Thrombin in Cardiac Surgery

Diagnosis and Management of Impaired Thrombin Generation in Cardiac Surgery

Coagulopathy, bleeding, and transfusion are common in cardiac surgical patients. Our collaborator has developed a novel point of care device that can be used to assess thrombin generation in real-time in cardiac surgical patients. The investigators will measure thrombin generation using our novel device and compare it to standard methods, while examining the association of thrombin parameters with bleeding and other clinical outcomes.

Study Overview

• Status: Recruiting
• Conditions: Coagulation Disorder; Surgical Blood Loss; Hemostatic Disorder; Thrombin; Cardiovascular Surgical Procedures

Detailed Description

This is a prospective observational cohort study of 200 cardiac surgical patients. Thrombin generation via our novel point of care thrombin generation assay as well as calibrated automated thrombography (CAT) will be measured at three time points: (1) before surgery; (2) post-CPB after heparin reversal with protamine; (3) at the time of chest closure or 60 minutes after heparin reversal with protamine. Clinicians will remain blinded to the measures. Recruitment will continue until the investigators enroll 50 patients with significant impaired thrombin generation capacity (>50% drop from baseline) and 50 patients who receive hemostatic therapies. Patients will be followed for 7 days postoperatively to assess individual products transfused.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Justyna Bartoszko, MD MSc FRCPC; Phone Number: 3243 416-340-4800; Email: justyna.bartoszko@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • Toronto General Hospital - University Health Network
      • Contact: Justyna Bartoszko, MD MSc FRCPC; Phone Number: 3243 416-340-4800; Email: justyna.bartoszko@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with cardiovascular disease undergoing cardiac surgical procedures at Toronto General Hospital.

Description

Inclusion Criteria:

-All adult patients (> 18 years of age) undergoing cardiac surgery at Toronto General Hospital will be offered participation.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Cardiac Surgical Patients; All consenting adults undergoing cardiac surgery at Toronto General Hospital.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thrombin Generation, as assessed by the Endogenous Thrombin Potential (ETP)	The primary thrombin generation parameter of interest is the endogenous thrombin potential, or ETP, expressed in nM*min. The change in thrombin generation in patients undergoing cardiac surgery before and after cardiopulmonary bypass using our new point-of-care thrombin sensor and the established laboratory-based calibrated automated thrombogram (CAT) assay will be assessed.	The change in thrombin generation will be assessed from preoperative baseline up until 12 hours post-operatively
Thrombin Generation, as assessed by the Lag Time	The co-primary thrombin generation parameter of interest is the Lag Time, expressed in seconds. The change in thrombin generation in patients undergoing cardiac surgery before and after cardiopulmonary bypass using our new point-of-care thrombin sensor and the established laboratory-based calibrated automated thrombogram (CAT) assay will be assessed.	The change in thrombin generation will be assessed from preoperative baseline up until 12 hours post-operatively
Thrombin Generation, as assessed by the Time to Peak	The co-primary thrombin generation parameter of interest is the Time to Peak, expressed in seconds. The change in thrombin generation in patients undergoing cardiac surgery before and after cardiopulmonary bypass using our new point-of-care thrombin sensor and the established laboratory-based calibrated automated thrombogram (CAT) assay will be assessed.	The change in thrombin generation will be assessed from preoperative baseline up until 12 hours post-operatively
Thrombin Generation, as assessed by the Peak Height	The co-primary thrombin generation parameter of interest is the Peak Height, expressed in nM. The change in thrombin generation in patients undergoing cardiac surgery before and after cardiopulmonary bypass using our new point-of-care thrombin sensor and the established laboratory-based calibrated automated thrombogram (CAT) assay will be assessed.	The change in thrombin generation will be assessed from preoperative baseline up until 12 hours post-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Units of Red Blood Cells Transfused	The total number of red blood cells units transfused will be recorded	From intra-operatively up to 12 hours post-operatively
Total Units of Platelets Transfused	The total number of platelets units transfused will be recorded	From intra-operatively up to 12 hours post-operatively
Total Units of Frozen Plasma Transfused	The total number of frozen plasma units transfused will be recorded	From intra-operatively up to 12 hours post-operatively
Total amount of Prothrombin Complex Concentrates transfused	The total number of prothrombin complex concentrate units will be recorded	From intra-operatively up to 12 hours post-operatively
Total amount of Fibrinogen Concentrate transfused	The total number of grams of fibrinogen concentrate transfused will be recorded	From intra-operatively up to 12 hours post-operatively

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chest tube drainage	Blood loss from chest tube drainage will be assessed in mL	From intra-operatively to within 12 hours post-operatively
Return to the Operating Room for Bleeding or Delayed Chest Closure	Instances of return to the operating room for re-exploration or a delay in chest closure will be assessed	From intra-operatively to within 12 hours post-operatively

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: McMaster University
• Investigators: Principal Investigator: Justyna Bartoszko, MD MSc FRCPC, Toronto General Hospital - University Health Network; Principal Investigator: Keyvan Karkouti, MD MSc FRCPC, Toronto General Hospital - University Health Network

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2022
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: February 2, 2021
• First Submitted That Met QC Criteria: February 16, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): November 9, 2022
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Intraoperative Complications; Hemostatic Disorders; Blood Coagulation Disorders; Disease; Blood Loss, Surgical
• Other Study ID Numbers: 20-5726

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No