A case report of type 2M Von Willebrand disease with unique mutations

Abstract

Abstract Von Willebrand disease (vWD) is the most common inherited bleeding disorder. It results from quantitative or qualitative defects of the von Willebrand factor (vWF) protein, and is divided into three types, namely type 1, type 2(2A, 2B, 2M, and 2N), and type 3 vWD. Here we report a case of 55-year-old female who presented with recurrent gastrointestinal bleeding due to angiodysplasia. Her past medical history is significant for vWD (type unknown) with hemoptysis, epistaxis and menorrhagia requiring Humate-P replacement multiple times. She has one sister with mild vWD of unknown type and 4 other siblings with no bleeding history. Coagulation testing shows normal PT and aPTT. Von Willebrand panel shows vWF antigen of 33%, VWF ristocetin cofactor activity of 15%, and Factor VIII of 87%. The ratio (VWF: RCo/VWF: Ag) is low (0.45) and the multimer pattern is normal. This is consistent with type 2M vWD. VWD gene sequencing shows heterozygous variants of c.4241T>G (p.Val1414Gly) and c.5227G>A (p.Val1743Met). Of note, one variant (c.4241T>G/p.Val1414Gly) has been reported in two individuals with type 2A but not in type 2M vWD. This may truly represent different types of vWD caused by same mutation or could be due to variation in testing and/or result interpretation among laboratories. The other variant c.5227G>A(p.Val1743Met) in A3 domain has never been reported with uncertain significance. Further investigation including vWF panel testing and genetic analysis in family members would help characterize those mutations.