Comparison of Three Thromboprophylactic Regimens in Patients Post Pancreatic Surgery

Introduction

Pancreatic surgeries are associated with a high rate of morbidity. Post-pancreatectomy bleeding occurs in 1-8% of pancreatic resections and is considered one of the most severe complications, with mortality rates ranging from 16-60%. Thromboembolic disease is also a common complication, and thromboprophylaxis is indicated in patients with malignant pancreatic tumors due to a hypercoagulable state.

There have been several changes in the recommendations regarding thromboprophylaxis in recent years. The aim of this study was to compare the efficacy and safety of three nadroparin dosing regimens in patients undergoing pancreatic resection for malignancy.

Study Methodology

Patients undergoing elective surgery at the same healthcare facility from November 2013 to September 2017 were included in the cohort study. Participants were evenly divided into three therapeutic groups. The first group received nadroparin at a dose of 2850 IU once daily for the duration of hospitalization only, the second group received nadroparin at a dose of 5700 IU once daily for 6 weeks post-operation, and the third group received nadroparin at a dose of 2850 IU twice daily for 6 weeks post-operation. The first dose of nadroparin was uniformly administered to all patients 4-6 hours after the operation.

The primary objectives of the study included assessing the incidence of clinically relevant post-pancreatectomy bleeding and thromboembolic disease within 6 weeks post-surgery.

Results

A total of 240 patients (80 in each group) were included in the analysis. The group receiving nadroparin at a dose of 5700 IU once daily had a significantly higher risk of post-pancreatectomy bleeding (hazard ratio [HR] 2.14; 95% confidence interval [CI] 1.16-3.94; p = 0.015) and a higher risk of relaparotomy compared to the other groups (16% vs. 3.8%; p = 0.002). Independent predictors of bleeding, in addition to higher doses of nadroparin, were high BMI and pancreatic fistula.

The group receiving the lowest dose of nadroparin, 2850 IU once daily, did not show a significant increase in the risk of thromboembolic disease compared to the other groups (HR 1.41; 95% CI 0.43-4.62; p = 0.570). The group receiving nadroparin at a dose of 2850 IU twice daily did not show a reduction in the risk of adverse events (HR 0.77; 95% CI 0.77-0.41; p = 0.422); specifically, adverse events occurred in 15 patients in the first group, 22 in the second group, and 16 in the third group.

Conclusion and Discussion

The study results indicate that administering nadroparin at a dose of 5700 IU once daily for 6 weeks post-operation was associated with a twofold increase in the risk of post-pancreatectomy bleeding, leading to a fourfold increase in the number of necessary relaparotomies. Patients administered the lowest dose of nadroparin only during hospitalization did not show a significant increase in the risk of thromboembolic disease.

According to the study results, it is not possible to clearly state which regimen is superior to the others; a future study with this aim should ideally address the administration of the lowest dose and divided doses for 6 weeks post-operation. At the healthcare facility where the study was conducted, routine thromboprophylaxis of 2850 IU nadroparin for 6 weeks post-operation was initiated after the study's conclusion.

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Source: Hanna-Sawires R. G., Groen J. V., Klok F. A. et al. Outcomes following pancreatic surgery using three different thromboprophylaxis regimens. Br J Surg 2019 May; 106 (6): 765-773, doi: 10.1002/bjs.11103.