title: Dominant von Willebrand disease type 2M and 2U are variable expressions of one distinct disease entity caused by loss-of-function mutations in the A1 domain of the von Willebrand factor gene.
abstract: A complete set of laboratory investigations, including bleeding time, PFA-100 closure time, factor VIII coagulant activity (FVIII:C), von Willebrand factor (VWF) ristocetin cofactor activity (RCo), collagen binding (CB) and antigen concentration (Ag), ristocetin-induced platelet aggregation (RIPA) and multimeric analysis of VWF in low and medium SDS-agarose resolution gels, is warranted to diagnose and classify all variants of von Willebrand disease (VWD). VWD type 2M and 2U are typically characterized by decreased RIPA and a poor response of VWF:RCo to desmopressin (DDAVP), but normal VWF:CB and good responses of VWF:CB, VWF:Ag and FVIII:C to DDAVP. VWF multimeric analysis in patients with VWD 2M and 2U show relative decreases in large VWF multimers with less resolved triplet structure of each of the multimeric bands in low-, medium- or high-resolution gels. VWD type 2M or 2U are caused by a loss-of-function mutation in the A1 domain. The laboratory manifestations and molecular defects in the A1 domain causing VWD type 2M and 2U are clearly distinct from all variants of type 1 VWD and also from all other variants [VWD type 2A, 2B, 2E (IIE) and 2C (IIC)].
authors.affiliation: Hemostasis and Thrombosis Research Center, Antwerp University Hospital, Wilrijkstraat 10, Edegem, Belgium. alain.gadisseur@uza.be
authors.forename: Alain
authors.initials: A
authors.lastname: Gadisseur
authors.forename: Marc
authors.initials: M
authors.lastname: van der Planken
authors.forename: Wilfried
authors.initials: W
authors.lastname: Schroyens
authors.forename: Zwi
authors.initials: Z
authors.lastname: Berneman
authors.forename: Jan Jacques
authors.initials: JJ
authors.lastname: Michiels
mesh_terms: D001760:Bleeding Time; D001797:Blood Protein Electrophoresis; D003094:Collagen / Q000378:metabolism; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005091:Exons / Q000235:genetics; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D008958:Models, Molecular; D008970:Molecular Weight; D020125:Mutation, Missense; D010974:Platelet Aggregation / Q000187:drug effects; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012310:Ristocetin / Q000494:pharmacology; D014842:von Willebrand Diseases / Q000145:classification / Q000188:drug therapy / Q000235:genetics*; D014841:von Willebrand Factor / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
chemical_list: D014841:von Willebrand Factor; D012310:Ristocetin; D003094:Collagen; D003894:Deamino Arginine Vasopressin