PREVENTION OF POSTOPERATIVE DEEP VEIN THROMBOSIS BY WARFARIN Two-stage regimen prevents excessive bleeding The risk of deep vein thrombosis in total hip or knee replacement is estimated at 45-70% in untreated patients. Warfarin sodium, dextran 40, aspirin and heparin sodium have been recommended for antithrombotic prophylaxis - warfarin particularly, though the risk of post-operative bleeding has limited its usage. In a randomised, prospective study of 100 patients, warfarin sodium was compared with dextran 40 in the prevention of venous thrombosis. In the dextran group, 43 patients were each given a loading dose (10 mljkg) as a continuous infusion beginning I hour before surgery, then a maintenance dose of 7 ml/kgj24 hours for 4.5 days. The 57 patients in the warfarin group were given doses (starting 10-14 days before surgery) which were adjusted to prolong prothrombin time to 1.5-3.0 seconds longer than the preoperative value and then to 1.5 times the postoperative control value. The mean daily preoperative dose was 3.0mg, ranging from 0.5-100mg. 53 warfarin and 37 dextran patients underwent postoperative venography. In the warfarin group, II (21 %) developed a venous thrombosis and only one had a thrombus in the femoral-popliteal region. A significantly higher proportion of the dextran group (19; 51 %) showed thrombi in the femoral-popliteal area and also in the minor veins of the calf. The incidence of femoral- popliteal thrombi was 2% (warfarin) and 16% (dextran). There was no significant correlation with factors thought to influence susceptibility to venous thrombosis, i.e. age, anaesthetic time, sex, prior history of thromboembolic disease or bone surgery on the legs. No difference in the incidence or degree of bleeding was noted between the 2 treatment groups. The favourable results seen with warfarin in this trial may be due to some aspects of the 2-stage dose regimen. By beginning treatment 10-14 days before surgery, a stable low level of anticoagulation is established and this allows: • Antithrombotic protection during surgery when risk of thrombus development is greatest, without causing excessive bleeding • After surgery, greater warfarin effect by increased dosage; usually to double the amount given before surgery • Calculation of correct individual dose ranges, which makes dose regulation easier in the critical perioperative period. Thus the ' ... elective nature of such surgery provides the time required to attain optimal anticoagulant protection, such as has been demonstrated for the two-step warfarin regimen described herein.' Francis, C.W. et al.: Journal of the American Medical Association 249: 374 (21 Jan 1983) 10 INPHARMA 12 Mar 1983 0156-2703/83/0312·0010/0$01.00/0 "ADIS Press

PREVENTION OF POSTOPERATIVE DEEP VEIN THROMBOSIS BY WARFARIN

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PREVENTION OF POSTOPERATIVE DEEP VEIN THROMBOSIS BY WARFARIN

Two-stage regimen prevents excessive bleedingThe risk of deep vein thrombosis in total hip or knee replacement is estimated at 45-70% in untreated patients.Warfarin sodium, dextran 40, aspirin and heparin sodium have been recommended for antithrombotic prophylaxis warfarin particularly, though the risk of post-operative bleeding has limited its usage.In a randomised, prospective study of 100 patients, warfarin sodium was compared with dextran 40 in the preventionof venous thrombosis. In the dextran group, 43 patients were each given a loading dose (10 mljkg) as a continuousinfusion beginning I hour before surgery, then a maintenance dose of 7 ml/kgj24 hours for 4.5 days. The 57 patientsin the warfarin group were given doses (starting 10-14 days before surgery) which were adjusted to prolongprothrombin time to 1.5-3.0 seconds longer than the preoperative value and then to 1.5 times the postoperative controlvalue. The mean daily preoperative dose was 3.0mg, ranging from 0.5-100mg. 53 warfarin and 37 dextran patientsunderwent postoperative venography. In the warfarin group, II (21 %) developed a venous thrombosis and only onehad a thrombus in the femoral-popliteal region. A significantly higher proportion of the dextran group (19; 51 %)showed thrombi in the femoral-popliteal area and also in the minor veins of the calf. The incidence of femoralpopliteal thrombi was 2% (warfarin) and 16% (dextran). There was no significant correlation with factors thought toinfluence susceptibility to venous thrombosis, i.e. age, anaesthetic time, sex, prior history of thromboembolic disease orbone surgery on the legs. No difference in the incidence or degree of bleeding was noted between the 2 treatmentgroups. The favourable results seen with warfarin in this trial may be due to some aspects of the 2-stage dose regimen.By beginning treatment 10-14 days before surgery, a stable low level of anticoagulation is established and this allows:

• Antithrombotic protection during surgery when risk of thrombus development is greatest, without causingexcessive bleeding

• After surgery, greater warfarin effect by increased dosage; usually to double the amount given before surgery• Calculation of correct individual dose ranges, which makes dose regulation easier in the critical perioperative

period.Thus the '... elective nature of such surgery provides the time required to attain optimal anticoagulant protection, suchas has been demonstrated for the two-step warfarin regimen described herein.'Francis, C.W. et al.: Journal of the American Medical Association 249: 374 (21 Jan 1983)

10 INPHARMA 12 Mar 1983 0156-2703/83/0312·0010/0$01.00/0 "ADIS Press