J Boender1, J Eikenboom2,3, J G van der Bom4,5, K Meijer6, J de Meris7, K Fijnvandraat8,9, M H Cnossen10, B A P Laros-van Gorkom11, W L van Heerde11, E P Mauser-Bunschoten12, M P M de Maat1, F W G Leebeek1. 1. Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands. 2. Internal Medicine, Division, Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands. 3. Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands. 4. Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. 5. Sanquin Research, Jon J van Rood Center for Clinical Transfusion Medicine, Leiden, the Netherlands. 6. Hematology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 7. Netherlands Hemophilia Society, Nijkerk, the Netherlands. 8. Pediatric Hematology, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands. 9. Department of Plasma Proteins, Sanquin Research, Amsterdam, the Netherlands. 10. Pediatric Hematology, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, the Netherlands. 11. Hematology, Radboud University Medical Center, Nijmegen, the Netherlands. 12. University Medical Center Utrecht, van Creveld Kliniek, University Utrecht, Utrecht, the Netherlands.
Abstract
Essentials It is unclear whether there are differences between von Willebrand factor (VWF) activity assays. We compared the four most used VWF activity assays in 661 von Willebrand disease (VWD) patients. All assays correlated excellently, but a discrepant classification was seen in 20% of patients. Differences between VWF activity assays have a large impact on the classification of VWD. SUMMARY: Background Measuring the ability of von Willebrand factor (VWF) to bind to platelets is crucial for the diagnosis and classification of von Willebrand disease (VWD). Several assays that measure this VWF activity using different principles are available, but the clinical relevance of different assay principles is unclear. Objective To compare the four most widely used VWF activity assays in a large VWD patient population. Methods We measured VWF:RCo (ristocetin to activate VWF + whole platelets), VWF:GPIbR (ristocetin + platelet glycoprotein Ib receptor [GPIb] fragments), VWF:GPIbM (gain-of-function GPIb fragments that bind VWF spontaneously without ristocetin) and VWF:Ab (monoclonal antibody directed against the GPIb binding epitope of VWF to mimic platelets) in 661 VWD patients from the nationwide 'Willebrand in the Netherlands' (WiN) Study. Results All assays correlated excellently (Pearson r > 0.9), but discrepant results led to a different classification for up to one-fifth of VWD patients. VWF:RCo was not sensitive enough to classify 18% of patients and misclassified half of genotypic 2B VWD patients, especially those with p.Arg1306Trp. VWF:GPIbR was more sensitive, accurately classified the vast majority of patients, and was unaffected by the p.Asp1472His variant that causes artificially low VWF:RCo. VWF:GPIbM was the most precise assay but misclassified over a quarter of genotypic 2A, 2B and 3 patients. VWF:Ab, often not considered an actual VWF activity assay, performed at least equally to the other assays with regard to accurate VWD classification. Conclusion Although the different VWF activity assays are often considered similar, differences between assays have a large impact on the classification of VWD.
Essentials It is unclear whether there are differences between von Willebrand factor (VWF) activity assays. We compared the four most used VWF activity assays in 661 von Willebrand disease (VWD) patients. All assays correlated excellently, but a discrepant classification was seen in 20% of patients. Differences between VWF activity assays have a large impact on the classification of VWD. SUMMARY: Background Measuring the ability of von Willebrand factor (VWF) to bind to platelets is crucial for the diagnosis and classification of von Willebrand disease (VWD). Several assays that measure this VWF activity using different principles are available, but the clinical relevance of different assay principles is unclear. Objective To compare the four most widely used VWF activity assays in a large VWDpatient population. Methods We measured VWF:RCo (ristocetin to activate VWF + whole platelets), VWF:GPIbR (ristocetin + platelet glycoprotein Ib receptor [GPIb] fragments), VWF:GPIbM (gain-of-function GPIb fragments that bind VWF spontaneously without ristocetin) and VWF:Ab (monoclonal antibody directed against the GPIb binding epitope of VWF to mimic platelets) in 661 VWDpatients from the nationwide 'Willebrand in the Netherlands' (WiN) Study. Results All assays correlated excellently (Pearson r > 0.9), but discrepant results led to a different classification for up to one-fifth of VWDpatients. VWF:RCo was not sensitive enough to classify 18% of patients and misclassified half of genotypic 2B VWDpatients, especially those with p.Arg1306Trp. VWF:GPIbR was more sensitive, accurately classified the vast majority of patients, and was unaffected by the p.Asp1472His variant that causes artificially low VWF:RCo. VWF:GPIbM was the most precise assay but misclassified over a quarter of genotypic 2A, 2B and 3 patients. VWF:Ab, often not considered an actual VWF activity assay, performed at least equally to the other assays with regard to accurate VWD classification. Conclusion Although the different VWF activity assays are often considered similar, differences between assays have a large impact on the classification of VWD.
Authors: Ferdows Atiq; Lisette M Schütte; Agnes E M Looijen; Johan Boender; Marjon H Cnossen; Jeroen Eikenboom; Moniek P M de Maat; Marieke J H A Kruip; Frank W G Leebeek Journal: Blood Adv Date: 2019-12-23
Authors: Paula D James; Nathan T Connell; Barbara Ameer; Jorge Di Paola; Jeroen Eikenboom; Nicolas Giraud; Sandra Haberichter; Vicki Jacobs-Pratt; Barbara Konkle; Claire McLintock; Simon McRae; Robert R Montgomery; James S O'Donnell; Nikole Scappe; Robert Sidonio; Veronica H Flood; Nedaa Husainat; Mohamad A Kalot; Reem A Mustafa Journal: Blood Adv Date: 2021-01-12
Authors: Johan Boender; Angelique Nederlof; Karina Meijer; Evelien P Mauser-Bunschoten; Marjon H Cnossen; Karin Fijnvandraat; Johanna G van der Bom; Joke de Meris; Britta A P Laros-van Gorkom; Karin P M van Galen; Jeroen Eikenboom; Moniek P M de Maat; Frank W G Leebeek Journal: Res Pract Thromb Haemost Date: 2020-10-31
Authors: Johan Boender; Ferdows Atiq; Marjon H Cnossen; Johanna G van der Bom; Karin Fijnvandraat; Joke de Meris; Moniek P M de Maat; Karin P M van Galen; Britta A P Laros-van Gorkom; Karina Meijer; Jeroen Eikenboom; Frank W G Leebeek Journal: Hemasphere Date: 2021-02-17