Attila Szederjesi1, Luciano Baronciani2, Ulrich Budde3, Giancarlo Castaman4, Paola Colpani2, Andrew S Lawrie5, Yuan Liu6, Robert Montgomery7, Flora Peyvandi2,8, Reinhard Schneppenheim9, Jürgen Patzke10, Imre Bodó1,6. 1. Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary. 2. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, A. Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy. 3. Laboratory of Hemostasis, Medilys Laboratory, Hamburg, Germany. 4. Center for Bleeding Disorders, Careggi University Hospital, Florence, Italy. 5. Haemostasis Research Unit, University College London, London, UK. 6. Winship Cancer Institute, Emory University, Atlanta, GA, USA. 7. MFRC, Medical College of Wisconsin, Milwaukee, WI, USA. 8. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy. 9. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 10. Department of Assay Development, Siemens Healthcare Diagnostics Products GmbH, Marburg, Germany.
Abstract
BACKGROUND: A number of new assays with different measuring principles are available to measure von Willebrand factor (VWF) glycoprotein Ib (GPIb)-binding activity, but little is known about how these assays might behave differently for subtypes of von Willebrand disease (VWD). OBJECTIVES: The Comparison of Assays to Measure VWF Activity (COMPASS-VWF) study was designed to compare all available VWF GPIb-binding activity assays for VWF. We specifically searched for particular assay behavior differences. PATIENTS/ METHODS: To sort out random differences from systematic assay behavior deviations, all assays were performed in different laboratories on the same samples in a blinded fashion. Samples from 53 normal controls and 42 well-characterized VWD patients were reanalyzed in this study to dissect assay-specific discrepancies. RESULTS: No assay behavior differences were found for 53 normal controls. For VWD patients, we found the following systematic assay behavior patterns: (a) All ELISA assays for VWF:GPIbR as well as VWF:GPIbM are insensitive to detect the low VWF activity of VWD type 2B patients with loss of high molecular weight multimers; (b) VWF:Ab assay reports higher activity for the p.V1665E mutation than all other assays; and (c) all ristocetin-based assays (including VWF:RCo using fixed platelets) but the AcuStar assay report discrepantly low VWF activity for the p.P1467S polymorphism. No systematic assay-specific difference was observed for either the particle agglutination VWF:GPIbM assay or the AcuStar assay using magnetic beads. CONCLUSIONS: Different assay principles may lead to discrepant results for certain VWD types or mutations. Therefore, a more extensive study for a large number of patients is needed to better characterize the incidence and relevance of such assay-specific differences.
BACKGROUND: A number of new assays with different measuring principles are available to measure von Willebrand factor (VWF) glycoprotein Ib (GPIb)-binding activity, but little is known about how these assays might behave differently for subtypes of von Willebrand disease (VWD). OBJECTIVES: The Comparison of Assays to Measure VWF Activity (COMPASS-VWF) study was designed to compare all available VWF GPIb-binding activity assays for VWF. We specifically searched for particular assay behavior differences. PATIENTS/ METHODS: To sort out random differences from systematic assay behavior deviations, all assays were performed in different laboratories on the same samples in a blinded fashion. Samples from 53 normal controls and 42 well-characterized VWDpatients were reanalyzed in this study to dissect assay-specific discrepancies. RESULTS: No assay behavior differences were found for 53 normal controls. For VWDpatients, we found the following systematic assay behavior patterns: (a) All ELISA assays for VWF:GPIbR as well as VWF:GPIbM are insensitive to detect the low VWF activity of VWD type 2B patients with loss of high molecular weight multimers; (b) VWF:Ab assay reports higher activity for the p.V1665E mutation than all other assays; and (c) all ristocetin-based assays (including VWF:RCo using fixed platelets) but the AcuStar assay report discrepantly low VWF activity for the p.P1467S polymorphism. No systematic assay-specific difference was observed for either the particle agglutination VWF:GPIbM assay or the AcuStar assay using magnetic beads. CONCLUSIONS: Different assay principles may lead to discrepant results for certain VWD types or mutations. Therefore, a more extensive study for a large number of patients is needed to better characterize the incidence and relevance of such assay-specific differences.
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