Impaired fibrinolysis as a risk factor for Budd-Chiari syndrome

Jildou Hoekstra, Ana H C Guimarães, Frank W G Leebeek, Sarwa Darwish Murad, Joyce J M C Malfliet, Aurelie Plessier, Manuel Hernandez-Guerra, Philippe Langlet, Elwyn Elias, Jonel Trebicka, Massimo Primignani, Juan Carlos Garcia-Pagan, Dominique C. Valla, Dingeman C. Rijken, Harry L A Janssen

Research output: Contribution to journalArticle

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 plasmabased 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 μg/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).Asubgroup of cases displayed clearly elevated CLTs. ACLT 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.

Original languageEnglish
Pages (from-to)388-395
Number of pages8
JournalBlood
Volume115
Issue number2
DOIs
Publication statusPublished - Jan 14 2010

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Budd-Chiari Syndrome
Fibrinolysis
Plasminogen Activator Inhibitor 1
Fibrin Clot Lysis Time
Carboxypeptidase B2
Confidence Intervals
Antifibrinolytic Agents
Hepatic Veins
Inferior Vena Cava
Plasmas
Single Nucleotide Polymorphism
Case-Control Studies
Proteins
Thrombosis
Polymorphism
Odds Ratio
Assays
Nucleotides

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Hoekstra, J., Guimarães, A. H. C., Leebeek, F. W. G., Murad, S. D., Malfliet, J. J. M. C., Plessier, A., ... Janssen, H. L. A. (2010). Impaired fibrinolysis as a risk factor for Budd-Chiari syndrome. Blood, 115(2), 388-395. https://doi.org/10.1182/blood-2009-03-211557

Impaired fibrinolysis as a risk factor for Budd-Chiari syndrome. / Hoekstra, Jildou; Guimarães, Ana H C; Leebeek, Frank W G; Murad, Sarwa Darwish; Malfliet, Joyce J M C; Plessier, Aurelie; Hernandez-Guerra, Manuel; Langlet, Philippe; Elias, Elwyn; Trebicka, Jonel; Primignani, Massimo; Garcia-Pagan, Juan Carlos; Valla, Dominique C.; Rijken, Dingeman C.; Janssen, Harry L A.

In: Blood, Vol. 115, No. 2, 14.01.2010, p. 388-395.

Research output: Contribution to journalArticle

Hoekstra, J, Guimarães, AHC, Leebeek, FWG, Murad, SD, Malfliet, JJMC, Plessier, A, Hernandez-Guerra, M, Langlet, P, Elias, E, Trebicka, J, Primignani, M, Garcia-Pagan, JC, Valla, DC, Rijken, DC & Janssen, HLA 2010, 'Impaired fibrinolysis as a risk factor for Budd-Chiari syndrome', Blood, vol. 115, no. 2, pp. 388-395. https://doi.org/10.1182/blood-2009-03-211557
Hoekstra J, Guimarães AHC, Leebeek FWG, Murad SD, Malfliet JJMC, Plessier A et al. Impaired fibrinolysis as a risk factor for Budd-Chiari syndrome. Blood. 2010 Jan 14;115(2):388-395. https://doi.org/10.1182/blood-2009-03-211557
Hoekstra, Jildou ; Guimarães, Ana H C ; Leebeek, Frank W G ; Murad, Sarwa Darwish ; Malfliet, Joyce J M C ; Plessier, Aurelie ; Hernandez-Guerra, Manuel ; Langlet, Philippe ; Elias, Elwyn ; Trebicka, Jonel ; Primignani, Massimo ; Garcia-Pagan, Juan Carlos ; Valla, Dominique C. ; Rijken, Dingeman C. ; Janssen, Harry L A. / Impaired fibrinolysis as a risk factor for Budd-Chiari syndrome. In: Blood. 2010 ; Vol. 115, No. 2. pp. 388-395.
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