Clinical trial NCT04762550: Thrombin Generation in Liver Transplant Surgery
Official title: Diagnosis and Management of Impaired Thrombin Generation in Liver Transplant Surgery
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Liver Transplantation
Thrombin
Hemostasis, Surgical
Blood Coagulation Disorder Due to Liver Disease
Blood Coagulation Disorders
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2021-02-21
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All consenting adults undergoing liver transplantation surgery at Toronto General Hospital

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.

Eligibility criteria: 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.

Exclusion Criteria:

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

Primary outcomes:
measure: Thrombin Generation - Endogenous Thrombin Potential (nM*min)
timeFrame: The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
measure: Thrombin Generation - Lag Time (Seconds)
timeFrame: The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
measure: Thrombin Generation - Time to Peak (Seconds)
timeFrame: The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
measure: Thrombin Generation - Peak Height (nM)
timeFrame: The pattern of change in thrombin generation will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Secondary outcomes:
measure: Conventional Hemostatic Tests - Platelet Count
timeFrame: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
measure: Conventional Hemostatic Tests - INR
timeFrame: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
measure: Conventional Hemostatic Tests - aPTT
timeFrame: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
measure: Conventional Hemostatic Tests - Fibrinogen Level
timeFrame: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
measure: Viscoelastic Testing
timeFrame: The pattern of change will be assessed intra-operatively at baseline through to study completion up to 12 hours post-operatively
Other outcomes:
measure: Transfusion Outcomes - Red Blood Cells
timeFrame: From intra-operatively to within 12 hours post-operatively
measure: Transfusion Outcomes - Platelets
timeFrame: From intra-operatively to within 12 hours post-operatively
measure: Transfusion Outcomes - Frozen Plasma
timeFrame: From intra-operatively to within 12 hours post-operatively
measure: Transfusion Outcomes - Prothrombin Complex Concentrate
timeFrame: From intra-operatively to within 12 hours post-operatively
measure: Transfusion Outcomes - Fibrinogen Concentrate
timeFrame: From intra-operatively to within 12 hours post-operatively
measure: Bleeding Outcomes - Delayed Abdominal Closure
timeFrame: From intra-operatively to within 12 hours post-operatively
measure: Bleeding Outcomes - Return to the Operating Room for Re-Exploration
timeFrame: From intra-operatively to within 12 hours post-operatively
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital - University Health Network
state: Ontario
Study officials:
affiliation: Toronto General Hospital - University Health Network
name: Justyna Bartoszko, MD MSc FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: Toronto General Hospital - University Health Network
name: Keyvan Karkouti, MD MSc FRCPC
role: PRINCIPAL_INVESTIGATOR
References: