"Venous Thromboembolism Prophylaxis in Orthopedic Surgery: Appendices" (see also "Venous Thromboembolism Prophylaxis in Orthopedic Surgery: Main Report") - Major orthopedic surgery (total hip replacement, total knee replacement or hip fracture surgery) carries a high risk of venous thromboembolism. Pulmonary embolism following orthopedic surgery is reported to be rare. However, without prophylaxis, historical data suggest that hospital acquired deep venous thrombosis has been estimated to occur in 40 to 60 percent of cases in the 7 to 14 days following surgery compared with 10 to 40 percent among medical or general surgical patients. While asymptomatic deep vein thrombosis is identified more frequently than symptomatic deep vein thrombosis in clinical trials due to routine screening, there is disagreement as to the clinical relevance of asymptomatic cases. While certain patient characteristics (i.e. age, immobility, comorbidities) have been suggested to increase the risk of venous thromboembolism regardless of the clinical setting, major orthopedic surgery contributes additional factors such as use of general anesthesia which may prolong immobility and surgical involvement of the femoral vein. A variety of strategies to prevent venous thromboembolism are available and with routine use, the rate of symptomatic venous thromboembolism in patients within 3 months of surgery is 1.3 to 10 percent. The main limitation of pharmacologic venous thromboembolism prophylaxis is the risk of bleeding. Based on historical data major bleeding following total hip replacement and total knee replacement is estimated to be 1 to 3 percent. Determining the incidence of major bleeding with pharmacologic thromboprophylaxis is complicated by the variability in the definitions used in published literature and paucity of data in control patients. Following removal of an infected prosthesis and extended intravenous antibiotic treatment further surgery may be required to either implant a new prosthesis or perform an arthrodesis of the joint. There are many unknowns that need to be explored in a comparative effectiveness review. In contemporary practice, the risk of venous thromboembolism, pulmonary embolism, and deep vein thrombosis, and the causal link between deep vein thrombosis and pulmonary embolism has not been well established. Previous observations of the incidence of pulmonary embolism in patients who have undergone orthopedic surgery with confirmed deep vein thrombosis suggests that pulmonary embolism and deep vein thrombosis are related disorders. However, whether the presence of deep vein thrombosis affects the risk of pulmonary embolism and to what degree if so remains unclear in the literature. Widespread use of anticoagulants to treat venous thrombomebolism for many decades along with the evolution of diagnostic strategies have limited the availability of literature regarding the natural history of venous thromboembolism. In addition to major orthopedic surgery, there are a variety of other orthopedic surgeries in which the impact of venous thromboembolic prophylaxis has not been well evaluated. These orthopedic surgeries of interest include knee athroscopy, surgical repair of lower extremity injuries distal to the hip, and elective spine surgery. While prophylactic strategies may decrease the risk of venous thromboembolism, pulmonary embolism, and deep vein thrombosis, the magnitude of benefit in contemporary practice using rigorous definitions of endpoints and the impact of duration of prophylaxis on outcomes is not well delineated. Whether dual prophylactic strategies are superior to a single modality is not well defined. In addition, in order to determine comparative effectiveness, both the benefits and harms need to be appreciated. Finally, several previous meta-analyses and guidelines allowed the use of medications or devices that are not available for use in the United States reducing their applicability.