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Minidose Warfarin and Failure to Prevent Deep Vein Thrombosis After Joint Replacement Surgery Despite Inhibiting the Postoperative Rise in Plasminogen Activator Inhibitor Activity

Department of Pathological Sciences, The University of Manchester

Jean M. Thomson, Ph.D.

Department of Pathological Sciences, The University of Manchester

Peter K. MacCallum, MRCP

Department of Pathological Sciences, The University of Manchester

David A. Nicholson, FRCR

Department of Radiology, Withington Hospital, Manchester, England, Department of Radiology, Withington Hospital, Manchester, England

Frank J. Weighill, FRCR

Department of Orthopaedic Surgery, Withington Hospital, Manchester, England

Jerry G. Lemon, FRCR

Department of Orthopaedic Surgery, Withington Hospital, Manchester, England

In a prospective randomised study in patients undergoing elective total hip or knee replacement surgery, the antithrombotic efficacy of fixed-minidose warfarin (1 mg daily commenced 7 days before surgery) was compared 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 postsurgery. Venographically detected deep vein thromboses (DVTs) occurred in 15 of the 31 patients (48.4%) in the minidose warfarin group and in eight of the 37 patients (21.6%) receiving heparin. The absolute difference in the incidence of DVT was 26.8% in favour of heparin (95%l confidence interval [CI] -4.&--48.8%; p = 0.039). Proximal DVTs were detected in three patients receiving minidose warfarin and in none of those on heparin (p = 0.09). Minidose warfarin appeared to prevent the postoperative rise in the activity of plasminogen activator inhibitor (PAI) that occurred with heparin, although preoperative PAI activity was greater in the warfarin group. The prothrombin time (PT) and activated partial thromboplastin time (APTT) were within the normal range on the day of surgery in both treatment groups. Postsurgery, the minidose warfarin regimen produced a small, but significant prolongation of the PT compared with the group receiving heparin, In contrast to heparin, 1 mg warfarin daily failed to prevent postoperative acceleration of the APTT. There was no significant difference between the two regimens in bleeding complications. In conclusion, the fixed-minidose warfarin regimen cannot be recommended for prevention of DVT after hip or knee replacement surgery. Inhibition of the postoperative rise in PAI activity appears not to protect against DVT after major joint replacement surgery. Key Words: Warfarin—Heparin—Deep vein thrombosis prophylaxis—Coagulation—Fibrinolysis— Plasminogen activator inhibitor.

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