Do blood thinner injections given after abdominal surgery further reduce blood clots if continued after discharge from the hospital?

Review question

For persons having surgery on the abdomen and pelvis, does continuing blood thinner injections after discharge from a hospital stay decrease the likelihood of developing a blood clot in the lower limbs or lungs when compared to usual treatment in the hospital?

Why is this important?

The complication of developing a blood clot can range from asymptomatic to potentially fatal, depending on the location and severity of the clot. After a postoperative patient is considered safe for discharge from the hospital, evidence suggests an ongoing risk for developing a blood clot in the weeks to months following the operation. Although recommended by some guidelines, not all physicians recommend discharging a postoperative patient home with a prolonged course of blood thinner injections.

What was found?

Seven studies were found that addressed this question, including a total of 1728 patients. Continuing blood thinning injections after hospital discharge decreased the risk of both blood clots in the limbs and in the lungs. This review determined that the overall incidence of having a blood clot is reduced from 13.2%, when no post-discharge blood thinner injections are used, to 5.3% when a blood thinner injection is prescribed for at least 14 days following discharge in 30 days follow-up. Both symptomatic and asymptomatic blood clots decreased with the use of prolonged duration blood thinner injections in postoperative patients. No increase in bleeding complications or death, common concerns when blood thinners are used, were observed in patients treated with prolonged duration blood thinner injections.

What does this mean?

Continuation of blood thinning injections for at least 14 days after abdominal or pelvic surgery reduces the risk of blood clots.

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.

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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 strategy: 

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; I2 = 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; I2 = 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; I2 = 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 (M-H OR 0.30, 95% CI 0.08 to 1.11; I2 = 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; I2 = 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.

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