Diagnostic challenges in von Willebrand disease. Report of two cases with emphasis on multimeric and molecular analysis

Abstract

Identification of qualitative variants of von Willebrand disease (VWD) can be a diagnostic challenge because of discrepant results obtained in the multiple laboratory tests available for its appropriate classification. We report two cases of infrequent inherited variants of VWD with unclear preliminary results with the test panel available at the time of first consultation and that were finally diagnosed as a VWD type 2A/IID with a c.8318 G > C, p.Cys2773Ser mutation and a VWD type 2M with c.4225 T > G, p.Val1409Phe mutation, respectively. The description of these two cases highlights that despite the limited diagnostic panel for the evaluation of von Willebrand Factor (VWF) functionality, the multimeric analysis and genetic family studies were fundamental tools to achieve the final diagnosis.

Keywords:

• 2A IID
• 2M
• von Willebrand disease

Aknowledgements

Dr. Javier Batlle from Complexo Hospitalario Universitario a Coruña, INIBIC (Spain), who performed the multimeric analysis from case 1.

Conflicts of Interest Disclosure

The authors declare no conflicts of interest.

Author Contributions

ABM analyzed the results and wrote the manuscript. AR, MP, and ST conducted the laboratory analysis and data transcription. FV, IC, NB, and RP performed the molecular analysis and designed the images. MPa reviewed the manuscript. CA, GE, and MD supervised the work and reviewed the results and the manuscript.

Additional information

Funding

This work was partially granted by Instituto de Salud Carlos III, Spanish Government (PIE15/00027, DTS16/00133, FIS PI19/00888 ISCIII) and Generalitat de Catalunya (2017-SGR675, CERCA Programme).