The Timing of Drug Administration for Thromboprophylaxis Following Orthopaedic Surgery: Evidence and Controversies Related to Treatment Initiation and Duration

Costas      Papakostidis; Paul      J. Harwood; Efthimios      J. Karadimas; Hiang      Boon Tan; Peter      V. Giannoudis

doi:10.2174/157016111793744698

Abstract

Patients undergoing major orthopaedic surgery of the lower extremities or spine are at increased risk of venous thromboembolism (VTE). Although consensus exists as to the need for routine thromboprophylaxis in high risk patients, some aspects of this approach, such as the timing of the first dose and overall duration of the anticoagulation regimen, are subject to debate. Reviewing the available literature, there appears to be little evidence to support initiation of thromboprophylaxis more than 12 hours before surgery. Perioperative thromboprophylaxis (2 hours pre to 6 hours post -op) has been associated with an increased risk of bleeding complications whilst initiating prophylaxis more than 12 hours after surgery appears to increase the incidence of subsequent thromboembolic complications. Overall evidence would appear to support initiation of thromboprophylaxis 6 to 9 hours postoperatively, though further confirmatory studies investigating this variable in isolation would be useful to guide clinical decision making. Although evidence exists supporting extended duration thromboprophylaxis after major orthopaedic procedures, further evidence is required, using clinically important end points, prior to adoption of such an approach in all patients. Stratification of prophylaxis duration, based on risk factors for thromboembolic or bleeding complications, would seem a more rational approach than strict adherence to guidelines.

Keywords: Venous thromboembolism, orthopaedic surgery, trauma, rivaroxaban, dabigatran etexilate, Virchow's triad, hypercoagulability, intra-operative bleeding, neuraxial anaesthesia, randomized control trials (RCTs), meta-analyses, LMWH, bilateral venography, Fondaparinux, enoxaparin, meta-analysis, close-proximity to surgery, rivaroxaban, apixaban, Dabigatran etex-ilate, Pradaxa, Ri-varoxaban, PENTHIFRA, EPHESUS, PENTATHLON, PENTAMAKS, RE-NOVATE, RE-MODEL, RE-MOBILIZE, post-thrombotic syndrome, THR, TKR, ACCP, VTE, malignancy, obesity, heritable thrombophilia, pected prolonged immobilization, gastrointestinal bleed-ing, 95% CI, ns, PE, RCT, THA