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)

D-dimer and factor VIII levels raise in advanced cirrhosis. We investigated the behavior and the diagnostic usefulness of D-dimer and factor VIII in cirrhotic patients with asymptomatic portal venous thrombosis. Factor VIII coagulant and D-dimer values were measured in 136 consecutive outpatients with stable cirrhosis divided according to Child-Pugh (CP) classification, who underwent color/power ultrasonography to detect portal thrombosis. Portal thrombosis was found in 33 patients (24.2%). In patients without thrombosis, factor VIII was significantly higher in CP class C compared with class A and B. Conversely, class C patients with portal thrombosis had lower factor VIII levels than those without thrombosis. In both groups, D-dimer was significantly increased in class C compared with class A and B. In class C, thrombotic patients showed higher D-dimer values than did patients without thrombosis. In class C, a D-dimer value > or = 0.55 microg/mL provided a sensitivity and a negative predictive value for portal thrombosis of 100%, and a factor VIII coagulant level < or = 80% showed a specificity and a negative predictive value of 76% and 84%, respectively. In class B, a D-dimer value > or = 0.225 microg/mL had a sensitivity of 89% and a negative predictive value of 82%. In conclusion, our study shows that factor VIII values increase in severe cirrhosis but significantly decrease in the presence of concomitant portal thrombosis, likely because of consumption during thrombosis; D-dimer is enhanced by both liver failure and portal thrombosis; in severe cirrhosis, normal D-dimer and factor VIII values may safely exclude the presence of asymptomatic portal thrombosis.
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PMID:Evaluation of D-dimer and factor VIII in cirrhotic patients with asymptomatic portal venous thrombosis. 1619 85

Liver transplantation may induce immune tolerance to factor VIII inhibitors but de novo development of inhibitors after transplantation may cause intractable haemorrhage. We report a patient with mild haemophilia A and high-titre FVIII inhibitors who received an orthotopic liver transplantation for complications of hepatitis C virus cirrhosis. Recombinant activated FVII was used in addition to routine haemostatic agents. Conventional immunosuppression was supplemented with antithymocyte globulin and cyclophosphamide. FVIII inhibitors disappeared from the circulation with liver transplantation but they were found to have bound to the graft endothelium, which became activated and induced catastrophic microangiopathy. A subsequent anamnestic response resulted in FVIII inhibitor titres of 1000 Bethesda Units. Uncontrollable haemorrhage persisted until the recipient's death. In patients with high-titre FVIII inhibitors resilient desensitization is required before liver transplantation.
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PMID:Catastrophic microangiopathy induced by high-titre factor VIII inhibitors after liver transplantation for haemophilia A with cirrhosis. 1623 13

Patients with cirrhosis and impaired coagulation often pose major therapeutic problems during bleeding episodes or invasive procedures. Recombinant activated factor VII (rFVIIa), which has been licensed for the treatment of haemophilia patients with factor VIII or IX inhibitors, has been occasionally used in cirrhotic patients. We present five patients with cirrhosis and coagulopathy who received 1-4 recombinant activated factor VII infusions either prophylactically in order to safely undergo an invasive procedure or therapeutically in order to control a severe bleeding episode which did not respond to standard supportive care. In particular, recombinant activated factor VII infusions were given in two patients before a percutaneous liver biopsy, in one patient before teeth extraction and in two patients with haemoperitoneum after an invasive procedure. Infusions of recombinant activated factor VII achieved rapid correction of prothrombin time in all cases allowing the safe performance of invasive procedures or resulting in efficient control of the bleeding episode. In conclusion, recombinant activated factor VII seems to be a rather promising agent for the prevention or treatment of complications of haemostasis impairment in cirrhotic patients. However, its exact role in this setting needs to be evaluated within well-designed, controlled clinical trials.
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PMID:Prophylactic and therapeutic use of recombinant activated factor VII in patients with cirrhosis and coagulation impairment. 1678 69

The prevalence of portal hypertension and its complications is increasing among patients with hemophilia and cirrhosis. The authors evaluated the safety and efficacy of transjugular intrahepatic postosystemic shunt (TIPS) placement in this population. A retrospective analysis was performed of adult patients who underwent TIPS placement at a single center. Four patients with hemophilia and cirrhosis were identified. Outcome measures included technical success and complications, recurrent gastrointestinal hemorrhage, shunt patency, hepatic encephalopathy, ascites control, and mortality. With periprocedural factor VIII supplementation, TIPS were placed in all patients without complications and with improvement in portal hypertension. Outcomes after TIPS placement appear to be comparable to those in patients without hemophilia.
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PMID:Safety and efficacy of TIPS in patients with hemophilia and cirrhosis. 1732 67

We present an unusual case of percutaneous liver biopsy complicated by delayed haemothorax in a 55-year-old Chinese man with hepatitis C cirrhosis and severe haemophilia A. The patient presented ten days after the initial liver biopsy, and was managed with prompt investigations for confirming the diagnosis, infusion of factor VIII and fresh frozen plasma, and early referral to the surgeon for consideration of surgical repair. The importance of early detection and aggressive therapy is emphasised.
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PMID:Delayed bleeding after liver biopsy: a dreaded complication. 1820 74

Observations that hepatic inflammation and cirrhosis are associated with the presence of thrombi within the hepatic microvasculature and fibrin-fibrinogen deposition have led to epidemiologic studies showing that carriage of the factor V Leiden mutation, protein C deficiency, and increased expression of factor VIII are associated with rapid progression to cirrhosis in a chronic hepatitis C virus. Additional data suggest that this process may extend more broadly to progression in many forms of chronic liver disease. This article discusses the evidence for a role for coagulation cascade activity in hepatic fibrogenesis and explores the proposed pathogenic mechanisms including the downstream events of thrombin activation. Interference with either the generation of thrombin or its downstream activity may reduce hepatic fibrosis. Also examined are the implications for future therapeutic intervention.
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PMID:Parenchymal extinction: coagulation and hepatic fibrogenesis. 1915 Mar 16

A 68-year-old man with hemophilia A and liver cirrhosis caused by hepatitis C virus was referred to our hospital to receive prophylactic endoscopic treatment for gastroesophageal varices (GOV). He had large, tense, and winding esophageal varices (EV) with cherry red spots extending down to lesser curve, predicting the likelihood of bleeding. Esophageal endoscopic injection sclerotherapy (EIS) was performed with a total 15 mL of 5% ethanolamine oleate with iopamidol (EOI). Radiographic imaging during EIS demonstrated that 5% EOI reached the afferent vein of the varices. He was administered sufficient factor VIII concentrate before and after EIS to prevent massive bleeding from the varices. Seven days after EIS, upper gastrointestinal endoscopy (UGIE) showed that the varices were eradicated almost completely. Eighteen months after EIS, the varices continued to diminish. We report a successful case of safe and effective EIS for GOV in a high-risk cirrhotic patient with hemophilia A.
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PMID:Successful endoscopic injection sclerotherapy of high-risk gastroesophageal varices in a cirrhotic patient with hemophilia A. 2045 1

Portal vein thromboses are frequent in cirrhotic patients and may be favoured by hypercoagulability in the splanchnic venous system. The coagulation balance and thrombin generation (TG) were evaluated in platelet-free plasma obtained from portal and systemic blood samples in 28 cirrhotic patients while undergoing transjugular intrahepatic porto-systemic shunt. TG assay (TGA) was performed with all samples from cirrhotic patients and with plasma samples from 14 healthy controls, with varying concentrations of tissue factor and phospholipids, with or without thrombomodulin. Screening tests and specific assays were also performed and activated partial thromboplastin time was shorter in portal plasma samples with higher FVIII and lower protein C levels, well correlated with Child-Pugh scores, and higher D-dimers and F1+2 levels However, all TGA parameters were similar in portal and jugular samples, possibly due in part to similar concentrations of factor II and antithrombin in these two sites of plasma sampling. TGA showed lower thrombin peaks and endogenous thrombin potential values in cirrhotic plasma compared to those of healthy controls. Importantly, a resistance to thrombomodulin that well correlated with factor VIII and PC levels, was evidenced in all samples from patients with cirrhosis, and was more significant in those from severely affected cases. This study therefore supports the existence of a relative hypercoagulability in the portal vein of cirrhotic patients that is likely due to protein C/S deficiency and to high FVIII levels.
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PMID:Comparative study of coagulation and thrombin generation in the portal and jugular plasma of patients with cirrhosis. 2080 6

The development of hepatic fibrosis on a background of chronic liver injury represents a complex disease trait modulated through the interaction of host genetic factors and environmental influences. Early observations that hepatic inflammation and cirrhosis are associated with the presence of microthrombi within the hepatic vasculature and fibrin/fibrinogen deposition were followed by epidemiological studies showing that carriage of the Factor V Leiden (FvL) mutation, protein C deficiency and increased expression of factor VIII are associated with accelerated progression to cirrhosis in a chronic hepatitis C infection. Additional data suggest that these factors may influence fibrogenesis in many forms of chronic liver disease and extra-hepatic fibrotic processes. Drawing evidence both from liver research and studies of fibrogenesis in other organ systems, two hypotheses may explain how activity of the coagulation cascade influences the rate of hepatic fibrogenesis: tissue ischaemia and parenchymal extinction and direct thrombin mediated stellate cell activation via PAR-1 cleavage. Drawing on preclinical and clinical studies we discuss the evidence for a role for coagulation cascade activity in hepatic fibrogenesis and explore the proposed pathogenic mechanisms that lead to stellate cell activation. The corollary of an association between hypercoagulation and increased fibrosis is that interference with the coagulation cascade may reduce hepatic fibrosis. We conclude this article by examining the implications for future therapeutic intervention.
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PMID:The role of hypercoagulability in liver fibrogenesis. 2157 Sep 30

Decreased levels of most coagulation factors and thrombocytopenia are the main haemostatic abnormalities of cirrhosis. As a consequence, this condition was, until recently, considered as the prototype acquired coagulopathy responsible for bleeding. However, recent evidence suggests that it should, rather, be regarded as a condition associated with normal or even increased thrombin generation. The bleeding events that occur in these patients should, therefore, be explained by the superimposed conditions that frequently occur in this setting. Due to elevated levels of factor VIII (procoagulant driver) in combination with decreased protein C (anticoagulant driver), which are typically found in patients with cirrhosis, a procoagulant imbalance, defined as a partial resistance to the in vitro anticoagulant action of thrombomodulin, can be demonstrated. Whether this in vitro hypercoagulability is truly representative of what occurs in vivo remains to be established. However, the hypothesis that it may have clinical consequences is attractive and deserves attention. The possible consequences that we discuss herein include whether (i) cirrhosis is a condition associated with increased risk of venous thromboembolism or portal vein thrombosis; (ii) the hypercoagulability associated with cirrhosis has any other role outside coagulation (i.e. progression of liver fibrosis); and (iii) anticoagulation should be used in cirrhosis. Although apparently provocative, considering anticoagulation as a therapeutic option in patients with cirrhosis is now supported by a rationale of increasing strength. There may be subgroups of patients who benefit from anticoagulation to treat or prevent thrombosis and to slow hepatic fibrosis. Clinical studies are warranted to explore these therapeutic options.
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PMID:Hypercoagulability in cirrhosis: causes and consequences. 2172 37


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