Factor VIII/Protein C and Not ADAMTS13/VWF:Ag Ratio Is a Prognostic Risk Factor for Patients with Cirrhosis and Low MELD Score

N. Bitto¹, G. Tosetti², A. Tripodi³, I. Mancini⁴, L. Baronciani³, C. Valsecchi³, P. Lampertico², F. Peyvandi^1,3, M. Primignani², V. La Mura^1,2

¹Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, U.O.C. Medicina Generale Emostasi e Trombosi, Università degli Studi di Milano, Milan, Italy, ²Fondazione IRCC Ca' Granda, Ospedale Maggiore Policlinico, C.R.C. 'A.M. e A. Migliavacca' per lo Studio e la Cura delle Malattie del Fegato, Università degli Studi di Milano, Milan, Italy, ³Angelo Bianchi Bonomi Haemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and Fondazione Luigi Villa, Milan, Italy, ⁴Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy

Abstract Number: PB1946

Meeting: ISTH 2020 Congress

Theme: Thrombotic Microangiopathies » Non HUS/TTP Microangiopathies

Background: Hemostasis can be mechanism of liver damage in cirrhosis. Low ADAMTS13/Von Willebrand Factor antigen (VWF:Ag) ratio and high factor VIII/protein C (FVIII/PC) mark platelet hyperaggregation and hypercoagulation, respectively.

Aims: Our study aimed at exploring the association of such parameters with the severity of liver disease measured by the Child-Pugh, MELD, MELD-Na scores and their prognostic role on clinical outcome.

Methods: We investigated 123 cirrhotic patients (age 62±12, 58% in-hospital, Child-Pugh:8.2±2.2, MELD:15.6±7.7, MELD-Na:16.3±6.6). Main etiologies were virus/alcohol (40/60%). Hemostatic parameters measured at inclusion were VWF:Ag, ADAMTS13 activity, FVIII, FII, antithrombin, PC and were correlated with the severity of liver disease (Pearson coefficient). Liver decompensations requiring hospitalization, death or transplantation were retrospectively collected and presented as cumulative risk at 12 months from baseline evaluation. The prognostic role of the hemostatic parameters was tested by logistic regression and expressed as risk of adverse outcome predicted by the model.

Results: A pro-hemostatic imbalance was resumed by ADAMTS13/VWF:Ag of 0.21+/-0.14 and FVIII/PC of 6.0+/-6.5. All the hemostatic parameters correlated with cirrhosis severity (p< 0.05).
At 12 months: 35 patients (28%) experienced a clinical decompensation, 23 (19%) died, 16 (13%) were transplanted. MELD-Na had the highest prognostic accuracy (AUC=0.809), compared to MELD (AUC=0.774) and Child-Pugh (AUC=0.771). FVIII/PC was the only hemostatic variable associated with the composite clinical end-point (OR:1.215;95%-CI:1.05-1.38;p=0.006).
A prognostic model including MELD-Na and FVIII/PC led to a slight increase of the AUC vs MELD-Na alone (AUC:0.815 vs 0.809). A FVIII/PC≥2.78, the lowest tertile in our series, marked a high predicted-risk of clinical outcome in the category of MELD-Na< 15 (45% vs 27%) compared to MELD-Na≥15 (83% vs 75%).

Conclusions: Markers of primary and secondary hemostasis correlate with common indexes of liver disease severity. FVIII/PC ratio may have a relevant prognostic role in patients with
MELD-Na< 15.

To cite this abstract in AMA style:

Bitto N, Tosetti G, Tripodi A, Mancini I, Baronciani L, Valsecchi C, Lampertico P, Peyvandi F, Primignani M, La Mura V. Factor VIII/Protein C and Not ADAMTS13/VWF:Ag Ratio Is a Prognostic Risk Factor for Patients with Cirrhosis and Low MELD Score [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/factor-viii-protein-c-and-not-adamts13-vwfag-ratio-is-a-prognostic-risk-factor-for-patients-with-cirrhosis-and-low-meld-score/. Accessed May 16, 2022.

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