Mucosal Bleeding in a Newborn With Low Factor VIII Activity: An Unusual Combination of Type 2A and Type 2N von...

This case report describes a newborn male presenting with mucosal bleeding and low Factor VIII activity, ultimately diagnosed with a rare compound heterozygous form of von Willebrand Disease (VWD) involving both type 2A and type 2N variants through previously unknown pathogenic mutations.

A single patient case report.

Genetic testing revealed two heterozygous variants in the VWF gene c.2422_2424del [p.Cys808del] and c.2999A > G [p.Asp1000Gly]), previously described as variants of unknown significance, inherited in trans from each parent, resulting in a severe VWD phenotype marked by significantly reduced von Willebrand Factor (VWF) antigen, GpIbM activity, collagen binding, and FVIII activity. Laboratory analysis revealed abnormal VWF multimer patterns distinct from those of classic type 2A or 2N VWD. The patient was managed with emicizumab prophylaxis and intermittent antifibrinolytics.

This case highlights the diagnostic and therapeutic challenges of atypical VWD presentations influenced by novel genetic variants. These findings underscore the importance of comprehensive clinical, laboratory, and genetic evaluation in complex bleeding disorders.