thromboplastin and Hepatic-Encephalopathy

Microparticles (MPs), membrane fragments of 0.1-1.0 μm, are derived from many cell types in response to systemic inflammation. Acute liver failure (ALF) is a prototypical syndrome of systemic inflammatory response syndrome (SIRS) associated with a procoagulant state. We hypothesized that patients with ALF develop increased procoagulant MPs in proportion to the severity of systemic complications and adverse outcome. Fifty patients with acute liver injury (ALI), 78% of whom also had hepatic encephalopathy (HE; ALF), were followed until day 21 after admission. MPs were characterized by Invitrox Sizing, Antigen Detection and Enumeration, a light-scattering technology that can enumerate MPs as small as 0.15 μm, and by flow cytometry. Procoagulant activity was assessed by a functional MP-tissue factor (MP-TF) assay. Sixteen patients (32%) died and 27 (54%) recovered without liver transplantation (LT). Total MPs (0.15-1.0 μm) were present in nearly 19-fold higher concentrations in ALI/ALF patients, compared to healthy controls (P < 0.0001). MP-TF assays revealed high procoagulant activity (9.05 ± 8.82 versus 0.24 ± 0.14 pg/mL in controls; P = 0.0008). MP concentrations (0.28-0.64 μm) were higher in patients with the SIRS and high-grade HE, and MPs in the 0.36-0.64-μm size range increased in direct proportion to SIRS severity (P < 0.001) and grade of HE (P < 0.002). Day 1 MPs (0.28-0.64 μm) correlated with laboratory predictors of death/LT (higher phosphate and creatinine; lower bicarbonate), and day 1 and 3 MPs were higher in patients who died or underwent LT, compared to spontaneous survivors (P ≤ 0.01). By flow cytometry, 87% of patients had circulating CD41(+) MPs, indicating platelet origin.. Highly procoagulant MPs of specific size ranges are associated with the SIRS, systemic complications, and adverse outcome of ALI/ALF. MPs may contribute to the multiorgan system failure and high mortality of ALF.

Topics: Adult; Cell-Derived Microparticles; Female; Hepatic Encephalopathy; Humans; Liver Failure, Acute; Male; Middle Aged; Platelet Membrane Glycoprotein IIb; Systemic Inflammatory Response Syndrome; Thromboplastin

Activation of the immune coagulation system has been implicated in the pathogenesis of fulminant liver failure caused by murine hepatitis virus strain 3 (MHV-3). The recent discovery of the fgl2 gene, which encodes for MHV-3-induced prothrombinase (fgl2 prothrombinase), allows for fundamental studies to determine the molecular basis for fulminant liver failure. Transcription of the fgl2 gene and translation of the protein it encodes were examined in the liver and other organs of susceptible mice following MHV-3 infection. No constitutive expression of the fgl2 gene or the fgl2 prothrombinase was detected. Within 12 to 24 h of MHV-3 infection, however, fgl2 gene transcripts were detected in large amounts in the liver, spleen, and lungs, all of which are rich in reticuloendothelial cells, but were only focally present in small amounts in the kidney and brain. There was sequential detection of fgl2 prothrombinase in the liver, where it was localized specifically to the endothelium of intrahepatic veins and hepatic sinusoids; this was allowed by fibrin deposition, which resulted in confluent hepatocellular necrosis. These results provide further evidence for the role of the selective expression of this novel fgl2 prothrombinase in the pathogenesis of MHV-3-induced fulminant liver failure.

Topics: Animals; Coronavirus Infections; Female; Fibrinogen; Fluorescent Antibody Technique, Indirect; Gene Expression; Hepatic Encephalopathy; Immunoenzyme Techniques; In Situ Hybridization; Liver; Mice; Mice, Inbred BALB C; Murine hepatitis virus; Rabbits; RNA, Messenger; Thromboplastin

Topics: Adolescent; Adult; Ascites; Bilirubin; Edema; Hepatic Encephalopathy; Hepatitis B Antigens; Humans; Immunologic Techniques; Laparoscopy; Liver Cirrhosis; Liver Function Tests; Neoplasm Proteins; Prognosis; Serum Albumin; Sulfobromophthalein; Thromboplastin; Transaminases; Urobilinogen

Liver biopsy was performed in 38 patients with fulminant hepatitis and coma and repeated in 22. Stereological estimation of hepatocyte volume was correlated with levels of clotting factors. Early liver biopsy allowed prognosis in 55% of the cases. All patients with a hepatocyte volume of <35% and thromboplastin time /=35% and thromboplastin time >10% recovered consciousness (n = 9) or at least showed evidence of marked liver regeneration (n = 2). On serial liver biopsy a significant increase in hepatocyte volume and clotting factors was only observed in patients who recovered consciousness. The estimated liver cell mass after regeneration in patients who recovered consciousness was >/=45% and <45% in the patients who did not.

Topics: Acute Disease; Biopsy; Factor V; Hepatic Encephalopathy; Hepatitis; Hepatitis A; Humans; Liver; Liver Diseases; Prognosis; Thromboplastin; Time Factors

Topics: Blood Coagulation Tests; Chronic Disease; Factor VII; Hemorrhage; Hepatic Encephalopathy; Humans; Methods; Prothrombin Time; Thromboplastin