Type 2M-C von Willebrand disease: a fugitive diagnosis. About a case.

Abstract

The type 2M-C von Willebrand disease (VWD2M-C) is characterized by a decreased VWF:CB but normal VWF and VWF:RCo levels. This defect is caused by disease-causing variants (DCVs) at the A3 domain of VWF affecting VWF-collagen binding. We describe the phenotypic and genotypic findings in a 60-year-old male with laboratory results suggestive of VWD2 presenting an ISTH-BAT of 5, without family bleeding history.Methods. Hemostatic assessment was performed including PFA-200 closure time (CT), FVIII, VWF:Ag, VWF:RCo, VWF:GPIbR, VWF:CB1, VWF:CB3, VWF multimers, platelet functional studies (lumi-aggregometry, mepacrine uptake), and genetic studies of VWF-A1, A2 and A3-domains. Results. First study: the patient presented PFA200CT extremely prolonged with Col/Epi cartridge and slightly prolonged Col/ADP one, and abnormal VWF:GPIbR/VWF:Ag ratio. Second study: the patient showed normal VWF:Ag, VWF:RCo and VWF multimers, but low VWF:CB1 and VWF:CB3 levels. The lumi-aggregometric studies showed normal ristocetin (RIPA, standard and low concentrations), arachidonic acid and collagen induced platelet aggregation; absence of the second wave and ATP release under ADP and epinephrine timulation, and normal content of platelets’ dense granules. By genetic studies, the missense change c.5191T>A → p.Ser1731Thr in exon 30 (A3-domain) was identified in heterozygous state. The patient was diagnosed as VWD2M-C. Conclusion. In our patient, p.Ser1731Thr seemed to be responsible for the abnormal PFA-200CT. Since the VWF:RCo and VWF:GPIbR measure the VWF-platelet interaction, while the VWF:CB, the VWF-collagen interaction, it is of utmost importance to perform both assays types to overcome the potential lack of VWD2M-C patients' diagnosis.