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 people 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 effective in preventing VTE, but also have 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, it is not clear which method is best for people having a lower limb amputation. This review aimed to establish the best method.

Study characteristics and main results

This review was first published in 2013, and we searched for any studies that have taken place since then (up to 5 November 2019). We did not find any eligible new studies for this update. The review includes the original two studies with a combined total of 288 participants.

One study compared two forms of the anticoagulant heparin. We found no evidence of a difference between unfractionated heparin and low molecular weight heparin in the prevention of DVT. None of the participants reported any 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 because the study did not adequately describe the process of randomly allocating treatment.

The second study found no evidence of a benefit for heparin compared with placebo in preventing a PE, 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 we could not analyse this. This study did not report the methods used to conceal how treatment was allocated, but we judged it 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.

Certainty of the evidence

The certainty of the evidence provided by these studies is very low for the comparison of unfractionated heparin against low molecular weight heparin, and low for the comparison of heparin against placebo. We downgraded the certainty of evidence due to the small size and low number of studies, and concerns over the methods used (risk of bias). Further larger studies are required to determine optimal venous thromboembolism prophylaxis in people undergoing major lower extremity amputation.

Authors' conclusions: 

We did not identify any eligible new studies for this update. As we only included two studies in this review, each comparing different interventions, there is insufficient evidence to make any conclusions regarding the most effective thromboprophylaxis regimen in people undergoing lower limb amputation. Further large-scale studies of good quality are required.

Read the full abstract...

People 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 (e.g. heparin, factor Xa inhibitors, vitamin K antagonists, direct thrombin inhibitors, antiplatelets) is effective in preventing deep vein thrombosis (DVT), but is associated with an increased risk of bleeding. Mechanical prophylaxis (e.g. antiembolism stockings, intermittent pneumatic compression and foot impulse devices), on the other hand, is non-invasive and has minimal side effects. However, mechanical prophylaxis is not always appropriate for people with contraindications such as peripheral arterial disease (PAD), arteriosclerosis or bilateral lower limb amputations. It is important to determine the most effective thromboprophylaxis for people undergoing major amputation and whether this is one treatment alone or in combination with another. This is an update of the review first published in 2013.


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

Search strategy: 

The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase and Cumulative Index to Nursing and Allied Health Literature databases, the World Health Organization International Clinical Trials Registry Platform and trials registers to 5 November 2019. We planned to undertake reference checking of identified trials to identify additional studies. We did not apply any language restrictions.

Selection criteria: 

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

Data collection and analysis: 

Two review authors independently selected studies, extracted data and assessed risk of bias. We resolved any disagreements by discussion. Outcomes of interest were VTE (DVT and pulmonary embolism (PE)), mortality, adverse events and bleeding. We used GRADE criteria to assess the certainty of the evidence. The two included studies compared different treatments, so we could not pool the data in a meta-analysis.

Main results: 

We did not identify any eligible new studies for this update. Two studies with a combined total of 288 participants met the inclusion criteria for this review.

Unfractionated heparin compared to low molecular weight heparin

One study compared unfractionated heparin with low molecular weight heparin and found no evidence of a difference between the treatments in the prevention of DVT (odds ratio (OR) 1.23, 95% confidence interval (CI) 0.28 to 5.35; 75 participants; very low-certainty evidence). No bleeding events occurred in either group. Deaths and adverse events were not reported. This study was open-label and therefore at a high risk of performance bias. Additionally, the study did not report the method of randomisation, so the risk of selection bias was unclear.

Heparin compared to placebo

In the second study, there was no evidence of a benefit from heparin use in preventing PE when compared to placebo (OR 0.84, 95% CI 0.35 to 2.01; 134 participants; low-certainty evidence). Similarly, no evidence of improvement was detected when the level of amputation was considered, with a similar incidence of PE between the two treatment groups: above knee amputation (OR 0.79, 95% CI 0.31 to 1.97; 94 participants; low-certainty evidence); and below knee amputation (OR 1.53, 95% CI 0.09 to 26.43; 40 participants; low-certainty evidence). Ten participants died during the study; five underwent a post-mortem and three were found to have had a recent PE, all of whom had been on placebo (low-certainty evidence). Bleeding events were reported in less than 10% of participants in both treatment groups, but the study did not present specific data (low-certainty evidence). There were no reports of other adverse events. This study did not report the methods used to conceal allocation of treatment, so it was unclear whether selection bias occurred. However, this study appeared to be free from all other sources of bias.

No study looked at mechanical prophylaxis.