New insights into haemostasis in liver failure

Abstract

The precise mechanisms leading to the coagulopathy of acute liver injury are unclear. To study this further, coagulation and immune changes have been compared in patients with acute liver injury secondary to paracetamol overdose, with chronic cirrhosis, and normal healthy controls. In acute liver injury, coagulation factors II, V, VII and X were reduced to a similar degree, and were significantly lower than factors IX and XI. In cirrhosis, by contrast, these coagulation factors were reduced to similar levels. Factor VIII increased in acute liver injury, but was normal in cirrhosis. Interleukin-6 and tumour necrosis factor-alpha levels increased in both patient groups, but were higher in paracetamol overdose. Thrombin-antithrombin and soluble tissue factor levels increased in those with acute liver injury, but were normal in patients with cirrhosis. Functional antithrombin was reduced in both acute liver injury and cirrhosis. It is hypothesized that in acute paracetamol-induced liver injury, immune activation leads to tissue factor-initiated consumption of factors II, V, VII and X, but that levels of factors IX and XI are better preserved because of inhibition of the thrombin-induced amplification phase of coagulation. These findings have implications for appropriate coagulation factor support for patients with acute liver injury.

Impairment of α₂-Macroglobulin Synthesis in Experimental Hepatopathic Rats Treated with Turpentine Oil

“…it was reported that the levels of IL-6 are elevated in liver injury patients, as well as in mice and rats with induced liver damage [15][16][17]25]. iL-6 levels are thus considered to be affected by factors other than liver damage.…”

“…high-dose administration of acetaminophen is known to induce hepatopathy [1,15]. bruck et al reported that hepatopathy is induced by a one-time administration of acetaminophen at 1 g/kg in rats [2].…”

Hemostasis, Disorders of Coagulation and Transfusion in Cirrhosis

“…These levels are affected by acute clotting and other disease processes and there is no clear relationship to bleeding or clotting risks in cirrhosis patients; also shows significant laboratory variations and are expensive. Euglobulin lysis time is a validated measure of fibrinolysis and can be used as a measure of treatment efficacy in hyperfibrinolysis, but is not widely available [29].…”

Predictors of Bleeding from Esophageal Varices: The Role of Factor VII and von Willebrand Factor (vWF)

“…FVII deficiency develops in 75% -85% of patients, and levels range from 23% to 74% of normal in compensated cirrhosis [4]- [7]. FVII levels are significantly lower in decompensated cirrhosis, but 30% of normal ones are in most patients with stable disease [4] [5] [8].…”

“…Another possible mechanism of elevated vWF in cirrhosis is induction of synthesis of vWF in the liver with cirrhosis itself [8] or reduced liver-mediated clearance. Although it is established that vWF antigen levels are increased in patients with cirrhosis, relatively little is known on the relation between it and the bleeding from esophageal varices [9] [10] so we aimed in this study to determine the clinical predictors of bleeding esophageal varices and study the role of FVII and vWF in predicting bleeding in patients with eosphogeal varices.…”