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Von Willebrand Factor Neutralizing and Non-Neutralizing Alloantibodies in 213 Subjects With Type 3 Von Willebrand Disease Enrolled in 3Winters-Ips Publisher Pubmed



Pagliari MT1 ; Budde U2 ; Baronciani L1 ; Eshghi P3 ; Ahmadinejad M3, 4 ; Badiee Z5 ; Baghaipour MR6 ; Hidalgo OB7 ; Biguzzi E1 ; Bodo I8 ; Castaman G9 ; Goudemand J10 ; Karimi M11 ; Keikhaei B12 Show All Authors
Authors
  1. Pagliari MT1
  2. Budde U2
  3. Baronciani L1
  4. Eshghi P3
  5. Ahmadinejad M3, 4
  6. Badiee Z5
  7. Baghaipour MR6
  8. Hidalgo OB7
  9. Biguzzi E1
  10. Bodo I8
  11. Castaman G9
  12. Goudemand J10
  13. Karimi M11
  14. Keikhaei B12
  15. Lassila R13
  16. Leebeek FWG14
  17. Lopez Fernandez MF15
  18. Marino R16
  19. Oldenburg J17
  20. Peake I18
  21. Santoro C19
  22. Schneppenheim R20
  23. Tiede A21
  24. Toogeh G22
  25. Tosetto A23
  26. Trossaert M24
  27. Yadegari H17
  28. Zetterberg EMK25
  29. Mannucci PM1
  30. Federici AB26
  31. Eikenboom J27
  32. Peyvandi F1, 28
Show Affiliations
Authors Affiliations
  1. 1. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
  2. 2. Hemostaseology Medilys Laborgesellschaft mbH, Hamburg, Germany
  3. 3. Pediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
  5. 5. Hemophilia-Thalassemia Center, Mashhad University of Medical Science, Mashad, Iran
  6. 6. Iranian Hemophilia Comprehensive Treatment Centre, Tehran, Iran
  7. 7. Hemophilia Unit, Hematology Department, Hospital Universitari Vall d'Hebron, Spain
  8. 8. Department of Internal Medicine and Hematology – Semmelweis University, Budapest, Hungary
  9. 9. Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy
  10. 10. Department of Hematology and Transfusion, University of Lille, CHU Lille, Lille, France
  11. 11. Hematology Research Center, Nemazee Hospital, Shiraz University of Medical Science, Shiraz, Iran
  12. 12. Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur, University of Medical Sciences, Ahvaz, Iran
  13. 13. Research Program Unit in Oncology, University of Helsinki, Helsinki University Central Hospital, Coagulation disorders, Helsinki, Finland
  14. 14. Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
  15. 15. Complejo Hospitalario Universitario de A Coruna - Servicio de Hematologia y Hemoterapia, A Coruna, Spain
  16. 16. Hemophilia and Thrombosis Centre, University Hospital Policlinico, Bari, Italy
  17. 17. Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany
  18. 18. Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, United Kingdom
  19. 19. Hematology, Hemophilia and Thrombosis Center, University Hospital Policlinico Umberto I, Rome, Italy
  20. 20. Department of Pediatric Hematology and Oncology, University Medical Centre, Hamburg-Eppendorf, Hamburg, Germany
  21. 21. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
  22. 22. Thrombosis Hemostasis Research Center, Tehran University of Medical Sciences, Tehran, Iran
  23. 23. Hemophilia and Thrombosis Center, Hematology Department, San Bortolo Hospital, Vicenza, Italy
  24. 24. Centre Regional de Traitement de l'Hemophilie – Laboratoire d'Hematologie, Nantes, France
  25. 25. Skane University Hospital, Malmo, Sweden
  26. 26. Department of Oncology and Oncohematology, Hematology and Transfusion Medicine, L. Sacco University Hospital, University of Milan, Milan, Italy
  27. 27. Department of Internal Medicine, Division of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, Netherlands
  28. 28. Department of Pathophysiology and Transplantation, Universita degli Studi di Milano, Milan, Italy

Source: Journal of Thrombosis and Haemostasis Published:2023


Abstract

Background: Type 3 von Willebrand disease (VWD) is the most severe form of this disease owing to the almost complete deficiency of von Willebrand factor (VWF). Replacement therapy with plasma-derived products containing VWF or recombinant VWF rarely cause the development of alloantibodies against VWF that may be accompanied by anaphylactic reactions. Objective: The objective of this study was to assess the prevalence of anti-VWF alloantibodies in subjects with type 3 VWD enrolled in the 3WINTERS-IPS. Methods: An indirect in-house enzyme-linked immunosorbent assay has been used to test all the alloantibodies against VWF. Neutralizing antibodies (inhibitors) have been tested with a Bethesda-based method by using a VWF collagen binding (VWF:CB) assay. Samples positive for anti-VWF antibodies were further tested with Bethesda-based methods by using the semiautomated gain-of-function glycoprotein-Ib binding (VWF:GPIbM) and a VWF antigen (VWF:Ag) enzyme-linked immunosorbent assay. Results: In total, 18 of the 213 (8.4%) subjects tested positive for anti-VWF antibodies and 13 of 213 (6%) had VWF:CB inhibitors. These 13 were among the 18 with anti-VWF antibodies. Of the 5 without VWF:CB inhibitors, 3 had non-neutralizing antibodies, 1 only inhibitor against VWF:GPIbM, and one could not be tested further. Ten of the 13 subjects with VWF:CB inhibitors also had VWF:GPIbM inhibitors, 6 of whom also had VWF:Ag inhibitors. Subjects with inhibitors were homozygous for VWF null alleles (11/14), homozygous for a missense variant (1/14), or partially characterized (2/14). Conclusions: Anti-VWF antibodies were found in 8.4% of subjects with type 3 VWD, whereas neutralizing VWF inhibitors were found in 6%, mainly in subjects homozygous for VWF null alleles. Because inhibitors may be directed toward different VWF epitopes, their detection is dependent on the assay used. © 2023 International Society on Thrombosis and Haemostasis
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