Thrombin Generation in Liver Transplant Surgery

• Conditions: Liver Transplantation; Blood Coagulation Disorder Due to Liver Disease; Blood Coagulation Disorders; Thrombin; Hemostasis, Surgical

• Registration Number: NCT04762550
• Lead Sponsor: University Health Network, Toronto

Brief Summary

This is a prospective observational study of 100 patients undergoing liver transplantation at a single centre. Thrombin generation and kinetics will be assessed using a novel point-of-care device, and compared to conventional measures of hemostasis as well as viscoelastic tests to pinpoint specific coagulation deficits and identify potential therapeutic targets. The clinical course of patients will be followed for major bleeding and transfusion outcomes.

Detailed Description

Liver transplantation is the only curative option for end stage liver disease, but is associated with high morbidity and mortality. End stage liver disease is known to be accompanied by dysregulated coagulation, which is further exacerbated in the immediate perioperative period by transplantation, leading to both coagulopathic bleeding and thrombosis. Altered thrombin generation is thought to play a key role in the predisposition of these patients for both severe coagulopathic hemorrhage and life-threatening thromboembolic complications. Despite this, thrombin generation during the immediate transplant period in patients with end-stage liver disease is poorly characterized, in part because it is not well reflected by conventional measures of coagulation. This study aims to characterize changes in thrombin generation capacity pre, intra- and post-transplant utilizing a novel point-of-care thrombin generation assay. Other specific aims of the study are to identify risk factors for patients with impaired thrombin generation and will assess the association of impaired thrombin generation with overall clinical bleeding risk. The overarching goal of this work is to develop a point-of-care-testing guided algorithm addressing dysregulated thrombin formation that improves coagulation management without increasing the risk of thromboembolic complications. Ultimately, this line of research will improve the outcomes of liver transplantation.

Study Timeline

• Status Verified: 2021-02
• Study First Submitted: 2021-02-02
• Study First Submitted QC: 2021-02-16
• Study First Posted: 2021-02-21
• Study Start: 2021-03-08
• Last Update Submitted: 2021-04-29
• Last Update Posted: 2021-05-03
• Primary Completion: 2022-01-01
• Study Completion: 2022-01-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• All adult patients (> 18 years of age) proceeding to imminent (within 24 hours) liver transplantation surgery at Toronto General Hospital will be offered participation.
• Patients should have end stage liver disease necessitating transplantation. All etiologies of end stage liver disease will be accepted.

Read More

Exclusion Criteria

• Patients who are unable to consent to the study or who refuse participation will be excluded.

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Thrombin Generation - Time to Peak (Seconds)	The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively	The change in thrombin generation will be measured in patients undergoing liver transplantation by the Time to Peak (Seconds)
Thrombin Generation - Lag Time (Seconds)	The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively	The change in thrombin generation will be measured in patients undergoing liver transplantation as assessed by the Lag Time (Seconds)
Thrombin Generation - Endogenous Thrombin Potential (nM*min)	The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively	The change in thrombin generation will be measured in patients undergoing liver transplantation, as assessed through the Endogenous Thrombin Potential (nM\*min)
Thrombin Generation - Peak Height (nM)	The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively	The change in thrombin generation will be measured in patients undergoing liver transplantation by the Peak Height (nM)

Secondary Outcome Measures

Name	Time	Method
Conventional Hemostatic Tests - Fibrinogen Level	The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively	The Clauss Fibrinogen level in g/L
Viscoelastic Testing	The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively	Rotational thromboelastometry (ROTEM)
Conventional Hemostatic Tests - INR	The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively	The international normalized ratio (INR) in seconds
Conventional Hemostatic Tests - aPTT	The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively	The activated partial thromboplastin time (aPTT) in seconds
Conventional Hemostatic Tests - Platelet Count	The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively	The platelet count from the complete blood count in x10\^9/L

Trial Locations

Locations (1)

Toronto General Hospital - University Health Network; 🇨🇦 Toronto, Ontario, Canada