Laboratory Variability in the Diagnosis of Type 2 VWD Variants.

INTRODUCTION Type 2 von Willebrand disease (VWD) refers to patients with a qualitative defect in von Willebrand factor (VWF). Accurate diagnosis of type 2 VWD subtypes can be challenging. AIM OF THE STUDY to compare the historical diagnosis of type 2 VWD with current laboratory testing. METHODS Subjects were enrolled in the Zimmerman Program either due to a pre-existing diagnosis of VWD (retrospective cohort) or due to evaluation for bleeding symptoms or suspected VWD (prospective cohort). Original diagnosis was assigned by the local center and central diagnosis was based on central laboratory testing. RESULTS 217 index cases in the retrospective cohort and 35 subjects in the prospective cohort carried a local diagnosis of type 2 VWD (29% and 6% of enrolled index cases respectively). In the retrospective cohort, the diagnosis was confirmed in 66% of cases with a pre-existing diagnosis of 2A, 77% 2B, 54% 2M, and 72% 2N. In the prospective cohort, 31% were confirmed 2A, 60% 2B, 23% 2M, and 100% 2N. Several genetic variants were repeatedly implicated in subjects with changed diagnosis: p.M1304R, p.R1315C, p.R1374C, and p.R1374H. CONCLUSIONS Both the prospective and retrospective cohorts demonstrated consistent variation in subjects whose diagnosis changed between 2A, 2B, and 2M. The importance of accurately diagnosing type 2 VWD may be most significant in the 2B subtype given potential concerns with the use of desmopressin in type 2B VWD. Some genetic variants appear in multiple types of VWD, making specific diagnoses challenging.