fibrin and Liver-Diseases

Strong experimental evidence indicates that components of the hemostatic system, including thrombin, exacerbate diverse features of experimental liver disease. Clinical studies have also begun to address this connection and some studies have suggested that anticoagulants can improve outcome in patients with liver disease. Among the evidence of coagulation cascade activation in models of liver injury and disease is the frequent observation of thrombin-driven hepatic fibrin(ogen) deposition. Indeed, hepatic fibrin(ogen) deposition has long been recognized as a consequence of hepatic injury. Although commonly inferred as pathologic due to protective effects of anticoagulants in mouse models, the role of fibrin(ogen) in acute liver injury and chronic liver disease may not be universally detrimental. The localization of hepatic fibrin(ogen) deposits within the liver is connected to the disease stimulus and in animal models of liver toxicity and chronic disease, fibrin(ogen) deposition may not always be synonymous with large vessel thrombosis. Here, we provide a balanced review of the experimental evidence supporting a direct connection between fibrin(ogen) and liver injury/disease pathogenesis, and suggest a path forward bridging experimental and clinical research to improve our knowledge on the nature and function of fibrin(ogen) in liver disease.

Topics: Acute Disease; Animals; Chronic Disease; Disease Models, Animal; Fibrin; Fibrinogen; Humans; Liver Diseases; Mice

Topics: Animals; Biomarkers; Fibrin; Fibrinolysis; Humans; Liver; Liver Diseases; Peptide Fragments; Procollagen

Topics: Fibrin; Hepatectomy; Humans; Kupffer Cells; Liver; Liver Diseases; Macrophage Activation; Macrophages; Necrosis

The fibrinolytic system comprises a proenzyme, plasminogen, which can be activated to the active enzyme plasmin, that will degrade fibrin by different types of plasminogen activators. Inhibition of fibrinolysis may occur at the level of plasmin or at the level of the activators. Fibrinolysis in human blood seems to be regulated by specific molecular interactions between these components. In plasma, normally no systemic plasminogen activation occurs. When fibrin is formed, small amounts of plasminogen activator and plasminogen adsorb to the fibrin, and plasmin is generated in situ. The formed plasmin, which remains transiently complexed to fibrin, is only slowly inactivated by alpha 2-antiplasmin, while plasmin, which is released from digested fibrin, is rapidly and irreversibly neutralized. The fibrinolytic process, thus, seems to be triggered by and confined to fibrin. Thrombus formation may occur as the result of insufficient activation of the fibrinolytic system and (or) the presence of excess inhibitors, while excessive activation and/or deficiency of inhibitors might cause excessive plasmin formation and a bleeding tendency. Evidence obtained in animal models suggests that tissue-type plasminogen activator, obtained by recombinant DNA technology, may constitute a specific clot-selective thrombolytic agent with higher specific activity and fewer side effects than those currently in use.

Topics: alpha-2-Antiplasmin; alpha-Macroglobulins; Animals; Behcet Syndrome; Binding Sites; Disseminated Intravascular Coagulation; Embolism; Female; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Humans; In Vitro Techniques; Kidney Diseases; Kinetics; Liver Diseases; Lysine; Plasminogen; Plasminogen Activators; Plasminogen Inactivators; Pregnancy; Streptokinase; Thrombosis; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

The existence of a system in the human body capable of inducing the dissolution of endogenous pathologically formed thrombi was appreciated in ancient times. Considered in detail in this article are the data that have elucidated the physiologic regulation of which plasmin formation is dependent on, the plasma concentration of plasminogen, availability of activators of plasminogen in the plasma and surrounding tissue environment, the concentration of naturally present inhibitors, and the existence of fibrin in the circulation. Important in this rapidly progressive scientific discipline is consideration of the factors which control the synthesis of the components of this proteolytic enzyme system. Recently abundant information has indicated that this plasminogen-plasmin proteolytic enzyme system can be utilized therapeutically. Knowledge of the mechanisms of this system has permitted identification of agents that can be exogenously administered to releave thrombotic obstruction to blood flow in the venous (pulmonary emboli, deep vein thrombosis) and arterial (peripheral and central vessels) circulatory systems. Particularly important is the demonstration that thrombolytic agents can directly attack and alleviate the immediate cause of acute myocardial infarction. As a result of the innovations in the present decade, it is evident that the plasminogen system can be advantageously employed to reverse the pathologic effects of all thrombotic diseases.

Topics: alpha 1-Antitrypsin; alpha-2-Antiplasmin; alpha-Macroglobulins; Antifibrinolytic Agents; Antithrombin III; Arterial Occlusive Diseases; Arteriosclerosis; Complement C1 Inactivator Proteins; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Humans; Kidney Diseases; Liver Diseases; Myocardial Infarction; Neoplasms; Plasminogen; Pulmonary Embolism; Thrombophlebitis

Topics: Adsorption; alpha-2-Antiplasmin; alpha-Macroglobulins; Animals; Disseminated Intravascular Coagulation; Endopeptidases; Fibrin; Fibrinolysis; Humans; Liver Diseases; Plasminogen; Thrombosis

Topics: Adult; Blood Coagulation Disorders; Fibrin; Fibrinogen; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver Diseases; Protein Conformation; Sialic Acids

Topics: Amino Acids; Blood Coagulation; Blood Platelets; Carbohydrates; Electrophoresis, Polyacrylamide Gel; Factor XIII; Factor XIII Deficiency; Fibrin; Humans; Liver Diseases; Molecular Weight; Neoplasms; Placenta

Topics: Adult; Afibrinogenemia; Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Chemical Phenomena; Chemistry; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Humans; Infant, Newborn; Kidney Diseases; Liver Diseases; Male; Models, Biological; Pregnancy

The evidence for intravascular coagulation in liver diseases is critically reviewed. Alternative mechanisms for hypofibrinogenemia and the accelerated disappearance of fibrinogen from blood are proposed, such as loss into extravascular compartments (e.g., ascites, areas of liver necrosis, etc.). Possible mechanisms other than DIC for the elevation of serum FDP are also considered, such as extravascular fibrinogen proteolysis with subsequent transfer of FDP to blood. Therapy is discussed with reference to the current knowledge on pathophysiology of the coagulation defect in liver diseases.

Topics: Afibrinogenemia; Blood Cell Count; Blood Platelets; Disseminated Intravascular Coagulation; Factor V Deficiency; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Half-Life; Hemophilia A; Heparin; Humans; Liver Diseases; Peptide Hydrolases; Thrombocytopenia; Thrombosis

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Calcium; Factor IX; Factor V; Factor VIII; Factor X; Factor XII; Fibrin; Fibrinogen; Humans; Liver Diseases; Phospholipids; Prothrombin; Prothrombin Time; Thromboplastin; Vitamin K Deficiency

Topics: Abruptio Placentae; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Blood Transfusion; Disseminated Intravascular Coagulation; Embolism, Amniotic Fluid; Factor XIII Deficiency; Female; Fetal Death; Fetal Diseases; Fibrin; Fibrinogen; Fibrinolysis; Hemophilia A; Humans; Liver Diseases; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Sepsis; Uterine Hemorrhage; Vitamin K

Topics: Age Factors; Animals; Avitaminosis; Biomechanical Phenomena; Cats; Cicatrix; Collagen; Connective Tissue; Dehydration; Fibrin; Granulation Tissue; Hormones; Humans; Liver Diseases; Oxygen; Protein Deficiency; Radiation Effects; Rats; Tissue Extracts; Wound Healing; Wounds and Injuries

Topics: Adenine Nucleotides; Blood Coagulation; Blood Platelet Disorders; Blood Platelets; Clot Retraction; Collagen; Fibrin; Fibrinogen; Hemostasis; Kidney Diseases; Liver Diseases; Platelet Adhesiveness; Thrombocytopenia; Thrombocytosis

Background: Endotoxemia causes endothelial dysfunction and microthrombosis, which are pathogenic mechanisms of coagulopathy and organ failure during sepsis. Simvastatin has potential anti-thrombotic effects on liver endothelial cells. We investigated the hemostatic changes induced by lipopolysaccharide (LPS) and explored the protective effects of simvastatin against liver vascular microthrombosis. Methods and results: We compared male Wistar rats exposed to LPS (5 mg/kg one i.p. dose) or saline in two experimental protocols—placebo (vehicle) and simvastatin (25 mg/kg die, orally, for 3 days before LPS). Morphological studies were performed by light- and electron-microscopy analyses to show intravascular fibrin deposition, vascular endothelial structure and liver damage. Peripheral- and organ-hemostatic profiles were analyzed using whole blood viscoelastometry by ROTEM, liver biopsy and western-blot/immunohistochemistry of thrombomodulin (TM), as well as immunohistochemistry of the von Willebrand factor (VWF). LPS-induced fibrin deposition and liver vascular microthrombosis were combined with a loss of sinusoidal endothelial TM expression and VWF-release. These changes were associated with parenchymal eosinophilia and necrosis. ROTEM analyses displayed hypo-coagulability in the peripheral blood that correlated with the degree of intrahepatic fibrin deposition (p < 0.05). Simvastatin prevented LPS-induced fibrin deposition by preserving TM expression in sinusoidal cells and completely reverted the peripheral hypo-coagulability caused by endotoxemia. These changes were associated with a significant reduction of liver cell necrosis without any effect on eosinophilia. Conclusions: Simvastatin preserves the antithrombotic properties of sinusoidal endothelial cells disrupted by LPS, deserving pharmacological properties to contrast sepsis-associated coagulopathy and hepatic failure elicited by endotoxemia

Topics: Animals; Disease Models, Animal; Endothelial Cells; Endotoxemia; Fibrin; Hemostatics; Lipopolysaccharides; Liver Diseases; Male; Necrosis; Rats; Rats, Wistar; Sepsis; Simvastatin; Thrombosis; von Willebrand Factor

Liver injury has been reported in patients with COVID-19. This condition is characterized by severe outcome and could be related with the ability of SARS-CoV-2 to activate cytotoxic T cells. The purpose of this study is to show the histological and scanning electron microscopy features of liver involvement in COVID-19 to characterize the liver changes caused by the activation of multiple molecular pathways following this infection.. Liver biopsies from 4 patients (3 post-mortems and 1 in vivo) with COVID-19 were analyzed with histology and by scanning electron microscopy.. The liver changes showed significant heterogeneity. The first case showed ground glass hepatocytes and scattered fibrin aggregates in the sinusoidal lumen. The second evidenced intra-sinusoidal thrombi. The third was characterized by sinusoidal dilatation, atrophy of hepatocytes, Disse's spaces dilatation and intra-sinusoidal aggregates of fibrin and red blood cells. The fourth case exhibited diffuse fibrin aggregates in the dilated Disse spaces and microthrombi in the sinusoidal lumen.. In COVID-19-related liver injury, a large spectrum of pathological changes was observed. The most peculiar features were very mild inflammation, intra-sinusoidal changes, including sinusoidal dilatation, thrombotic sinusoiditis and diffuse intra-sinusoidal fibrin deposition. These findings suggested that a thrombotic sinusoiditis followed by a local diffuse intra-vascular (intra-sinusoidal) coagulation could be the typical features of the SARS-CoV-2-related liver injury.

Topics: Aged; Autopsy; Biopsy; Blood Coagulation Disorders; COVID-19; Erythrocytes; Fibrin; Hepatocytes; Humans; Liver; Liver Diseases; Male; Microscopy, Electron, Scanning; Middle Aged; Thrombosis; Young Adult

Oral anticoagulant therapy (OAT) patients have international normalized ratio (INR) safety windows for oral surgery, the lower limit of which is determined by the thromboembolic risk, with the upper limit typically 3.0. We sought to assess whether these limits will also be true with comorbidities that favor bleeding, such as diabetes, liver disease, and chronic renal failure.. The study was designed for 500 consecutive extractions. Patients with an INR greater than 3.0 were switched to heparin and used as controls. The primary outcome was the incidence of bleeding with the need for reoperation, in connection with 3 principal predictors: the INR, reasons for OAT, and comorbidity type. Continuous variables were analyzed using the Mann-Whitney U test and categorical variables using χ2 or Fisher's exact test. Statistical significance was set at P < .05. The reliability of the INR as a bleeding predictor was assessed using receiver operating characteristic (ROC) curves.. Extractions in patients receiving OAT without comorbidities had a success rate of 99.7% against severe bleeding. Despite equivalent INR values, patients with comorbidities had a significantly lower rate (81.3%, P < .001). For these patients, the ROC curve procedure indicated lower INR upper limits, 2.8 for mechanical heart prosthesis subjects and 2.3 for all others. Among the comorbidities, diabetes was associated with the greatest frequency of bleeding (31%) compared with liver disease (15%) and kidney failure (11%).. Patients with comorbidities should be advised to bring their INR within narrower safety windows (upper limit of 2.5 to 2.8 for mechanical prosthesis and 2.0 to 2.3 otherwise) or be switched to heparin. Alternatively, we propose applying to the socket, a platelet-rich growth factor preparation to foster hemostasis.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Area Under Curve; Chronic Disease; Diabetes Complications; Female; Fibrin; Follow-Up Studies; Heart Valve Prosthesis; Hematoma; Hemostatics; Heparin; Humans; International Normalized Ratio; Liver Diseases; Male; Middle Aged; Oral Hemorrhage; Postoperative Hemorrhage; Prospective Studies; Renal Insufficiency; ROC Curve; Thromboembolism; Tooth Extraction; Tooth Socket; Treatment Outcome; Young Adult

Studies in rodents suggest that the adipocytokine resistin causes insulin resistance via impairing normal insulin signaling. However, in humans, resistin may play a more important role in inflammation than in insulin resistance. Whether resistin contributes to inflammation in rodents is unclear. Therefore, the purpose of the present study was to determine the effect of resistin exposure on the basal and stimulated [lipopolysaccharide (LPS)] inflammatory response in mouse liver in vivo. Resistin alone had no major effects on hepatic expression of insulin-responsive genes, either in the presence or absence of LPS. Although it had no effect alone, resistin significantly enhanced hepatic inflammation and necrosis caused by LPS. Resistin increased expression of proinflammatory genes, e.g., plasminogen activator inhibitor (PAI)-1, and activity of mitogen-activated protein (MAP) kinase, extracellular signal-regulated kinase 1/2, caused by LPS, but had little effect on anti-inflammatory gene expression. Resistin also enhanced fibrin deposition (an index of hemostasis) caused by LPS. The increase in PAI-1 expression, fibrin deposition, and liver damage caused by LPS + resistin was almost completely prevented either by inhibiting the coagulation cascade, hirudin, or by blocking MAP kinase signaling, U0126 [1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio) butadiene], indicating that these pathways play a causal role in observed enhanced liver damage caused by resistin. Taken together, the augmentation of LPS-induced liver damage caused by resistin seems to involve, at least in part, up-regulation of hepatic inflammation via mechanisms most likely involving the coagulation cascade and fibrin accumulation. These data also suggest that resistin may have proinflammatory roles in mouse liver independent of its effects on insulin signaling, analogous to previous work in humans.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Blood Glucose; Chemical and Drug Induced Liver Injury; Fibrin; Gene Expression Regulation; Glucose; Insulin; Lipopolysaccharides; Liver; Liver Diseases; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Resistin; RNA, Messenger; Tumor Necrosis Factor-alpha

The liver can be injured and its functions altered by activation of the coagulation and inflammatory processes in sepsis. The objective of the present study was to investigate the pattern of protease- activated receptors (PARs) over time in a model of acute liver injury induced by lipopolysaccharide (LPS); and whether PARs play a role in this process and exert their effects through inflammation and coagulation. Levels of tumor necrosis factor-a (TNF-a) were significantly expressed 1 h after LPS administration followed by: i) an increase in levels of tissue factor, factor VIIa, thrombin and plasminogen activator inhibitor-1; ii) unchanged or steady levels of tissue factor pathway inhibitor; and iii) subsequent deposition of fibrin in the liver tissue, that led to the elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are associated with liver injury. The expression of all PAR isoforms (1-4) was elevated, and each isoform had a distinct cellular localization (hepatocytes, Kupffer cells, the portal triad area, and central veins) and a time-dependent pattern of expression. The immuno-reactivity of PAR2 and 4 in Kupffer cells was intense. Interestingly, PAR2 blocking peptide improved the healing of liver injuries, an effect that was associated with suppression of TNF-a elevation, and normalization of coagulation and fibrinolysis. This ultimately led to decreased fibrin formation in the injured liver. The present study reveals a distinct chronological expression and cellular localization of PARs in LPS-mediated liver injury and shows that blockade of PAR2 may play a crucial role in treating liver injury, via normalization of inflammation, coagulation and fibrinolytic pathways.

Topics: Acute Disease; Animals; Blood Coagulation; Blood Coagulation Factors; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Fibrin; Fibrinolysis; Humans; Lipopolysaccharides; Liver; Liver Diseases; Peptides; Protein Isoforms; Rats; Rats, Wistar; Receptor, PAR-1; Receptor, PAR-2; Receptors, Proteinase-Activated; Receptors, Thrombin; RNA, Messenger; Sepsis; Time Factors; Tumor Necrosis Factor-alpha

The regeneration after liver injury is regulated by the release and activation of several growth factors. The role of the plasmin/alpha(2)-antiplasmin (alpha(2)-AP) system in liver regeneration was investigated.. CCl(4) was injected intraperitoneally into the mice deficient (-/-) in fibrinolytic factors: alpha(2)-AP-/-, plasminogen (Plg) -/-, and Plg-/-.alpha(2)-AP-/-, and wild-type (WT) mice. The liver tissue was examined for its microscopic appearance, fibrinolytic activity, and fibronectin levels.. In the gene deficient and WT mice, the livers exhibited the same extent of necrosis 2 days after the CCl(4) injection. The livers of the WT mice normalized after 7 days, and the alpha(2)-AP-/- mice normalized after 5 days. In contrast, the livers of the Plg-/- and Plg-/-.alpha(2)-AP-/- mice remained in the damaged state until 14 days after the liver injury. The injection of anti-alpha(2)-AP antibody in the WT mice improved the regeneration after the liver injury, and the injection of tranexamic acid in the alpha(2)-AP-/- mice reduced.. These results suggest that the plasmin/alpha(2)-AP system played an important role in hepatic repair via clearance from the injury area.

Topics: alpha-2-Antiplasmin; Animals; Carbon Tetrachloride; Cell Division; Chemical and Drug Induced Liver Injury; Extracellular Matrix Proteins; Fibrin; Fibrinolysin; Fibrinolysis; Fibronectins; Injections; Liver; Liver Diseases; Liver Regeneration; Mice; Mice, Knockout; Necrosis; Neutralization Tests; Plasminogen Activator Inhibitor 2; Tranexamic Acid

Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation leading to the widespread deposition of fibrin in the circulation. Therefore, the determination of soluble fibrin is crucial for the diagnosis of DIC. Thrombus precursor protein (TpP) levels can be determined as a measure of soluble polymers, which are the immediate precursors of insoluble fibrin. In this study, the potential diagnostic usefulness of this TpP test was investigated in septic patients with DIC and liver diseases.. TpP analysis was performed on 155 plasma samples from 95 septic patients, including 72 patients without liver disease and 23 patients with liver diseases, and on 42 plasma samples from normal healthy subjects. The study population was subdivided according to three phases of DIC described as compensated, decompensated and full-blown DIC. Plasma TpP level was determined using a new assay, the TpPTM (American Biogenetic Sciences, USA), which is based on an ELISA method.. Septic patients with decompensated (16.1 9.1 mg/mL) or full- blown (20.9 12.4 mg/mL) phases of DIC had significantly higher TpP levels than those with the compensated (5.6 6.2 mg/mL) phase of DIC or healthy controls (2.9 1.6 mg/mL). In septic patients with liver disease, a significant difference was found between the TpP levels of patients with full- blown DIC (21.6 10.6 mg/mL) and those of patients with the decompensated phase (13.4 6.5 mg/mL). Plasma TpP levels correlated significantly with other DIC parameters including platelet count, fibrinogen, antithrombin and TAT, and correlated weakly with D-dimer.. Our findings indicate that septic patients who developed decompensated or full-blown DIC or organ dysfunction have significantly higher plasma levels of TpP, and suggest the potential usefulness of the TpP assay as an aid to the diagnosis of DIC in cases of sepsis and liver disease complicated by sepsis.

Topics: Adult; Aged; Antithrombins; Female; Fibrin; Fibrinogen; Humans; Liver Diseases; Male; Middle Aged; Platelet Count; Sepsis

Tissue repair requires an adequate cellular proliferation coordinated with the timely proteolysis of matrix elements. Based on the properties of plasminogen activators in liver cell proliferation and tissue proteolysis, we explored the regulatory role of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) in liver repair. Using carbon tetrachloride (CCl(4)) intoxication as a model of acute liver injury, we found that tPA-deficient mice displayed a mild defect in hepatic repair, whereas livers of uPA-deficient mice had a more substantial delay in repair, with injury of centrilobular hepatocytes persisting up to 14 days after CCl(4). Notably, functional cooperativity between plasminogen activators was strongly inferred from the profound reparative defect in livers of mice lacking tPA and uPA simultaneously, with persistence of centrilobular injury as far out as 35 days. The defective repair was not because of increased susceptibility of experimental mice to the toxin or to inadequate cellular proliferation. Instead, lack of plasminogen activators led to the accumulation of fibrin and fibronectin within injured areas and poor removal of necrotic cells. These data demonstrate that tPA and uPA play a critical role in hepatic repair via proteolysis of matrix elements and clearance of cellular debris from the field of injury.

Topics: Acute Disease; Animals; Carbon Tetrachloride; Cell Division; Extracellular Matrix Proteins; Fibrin; Gene Targeting; Liver; Liver Diseases; Liver Regeneration; Mice; Mice, Mutant Strains; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

To determine the regulatory role of plasminogen in hepatic repair following a chronic liver injury, we injected carbon tetrachloride (CCl(4)) biweekly into mice lacking plasminogen (Plg(0)) and plasminogen-sufficient littermates (Plg(+)). On gross examination, we found that Plg(0) livers became enlarged and pale with foci of red nodules as early as 4 weeks after CCl(4) injection, while Plg(+) livers appeared minimally affected by 6 weeks. Microscopically, Plg(0) livers had a pronounced pericentral linking, with accumulation of centrilobular eosinophilic material in injured areas, which resulted in a significant increase in liver mass and total protein. Immunohistochemistry revealed that fibrin accumulated progressively in injured regions. However, the combined genetic loss of plasminogen and fibrinogen did not correct the abnormal phenotype. Mason's trichrome staining revealed intense signal in centrilobular regions and electron microscopy showed a marked increase in fibrillary material demonstrating an excessive accumulation of extracellular matrix in Plg(0) mice. The zone-specific increase in matrix components was associated with an increase in the number of activated hepatic stellate cells within injured sites of Plg(0) livers. Taken together, these data suggest that the progressive accumulation of fibrin-unrelated matrix substrates in Plg(0) livers after a chronic injury results from the combined effects of impaired proteolysis and increased matrix production.

Topics: Afibrinogenemia; Animals; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Chronic Disease; Extracellular Matrix; Fibrin; Liver; Liver Diseases; Matrix Metalloproteinase 9; Mice; Mice, Knockout; Microscopy, Electron; Plasminogen; Time Factors

Plasminogen directs matrix proteolysis during liver repair. Based on the role of hepatic stellate cells (HSCs) on matrix production, we investigated whether plasminogen-driven matrix proteolysis modulates the phenotype of HSCs.. Carbon tetrachloride was injected intraperitoneally into mice deficient in plasminogen, fibrinogen, or both, and to normal littermates, followed by determination of the phenotype of HSCs, matrix deposition, and apoptosis.. Activation of HSCs was restricted to the zone of injury and increased >ten-fold above baseline regardless of the plasminogen status 2 days after toxin. Thereafter, the number of activated HSCs decreased to baseline levels between 7 and 14 days in normal mice, but remained elevated in plasminogen-deficient livers approximately ten-fold above non-targeted littermates. Despite the zonal increase in activated HSCs, the total number of desmin-stained HSCs was similar along the lobule in both genotypes. No appreciable difference in apoptosis of perisinusoidal cells was found between genotypes; however, fibrillary material was present in the subsinusoidal space of Plg(0) livers. This fibrillary material was not fibrin, as demonstrated by similar findings in Plg(0)/Fib(0) mice, which accumulated fibronectin in injured areas.. Proteolytic clearance of non-fibrin matrix components by plasminogen must occur for HSCs to restore the quiescent phenotype during liver repair.

Topics: Animals; Apoptosis; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Extracellular Matrix; Fibrin; Growth Substances; Liver; Liver Diseases; Mice; Mice, Knockout; Peptide Hydrolases; Phenotype; Plasminogen

The photometric method of Fickenscher et al. for the determination of factor XIII (FXIII) activity has been used in the study of 35 patients with severe chronic hepatopathy, in comparison with 25 normal subjects. The FXIII proteic fractions a and b were determined by quantitative immuno-electrophoresis after Laurell. The plasmatic FXIII activity, as well as the proteic fractions a and b, were significantly reduced in hepatopatic patients, in comparison to controls, and proportional to the prolongation of prothrombin times. Ratios between functional and immunological levels of FXIII in hepatopatics were similar to those observed in controls. These results confirm the involvement of fibrin stabilization deficiency in the coagulation defect of severe chronic hepatopathies. The correlations between functional and antigenic values are in agreement with the hepatic origin of FXIII. The method of Fickenscher has been proved to be rapid and simple, and it may be useful in the routine study of hepatopathies, for a better knowledge of the role of FXIII deficiency in the complex coagulopathy of liver diseases, as well as of other acquired FXIII deficiencies.

Topics: Adult; Aged; Chronic Disease; Evaluation Studies as Topic; Factor XIII; Factor XIII Deficiency; Female; Fibrin; Humans; Immunoelectrophoresis; Liver Diseases; Male; Middle Aged; Photometry; Prothrombin Time

During liver fibrosis, there is a putative pacemaker role of fibronectin. Fibrinogen is closely linked to fibronectin during clotting processes. The aim of this study was to show fibrinogen gene expression during liver damage.. Fibrinogen/fibrin deposition in damaged livers was studied by immunohistology. Fibrinogen gene expression was analyzed in vivo in a model of CCl4-induced rat liver damage and in vitro in isolated liver cells by means of Northern blot analysis and in situ hybridization.. Immunohistology showed striking amounts of fibrinogen and fibrin deposits in pericentral necrotic areas (short-term damage) and within fibrotic septa (long-term damage). Total RNA extracted from short-term-damaged livers contained an increased fibrinogen messenger RNA level. By in situ hybridization, fibrinogen transcripts were localized in cells of the nonnecrotic areas (short-term damage) and outside fibrotic septa (long-term damage). In vitro studies showed fibrinogen de novo synthesis restricted to hepatocytes.. The results show fibrinogen/fibrin deposition during short-term liver injury and liver fibrogenesis, which may suggest the involvement of a "clotting-like process" in short-term liver damage and liver fibrosis. The data might indicate that fibrin/fibronectin constitute a "provisional matrix," which affects the attraction and proliferation of inflammatory and matrix-producing cells.

Topics: Animals; Blotting, Northern; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Female; Fibrin; Fibrinogen; Gene Expression; Immunohistochemistry; In Situ Hybridization; Liver; Liver Cirrhosis, Experimental; Liver Diseases; Necrosis; Rats; Rats, Wistar; RNA, Messenger

Endothelial cell damage causes massive hepatic necrosis as a result of fibrin deposition in the hepatic sinusoids. When a stable analog of prostaglandin I2, beraprost sodium, was administered to rats given either dimethylnitrosamine, carbon tetrachloride, or endotoxin following Corynebacterium parvum administration, the hepatic necrosis produced in each was attenuated, but to a greater extent in the dimethylnitrosamine and endotoxin/Corynebacterium parvum models, where fibrin deposition in the hepatic sinusoids occurs, as compared to the carbon tetrachloride model, where such fibrin deposition does not occur. Beraprost sodium reduced the expected increase of portal venous pressure in the endotoxin/Corynebacterium parvum model without affecting plasma thrombin-antithrombin III complex levels. Beraprost sodium also significantly reduced cell killing of both isolated rat hepatocytes and hepatic sinusoidal endothelial cells exposed to tert-butyl hydroperoxide when compared to controls. Beraprost sodium could prove to be a therapeutic candidate for the treatment of hepatic necrosis, particularly in cases associated with fibrin deposition in the hepatic sinusoids because of its fibrin clot-clearing action.

Topics: Animals; Antithrombin III; Capillaries; Carbon Tetrachloride; Cells, Cultured; Dimethylnitrosamine; Endothelium, Vascular; Endotoxins; Epoprostenol; Fibrin; Liver; Liver Diseases; Male; Necrosis; Peptide Hydrolases; Portal Pressure; Propionibacterium acnes; Prothrombin Time; Rats; Rats, Inbred F344

Hepatic fibrin-ring granulomas were found in a 70-year-old man with prolonged fever and inflammatory syndrome. Diagnosis of giant cell arteritis was confirmed by temporal artery biopsy. Other diseases usually associated with fibrin-ring granulomas in liver, such as Q fever, cytomegalovirus hepatitis, infectious mononucleosis, Hodgkin's disease, non-Hodgkin's lymphoma, allopurinol treatment, and visceral leishmaniasis, were ruled out. This report suggests that giant cell arteritis should be considered as an additional cause of hepatic fibrin-ring granulomas.

Topics: Aged; Fibrin; Giant Cell Arteritis; Granuloma; Humans; Liver; Liver Diseases; Male

Patients with liver disease have a variety of coagulation abnormalities. These derangements are of uncertain origin and do not always correlate with disease severity or activity. We have measured the levels and proportions of the total fibrin-related and fibrinogen-related antigens, the principal fibrin (D-dimer) and fibrinogen (D-monomer) degradation fragments and intermediates of fibrin formation (fibrin monomers) in patients with a variety of acute and chronic liver diseases in whom all known other precipitating causes of disseminated intravascular coagulation had been excluded. Fibrin-related and fibrinogen-related antigens were extracted from serum using antihuman fibrinogen-IgG covalently bound to activated amino-phenylthioether paper disks and were subjected to 4% to 11% sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. Fibrin-related and fibrinogen-related antigen proportions were determined by densitometry, and their levels were measured by radioimmunoassay. Levels of total fibrin-related and fibrinogen-related antigens (and D-dimer) were significantly elevated (p less than 0.01) in patients with cirrhosis (121 to 641 ng/ml) and hepatocellular carcinoma (416 to 8,786 ng/ml) when compared with patients with acute viral hepatitis (84 to 322 ng/ml) and control subjects (38 to 186 ng/ml). In addition, D-monomer levels were elevated. These findings strongly suggest that disseminated intravascular coagulation is a component of the coagulopathy of certain liver diseases. Because fibrin-related and fibrinogen-related antigens have anticoagulant, vasoactive and immunosuppressive properties, their elevated presence may be biologically significant in these patients.

Topics: Adult; Antigens; Carcinoma, Hepatocellular; Electrophoresis, Polyacrylamide Gel; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Liver Diseases; Liver Neoplasms; Male; Peptide Fragments

Fibrin ring granuloma is characterized by a fibrinous ring surrounding a central fat vacuole. It has been found in the liver and bone marrow of patients with Q fever, and occasionally with visceral leishmaniasis, cytomegalovirus, Epstein-Barr virus, Staphylococcus epidermidis infections, Hodgkin's lymphoma, and hypersensitivity to allopurinol. We describe a case of serologically confirmed viral hepatitis A with this lesion in the liver biopsy. A false positive anti-hepatitis A virus IgM result has been excluded. This is, to our knowledge, the second reported case of type A hepatitis with hepatic fibrin ring granulomas. It confirms that hepatitis A should be included in the differential diagnosis of this lesion.

Topics: Acute Disease; Female; Fibrin; Granuloma; Hepatitis A; Humans; Liver; Liver Diseases; Middle Aged; Q Fever

Hepatic fibrin-ring granulomas were found in a 30-year-old patient with serologically confirmed hepatitis A. Other causes associated with the presence of fibrin-ring granulomas in the liver, such as Hodgkin's and non-Hodgkin's lymphoma, cytomegalovirus infection, visceral leishmaniasis, and consumption of allopurinol, were ruled out. It is suggested that hepatitis A must be included in the differential diagnosis of a patient with hepatic fibrin-ring granulomas.

Topics: Adult; Fibrin; Granuloma; Hepatitis A; Humans; Liver Diseases; Male

Ten Pericarbon valve bioprostheses were examined after being implanted in tricuspid position in two different groups of animals: group I sheep with increased immunoglobulins, plasma levels, and eosinophilis count of more than 10%, due to parasitic infection, and group II sheep without any parasitic infection, i.e. with normal blood data. The explanted valve follow up was between 60-95 hours in both groups. Microscopic observation of group I valves revealed a massive blood cell (lymphocytes, eosinophilis and large mononuclear cells) infiltration especially around the natural pericardial blood vessels in the region of flexion and attachment. The epipericardial surface was covered by fibrin sheath, and immunofluorescence studies showed a strongly positive reaction for immunoglobulins (IgG and IgE) on leaflet surfaces and lamellar stratification into the fibrosa. Microcalcifications were detected around pericardial blood vessels in the same zones where infiltrated blood cells were found. In group II valves cell infiltration was absent with no signs of calcification and immunofluorescence was negative. Our data suggest that immunoglobulins adherence followed by blood cell infiltration may be one of the early causes of tissue leaflet degeneration and there is a parallel trend between plasma immunoglobulin levels and the early tissue alteration. Our data show that the experimental model for testing bioprostheses in sheep is influenced by the pre-immunological status and it is important to control it before surgery.

Topics: Animals; Bioprosthesis; Cell Movement; Fibrin; Fluorescent Antibody Technique; Heart Valve Prosthesis; Immunity; Immunoglobulins; Liver Diseases; Lung Diseases; Lymphocytes; Parasitic Diseases; Prosthesis Failure; Reference Values; Sheep

Rats received a dose of dimethylnitrosamine (DMN) or carbon tetrachloride (CCl4). In the liver of rats given DMN, apoptosis of fat-storing cells occurred at 7.5 h, and sinusoidal endothelial cell degeneration followed, with parenchymal cell necrosis after 9 h. Fibrin thrombi appeared in the sinusoids as well as in these necrotic areas after 12 h. In contrast, in the liver of rats given CCl4, parenchymal cell degeneration was seen after 6 h and necrosis with fibrin thrombi developed after 9 h. Fat-storing cells and endothelial cells were almost intact, and fibrin thrombi were not present in the sinusoids. SGPT values increased with decreased plasma levels of fibrinogen and antithrombin III and prolonged prothrombin time after 3 and 6 h, in the CCl4 and DMN models, respectively. An extensive reduction in plasma factor VIIIC levels and peripheral platelets was seen after 18 and 24 h, respectively, only in the DMN model. These results suggest that endothelial cells destruction can cause fibrin formation in the hepatic sinusoids in acute liver injury. Fat-storing cell injury may contribute to the destruction.

Topics: Animals; Carbon Tetrachloride; Cell Survival; Chemical and Drug Induced Liver Injury; Dimethylnitrosamine; Disseminated Intravascular Coagulation; Endothelium, Vascular; Fibrin; Liver; Liver Diseases; Male; Microscopy, Electron; Rats

Topics: Adult; Female; Fibrin; Granuloma; Humans; Liver Diseases; Staphylococcal Infections; Staphylococcus epidermidis

This study reviews liver disease in toxemia of pregnancy based on 102 cases submitted to the Armed Forces Institute of Pathology. The common clinical features were right upper quadrant and epigastric pain, nausea, vomiting, and elevation of the serum transaminases. Jaundice occasionally developed. These occurred in severe preeclampsia or eclampsia and their cause was usually recognized. However, hepatic symptoms and signs did result in inappropriate diagnoses and misdirected therapy. Such confusion occurred when these were the initial problems confronting the clinician in women presenting with advanced toxemia due to poor prenatal care. They were also likely to be misleading when other more classic parameters, such as blood pressure and proteinuria, were only midly abnormal. Central nervous system complications were the common cause of death but liver disease could be partially or wholly responsible. Extensive periportal lesions, hepatic hematomas, spontaneous rupture, and infarction all contributed to hepatic injury and to morbidity. Fibrin deposition, hemorrhage, or both in the periportal areas was characteristic of the histopathology. Scanning electron microscopy validated this spectrum of change. A toxemic vasculopathy related to severe vasospasm in the hepatic arterial circulation may be responsible.

Topics: Eclampsia; Female; Fibrin; Hemorrhage; Humans; Infarction; Liver; Liver Diseases; Necrosis; Pre-Eclampsia; Pregnancy

A method for photometric determination of prothrombin time (PT) with a chromogenic peptide as substrate is described. The reagent contains human placental thromboplastin, a chromogenic substrate, calcium, a heparin antagonist and buffer. The new prothrombin time method has been calibrated against international reference preparations for thromboplastin. The reagent is sensitive to deficiency of all coagulation factors of the extrinsic pathway. However, it is not sensitive for heparin up to 1 IU/ml. The precision of this fast and simple method is comparable to that of mechanised assays for clinical chemistry.

Topics: Blood Coagulation; Fibrin; Heparin; Humans; Indicators and Reagents; Liver Diseases; Photometry; Prothrombin Time; Reference Values; Thromboplastin

Hepatic fibrin-ring granulomas were found in a 35-yr-old man who developed fever, myalgias, rash, eosinophilia, and abnormal liver function tests 4 wk after the beginning of allopurinol treatment. All clinical and biochemical abnormalities spontaneously resolved within 6 wk after cessation of therapy. There was no evidence for Q fever or Hodgkin's disease, which are the recognized causes of hepatic fibrin-ring granulomas. It is suggested that allopurinol hypersensitivity might be an additional cause of these peculiar granulomas.

Topics: Adult; Allopurinol; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Fibrin; Granuloma; Humans; Liver; Liver Diseases; Male

Soluble crosslinked fibrin derivatives (XDP) in serum were determined by enzyme immunoassay utilizing monoclonal antibodies and compared with serum fibrinogen/fibrin degradation products (FDP) assayed by conventional techniques. In healthy subjects and patients with miscellaneous disorders not usually associated with activation of the haemostasis mechanism, mean XDP levels were 45 and 70 ng/ml respectively. However, elevated levels of XDP occurred in conditions commonly associated with intravascular and possibly extravascular activation of the coagulation system. Markedly raised mean XDP values (677-6900 ng/ml) occurred in treated pulmonary embolism, disseminated neoplasia, severe inflammatory disorders and complicated postoperative states, and lesser but significant elevation (mean 150-400 ng/ml) in treated venous thrombosis, uneventful postsurgical states, localized neoplasia, liver disease and symptomatic arterial disease. Levels during initial streptokinase therapy (mean 24 000 ng/ml) fell tenfold as treatment was continued. The degree of XDP elevation over normal values was significantly higher than that of FDP in conditions with a propensity for venous thrombosis (post-operative states, disseminated neoplasia and inflammatory diseases) than in liver disease, localized neoplasia or patients receiving heparin therapy for venous thromboembolism.

Topics: Adult; Aged; Antibodies, Monoclonal; Blood Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Immunoenzyme Techniques; Inflammation; Liver Diseases; Middle Aged; Neoplasms; Streptokinase; Thromboembolism; Vascular Diseases

Topics: Biopolymers; Blood Coagulation Tests; Fibrin; HEPES; Humans; Liver Diseases; Piperazines; Thrombin Time

Topics: Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibronectins; Humans; Immunoelectrophoresis, Two-Dimensional; Liver Diseases

Topics: Afibrinogenemia; Carbohydrates; Fibrin; Fibrinogen; Humans; Liver Diseases; Sialic Acids; Thrombin Time

Topics: Adolescent; Adult; Blood Coagulation Tests; Child; Chronic Disease; Esophageal and Gastric Varices; Female; Fibrin; Humans; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Polymers; Portacaval Shunt, Surgical; Prognosis

A 13-year-old girl with chronic aggressive hepatitis, postnecrotic cirrhosis, ulcerative colitis, and a coagulation defect acquired an antibody that specifically interfered with fibrin formation. We sought to characterize the antibody and determine the mechanism of its inhibitory activity. The patient's purified fibrinogen was functionally normal; however, the antibody inhibited the self-assembly of fibrin and prolonged the clotting times of the patient's plasma. This antibody, which belonged to the IgG class of immunoglobulins, acted early in the polymerization process to inhibit the association of fibrin monomers, as indicated by a prolonged lag time and a decreased slope in the polymerization curves. It did not inhibit fibrinopeptide cleavage or fibrin cross-linking. Affinity chromatography indicated that the antibody bound strongly to both fibrinogen and fibrin monomer.

Topics: Adolescent; Autoantibodies; Blood Coagulation Disorders; Blood Coagulation Tests; Colitis, Ulcerative; Female; Fibrin; Fibrinogen; Humans; Immunoglobulin G; Liver Diseases; Polymers

Twenty patients with the ascites of chronic liver disease were investigated for in vivo evidence of active coagulation within ascites by detection of fibrin monomer. Increased levels of fibrin monomer, increased fibrin/fibrinogen degradation products, and absent or low levels of fibrinogen in the ascites of all patients tested confirmed the presence of intraperitoneal coagulation when ascites is present.

Topics: Ascites; Ascitic Fluid; Blood Coagulation; Blood Proteins; Chronic Disease; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Liver Diseases; Peritoneal Cavity

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Transfusion; Calcium; Disseminated Intravascular Coagulation; Factor XIII; Factor XIII Deficiency; Female; Fibrin; Fibrinogen; Half-Life; Hemorrhage; Humans; Leukemia; Liver Diseases; Male; Plasma; Pregnancy; Thrombin; Time Factors

Souble fibrin monomer complexes (SFMC) have been quantitated in 18 patients with liver cirrhosis by means of plasma gel filtration on an agarose column. The concentration of SFMC (as related to total fibrinogen) was increased in cirrhotic patients. The difference between controls and patients, as well as the difference between compensated and decompensated cirrhotic subjects, was statisically significant. Although these data, together with the results of heparin administration in one reported case, suggest intravascular coagulation, some alternative explanations should also be considered.

Topics: Bacteriological Techniques; Blood Coagulation; Blood Coagulation Tests; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Heparin; Humans; Injections, Subcutaneous; Liver Cirrhosis; Liver Diseases; Solubility; Staphylococcus

Topics: Batroxobin; Fibrin; Fibrinolysis; Humans; Liver Diseases; Liver Neoplasms; Polymers; Thrombin

184 autopsy cases with liver diseases were examined clinicopathologically with special reference to the incidence and distribution of microthrombi and classic thrombi in various organs. Microthrombi and/or classic thrombi were found in one or more organs in 50.0% to 59.4% of the patients with various liver diseases. But only 4 among 184 patients had many microthrombi in more than three organs and the incidence of disseminated intravascular coagulation seemed to be low in autopsy cases with liver diseases. Incidence of microthrombi showed no significant difference in the groups with and without portal vein thrombosis. Hemorrhage in the upper alimentary tracts of the patients with liver cirrhosis did not seem to develop by disseminated intravascular coagulation. Consumption of clotting factors in liver diseases seemed to occur by thrombus formation in portal vein and esophageal varices and by hemorrhage in various organs.

Topics: Autopsy; Blood Platelets; Disseminated Intravascular Coagulation; Fibrin; Fibrinolysis; Hemorrhage; Humans; Kidney; Liver Diseases; Lung; Spleen

The frequent occurrence of abnormal fibrin polymerisation in patients with liver disease has recently been reported. To investigate this further, fibrin polymerisation was studied in 68 patients with cirrhosis or chronic active liver disease. Thirty-three of these patients demonstrated impairment of this phase of blood coagulation. When other tests of liver function were compared in patients demonstrating this abnormality and those in whom fibrin polymerisation was normal, it was found that the former group demonstrated significantly reduced albumin concentrations (p less than 0.0002), raised bilirubin and aspartate aminotransferase levels (p less than 0.0006 and less than 0.003 respectively), and greater prolongation of the one-stage prothrombin time (p less than 0.001) with more marked reduction in factor VII levels (p less than 0.002) compared with the latter patients. It is concluded that defective fibrin polymerisation occurring in patients with liver disease indicates the presence of severely impaired hepatocellular function. This might account for the grave prognosis reported in cirrhotic patients with abnormal fibrin polymerisation who also suffer bleeding from gastro-oesophageal varices.

Topics: Aspartate Aminotransferases; Bilirubin; Blood Coagulation Disorders; Chronic Disease; Factor VII; Fibrin; Fibrinogen; Humans; Liver Cirrhosis; Liver Diseases; Prothrombin Time; Serum Albumin; Serum Globulins

Plasma from patients with both acute and chronic liver disease has been examined for evidence of acquired dysfibrinogenaemia, using electrophoretic methods and coagulation tests. An examination of isolated fibrins upon SDS polyacryamide gel electrophoresis failed to demonstrate any molecular or structural defect associated with the polypeptide chains of the patients' fibrinogen or fibrinogen derivatives produced by thrombin or plasmin. However, purified fibrin monomers isolated from plasma using both Reptilase and thrombin exhibited delayed polymerization rates and the occurrence of acquired dysfibrinogenaemia in liver disease is therefore confirmed.

Topics: Acute Disease; Ancrod; Batroxobin; Blood Coagulation Disorders; Blood Coagulation Tests; Chronic Disease; Fibrin; Fibrinogen; Humans; Liver Diseases; Thrombin

To test the possibility that a functionally abnormal fibrinogen may exist in some patients with liver disease, we studied the plasma and purified fibrinogens of five patients whose plasma thrombin times were prolonged at least 40% over normal controls. In no patient was there evidence of disseminated intravascular coagulation and/or fibrinolysis. No abnormalities were detected by immunoelectrophoresis of plasmas or purified fibrinogens. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reduced patient fibrinogens showed normal mobility and amount of Aalpha, Bbeta, and gamma chains. Alkaline polyacrylamide gel electrophoresis and gradient elution, DEAE-cellulose chromatography of admixtures of radio-iodinated patient (125)I-fibrinogen and normal (131)I-fibrinogen showed identical mobility in the gel and simultaneous elution from the column, respectively. Thrombin and Reptilase (Abbott Scientific Products Div., Abbott Laboratories, South Pasadena, Calif.) times of purified patient fibrinogens were prolonged, and calcium ions improved but did not completely correct these defects. Increasing amounts of thrombin progressively shortened the clotting times of patient fibrinogens but not to the level of normal. Addition of equal amounts of patient fibrinogen to normal fibrinogen resulted in a prolongation of the thrombin time of the normal protein. Thrombin-induced fibrinopeptide release was normal. Fibrin monomers prepared from patient plasmas and purified fibrinogens demonstrated impaired aggregation at low (0.12) and high (0.24) ionic strength. These studies demonstrate that some patients with liver disease and prolonged plasma thrombin times have a dysfibrinogenemia functionally characterized by an abnormality of fibrin monomer polymerization.

Topics: Alcoholism; Batroxobin; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Chemical and Drug Induced Liver Injury; Fibrin; Fibrinogen; Humans; Liver Cirrhosis; Liver Diseases; Prothrombin Time; Thrombin

Liver biopsies of sixty patients with different forms of hepatitis and ten control subjects without hepatic disorders were examined by means of direct immunofluorescent methods for the HBsAg, immunoglobulins, fibrin and C3. The presence of fluorescent particles of HBsAg in the cytoplasm of hepatocytes were correlated with the presence of HBsAg in the serum. The fluorescence did not seem specific of histological stage of hepatitis. Immunoglobulins and fibrin were often demonstrated in hepatic sinusoids, especially in chronic aggressive hepatitis. In contrast, C3 is rarely observed.

Topics: Biopsy; Complement C3; Complement System Proteins; Cytoplasm; Epitopes; Fatty Liver; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Hepatitis; Hepatitis B Antigens; Humans; Immunoglobulins; Liver; Liver Cirrhosis; Liver Diseases; Renal Dialysis

Although there have been isolated reports of an acquired abnormal fibrinogen in patients with liver disease, its frequency and clinical significance is not known. In this study 121 consecutive patients with a wide spectrum of hepatic disorders were screened for abnormal fibrin polymerization. A simple colorimetric method using Reptilase was employed. Of 32 patients with proven cirrhosis, 16 (50%) showed abnormal fibrin polymerization. The incidence in decompensated alcoholic cirrhosis was particularly high. The abnormality was also detected in all patients with acute liver failure and seven of 15 with chronic active liver disease. Clinical improvement often correlated with its disappearance. Two patients with primary liver cell tumours demonstrated the abnormal polymerization. In patients with bleeding oesophageal varices the detection of abnormal fibrin polymerization was associated with a poor prognosis. None of the patients with surgical obstructive jaundice (26) or miscellaneous liver disorders (37) had abnormal fibrin polymerization. The occurrence of abnormal fibrin polymerization in liver disease is more frequent than previously suspected and usually signifies severe primary hepatocellular dysfunction. Evidence is presented to support the presence of a primary abnormality of fibrinogen as the cause of impaired fibrin monomer polymerization.

Topics: Batroxobin; Blood Coagulation Tests; Carcinoma, Hepatocellular; Cholestasis; Chronic Disease; Fibrin; Fibrinogen; Hepatic Encephalopathy; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Polymers; Thrombin; Time Factors

The effects of intravenously administered endotoxin on the hepatic and systemic circulation as well as on the coagulation system were evaluated in normal rats (n = 26), in rats with experimental portal hypertension (n = 15), and in rats with portacaval anastomosis (n = 22). Endotoxin (1-5 mg/kg) in the normal rat leads to a prompt increase of transaminase activity and to a hyperdynamic circulation with a consequent increase in the total hepatic blood flow. In a later phase (6 h postoperatively) the hepatic artery dilated with a consequent hepatic arterial hyperperfusion. The coagulation system was affected with signs of consumption coagulopathy. In the rats with portal hypertension and portacaval collaterals as well as in those with portacaval anastomosis, the endotoxin injection resulted in acute liver necrosis within 12 to 15 hours. The hepatic artery became overdilated with a cardiac output fraction of 25% (normal 5-5%). Blood extravasates and thrombi, rich in fibrin, were detected in the liver. It is suggested that this exaggeration of the endotoxin effect was due to an impaired clearance function of the reticuloendothelial system, probably as consequence of portacaval collateral circulation. It is concluded that endotoxins (1) damage the liver even in a normal organism; (2) are potent to induce acute liver necrosis, if the reticuloendothelial system is altered; (3) have to be taken into consideration as contribution to the pathogenesis of acute as well as chronic liver diseases.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Bilirubin; Blood Coagulation Factors; Blood Glucose; Blood Volume; Cardiac Output; Collateral Circulation; Endotoxins; Erythrocyte Aggregation; Fibrin; Fibrinogen; Hypertension, Portal; Liver; Liver Circulation; Liver Diseases; Necrosis; Phagocytosis; Portacaval Shunt, Surgical; Rats; Regional Blood Flow; Time Factors

The intravenous injection of mice with toxic doses of vaccinia virus, prepared in the Ehrlich ascites carcinoma, usually produces fatal intravascular coagulation, within 24 hours. Light and electron microscope studies demonstrate occlusion of the microcirculation of lungs and livers by fibrin. Fibrin deposition appears to be prevented in mice injected with heparinized virus preparations. However, in lieu of fibrin deposition, within the microcirculation widespread intravascular platelet aggregation occurs. Platelets within these aggregates are in various stages of degranulation, and some platelets have phagocytosed vaccinia virus. Platelet aggregation was not observed in mice receiving injections of heparinized material prepared from uninfected tumors. In mice surviving longer than 12 hours, hepatocytes and endothelial cells of pulmonary capillaries are the sites of viral replication. Although many hepatocytes are infected in mice surviving longer than 12 hours, it is postulated that hepatocyte necrosis is in part due to the congestive effects resulting from obstruction of liver and pulmonary capillaries. These studies suggest that vaccinia virus may trigger in vivo platelet aggregation, and that obstruction of the lung and liver microcirculation by these aggregates is the initial lesion of vaccinia virus toxicity.

Topics: Animals; Blood Platelets; Capillaries; Erythrocyte Aggregation; Fibrin; Heparin; Kupffer Cells; Liver; Liver Diseases; Lung; Mice; Microcirculation; Phagocytosis; Platelet Aggregation; Pulmonary Embolism; Thrombosis; Vaccinia virus; Virus Replication

Topics: Fibrin; Fibrinogen; Hemorrhage; Humans; Liver Cirrhosis; Liver Diseases

Topics: Aged; Arthritis, Rheumatoid; Blood Cell Count; Blood Platelets; Carbon Radioisotopes; Collagen Diseases; Factor XIII; Female; Fibrin; Fibrinolysis; Heart Failure; Humans; Hypertension, Malignant; Infections; Leukemia; Liver Diseases; Neoplasms; Pulmonary Embolism; Sepsis; Streptokinase

Topics: Diabetes Mellitus; Evaluation Studies as Topic; Female; Fibrin; Fibrinogen; Glycosuria; Humans; Immunoelectrophoresis; Latex Fixation Tests; Liver Diseases; Methods; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Urinary Tract Infections

Twenty-two patients with acute hepatic failure were studied to determine the incidence and magnitude of intravascular coagulation and fibrinolysis and their relation to the severity of bleeding and prognosis. The mean platelet count, Thrombotest, plasminogen activator, and plasminogen were reduced; the reduction in fibrinogen was not statistically significant. Fibrin/fibrinogen degradation products were only moderately increased. Hepatic fibrin deposition was not extensive, being present in 11 of 22 hepatic sections, more in areas of confluent necrosis than in the sinusoids. The combination of increased fibrin/fibrinogen degradation products with decreased plasminogen activator, plasminogen, and thrombocytopenia is consistent with a diagnosis of intravascular coagulation and secondary local fibrinolysis. However, neither of these processes was severe. Severity of bleeding was related only to plasminogen levels and prognosis only to Thrombotest levels. There was no relation between hepatic histological and haematological findings. Heparin therapy is not indicated in the routine management of acute hepatic failure, as intravascular coagulation is not severe and heparin may itself cause massive bleeding.

Topics: Acute Disease; Adolescent; Adult; Aged; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Child; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemoglobins; Humans; Liver; Liver Diseases; Male; Middle Aged; Plasminogen; Prognosis

Topics: Acute Disease; Blood Cell Count; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemoglobins; Heparin; Humans; Liver Diseases; Male; Methods

Topics: Acute Disease; Disseminated Intravascular Coagulation; Fibrin; Hemorrhagic Disorders; Humans; Liver Diseases; Prothrombin Time

Topics: Biliary Tract Diseases; Blood Protein Electrophoresis; Complement System Proteins; False Negative Reactions; False Positive Reactions; Fibrin; Hepatitis B Antigens; Humans; Immunoglobulin M; Latex Fixation Tests; Liver Diseases; Quality Control; Radioimmunoassay; Respiratory Tract Diseases; Rheumatoid Factor

Topics: Acetaminophen; Adult; Bilirubin; Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Chemical and Drug Induced Liver Injury; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemostasis; Hepatic Encephalopathy; Humans; Iodine Radioisotopes; Liver Diseases; Liver Function Tests; Male; Middle Aged; Plasminogen; Prothrombin Time

Topics: Animals; Cell Transformation, Neoplastic; Collagen; Connective Tissue; Cysts; Dose-Response Relationship, Drug; Fibrin; Hepatic Veins; Injections, Subcutaneous; Kupffer Cells; Liver; Liver Diseases; Liver Neoplasms; Lymphatic System; Lymphoma, Large B-Cell, Diffuse; Male; Microscopy, Electron; Mitosis; Monocytes; Rats; Rats, Inbred Strains; Sarcoma, Experimental; Trypan Blue

Topics: Animals; Blood Coagulation Tests; Ethanol; Evaluation Studies as Topic; Female; Fibrin; Fibrinogen; Hematologic Diseases; Humans; Kidney Diseases; Liver Diseases; Male; Neoplasms; Peptide Hydrolases; Postoperative Complications; Postpartum Period; Pregnancy; Protamines; Snakes; Thrombin; Venoms

Topics: Adolescent; Adult; Angina Pectoris; Chronic Disease; Diabetes Mellitus; Female; Fibrin; Fibrinogen; Hematologic Diseases; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; Myocardial Infarction; Neoplasms

Topics: Acute Disease; Adolescent; Adult; Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Child, Preschool; Exchange Transfusion, Whole Blood; Factor V Deficiency; Factor VII Deficiency; Female; Fibrin; Fibrinolysis; Hemorrhage; Hemostasis; Hepatitis A; Humans; Hypoprothrombinemias; Liver Diseases; Liver Function Tests; Male; Middle Aged; Plasminogen; Prothrombin Time

A rapid slide test for the detection of degradation products of fibrinogen/fibrin (FDP) using a new antibody-coated latex particle is described. The latex particle has been specifically coated with antibody to fragments D and E. The latex agglutination test (Thrombo-Wellcotest) has been compared with the tanned red cell haemagglutination inhibition immunoassay (TRCHII) in 143 patients with a variety of clinical conditions. There is a high degree of agreement between the methods with a coefficient of correlation of 0.83. The method provides a rapid, simple screening test for fibrin degradation products.

Topics: Antibodies; Fibrin; Fibrinogen; Hemagglutination Inhibition Tests; Humans; Hyperthyroidism; Kidney Diseases; Latex; Liver Diseases; Methods; Microspheres; Neoplasms; Pulmonary Embolism

Topics: Animals; Cyclohexanecarboxylic Acids; Cysteine; Embryo, Mammalian; Factor XIII; Female; Fibrin; Fibrinolysin; Fibrinolysis; Humans; Infant, Newborn; Liver Diseases; Pregnancy; Rabbits

Topics: Blood Coagulation Factors; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Humans; Liver Diseases; Platelet Adhesiveness

A single dose of endotoxin given to rats with obstructive jaundice produced death with intravascular coagulation. This action was apparently due to delayed clearance of endotoxin from the circulation. The finding is relevant to "hepatorenal failure," which can be caused by bacteraemia after biliary tract operations.

Topics: Acute Kidney Injury; Animals; Blood Coagulation Tests; Blood Platelets; Cholestasis; Endotoxins; Escherichia coli; Fibrin; Fibrinogen; Kidney Diseases; Liver Diseases; Prothrombin Time; Rats; Thrombelastography; Thrombin

Topics: Aminocaproates; Aprotinin; Cellulose; Chromatography; Chromatography, Gel; Fibrin; Fibrinogen; Hematologic Diseases; Humans; Immunoelectrophoresis; Liver Diseases; Macroglobulins; Neoplasms; Plasminogen; Streptokinase; Thrombin; Thrombosis

Topics: Adrenal Gland Diseases; Adult; Afibrinogenemia; Arteries; Cerebral Hemorrhage; Female; Fetal Death; Fetal Diseases; Fibrin; Humans; Infant, Newborn; Liver Diseases; Portal Vein; Pregnancy; Splenic Diseases; Thromboembolism; Umbilical Arteries; Umbilical Cord

Topics: Blood Coagulation Factors; Factor XIII; Fibrin; Humans; Liver Diseases

Topics: Alpha-Globulins; Anemia; Biological Assay; Biomedical Research; Blood Coagulation; Blood Coagulation Factors; Calcium; Collagen Diseases; Cysteine; Factor XIII; Fibrin; Hemorrhagic Disorders; Humans; Leukemia; Liver; Liver Diseases; Lymphoma; Neoplasms; Pathology; Serum Globulins; Sulfhydryl Compounds; Thrombin

Topics: Fibrin; Hot Temperature; Humans; Liver Diseases; Vascular Diseases

Topics: Diet; Fibrin; Hot Temperature; Humans; Liver Diseases; Liver Function Tests

Topics: Bone Plates; Fibrin; Fibrinolysis; Humans; Liver Diseases; Vascular Diseases

Topics: Fibrin; Fibrinolysis; Humans; Liver Diseases

Topics: Biliary Tract; Biliary Tract Diseases; Diagnosis, Differential; Fibrin; Humans; Liver Diseases

Topics: Fibrin; Fibrinolysis; Hemorrhagic Disorders; Hepatophyta; Liver Diseases