title: Plasma levels of plasminogen activator inhibitor-1 and bleeding phenotype in patients with von Willebrand disease.
abstract: BACKGROUND
  von Willebrand disease (VWD) is the most common inherited bleeding disorder. In VWD patients, large variations in bleeding tendency are observed, which cannot be completely explained by the variation in von Willebrand factor levels or activities. Thus, there must be additional factors, for instance, changes in fibrinolysis that have an effect on the variation in bleeding tendency in VWD patients.
  
  
  OBJECTIVE
  To investigate whether plasminogen activator inhibitor-1 (PAI-1) level influences the variation in bleeding tendency in VWD patients.
  
  
  METHODS
  PAI-1 antigen levels were measured in the plasma of 633 patients with moderate or severe VWD who participated in the 'Willebrand in the Netherlands' (WiN) study, a nationwide multicentre cross-sectional study. Bleeding severity was assessed using the Tosetto bleeding score.
  
  
  RESULTS
  PAI-1 levels increased with age (Spearman's rho: 0.225, P < 0.001) and were higher in men (23 [IQR 12-60] vs. 20 [IQR 10-44] ng mL-1in women, P = 0.039), whereas the bleeding score was higher in women (11 [IQR 7-17] vs. 9 [IQR 5-14] ng mL-1in men, P = 0.002). After adjustment for age and sex by stratification, PAI-1 level and bleeding score were negatively correlated (Spearman's rho: -0.170, P = 0.017) in the group of 196 young (age ≤ 45 year) female VWD patients, accounting for 31% of our study population.
  
  
  CONCLUSIONS
  In young female VWD patients, we observed that low PAI-1 levels were associated with a higher bleeding score, which may partly explain the observed variability in bleeding phenotype in VWD patients.
authors.affiliation: Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Abdul
authors.affiliation: Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Boender
authors.affiliation: Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: J J M C
authors.initials: JJMC
authors.lastname: Malfliet
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Eikenboom
authors.affiliation: Pediatric Hematology, Emma Children's Hospital AMC, Amsterdam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Fijn van Draat
authors.affiliation: Van Creveldkliniek department of benign Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: E P
authors.initials: EP
authors.lastname: Mauser-Bunschoten
authors.affiliation: Hematology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Meijer
authors.affiliation: Netherlands Hemophilia Society, Leiden, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: de Meris
authors.affiliation: Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: B A P
authors.initials: BAP
authors.lastname: Laros-van Gorkom
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.|Jon J Van Rood Center for Clinical Transfusion Medicine, Sanquin Research, Leiden, The Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: van der Bom
authors.affiliation: Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: F W G
authors.initials: FWG
authors.lastname: Leebeek
authors.affiliation: Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: D C
authors.initials: DC
authors.lastname: Rijken
authors.affiliation: Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: S
authors.identifier: http://orcid.org/0000-0002-2035-4485
authors.initials: S
authors.lastname: Uitte de Willige
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006470:Hemorrhage / Q000150:complications*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics; D055815:Young Adult; D014842:von Willebrand Diseases / Q000097:blood* / Q000150:complications* / Q000235:genetics
chemical_list: D017395:Plasminogen Activator Inhibitor 1
keywords: bleeding score; fibrinolysis; plasminogen activator inhibitor-1; von Willebrand disease