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)

Factor VII and prekallikrein activities were studied in 37 patients with liver cirrhosis who were in a decompensated state. Sixteen of them died 30-70 days after admission; 21 survived and were discharged after 30-80 days. Seven who died and six survivors had signs of hyperfibrinolysis: factor VII activity differentiated the two groups independently of the presence of hyperfibrinolysis. The presence of hyperfibrinolysis significantly reduced prekallikrein activity, which did not differentiate clearly survivors from non-survivors. Long term follow up of survivors showed a good correlation between factor VII and prekallikrein activities with long term survival. Hyperfibrinolysis seemed to influence the clinical course of patients: 87% of patients with hyperfibrinolysis who died had fatal haemorrhagic episodes. Low factor VII activity may be a precursor of terminal liver insufficiency.
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PMID:Interrelation between factor VII, prekallikrein, and hyperfibrinolysis in advanced cirrhosis. 261 16

Repeated plasmaphereses were done in 7 patients with acute hepatic failure (5 of them with coma stage IV and two with stage III). Acute liver insufficiency was induced by fulminant viral hepatitis in 4 cases, by drugs in one case, and was caused by a dystrophic exacerbation of liver cirrhosis in two further cases. Four of the 7 treated patients have survived. Beginning improvement of hepatic function was evidenced by an increase of factor VII and prothrombin in plasma. Significant lowering of bilirubin could be observed in all cases. While ammonia values decreased continuously in the four successfully treated patients while on plasmapheresis, the opposite behaviour was observed in the decreased patients. The influence of plasmapheresis on the pathologically altered aminoacid pattern in hepatic coma was investigated in two patients: Before treatment clearly to excessively increased values of methionine and aromatic aminoacids (phenylalanine and tyrosine) were seen. Branched-chain aminoacids leucine, isoleucine and valine were normal to moderately decreased. After termination of plasmapheresis methionine and aromatic aminoacids were significantly lower, branched-chain aminoacids were slightly below the initial values. Improvement of consciousness correlated with increase of the quotient (val+leu+ile)/(phe+tyr).
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PMID:[Treatment of acute liver failure by plasmapheresis]. 640 57

Factor VII activity and factor VII cross-reacting material (CRM) in plasma of patients with liver cirrhosis have been studied before and after vitamin K1 parenteral administration. Subjects were divided into two groups according to the absence (group I) or the presence (group II) of the following clinical findings: ascites, portal hypertension, encephalopathy. Factor VII activity and CRM show a statistically significant correlation (p less than 0.001) in all patients. In group II, significantly reduced levels of both activity and CRM were found as compared to the reference and the group I values. No variations were found after vitamin K administration. Different thromboplastins, investigated with respect to their sensitivity for factor VII, acted differently. Patients with normal albumin levels also showed normal levels of factor VII activity and antigen. No correlation was found in group II. The data discussed suggest that in liver cirrhosis with unknown aetiology no immunologically detectable precursor of factor VII is present.
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PMID:Factor VII in liver cirrhosis. 708 11

One hundred sixty-five patients with cirrhosis diagnosed by needle liver biopsy were followed for 2 years to evaluate the relation between clotting factors and survival. Patients with spontaneous bacterial peritonitis, hepatic carcinoma, and cholestatic liver diseases were excluded. Patients were classified as A (n = 34), B (n = 75), or C (n = 56) according to Child-Pugh criteria. During the follow-up 45 patients died of liver failure or gastrointestinal hemorrhage. Nonsurvivor patients had significantly higher values of bilirubin and D-dimer, a marker of fibrinolysis in vivo, lower values of albumin, prothrombin activity, fibrinogen, prekallikrein, factor VII, and a more prolonged activated partial thromboplastin time than survivors. All these variables and Child-Pugh classification were significantly associated with survival in a univariate analysis. Multivariate analysis (Cox's model) showed that only prekallikrein and factor VII were independently predictors of survival. Ninety-three percent of patients with prekallikrein values < 32% died within 32 months of follow-up, whereas factor VII < 34% identified 93% of patients who died within 10 months of follow-up. This study suggests that factor VII is an early predictor of survival and may be a useful test to better identify cirrhotic patients who should be candidates for liver transplantation.
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PMID:Prognostic value of clotting and fibrinolytic systems in a follow-up of 165 liver cirrhotic patients. CALC Group. 760 39

A normally functioning hemostasis system is closely related to liver function. The liver parenchymal cells produce most of the factors and inhibitors of the clotting and fibrinolytic systems, and the RES of the liver greatly aids in the clearance of activation products. Hemostasis defects thus depend on the extent of liver damage. A wide spectrum of defects is found in patients with liver cirrhosis. Owing to impaired protein synthesis, most factors and inhibitors of the clotting and the fibrinolytic systems are markedly reduced. Additionally, abnormal vitamin K-dependent factor and fibrinogen molecules have been encountered. Most patients have hyperfibrinolysis that could be DIC in nature. Thrombocytopenia and thrombocytopathy are also found. Acute or chronic hepatocellular disease may display decreased vitamin K-dependent factor levels, especially factor VII and protein C, with other factors still being normal. If patients go into hepatic failure, the abnormalities resemble those found in liver cirrhosis. Vitamin K deficiency is associated with the production of poorly functioning vitamin K-dependent factors. All other hemostasis parameters are normal. Disturbances associated with liver surgeries again depend on the underlying liver problem. Peritoneovenous shunts (LeVeen) may lead to DIC; bleeding from partially resected liver surfaces is usually a mechanical problem. Severe bleeding is encountered with orthotopic liver transplantation. It is greatly influenced by the activation of the fibrinolytic system. This occurs during the anhepatic phase and during the reperfusion phase. The hyperfibrinolysis is mediated by an intense release of t-PA. Antifibrinolytic drugs, if used cautiously, have markedly reduced bleeding and thus reduced need for blood and blood product substitution.
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PMID:Coagulation defects in liver disease. 817 Feb 58

Liver cirrhosis leads to a protido-synthetic impairment that alters the levels of blood clotting factors and haemostasis. The aim of this study was to assess the alterations of haemostatic parameters in the evolution of liver cirrhosis scored according to Child's classification, with Pugh's modifications. Thirty-seven patients suffering from alcoholic and non-alcoholic liver cirrhosis, representing stages A5, A6, B7, B8 and C10, were tested for the main blood clotting parameters, i.e. prothrombin time, factor VII, partial activated thromboplastin time, fibrinogen, plasminogen, alpha 2-antiplasmin and physiological inhibitors [antithrombin III (ATIII), protein C (PC), protein S (PS)]. No variations were observed between substages A5 and A6 in any of the parameters, except for coagulation inhibitor levels. Most parameters showed a progressive decrease in stages B and C of the disease. The most significant alterations were found in the physiological coagulation inhibitors, with a sharper decrease in PC and AT III level and a lesser decrease in the level of PS through stages A5 and B8: this evidence could assume an important biological and diagnostic significance.
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PMID:Haemostasis unbalance in Pugh-scored liver cirrhosis: characteristic changes of plasma levels of protein C versus protein S. 831 73

We evaluated the efficacy of recombinant factor VII to correct impaired haemostasis in a patient with liver cirrhosis requiring an invasive procedure. A test intravenous bolus of 80 microg/kg of recombinant factor VII was given to a Jehovah's Witness, with a solitary 4.4-cm hepatocellular carcinoma and underlying hepatitis C virus cirrhosis, in an attempt to correct his haemostatic disorders and safely inject the tumour with alcohol. An extensive portal block had precluded consideration of liver transplantation. Haemostasis was evaluated by clotting assays, bleeding time and thromboelastography 10 min before and 10 min and 1, 2, 4, 8 and 24 h after factor VII infusion. Parameters of both coagulation (prothrombin time) and platelet function (bleeding time and the alpha and ma parameters of thrombelastography) were improved 10 min after factor VII infusion; improvements lasted 4 to 8 h or more. Platelet count did not change and there was no evidence of disseminated intravascular coagulation. The improvements in haemostatic parameters correlated significantly with the increases in factor VII plasma concentrations (p<0.04). Factor VII clearance was 25.1 U/h/kg and its half-life was 5.8 h. The same dose of recombinant factor VII was given to the patient 1 week later, just before the alcohol injections. The patient had no subsequent bleeding or other complication, with no change in haemoglobin levels over 24 h. Thus, recombinant factor VII represents a therapeutic advance, as it can correct fully both coagulation and platelet function defects in cirrhosis and allow invasive procedures to be performed safely.
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PMID:Correction of both prothrombin time and primary haemostasis by recombinant factor VII during therapeutic alcohol injection of hepatocellular cancer in liver cirrhosis. 1055 1

Three topics are addressed in this manuscript: (1) the causes of abnormal hemostasis in cirrhosis; (2) the evaluation of hemostasis in cirrhotic patients before invasive procedures or in the presence of bleeding; and (3) the assessment of the effect of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) on hemostatic function in cirrhotic patients. Laboratory experiments are described that could enhance the understanding of the effect of rFVIIa on blood coagulation during hemostasis in cirrhotic patients.
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PMID:Coagulation problems in liver disease. 1085 May 68

Patients with advanced liver cirrhosis have a serious disturbance in their hemostasis system that leads to increased morbidity and mortality. The vitamin K-dependent clotting factors, especially factor VII, are markedly reduced in these patients. Present treatment modalities include fresh frozen plasma (FFP), vitamin K, and desmopressin. FFP has to be given in large volume and entails the risk of transmitting infectious agents. The introduction of recombinant activated factor VII (rFVIIa) has offered another treatment option for patients with liver cirrhosis and bleeding. The clinical experience with rFVIIa is reviewed. Management seems to be effective and safe and the concern that rFVIIa might activate the hemostasis system in these patients has not materialized. Administration of rFVIIa not only corrected the abnormal clotting tests in these patients but also allowed several invasive procedures without the complication of bleeding.
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PMID:Effectiveness of the recombinant factor VIIa in patients with the coagulopathy of advanced child's B and C cirrhosis. 1109 21

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.
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PMID:Tissue factor and thrombomodulin levels are correlated with stage of cirrhosis in patients with liver disease. 1168 41


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