PB0857 - Increased Platelet Activation and Platelet-Leukocyte Aggregate Formation in Primary Sclerosing Cholangitis

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

JG

Julian C. Gerwers

MD Student
University Medical Center Hamburg Eppendorf
Hamburg, Hamburg, Germany

Co-Author(s)

Hanna Englert, MSc

PhD Candidate
University Medical Center Hamburg Eppendorf
Hamburg, Hamburg, Germany
NW

Nina Wolska

Postdoc
University Medical Centre Hamburg-Eppendorf
Hamburg, Hamburg, Germany
FG

Fabian Glaser

MD
University Medical Centre Hamburg-Eppendorf
Hamburg, Hamburg, Germany
JH

Johannes Hartl

MD
University Medical Centre Hamburg-Eppendorf
Hamburg, Hamburg, Germany
IS

Ida Schregel

MD
University Medical Centre Hamburg-Eppendorf
Hamburg, Hamburg, Germany
MS

Marcial Sebode

MD
University Medical Centre Hamburg-Eppendorf
Hamburg, Hamburg, Germany
SS

Silja Steinmann

MD
University Medical Centre Hamburg-Eppendorf
Hamburg, Hamburg, Germany
JW

Jan Philipp Weltzsch

MD
University Medical Centre Hamburg-Eppendorf
Hamburg, Hamburg, Germany
CW

Christina Weiler-Normann

MD
University Medical Centre Hamburg-Eppendorf
Hamburg, Hamburg, Germany
CS

Christoph Schramm

MD
University Medical Centre Hamburg Eppendorf
Hamburg, Hamburg, Germany
TR

Thomas Renné

Head of Department
Institut für Klinische Chemie und Laboratoriumsmedizin, Zentrum für Diagnostik, UKE, Hamburg, Germany
Hamburg, Hamburg, Germany
Carsten Deppermann, PhD

Assistant Professor
University Medical Centre Mainz
Mainz, Rheinland-Pfalz, Germany

Background: Primary sclerosing cholangitis (PSC) is an inflammatory disease of the intra- and extrahepatic bile ducts resulting in cholestatic liver disease, liver failure and potentially cholangiocarcinoma. The pathophysiology of PSC is still largely unknown.
Platelets and leukocytes contribute to inflammatory processes and regulate immune reactions in liver disease. A previous study showed an increased expression of glycoprotein Ibɑ (GPIbɑ) on the platelet surface in patients with PSC compared to a control cohort indicating a hypercoagulable state in PSC patients.

Aims: We aimed to investigate platelet functions in PSC to explore if platelets play a role in PSC pathogenesis.

Methods: Blood was collected from PSC patients and healthy controls. We used platelet aggregometry and flow chambers assays (vWF and collagen) to analyze thrombus formation under static conditions and flow. Flow cytometry was used to quantify the surface expression of major platelet receptors, platelet reactivity upon stimulation with ADP, CRP-XL and TRAP-6 and formation of platelet-leukocyte-aggregates (PLAs) in blood samples from PSC patients. We further used ELISAs to detect platelet surface receptor shedding.

Results: Platelets from PSC patients formed larger and denser clots compared to healthy controls, implicating a hyper-activated state.
GPIbɑ and P-Selectin expression on the platelet surface in the resting state was lower compared to controls. We observed increased soluble glycoprotein VI (sGPVI) levels in plasma. Threshold for platelet activation – assessed by P-Selectin exposure and aIIbb3-integrin activation - was higher. We also found an increased tendency of PLA formation both in resting and activated state in blood from PSC patients.

Conclusion(s): Higher platelet activation threshold and an increased tendency to form PLAs suggest that platelets have an exhausted phenotype in PSC and that they contribute to thromboinflammatory processes in PSC.