A novel von Willebrand factor mutation (I1372S) associated with type 2B-like von Willebrand disease: an elusive phenotype and a difficult diagnosis.
Thromb Haemost
; 98(6): 1182-7, 2007 Dec.
Article
em En
| MEDLINE
| ID: mdl-18064311
ABSTRACT
Mutations in the A1 domain of von Willebrand factor (VWF) may be associated with gain of function in the VWF-platelet GPIb interaction and consumption of large VWF multimers, as seen in type 2B von Willebrand disease (VWD). We report a new VWF abnormality associated with greater VWF-GPIb interaction in the presence of all VWF multimers. The index case is a woman with a lifelong history of bleeding, found hyperresponsive to ristocetin with spontaneous platelet aggregation (SPA). She had normal factor VIII, VWFAg, VWFRCo and VWFCB levels, normal VWFRCo/VWFAg and VWFCB/VWFAg ratios, and a full panel of plasma and platelet VWF multimers. A missense mutation (4115T>G) was found in exon 28 of the VWF gene, which replaced a isoleucine with a serine at position 1372 of pre-pro-VWF (I1372S) at heterozygous level. Recombinant VWF carrying the I1372S mutation and showing a normal VWF multimer organisation was capable of inducing SPA on normal platelet-rich plasma (unlike wild-type VWF), as well as a hyper-response to ristocetin in the same platelets (0.6 mg/ml ristocetin vs. 1.2 of wild-type VWF). The new I1372S VWF mutation, characterized by SPA and hyper-responsiveness to ristocetin thus has some of the features of type 2B VWD, but not the lack of large VWF multimers, so we defined this variant as type 2B-like VWD. Why I1372S VWF is associated with bleeding symptoms, despite normal VWF levels and multimer organisation, remains to be seen.
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Base de dados:
MEDLINE
Assunto principal:
Doenças de von Willebrand
/
Plaquetas
/
Fator de von Willebrand
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Agregação Plaquetária
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Complexo Glicoproteico GPIb-IX de Plaquetas
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Mutação de Sentido Incorreto
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Hemorragia
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article