MINIDOSE WARFARIN AND FAILURE TO PREVENT DEEP-VEIN THROMBOSIS AFTER JOINT REPLACEMENT SURGERY DESPITE INHIBITING THE POSTOPERATIVE RISE IN PLASMINOGEN-ACTIVATOR INHIBITOR ACTIVITY

In a prospective randomised study in patients undergoing elective tota l hip or knee replacement surgery, the antithrombotic efficacy of fixe d-minidose warfarin (1 mg daily commenced 7 days before surgery) was c ompared with that of subcutaneous calcium heparin (Calciparine, 5,000 IU t.d.s. commenced 2 h before surgery). Both regimens were continued until venography of the operated limb was performed 9-14 days postsurg ery. Venographically detected deep vein thromboses (DVTs) occurred in 15 of the 31 patients (48.4%) in the minidose warfarin group and in ei ght of the 37 patients (21.6%) receiving heparin. The absolute differe nce in the incidence of DVT was 26.8% in favour of heparin (95% confid ence interval [CI] -4.8--48.8%; p = 0.039). Proximal DVTs were detecte d in three patients receiving minidose warfarin and in none of those o n heparin (p = 0.09). Minidose warfarin appeared to prevent the postop erative rise in the activity of plasminogen activator inhibitor (PAI) that occurred with heparin, although preoperative PAI activity was gre ater in the warfarin group. The prothrombin time (PT) and activated pa rtial thromboplastin time (APTT) were within the normal range on the d ay of surgery in both treatment groups. Postsurgery, the minidose warf arin regimen produced a small, but significant prolongation of the PT compared with the group receiving heparin. In contrast to heparin, 1 m g warfarin daily failed to prevent postoperative acceleration of the A PTT. There was no significant difference between the two regimens in b leeding complications. In conclusion, the fixed-minidose warfarin regi men cannot be recommended for prevention of DVT after hip or knee repl acement surgery. Inhibition of the postoperative rise in PAI activity appears not to protect against DVT after major joint replacement surge ry.