Abstract Number: PB0360
Meeting: ISTH 2020 Congress
Background: Portal Vein Thrombosis (PVT) is one of the most relevant complication of cirrhosis. PVT prevalence, as showed in PRO-LIVER study, is 17%. Previous studies by our research group found that, a reduced portal flow velocity seems to be the most important predictive variable for PVT development in patients with cirrhosis. An unbalance between the decreased ADAMTS-13 level, due to myofibrillar transformation of stellate cells, and the inflammatioin-driven heightened levels of von Willebrand factor (VWF) released from endothelium, may predispose to platelet/VWF-rich thrombi formation in micro- and macrocirculation.
Aims: Our prospective clinical trial (ClinicalTrials.gov Identifier:NCT03322696) is aimed at unraveling the linkage between ADAMTS-13/VWF changes and PVT development in cirrhosis.
Methods: Currently, 118 cirrhotic patients (viral etiology represent ~42%, any other etiology ~58%) were enrolled (2017-2019). The CHILD-PUGH score assessed the severity of liver function failure. In all patients, portal vein flow velocity was measured. with eco-Doppler sonography. ADAMTS-13 activity (A13:act) was measured by a fluorescence resonance energy transfer-based 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 regression analysis to identify prognostic factors (two-sided p< 0.05).
Results: CHILD-PUGH score was positively correlated with VWF (VWF:act: rho=0.347, p< 0.0001; VWF:Ag: rho=0.342, p< 0.0001) and inversely correlated with A13:act and A13/VWF:act ratio(rho=-0.249, p=0.01, rho=-0.306 p< 0.0001, respectively). Multivariable regression analysis showed that A13:act(β=-0.278, p=0.001) and A13:VWF:act ratio (β=-0.219, p=0.006) 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 would suggest that the enzyme availability (A13:act) decreases as a function of disease progression, triggering an accumulation of UL-VWF multimers, which may predispose to PVT. Thus, the A13:act/VWF:act is significantly associated with liver failure and could be a predictive biomarker for PVT development.
To cite this abstract in AMA style:Sacco M, Lancellotti S, De Magistris A, Tardugno M, Basso M, Pompili M, De Cristofaro R. ADAMTS-13/VWF as Biomarker for Portal Vein Thrombosis Development in Cirrhotic Patients: A Prospective Study [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/adamts-13-vwf-as-biomarker-for-portal-vein-thrombosis-development-in-cirrhotic-patients-a-prospective-study/. Accessed January 27, 2022.
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