Venous blood clot prevention in people undergoing lower limb amputation

Amputation of the leg is most often performed to remove dead tissue (gangrene), painful ulcers, tumours, or tissue with an inadequate blood supply. One of the most common causes of an inadequate blood supply is a narrowing of the arteries of the legs, which accounts for approximately 70% of amputations. In patients with this condition, blood clots are more likely to cause problems such as venous thromboembolism (VTE). This comprises two conditions, a blood clot in the legs (deep vein thrombosis (DVT)) or a blood clot in the arteries of the lungs (pulmonary embolism (PE)). The risk of these events occurring is higher in people undergoing amputations. There are two forms of preventive measures for VTE, drugs or compression devices. Drugs are proven to be effective in preventing VTE but are also associated with adverse side effects. Compression stockings or devices do not cause side effects but are not suitable for everyone. Current guidelines recommend that any person undergoing an amputation of the lower limb should be offered drugs to prevent a blood clot. However, in people with amputations it is not clear which method is best. This review aimed to establish the best method.

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.

Authors' conclusions: 

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.

Read the full abstract...

Patients undergoing major amputation of the lower limb are at increased risk of venous thromboembolism (VTE). Risk factors for VTE in amputees include advanced age, sedentary lifestyle, longstanding arterial disease and an identifiable hypercoagulable condition. Evidence suggests that pharmacological prophylaxis (for example heparin, factor Xa inhibitors, vitamin K antagonists, direct thrombin inhibitors, antiplatelets) is effective in preventing deep vein thrombosis (DVT) but it is associated with an increased risk of bleeding. Mechanical prophylaxis (for example antiembolism stockings, intermittent pneumatic compression and foot impulse devices), on the other hand, is non-invasive and has no side effects. However, it is not always appropriate in patients with contraindications such as peripheral arterial disease (PAD), arteriosclerosis or bilateral lower limb amputations. It is important to determine the most effective thromboprophylaxis and whether this is one treatment alone or in combination with another. To date, no systematic review has been conducted examining the effectiveness of thromboprophylaxis in preventing VTE in people undergoing amputation.


To determine the effectiveness of thromboprophylaxis in preventing VTE in people undergoing major amputation of the lower extremity.

Search strategy: 

The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2013) and CENTRAL (2013, Issue 4). Clinical trials databases were searched (May 2013). No date or language restrictions were applied. Non-English trials were translated where required and reference lists of identified studies were handsearched.

Selection criteria: 

Randomised controlled trials and quasi-randomised controlled trials in which people undergoing a major unilateral or bilateral amputation (for example hip disarticulation, transfemoral, knee disarticulation and transtibial) of the lower extremity were allocated to different types or regimens of thromboprophylaxis (including pharmacological or mechanical prophylaxis) or placebo.

Data collection and analysis: 

Selection of studies, data extraction and risk of bias were completed independently by two review authors. Any disagreements were resolved by discussion. Meta-analysis could not be completed as the two included studies compared different treatments and therefore the data could not be pooled.

Main results: 

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.