| 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. | | Author(s) | Gadisseur A, van der Planken M, Schroyens W, Berneman Z, Michiels JJ | | Institution | Hemostasis Unit, Department of Hematology, Antwerp University Hospital, Edegem, Belgium. | | Source | Acta Haematol 2009; 121(2-3):145-153. | | 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)]. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19506361 |
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