Effect of Very Dose Warfarin therapy Upon the Markers of Activcation of Clotting Following Major Joint Replacement Surgery

Abstract 4395

Prophylaxis against post-operative deep vein thrombosis using low dose warfarin is appealing as it is inexpensive and with low risk of hemorrhage. Investigators have examined this issue with variable outcomes. Critical to our thinking is that the drug must be started prior to the elective surgical intervention in order to be an effective antithrombotic agent, while not causing potential hemorrhagic anticoagulation. This abstract describes the effect of such a regimen on the generation of markers of coagulation activation, comparing fixed very low dose warfarin (1 mg daily) to variable dose warfarin among patients having elective replacement of hip or knee surgery. The fixed low dose warfarin is begun 7 days prior to surgery and continued 28 days post operatively. Variable dose warfarin is begun at 5 mg the night prior to surgery and is continued for 28 days post operatively with the target INR 2.0–2.5, adjusted twice per week. For this study the markers of coagulation activation are prothrombin fragment F1+2 and thrombin-anti-thrombin complex (T-AT). They are measured prior to start of warfarin therapy (baseline), on the morning of surgery (OR Day), and on postoperative days 3 and 28. PIVKA II is measured at the same time points as a measure of warfarin activity other than the INR. For this study 10 patients for each group are taken from a larger group of patients participating in a randomized prospective study of this regimen now in progress. Both studies are IRB approved. Table 1 demonstrates the results.

As expected the PIVKA II is increased over normal for both groups by OR Day and on post-operative days 3 and 28. Greater increases in PIVKA II, as expected, occur among patients receiving variable dose warfarin, as this group received higher doses. The T-AT is elevated by post-operative day 3 and is returned to normal on post-operative day 28 in both groups. At each time point the T-AT values are equal for the two study groups. The F1+2 values are modestly increased for both groups on post-operative day 3, with better suppression of F1+2 generation by the variable dose regimen on day 28. In conclusion, the fixed low dose warfarin regimen is as effective as the variable dose warfarin as measured by the generation of T-AT, and is possibly somewhat less effective as determined by the generation of F1+2. The clinical significance of this difference is unknown, especially given the suppression of the T-AT. None of these patients suffered postoperative thromboembolic disease.

Adcock:Esoterix Laboratory Services, Inc: Employment.