Procoagulant imbalance aggravated with falling liver function reserve, but not associated with the presence of portal vein thrombosis in cirrhosis

Wen, Tao; Wang, Yu; Zhao, Xinyan; Wang, Xiaoming; Zhang, Tao; Ou, Xiaojuan; Shou, Wei-ling; You, Hong; Jia, Jidong

doi:10.1097/meg.0000000000000352

Cited by 26 publications

(31 citation statements)

References 25 publications

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“…The APC pathway plays a central role in rebalancing the coagulation of patients with cirrhosis. Previous studies showed that, in experimental conditions that allow PC activation by generated thrombin, TG is normal or even increased, depending on the experimental conditions and the studied patients . Here, we report that the ETP decreased after normalization of FVIII (by addition of an inhibitory antibody) or PC (by addition of PC), and that a normal coagulation phenotype could be fully restored after normalization of both FVIII and PC levels.…”

Section: Discussionmentioning

confidence: 49%

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Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis

Sinegre

Duron

Lecompte

et al. 2018

Journal of Thrombosis and Haemostasis

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Background In cirrhosis, thrombin generation (TG) studied in the presence of thrombomodulin (TM) indicates plasma hypercoagulability. Although the role of protein C (PC) deficiency has been investigated, the influence of an increase in the factor VIII level has never been addressed. Objectives We investigated the roles of high FVIII and low PC levels in increased TG in the presence of TM. Methods Blood samples were prospectively collected from 35 healthy controls and 93 patients with cirrhosis (Child-Turcotte-Pugh [CTP]-A, n = 61; CTP-B, n = 19; and CTP-C, n = 13) and FVIII levels > 150% (n = 48) and/or PC levels < 70% (n = 88). TG was performed with tissue factor (5 pm), phospholipids, and TM (4 nm). FVIII and PC levels were normalized by adding an inhibitory anti-FVIII antibody and exogenous PC, respectively. Results The endogenous thrombin potential (ETP) in the presence of TM was higher in patients than in controls. After FVIII normalization, the ETP (median) decreased from 929 nm min to 621 nm min (CTP-A), 1122 nm min to 1082 nm min (CTP-B), and 1221 nm min to 1143 nm min (CTP-C); after PC normalization, it decreased from 776 nm min to 566 nm min (CTP-A), 1120 nm min to 790 nm min (CTP-B), and 995 nm min to 790 nm min (CTP-C). The ETP was reduced by 17% and 30%, respectively, but normal TG was not restored. When both FVIII and PC levels were normalized, the ETP decreased from 929 nm min to 340 nm min (CTP-A), 1122 nm min to 506 nm min (CTP-B), and 1226 nm min to 586 nm min (CTP-C), becoming similar to control levels. Conclusion Cirrhosis-induced plasma hypercoagulability, as demonstrated in these experimental conditions, can be partly explained by opposite changes in two factors: PC level (decrease) and FVIII level (increase).

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis

Sinegre

Duron

Lecompte

et al. 2018

Journal of Thrombosis and Haemostasis

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“…(33) It is known that patients with cirrhosis have a reduction in antithrombin levels directly related to the degree of liver dysfunction. (34,35) RVXB, in contrast to a LMWH such as enoxaparin, is an antithrombinindependent inhibitor with highly selective inhibitory action against factor Xa (inhibits both free factor Xa and factor Xa bound in the prothrombinase complex) and therefore its effect is not related to antithrombin levels. Moreover, rivaroxaban has the advantage of oral bioavailability and rapid onset of action.…”

Section: Discussionmentioning

confidence: 99%

The anticoagulant rivaroxaban lowers portal hypertension in cirrhotic rats mainly by deactivating hepatic stellate cells

et al. 2017

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“…ATIII is primarily synthesized by hepatocytes[11]. Furthermore, levels of ATIII have been shown to be altered in patients with liver disease[12, 13]. Recently, ATIII was reported to be a valuable marker for clinical outcome in hepatocellular carcinoma (HCC) patients undergoing curative intended liver resection[14–16].…”

Section: Introductionmentioning

confidence: 99%

Early prediction of postoperative liver dysfunction and clinical outcome using antithrombin III-activity

et al. 2017

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Background and aimsAntithrombin III (ATIII) has been reported to be associated with liver pathologies and was shown to predict outcome in patients undergoing liver resection for hepatocellular carcinoma. We now aimed to assess whether perioperative ATIII-activity could predict postoperative outcome in patients without underlying liver disease, as well as in a routine clinical setting of patients undergoing hepatic resection.MethodsATIII-activity was evaluated preoperatively and on the first (POD1) and fifth day after liver resection in a retrospective evaluation cohort of 228 colorectal cancer patients with liver metastasis (mCRC). We further aimed to prospectively validate our results in a set of 177 consecutive patients undergoing hepatic resection.ResultsPatients developing postoperative liver dysfunction (LD) had a more pronounced postoperative decrease in ATIII-activity (P<0.001). ATIII-activity on POD1 significantly predicted postoperative LD (P<0.001, AUC = 84.4%) and remained independent upon multivariable analysis. A cut-off value of 61.5% ATIII-activity was determined using ROC analysis. This cut-off was vital to identify high-risk patients for postoperative LD, morbidity, severe morbidity and mortality (P<0.001, respectively) with a highly accurate negative predictive value of 97%, which could be confirmed for LD (P<0.001) and mortality (P = 0.014) in our independent validation cohort. Further, mCRC patients below our cut-off suffered from a significantly decreased overall survival (OS) at 1 and 3 years after surgery (P = 0.011, P = 0.025).ConclusionsThe routine laboratory parameter ATIII-activity on POD1 independently predicted postoperative LD and was associated with clinical outcome. Patients with a postoperative ATIII-activity <61.5% might benefit from close monitoring and timely initiation of supportive therapy.Trial registrationClinicalTrials.gov NCT01700231

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Procoagulant imbalance aggravated with falling liver function reserve, but not associated with the presence of portal vein thrombosis in cirrhosis

Abstract: Procoagulant imbalance is not associated with the presence of PVT in patients with cirrhosis, although the imbalance worsens with the severity of cirrhosis.

Cited by 26 publications

References 25 publications

Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis

Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis

The anticoagulant rivaroxaban lowers portal hypertension in cirrhotic rats mainly by deactivating hepatic stellate cells

Early prediction of postoperative liver dysfunction and clinical outcome using antithrombin III-activity

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