Type 3 von Willebrand disease mistaken for moderate haemophilia A: a lesson still to be learned

Galletta, Eva; Daidone, Viviana; Zanon, Ezio; Casonato, Sandra

doi:10.1111/hae.13490

Cited by 2 publications

(2 citation statements)

References 14 publications

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“…A different contribution of aberrant VWF mRNAs in endothelial cells and platelets is less plausible, but mRNAs in endothelial cells would need to be explored to say for sure. (42), or its levels only being reduced (43). In our patient, the two new acceptor sites activated due to the mutation are one a canonical "AG", and the other an unusual "CG" acceptor splicing site, respectively generating RNAII and RNAIII.…”

Section: Discussionmentioning

confidence: 61%

Cryptic non-canonical splice site activation is part of the mechanism that abolishes multimer organization in the c.2269_2270del von Willebrand factor

et al. 2019

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Section: Discussionmentioning

confidence: 61%

Cryptic non-canonical splice site activation is part of the mechanism that abolishes multimer organization in the c.2269_2270del von Willebrand factor

et al. 2019

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“…This means that establishing a diagnosis of type 2N VWD includes differentiating it from hemophilia A, and there have been numerous reports of patients with type 2N VWD being misdiagnosed as cases of hemophilia A. 22,23 Diagnosing type 2N VWD necessitates measuring the exogenous FVIII-binding capacity of a patient's VWF in vitro. The method currently employed is the VWF:FVIIIB test, using exogenous recombinant FVIII (rFVIII).…”

Section: Introductionmentioning

confidence: 99%

The Lesson Learned from the New c.2547-1G > T Mutation Combined with p.R854Q: When a Type 2N Mutation Reveals a Quantitative von Willebrand Factor Defect

et al. 2022

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Type 2N is a rare von Willebrand disease (VWD) variant involving an impairment in the FVIII carrier function of von Willebrand factor (VWF). It has a phenotype that mimics hemophilia A, and FVIII binding to VWF (VWF:FVIIIB) is tested to differentiate between the two disorders. Type 2N VWF defects may also be associated with quantitative VWF mutations (type 2N/type 1), further complicating the identification of cases. We report on a new quantitative VWF mutation (c.2547-1G>T) revealed by a p.R854Q type 2N mutation acting as homozygous despite being carried as a heterozygous defect. The proband had near-normal VWF levels (initially ruling out a defective VWF synthesis) and slightly reduced FVIII levels, while a VWF:FVIIIB test showed significantly reduced binding. Routine tests on type 2N homozygotes or heterozygotes combined with quantitative VWF defects in our cohort showed reduced FVIII levels in both groups, but it was only in the former that the FVIII/VWF:Ag ratio was always significantly reduced. The two tests are therefore not enough to identify all forms of type 2N VWD. While relatives of type 2N homozygotes usually have normal FVIII levels and FVIII/VWF:Ag ratios, relatives of type 2N/type 1 may have high FVIII/VWF:Ag ratios, but their VWF:FVIIIB and/or VWF:FVIIIB/VWF:Ag ratios are always low. Measuring FVIII and VWF levels may therefore suggest type 2N VWD in patients carrying type 2N mutations alone, but not in type 2N combined with quantitative VWF defects. The VWF:FVIIIB test should consequently always be included when exploring VWF function, whatever VWD patient’s phenotype.

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Type 3 von Willebrand disease mistaken for moderate haemophilia A: a lesson still to be learned

Cited by 2 publications

References 14 publications

Cryptic non-canonical splice site activation is part of the mechanism that abolishes multimer organization in the c.2269_2270del von Willebrand factor

Cryptic non-canonical splice site activation is part of the mechanism that abolishes multimer organization in the c.2269_2270del von Willebrand factor

The Lesson Learned from the New c.2547-1G > T Mutation Combined with p.R854Q: When a Type 2N Mutation Reveals a Quantitative von Willebrand Factor Defect

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