Blood Coagulation Disorder Due to Liver Disease, Blood Coagulation Disorders, Hemostasis, Surgical, Liver Transplantation, Thrombin
Conditions
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.
Interventions
None listed
Sponsors
University Health Network, Toronto
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 - 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 |
| 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 - 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) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Transfusion Outcomes - Prothrombin Complex Concentrate | From intra-operatively to within 12 hours post-operatively | The total number of units transfused |
| Transfusion Outcomes - Frozen Plasma | From intra-operatively to within 12 hours post-operatively | The total number of frozen plasma units transfused |
| Transfusion Outcomes - Platelets | From intra-operatively to within 12 hours post-operatively | The total number of platelet units transfused |
| Bleeding Outcomes - Delayed Abdominal Closure | From intra-operatively to within 12 hours post-operatively | Clinical bleeding outcome such as delayed abdominal |
| Bleeding Outcomes - Return to the Operating Room for Re-Exploration | From intra-operatively to within 12 hours post-operatively | Clinical bleeding outcome such as return to the operating room for re-exploration or evacuation of hematoma |
| Transfusion Outcomes - Fibrinogen Concentrate | From intra-operatively to within 12 hours post-operatively | The total number of grams of fibrinogen transfused |
| Transfusion Outcomes - Red Blood Cells | From intra-operatively to within 12 hours post-operatively | The total number of red blood cells transfused |
Countries
Canada
Contacts
Primary ContactJustyna Bartoszko, MD MSc FRCPC
Outcome results
None listed