Abstract Number: PB0330
Meeting: ISTH 2021 Congress
Background: The diagnosis of von Willebrand disease (VWD) relies on measurements of von Willebrand factor antigen (VWF:Ag) and functional activity (VWF:Act). Measuring VWF:Act is based on the quantification of VWF binding to platelets through GpIbα, with or without using ristocetin. Some polymorphisms are known to cause discordances between the different techniques, as the variant D1472H that falsely decreases the ristocetin cofactor activity (VWF:Rco) by interacting with ristocetin.
Aims: To identify if other variants located in the A1 domain of VWF (containing the binding sites for GpIbα) can interfere with the different techniques for measuring VWF:Act.
Methods: After being notified that 2 VWD type 2M patients (one carrying E1359K and the other one V1360A) completely normalized their ratios measured with the Acustar® VWF:GpIbR assay (using ristocetin) comparing to the VWF:Rco agregometry technique, we decided to retest all the patients from the database of the French VWD Reference Center presenting the same variants. We tested in total 15 patients with the Acustar® assay and the Innovance® VWF:GpIbM assay (no ristocetin).
Results: All the 15 patients have a low ratio with the Innovance® assay (mean = 0.20, interval range = <0.1–0.37). Among them, 11 have a completely normal ratio with the Acustar® assay (mean = 0.86 interval range = 0.70–1.21). Two patients have a very low ratio (<0.1) with the 2 techniques including one who also has a VWD type 3 variant. The variants E1359K and V1360A, localized in the A1 domain, might interfere with the Acustar® assay, either with the ristocetin or with the chemiluminescence detection, rendering it insensitive to the binding defect.
Conclusions: This study is another proof about the complexity to measure VWF:Act and to choose the right technique. Due to their VWF genetics, the diagnosis of VWD for these patients could have been missed if only the Acustar® assay has been performed.
To cite this abstract in AMA style:Lassalle F, Jeanpierre E, Zawadzki C, Pouymayou C, Castet S, Huguenin Y, Marlu R, Voyer A, Chamouni P, Goudemand J, Susen S. Risk of Misdiagnosis for Patients Presenting the Closed Variants E1359K or V1360A in Exon 28 of VWF due to a Major Discordance on VWF Activity Results between the VWF:GpIbM and VWF:GpIbR Assays [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/risk-of-misdiagnosis-for-patients-presenting-the-closed-variants-e1359k-or-v1360a-in-exon-28-of-vwf-due-to-a-major-discordance-on-vwf-activity-results-between-the-vwfgpibm-and-vwfgpibr-assays/. Accessed September 24, 2021.
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