Alterations in Coagulation Factor Levels in Patients With End Stage Liver Disease

Understanding the Alterations in Coagulation Factor Levels in Patients With End Stage Liver Disease

The goal of this observational study is to learn about the changes in coagulation factor VIII and IX levels in patients undergoing liver transplantation to help guide future management of coagulation factor replacement in patients with hemophilia and liver disease. The question we aim to answer is: should the recommendations for factor replacement in patients with hereditary bleeding disorders be altered in the setting of end stage liver cirrhosis?

Participants will be asked to provide two blood samples, one at the beginning of their liver transplant, and one after their liver transplant.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Failure; Liver Cirrhosis; Hemophilia A; Hemophilia B; Hemophilia; Liver Transplant Disorder; Coagulation Factor Deficiency

Detailed Description

Current guidelines for management of hemophilia B suggest replacement of factor IX to 100% prior to major abdominal surgery. However, in patients with concurrent liver cirrhosis where the liver does not produce Factor IX, is it worth considering adjusting the factor replacement strategy? We recently had a case of a patient with Hemophilia B and end-stage liver disease (ESLD) who underwent orthotopic liver transplantation and received the standard pre-operative recombinant factor IX replacement. His case was complicated by intra-cardiac thrombus and hypotension. We conduct a small study to assess the pre-operative thromboelastography (TEG) and factor levels in ESLD patient which we hope will help guide clinical decision making in future hemophilia B patients with cirrhosis.

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Alexandra Ruan, MD; Phone Number: 650-723-4000; Email: aruan@stanford.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited for the study who have end stage liver disease and are undergoing liver transplant at Stanford hospital

Description

Inclusion Criteria:

• participants who have end stage liver disease who are listed for liver transplantation and have an accepted organ offer
• age > 18+
• MELD > 25

Exclusion Criteria:

• undergoing multi-organ transplant
• tumor MELD exception points
• has hereditary coagulation disease
• currently on therapeutic blood thinner or anti-platelet medication (ie. aspirin, plavix, warfarin, heparin)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ESLD; All participants recruited will belong to this group. These participants will all have end stage liver disease and be listed for liver transplant with an accepted organ offer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Factor VIII level	We will collect Factor VIII level pre- and post- transplant	12 hours
Factor IX level	We will collect Factor IX level pre- and post- transplant	12 hours
Thromboelastography (TEG) values	We will collect thromboelastography values pre- and post- transplant	12 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications	We will collect data on bleeding or clotting events during the liver transplant surgery and 24 hours post-operatively	24 hours

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Study Director: Alexandra Ruan, MD, Stanford University; Principal Investigator: Martin Angst, MD, Stanford University

Publications and helpful links

General Publications

• Alonso Madrigal C, Dobon Rebollo M, Laredo de la Torre V, Palomera Bernal L, Garcia Gil FA. Liver transplantation in hemophilia A and von Willebrand disease type 3: perioperative management and post-transplant outcome. Rev Esp Enferm Dig. 2018 Aug;110(8):522-526. doi: 10.17235/reed.2018.5204/2017.
• Togashi J, Akamatsu N, Tanaka T, Sugawara Y, Tsukada K, Kaneko J, Arita J, Sakamoto Y, Hasegawa K, Kokudo N. Living donor liver transplantation for hemophilia with special reference to the management of perioperative clotting factor replacement. Liver Transpl. 2016 Mar;22(3):366-70. doi: 10.1002/lt.24341. Epub 2016 Feb 15. No abstract available.
• Kadry Z, de Moerloose P, Giostra E, Morel P, Huber O, Meili E, Blum HE, Mentha G. Orthotopic liver transplantation in hemophilia B: a case report. Transpl Int. 1995;8(6):485-7. doi: 10.1007/BF00335602.
• Ramiz S, Hartmann J, Young G, Escobar MA, Chitlur M. Clinical utility of viscoelastic testing (TEG and ROTEM analyzers) in the management of old and new therapies for hemophilia. Am J Hematol. 2019 Feb;94(2):249-256. doi: 10.1002/ajh.25319. Epub 2018 Dec 7.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: August 23, 2023
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 28, 2023

Study Record Updates

• Last Update Posted (Actual): August 28, 2023
• Last Update Submitted That Met QC Criteria: August 23, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: bleeding; cirrhosis; coagulation; hemophilia; thrombosis; liver transplant
• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Pathologic Processes; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Liver Diseases; End Stage Liver Disease; Fibrosis; Liver Failure; Hemophilia A; Hemophilia B; Liver Cirrhosis
• Other Study ID Numbers: 71275

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