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NIHR Signal Continuing an anticoagulant at home after abdominal surgery cuts thrombosis risk

Published on 10 December 2019

doi: 10.3310/signal-000850

Continuing to take low molecular weight heparin for two to four weeks after major abdominal surgery significantly reduces the risk of developing a dangerous blood clot.

A review of seven studies, mainly in cancer surgery, has found that 13% of patients who received anticoagulant treatment only during their hospital stay developed a clot in the deep veins or lungs, compared with 5% of those who continued with the treatment beyond discharge. There was no increased risk of bleeding complications with prolonged treatment.

This update to a Cochrane review first published in 2009 included three new randomised controlled trials, from Italy, Denmark and Japan, boosting the overall number of participants to 1,728.

The quality of the evidence in this review was moderate overall. The results are consistent with previous studies and strengthen the case for prolonged anticoagulation in an area where there is some uncertainty and variation in practice.

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Why was this study needed?

Patients recovering from major abdominal and pelvic surgery are at increased risk of developing venous thromboembolism (VTE), a blood clot in the deep veins or lungs. This risk has been estimated at between 19% and 29% in the most vulnerable patients and is thought to contribute significantly to post-surgery deaths in cancer patients.

While we know that treatment with low molecular weight heparin (LMWH) in hospital is effective, around a third of dangerous blood clots occur after the patient has been discharged from hospital. A 2009 UK prospective study found that the risk of VTE remained 10 to 50 times greater 7 to 12 weeks following inpatient surgery.

We don’t know how long after surgery it is appropriate to continue anticoagulants.

This study sought to evaluate the efficacy and safety of prolonged treatment with heparin for at least 14 days after abdominal or pelvic surgery.

What did this study do?

This systematic review and meta-analysis pooled the results of seven randomised controlled trials, with a total of 1,728 patients. The studies compared prolonged treatment with heparin for 14-28 days, with a shorter duration of treatment during hospital stay only. This review excluded studies where other anticoagulant drugs or devices, such as compression stockings, were evaluated.

Five studies included only people with cancer. Patients in six studies underwent open surgery. In one study, they underwent minimally invasive abdominal surgery. VTEs were confirmed using venograms or compression ultrasound.

Some limitations are noted, including variations in study design and to what extent trials were blinded. One trial received editorial support from a pharmaceutical company.

Overall, the quality of evidence, scale of the review and consistency of the findings indicate these results are reliable.

What did it find?

  • Those who received heparin treatment for up to 28 days after surgery had reduced risk of VTE. The incidence was 5.3% in the patients receiving prolonged anticoagulation, compared with 13.2% in the control group (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.26 to 0.54).
  • When only the six studies involving open surgery were looked at, the results were similar, with 6.0% of the intervention group and 13.8% in the control group developing VTE (OR 0.42, 95% CI 0.29 to 0.60).
  • There was no difference in the incidence of bleeding between the intervention group, affecting 3.4% compared with 2.8% of the control group up to three months after surgery (OR 1.10, 95% CI 0.67 to 1.81).
  • There was no difference in death rate at 3.9% of the intervention group and 3.8% of the control group (OR 1.15, 95% CI 0.72 to 1.84).

What does current guidance say on this issue?

NICE states in its guideline (NG89) that following abdominal surgery, patients whose risk of VTE outweighs their risk of bleeding should have VTE prophylaxis for a minimum of seven days.

NICE recommends that following major abdominal cancer surgery clinicians should consider extending VTE prophylaxis for up to 28 days taking into account individual patient risks.

What are the implications?

These results strengthen the existing evidence and support the current clinical practice guidelines issued by NICE. However, this study looked only at low molecular weight heparin, and there are alternative newer anticoagulants.

The newer oral anticoagulants, removing the need for daily injection, may help to increase the use of anticoagulation at home, but further studies would be needed to assess them for this indication.

Citation and Funding

Felder S, Rasmussen MS, King R et al. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. Cochrane Database Syst Rev. 2019;(8):CD004318.

This review was carried out by the Cochrane Colorectal group, which receives funding from the Danish government.

Why was this study needed?

Patients recovering from major abdominal and pelvic surgery are at increased risk of developing venous thromboembolism (VTE), a blood clot in the deep veins or lungs. This risk has been estimated at between 19% and 29% in the most vulnerable patients and is thought to contribute significantly to post-surgery deaths in cancer patients.

While we know that treatment with low molecular weight heparin (LMWH) in hospital is effective, around a third of dangerous blood clots occur after the patient has been discharged from hospital. A 2009 UK prospective study found that the risk of VTE remained 10 to 50 times greater 7 to 12 weeks following inpatient surgery.

We don’t know how long after surgery it is appropriate to continue anticoagulants.

This study sought to evaluate the efficacy and safety of prolonged treatment with heparin for at least 14 days after abdominal or pelvic surgery.

What did this study do?

This systematic review and meta-analysis pooled the results of seven randomised controlled trials, with a total of 1,728 patients. The studies compared prolonged treatment with heparin for 14-28 days, with a shorter duration of treatment during hospital stay only. This review excluded studies where other anticoagulant drugs or devices, such as compression stockings, were evaluated.

Five studies included only people with cancer. Patients in six studies underwent open surgery. In one study, they underwent minimally invasive abdominal surgery. VTEs were confirmed using venograms or compression ultrasound.

Some limitations are noted, including variations in study design and to what extent trials were blinded. One trial received editorial support from a pharmaceutical company.

Overall, the quality of evidence, scale of the review and consistency of the findings indicate these results are reliable.

What did it find?

  • Those who received heparin treatment for up to 28 days after surgery had reduced risk of VTE. The incidence was 5.3% in the patients receiving prolonged anticoagulation, compared with 13.2% in the control group (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.26 to 0.54).
  • When only the six studies involving open surgery were looked at, the results were similar, with 6.0% of the intervention group and 13.8% in the control group developing VTE (OR 0.42, 95% CI 0.29 to 0.60).
  • There was no difference in the incidence of bleeding between the intervention group, affecting 3.4% compared with 2.8% of the control group up to three months after surgery (OR 1.10, 95% CI 0.67 to 1.81).
  • There was no difference in death rate at 3.9% of the intervention group and 3.8% of the control group (OR 1.15, 95% CI 0.72 to 1.84).

What does current guidance say on this issue?

NICE states in its guideline (NG89) that following abdominal surgery, patients whose risk of VTE outweighs their risk of bleeding should have VTE prophylaxis for a minimum of seven days.

NICE recommends that following major abdominal cancer surgery clinicians should consider extending VTE prophylaxis for up to 28 days taking into account individual patient risks.

What are the implications?

These results strengthen the existing evidence and support the current clinical practice guidelines issued by NICE. However, this study looked only at low molecular weight heparin, and there are alternative newer anticoagulants.

The newer oral anticoagulants, removing the need for daily injection, may help to increase the use of anticoagulation at home, but further studies would be needed to assess them for this indication.

Citation and Funding

Felder S, Rasmussen MS, King R et al. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. Cochrane Database Syst Rev. 2019;(8):CD004318.

This review was carried out by the Cochrane Colorectal group, which receives funding from the Danish government.

Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery

Published on 27 August 2019

Felder, S.,Rasmussen, M. S.,King, R.,Sklow, B.,Kwaan, M.,Madoff, R.,Jensen, C.

Cochrane Database Syst Rev Volume 8 , 2019

BACKGROUND: This an update of the review first published in 2009.Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) administered during the in-hospital period is well-documented, but the optimal duration of prophylaxis after surgery remains controversial. Some studies suggest that patients undergoing major abdominopelvic surgery benefit from prolongation of the prophylaxis up to 28 days after surgery. OBJECTIVES: To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 14 days after abdominal or pelvic surgery compared with thromboprophylaxis administered during the in-hospital period only in preventing late onset VTE. SEARCH METHODS: We performed electronic searches on 28 October 2017 in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS and registered trials (Clinicaltrials.gov October 28, 2017 and World Health Organization International Clinical Trials Registry Platform (ICTRP) 28 October 2017). Abstract books from major congresses addressing thromboembolism were handsearched from 1976 to 28 October 2017, as were reference lists from relevant studies. SELECTION CRITERIA: We assessed randomized controlled clinical trials (RCTs) comparing prolonged thromboprophylaxis (>/= fourteen days) with any LMWH agent with placebo, or other methods, or both to thromboprophylaxis during the admission period only. The population consisted of persons undergoing abdominal or pelvic surgery for both benign and malignant pathology. The outcome measures included VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective means (venography, ultrasonography, pulmonary ventilation/perfusion scintigraphy, spiral computed tomography (CT) scan or autopsy). We excluded studies exclusively reporting on clinical diagnosis of VTE without objective confirmation. DATA COLLECTION AND ANALYSIS: Review authors identified studies and extracted data. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcomes were defined as bleeding complications and mortality within three months after surgery. Sensitivity analyses were also performed with unpublished studies excluded, and with study participants limited to those undergoing solely open and not laparoscopic surgery. We used a fixed-effect model for analysis. MAIN RESULTS: We identified seven RCTs (1728 participants) evaluating prolonged thromboprophylaxis with LMWH compared with control or placebo. The searches resulted in 1632 studies, of which we excluded 1528. One hundred and four abstracts, eligible for inclusion, were assessed of which seven studies met the inclusion criteria.For the primary outcome, the incidence of overall VTE after major abdominal or pelvic surgery was 13.2% in the control group compared to 5.3% in the patients receiving out-of-hospital LMWH (Mantel Haentzel (M-H) odds ratio (OR) 0.38, 95% confidence interval (CI) 0.26 to 0.54; I(2) = 28%; moderate-quality evidence).For the secondary outcome of all DVT, seven studies, n = 1728, showed prolonged thromboprophylaxis with LMWH to be associated with a statistically significant reduction in the incidence of all DVT (M-H OR 0.39, 95% CI 0.27 to 0.55; I(2) = 28%; moderate-quality evidence).We found a similar reduction when analysis was limited to incidence in proximal DVT (M-H OR 0.22, 95% CI 0.10 to 0.47; I(2) = 0%; moderate-quality evidence).The incidence of symptomatic VTE was also reduced from 1.0% in the control group to 0.1% in patients receiving prolonged thromboprophylaxis, which approached significance (M-H OR 0.30, 95% CI 0.08 to 1.11; I(2) = 0%; moderate-quality evidence).No difference in the incidence of bleeding between the control and LMWH group was found, 2.8% and 3.4%, respectively (M-H OR 1.10, 95% CI 0.67 to 1.81; I(2) = 0%; moderate-quality evidence).No difference in mortality between the control and LMWH group was found, 3.8% and 3.9%, respectively (M-H OR 1.15, 95% CI 0.72 to 1.84; moderate-quality evidence).Estimates of heterogeneity ranged between 0% and 28% depending on the analysis, suggesting low or unimportant heterogeneity. AUTHORS' CONCLUSIONS: Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications or mortality after major abdominal or pelvic surgery. This finding also holds true for DVT alone, and for both proximal and symptomatic DVT. The quality of the evidence is moderate and provides moderate support for routine use of prolonged thromboprophylaxis. Given the low heterogeneity between studies and the consistent and moderate evidence of a decrease in risk for VTE, our findings suggest that additional studies may help refine the degree of risk reduction but would be unlikely to significantly influence these findings. This updated review provides additional evidence and supports the previous results reported in the 2009 review.

Expert commentary

Heparin injections are given once daily to thin the blood and reduce clots after surgery. This is usually administered by nurses for a few days whilst the patients are in hospital, but it is obviously more complicated for patients to do their own injections if they are discharged home.

This study shows that heparin injections are effective in reducing clots when given for up to two weeks after abdominal and pelvic surgery. So, hospital teams need to set up a pathway where patients can be counselled about giving the injections themselves, and sufficient heparin needs to be supplied to cover that time period because the drug is not easily available in the community pharmacy.

Major limitations are that the patients may not be keen or physically able to do so, or that those with memory problems are unable to recall the instructions. The data from the trials also do not demonstrate reduction in post-operative deaths, and neither are the more convenient oral medications covered in this article.

Yoon K Loke, Professor of Medicine and Pharmacology, Norwich Medical School

The commentator declares no conflicting interests