Rotational Thromboelastometry (ROTEM) TRUE-NATEM Reference Value Validation in Liver Transplantation

Background: Rotational thromboelastometry (ROTEM) has been used widely in liver transplantation for coagulation management. However, a TRUE-NATEM (TRUE-Non-Activated Rotational Thromboelastometry) reference value has never been established. A TRUE-NATEM value is of clinical significance since no coagulation activators or reagents will be added to the blood sample for analysis. Therefore, the result will reflect the true coagulation profile of the patient.

Methods: Non-citrated whole blood will be used for analysis. Blood will be drawn from the patient and transferred into a plastic reagent cup that has no reagent. Test will be performed within 4 minutes of blood draw to avoid activation of coagulation. Primary outcome measure will be clotting time (CT), clot formation time (CFT) and maximum clot firmness (MCF). The specific aims of the study are to establish a TRUE-NATEM reference value using Rotational Thromboelastometry (ROTEM®) in patients undergoing liver transplantation. Our hypothesis is that clotting time (CT), clot formation time (CFT) is prolonged and maximum clot firmness (MCF) decreased compared to healthy volunteers in patient undergoing liver transplantation due to synthetic coagulation factor deficiency.

Study Overview

• Status: Completed
• Conditions: Coagulation in Liver Transplantation

Detailed Description

This study is a prospective cohort study establishing a TRUE-NATEM reference value using Rotational Thromboelastometry (ROTEM®) in patients undergoing liver transplantation.

The study population will include 20 adults (age range of 18 - 75 years) who are undergoing liver transplantation. Inclusion criteria are patients undergoing liver transplantation with English as their native language.

Exclusion criteria include patient's refusal, or on medical anticoagulation therapy. Informed consents will be obtained from the patients who agree to participate in this clinical study.

Currently, all patients undergoing liver transplantation will have hourly ROTEM analysis as standard of care. An additional TRUE-NATEM test will be performed after induction if anesthesia. 5 mL of whole blood will be obtained via a preexisting peripheral IV catheter or arterial line using a sterile technique. The blood will be transferred into a plastic reagent cup that has no additives. Test will be performed within 4 minutes of blood draw.3 All patients will undergo the standard anesthesia care and intraoperative coagulation monitoring and blood transfusion will be carried out using the standard practice guideline of the TJUH.

The control population will include 20 adult volunteers (age 18-65 years) who meet the in the American Society of Anesthesiologists (ASA) Physical Status (PS) Classes 1 criteria. Exclusion criteria will be refusal, volunteers on any medication or significant history of bleeding.

In the control group 5 mL of whole blood will be obtained after placing a peripheral IV catheter using a sterile technique. Blood draw from steel needle will be avoided because steel will activate coagulation. The blood will be transferred into a plastic reagent cup that has no additives. Test will be performed within 4 minutes of blood draw.

For each patient and control group four channels of ROTEM (TRUE-NATEM, NATEM, INTEM, EXTEM,) will be performed following the standard guideline at the Anesthesiology Coagulation Laboratory by a certified ROTEM specialists. Primary outcome measure will be clotting time (CT), clot formation time (CFT) and maximum clot firmness (MCF). The following demographic information will be collected; ASA physical status, age, height, weight, gender, home medication use, past medical history, and past surgical history.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study population will include 20 adults (age range of 18 - 75 years) who are undergoing liver transplantation.

Description

Inclusion Criteria:

• Inclusion criteria are patients undergoing liver transplantation with English as their native language.

Exclusion Criteria:

• Exclusion criteria include patient's refusal, or on medical anticoagulation therapy. Informed consents will be obtained from the patients who agree to participate in this clinical study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Liver transplantation group; The study population will include 20 adults (age range of 18 - 75 years) who are undergoing liver transplantation. Inclusion criteria are patients undergoing liver transplantation with English as their native language. Exclusion criteria include patient's refusal, or on medical anticoagulation therapy. Informed consents will be obtained from the patients who agree to participate in this clinical study.
Healthy volunteer; The control population will include 20 adult volunteers (age 18-65 years) who meet the in the American Society of Anesthesiologists (ASA) Physical Status (PS) Classes 1 criteria. Exclusion criteria will be refusal, volunteers on any medication or significant history of bleeding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clotting time (CT)	clotting time (CT) in seconds	1 year
clot formation time (CFT)	clot formation time (CFT) in seconds	1 year
maximum clot firmness (MCF)	maximum clot firmness (MCF) in mm	1 year

Collaborators and Investigators

• Sponsor: Thomas Jefferson University

Publications and helpful links

General Publications

• Kang YG, Martin DJ, Marquez J, Lewis JH, Bontempo FA, Shaw BW Jr, Starzl TE, Winter PM. Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation. Anesth Analg. 1985 Sep;64(9):888-96.
• Durila M. Nonactivated thromboelastometry able to detect fibrinolysis in contrast to activated methods (EXTEM, INTEM) in a bleeding patient. Blood Coagul Fibrinolysis. 2016 Oct;27(7):828-830. doi: 10.1097/MBC.0000000000000479.
• Meesters MI, Koch A, Kuiper G, Zacharowski K, Boer C. Instability of the non-activated rotational thromboelastometry assay (NATEM) in citrate stored blood. Thromb Res. 2015 Aug;136(2):481-3. doi: 10.1016/j.thromres.2015.05.026. Epub 2015 May 27.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 6, 2020
• Primary Completion (ACTUAL): February 1, 2021
• Study Completion (ACTUAL): February 1, 2021

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: February 21, 2020
• First Posted (ACTUAL): February 25, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 6, 2021
• Last Update Submitted That Met QC Criteria: April 2, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: liver transplantation; ROTEM; Coagulation; Rotational Thromboelastometry; NATEM; TRUE-NATEM
• Other Study ID Numbers: 20D.086

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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