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.

Central Laboratory Asklepios Kliniken Hamburg Germany

Department of Clinical Hematology University Hospital Masaryk University Brno Czech Republic 4 Faculty of Medicine Department of Laboratory Methods Masaryk University Brno Czech Republic

Department of Hemostasis and Thrombosis National Hemophilia Center Medical School of Comenius University Bratislava Slovakia

Goodheart Institute in Nature Medicine and Health Blood Coagulation and Vascular Medicine Center Rotterdam The Netherlands 2 Hemostasis Research Unit Department of Hematology Antwerp University Hospital Belgium

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

Hemostasis Research Unit Department of Hematology Antwerp University Hospital Belgium 8 Hemostasis Research Unit Antwerp University Hospital Antwerp Belgium

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