Frequency of type 2N von Willebrand disease among patients with mild or moderate factor VIII deficiency in an 18-month period in Iran

Abstract

Background - Type 2N von Willebrand disease (VWD) increases the clearance rate of factor VIII (FVIII) in patient’s plasma, leading to clinical symptoms and laboratory findings similar to those of mild or moderate hemophilia A. Differentiating between these conditions is crucial for genetic counseling and treatment. This research aims to use genetic analysis to distinguish type 2N VWD from mild or moderate FVIII deficiency.

Materials and methods - During 18 months, suspected type 2N patients with mild or moderate FVIII deficiency, were selected from those referred to the Iranian Blood Transfusion Organization (IBTO) coagulation laboratory. Exons 18, 19, and 20 of the VWF gene were sequenced using Sanger's method. Subsequently, sequenced data were analyzed using NCBI's BLAST database and Chromas Pro.

Results - In the current study of 35 participants with mild or moderate FVIII deficiency, 5 were found to have type 2N VWD mutations. The mutations detected were p.Arg816Gln (No.=3) and p.Thr789Pro (No.=2), which are common in Iran. Three patients were misdiagnosed with hemophilia A at a young age, while 2 were not diagnosed until later in life.

Discussion - The current study discovered that 14.2% of the participants carried known type 2N VWD mutations, a higher prevalence compared to previous studies using a similar approach. Additionally, the study indicated that the limited availability of accurate diagnostic tests for type 2N VWD in our country could lead to a high probability of misdiagnosing or underdiagnosing patients with this condition.