Hepatocellular carcinoma in Budd-Chiari syndrome: characteristics and risk factors.

BACKGROUND AND AIMS: To analyse the characteristics of and the factors associated with the development of hepatocellular carcinoma (HCC) in patients with Budd-Chiari syndrome (BCS). PATIENTS AND METHODS: 97 consecutive patients with BCS and a follow-up > or = 1 year were evaluated retrospectively. Liver nodules were evaluated using serum alpha-fetoprotein (AFP) level and imaging features (CT/MRI). Biopsy of nodules was obtained when one of the following criteria was met: number < or = 3, diameter > or = 3 cm, heterogeneity, washout on portal venous phase, increase in size on surveillance, or increase in AFP level. RESULTS: Patients were mainly Caucasian (69%) and female (66%). Mean age at the diagnosis of BCS was 35.8 (SE 1.2 years), and median follow-up 5 years (1-20 years). The inferior vena cava (IVC) was obstructed in 13 patients. Liver nodules were found in 43 patients, 11 of whom had HCC. Cumulative incidence of HCC during follow-up was 4%. Liver parenchyma adjacent to HCC showed cirrhosis in nine patients. HCC was associated with male sex (72.7% v 29.0%, p = 0.007); factor V Leiden (54.5% v 17.5%, p = 0.01); and IVC obstruction (81.8% v 4.6%, p < 0.001). Increased levels of serum AFP were highly accurate in distinguishing HCC from benign nodules: PPV = 100% and NPV = 91% for a cut-off level of 15 ng/ml. CONCLUSION: The incidence of HCC in this large cohort of BCS patients was similar to that reported for other chronic liver diseases. IVC obstruction was a major predictor for HCC development. Serum AFP appears to have a higher utility for HCC screening in patients with BCS than with other liver diseases.

The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage (PPH) is a major source of maternal morbidity. OBJECTIVES: This study's objective was to determine whether changes in hemostasis markers during the course of PPH are predictive of its severity. PATIENTS AND METHODS: We enrolled 128 women with PPH requiring uterotonic prostaglandin E2 (sulprostone) infusion. Two groups were defined (severe and non-severe PPH) according to the outcome during the first 24 hours. According to our criteria, 50 of the 128 women had severe PPH. Serial coagulation tests were performed at enrollment (H0), and 1, 2, 4 and 24 hours thereafter. RESULTS: At H0, and through H4, women with severe PPH had significantly lower fibrinogen, factor V, antithrombin activity, protein C antigen, prolonged prothrombin time, and higher D-dimer and TAT complexes than women with non-severe PPH. In multivariate analysis, from H0 to H4, fibrinogen was the only marker associated with the occurrence of severe PPH. At H0, the risk for severe PPH was 2.63-fold higher for each 1 gL(-1) decrease of fibrinogen. The negative predictive value of a fibrinogen concentration >4 gL(-1) was 79% and the positive predictive value of a concentration

Fibrinogen Poissy I: a new case of the A alpha Arg 16His fibrinogen variant.

A fibrinogen variant was identified in a patient with disseminated intravascular coagulation and in one member of her family. Coagulation studies showed marked prolongation of both the thrombin and reptilase times and discrepancy was noted between the levels of plasma fibrinogen, determined by a kinetic vs immunological determination or light scattering assay. Studies on purified fibrinogen revealed an impaired release of fibrinopeptides by thrombin. DNA sequencing revealed a heterozygous A to G point mutation in exon 2 of the A alpha chain, which substituted Arg for His at position 16. This mutation creates a Nla III cleavage site which was used to confirm the mutation.

[Blood salvage: a conditional safety]. / Récupérateurs de sang: une sécurité conditionnelle.

Recovery of shed blood is part of the allogenic blood saving policy of particular importance even though the risk of viral infection via transfusion has been considerably reduced. Blood transfusion requirements in vascular surgery are discussed together with alternatives to allogenic transfusion. Differed withdrawal of autologous blood can involve pre-operative autologous plasmapheresis and cytapheresis. Per-operative haemodilution is another variant of pre-operative isovolemic haemodilution and erythrocytapheresis. Recovery of shed blood can be done with or without lavage. Technical and pharmacologic measurements complete the method. Simultaneous use of different techniques can be useful. Recovery is particularly interesting in highly haemorhagic vascular procedures or those which must be done quite rapidly. Care must be taken to avoid the "recovery syndrome". Improvement in material will assure safety.

[Hippocampothalamic infarction. A limited form of infarction in the posterior cerebral artery area]. / Infarctus hippocampo-thalamique: une forme limitée d'infarctus du territoire de l'artère cérébrale postérieure.

Infarction of the hippocampus and the right ventroposterolateral thalamus was observed. Angiography revealed a posterior cerebral artery occluded near its origin, immediately upstream from the posterior communicating artery. The infarction was limited to the areas irrigated by the branches originating in the proximal part of the artery. More distal branches for the calcarine scissure and the temporooccipital gyruses were not involved.

[Nadroparin-induced skin necrosis then thrombocytosis in intensive care unit: difficulty in diagnosis]. / Nécrose cutanée et thrombocytose induites par la nadroparine en réanimation: un diagnostic inhabituel.

Skin necrosis is a rare complication in intensive care unit. A case-report of nadroparine-induced skin necrosis and thrombocytosis in a patient with traumatic paraplegia is reported. This case emphasised the difficulty in diagnosis despite absence of thrombopenia. A skin necrosis could suggest the diagnosis and a substitutive therapy must be administrated after heparin therapy withdrawal. A thrombocytosis is a little reported complication of low-molecular-weight heparins without complication.

Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation.

BACKGROUND AND AIMS: Splanchnic vein thrombosis is a significant source of complications in candidates for liver transplantation. The aims of this study were: (a) to determine the prevalence of and risk factors for splanchnic vein thrombosis in cirrhotic patients awaiting transplantation and (b) to assess the usefulness of anticoagulation. METHODS: A total of 251 cirrhotic patients listed for transplantation were analysed. All underwent systematic screening for thrombosis with Doppler ultrasonography. During the second period of the study, all patients with thrombosis received anticoagulation up to transplantation while during the first period none had received anticoagulation. RESULTS: The incidence of splanchnic vein thrombosis at evaluation was 8.4%. Seventeen additional patients (7.4%) developed de novo thrombosis after evaluation. Independent risk factors for thrombosis were low platelet count (77.4 (36.3) v 111.6 (69.2) 10(9)/l; p = 0.001), a past history of variceal bleeding (47.4% v 29.1%; p = 0.003), and a prolonged interval from listing to transplantation (8.5 (6.8) v 4.8 (4.4) months; p = 0.002). The proportion of partial or complete recanalisation was significantly higher in those who received (8/19) than in those who did not receive (0/10, p = 0.002) anticoagulation. Survival was significantly lower in those who had complete portal vein thrombosis at the time of surgery (p = 0.04). CONCLUSION: These results support a systematic screening for splanchnic vein thrombosis in patients awaiting transplantation. They suggest that in these patients, anticoagulation is safe and has a significant impact on recanalisation as well as prevention of extension of thrombosis.

[Liver diseases and hemostasis]. / Maladies du foie et hémostase.

The liver plays a key role in the regulation of hemostasis. By producing most clotting factors and inhibitors, as well as a number of the proteins involved in fibrinolysis, and by clearing from the bloodstream activated enzymes involved in clotting or fibrinolysis, the liver protects against both bleeding and undue activation of coagulation. It follows that liver diseases are commonly responsible for hemostasis abnormalities including decreased production of clotting factors, thrombocytopenia, platelet dysfunction, and increased circulating fibrinolytic activity. With the exception of cholestasis and in the absence of a specific setting such as pregnancy, the abnormalities are the same in all liver diseases, and their severity varies only with the degree of hepatocellular failure. Although liver diseases do not directly cause disseminated intravascular coagulation (DIC), they are a major risk factor for DIC in patients with infection or shock, as well as during pregnancy. In patients with liver diseases, hemostasis tests can be required to evaluate the degree of hepatocellular failure, the severity of hemostasis disorders manifesting as bleeding, or the bleeding risk before an invasive procedure. Prothrombin time determination is usually sufficient to evaluate the degree of hepatocellular failure, although in some cases assays of fibrinogen and factors II, VII, X, V are also useful. Evaluation of the bleeding risk prior to an invasive procedure requires a study of platelet function and measurement of circulating fibrinolytic activity, which is particularly likely to be abnormal in patients with severe hepatocellular failure and/or alcohol abuse. A less common reason for investigating hemostasis is a search for the cause of a thrombotic condition, such as portal vein thrombosis or Budd-Chiari syndrome.

Interaction of human alpha-thrombin and gamma-thrombin with antithrombin III, protein C and thrombomodulin.

Conversion of human alpha-thrombin to gamma-thrombin by limited proteolysis resulted in a decrease in the inactivation rate of the enzyme by antithrombin III. The second-order rate constants were similar but significantly different: 11 +/- 1.7 X 10(3) and 7 +/- 0.5 X 10(3) M-1 s-1 for alpha- and gamma-thrombin respectively. This difference is probably related to a slight change in reactivity of the catalytic site, rather than to a structural alteration of the recognition site for antithrombin III. The rate of protein C activation, measured in the absence of thrombomodulin, was greatly reduced by conversion of alpha-thrombin to gamma-thrombin. In addition, gamma-thrombin failed to displace alpha-thrombin from its complex with thrombomodulin, as demonstrated by measuring either the rate of protein C activation by thrombin-thrombomodulin, or the fibrinogen clotting activity of thrombin-thrombomodulin, in the presence of competing diisopropylphospho-thrombin. It is concluded that the recognition sites involved in protein-C-thrombin and thrombomodulin-thrombin interactions are both dramatically affected by the loss of peptide material occurring during the conversion of alpha-thrombin to gamma-thrombin and/or by the resulting conformational changes.

Portal vein thrombosis with ruptured oesophageal varices as presenting manifestation of hereditary protein C deficiency.

The protein C system is essential in limiting the activation of coagulation in vivo. We report the case of a 45 year old man with portal vein thrombosis complicated by ruptured oesophageal varices. Low concentration of plasma protein C was found in the patient and subsequently in one brother with a history of venous thromboembolism, and also in one son and one nephew who were asymptomatic. Hereditary protein C deficiency should be considered in patients with portal hypertension due to portal vein thrombosis.

Case report: cytomegalovirus infection as a cause of acute portal vein thrombosis.

We report on the case of a 31-year-old woman who developed acute portal vein thrombosis during the course of an acute cytomegalovirus (CMV) infection. We suggest a relationship between CMV infection, its endothelial cell-damaging effects and portal vein thrombosis.

Role of factor VIII on activated protein C resistance ratio in inflammatory diseases.

Activated protein C resistance ratio (APC-Rr), factor VIIIC (FVIIIC) and plasma fibrinogen levels were studied in patients with inflammatory disease. The patient mean APC-Rr was significantly lower than in the control group. This decreased ratio in inflammatory diseases appeared to be connected with increased FVIIIC. Moreover, supplementation of plasmas with purified factor VIII decreased the APC-Rr in plasma from both groups, and suppressed the difference between groups. These data suggest that factor VIIIa and factor Va compete for protein C-catalysed cleavage. Ratios were identical in both groups when FVIIIC level was lowered by dilution in factor V deficient plasma.

Clopidogrel antiplatelet activity is independent of age and presence of atherosclerosis.

The pharmacodynamic and pharmacokinetic effects of clopidogrel 75 mg taken once daily in the morning before breakfast for 10 days were compared among three groups: 12 healthy young subjects, 10 healthy elderly subjects (>65 years) and 10 otherwise healthy elderly subjects with atherosclerosis, manifested by intermittent claudication. Platelet aggregation induced by 5 microM of ADP was measured in plasma samples taken at screening, 2 hours after dosing on day 1 to day 9; 2, 5, and 24 hours after dosing on day 10; and on alternate days until day 24. The inhibition of platelet aggregation was expressed as the percent reduction in maximum platelet aggregation with respect to baseline. The bleeding time was measured at screening, 5 hours after dosing on day 10, and on day 18. Plasma concentrations of SR26334, the main circulating metabolite of clopidogrel, were determined before dosing on day 1 to day 10 and at regular intervals over 72 hours after dosing on day 10. Inhibition of platelet aggregation appeared 2 hours after the first dose, became significant after the second dose, and progressed to a steady-state value of 55 to 57% by day 7 in the three groups, with no statistically significant difference between groups. A moderate, statistically significant prolongation of bleeding time of similar extent (prolongation factor of 1.5 to 1.6) was found on day 10 in the three groups. The pharmacodynamic parameters generally returned to baseline within 8 days after treatment. Based on AUC(0-24th) values, drug exposures were very similar for the two groups of elderly subjects but approximately twice that for the young group. The pharmacodynamic effects of clopidogrel were comparable in all three groups.

Auxiliary liver transplantation: how to improve regeneration of the native liver by surgery.

The technical factors which could influence regeneration of the native liver (NL) in auxiliary liver transplantation (ALT) for fulminant hepatic failure (FHF) are not well known. We studied NL regeneration according to the location of graft anastomosis in the recipient's portal system (superior mesenteric vein versus portal vein), and graft weight (50% reduced-size versus full-size graft) in a rat model of ALT with 80% reduction of the NL, and graft arterialization. NL regeneration was significantly more obvious when the graft was anastomosed on the recipient's superior mesenteric vein, thus establishing venous flow to the NL from the pancreas, the spleen, and the stomach, and when a full-size graft was used. The influence of portal venous flow on NL regeneration, assessed by 3H[-thymidine incorporation, was measurable as early as day 2. Both technical variables in combination resulted in significantly greater regeneration (ratio weight of NL/body weight at day 30: 2.32 +/- 0.68% versus 1.21 +/- 0.63% respectively, P = 0.02). Early preservation of portal flow to the NL is advisable to maximize NL regeneration in ALT. In any case, this regeneration is not impeded by the use of large auxiliary grafts.

Idiopathic non-cirrhotic intrahepatic portal hypertension in the West: a re-evaluation in 28 patients.

BACKGROUND: Non-cirrhotic portal hypertension of unknown cause is a poorly understood condition attributed to obstructive portal venopathy. AIM: To reassess the manifestations, course, and causes, with special attention to thrombosis. METHODS: Analysis of a cohort of 28 patients. RESULTS: Gastrointestinal bleeding occurred in 11 patients. Liver failure developed at the time of concurrent disease in eight patients, including all four patients who died. Portal vein thrombosis developed in 13 patients. A prothrombotic disorder was found in 12 of 23 fully investigated patients. Hepatoportal sclerosis was observed in 11 patients (with associated perisinusoidal fibrosis and/or nodular regenerative hyperplasia in six); periportal fibrosis, perisinusoidal fibrosis, nodular regenerative hyperplasia, or a combination thereof were observed in other patients. A morphometric evaluation showed an increased number of portal vessels in patients with hepatoportal sclerosis. There was no relation between pathological results and haemodynamic findings or prothrombotic disorders. CONCLUSIONS: Outcome was related to associated conditions. Overlap in pathological, haemodynamic, and causal features suggests a single entity, with prothrombotic disorders as major causal factors, and injury to sinusoids as well as to portal venules as the primary mechanism. Activated coagulation could mediate vascular injury in the absence of thrombosis. Anticoagulation should be considered.