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DOI: 10.1055/a-2052-9381
Increased Factor VIII Activity Is Predictive of the Occurrence of Portal Vein Thrombosis in Cirrhosis
Funding This study was supported by Shanghai Sailing Program (No. 19YF1406500), the National Natural Science Foundation of China (No. 81900511), and Zhongshan Hospital Foundation (No. 2021ZSYQ03). The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Abstract
Background The aim of this study was to identify the role of factor VIII (FVIII) in portal vein thrombosis (PVT) occurrence in cirrhotic patients with gastroesophageal variceal bleeding.
Methods A total of 453 cirrhotic patients with gastroesophageal varices were enrolled. Computed tomography was performed at baseline and patients were divided into PVT and non-PVT groups (n = 131 vs. 322). Individuals without PVT at baseline were followed up for the development of PVT. Time-dependent receiver operating characteristic analysis of FVIII for PVT development was performed. The Kaplan–Meier methodology was used to analyze the predictive ability of FVIII for PVT incidence at 1 year.
Results FVIII activity (177.00 vs. 153.70, p = 0.001) was significantly increased in the PVT group compared with the non-PVT group in cirrhotic patients with gastroesophageal varices. FVIII activity was positively correlated with the severity of PVT (161.50 vs. 171.07 vs. 187.05%, p = 0.001). Furthermore, FVIII activity (hazard ratio [HR]: 3.48, 95% confidence interval [CI]: 1.14–10.68, p = 0.029 in model 1; HR: 3.29, 95% CI: 1.03–10.51, p = 0.045 in model 2) was an independent risk factor of 1-year PVT development in patients without PVT at baseline, which was confirmed by two separate Cox regression analysis and competing risk models. Patients with elevated FVIII activity exhibit a higher incidence of PVT in the non-PVT group at 1 year (15.17 vs. 3.16%, p < 0.001). The predictive value of FVIII remains significant in individuals who have never received splenectomy (14.76 vs. 3.04%, p = 0.002).
Conclusion Elevated FVIII activity was potentially associated with the occurrence and the severity of PVT. It might be helpful to identify cirrhotic patients at risk of PVT.
Ethical Statement
Ethics Committee of Zhongshan Hospital of Fudan University approved the study protocol (B2015–133R). The study was conducted in accordance with the Helsinki Declaration as revised in 2013. Informed consent was obtained from all participants.
Data Availability Statement
All data included in this study are available upon request by contact with the corresponding author.
Authors' Contribution
S.J. analyzed, interpreted the data, and drafted the manuscript. Y.A. and X.F. undertook data analysis and revised the manuscript. X.H. conceived the study, collected and interpreted the data, and revised the manuscript. L.W. and L.N. helped with the data collection and analysis. F.L. helped with data interpretation and the revision of the manuscript. S.C. conceived the study and performed the critical revision of the manuscript. All authors were involved in the critical revision of the manuscript for important intellectual content.
* Siyu Jiang, Yingjie Ai, and Xiaowen Fan contributed equally to this manuscript.
Publikationsverlauf
Eingereicht: 04. Dezember 2022
Angenommen: 01. März 2023
Accepted Manuscript online:
13. März 2023
Artikel online veröffentlicht:
04. April 2023
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References
- 1 Nery F, Chevret S, Condat B. et al; Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire. Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: results of a longitudinal study. Hepatology 2015; 61 (02) 660-667
- 2 Violi F, Corazza GR, Caldwell SH. et al; PRO-LIVER Collaborative Group. Incidence and recurrence of portal vein thrombosis in cirrhotic patients. Thromb Haemost 2019; 119 (03) 496-499
- 3 Senzolo M, Garcia-Tsao G, García-Pagán JC. Current knowledge and management of portal vein thrombosis in cirrhosis. J Hepatol 2021; 75 (02) 442-453
- 4 Intagliata NM, Caldwell SH, Tripodi A. Diagnosis, development, and treatment of portal vein thrombosis in patients with and without cirrhosis. Gastroenterology 2019; 156 (06) 1582.e1-1599.e1
- 5 Qi XS, Dai JN, Yang M, Ren WR, Jia J, Guo XZ. Association between portal vein thrombosis and survival in non-liver-transplant patients with liver cirrhosis: a systematic review of the literature. Gastroent Res Pract 2015; 2015: 480842
- 6 Violi F, Ferro D, Basili S. et al. Ongoing prothrombotic state in the portal circulation of cirrhotic patients. Thromb Haemost 1997; 77 (01) 44-47
- 7 Praktiknjo M, Trebicka J, Carnevale R. et al. Von Willebrand and factor VIII portosystemic circulation gradient in cirrhosis: implications for portal vein thrombosis. Clin Transl Gastroenterol 2020; 11 (02) e00123
- 8 Stine JG, Wang J, Shah PM. et al. Decreased portal vein velocity is predictive of the development of portal vein thrombosis: a matched case-control study. Liver Int 2018; 38 (01) 94-101
- 9 Xu X, Guo X, De Stefano V. et al. Nonselective beta-blockers and development of portal vein thrombosis in liver cirrhosis: a systematic review and meta-analysis. Hepatol Int 2019; 13 (04) 468-481
- 10 Mannully ST, L NR, Pulicherla KK. Perspectives on progressive strategies and recent trends in the production of recombinant human factor VIII. Int J Biol Macromol 2018; 119: 496-504
- 11 Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med 2011; 365 (02) 147-156
- 12 Martinelli I, Primignani M, Aghemo A. et al. High levels of factor VIII and risk of extra-hepatic portal vein obstruction. J Hepatol 2009; 50 (05) 916-922
- 13 Rietveld IM, Lijfering WM, le Cessie S. et al. High levels of coagulation factors and venous thrombosis risk: strongest association for factor VIII and von Willebrand factor. J Thromb Haemost 2019; 17 (01) 99-109
- 14 Yerdel MA, Gunson B, Mirza D. et al. Portal vein thrombosis in adults undergoing liver transplantation: risk factors, screening, management, and outcome. Transplantation 2000; 69 (09) 1873-1881
- 15 Ma J, Yan Z, Luo J, Liu Q, Wang J, Qiu S. Rational classification of portal vein thrombosis and its clinical significance. PLoS One 2014; 9 (11) e112501
- 16 Bauer J, Johnson S, Durham J. et al. The role of TIPS for portal vein patency in liver transplant patients with portal vein thrombosis. Liver Transpl 2006; 12 (10) 1544-1551
- 17 de Franchis R, Bosch J, Garcia-Tsao G. et al. Baveno VII – renewing consensus in portal hypertension. J Hepatol 2022; 76 (04) 959-974
- 18 Weinberg EM, Palecki J, Reddy KR. Direct-acting oral anticoagulants (DOACs) in cirrhosis and cirrhosis-associated portal vein thrombosis. Semin Liver Dis 2019; 39 (02) 195-208
- 19 Villa E, Cammà C, Marietta M. et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 2012; 143 (05) 1253-1260 .e4
- 20 Sarin SK, Philips CA, Kamath PS. et al. Toward a comprehensive new classification of portal vein thrombosis in patients with cirrhosis. Gastroenterology 2016; 151 (04) 574.e3-577.e3
- 21 Rugivarodom M, Charatcharoenwitthaya P. Nontumoral portal vein thrombosis: a challenging consequence of liver cirrhosis. J Clin Transl Hepatol 2020; 8 (04) 432-444
- 22 Turon F, Driever EG, Baiges A. et al. Predicting portal thrombosis in cirrhosis: a prospective study of clinical, ultrasonographic and hemostatic factors. J Hepatol 2021; 75 (06) 1367-1376
- 23 Anton A, Campreciós G, Pérez-Campuzano V, Orts L, García-Pagán JC, Hernández-Gea V. The pathophysiology of portal vein thrombosis in cirrhosis: getting deeper into Virchow's triad. J Clin Med 2022; 11 (03) 800
- 24 Scheiner B, Balcar L, Nussbaumer RJ. et al. Factor VIII/protein C ratio independently predicts liver-related events but does not indicate a hypercoagulable state in ACLD. J Hepatol 2022; 76 (05) 1090-1099
- 25 Driever EG, Magaz M, Adelmeijer J. et al. The portal vein in patients with cirrhosis is not an excessively inflammatory or hypercoagulable vascular bed, a prospective cohort study. J Thromb Haemost 2022; 20 (09) 2075-2082
- 26 La Mura V, Tripodi A, Tosetti G. et al. Resistance to thrombomodulin is associated with de novo portal vein thrombosis and low survival in patients with cirrhosis. Liver Int 2016; 36 (09) 1322-1330
- 27 Gîrleanu I, Trifan A, Stanciu C, Sfarti C. Portal vein thrombosis in cirrhotic patients - it is always the small pieces that make the big picture. World J Gastroenterol 2018; 24 (39) 4419-4427
- 28 Ferlitsch M, Reiberger T, Hoke M. et al. von Willebrand factor as new noninvasive predictor of portal hypertension, decompensation and mortality in patients with liver cirrhosis. Hepatology 2012; 56 (04) 1439-1447
- 29 Raffa S, Reverter JC, Seijo S. et al. Hypercoagulability in patients with chronic noncirrhotic portal vein thrombosis. Clin Gastroenterol Hepatol 2012; 10 (01) 72-78
- 30 Tripodi A, Primignani M, Lemma L. et al. Detection of the imbalance of procoagulant versus anticoagulant factors in cirrhosis by a simple laboratory method. Hepatology 2010; 52 (01) 249-255
- 31 Carnevale R, Raparelli V, Nocella C. et al. Gut-derived endotoxin stimulates factor VIII secretion from endothelial cells. implications for hypercoagulability in cirrhosis. J Hepatol 2017; 67 (05) 950-956