Clinical trial NCT06014320: Alterations in Coagulation Factor Levels in Patients With End Stage Liver Disease
Official title: Understanding the Alterations in Coagulation Factor Levels in Patients With End Stage Liver Disease
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Liver Cirrhosis
Hemophilia
Hemophilia A
Hemophilia B
Liver Transplant Disorder
Liver Failure
Coagulation Factor Deficiency
Keywords: liver transplant
hemophilia
coagulation
thrombosis
bleeding
cirrhosis
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2023-08-28
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Factor VIII level
timeFrame: 12 hours
measure: Factor IX level
timeFrame: 12 hours
measure: Thromboelastography (TEG) values
timeFrame: 12 hours
Secondary outcomes:
measure: Complications
timeFrame: 24 hours
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Hospital
state: California
Study officials:
affiliation: Stanford University
name: Alexandra Ruan, MD
role: STUDY_DIRECTOR
affiliation: Stanford University
name: Martin Angst, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.