Platelet adhesion assessed by PFA-100 is not linked to progression of ACLD

Lorenz Balcar; Benedikt Simbrunner; Rafael Paternostro; Mathias Jachs; Lukas Hartl; Georg Semmler; Benedikt Silvester Hofer; Albert Friedrich Stättermayer; Matthias Pinter; Ton Lisman; Michael Trauner; Peter Quehenberger; Thomas Reiberger; Bernhard Scheiner; Mattias Mandorfer

doi:10.1016/j.jhepr.2023.100934

Platelet adhesion assessed by PFA-100 is not linked to progression of ACLD

JHEP Rep. 2023 Oct 12;6(1):100934. doi: 10.1016/j.jhepr.2023.100934. eCollection 2024 Jan.

Authors

Lorenz Balcar^{1

2}, Benedikt Simbrunner^{1

2}, Rafael Paternostro^{1

2}, Mathias Jachs^{1

2}, Lukas Hartl^{1

2}, Georg Semmler^{1

2}, Benedikt Silvester Hofer^{1

2}, Albert Friedrich Stättermayer^{1

2}, Matthias Pinter¹, Ton Lisman³, Michael Trauner¹, Peter Quehenberger⁴, Thomas Reiberger^{1

2}, Bernhard Scheiner^{1

2}, Mattias Mandorfer^{1

2}

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
² Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
³ Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁴ Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

Abstract

Background & aims: Increased aggregation of individual platelets upon activation, as assessed by whole blood aggregometry standardised to platelet count (PLT), has recently been linked to progression of advanced chronic liver disease (ACLD). Moreover, changes in primary haemostasis have been implicated in bleeding and thrombosis in patients with ACLD.We aimed (i) to identify the determinants of the primary haemostatic capacity - as assessed by Platelet Function Analyzer 100 (PFA-100) ('in vitro bleeding time') - in patients with ACLD and (ii) to investigate its potential association with clinical outcomes.

Methods: PFA-100 was performed in 688 patients with ACLD undergoing hepatic venous pressure gradient measurement. Hepatic decompensation and liver-related death as well as bleeding and thrombosis were the outcomes of interest.

Results: Sixty-three percent of patients had a PFA-100 collagen/epinephrine closure time (CT) of >150 s (i.e. prolonged). PLT and haematocrit were the main determinants of CT, whereas it was not impacted by von Willebrand factor antigen. Mirroring the increasing prevalence/severity of thrombocytopaenia and anaemia, we observed a progressive prolongation of CT (i.e. decreased primary haemostatic capacity) with more advanced disease, as indicated by clinical stage, Child-Turcotte-Pugh score, United Network for Organ Sharing model for end-stage liver disease (2016) score, and hepatic venous pressure gradient. Although increased CT (i.e. decreased primary haemostatic capacity) was associated with an increased risk of hepatic decompensation/liver-related death, these associations were less consistent after adjusting/correcting for PLT/haematocrit and established prognostic indicators. Finally, CT was not associated with the incidence of major bleedings or thromboses.

Conclusions: These findings do not support the hypothesis that increased platelet adhesion - assessed in vitro under shear stress by PFA-100 - promotes ACLD progression.

Impact and implications: The potential of platelets to aggregate in the bloodstream may be increased in patients with advanced chronic liver disease. Platelet Function Analyzer 100 (PFA-100), a blood test reflecting in vitro bleeding time, might be suggestive of an impaired primary clot forming capacity. In our study, we could show that PFA-100 results were not linked to bleeding/thrombotic events. Our findings do not support the hypothesis that an increased adhesion of platelets (assessed by PFA-100) might lead to a disease progression in patients with advanced chronic liver disease.

Keywords: Acute-on-chronic liver failure; Cirrhosis; Platelet; Portal hypertension.