Drs. Basskin and Jacobson raise important points about our study. Investigators in one contemporary trial, which compared enoxaparin with placebo after major knee surgery, obtained a 60% rate of total deep venous thrombosis in patients who received placebo [1]. These results indicate that deep venous thrombosis is an ongoing problem despite improved surgical care and early patient ambulation.

Compliance with enoxaparin was not a major issue in our trial because enoxaparin was administered by the nursing staff during hospitalization.

We did not do subgroup analyses for age, mobility status, or other variables. Most of our patients were able to bear weight at the time of discharge but were not fully ambulatory. The randomization process, however, should have distributed patients equally between the two treatment arms so that the differences in outcome would be due to the intervention.

As prophylaxis, warfarin is usually administered alone, without heparin. To our knowledge, no study has formally evaluated the combination of warfarin and low-molecular-weight heparin in patients having knee surgery. One potential concern about such combination therapy would be a higher risk for early postoperative bleeding in a type of surgery that carries a significant risk for hemorrhage. Blood losses in our trial were in excess of 800 mL in each treatment arm.

We did not do an economic analysis because it was beyond the scope of our study. O'Brien and coworkers [2] have reported on the cost-effectiveness of warfarin relative to that of low-molecular-weight heparin in patients having hip arthroplasty.

We used a postoperative regimen not to bias our results but to allow prophylaxis for patients who had surgery while under regional anesthesia. Indeed, our anesthesiologists would have been reluctant to do regional anesthesia in the presence of warfarin. Because of the lack of comparative data, it is also not entirely clear whether preoperative warfarin is superior to postoperative warfarin. The RD Heparin Arthroplasty Group investigators [3] obtained a 41% rate of total deep venous thrombosis in their patients receiving warfarin, despite preoperative prophylaxis.

Overall, the main advantages of enoxaparin over warfarin are simplicity of administration (no need for laboratory monitoring) and greater efficacy in preventing total deep venous thrombosis. The need for warfarin monitoring is a major limitation of this type of prophylaxis, particularly in routine practice, where it is often difficult to maintain the international normalized ratio within the targeted range of 2.0 to 3.0.