Subcutaneous Low-Molecular Weight Heparin or Oral Anticoagulants for the Prevention of Deep-Vein Thrombosis in Elective Hip and Knee Replacement?

Abstract

SummaryObjective. To compare efficacy, safety, and feasibility of adjusted- dose oral anticoagulants (OAC) versus fixed-dose subcutaneous low molecular weight heparin (LMWH) for the prevention of deep venous thrombosis (DVT) in patients who have undergone elective hip or knee replacement.Design. Multicentre, single blind randomised trial. OAC (acenocoumarol, target International Normalised Ratio, 2.0-3.0) and LMWH (nadroparine, 60 aXa IU/kg once daily) were started preoperatively and continued for 10 days. All outcome measures were adjudicated by an independent committee unaware of treatment allocation.Subjects. 672 consecutive patients scheduled for elective hip or knee replacement surgery. All patients wore bilateral graduated compression stockings.Main outcome measures. The endpoint for the assessment of efficacy was venography confirmed DVT or confirmed symptomatic pulmonary embolism. The endpoint for the assesment of safety was clinically important bleeding during study treatment or within 48 h of the end of treatment.Results. Among the 517 patients with interpretable venograms, 391 had a hip replacement and 126 had a knee implant. DVT was demonstrated in 50 (20%) of 257 patients allocated to OAC and 43 (17%) of 260 patients allocated to nadroparine (p = 0.45), for an absolute difference in DVT incidence of 2.9% in favour of nadroparine (95% Cl, -3.7-9.5). Clinically important bleeding occurred in eight (2.3%) of the 342 oral anticoagulant treated patients and in five (1.5%) of the 330 nadroparine treated patients (p = 0.62), for an absolute difference in favour of nadroparine of 0.8% (95% Cl, -1.3-2.9).Conclusion. Patients who undergo major orthopaedic operations have a high risk of venous thromboembolism. Once daily fixed-dose subcutaneous nadroparine is at least as efficacious and safe as daily adjusted OAC for prophylaxis against DVT after hip or knee implantation but is more simple to administer.

Towards evidence-based guidelines for the prevention of venous thromboembolism: systematic reviews of mechanical methods, oral anticoagulation, dextran and regional anaesthesia as thromboprophylaxis

“…The majority of trials had compared oral anticoagulation with LMWH (nine trials, [89][90][91][92][93][94][95][96]99 7260 patients), whereas the comparator was lowdose unfractionated heparin in four trials 82,85,87,97 among 382 patients ( Figure 19). Overall, an oral anticoagulant regimen appeared less effective than either an unfractionated or LMWH regimen for the prevention of DVT.…”

Time course of thrombosis and fibrinolysis during total hip surgery

“…Thromboprophylaxis in close proximity to hip arthroplasty, either preoperatively or postoperatively, may balance efficacy and safety to prevent thrombosis on one hand and bleeding on the other hand. Clinical observations indicated that LMWH at half the usual high-risk dose begun in close proximity to THA either preoperatively or postoperatively [39,40] was more effective than LMWH administered 12 hours preoperatively or 12-18 hours postoperatively [17,19]. However, administration less than 2 hours before surgery resulted in increased major bleeding, while a postoperative regimen of LMWH 4-6 hours after surgery provided efficacy without significantly increasing bleeding [40].…”

“…In Europe, it is recognized that deep vein thrombosis originates perioperatively and that preoperative prophylaxis may optimize antithrombotic effects [3][4][5][6][7]. Low-molecular-weight heparin (LMWH) is usually initiated 12 hours preoperatively [8][9][10][11][12][13][14][15][16][17][18][19][20][21]. In North America, LMWH proIn orthopaedic surgery, blood loss can be quite substantial.…”

Structure and anticoagulant properties of sulfated glycosaminoglycans from primitive Chordates

“…How-ever, the unrestricted use of heparin as an antithrombotic agent is limited due to its various side effect, such as thrombocytopenia, osteoporosis, and hemorrhagic complications (Ockelford et al 1982, Carreras 1980, Mätzsch et al 1986). More recently, heparin has been gradually replaced by its low molecular weight derivative (less than 3,000 and ∼ 9,000, comparing to ∼ 13,000 of native heparin), obtained by partial fragmentation and fractionation of native heparin (Hamulyák et al 1995, Meyer et al 1995. Fragments below 16 to 20 monosaccharide units per heparin molecule (MW < 5, 000), while containing the specific pentasaccharide sequence essential for binding AT III, are not long enough to permit binding to thrombin; they therefore inhibit only activated factor X (Choay et al 1981).…”