Efficacy and Safety of Enoxaparin for Prophylaxis of Postoperative Venous Thromboembolism After Esophagectomy: A Single-center Prospective Randomized Controlled Phase II Study

Abstract

Background/Aim: This study aimed to assess whether low-molecular-weight heparin (LMWH) is effective and safe in preventing postoperative venous thromboembolism (VTE) in patients undergoing esophageal cancer surgery. Patients and Methods: In this single-institution, prospective, randomized trial, 73 patients with esophageal cancer undergoing esophagectomy were randomly divided into the enoxaparin group (E group) and intermittent pneumatic compression group (I group). The primary endpoint was efficacy of enoxaparin, and secondary endpoints were evidence of bleeding and serum anti-Xa activity in the E group. Results: The E group comprised 42 patients and the I group comprised 31 patients. Deep vein thrombosis was observed in 0 (0%) patients in the E group and 7 (22.6%) patients in the I group (p=0.002). Soluble fibrin monomer complex was significantly lower in the E versus I group on day 8 (p<0.001). D-dimer was significantly lower in the E versus I group on days 2, 8, and 15 (p=0.008, p<0.001, p<0.001, respectively). Conclusion: VTE was significantly reduced by using enoxaparin. Venous thromboembolism (VTE) is the second leading cause of death in cancer patients receiving outpatient chemotherapy (1). As represented by Trousseau's syndrome, multiple pathophysiologic mechanisms contribute to the hypercoagulability associated with cancer (2). The Japan VTE Treatment Registry revealed the maximal risk factor for VTE to be cancer (3). Major surgery for cancer located in the abdomen or chest is associated with a high incidence of VTE, as the major postoperative complication, including deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE) (4). According to previous reports, the incidence of symptomatic VTE after esophagectomy is reported to range from 2.9 to 3.8%, (5, 6), whereas that of asymptomatic VTE after esophagectomy ranges from 5.9 to 23.3% (7-9). Thus, the prevalence of asymptomatic VTE is not small after esophageal cancer surgery, and occasionally, unfortunate outcomes can occur; thus, prevention of VTE is very important. The use of low-molecular-weight heparin (LMWH) was recommended to prevent VTE after cancer surgery (10). Lee et al. reported that in patients with cancer and acute VTE, LMWH was more effective than an oral anticoagulant in reducing the risk of recurrent VTE, without increasing the risk of bleeding (11). However, an optimal strategy of thromboprophylaxis for esophagectomy has not been formulated, and to the best of our knowledge, there are no reports comparing the effects of LMWH through randomized controlled trials (RCTs). Enoxaparin is a LMWH that functions as an anticoagulant agent by forming a complex with antithrombin 3 (AT-III) and promoting AT-III activity. The evidence for enoxaparin in orthopedic, gynecologic malignancy and abdominal or pelvic malignancy has already been established (12-14). In 2615 This article is freely accessible online.

Asymptomatic pulmonary thromboembolism diagnosed based on prolonged fever after gastric cancer surgery: A case report with literature review

“…However, D-dimer has low specificity for VTE and is generally elevated after surgery. Tanaka et al reported that D-dimer increases to about 20 μg/mL after gastric cancer surgery [13] . Therefore, D-dimer is not useful for confirming PE, and it should be measured only when PE is clinically suspected.…”

The venous thromboembolism prophylaxis in patients receiving thoracic surgery: A systematic review

“…26,28,29,31,38,43 Prophylaxis with LMWH was performed in the studies of Daddi, Attaran, Song, Mantziari, Christensen, Song, Pannucci, and Esme. 30,33,35,36,40,41,42,44 Dentali, Agzarian, and Alai 37,47 compared prophylaxis of LMWH or heparin in patients receiving lung surgery; Tanaka 46 compared prophylaxis of an IPC or enoxaparin in patients who underwent esophagectomy for esophageal cancer;…”

“…Tanaka 46 conducted a randomized trial including surgical esophageal cancer patients that were randomly assigned to either prophylaxis of IPC applied from the start of operation to the first ambulation from bed or combination subcutaneous injection of enoxaparin (06:00 PM on the first operation day then twice daily on PODs 2-14) on the first operation day and the same IPC procedure.…”

2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19

“…Five small Japanese randomised controlled trials assessed mechanical methods of thromboprophylaxis in surgical patients with cancer, with inconsistent findings. 44 , 45 , 46 , 47 , 48 In a network meta-analysis of patients with gynaecological cancer undergoing major abdominopelvic surgery, comparing different methods of thromboprophylaxis, intermittent pneumatic compression plus LMWH was best for VTE prevention. 42 …”