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The role played by coagulation defects in the occurrence of bleeding in cirrhosis is still unclear. This is partly due to the lack of tests that truly reflect the balance of procoagulant and anticoagulant factors in vivo. Conventional coagulation tests such as prothrombin time and activated partial thromboplastin time are inadequate to explore the physiological mechanism regulating thrombin, because they do not allow full activation of the main anticoagulant factor, protein C, whose levels are considerably reduced in cirrhosis. We used a thrombin generation test to investigate the coagulation function in patients with cirrhosis. Thrombin generation measured without thrombomodulin was impaired, which is consistent with the reduced levels of procoagulant factors typically found in cirrhosis. However, when the test was modified by adding thrombomodulin (i.e., the protein C activator operating in vivo), patients generated as much thrombin as controls. Hence, the reduction of procoagulant factors in patients with cirrhosis is compensated by the reduction of anticoagulant factors, thus leaving the coagulation balance unaltered. These findings help clarify the pathophysiology of hemostasis in cirrhosis, suggesting that bleeding is mainly due to the presence of hemodynamic alterations and that conventional coagulation tests are unlikely to reflect the coagulation status of these patients. In conclusion, generation of thrombin is normal in cirrhosis.

Current recommendations for early anticoagulation in acute portal vein thrombosis unrelated to cirrhosis or malignancy are based on limited evidence. The aim of this study was to prospectively assess the risk factors, outcome, and prognosis in patients managed according to these recommendations. We enrolled 102 patients with acute thrombosis of the portal vein, or its left or right branch. Laboratory investigations for prothrombotic factors were centralized. Thrombus extension and recanalization were assessed by expert radiologists. A local risk factor was identified in 21% of patients, and one or several general prothrombotic conditions in 52%. Anticoagulation was given to 95 patients. After a median of 234 days, the portal vein and its left or right branch were patent in 39% of anticoagulated patients (versus 13% initially), the splenic vein in 80% (versus 57% initially), and the superior mesenteric vein in 73% (versus 42% initially). Failure to recanalize the portal vein was independently related to the presence of ascites (hazard ratio 3.8, 95% confidence interval 1.3-11.1) and an occluded splenic vein (hazard ratio 3.5, 95% confidence interval 1.4-8.9). Gastrointestinal bleeding and intestinal infarction occurred in nine and two patients, respectively. Two patients died from causes unrelated to thrombosis or anticoagulation therapy. Conclusion: Recanalization occurs in one-third of patients receiving early anticoagulation for acute portal vein thrombosis, whereas thrombus extension, intestinal infarction, severe bleeding, and death are rare. Alternative therapy should be considered when ascites and splenic vein obstruction are present. (HEPATOLOGY 2010;51:210-218.) A cute portal vein thrombosis (PVT) is characterized by the recent development of a thrombus in the portal vein or its left or right branches. 1,2 Extension to mesenteric venous arches causes intestinal infarction, with a reported mortality of up to 50%. 3,4 Without recanalization, a cavernoma develops, associated with a permanent risk of potentially fatal gastrointestinal bleeding, recurrent thrombosis, or biliary obstruction. 1,5,7 Recanalization is therefore a major goal for the treatment of acute PVT and is often a pressing challenge, because most PVT cases are recognized at the acute stage. 8 Expert panels have recommended early anticoagulation therapy for acute PVT. 2 However, these recommendations are based on small retrospective cohort studies performed over several decades. [9][10][11] The aim of this study was to prospectively assess (1) patient characteristics of those presenting with acute PVT unrelated to cirrhosis or malignancy; (2) the incidence and predictive factors of recanalization in patients managed according to recent recommendations; and (3) the incidence of disease-and treatment-related complications.

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Fifth Framework Programme of the European Commission.

Coagulation factor defects, thrombocytopenia, and thrombocytopathy are associated with cirrhosis. However, bleeding in patients who have cirrhosis does not entirely correlate with abnormal coagulation tests. Recently, it was shown that because of the concomitant abnormalities of the procoagulant and anticoagulant drives, thrombin generation in plasma patients with cirrhosis is normal when assessed with assays that include thrombomodulin (the main protein C activator). However, thrombin is also generated in vivo as a function of platelets, suggesting that thrombocytopenia and thrombocytopathy might affect thrombin generation in patients with cirrhosis. We addressed this issue using an assay that accounts for the contribution of plasma and platelets. The study showed that platelet-rich plasma with platelets adjusted by dilution of autologous platelet-rich into autologous platelet-poor plasma to a standard count (100 ؋ 10 9 /L) generates as much thrombin in patients with cirrhosis as in controls (1,063 nmol/L vs. 1,167 nmol/L; P value not significant). When platelets were adjusted to correspond to whole-blood counts, patients with cirrhosis generated significantly less thrombin than controls (949 nmol/L vs. 1,239 nmol/L; P < .001). Furthermore, thrombin generation correlated with platelet numbers ( ‫؍‬ 0.50; P < .001). In addition, the amount of thrombin generated as a function of the whole-blood patients' platelet counts increased significantly when the numbers were adjusted to 100 ؋ 10 9 /L (953 nmol/L vs.1,063 nmol/L; P < .001). In conclusion, severe thrombocytopenia may limit thrombin generation in patients with cirrhosis. These findings might justify platelet transfusion in patients with low platelet counts when they bleed spontaneously or before undergoing surgery or liver biopsy. Controlled clinical trials supporting this indication are warranted. (HEPATOLOGY 2006;44:440-445.)

Budd-Chiari syndrome (BCS) is a rare, life-threatening disease caused by obstruction of hepatic venous outflow. The aim of the study was to assess long-term outcome and identify prognostic factors in BCS patients managed by a step-wise approach using anticoagulation, angioplasty/thrombolysis, transjugular intrahepatic portosystemic shunting (TIPS), and orthotopic liver transplantation (OLT). We reviewed long-term data on 157 patients previously included by the European Network for Vascular Disorders of the Liver, a multicenter prospective study of newly diagnosed BCS patients in nine European countries. Patients were followed for a median of 50 months (range, 0.1-74.0). During the study, 88 patients (56%) received at least one invasive intervention (22 patients angioplasty/thrombolysis, 62 TIPS, and 20 OLT) and 36 (22.9%) died. Most interventions and/or deaths occurred in the first 2 years after diagnosis. The Rotterdam score was excellent in predicting intervention-free survival, and no other variable could significantly improve its prognostic ability. Moreover, BCS-TIPS prognostic index (PI) score (based on international normalized ratio, bilirubin, and age) was strongly associated with survival and had a discriminative capacity, which was superior to the Rotterdam score. Conclusions: The current study confirms, in a large cohort of patients with BCS recruited over a short period, that a step-wise treatment approach provides good long-term survival. In addition, the study validates the Rotterdam score for predicting intervention-free survival and the BCS-TIPS PI score for predicting survival. (HEPATOLOGY 2013;57:1962-1968