Pre- vs Postoperative Thromboprophylaxis for Liver Resection

Study Overview
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Brief Summary
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Thromboprophylaxis for liver surgery can be commenced either preoperatively or postoperatively. Despite a clear trade-off between thrombosis and bleeding in liver surgery patients, there is no international consensus when thrombosis prophylaxis should be commenced in patients undergoing liver surgery. As far as we know, there are no prospective randomized trials in this field, and current guidelines are unfortunately based on very low quality evidence, that is, a few retrospective studies and expert opinion. Both American and European thromboprophylaxis guidelines for abdominal cancer surgery support the preoperative initiation of thromboprophylaxis, but these guidelines do not specifically address the increased bleeding risk associated with liver surgery. On the contrary, Dutch guidelines recommend postoperative thromboprophylaxis only, because of lack of evidence for preoperative thromboprophylaxis. Traditionally, many liver surgery units have been reluctant in using preoperative thromboprophylaxis due to the potentially increased risk of bleeding complications. Enhanced Recovery After Surgery (ERAS) Society Guidelines recommend preoperative thromboprophylaxis in liver surgery, but the guidelines provide no supporting evidence for this recommendation. Overall, the amount of evidence is scarce and somewhat contradictory in this clinically relevant field of thromboprophylaxis in liver surgery. The aim of this study is to compare pre- and postoperatively initiated thromboprophylaxis regimens in liver surgery in a randomized controlled trial.

Official Title
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Pre- vs Postoperative Thromboprophylaxis for Liver Resection - a Prospective, Multicenter, Randomized Controlled Trial

Conditions
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Liver Cancer, Surgery, Thrombosis, Deep Vein, Embolism, Pulmonary, Bleeding

Intervention / Treatment
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* Drug: enoxaparin or tinzaparin or dalteparin
* Drug: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients undergoing liver resection Exclusion Criteria: Patient on anticoagulative medication (heparin, low-molecular weight heparin, warfarin, direct oral anticoagulants) during last month pre-surgery Emergency operation (e.g. for trauma or infection) Age < 18 years Allergy or other contraindication to planned low-molecular weight heparin Inability to give written informed consent Liver resection not performed (removed from analyses after randomization)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Preoperative thromboprophylaxis<br>Preoperatively initiated tromboprophylaxis | Drug: enoxaparin or tinzaparin or dalteparin<br>* Thromboprophylaxis initiated approximately 14 hours prior to the planned liver resection skin incision. Thromboprophylaxis can be initiated using enoxaparin (20 - 40 mg), tinzaparin (2500 - 4500 IU), or dalteparin (2500 - 5000 IU), with the dose based on patient's renal function<br>|
| Other: Postoperative thromboprophylaxis<br>Postoperatively initiated thromboprophylaxis | Drug: No intervention<br>* No preoperative thromboprophylaxis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Venous thromboembolisms | Number of patients with venous thromboembolism defined as either 1) symptomatic deep venous thromboembolism (includes all deep veins e.g. all extremities, portal vein, and superior mesenteric) diagnosed using ultrasound or computed tomography or magnetic resonance imaging, or in re-laparatomy/surgery, 2) pulmonary embolism diagnosed using computed tomography, magnetic resonance imaging, or lung perfusion imaging, or 3) death due to venous thromboembolism | within 30 days from liver resection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Posthepatectomy haemorrhage | Number of patients with posthepatectomy haemorrhage, any grade in ISGLS classification | within 30 days from liver resection | 
| Postoperative complications | Comprehensive Complication Index - score | within 30 days from liver resection | 
| Length of postoperative hospital stay | Length of postoperative hospital stay, days | within 30 days from liver resection | 
| Blood transfusion | Total amount of transfused red blood cells, units | during and within 30 days from liver resection |