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      Imbalance of Pro- vs. Anti-Coagulation Factors in Chinese Patients with Budd-Chiari Syndrome and Non-Cirrhotic Portal Vein Thrombosis

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          Abstract

          Background and Aim

          The coagulation abnormalities in non-cirrhotic Budd-Chiari syndrome (NC-BCS) and non-cirrhotic portal vein thrombosis (NC-PVT) are unclear. We conducted this case-control study to investigate the coagulation profile of NC-BCS and NC-PVT in Chinese patients.

          Methods

          We measured the levels of factors II, V, VII, VIII, IX, X, XI, XII, protein C (PC), protein S (PS) and antithrombin (AT) in blood samples from 37 NC-BCS patients, 74 NC-PVT patients, and 100 healthy controls. The levels and ratios of pro- and anti-coagulation factors were compared between patients with NC-BCS and healthy controls, between different types of NC-BCS and between NC-PVT and healthy controls.

          Results

          In patients with NC-BCS, factor VIII (P<0.001) was significantly elevated; factor V (P<0.001), VII (P<0.001), IX (P = 0.003), X (P<0.001), XI (P<0.001), XII (P<0.001), PC (P<0.001) and AT (P<0.001) were significantly decreased; and no difference was observed for factor II (P = 0.088) and PS (P = 0.199) compared with healthy controls. Factor VIII-to-PC (P = 0.008), factor VIII-to-PS (P = 0.037) and factor VIII-to-AT (P = 0.001) were significantly increased; other ratios were significantly reduced or did not show any difference. No differences were observed between different types of NC-BCS for individual pro- and anti-coagulation factors or the ratios between them. Among patients with NC-PVT, factor VIII (P<0.001) was significantly elevated and other factors were significantly decreased. Factor II-to-PC (P<0.001), factor VIII-to-PC (P<0.001), factor IX-to-PC (P<0.001), factor VIII-to-PS (P<0.001), factor II-to-AT (P<0.001), factor VIII-to-AT (P<0.001) and factor IX-to-AT (P<0.001) were significantly increased; all other ratios for NC-PVT were significantly reduced or did not show any significant difference.

          Conclusions

          NC-BCS and NC-PVT are associated with elevated levels of factor VIII and the decreased levels of PC and AT were probably the most significant features of coagulation imbalance. Additionally, NC-PVT was associated with decreased levels of PS.

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          An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis.

          Veena Chantarangkul, Alessandra Dell'Era, Massimo Primignani … (2009)
          Patients with cirrhosis have an increased tendency to develop thromboses despite the longer coagulation times of their plasma, compared with that of healthy individuals. We investigated whether plasma from cirrhotic patients has an imbalance of pro- vs anti-coagulation factors. We analyzed blood samples from 134 cirrhotic patients and 131 healthy subjects (controls) for levels of pro- and anti-coagulants and for thrombin generation in the presence or absence of thrombomodulin (the main physiologic activator of the protein C anticoagulant pathway). The median ratio of thrombin generation (with/without thrombomodulin) was higher in patients (0.80; range, 0.51-1.06) than controls (0.66; range, 0.17-0.95), indicating that cirrhotic patients are resistant to the action of thrombomodulin. This resistance resulted in greater hypercoagulability of plasma from patients of Child-Pugh class C than of class A or B. The hypercoagulability of plasma from patients of Child-Pugh class C (0.86; range, 0.70-1.06) was slightly greater than that observed under the same conditions in patients with congenital protein C deficiency (0.76; range, 0.60-0.93). Levels of factor VIII, a potent pro-coagulant involved in thrombin generation, increased progressively with Child-Pugh score (from Child-Pugh class A to C). Levels of protein C, one of the most potent naturally occurring anti-coagulants, showed the opposite trend. The hypercoagulability of plasma from patients with cirrhosis appears to result from increased levels of factor VIII and decreased levels of protein C-typical features of patients with cirrhosis. These findings might explain the risk for venous thromboembolism in patients with chronic liver disease.
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            Etiology, management, and outcome of the Budd-Chiari syndrome.

            Frits Rosendaal, Elwyn Elias, Nicole A H Janssen … (2009)
            The Budd-Chiari syndrome (BCS) is hepatic venous outflow obstruction. What is known about the syndrome is based on small studies of prevalent cases. To characterize the causes and treatment of incident BCS. Consecutive case series of patients with incident BCS, enrolled from October 2003 to October 2005 and followed until May 2006. Academic and nonacademic hospitals in France, Spain, Italy, Great Britain, Germany, Belgium, the Netherlands, Portugal, and Switzerland. Persons older than 16 years with definite hepatic outflow obstruction diagnosed by imaging. Persons with hepatic outflow obstruction due to heart failure, sinusoidal obstruction syndrome, cancer, or liver transplantation were excluded. Signs and symptoms; laboratory and imaging findings; diagnosis; treatment; and overall, transplantation-free, and intervention-free survival. 163 incident cases of BCS were identified. Median follow-up was 17 months (range, 0.1 to 31 months). Most patients (84%) had at least 1 thrombotic risk factor, and many (46%) had more than 1; the most common was myeloproliferative disorders (49% of 103 tested patients). Patients were mainly treated with anticoagulation (140 patients [86%]), transjugular intrahepatic portosystemic shunting (56 patients [34%]), or liver transplantation (20 patients [12%]), and 80 patients (49%) were managed noninvasively. Only 3 patients underwent surgical shunting. The survival rate was 87% (95% CI, 82% to 93%) at 1 year and 82% (CI, 75% to 88%) at 2 years. Treatment was not standardized across all centers, and data on important clinical variables were missing for some patients. Most patients with BCS have at least 1 thrombotic risk factor, and many have more than 1; myeloproliferative disorders are most common. One- and 2-year survival rates are good with contemporary management, which includes noninvasive therapies (anticoagulation and diuretics) and invasive techniques. Transjugular intrahepatic portosystemic shunting seems to have replaced surgical shunting as the most common invasive therapeutic procedure. Fifth Framework Programme of the European Commission.
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              High plasma levels of factor VIII and the risk of recurrent venous thromboembolism.

              C Bialonczyk, A Weltermann, Christian Eichinger … (2000)
              A high plasma level of factor VIII is a risk factor for venous thromboembolism. We evaluated the risk of a recurrence of thrombosis after an initial episode of spontaneous venous thromboembolism among patients with high plasma levels of factor VIII. We studied 360 patients for an average follow-up period of 30 months after a first episode of venous thromboembolism and discontinuation of oral anticoagulants. Patients who had recurrent or secondary venous thromboembolism, a congenital deficiency of an anticoagulant, the lupus anticoagulant, hyperhomocysteinemia, cancer, or a requirement for long-term treatment with antithrombotic drugs or who were pregnant were excluded. The end point was objectively documented, symptomatic recurrent venous thromboembolism. Recurrent venous thromboembolism developed in 38 of the 360 patients (10.6 percent). Patients with recurrence had higher mean (+/-SD) plasma levels of factor VIII than those without recurrence (182+/-66 vs. 157+/-54 IU per deciliter, P=0.009). The relative risk of recurrent venous thrombosis was 1.08 (95 percent confidence interval, 1.04 to 1.12; P<0.001) for each increase of 10 IU per deciliter in the plasma level of factor VIII. Among patients with a factor VIII level above the 90th percentile of the values in the study population, the likelihood of recurrence at two years was 37 percent, as compared with a 5 percent likelihood among patients with lower levels (P<0.001). Among patients with plasma factor VIII levels above the 90th percentile, as compared with those with lower levels, the overall relative risk of recurrence was 6.7 (95 percent confidence interval, 3.0 to 14.8) after adjustment for age, sex, the presence or absence of factor V Leiden or the G20210A prothrombin mutation, and the duration of oral anticoagulation. Patients with a high plasma level of factor VIII have an increased risk of recurrent venous thromboembolism.
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                Author and article information

                Contributors
                Zhuoli Zhang: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 30 March 2015
                Publication date Collection: 2015
                Volume: 10
                Issue: 3
                Electronic Location Identifier: e0119909
                Affiliations
                [1 ]Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an, China
                [2 ]State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an, China
                Northwestern University Feinberg School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: HC LL XQ GH. Performed the experiments: HC CH ZY FW. Analyzed the data: HC LL XQ GH. Contributed reagents/materials/analysis tools: CH ZY FW. Wrote the paper: HC XQ. Study supervision: DF GH.

                Article
                Publisher ID: PONE-D-14-46966
                DOI: 10.1371/journal.pone.0119909
                PMC ID: 4378932
                PubMed ID: 25823002
                SO-VID: 234c55d1-a48a-4d13-899a-9e0d498dba92
                Copyright statement: Copyright @ 2015
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                Date received : 22 October 2014
                Date accepted : 16 January 2015
                Page count
                Figures: 2, Tables: 5, Pages: 12
                Funding
                This work was supported by grant 81172145 from the National Natural Science Foundation of China ( http://www.nsfc.gov.cn/) and this study was also funded by a translational research project (XJZT11ZO5) of the Xijing Hospital, Fourth Military Medical University, Xi’an, China. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Custom metadata
                Data Availability All relevant data are within the paper.

                ScienceOpen disciplines: Uncategorized
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