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A NEW (I1372S) MUTATION IN THE A1 DOMAIN OF VON WILLEBRAND FACTOR ASSOCIATED WITH A TYPE 2B-LIKE VON WILLEBRAND DISEASE PHENOTYPE
Abstract number: P-W-172
Sartorello1 F., Pontara1 E., Gallinaro1 L., Cattini1 M., Bertomoro1 A., Sztukowska1 M., Pagnan1 A., Casonato1 A.
1Department of Medical and Surgical Sciences, University of Padua, Padua, Italy
How-to-cite Sartorello F, Pontara E, Gallinaro L, Cattini M, Bertomoro A, Sztukowska M, Pagnan A, Casonato A. A NEW (I1372S) MUTATION IN THE A1 DOMAIN OF VON WILLEBRAND FACTOR ASSOCIATED WITH A TYPE 2B-LIKE VON WILLEBRAND DISEASE PHENOTYPE. J Thromb Haemost 2007; 5 Supplement 2: P-W-172
Abstract
Introduction: 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).
Methods: We report a new VWF abnormality associated with increased VWF-GPIb interaction in the presence of all VWF multimers.
Results: The index case, a women with a lifelong history of bleeding showed hyperesponsiveness to ristocetin, with platelet aggregation up to 0.45 mg/mL ristocetin (normal 1.0 mg/mL or more) and spontaneous platelet aggregation (SPA) (10% vs normally absent). She had normal factor VIII, VWF:Ag, VWF:RCo and VWF:CB levels, with normal VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios, suggesting that large VWF multimers were normally represented. This was confirmed by the finding a full panel of plasma and platelet VWF multimers. A missense mutation (4115T>G) was found in the exon 28 of VWF gene, which changed a histidine 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 organization was capable of inducing SPA on normal platelet-rich plasma, unlike wild-type VWF, as well as inducing a hyper-response to ristocetin in the same platelets (0.6 mg/mL ristocetin vs 1.2 of wild-type VWF).
Conclusions: The new I1372S VWF mutation, characterized by SPA and hyper-responsiveness to ristocetin therefore has some features of the type 2B VWD, but not the lack of large VWF multimers. That is why we defined this variant as type 2B-like VWD. Why I1372S VWF is associated with bleeding symptoms, in spite of normal VWF levels and multimer organization, remains to be seen.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
Session Details
| Date: |
01/08/2007
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| Time: |
00:00-00:00
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| Session name: |
XXIst ISTH Congress |
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| Location: |
Oxford, UK |
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