title: Diagnostic Differentiation of von Willebrand Disease Types 1 and 2 by von Willebrand Factor Multimer Analysis and DDAVP Challenge Test.
abstract: The European Clinical Laboratory and Molecular (ECLM) classification of von Willebrand disease (vWD) is based on the splitting approach which uses sensitive and specific von Willebrand factor (vWF) assays with regard to the updated molecular data on structure and function of vWF gene and protein defects. A complete set of FVIII:C and vWF ristocetine cofactor, collagen binding, and antigen, vWF multimeric analysis in low- and medium-resolution gels, and responses to desmopressin (DDAVP) of FVIII:C and vWF parameters are mandatory. The ECLM classification distinguishes recessive types 1 and 3 vWD from recessive vWD 2C due to mutations in the D1 and D2 domains and vWD 2N due to mutations in the D'-FVIII-binding domain of vWF. The ECLM classification differentiates between mild vWD type 1 with variable penetrance of bleedings from symptomatic dominant type 1 vWD secretion defect and/or clearance defect with normal vWF multimers versus vWD 1M and 2M with normal or smeary vWF multimers in low- and medium-resolution gels. High-quality multimeric analysis of vWF in medium-resolution gels based on a DDAVP challenge test clearly delineates and distinguishes each of the dominant type 2 vWDs 1/2E, 2M, 2B, 2A, and 2D caused by vWF gene mutations in the D3 multimerization domain, loss or gain-of-function mutations in the glycoprotein Ib receptor A1 domain, gene mutations in the A2 proteolytic domain, and the C-terminal dimerization domain, respectively.
authors.affiliation: 1 Goodheart Institute in Nature Medicine & Health, Blood Coagulation and Vascular Medicine Center, Rotterdam, The Netherlands.|2 Hemostasis Research Unit, Department of Hematology, Antwerp University Hospital, Belgium.
authors.forename: Jan Jacques
authors.initials: JJ
authors.lastname: Michiels
authors.affiliation: 3 Department of Clinical Hematology, University Hospital, Masaryk University, Brno, Czech Republic.|4 Faculty of Medicine, Department of Laboratory Methods, Masaryk University, Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Smejkal
authors.affiliation: 3 Department of Clinical Hematology, University Hospital, Masaryk University, Brno, Czech Republic.|4 Faculty of Medicine, Department of Laboratory Methods, Masaryk University, Brno, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Penka
authors.affiliation: 5 Department of Hemostasis and Thrombosis, National Hemophilia Center, Medical School of Comenius University, Bratislava, Slovakia.
authors.forename: Angelika
authors.initials: A
authors.lastname: Batorova
authors.affiliation: 5 Department of Hemostasis and Thrombosis, National Hemophilia Center, Medical School of Comenius University, Bratislava, Slovakia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Pricangova
authors.affiliation: 6 Central Laboratory, Asklepios Kliniken, Hamburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Budde
authors.affiliation: 2 Hemostasis Research Unit, Department of Hematology, Antwerp University Hospital, Belgium.|8 Hemostasis Research Unit, Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: Vangenechten
authors.affiliation: 2 Hemostasis Research Unit, Department of Hematology, Antwerp University Hospital, Belgium.|7 Department of Hematology, Antwerp University Hospital, Antwerp, Belgium.|8 Hemostasis Research Unit, Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Gadisseur
mesh_terms: D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D003937:Diagnosis, Differential; D006801:Humans; D009154:Mutation; D055503:Protein Multimerization; D056725:von Willebrand Disease, Type 1 / Q000175:diagnosis*; D056728:von Willebrand Disease, Type 2 / Q000175:diagnosis*; D014841:von Willebrand Factor / Q000032:analysis* / Q000235:genetics
chemical_list: D014841:von Willebrand Factor; D003894:Deamino Arginine Vasopressin
keywords: ADAMTS13; DDAVP; von Willebrand disease; von Willebrand factor; von Willebrand factor assays; von Willebrand factor multimers; von Willebrand factor mutations