Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-five patients with different stages of liver cirrhosis were evaluated with regard to the degree of liver synthesis reduction, the extent of the decrease of blood coagulation factors and/or alterations of the fibrinolytic system. For the assessment of the residual level of liver synthesis we used pseudo-cholinesterase and serum albumin as references. We did not find a correlation between these quantities and antithrombin III or fibrinogen, but highly significant inverse correlations with tissue plasminogen activator activity and D-dimer concentration. We found considerable alterations in the concentrations of the coagulation and fibrinolysis factors, with the exception of fibrinogen and plasminogen activator inhibitor. Significant increases were seen for thrombin-antithrombin III complex, tissue plasminogen activator activity and D-dimer, while significant decreases were seen for antithrombin III and alpha 2-antiplasmin, compared with a group of healthy volunteers. In the group of patients with liver cirrhosis and reduced liver synthesis, as documented by lowered pseudo-cholinesterase and serum albumin, the reduction of both antithrombin III and alpha 2-antiplasmin was most prominent. Intravascular coagulation was negligibly small. For the fibrinolytic system, the increase of tissue plasminogen activator, the decrease of the fibrinolysis inhibitor (alpha 2-antiplasmin) and the elevated D-dimer concentration seem to be important. These results suggest an acceleration of fibrinolysis and the prolonged presence of cross-linked fibrin degradation products.
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PMID:The extent of diffuse intravascular coagulation and fibrinolysis in patients with liver cirrhosis. 162 24

Previous studies have demonstrated that plasma tissue plasminogen activator (t-PA) level was elevated in patients with liver disease. In this study, t-PA antigen levels were investigated in patients with acute hepatitis (AH; N = 12), chronic hepatitis (CH; N = 8), compensated liver cirrhosis (CLC; N = 40), decompensated liver cirrhosis (DLC; N = 23) and hepatocellular carcinoma (HCC; N = 35). The increased t-PA levels (higher than 14 ng/ml) were found in 33% (4/12) of AH on the early hospital days, 25% (2/8) of CH, 45% (18/40) of CLC and 91% (21/23) of DLC, and 60% (21/35) of Hcc cases. In patient with LC, the correlations between t-PA levels and serum total bilirubin (T.Bill) and hepatic synthetic functions were investigated. The results were that the t-PA levels correlated positively with T. Bil and negatively with liver synthetic functions such as albumin, protein C and choline-esterase, indicating that t-PA increased almost in proportion to the deterioration of hepatic function. Serial determination of t-PA in patients with HCC treated by transcatheter arterial embolization (TAE) revealed that TAE failed to normalize the t-PA levels. In one case of HCC complicated with disseminated intravascular coagulation (DIC), t-PA showed a marked increase at acute phase of DIC and subsequent decrease after the successful treatment for DIC by gabexate mesilate (FOY) infusion. These results suggest that increased t-PA in liver disease is due mainly to deterioration of hepatic function, and that secondary fibrinolytic state, such as DIC, is also a contributing factor.
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PMID:[Evaluation of plasma tissue plasminogen activator (I-PA) levels in patients with liver diseases]. 210 6

Plasma levels of alpha 2 plasmin inhibitor (alpha 2 PI) were measured by both an immunological and a functional assay, and a good correlation (r = 0.793; p less than 0.001) was found between the two methods. When compared to values recorded in 17 control subjects (69.55 micrograms/ml +/- 2.04) alpha 2 PI antigen levels were found to be obviously decreased in the 10 patients with decompensated cirrhosis of the liver (41.06 micrograms/ml +/- 4.66) and slightly increased in the 13 nephrotic patients (79.73 micrograms/ml +/- 2.35) and in the 23 hypertriglyceridemic and obese patients (78.59 micrograms/ml +/- 2.23). In spite of similar plasma levels of alpha 2 PI, dilute blood clot lysis was rather accelerated in patients with the nephrotic syndrome (240 min +/- 12) and obviously delayed in patients with endogenous hypertriglyceridemia (739 min +/- 131). Apparently the rate of clot lysis is mainly determined at an earlier stage of the fibrinolytic process, represented by the balance between tissue plasminogen activator and its inhibitor. Severe decrease of alpha 2 PI may nevertheless contribute to accelerated clot lysis as noted in a patient with familial heterozygous alpha 2 PI deficiency. On the other hand increased level of factor XIII and alpha 2 PI associated to an impaired plasminogen activation would render the fibrin network more resistant to fibrinolysis.
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PMID:Clinical studies on alpha 2 plasmin inhibitor. 212 40

The pathogenesis of accelerated fibrinolysis in liver cirrhosis was investigated by comparing the results of specific assays for tissue plasminogen activator (tpa) antigen, tpa activity, tpa inhibitor, and alpha-2 plasmin inhibitor (a2PI) in 12 patients with cirrhosis and markedly accelerated fibrinolysis (dilute whole blood clot lysis time (DWBCLT) less than two hours), in nine patients with cirrhosis and moderately accelerated fibrinolysis (DWBCLT two to four hours), and in nine patients with cirrhosis and normal fibrinolysis (DWBCLT greater than four hours). Mean tpa antigen was markedly increased in all three groups, but no correlation was observed between overall fibrinolytic activity as measured by the DWBCLT and the level of tpa antigen. In contrast, there was a significant correlation between overall fibrinolytic activity and tpa activity and an equally significant correlation between fibrinolytic activity and decreased tpa inhibition. Mean a2PI activity was significantly lower than normal in groups 1 and 2 but was normal in group 3. The pathogenesis of accelerated fibrinolysis in liver cirrhosis thus appears to depend critically on the capacity of plasma inhibitors to inhibit increased circulating tpa antigen. Reduced a2PI also appears to play a role.
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PMID:The pathogenesis of accelerated fibrinolysis in liver cirrhosis: a critical role for tissue plasminogen activator inhibitor. 243 84

Bleeding complications during liver transplantation have been attributed to accelerated fibrinolysis. In order to determine its cause, 11 adults (mean age: 38.9 +/- 13.2 yr) undergoing liver transplantation were studied. There were three groups of patients: cirrhosis (n = 4), fulminating hepatitis (n = 4) and one group including a primary biliary cirrhosis, a hepatic metastasis and a hepatoma. The following factors were studied in the immediate preoperative period, at different surgical times throughout the procedure and 2-3 h after the end of the abdominal sutures: platelet count, prothrombin concentration, fibrinogen, activated kephalin time, factors II, V, VII + X and VIIIc, antithrombin III, protein C, D-dimers, fibrinogen and fibrin degradation products (PDF), plasma plasminogen, tissue plasminogen activator (tPA) and the fast tPA inhibitor (PAi). Preoperatively, only the two patients with hepatic cancer had a normal haemostatic profile. Throughout the procedure, all patients had only moderate changes in platelets, coagulation factors and their inhibitors, and plasminogen, because platelet concentrates and fresh frozen plasma were transfused. Levels of tPA rose, becoming very high during the anhepatic period and just after graft reperfusion. An abrupt fall occurred at the end of surgery. There were important individual differences in tPA activity. PAi activity was low during the preanhepatic and anhepatic stages, rising rapidly after revascularization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Fibrinolytic activity in patients undergoing hepatic transplantation]. 249 27

In 1942, 53% of medically treated patients with cirrhosis were dead 6 months after the onset of ascites. Only 30% survived 1 year. This dismal outlook has improved only slightly with advances in medicine. Yet, some internists reject the peritoneovenous shunt (PVS) for this fatal condition even if they are aware that a diminished blood volume causes the abnormal sodium retention responsible for ascites. Their objections are based on life-threatening complications of PVS, especially post shunt coagulopathy (PSC). Blood shed into the peritoneal cavity becomes incoagulable. Such blood is immediately coagulated by a protocoagulant (soluble collagen) and concurrently lysed by tissue plasminogen activator (TPA) secreted by the peritoneal serosa. Wide zones of lysis surround peritoneal tissue placed on fibrin plates. Large volumes of ascitic fluid infused into circulating blood simulates the fate of blood shed into the peritoneal cavity with lysis playing the major role. Addition of ascitic fluid to normal platelet-rich plasma in vitro initiates clot lysis on thromboelastogram (TEG). Epsilon-aminocaproic acid (EACA) counteracts this lysis. EACA and clotting factors normalize the TEG and arrest PSC. Disposal of ascitic fluid at surgery prevents or ameliorates PSC. Mild PSC was encountered only twice in 150+ consecutive patients (1.3%) with only one case being clinically significant (0.6%). Severe PSC occurred seven times in 98 early shunt patients whose ascitic fluid was not discarded. Severe PSC requires shunt interruption and control of bleeding with clotting factors and EACA. Peritoneal lavage with saline prevents the recurrence of PSC on reopening the shunt. In four patients, EACA and clotting factors were adequate to arrest coagulopathy. Three earlier patients died of PSC before its cause and treatment were understood. Proper management eliminates this life-threatening complication, and PSC cannot be considered a deterrent to PVS. Disseminated intravascular coagulopathy (DIC) is produced in experimental animals only by the injection of thrombin or thromboplastin. PSC is a distinct entity differing from DIC; EACA and not heparin is the antidote for PSC.
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PMID:Coagulopathy post peritoneovenous shunt. 310 56

Ascitic fluid reinfusion in severe cirrhosis has frequently been associated with intravascular coagulation (DIC). A low-grade DIC has been postulated to be present in liver cirrhosis. PT, APTT, fibrinogen, plasminogen, antiplasmin, fibrin degradation producers (FDP), euglobulin lysis time, tissue plasminogen activator, and fibrinopeptide A were investigated both in the plasma and ascitic fluid of cirrhotic patients before and after the concentration-reinfusion technique. Our results indicate that increased thrombin formation associated with hyperfibrinolysis is present in the plasma of cirrhotic patients. In ascitic fluid very high levels of thrombin and fibrinolysis activation were found. We conclude that (1) a DIC-like picture exists in ascites and (2) after ascites reinfusion procedures, ascitic fluid is the principal factor in the pathogenesis of DIC. During ascitic fluid reinfusion heparin treatment could be used successfully.
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PMID:A DIC-like picture on plasma and ascitic fluid of cirrhotic patients. 314 1

High levels of tissue plasminogen activator (t-PA) have been reported to be the main component of the high fibrinolytic activity measured in patients during orthotopic liver transplantation. However, a previous study of our group suggested that specific t-PA may not completely account for the massive fibrinolytic activities recorded. In the present study we investigated the fibrinolytic patterns in 10 consecutive liver cirrhosis patients undergoing OLT. Euglobulin fibrinolytic activity, measured either on physiologic (fibrin plates) or amidolytic substrates, increased as expected during anhepatic and reperfusion phases, but largely exceeded the specific activity of t-PA, as proved by quenching procedures using anti-t-PA antibodies. The presence of plasmin- and trypsin-like amidolytic activities was detected in native plasmas at the end of anhepatic and reperfusion phases, together with decreased levels of protease inhibitors, especially alpha 1 Antitrypsin. In conclusion, the hyperfibrinolytic pattern recorded in the central OLT phases is not only attributable to an increased t-PA concentration, and is better described as a complex "lytic" state also including the presence of free proteases (plasmin- and trypsin-like), with limited participation of u-PA. Although t-PA increase is probably the main mechanism of stimulation of the fibrinolytic system during OLT, actual and not just potential proteolytic activities can be found in this condition independent of the occurrence of major hemorrhagic complications.
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PMID:Protease activities, as well as plasminogen activators, contribute to the "lytic" state during orthotopic liver transplantation. 769 27

Platelet glycocalicin (GC) is the extramembranous portion of GPIb alpha that can be rapidly cleaved by enzymes such as calpain, plasmin, trypsin, elastase, etc. Quantitative cleavage will ultimately result in an acquired Bernard-Soulier-like bleeding disorder, and circulating GC may act as a potential inhibitor of platelet adhesion. We have developed and standardized a new enzyme-linked immunosorbent assay (ELISA), which uses two monoclonal antibodies (mAbs), both of which bind to the amino-terminal 45-kD fragment of GC and inhibit platelet-von Willebrand interactions and the streptavidin-biotin system. First, the methodology was evaluated and standardized with special emphasis on the anticoagulant and the inhibitors (EDTA, prostaglandin E1 [PGE1], aprotinin, N-ethyl-maleimide), the mode of high-speed centrifugation (to avoid platelet microparticles), and the standards used (purified GPIb and GC). This assay was then used to analyze the GC levels of healthy subjects (2.04 +/- 0.46 micrograms/mL) and of patients with selected diseases. The results of patients with aplastic anemia and thrombocytosis confirmed that GC levels are clearly dependent on the platelet count, which was the basis for the introduction of the GC index, the standardization of GC for a platelet count of 250 x 10(9)/L. The GC index discriminates reliably patients with active immune thrombocytopenic purpura from those in remission. GC levels are elevated in patients on hemodialysis (3.62 +/- 0.75 micrograms/mL, P < .001). The high GC index (6.93 +/- 4.21, P < .001) in cirrhosis patients suggests an increased platelet turnover and/or abnormal proteolysis. In contrast to other groups, we have not found that recombinant tissue plasminogen activator (rtPA) treatment of patients with myocardial infarction increases GC levels. However, concentrations are elevated in leukemia and the highest levels found are approximately 40 micrograms/mL. These studies suggest that GC is a useful platelet marker in certain diseases, which directly reflects platelet damage and possibly platelet dysfunction.
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PMID:Glycocalicin: a new assay--the normal plasma levels and its potential usefulness in selected diseases. 829 32

This study explored the relationship between clotting activation and tissue plasminogen activator and its inhibitor in cirrhotic patients with different degrees of liver failure. Sixty-seven patients (40 men, 27 women; age = 31-77 yr) with cirrhosis diagnosed by liver biopsy were divided into three subgroups (A, B and C) on the basis of Child-Pugh classification. Tissue plasminogen activator antigen and activity, plasminogen activator inhibitor antigen and activity, fibrin/fibrinogen degradation products, and D-dimer were measured in each patient. Forty-two patients with normal levels of fibrin/fibrinogen degradation products and D-dimer showed significant progressive decreases of plasminogen activator inhibitor antigen levels (p < 0.01) and activity (p < 0.0001) from class A to class C. This decrease was significantly related to prothrombin time (p < 0.003). Tissue plasminogen activator values were not different in the three Child classes. Twenty-five patients (7 class B and 18 class C) with high circulating values of fibrin/fibrinogen degradation products and D-dimer had higher values of tissue plasminogen activator antigen (20.0 +/- 10.1 ng/ml vs. 5.9 +/- 3.0 ng/ml; p < 0.0001) and activity (6.9 +/- 2.2 U/ml vs. 2.1 +/- 1.3 U/ml; p < 0.0001) and lower values of plasminogen activator inhibitor antigen (6.9 +/- 4.1 ng/ml vs. 14.8 +/- 5.6 ng/ml; p < 0.0001) and activity (4.1 +/- 2.8 U/ml vs. 9.8 +/- 3.7 U/ml; p < 0.0001) than did patients with normal values of fibrin/fibrinogen degradation products and D-dimer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperfibrinolysis resulting from clotting activation in patients with different degrees of cirrhosis. The CALC Group. Coagulation Abnormalities in Liver Cirrhosis. 842 44


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