Jan Man Wong, Yoon Kong LokeNorwich Medical School, University of East Anglia, Norwich, United KingdomAbstract: Orthopedic surgery is considered one of the most prominent risk factors for venous thromboembolism (VTE), but the optimal strategy for thromboprophylaxis remains a debatable topic. Consistent and reliable definitions of clinically relevant VTE and major bleeds in orthopedic research are particularly contentious areas, resulting in uncertainty about the actual benefit&ndash;harm balance of available interventions. For the newer oral anticoagulants, short-term clinical trials in highly selected patients with asymptomatic VTE (from mandatory radiological screening) must be supplemented by long-term efficacy and safety data in real-world settings (such as the Global Orthopedic Registry). The evidence gap leads to visible differences among recent recommendations from bodies such as the American College of Chest Physicians (2012), the American Academy of Orthopedic Surgeons (2011), and the National Institute of Clinical Excellence, England (NICE, 2012). While thromboprophylaxis after hip and knee arthroplasty is clearly recommended by all three bodies, there is no consistent agreement on the optimal agent or the duration of prophylaxis. Differences in opinion stem from subjective judgments on the relative weighting given to asymptomatic as opposed to symptomatic VTE, and the impact of major bleeding. While the newer oral anticoagulants (such as rivaroxaban and apixaban) seem to offer significant benefits compared to enoxaparin in the reduction of asymptomatic VTE, the data are limited by the paucity of symptomatic VTE and inconsistencies in capturing major bleeds. The lack of long-term experience in real world patients means that it is too early to judge whether the obvious convenience of newer oral anticoagulants will result in better patient adherence, safety, and quality of life as compared to enoxaparin. Further research should focus on clinically relevant outcomes, with clear definitions of bleeding, so that the benefit&ndash;harm trade-offs related to the diverse agents can be assessed through methods such as multiple treatment comparison meta-analysis.Keywords: enoxaparin, low-molecular-weight heparin, orthopedic surgery, venous thromboembolism, thromboprophylaxis, Global Orthopedic Registry (GLORY
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