A-134 Assessment of vWF:Ac on improvement of VWD diagnostic workflow and characterization of VWD: a tertiary hospital experience

Abstract Background Measuring vWF platelet-dependent activity is crucial for initial diagnosing and managing VWD. While vWF:RCo has been the traditional standard for assessing vWF activity, it*s known for low sensitivity, high variability, and susceptibility to Ristocetin-binding polymorphisms. vWF:Gp1bM and vWF:Gp1bR are recommended by ISTH/ASH. We recently validated the Siemens vWF:Ac assay (vWF:Gp1bM) on Stago instruments and assessed its performance. The aim is to evaluate the impact of vWF:Ac on vWD laboratory workup, and its effect on the initial diagnosis and classification of VWD. Methods Data was collected from January-October 2024. Chart reviews documented patient race/ethnicity, history, multimer results, and genetic findings. A significant difference was defined as =25% (vWF:RCo =30%). A vWF activity-to-antigen ratio of 0.7 was used as the cutoff, potentially triggering further testing and aiding in differentiating VWD types. Results Patient population is predominantly Hispanic (Table1). Like African American, high percentage of Hispanics (52.87%) exhibit a significant difference between vWF:RCo and vWF:Gp1bM, with most showing a shift in the activity-to-antigen ratio from <0.7 to >0.7, primarily due to ristocetin-binding polymorphisms (e.g., D1472H). As a result, further multimer analysis and genetic testing have been reduced. vWF:Ac demonstrated high sensitivity and specificity in diagnosing and classifying VWD. Notably, five cases exhibited significantly higher vWF:Gp1bM than vWF:RCo without the D1472H polymorphism. Three of these cases carried the vWF c.3467C>T (p.Thr1156Met) variant, previously reported in type 1 VWD, while two had the c.7464C>T (p.Gly2488=) variant, associated with both type 1 and type 2M VWD. One patient with the c.7464C>T variant is currently receiving Humate-P therapy. While the discrepancy may be attributed to assay interference or other benign SNPs, these findings raise concerns that vWF:Gp1bM may yield artificially elevated results in specific vWF variants. Further investigation is warranted to elucidate the underlying mechanisms of these discrepancies. Conclusion To our best knowledge, this is the first report comparing vWF:RCo and vWF:Gp1bM in the Hispanic population, highlighting a high prevalence of ristocetin-binding polymorphism in Hispanics. Using vWF:Gp1bM instead of vWF:RCo helps reduce unnecessary follow-ups and overdiagnosis of VWD. Further research is needed to understand higher vWF:Gp1bM levels in cases with likely pathogenic variants but no D1472H.