thromboplastin and Liver-Cirrhosis

Topics: Aminocaproates; Animals; Anticoagulants; Antifibrinolytic Agents; Antigens; Aprotinin; Blood Cell Count; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Chromatography; Chromatography, Gel; Dogs; Epidermolysis Bullosa; Fibrinogen; Fibrinolysis; Hematocrit; Immunoelectrophoresis; Injections, Intravenous; Iodine Isotopes; Liver Cirrhosis; Peptides; Polycythemia Vera; Potassium Iodide; Thrombin; Thromboplastin; Thrombosis

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Flow Velocity; Child; Child, Preschool; Clinical Laboratory Techniques; Dextrans; Female; Fibrinolytic Agents; Glomerulonephritis; Hemangioma, Cavernous; Heparin; Humans; Infections; Liver Cirrhosis; Male; Mycoses; Parasitic Diseases; Pregnancy; Pregnancy Complications; Purpura; Shock; Thrombocytopenia; Thromboplastin; Uremia

Topics: Blood Transfusion; Enzyme Inhibitors; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Hemostatics; Humans; Leukemia; Liver Cirrhosis; Male; Pathology; Physiology; Polycythemia Vera; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Prostatectomy; Prostatic Neoplasms; Prothrombin; Thrombin; Thromboplastin

A large amount of endotoxin can be detected in the peripheral venous blood of patients with liver cirrhosis, contributing to the pathogenesis of hepatotoxicity because of its role in oxidative stress. The present study aimed to test the effect of the supplementation with red palm oil (RPO), which is a natural oil obtained from oil palm fruit (Elaeis guineensis) rich in natural fat-soluble tocopherols, tocotrienols and carotenoids, on lipid peroxidation and endotoxemia with plasma endotoxin-inactivating capacity, proinflammatory cytokines profile, and monocyte tissue factor in patients with chronic liver disease.. The study group consisted of sixty patients (34 males and 26 females; mean age 62 years, range 54-75) with Child A/B, genotype 1 HCV-related cirrhosis without a history of ethanol consumption, randomly enrolled into an 8-week oral daily treatment with either vitamin E or RPO. All patients had undergone an upper gastrointestinal endoscopy 8 months before, and 13 out of them showed esophageal varices.. Both treatments significantly decreased erythrocyte malondialdehyde and urinary isoprostane output, only RPO significantly affected macrophage-colony stimulating factor and monocyte tissue factor. Liver ultrasound imaging did not show any change.. RPO beneficially modulates oxidative stress and, not least, downregulates macrophage/monocyte inflammatory parameters. RPO can be safely advised as a valuable nutritional implementation tool in the management of chronic liver diseases.

Topics: Aged; Cells, Cultured; Dietary Supplements; Erythrocytes; Female; Hepatitis C; Humans; Inflammation Mediators; Isoprostanes; Italy; Lipid Peroxidation; Liver; Liver Cirrhosis; Macrophage Colony-Stimulating Factor; Male; Malondialdehyde; Middle Aged; Monocytes; Oxidative Stress; Palm Oil; Plant Oils; Thromboplastin; Time Factors; Treatment Outcome

Clotting activation may occur in liver cirrhosis, but the pathophysiological mechanism has not been fully elucidated. Because a previous study demonstrated that lipid peroxidation is increased in cirrhosis, we analyzed whether there is a relationship between lipid peroxidation and clotting activation. Thirty cirrhotic patients (19 men and 11 women; age, 34 to 79 years) and 30 controls matched for sex and age were investigated. In all subjects, monocyte expression of tissue factor (TF) antigen and activity; plasma levels of prothrombin fragment 1+2 (F1+2), a marker of thrombin generation; and urinary excretion of Isoprostane-F2alpha-III, a marker of lipid peroxidation, were measured. Furthermore, the above-reported variables were re-evaluated after 30 days of treatment with standard therapy (n = 5) or standard therapy plus 300 mg vitamin E twice daily (n = 9). In addition, we analyzed in vitro if vitamin E (50 micromol/L) influenced monocyte TF expression and F1+2 generation. Cirrhotic patients had higher values of Isoprostane-F2alpha-III (P <. 0001), F1+2 (P <.0001), and monocyte TF antigen (P <.0001) and activity (P <.03) than controls. Isoprostane-F2alpha-III was significantly correlated with F1+2 (Rho = 0.85; P <.0001) and TF antigen (Rho = 0.95; P <.0001) and activity (Rho = 0.94; P <.0001). After vitamin E treatment, Isoprostane-F2alpha-III (P =.008), F1+2 (P <.008), and monocyte TF antigen (P =.012) and activity (P =.008) significantly decreased; no changes of these variables were detected in patients not receiving vitamin E. In vitro, vitamin E significantly reduced the expression of monocyte TF antigen (-52%; P =.001) and activity (-55%; P =.003), as well as F1+2 generation (-51%; P =.025). This study shows that vitamin E reduces both lipid peroxidation and clotting activation and suggests that lipid peroxidation may be an important mediator of clotting activation in liver cirrhosis.

Topics: Adult; Aged; Cross-Sectional Studies; Dietary Supplements; Dinoprost; Female; Humans; In Vitro Techniques; Lipid Peroxidation; Lipopolysaccharides; Liver Cirrhosis; Male; Middle Aged; Monocytes; Peptide Fragments; Placebos; Protein Precursors; Prothrombin; Reference Values; Thromboplastin; Vitamin E

Microvesicles (MVs) play a role in inflammation, coagulation, and vascular homeostasis in liver disease.. To characterize circulating plasma MVs profile in patients with decompensated cirrhosis and acute kidney injury (AKI).. We measured the levels of total, endothelial, platelet, tissue factor (TF)+, leukocyte and hepatocyte MVs by new generation flow-cytometry in a prospective cohort of patients with decompensated cirrhosis with and without AKI.. Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Patients with cirrhosis with AKI had significantly higher calcein+ (total), endothelial, and platelet-MVs. Conversely, TF+, leukocyte, and hepatocyte-MVs were comparable between groups. Resolution of AKI was associated with significantly decreased total and endothelial-MVs that became comparable with those in patients without AKI. Platelet MVs significantly decreased but remained higher compared to patients without AKI. TF+MVs significantly decreased and became lower than patients without AKI. Leukocyte and hepatocyte-MVs remained unchanged. Creatinine (OR 4.3 [95%CI 1.8-10.7]), MELD (OR 1.13 [95%CI 1.02-1.27]), any bleeding (OR 9.07 [95%CI 2.02-40.6]), and hepatocyte-MVs (OR 1.04 [95%CI 1.02-1.07]) were independently associated with 30-day mortality.. AKI worsened vascular and cellular homeostasis in patients with cirrhosis, particularly by inducing endothelial dysfunction and platelet activation. AKI did not worsen systemic inflammation and hepatocytes activation.

Topics: Acute Kidney Injury; Aged; Biomarkers; Blood Platelets; Cell-Derived Microparticles; Endothelial Cells; Female; Hepatocytes; Humans; Leukocytes; Liver Cirrhosis; Male; Middle Aged; Platelet Activation; Prospective Studies; Thromboplastin

In patients with chronic liver diseases, hypercoagulability can contribute to the progression of fibrosis and complications of cirrhosis. Tissue factor (TF) is a transmembrane glycoprotein that initiates the extrinsic pathway of blood coagulation. Recent investigations have established that TF is elevated in patients with pancreatic cancer, blood disorders, diabetes, and cardiovascular disease. Alternatively spliced tissue factor (asTF), a secreted form of TF, induces angiogenesis and exhibits low-level procoagulant activity. The aim of this study was to investigate whether the circulating levels of asTF are elevated in the plasma of patients with liver disease.. In a single-center study, we retrospectively analyzed asTF plasma levels in healthy participants and patients having stage F0-F3 liver fibrosis, liver cirrhosis, as well as hepatocellular carcinoma (HCC). AsTF plasma levels were measured using a sandwich enzyme-linked immunosorbent assay. Values were expressed as median with interquartile range (IQR).. The lowest median plasma asTF concentration (94 pg/ml, IQR: 33-275) was found in the healthy control group. The patients with low-grade liver fibrosis (F0-F1 group) displayed the highest median asTF concentration (404 pg/ml, IQR: 277-789). Significant differences between the asTF levels in the plasma of healthy participants and those in patients with grade F0-F1 fibrosis (P<0.001), patients with grade F2-F3 fibrosis (P=0.019), patients with cirrhosis (P=0.004), and patients with HCC (P<0.001) were found using a Wilcoxon rank-sum test. Treatment-naive patients with HCC had significantly higher asTF levels (P=0.018) than those receiving treatment. AsTF levels were found to increase with worsening Child-Pugh scores and heightened liver disease activity.. AsTF levels are elevated in patients with chronic liver diseases, which increase with worsening Child-Pugh scores and decrease following HCC therapy.

Topics: Adult; Alternative Splicing; Biomarkers; Carcinoma, Hepatocellular; Chronic Disease; Female; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Thromboplastin

Interleukin-17A (IL-17A), an inflammatory cytokine, is elevated in liver cirrhosis. Inflammation and coagulation dysfunction are closely related. Tissue factor (TF) is a bridge between endothelial activation, blood coagulation and inflammation. The aims of the present study were to evaluate endothelial TF expression in liver cirrhosis and identify the possible underlying role of IL-17A in TF expression. In the present study, we found that TF expression was increased on endothelium of splenic vein from cirrhotic patients and significantly correlated with intima/media ratios of splenic vein and coagulation parameters. Serum levels of IL-17A were significantly higher in cirrhotic patients as compared with normal controls. Cirrhotic serum and IL-17A stimulated TF expression in HUVECs, which was reduced by blockade of IL-17A, p38, and reactive oxygen species (ROS). Taken together, our data show that enhanced expression of endothelial TF, which plays an important role in coagulopathy and splenic vein remodeling in liver cirrhosis, is induced by IL-17A in a ROS dependent manner.

Topics: Endothelium, Vascular; Gene Expression Regulation; Humans; Interleukin-17; Liver Cirrhosis; p38 Mitogen-Activated Protein Kinases; Reactive Oxygen Species; Signal Transduction; Splenic Vein; Thromboplastin; Up-Regulation

Topics: Bacteria; Endotoxemia; Endotoxins; Factor VIII; Gene Expression Regulation; Humans; Liver; Liver Cirrhosis; Nitric Oxide; Portal Vein; RNA, Messenger; Signal Transduction; Thromboplastin; Venous Thrombosis; von Willebrand Factor

Tissue factor (TF) is a protein that mediates the initiation of the coagulation cascade. TF expression is increased in patients with poorly-controlled HIV, and may be associated with increased immune activation that leads to cardiovascular morbidity. The role of TF in immune activation in liver disease in hepatitis C virus (HCV)-monoinfection and HIV/HCV-coinfection has not been explored.. Fifty-nine patients were stratified: A) HIV-monoinfection (N = 15), B) HCV-monoinfection with chronic hepatitis C (CHC) (N = 15), C) HIV/HCV-coinfection with CHC (N = 14), and D) HIV/HCV-seropositive with cleared-HCV (N = 15). All HIV+ patients had undetectable HIV viremia. Whole blood was collected for CD4/CD8 immune activation markers by flow cytometry and plasma was assayed for microparticle TF (MPTF) activity. Subjects underwent transient elastography (TE) to stage liver fibrosis. Undetectable versus detectable MPTF was compared across strata using Fisher's Exact test.. MPTF activity was more frequently detected among patients with HCV-monoinfection (40%), compared to HIV-monoinfection and HIV/HCV-seropositive with cleared HCV (7%) and HIV/HCV-coinfection with CHC (14%) (p = 0.02). Mean TE-derived liver stiffness score in kPa was higher in patients with detectable MPTF (12.4 ± 8.5) than those with undetectable MPTF (6.4 ± 3.0) (p = 0.01). Mean CD4 + HLADR+ and CD4 + CD38-HLADR+ expression were higher in those with detectable MPTF (44 ± 9.8% and 38 ± 8.7%, respectively) than those with undetectable MPTF (36 ± 11% and 31 ± 10.4% respectively) (p = 0.05 and 0.04 respectively).. HCV-monoinfection and HIV/HCV-coinfection with CHC were associated with MPTF activity. MPTF activity is also associated with advanced liver fibrosis and with CD4 + HLADR+ immune activation.

Topics: Adult; Biomarkers; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Coinfection; Cross-Sectional Studies; Female; Flow Cytometry; Hepatitis C; Hepatitis C, Chronic; HIV Infections; Humans; Liver; Liver Cirrhosis; Male; Middle Aged; Thromboplastin; Ultrasonography

The international normalized ratio (INR) may not be directly applicable to patients with liver disease. We aimed to establish an alternative INR calibration system for patients with liver disease and to evaluate the effect of their use in chronic liver disease patients. Eighty-two patients with liver cirrhosis (LC) were included, and their prothrombin times (PTs) were measured by using 5 commercial thromboplastins. Each of the thromboplastins was also assigned an international sensitivity index (ISIliver) by the plasmas from LC patients. INRvka, INRliver, model for end-stage liver disease (MELD)vka, MELDliver, Child-Pugh (Child)vka, and Childliver scores were calculated. The coefficient of variance of INRvka was significantly larger than that of INRliver (P < 0.01). The mean difference in INRvka between the thromboplastins was also significantly larger than that in INRliver (P < 0.01). The total mean MELDliver score was higher than the total mean MELDvka score. The mean difference between the MELDvka and MELDliver scores (MELD score ≥15) was 3.2 %. We reconfirmed that the use of the alternative calibration system described herein for patients with liver disease may resolve the variability of INR measurement. Our data suggest that we would need to reevaluate the correlation between Child-Pugh class, MELD score, and clinical prognosis by using INRliver for patients with LC.

Topics: Aged; Chronic Disease; Female; Humans; International Normalized Ratio; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Prothrombin Time; Reference Values; Thromboplastin

Topics: Case-Control Studies; Cell-Derived Microparticles; Humans; Liver Cirrhosis; Thromboplastin

Topics: Adult; Aged; Biomarkers; Blood Coagulation Tests; Case-Control Studies; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Predictive Value of Tests; Reproducibility of Results; Severity of Illness Index; Thrombin; Thrombomodulin; Thrombophilia; Thromboplastin

Patients with liver disease often show substantial changes in their hemostatic system, which may aggravate further during liver transplantation. Recently, thrombin generation in patients with stable disease was shown to be indistinguishable from controls provided thrombomodulin, the natural activator of the anticoagulant protein C system, was added to the plasma. These results indicated that the hemostatic balance is preserved in patients with liver disease, despite conventional coagulation tests suggest otherwise.. Here we examined thrombin generation profiles in serial plasma samples taken from ten consecutive patients undergoing liver transplantation.. At all time points, the endogenous thrombin potential (ETP) was slightly lower compared to healthy volunteers, despite substantially prolonged PT and APTT values. However, when thrombin generation was tested in the presence of thrombomodulin, the ETP was equal to or even higher than that in healthy subjects. In fact, thrombin generation was hardly affected by thrombomodulin, while thrombin generation in healthy subjects decreased profoundly upon the addition of thrombomodulin. In patients undergoing liver transplantation, efficient thrombin generation in the presence of thrombomodulin may be explained by decreased levels of protein C, S, and antithrombin, and by elevated levels of FVIII.. Thrombin generation in patients undergoing liver transplantation is equal or even superior to thrombin generation in healthy volunteers when tested in the presence of exogenous thrombomodulin. These results support the recently advocated restrictive use of plasma during liver transplantation and warrants further study of the prophylactic use of anticoagulants to reduce thromboembolic complications after transplantation.

Topics: Adult; Blood Coagulation Tests; Case-Control Studies; Cholangitis, Sclerosing; Factor VIII; Female; Hepatitis C; Humans; Liver Cirrhosis; Liver Diseases; Liver Transplantation; Male; Middle Aged; Prothrombin Time; Thrombin; Thrombomodulin; Thromboplastin; Time Factors

Chronic injury to intrahepatic bile duct epithelial cells (BDECs) elicits expression of various mediators, including the αVβ6 integrin, promoting liver fibrosis. We tested the hypothesis that tissue factor (TF)-dependent thrombin generation and protease activated receptor-1 (PAR-1) activation contribute to liver fibrosis induced by cholestasis via induction of αVβ6 expression. To test this hypothesis, mice deficient in either TF or PAR-1 were fed a diet containing 0.025% α-naphthylisothiocyanate (ANIT), a BDEC-selective toxicant. In genetically modified mice with a 50% reduction in liver TF activity fed an ANIT diet, coagulation cascade activation and liver fibrosis were reduced. Similarly, liver fibrosis was significantly reduced in PAR-1(-/-) mice fed an ANIT diet. Hepatic integrin β6 mRNA induction, expression of αVβ6 protein by intrahepatic BDECs, and SMAD2 phosphorylation were reduced by TF deficiency and PAR-1 deficiency in mice fed the ANIT diet. Treatment with either an anti-αVβ6 blocking antibody or soluble transforming growth factor-β receptor type II reduced liver fibrosis in mice fed the ANIT diet. PAR-1 activation enhanced transforming growth factor-β1-induced integrin β6 mRNA expression in both transformed human BDECs and primary rat BDECs. Interestingly, TF and PAR-1 mRNA levels were increased in livers from patients with cholestatic liver disease. These results indicate that a TF-PAR-1 pathway contributes to liver fibrosis induced by chronic cholestasis by increasing expression of the αVβ6 integrin, an important regulator of transforming growth factor-β1 activation.

Topics: Adult; Aged; Animals; Bile Ducts, Intrahepatic; Blood Coagulation Factors; Cells, Cultured; Cholestasis; Female; Gene Expression; Humans; Integrin alphaV; Integrin beta Chains; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Rats; Receptor, PAR-1; Thromboplastin

The coagulation "cascade" model accurately represents the mechanisms of the prothrombin time and activated partial thromboplastin time tests. However, these tests and the "cascade" model do not accurately reflect the risk of hemorrhage or thrombosis in vivo. In hepatic insufficiency, a balanced reduction in the levels of most of pro- and anticoagulant proteins produced in the liver does not impair thrombin generation until levels are quite low. However, the ability of the coagulation system to tolerate or recover from an insult is markedly impaired in liver disease. This allows the coagulation system to be more easily tipped into a state favoring either hemorrhage or thrombosis.

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Hemorrhage; Hemostasis; Humans; Liver Cirrhosis; Liver Failure; Models, Biological; Prothrombin Time; Thrombin; Thromboplastin; Thrombosis

Thrombin, acting via protease-activated receptors (PARs), and tissue factor (TF) are involved in inflammation, tissue repair and tumorigenesis. Hepatocellular carcinomas (HCCs) usually complicate chronic liver diseases characterised by inflammation and fibrosis. The aim of this study was to describe the expression of PARs and TF in normal liver, cirrhosis and HCCs. We performed an immunohistochemical detection of PAR-1, PAR-3, PAR-4 and human TF in human tissue samples from 19 subnormal livers, 33 cirrhosis and 30 HCCs. PAR-1 was found on endothelial cells of sinusoids and larger vessels. In cirrhosis, spindle-shaped cells within septa and T lymphocytes were PAR-1 positive. A few PAR-1-positive tumour cells were found in 10% of HCCs. PAR-4 expression was restricted to macrophages, B lymphocytes and nerves. PAR-3 expression was rare. Unexpectedly, TF was expressed in 95% of normal livers and in 94% of cirrhosis but only in 50% of HCCs (p<0.001). Staining was mostly hepatocellular. No association existed between TF labelling and clinicopathological characteristics of HCCs. In conclusion, the pattern of expression of PARs is compatible with its role in chronic liver disease by promoting inflammation via immune cells and neurogenic stimulation. However, our data do not support a role for PARs or TF in HCC progression.

Topics: Carcinoma, Hepatocellular; Female; Humans; Immunohistochemistry; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Receptors, Proteinase-Activated; Thromboplastin

Recombinant human factor VIIa (rhFVIIa) is used to treat hemophilia and occasionally individuals with liver disease. The aim of the present study was to investigate the consequences of rhFVIIa in individuals with advanced liver disease in an attempt to understand the mechanism of action of rhFVIIa in this unique population.. Levels of plasma tissue factor, plasminogen activator inhibitor-1, tissue factor pathway inhibitor, fibrin split products, D-dimers and free thrombomodulin were measured following the administration of rhFVIIa in 17 subjects. The results were compared to normal controls.. The prothrombin time declined from 20.2 +/- 2.8 s to 14.3 +/- 3.9 s (P < 0.01). No change in the activated partial thromboplastin time occurred. A 15.6% reduction in thrombomodulin was observed (P < 0.05). A mean 75.2% reduction in plasma tissue factor occurred (P < 0.01). Tissue factor pathway inhibitor levels declined to less than the control value (P < 0.05). No changes in plasminogen activator inhibitor-1, fibrin split products or D-dimer levels occurred.. These data demonstrate that rhFVIIa administration to individuals with liver disease results in (i) a transient improvement in the prothrombin time; (ii) no change in the activated partial thromboplastin time; and (iii) a marked reduction in the levels of thrombomodulin and tissue factor. These data suggest that rhFVIIa binds tissue factor and enhances tissue factor and thrombomodulin clearance from the circulation.

Topics: Adult; Aged; Biomarkers; Enzyme-Linked Immunosorbent Assay; Factor VII; Factor VIIa; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Recombinant Proteins; Thrombomodulin; Thromboplastin; Treatment Outcome

The mechanisms leading to the hemostatic changes of acute liver injury are poorly understood. To study these further we have assessed coagulation and immune changes in patients with acute paracetamol overdose and compared the results to patients with chronic cirrhosis and normal healthy controls. The results demonstrate that in paracetamol overdose coagulation factors (F)II, V, VII and X were reduced to a similar degree and were significantly lower than FIX and FXI (mean levels 0.28, 0.16, 0.13, 0.19, 0.51 and 0.72 IU mL(-1), respectively). In cirrhosis, by contrast, FII, FV, FVII, FIX and FX were equally reduced whilst FXI was lower than the other factors (mean levels 0.64, 0.69, 0.62, 0.60, 0.66 and 0.40 IU mL-1, respectively). FVIII was raised in paracetamol overdose patients but normal in those with cirrhosis (mean levels 1.95 and 1.01 IU mL(-1), respectively). Interleukin-6 and tumor necrosis factor-alpha levels were raised in both patient groups, but higher levels were found in paracetamol overdose, compared to cirrhosis. Thrombin-antithrombin and soluble tissue factor levels were higher in those with acute liver injury but normal in cirrhosis. Antithrombin levels were reduced in both acute liver injury and cirrhosis. From these data we put forward a novel mechanism for the coagulation changes in acute paracetamol induced liver injury. We propose that immune activation leads to tissue factor-initiated consumption of FII, FV, FVII and FX, but that levels of FIX and FXI are better preserved because antithrombin inhibits the thrombin induced positive feedback loop that activates these latter factors.

Topics: Acetaminophen; Adolescent; Adult; Aged; Aged, 80 and over; Antithrombin III; Blood Coagulation; Blood Coagulation Factors; Case-Control Studies; Humans; Interleukin-6; Liver Cirrhosis; Liver Failure, Acute; Middle Aged; Models, Biological; Peptide Hydrolases; Thromboplastin; Tumor Necrosis Factor-alpha

Liver cirrhosis is associated with alterations of the coagulation system commonly causing bleeding as well as thromboembolic complications. The potential pathophysiological roles of tissue factor (TF) (the initiator of the extrinsic coagulation pathway) and thrombomodulin (TM) (an initiator of the anticoagulatory protein C pathway) are unknown. We therefore measured plasma concentrations of TF and TM in 111 patients with liver diseases who were evaluated for liver transplantation. We could demonstrate that the levels of both molecules increased with the Child's class of liver cirrhosis, independently of aetiology. TM was significantly elevated in Child A, B and C patients compared with patients without cirrhosis; TF only in Child C patients. The plasma TM and TF concentrations correlated with prothrombin time, activated partial thromboplastin time, and inversely with factor VII activity, cholinesterase serum activity, and serum albumin concentration. TM was elevated in patients with a bleeding tendency, but TM and TF did not differ between patients with or without prior thrombotic events. Further studies are warranted to clarify the underlying mechanisms that raise TM and TF plasma levels in liver disease with possible clinical consequences.

Topics: Adolescent; Adult; Aged; Alanine Transaminase; Aspartate Aminotransferases; Female; Hemorrhage; Humans; Liver Cirrhosis; Male; Middle Aged; Partial Thromboplastin Time; Platelet Count; Prothrombin Time; Reference Values; Thromboembolism; Thrombomodulin; Thromboplastin

Previous studies have shown that cirrhotic patients produce increased amounts of thrombin but the underlying mechanism is still unknown.. To analyse the relation between the rate of thrombin generation and monocyte expression of tissue factor (TF) in cirrhosis.. Thirty three cirrhotic patients classified as having low (n = 7), moderate (n = 17), or severe (n = 9) liver failure according to Child-Pugh criteria.. Prothrombin fragment F1 + 2, monocyte TF activity and antigen, and endotoxaemia were measured in all patients. Polymerase chain reaction (PCR) analysis of TF mRNA was performed in monocytes of five cirrhotic patients.. Prothrombin fragment F1 + 2 was higher in cirrhotic patients than in controls (p < 0.0001). Monocytes from cirrhotic patients had higher TF activity and antigen than those from controls (p < 0.001) with a progressive increase from low to severe liver failure. Monocyte expression of TF was significantly correlated with plasma levels of F1 + 2 (TF activity: r = 0.98, p < 0.0001; TF antigen: r = 0.95, p < 0.0001) and with endotoxaemia (TF activity: r = 0.94, p < 0.0001; TF antigen: r = 0.91, p < 0.0001). PCR analysis of TF mRNA showed TF expression only in three patients with endotoxaemia (more than 15 pg/ml).. Cirrhotic patients have enhanced expression of TF which could be responsible for clotting activation, suggesting that endotoxaemia might play a pivotal role.

Topics: Adult; Aged; Antigens; Blood Coagulation; Case-Control Studies; Cross-Sectional Studies; Endotoxemia; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Monocytes; Peptide Fragments; Polymerase Chain Reaction; Prothrombin; Regression Analysis; RNA, Messenger; Thromboplastin

The pathophysiologic mechanism underlying the association between endotoxaemia and clotting activation in liver cirrhosis is still to be explained.. To investigate the relationship between endotoxaemia, endothelial perturbation and clotting system activation in liver cirrhosis patients.. The study was carried out in 30 consecutive patients (17 males, 13 females, age range 42 to 71 years) with liver cirrhosis.. Prothrombin fragment F1 + 2, endotoxaemia, von Willebrand factor and ristocetin cofactor activity were studied in all patients. Von Willebrand factor antigen release and tissue factor expression were also evaluated in cultured endothelial cells incubated with low endotoxin concentrations (125-500 pg/ml).. Thirteen (43%) out of 30 liver cirrhosis patients showing von Willebrand factor antigen levels > 157 IU/dl (mean +/- 2SD of controls) were considered to have signs of endothelial perturbation; they had more severe liver failure (p = 0.0001), higher ristocetin cofactor activity (p = 0.0001), endotoxin (p = 0.0001) and prothrombin fragment F1 + 2 (p = 0.0001) plasma values than liver cirrhosis with normal von Willebrand factor antigen. A strong correlation (r = 0.97; p = 0.0001) was found between prothrombin fragment F1 + 2 and von Willebrand factor antigen. In in vitro experiments endotoxin induced a concentration-dependent release of von Willebrand factor antigen (p = 0.0001) and expression of tissue factor activity (p = 0.0001) and antigen (p = 0.0001) from cultured endothelial cells.. This study suggests that the endothelial procoagulant activation induced by low-grade endotoxaemia may represent a trigger for systemic clotting activation in liver cirrhosis patients.

Topics: Adult; Aged; Blood Coagulation; Cells, Cultured; Endothelium, Vascular; Endotoxemia; Female; Fibrinolysis; Humans; Liver Cirrhosis; Male; Middle Aged; Peptide Fragments; Prothrombin; Thromboplastin; von Willebrand Factor

Topics: Animals; Antithrombin III; Humans; Liver Cirrhosis; Prothrombin Time; Rabbits; Species Specificity; Thromboplastin

Topics: Adult; Aged; Blood Coagulation Factors; Blood Coagulation Tests; Factor XI; Female; Humans; Liver Cirrhosis; Lupus Erythematosus, Systemic; Thromboplastin

20 coagulation parameters were investigated in 144 patients with different liver diseases. The groups of acute hepatitis, chronic active hepatitis and liver cirrhosis were compared and the prognostic value of the coagulation analyses investigated. It is clear that the determination of the factor V activity is a good and easy test for detection of actual liver function. Repeated controls over several weeks revealed with a statistical significance (p less than 0.0005) that all patients with a factor XIII below 35% and a plasminogen below 19% will die in liver coma, if they have not died beforehand from acute gastrointestinal haemorrhage, acute infection or cardiac arrest. Plasminogen is also lower in the group of non-survivors but the values of the two groups are overlapping and of no prognostic help in a single case. The possible causes of the diminution of factor XIII activity are discussed.

Topics: Adolescent; Adult; Aged; Blood Coagulation Tests; Factor V; Factor XIII; Female; Fibrin Fibrinogen Degradation Products; Hepatitis; Humans; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Plasminogen; Prognosis; Prothrombin; Thromboplastin; Time Factors

Topics: Antithrombin III; Antithrombins; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Humans; Liver Cirrhosis; Plasminogen; Prothrombin Time; Thrombin; Thromboplastin; Thrombosis; Time Factors

Topics: Blood Coagulation Factors; Humans; Liver Cirrhosis; Thromboplastin

Topics: Antithrombins; Blood Coagulation Tests; Caseins; Factor V; Factor VIII; Fibrinogen; Fibrinolysis; Hepatitis; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Mushroom Poisoning; Plasminogen; Prothrombin Time; 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

Topics: Blood Cell Count; Blood Platelets; Chronic Disease; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Heparin; Humans; Liver Cirrhosis; Pregnancy; Pregnancy Complications, Hematologic; Prothrombin Time; Thrombin; Thromboplastin

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Factor VIII; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemagglutination Inhibition Tests; Humans; Liver Cirrhosis; Male; Plasminogen; Thromboplastin

Topics: Fibrinolysis; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Prothrombin Time; Serum Globulins; Thromboplastin

Topics: Ascites; Ascitic Fluid; Diagnosis, Differential; Gastrointestinal Neoplasms; Humans; Liver Cirrhosis; Methods; Prothrombin; Thromboplastin

Topics: Aged; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Fibrinolysis; Hemophilia B; Humans; Liver; Liver Cirrhosis; Male; Prothrombin Time; Thromboplastin

Topics: Blood Coagulation; Deoxyribonuclease I; Drug Therapy; Geriatrics; Hemophilia A; Humans; Liver Cirrhosis; Streptodornase and Streptokinase; Streptokinase; Thromboplastin

Topics: Barium Sulfate; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Coumarins; Factor IX; Factor V; Factor VIII; Factor X; Female; Humans; Infant; Infant, Newborn; Lanthanoid Series Elements; Liver Cirrhosis; Pharmacology; Pregnancy; Thorium; Thromboplastin

Topics: Antithrombins; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Humans; Lipoproteins; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Pathology; Thrombin; Thromboplastin

Topics: Animals; Coloring Agents; Lagomorpha; Liver Cirrhosis; Pathology; Pharmacology; Rabbits; Research; Spleen; Splenic Vein; Staining and Labeling; Thromboplastin; Wounds and Injuries

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Factor IX; Hemophilia B; Humans; Liver Cirrhosis; Research; Thromboplastin; Whole Blood Coagulation Time

Topics: Anticoagulants; Coumarins; Factor XI; Humans; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Thromboplastin

Topics: Ascitic Fluid; Humans; Liver Cirrhosis; Thromboplastin