title: Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms.
abstract: Essentials von Willebrand factor (VWF) and factor VIII (FVIII) levels are modulated by age and ABO status. The effect of aging and ABO blood type on VWF and FVIII was assessed in 207 normal individuals. Aging and ABO blood type showed combined and bidirectional influences on VWF and FVIII levels. Aging and ABO blood type influence VWF levels through both secretion and clearance mechanisms.
  
  
  
  Background The effect of aging and ABO blood type on plasma levels of von Willebrand factor (VWF) and factor VIII (FVIII) have been widely reported; however, a comprehensive analysis of their combined effect has not been performed and the mechanisms responsible for the age-related changes have not been determined. Objectives To assess the influence of aging and ABO blood type on VWF and FVIII levels, and to evaluate the contribution of VWF secretion and clearance to the age-related changes. Methods A cross-sectional observational study was performed in a cohort of 207 normal individuals, whose levels of VWF, FVIII, VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio and blood type A antigen content on VWF (A-VWF) were quantified. Results Aging and ABO blood type exerted interrelated effects on VWF and FVIII plasma levels, because the age-related increase in both proteins was significantly higher in type non-O individuals (β = 0.011 vs. 0.005). This increase with age in non-O subjects drove the differences between blood types in VWF levels, as the mean difference increased from 0.13 U/mL in the young to 0.57 U/mL in the old. Moreover, A-VWF was associated with both VWF antigen (β = 0.29; 95% confidence interval [CI], 0.09, 0.50) and VWF clearance (β = -0.15; 95% CI, -0.25, -0.06). We also documented an effect of ABO blood type on VWF secretion with aging, as old individuals with blood type non-O showed higher levels of VWFpp (mean difference 0.29 U/mL). Conclusions Aging and ABO blood type have an interrelated effect on VWF and FVIII levels, where the effect of one is significantly influenced by the presence of the other.
authors.affiliation: Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Albánez
authors.affiliation: Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Ogiwara
authors.affiliation: Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Michels
authors.affiliation: Department of Public Health Sciences, Queen's University, Kingston, ON, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Hopman
authors.affiliation: Department of Medicine, Queen's University, Kingston, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Grabell
authors.affiliation: Department of Medicine, Queen's University, Kingston, ON, Canada.
authors.forename: P
authors.initials: P
authors.lastname: James
authors.affiliation: Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Lillicrap
mesh_terms: D000017:ABO Blood-Group System; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001788:Blood Grouping and Crossmatching; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005169:Factor VIII / Q000032:analysis*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D000017:ABO Blood-Group System; D014841:von Willebrand Factor; C078147:F8 protein, human; D005169:Factor VIII
keywords: ABO blood group system; aging; metabolic clearance rate; secretion; von Willebrand factor