Association between low-grade disseminated intravascular coagulation and endotoxemia in patients with liver cirrhosis

doi:10.1016/0016-5085(95)90342-9

Gastroenterology

Volume 109, Issue 2, August 1995, Pages 531-539

https://doi.org/10.1016/0016-5085(95)90342-9 Get rights and content

Abstract

$Background & Aims :$ Hyperfibrinolysis may complicate the clinical course of liver cirrhosis. The aim of this study was to evaluate if, in cirrhosis, hyperfibrinolysis is primary or secondary to intravascular clotting activation and if endotoxemia is associated with activation of clotting and/or the fibrinolytic system. $Methods :$ Clotting, fibrinolytic indexes, and endotoxemia were studied in 41 cirrhotic patients and 20 healthy subjects. $Results :$ Twenty-seven cirrhotic patients (66%) had high plasma levels of prothrombin fragment F1+2, a marker of thrombin generation. Nineteen patients had elevated values of d-dimer, a marker of fibrinolysis in vivo. All patients with high values of d-dimer also had high values of prothrombin fragment F1+2. Endotoxemia was elevated in patients with severe liver failure and significantly correlated to prothrombin fragment F1+2. Thirty patients were treated for 7 days either with standard therapy (n = 15) or with standard therapy plus nonabsorbable antibiotics (n = 15). Although standard therapy did not significantly change laboratory indexes, a significant reduction of endotoxemia, prothrombin fragment F1+2, and d-dimer was found in those patients who received the combined treatment. $Conclusions :$ This study shows that, in cirrhotic patients, hyperfibrinolysis is not a primary phenomenon but occurs as a consequence of clotting activation and that endotoxemia might play a pathophysiological role.

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Citation Excerpt :
In vitro studies have revealed that LPS, even in low concentrations, may stimulate vWf release from the endothelium [13]. Moreover, Violi et al. provided evidence of a direct correlation between endotoxemia and the ongoing prothrombotic state in the portal venous system [14]. Therefore, it is plausible that endotoxemia, in combination with the coexisting increased vWf release frequently found in cirrhosis, may trigger prothrombotic mechanisms.
Portal vein thrombosis (PVT) is a common complication of cirrhosis, but its pathogenesis is unclear. We tested the hypotheses that PVT is the result of platelet hyperactivity or intestinal barrier disruption.
This study included 49 patients with cirrhosis (15 females) of mixed etiology. Based on spiral computed-tomography, the patients were divided into two groups: with PVT (n = 16) and without PVT (n = 33). Serum biomarkers of intestinal barrier integrity were endotoxins and zonulin, and platelet activity was assessed with multiple electrode aggregometry.
The levels of endotoxin (43.5 ± 18.3 ng/ml vs. 36.9 ± 7.5 ng/ml; P = 0.19) and zonulin (56.3 ± 31.1 ng/ml vs. 69.3 ± 63.1 ng/ml; P = 0.69) were not different between the patients with and without PVT. Moreover, endotoxin and zonulin did not correlate with the coagulation and platelet parameters. The platelet aggregability measured with the TRAP and the ADP tests was decreased in PVT patients. In the logistic regression analysis the PVT incidence was related to the levels of D-dimer and bilirubin as well as the TRAP test results. Patients with PVT presented with significantly higher levels of D-dimer (4.45 ± 2.59 vs. 3.03 ± 2.97 mg/l; P < 0.05) and prothrombin levels (175 ± 98.8 μg/ml vs. 115 ± 72.9 μg/ml; P < 0.05) than patients without thrombosis. PVT could be excluded with a 90% negative predictive value when the D-dimer level was below 1.82 mg/l.
Endotoxemia and platelet activity are not determinants of PVT in patients with cirrhosis. The D-dimer measurement has diagnostic significance for PVT in patients with liver cirrhosis.

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^☆: Supported in part by the Andrea Cesalpino Foundation.

^☆☆: Presented in part at the Clinical Research Meeting, Baltimore, Maryland, April 29 to May 2, 1994, and published in abstract form (Clin Res 1994;42:242A).

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Association between low-grade disseminated intravascular coagulation and endotoxemia in patients with liver cirrhosis☆,☆☆

Abstract

Fibrinolysis

Blood

Gastroenterology

J Hepatol

Blood

J Hepatol

Clin Chim Acta

Blood

Fibrinolysis

Blood

Gastroenterology

J Hepatol

J Hepatol

Hemostatic abnormalities in liver disease

Clotting abnormalities in chronic liver disease

Dig Dis Sci

Disseminated intravascular coagulation in cirrhosis

Hepatology

Hyperfibrinolysis resulting from clotting activation in patients with different degrees of cirrhosis

Hepatology

In vivo metabolism of human tissue type plasminogen activator

Scand J Haematol

α2-plasmin inhibitor mechanism in patients with liver cirrhosis

J Lab Clin Med

Fibrinogen survival in cirrhosis: improvement by “low dose” heparin

Ann Intern Med

Improvement of some blood coagulation factors in cirrhotic patients treated with low doses of heparin

Scand J Haematol

Exchange between intravascularly and extravascularly injected radioiodinated fibrinogen and its in vivo derivatives

J Lab Clin Med

Significance of plasma fibrinopeptide A and high molecular weight fibrinogen in patients with liver cirrhosis

Br J Haematol

Relationship between fibrinopeptide A and fibrinogen/fibrin fragment E in thromboembolism, DIC, and various non-thromboembolic diseases

Thromb Haemost

α₂-plasmin inhibitor mechanism in patients with liver cirrhosis