title: Impaired fibrinolysis as a risk factor for Budd-Chiari syndrome.
abstract: In Budd-Chiari syndrome (BCS), thrombosis develops in the hepatic veins or inferior vena cava. To study the relationship between hypofibrinolysis and BCS, we measured plasma levels of fibrinolysis proteins in 101 BCS patients and 101 healthy controls and performed a plasma-based clot lysis assay. In BCS patients, plasminogen activator inhibitor 1 (PAI-1) levels were significantly higher than in controls (median, 6.3 vs 1.4 IU/mL, P < .001). Thrombin-activatable fibrinolysis inhibitor and plasmin inhibitor levels were lower than in controls (13.8 vs 16.9 microg/mL and 0.91 vs 1.02 U/L, both P < .001). Median plasma clot lysis time (CLT) was 73.9 minutes in cases and 73.0 minutes in controls (P = .329). A subgroup of cases displayed clearly elevated CLTs. A CLT above the 90th or 95th percentile of controls was associated with an increased risk of BCS, with odds ratios of 2.4 (95% confidence interval, 1.1-5.5) and 3.4 (95% confidence interval, 1.2-9.7), respectively. In controls, only PAI-1 activity was significantly associated with CLT. Analysis of single nucleotide polymorphisms of fibrinolysis proteins revealed no significant differences between cases and controls. This case-control study provides the first evidence that an impaired fibrinolytic potential, at least partially caused by elevated PAI-1 levels, is related to the presence of BCS.
authors: Departments of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Jildou
authors: J
authors: Hoekstra
authors: Ana H C
authors: AH
authors: Guimarães
authors: Frank W G
authors: FW
authors: Leebeek
authors: Sarwa
authors: S
authors: Darwish Murad
authors: Joyce J M C
authors: JJ
authors: Malfliet
authors: Aurelie
authors: A
authors: Plessier
authors: Manuel
authors: M
authors: Hernandez-Guerra
authors: Philippe
authors: P
authors: Langlet
authors: Elwyn
authors: E
authors: Elias
authors: Jonel
authors: J
authors: Trebicka
authors: Massimo
authors: M
authors: Primignani
authors: Juan-Carlos
authors: JC
authors: Garcia-Pagan
authors: Dominique C
authors: DC
authors: Valla
authors: Dingeman C
authors: DC
authors: Rijken
authors: Harry L A
authors: HL
authors: Janssen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000933:Antifibrinolytic Agents / Q000097:blood*; D001780:Blood Coagulation Tests / Q000379:methods; D006502:Budd-Chiari Syndrome / Q000097:blood* / Q000235:genetics; D025901:Carboxypeptidase B2 / Q000097:blood* / Q000235:genetics; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D014682:Vena Cava, Inferior / Q000378:metabolism
chemical_list: D000933:Antifibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D025901:Carboxypeptidase B2