Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII
In 2018, Refacto AF R , a B-domain-deleted third-generation FVIII concentrate, became our preferential product. After the introduction, the development of inhibitors was prospectively monitored; retrospectively, we sought for risk factors in the patients who developed a de-novo inhibitor. Over a per...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-03-01
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| Series: | Clinical and Applied Thrombosis/Hemostasis |
| Online Access: | https://doi.org/10.1177/10760296231167416 |
| _version_ | 1827975698082430976 |
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| author | Louise H Hooimeijer MD Marjet A Stein-Wit MD Marja AJ Voskuilen RN Michaël V Lukens PhD Karina Meijer MD, PhD Anja BU Mäkelburg MD, PhD Rienk YJ Tamminga MD, PhD |
| author_facet | Louise H Hooimeijer MD Marjet A Stein-Wit MD Marja AJ Voskuilen RN Michaël V Lukens PhD Karina Meijer MD, PhD Anja BU Mäkelburg MD, PhD Rienk YJ Tamminga MD, PhD |
| author_sort | Louise H Hooimeijer MD |
| collection | DOAJ |
| description | In 2018, Refacto AF R , a B-domain-deleted third-generation FVIII concentrate, became our preferential product. After the introduction, the development of inhibitors was prospectively monitored; retrospectively, we sought for risk factors in the patients who developed a de-novo inhibitor. Over a period of 15 months, 4/19 adult patients with non-severe haemophilia who were treated on demand for surgery, developed high titer antibodies to FVIII after administration of Refacto AF R ; 5/52 mostly severe patients on prophylaxis, developed an inhibitor (3 ≥ 0.1 BU; 1 > 0.6 BU, 1 high titre) after they switched to Refacto AF R ; all were children <14 years of age and with >100 exposure days, none related to surgery or intensive treatment; all received Kovaltry R before. In conclusion: inhibitors were encountered in on demand patients and previously treated prophylaxis patients; this observation might be a coincidental finding, but also risk factors like genotype and surgery and/or that Refacto AF R is more immunogenic should be considered. For the patients on prophylaxis we hypothesize that loss of tolerance by preceding Kovaltry R might have contributed to inhibitor development. |
| first_indexed | 2024-04-09T20:14:28Z |
| format | Article |
| id | doaj.art-940ec3bfb93740f6aef3d62772b9fb28 |
| institution | Directory Open Access Journal |
| issn | 1938-2723 |
| language | English |
| last_indexed | 2024-04-09T20:14:28Z |
| publishDate | 2023-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Clinical and Applied Thrombosis/Hemostasis |
| spelling | doaj.art-940ec3bfb93740f6aef3d62772b9fb282023-03-31T10:33:59ZengSAGE PublishingClinical and Applied Thrombosis/Hemostasis1938-27232023-03-012910.1177/10760296231167416Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIIILouise H Hooimeijer MD0Marjet A Stein-Wit MD1Marja AJ Voskuilen RN2Michaël V Lukens PhD3Karina Meijer MD, PhD4Anja BU Mäkelburg MD, PhD5Rienk YJ Tamminga MD, PhD6 Pediatric Hematology, Beatrix Children's Hospital, Hemophilia Treatment Centre Groningen, , University of Groningen, Groningen, The Netherlands Pediatric Hematology, Beatrix Children's Hospital, Hemophilia Treatment Centre Groningen, , University of Groningen, Groningen, The Netherlands Division of Thrombosis and Hemostasis, Department of Hematology, Hemophilia Treatment Centre Groningen, , University of Groningen, Groningen, The Netherlands Laboratory Special Hematology, Department of Laboratory Medicine, Hemophilia Treatment Centre Groningen, , University of Groningen, Groningen, The Netherlands Division of Thrombosis and Hemostasis, Department of Hematology, Hemophilia Treatment Centre Groningen, , University of Groningen, Groningen, The Netherlands Division of Thrombosis and Hemostasis, Department of Hematology, Hemophilia Treatment Centre Groningen, , University of Groningen, Groningen, The Netherlands Pediatric Hematology, Beatrix Children's Hospital, Hemophilia Treatment Centre Groningen, , University of Groningen, Groningen, The NetherlandsIn 2018, Refacto AF R , a B-domain-deleted third-generation FVIII concentrate, became our preferential product. After the introduction, the development of inhibitors was prospectively monitored; retrospectively, we sought for risk factors in the patients who developed a de-novo inhibitor. Over a period of 15 months, 4/19 adult patients with non-severe haemophilia who were treated on demand for surgery, developed high titer antibodies to FVIII after administration of Refacto AF R ; 5/52 mostly severe patients on prophylaxis, developed an inhibitor (3 ≥ 0.1 BU; 1 > 0.6 BU, 1 high titre) after they switched to Refacto AF R ; all were children <14 years of age and with >100 exposure days, none related to surgery or intensive treatment; all received Kovaltry R before. In conclusion: inhibitors were encountered in on demand patients and previously treated prophylaxis patients; this observation might be a coincidental finding, but also risk factors like genotype and surgery and/or that Refacto AF R is more immunogenic should be considered. For the patients on prophylaxis we hypothesize that loss of tolerance by preceding Kovaltry R might have contributed to inhibitor development.https://doi.org/10.1177/10760296231167416 |
| spellingShingle | Louise H Hooimeijer MD Marjet A Stein-Wit MD Marja AJ Voskuilen RN Michaël V Lukens PhD Karina Meijer MD, PhD Anja BU Mäkelburg MD, PhD Rienk YJ Tamminga MD, PhD Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII Clinical and Applied Thrombosis/Hemostasis |
| title | Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII |
| title_full | Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII |
| title_fullStr | Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII |
| title_full_unstemmed | Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII |
| title_short | Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII |
| title_sort | occurrence of fviii inhibitors in hemophilia a patients following an institutional switch to a third generation b domain deleted fviii |
| url | https://doi.org/10.1177/10760296231167416 |
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