title: Effect of fibrinolysis on bleeding phenotype in moderate and severe von Willebrand disease.
abstract: Patients with von Willebrand disease (VWD), the most common inherited bleeding disorder, display large variation in bleeding tendency, which is not completely related to VWF levels. The cause of variability in clinical expression is largely unknown. The effect of plasma fibrinolytic capacity on bleeding tendency in VWD patients has not been investigated. We hypothesized that enhanced fibrinolysis may result in a more severe bleeding phenotype. Therefore, we measured the fibrinolytic potential in patients with moderate or severe VWD to investigate the contribution of fibrinolysis to the bleeding tendency. Fibrinolytic potential was measured as plasma clot lysis time (CLT) with and without addition of potato carboxypeptidase inhibitor (PCI) in 638 patients with moderate or severe VWD who participated in a nationwide multicentre cross-sectional study. Bleeding severity was measured using the Bleeding Score (BS).The CLTs were significantly longer, indicative of hypofibrinolysis, in men compared to women with VWD [106.2 (IQR 95.7-118.1) vs. 101.9 (IQR 92.8-114.0) min]. The CLTs prolonged with increasing age. No association was found between VWF or FVIII levels and CLT, or between VWF or FVIII levels and CLT(+PCI) . No association was observed for BS in a model with 10log-transformed CLT, adjusted for age, gender, VWF:Act and FVIII [b = 6.5 (95%CI -0.3 to 13.4)]. Our study showed that the plasma fibrinolytic potential does not influence bleeding tendency in VWD patients and therefore does not explain the variability in bleeding phenotype in VWD.
authors.affiliation: Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: De Wee
authors.forename: K
authors.initials: K
authors.lastname: Klaij
authors.forename: H C J
authors.initials: HC
authors.lastname: Eikenboom
authors.forename: J G
authors.initials: JG
authors.lastname: Van Der Bom
authors.forename: K
authors.initials: K
authors.lastname: Fijnvandraat
authors.forename: B A P
authors.initials: BA
authors.lastname: Laros-Van Gorkom
authors.forename: E P
authors.initials: EP
authors.lastname: Mauser-Bunschoten
authors.forename: K
authors.initials: K
authors.lastname: Meijer
authors.forename: G
authors.initials: G
authors.lastname: Goverde
authors.forename: P W G
authors.initials: PW
authors.lastname: Van Der Linden
authors.forename: D C
authors.initials: DC
authors.lastname: Rijken
authors.forename: F W G
authors.initials: FW
authors.lastname: Leebeek
mesh_terms: D000328:Adult; D000367:Age Factors; D003430:Cross-Sectional Studies; D005169:Factor VIII / Q000032:analysis; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006470:Hemorrhage / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010641:Phenotype; D012720:Severity of Illness Index; D014842:von Willebrand Diseases / Q000097:blood*; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D014841:von Willebrand Factor; D005169:Factor VIII