower nadir
post-operative hematocrit of 26.7 ± 3.1 as compared to 28.5 ± 3.2 (p <0.0001). Major
bleeding complications were associated with excessively prolonged INRs and occurred
in five patients in the two-step group and two in the night before group. Patients
in both groups who developed thrombosis had a significantly lower INR on post-operative
days two and three compared to those without thrombosis. We conclude that a prophylactic
warfarin regimen for prevention of deep vein thrombosis after total knee replacement
beginning the night before surgery is more convenient and may be associated with less
bleeding than a regimen beginning warfarin 10-14 days pre-operatively. Careful control
of anticoagulant intensity is needed to achieve maximum effectiveness and avoidance
of bleeding complications.
