Eugenia Biguzzi1, Filippo Castelli2, Willem M Lijfering3, Suzanne C Cannegieter3, Jeroen Eikenboom4, Frits R Rosendaal3, Astrid van Hylckama Vlieg5. 1. IRCCS Fondazione Ca' Granda Ospedale Policlinico, A. Bianchi Bonomi Hemophilia and Thrombosis Center, Via Pace 9, 20122 Milan, Italy. 2. University of Milan, Via Festa del Perdono, 20122 Milan, Italy. 3. Leiden University Medical Center, Department of Clinical Epidemiology, Albinusdreef 2, 2333ZA Leiden, the Netherlands. 4. Leiden University Medical Center, Department of Internal Medicine, Division of Thrombosis and Hemostasis, Albinusdreef 2, 2333ZA Leiden, the Netherlands. 5. Leiden University Medical Center, Department of Clinical Epidemiology, Albinusdreef 2, 2333ZA Leiden, the Netherlands. Electronic address: A.van_Hylckama_Vlieg@lumc.nl.
Abstract
BACKGROUND: Von Willebrand factor (VWF) levels are regulated by genetic and acquired factors. The acquired factors are mostly related to age and could be mediators of the age effect on VWF levels. OBJECTIVES: To disentangle the role of genetic (sex, blood group) and acquired factors (comorbidities, body mass index, reduced kidney function, hormone use, and inflammation) in regulating von Willebrand factor antigen (VWF:Ag) and factor VIII activity (FVIII:C) levels in the normal population. METHODS: Analysis were performed in a large population sample (2923 individuals) from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), after exclusion of individuals with active cancer and women who were pregnant or within nine months postpartum. The increase of VWF:Ag and FVIII:C with age was evaluated by linear regression after the age of 40 years. Analyses were adjusted for acquired factors and stratified for sex and blood group. RESULTS: VWF:Ag and FVIII:C increased with age: increase per decade of age for VWF:Ag 18 IU/dL (95%CI 15-20) and for FVIII:C 12 IU/dL (95%CI 10-14). After adjustment for acquired factors, the increase per decade was 13 IU/dL (95%CI 10-16) for VWF:Ag and 9 IU/dL (95%CI 6-11) for FVIII:C. The stratified analysis for blood group showed higher increase in the non-O group, but these differences were annulled after adjustment for acquired factors. CONCLUSIONS: VWF:Ag and FVIII:C increase with age. Carriers of blood group non-O present a steeper increase of VWF:Ag and FVIII:C with age, that is mediated by acquired factors.
BACKGROUND: Von Willebrand factor (VWF) levels are regulated by genetic and acquired factors. The acquired factors are mostly related to age and could be mediators of the age effect on VWF levels. OBJECTIVES: To disentangle the role of genetic (sex, blood group) and acquired factors (comorbidities, body mass index, reduced kidney function, hormone use, and inflammation) in regulating von Willebrand factor antigen (VWF:Ag) and factor VIII activity (FVIII:C) levels in the normal population. METHODS: Analysis were performed in a large population sample (2923 individuals) from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), after exclusion of individuals with active cancer and women who were pregnant or within nine months postpartum. The increase of VWF:Ag and FVIII:C with age was evaluated by linear regression after the age of 40 years. Analyses were adjusted for acquired factors and stratified for sex and blood group. RESULTS: VWF:Ag and FVIII:C increased with age: increase per decade of age for VWF:Ag 18 IU/dL (95%CI 15-20) and for FVIII:C 12 IU/dL (95%CI 10-14). After adjustment for acquired factors, the increase per decade was 13 IU/dL (95%CI 10-16) for VWF:Ag and 9 IU/dL (95%CI 6-11) for FVIII:C. The stratified analysis for blood group showed higher increase in the non-O group, but these differences were annulled after adjustment for acquired factors. CONCLUSIONS: VWF:Ag and FVIII:C increase with age. Carriers of blood group non-O present a steeper increase of VWF:Ag and FVIII:C with age, that is mediated by acquired factors.
Authors: Juliana Lago; Helena Groot; Diego Navas; Paula Lago; María Gamboa; Dayana Calderón; Diana C Polanía-Villanueva Journal: Genes (Basel) Date: 2021-11-18 Impact factor: 4.096
Authors: Sriram Krishnaswamy; Walter Ageno; Yaseen Arabi; Tiziano Barbui; Suzanne Cannegieter; Marc Carrier; Audrey C Cleuren; Peter Collins; Laurence Panicot-Dubois; Jane E Freedman; Kathleen Freson; Philip Hogg; Andra H James; Colin A Kretz; Michelle Lavin; Frank W G Leebeek; Weikai Li; Coen Maas; Kellie Machlus; Michael Makris; Ida Martinelli; Leonid Medved; Marguerite Neerman-Arbez; James S O'Donnell; Jamie O'Sullivan; Madhvi Rajpurkar; Verena Schroeder; Paul Clinton Spiegel; Simon J Stanworth; Laura Green; Anetta Undas Journal: Res Pract Thromb Haemost Date: 2021-07-16