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Arch Intern Med. 2000 Jul 24;160(14):2199-207.

Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients: a double-blind, randomized comparison. The North American Fragmin Trial Investigators.

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Thrombosis Research Unit, 601 S Tower, Foothills Hospital, 1403-29 St NW, Calgary, Alberta, Canada T2N 2T9.



Based on the current understanding that venous thrombosis starts perioperatively, administration of just-in-time low-molecular-weight heparin immediately before or in close proximity after hip arthroplasty may be more effective than usual clinical practice.


We performed a randomized, double-blind trial comparing subcutaneous dalteparin sodium given once daily immediately before or early after surgery with the use of postoperative warfarin sodium in 1472 patients undergoing elective hip arthroplasties. The primary end point was deep vein thrombosis detected using contrast venography performed after surgery (mean, 5. 7 days) in each group.


The frequencies of deep vein thrombosis for patients with interpretable venograms receiving preoperative and postoperative dalteparin for all deep vein thrombosis were 36 (10.7%) of 337 (P<.001) and 44 (13.1%) of 336 (P<.001), respectively, vs 81 (24.0%) of 338 for warfarin; for proximal deep vein thrombosis, 3 (0.8%) of 354 (P =.04) and 3 (0.8%) of 358 (P =.03), respectively, vs 11 (3.0%) of 363. Relative risk reductions for the dalteparin groups ranged from 45% to 72%. Symptomatic thrombi were less frequent in the preoperative dalteparin group (5/337 patients [1.5%]) vs the warfarin group (15/338 patients [4.4%]) (P =.02). Serious bleeding was similar among groups. Increased major bleeding at the surgical site was observed for patients receiving preoperative dalteparin vs warfarin (P =.01).


A modified dalteparin regimen in close proximity to surgery resulted in substantive risk reductions for all and proximal deep vein thrombosis, compared with warfarin therapy. Such findings have not been observed with low-molecular-weight heparin therapy commenced 12 hours preoperatively or 12 to 24 hours postoperatively vs oral anticoagulants. Increased major but not serious bleeding occurred in patients receiving preoperative dalteparin. Dalteparin therapy initiated postoperatively provided superior efficacy vs warfarin without significantly increased overt bleeding.

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