title: Factor VIII-von Willebrand factor binding defects in autosomal recessive von Willebrand disease type Normandy and in mild hemophilia A. New insights into factor VIII-von Willebrand factor interactions.
abstract: This concise review is focused on genetic, molecular and clinical aspects of von Willebrand disease (VWD) type 2N and of mild hemophilia A due to mutations impairing FVIII-von Willebrand factor (VWF) interactions. Missense mutations in the VWF gene impairing the binding to FVIII do not impair the structure of VWF multimers nor the ability of VWF to aggregate platelets but causes an accelerated clearance of FVIII. Missense mutations in the FVIII gene impairing the binding to VWF are a common cause of mild/moderate hemophilia A. The implications of these observations for the treatment of patients with coagulation factor concentrates and desmopressin are discussed.
authors.affiliation: Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O & N, Herestraat 49, Leuven, Belgium. marc.jacquemin@med.kuleuven.ac.be
authors.forename: Marc
authors.initials: M
authors.lastname: Jacquemin
mesh_terms: D001665:Binding Sites; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D042783:Endothelial Cells / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism*; D005808:Genes, Recessive; D006467:Hemophilia A / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000378:metabolism; D008657:Metabolic Clearance Rate; D020125:Mutation, Missense; D017354:Point Mutation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D014842:von Willebrand Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor; C069815:von Willebrand factor Normandy; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin