Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor


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    The Working Party on von Willebrand Disease Classification is part of the von Willebrand Disease Subcommittee of the Scientific and Standardization Committee of the ISTH.

J. Evan Sadler, Howard Hughes Medical Institute, Washington University School of Medicine, 660 South Euclid Avenue, Box 8022, St Louis, MO 63110, USA.
Tel.: +1 314 362 9029; fax: +1 314 454 3012; e-mail: esadler@im.wustl.edu


Summary.  von Willebrand disease (VWD) is a bleeding disorder caused by inherited defects in the concentration, structure, or function of von Willebrand factor (VWF). VWD is classified into three primary categories. Type 1 includes partial quantitative deficiency, type 2 includes qualitative defects, and type 3 includes virtually complete deficiency of VWF. VWD type 2 is divided into four secondary categories. Type 2A includes variants with decreased platelet adhesion caused by selective deficiency of high-molecular-weight VWF multimers. Type 2B includes variants with increased affinity for platelet glycoprotein Ib. Type 2M includes variants with markedly defective platelet adhesion despite a relatively normal size distribution of VWF multimers. Type 2N includes variants with markedly decreased affinity for factor VIII. These six categories of VWD correlate with important clinical features and therapeutic requirements. Some VWF gene mutations, alone or in combination, have complex effects and give rise to mixed VWD phenotypes. Certain VWD types, especially type 1 and type 2A, encompass several pathophysiologic mechanisms that sometimes can be distinguished by appropriate laboratory studies. The clinical significance of this heterogeneity is under investigation, which may support further subdivision of VWD type 1 or type 2A in the future.