Timing of Initial Administration of Low-Molecular-Weight Heparin Prophylaxis Against Deep Vein Thrombosis in Patients Following Elective Hip Arthroplasty

Hull, Russell D.; Pineo, Graham F.; Stein, Paul D.; Mah, Andrew F.; MacIsaac, Susan M.; Dahl, Ola E.; Ghali, William A.; Butcher, Matthew S.; Brant, Rollin; Bergqvist, David; Hamulyák, Karly; Francis, Charles W.; Marder, Victor J.; Raskob, Gary E.

doi:10.1001/archinte.161.16.1952

Cited by 150 publications

(119 citation statements)

References 59 publications

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“…However, increased plasma concentrations of F1.2 and D-Dimer were found to correlate with thrombosis [33,37], and our results support the view that the interval between surgery and the first administration of prophylaxis is a critical variable that 189 may influence the occurrence of deep vein thrombosis in patients undergoing elective hip arthroplasty [38]. 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.…”

Section: Discussionsupporting

confidence: 84%

Time course of thrombosis and fibrinolysis during total hip surgery

Reikerås¹,

Clementsen²,

Bjørnsen³

2006

J Orthopaed Traumatol

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Venous thrombosis is common in elective hip surgery, and prophylactic treatment is used up to 12 hours before or after surgery. Recent clinical trials suggested that the timing of initiating prophylaxis significantly influenced the antithrombotic effectiveness. Furthermore, the timing of initiating antifibrinolytic treatment to reduce blood loss has been a question of debate. We studied the time course of coagulation and fibrinolysis at all phases during total hip arthroplasty. Specific markers of thrombosis (prothrombin fragment F1.2) and of fibrinolysis (plasminantiplasmin (PAP) and D-dimer) were examined in eight female and two male patients aged 16–62 years. There was a progressive increase in plasma concentrations of F1.2 during the operation. From the end of operation to 4 hours afterwards, there was no further increase in F1.2. Levels of D-dimer did not change until wound closure, when they began to increase up to 4 hours postoperatively, but there were no changes in PAP during the operation or during the 4-h postoperative period. Therefore, surgery for total hip arthroplasty activates thrombin generation during operation with fibrin degradation at a later stage. These observations harmonize with the notion that the interval between surgery and first administration of antithrombotic treatment is a critical variable.

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Section: Discussionsupporting

confidence: 84%

Time course of thrombosis and fibrinolysis during total hip surgery

Reikerås¹,

Clementsen²,

Bjørnsen³

2006

J Orthopaed Traumatol

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“…However, the optimal timing for the initiation of pharmaco-prophylaxis is one of the issues raised by thromboprophylaxis, and the administration of anticoagulant agents following this screening test might be regarded as being relatively late. There has been debate in the literature regarding the issue of how to maximize efficacy while minimizing bleeding risk [32] because the peak efficacy of anticoagulant agents depends on the timing of the first injection [33,34]. According to a systematic review [33], the incidence of DVT was 19% in patients to whom low-molecular-weight heparin (LMWH) was administered 12 hours before surgery, 12% in patients given LMWH during surgery, and 14% in those treated postoperatively.…”

Section: Fibrinolysis and Thrombolysis 170mentioning

confidence: 99%

Coagulation and Fibrinolysis Markers and Their Use for the Prediction of High Risk Patients with Venous Thromboembolism Following Total Hip Arthroplasty

Inaba¹,

Yukizawa²,

Saito³

2014

Fibrinolysis and Thrombolysis

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“…LY517717 was first administered 6-8 h postoperatively, whereas enoxaparin was administered the night before surgery. In theory, this should have put LY517717 at a disadvantage in terms of efficacy, and perhaps at an advantage in terms of bleeding [5,20]. However, postoperative administration of LY517717 proved to be safe and efficacious.…”

Section: Discussionmentioning

confidence: 99%

A phase II study of the oral factor Xa inhibitor LY517717 for the prevention of venous thromboembolism after hip or knee replacement

Agnelli

Haas

Ginsberg

et al. 2007

Journal of Thrombosis and Haemostasis

106

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To cite this article: Agnelli G, Haas S, Ginsberg JS, Krueger KA, Dmitrienko A, Brandt JT. A phase II study of the oral factor Xa inhibitor LY517717 for the prevention of venous thromboembolism after hip or knee replacement. J Thromb Haemost 2007; 5: 746-53.Summary. Background: LY517717 is an oral direct inhibitor of activated factor X that is currently under clinical development. Objectives: The aims of this proof-of-concept study in patients undergoing total knee replacement (TKR) or total hip replacement (THR) were to determine whether LY517717 can safely reduce the risk of venous thromboembolism (VTE) and to identify at least one dose of LY517717 that is non-inferior to enoxaparin. Methods: In a double-blind, parallel-arm, doseranging study, patients undergoing TKR or THR were randomly allocated to receive once-daily oral LY517717 (25, 50, 75, 100, 125 or 150 mg), started 6-8 h after wound closure, or s.c. enoxaparin, 40 mg, started in the evening before surgery. The primary efficacy endpoint was the composite of deep venous thrombosis (DVT), detected by mandatory bilateral venography performed at the end of the study treatment (between days 5 and 9), and objectively confirmed symptomatic DVT and/or pulmonary embolism (PE), occurring during the treatment period. The combination of major and minor bleeding was the primary safety endpoint. Results: Five hundred and seven patients received at least one dose of LY517717 or enoxaparin (safety population). Three hundred and ninety-one patients had evaluable bilateral venography or experienced a clinical DVT and/or PE (primary efficacy population). LY517717 treatment resulted in a dose-dependent decrease in the incidence of thromboembolic events (P = 0.0001). The incidences of VTE with 100, 125, and 150 mg of LY517717 were 19%, 19% and 16%, respectively, compared to 21% with enoxaparin. The efficacies of 100-mg, 125-mg and 150-mg doses of LY517717 were non-inferior to that of enoxaparin according to prespecified criteria. Bleeding events were uncommon in both LY517717 and enoxaparin patients. Conclusions: Doses of 100, 125 and 150 mg of LY517717 are non-inferior to enoxaparin for the prevention of VTE after TKR or THR, and are associated with similar low rates of bleeding.

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Timing of Initial Administration of Low-Molecular-Weight Heparin Prophylaxis Against Deep Vein Thrombosis in Patients Following Elective Hip Arthroplasty

Cited by 150 publications

References 59 publications

Time course of thrombosis and fibrinolysis during total hip surgery

Time course of thrombosis and fibrinolysis during total hip surgery

Coagulation and Fibrinolysis Markers and Their Use for the Prediction of High Risk Patients with Venous Thromboembolism Following Total Hip Arthroplasty

A phase II study of the oral factor Xa inhibitor LY517717 for the prevention of venous thromboembolism after hip or knee replacement

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