Ongoing Prothrombotic State in the Portal Circulation of Cirrhotic Patients

Abstract

SummaryPortal thrombosis may complicate the clinical course of cirrhosis, but the pathophysiologic mechanism is unclear. Aim of the study was to evaluate the behavior of clotting system and endotoxemia in portal vein and in peripheral circulation of 11 cirrhotic patients undergoing transjugular port-systemic shunt (TIPS).Portal blood showed higher values of Fl+2 [Median (range): 2.5 (1.1-5.3) vs. 1.1 (0.6-2.1) nM, p <0.01], D-dimer [765 (184-1713) vs. 192 (64-813) ng/ml, p < 0.01] and endotoxemia [31 (16-47.2) vs. 13.7 (7.5-23.5) pg/ml, p <0.01] than peripheral circulation. In the portal vein, all but one sample had Fl+2 > 1.2 nM (upper limit of control values), all but one had D-dimer > 216 mg/dl (mean + 2 SD of controls) and 100% had values of endotoxemia > 9.6 pg/ml (upper limit of control values). Fibrinogen was lower in the portal circulation compared to peripheral circulation but the difference was not significant [85 (58-195) vs. 134 (75-244) mg/dl, p > 0.05].Endotoxemia was directly correlated with Fl+2 (Rho = 0.92 p <0.006) and D-dimer (Rho = 0.93, p <0.005).This study shows that an ongoing prothrombotic state is present in the portal circulation of cirrhotic patients and may play a pivotal role in the thrombotic episodes occurring in this clinical setting.

Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference

“…Bacterial translocation may act either as a pro-hemostatic or an anti-hemostatic factor. Chronic endotoxinrelated inflammation may raise the risk of PVT in cirrhosis [72,80]. Endotoxins favor a pro-thrombotic diathesis by increasing portal hypertension and slowing portal flow through endothelin-induced contraction of hepatic stellate cells [80], and/or by increasing the production of endothelium-associated factors [68].…”

“…Chronic endotoxinrelated inflammation may raise the risk of PVT in cirrhosis [72,80]. Endotoxins favor a pro-thrombotic diathesis by increasing portal hypertension and slowing portal flow through endothelin-induced contraction of hepatic stellate cells [80], and/or by increasing the production of endothelium-associated factors [68]. In addition, endotoxemia may trigger coagulation activation [68] in patients treated with non-absorbable antibiotics, a treatment that induces a concomitant reduction in endotoxemia and thrombin generation [81,82].…”

Portal Vein Thrombosis in Cirrhosis

“…29 Among other factors that may increase the risk of PVT is endotoxemia. 34 Endotoxemia is common with worsening liver disease when PVT is also more common. Development of endotoxemia may be a surrogate for severity of cirrhosis.…”

AICF and DIC in Liver Cirrhosis: Expressions of a Hypercoagulable State

“…Thus, the results of this study add further support to the concept, based on a large amount of published evidence, that AICF is not a common feature in patients with nonadvanced, stable liver cirrhosis without complications. However, because relatively few patients with end stage cirrhosis were enrolled and patients with complications such as recent esophageal or gastric bleeding and coexisting conditions such as shock, infection, recent surgery, trauma, and malignancy were excluded, the results of the study by Ben Ari et al (22) do not refute extensive, previously published evidence (12)(13)(14)(15)(16)(17)(18)(19)(20) that such patients may be prone to develop AICF and DIC as manifestations of a systemic hypercoagulable state with, perhaps, preferential expression in the portal circulation (23). This concept is supported by the findings that large vessel thrombosis, particularly portal vein thrombosis, may occur in 15% of patients with cirrhosis (24) and microvascular thrombosis in one or multiple organs was observed in 50% and 2%, respectively in one anatomic/pathologic study of 184 cases with liver disease (25).…”

“…AICF, DIC, and thrombosis may be precipitated or facilitated further in liver cirrhosis by a number of mechanisms and factors including endotoxemia (23,26), reduced blood flow (shock), surgery, or trauma. Although synthesis of both procoagulant and anticoagulant factors is progressively reduced with advancing cirrhosis, some important procoagulants such as factor VIII and fibrinogen, as well as prohemostatic factors synthesized in sites other than the liver, such as von Willebrand factor, are frequently elevated or remain normal (1), and clearance of activated coagulation factors may be impaired, raising the possibility of a global hemostatic system imbalance favoring increased platelet/fibrin deposition.…”