title: Baseline factor VIII plasma levels and age at first bleeding in patients with severe forms of von Willebrand disease.
abstract: BACKGROUND
  von Willebrand disease (VWD) is the most common inherited bleeding disorder. The age of bleeding onset is highly variable, also in patients with similar degree of severity.
  
  
  OBJECTIVE
  The primary aim of this study was to evaluate whether baseline factor VIII (FVIII) plasma levels correlate with age at first bleeding in patients with extremely low levels of VWF:RCo (<6 IU dL(-1) ).
  
  
  METHODS
  One hundred and three patients with VWF:RCo <6 IU dL(-1) (6 VWD1, 73 VWD2 and 24 VWD3) undergoing a medical examination between September 2010 and September 2013 were included. The relationship between baseline FVIII levels and age at first bleeding was tested in a multivariable linear regression model, adjusting for sex.
  
  
  RESULTS
  The median age at first bleeding was lower in patients with VWD3 than in those with severe forms of VWD1 or VWD2 (1 year vs. 7 and 8 years, respectively, P < 0.0001). A positive non-linear relationship between FVIII levels and age at first bleeding was found, the latter increasing by 5 years for every 10 IU dL(-1) increase of FVIII (β = 4.95 [95% CI: 2.02-7.87]) until levels of 30 IU dL(-1) , after which the age increased slowly. This relationship was not found in VWD 2A and 2B. In 65 patients (63%) there was a more than 6-month delay between bleeding onset and VWD diagnosis, with no difference over decades.
  
  
  CONCLUSIONS
  Baseline FVIII plasma levels influence the age at bleeding onset in VWD patients with extremely low levels of VWF:RCo, except in those with types 2A and 2B.
authors: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy.
authors: S M
authors: SM
authors: Siboni
authors: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy.
authors: E
authors: E
authors: Biguzzi
authors: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy.
authors: V
authors: V
authors: Caiani
authors: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy.
authors: C
authors: C
authors: Mistretta
authors: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy.
authors: P
authors: P
authors: Bucciarelli
authors: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy.
authors: F
authors: F
authors: Peyvandi
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000933:Antifibrinolytic Agents / Q000627:therapeutic use; D001803:Blood Transfusion; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000032:analysis*; D005260:Female; D006470:Hemorrhage; D006801:Humans; D016014:Linear Models; D008297:Male; D012720:Severity of Illness Index; D055815:Young Adult; D056725:von Willebrand Disease, Type 1 / Q000097:blood / Q000473:pathology; D056728:von Willebrand Disease, Type 2 / Q000097:blood / Q000473:pathology; D056729:von Willebrand Disease, Type 3 / Q000097:blood / Q000473:pathology; D014842:von Willebrand Diseases / Q000097:blood / Q000473:pathology* / Q000628:therapy; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000933:Antifibrinolytic Agents; D014841:von Willebrand Factor; D005169:Factor VIII
keywords: bleeding; blood coagulation disorders; factor VIII; von Willebrand disease; von Willebrand factor