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ADAMTS-13/VWF Ratio as Biomarker for Portal Vein Thrombosis (PVT) Development in Cirrhotic Patients: A Prospective Study

1Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Center for Hemorrhagic and Thrombotic Diseases and Haemophilia Center, Rome, Italy, 2Catholic University School of Medicine, Translational Medicine and Surgery Department, Rome, Italy, 3Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Department of Digestive, Endocrine and Metabolic System, Institute of Internal Medicine and Geriatrics, Rome, Italy

Abstract Number: OC 43.4

Meeting: ISTH 2021 Congress

Theme: Coagulation and Natural Anticoagulants » Hemostasis and Organ Dysfunction

Background: PVT is usually a late event in the natural history of liver cirrhosis with a consistent prevalence among patients with decompensated disease. The prospective clinical trial (ClinicalTrials.gov:NCT03322696) is ongoing to understand the prothrombotic diathesis in compensated cirrhotic patients, by identifying any prognostic factors. Based on our previous research group finding, the reduced portal flow velocity seems to be the most important predictive variable for PVT development and could lead an unbalance between the decreased ADAMTS-13 levels, due to the pro-fibrogenic transformation of stellate cells, and the inflammation-driven heightened von Willebrand factor (VWF) and factor VIII (FVIII)  levels, released from the endothelium.

Aims: We suggest the ADAMTS-13:activity/VWF:activity ratio as a predictive factor of  PVT development in cirrhotic patients.

Methods: One-hundred-eighteen cirrhotic patients (viral etiology ~42%, any other etiology ~58%) were enrolled (2017-2020). The severity of liver function failure was assessed by the CHILD-PUGH score, portal vein flow velocity was measured with eco-Doppler sonography.  ADAMTS-13 activity (A13:act) was measured by a FRET-assay; FVIII was assessed by a two-stage clotting assay, while VWF:antigen and VWF:activity were evaluated by chemiluminescence assays. The variables that resulted statistically significant in univariate Spearman analysis (p<0.05), were used in multivariable analysis to identify prognostic factors (two-sided p< 0.05).

Results: CHILD-PUGH score was positively correlated with VWF (VWF:act: rho=0.404, p<0.0001; VWF:Ag: rho=0.378, p<0.0001) and FVIII (rho=0.191, p=0.004), while inversely correlated with A13:act and A13:act/VWF:act ratio (rho=-0.250, p=0.01, rho=-0.404 p<0.0001, respectively). Multivariable regression analysis showed that A13:act (β=-0.200, p=0.008) and A13:act/VWF:act ratio (β=-0.318, p<0.0001) reflected the severity of liver failure and were inversely associated with PVT development (2/118 cases).

Conclusions: The inverse correlation between the A13:act/VWF:act ratio and the CHILD-PUGH score suggests that the enzyme levels decrease as a function of disease progression, triggering an accumulation of UL-VWF multimers. This may predispose to PVT development and could be a predictive biomarker for PVT development.

To cite this abstract in AMA style:

De Cristofaro R, Sacco M, Lancellotti S, Tardugno M, De Magistris A, Basso M, Grieco A, Pompili M. ADAMTS-13/VWF Ratio as Biomarker for Portal Vein Thrombosis (PVT) Development in Cirrhotic Patients: A Prospective Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/adamts-13-vwf-ratio-as-biomarker-for-portal-vein-thrombosis-pvt-development-in-cirrhotic-patients-a-prospective-study/. Accessed May 20, 2022.

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