PB0432 - The ADAMTS-13 / von Willebrand factor (VWF) ratio as a prognostic biomarker for the development of portal vein thrombosis (PVT) in patients with compensated cirrhosis.

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

RD

Raimondo De Cristofaro, MD, PhD

Professor, Haemostasis and Thrombosis Center Director
1.Fondazione Policlinico Universitario A. Gemelli, IRCCS, Center for Hemorrhagic and Thrombotic Diseases and Haemophilia Center, Rome, Italy; 2. Catholic University, Translational Medicine and Surgery Department Rome, Italy
Roma, Lazio, Italy

Co-Author(s)

Stefano Lancellotti, PhD

Biologist Health Manager
Fondazione Policlinico Universitario A. Gemelli, IRCCS, Center for Hemorrhagic and Thrombotic Diseases and Haemophilia Center, Rome, Italy
Roma, Lazio, Italy
MS

Monica Sacco

Post-doc
Catholic University, Translational Medicine and Surgery Department Rome, Italy
Roma, Lazio, Italy
Maira Tardugno, Dr

PhD Student
Catholic University, Translational Medicine and Surgery Department Rome, Italy
Roma, Lazio, Italy
AD

Antonio De Magistris

Medical Resident
Fondazione Policlinico Universitario A. Gemelli, IRCCS.
Rome, Lazio, Italy
MB

Maria Basso

Medical Doctor
Unità Malattie Emorragiche e Trombotiche, Fondazione Policlinico Universitario Agostino Gemelli IRCSS, Roma, Italia
Rome, Lazio, Italy
MP

Maurizio Pompili

Professor
Fondazione Policlinico Universitario A. Gemelli, IRCCS, Department of Digestive, Endocrine and Metabolic System, Institute of Internal Medicine and Geriatrics, Rome.
Rome, Lazio, Italy
FP

Francesca Ponziani

Dr, MD
Fondazione Policlinico Universitario A. Gemelli, IRCCS, Department of Digestive, Endocrine and Metabolic System, Institute of Internal Medicine and Geriatrics, Rome.
Rome, Lazio, Italy
FS

Francesco Santopaolo

Dr, MD
Fondazione Policlinico Universitario A. Gemelli, IRCCS, Department of Digestive, Endocrine and Metabolic System, Institute of Internal Medicine and Geriatrics, Rome.
Rome, Lazio, Italy
AG

Antonio Grieco

Professor
Fondazione Policlinico Universitario A. Gemelli, IRCCS, Department of Digestive, Endocrine and Metabolic System, Institute of Internal Medicine and Geriatrics, Rome.
Rome, Lazio, Italy

Background: Cirrhosis is associated with an increased risk of PVT in which the decrease of the portal vein flow velocity < 15cm/sec, leads an unbalance between the decreased zinc-protease ADAMTS-13, due to the pro-fibrogenic transformation of stellate cells, and the inflammation-driven heightened VWF and FVIII levels, predisposing to platelet/VWF-rich thrombi formation in micro-/macro-liver- circulation. Liver cirrhosis is characterized by the alteration of both pro and anticoagulant proteins. Thus, a significant reduction of the protein C/FVIII ratio was reported in patients with NAFLD. Other studies indicated a prevalence of congenital thrombophilia conditions, as risk factors of PVT development.

Aims: This observational prospective clinical trial on compensated cirrhotic patients (ClinicalTrial.gov: NCT03322696) could identify ADAMTS-13/VWF:GpIbR ratio as a key predictive factor of PVT development in cirrhotic patients. All participants signed informed consent.

Methods: The final 80/118 enrolled subjects were followed for 48 months and underwent Doppler-ultrasound liver examination and clinical (Child-Pugh and MELD-score) and hematochemical ( PT%, APTT%, AT%, PC%, PS%, LAC, fibrinogen, FVIII:C, D-dimer) assessment. VWF antigen and VWF:GpIbR were measured by chemiluminescence assays; ADAMTS-13:activity by a FRET-based-assay; both FV Leiden G1691A and the prothrombin G20210A polymorphisms by using the RT-PCR; statistical analyses by the SPSS-software.

Results: Five patients presented PVT (cumulative incidence=6.3%) (characteristics showed in Table1), occurred between 4 and 36 months after the enrollment. The ADAMTS-13/VWF:GpIbR ratio sensitivity and specificity as PVT predictor was assessed by a ROC curve (Figure 1), highlighting a cut-off-value=0.40, below which the risk to develop a PVT complication increases (OR 14.6, 95% C.I.:1.36-157.2, p=0.027) as also confirmed by a Cox-regression-analysis, where the risk to develop a PVT rises exponentially after 30th month-follow-up.

Conclusion(s): As a function of disease progression, the ADAMTS-13/VWF unbalance in the sinusoidal vessel predisposes to thrombotic diathesis. Thus, the ADAMTS-13/VWF:GpIbR ratio, significantly associated with liver failure, could be a predictive biomarker for PVT development.