Abstract: Two studies with a combined total of 288 participants met the inclusion criteria for this review. One study compared low molecular weight heparin with unfractionated heparin and found no difference between the treatments in the prevention of DVT (odds ratio (OR) 1.23, 95% confidence interval (CI) 0.28 to 5.35). No bleeding events or deaths occurred. This study was open label and therefore at a high risk of performance bias. Additionally, the method of randomisation was not reported and therefore the risk of selection bias was unclear. In the second study heparin did not significantly improve prevention of pulmonary embolism (OR 1.02, 95% CI 0.44 to 2.37) when compared to placebo. Furthermore, when the level of amputation was considered, the incidence of pulmonary embolism was similar between the two treatment groups: above knee amputation (OR 0.79, 95% CI 0.31 to 1.97) and below knee amputation (OR 1.53, 95% CI 0.09 to 26.43). Ten participants died during the study; five underwent a post-mortem and three were found to have had a recent pulmonary embolism, all of whom had been on placebo. Bleeding events were reported in less than 10% of participants in both treatment groups but specific data were not presented. This study did not report the methods used to conceal allocation of treatment and therefore it was unclear if selection bias occurred. However, this study appeared to be free from all other sources of bias. No study looked at mechanical prophylaxis. As only two studies were included in this review, each comparing different interventions, there is insufficient evidence to make any conclusions regarding the most effective thromboprophylaxis regimen in patients undergoing lower limb amputation. Further large-scale studies that are of good quality are required.

Plain-language summary: After searching for relevant studies, we found two studies with a combined total of 288 participants to be included in this review of evidence. One study compared two forms of the anticoagulant heparin. Low molecular weight heparin offered no significant improvement over unfractionated heparin in the prevention of DVT. Furthermore neither drug caused bleeding. However, in this study both the participants and study personnel were aware of which treatment was being administered. This may have biased the results. It is unclear if other bias was introduced in the study because the process of randomly allocating treatment was not adequately described. The second study concluded that heparin was not more effective in preventing a PE than placebo whether the amputation was above or below the knee. Bleeding occurred in less than 10% of each treatment group but the study authors did not report specific numbers and therefore this could not be analysed. This study did not report the methods used to conceal how treatment was allocated but it was judged to be free from other sources of bias. This review found that there are too few trials to determine the most effective strategy in preventing VTE in people undergoing amputation of the lower limb. No study looked at mechanical forms of preventing VTE, such as compression devices, and therefore it is not possible to make any conclusions about these. Further good quality and large-scale studies are required.