Inhibitor development and clinical characteristics in children with severe hemophilia A in the ATHN 8 US cohort study
Abstract: Clotting factor concentrate (CFC), used to treat and prevent bleeding in hemophilia, is rendered ineffective if clotting factor neutralizing antibodies (inhibitors) develop. Inhibitors occur most often in children, early in treatment. The American Thrombosis and Hemostasis Network (ATHN) 8...
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Elsevier
2025-08-01
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| Series: | Blood Vessels, Thrombosis & Hemostasis |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950327225000397 |
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| author | Courtney D. Thornburg H. Marijke van den Berg Martin Chandler Lynn Malec Matthew Manuel Carrie O’Neill Michael Recht Elizabeth Taggart Shannon L. Carpenter Christine Knoll Lynn Malec Michael Wang Michael Guerrera Cristina Tarango Robert Sidonio Nidra Rodriguez Kenneth D. Friedman Amy Shapiro Hassan Yaish Shannon Carpenter Maissaa Janbain Eric Grabowski Rajiv Pruthi Kristina Haley Courtney Thornburg Sanjay Ahuja Mindy Simpson Ulrike Reiss Tiffany Lucas Vinod Balasa Allison Wheeler |
| author_facet | Courtney D. Thornburg H. Marijke van den Berg Martin Chandler Lynn Malec Matthew Manuel Carrie O’Neill Michael Recht Elizabeth Taggart Shannon L. Carpenter Christine Knoll Lynn Malec Michael Wang Michael Guerrera Cristina Tarango Robert Sidonio Nidra Rodriguez Kenneth D. Friedman Amy Shapiro Hassan Yaish Shannon Carpenter Maissaa Janbain Eric Grabowski Rajiv Pruthi Kristina Haley Courtney Thornburg Sanjay Ahuja Mindy Simpson Ulrike Reiss Tiffany Lucas Vinod Balasa Allison Wheeler |
| author_sort | Courtney D. Thornburg |
| collection | DOAJ |
| description | Abstract: Clotting factor concentrate (CFC), used to treat and prevent bleeding in hemophilia, is rendered ineffective if clotting factor neutralizing antibodies (inhibitors) develop. Inhibitors occur most often in children, early in treatment. The American Thrombosis and Hemostasis Network (ATHN) 8: US Cohort Study of Previously Untreated Patients (PUPs) with Congenital Hemophilia, conducted in children born in 2010 to 2020 with severe or moderate hemophilia, was designed to determine the percentage of participants who developed a confirmed, clinically significant inhibitor within the first 50 CFC exposure days (EDs). Cox proportional hazards models were used to evaluate risk factors for inhibitor development in PUPs with severe hemophilia A (HA). A total of 171 males with severe HA enrolled: 39 (22.8%) developed an inhibitor, 30 (17.5%) developed a high-titer inhibitor, and 9 (5.3%) developed a low-titer inhibitor; 82.1% within 20 EDs. Product exposure at <1 month (hazard ratio [HR], 2.57; 95% confidence interval [CI], 1.22-5.44), large structural changes (HR,16.59; 95% CI, 1.94-142.20), and nonsense variants (HR, 12.53; 95% CI, 1.41-111.49) were associated with inhibitor development. Overall, inhibitor development remains a significant CFC complication especially in the first 10 to 20 EDs. Further study should evaluate the impact of new treatments on inhibitor rates and age at inhibitor development and identify strategies to reduce inhibitor development. |
| format | Article |
| id | doaj-art-2c85deaee2f44dfeaf86b1b4ea81afde |
| institution | DOAJ |
| issn | 2950-3272 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Vessels, Thrombosis & Hemostasis |
| spelling | doaj-art-2c85deaee2f44dfeaf86b1b4ea81afde2025-08-20T02:47:28ZengElsevierBlood Vessels, Thrombosis & Hemostasis2950-32722025-08-012310008210.1016/j.bvth.2025.100082Inhibitor development and clinical characteristics in children with severe hemophilia A in the ATHN 8 US cohort studyCourtney D. Thornburg0H. Marijke van den Berg1Martin Chandler2Lynn Malec3Matthew Manuel4Carrie O’Neill5Michael Recht6Elizabeth Taggart7Shannon L. Carpenter8Christine KnollLynn MalecMichael WangMichael GuerreraCristina TarangoRobert SidonioNidra RodriguezKenneth D. FriedmanAmy ShapiroHassan YaishShannon CarpenterMaissaa JanbainEric GrabowskiRajiv PruthiKristina HaleyCourtney ThornburgSanjay AhujaMindy SimpsonUlrike ReissTiffany LucasVinod BalasaAllison WheelerDivision of Hematology/Oncology, Rady Children’s Hospital San Diego, San Diego, CA; Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, CA; Correspondence: Courtney D. Thornburg, Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute, National Institutes of Health, 6705 Rockledge Dr, Bethesda, MD 20892;PedNet Haemophilia Research Foundation, Baarn, The NetherlandsAmerican Thrombosis and Hemostasis Network, Hickory, NCVersiti Blood Research Institute, Milwaukee, WI; Division of Hematology/Oncology, Departments of Medicine and Pediatrics, Medical College of Wisconsin, Milwaukee, WIAmerican Thrombosis and Hemostasis Network, Hickory, NCAmerican Thrombosis and Hemostasis Network, Hickory, NCDivision of Pediatric Hematology & Oncology, Department of Pediatrics, Yale School of Medicine, New Haven, CT; National Bleeding Disorders Foundation, Washington, DCAmerican Thrombosis and Hemostasis Network, Hickory, NCDivsion of Hematology, Oncology & Bone Marrow Transplantation, Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MOAbstract: Clotting factor concentrate (CFC), used to treat and prevent bleeding in hemophilia, is rendered ineffective if clotting factor neutralizing antibodies (inhibitors) develop. Inhibitors occur most often in children, early in treatment. The American Thrombosis and Hemostasis Network (ATHN) 8: US Cohort Study of Previously Untreated Patients (PUPs) with Congenital Hemophilia, conducted in children born in 2010 to 2020 with severe or moderate hemophilia, was designed to determine the percentage of participants who developed a confirmed, clinically significant inhibitor within the first 50 CFC exposure days (EDs). Cox proportional hazards models were used to evaluate risk factors for inhibitor development in PUPs with severe hemophilia A (HA). A total of 171 males with severe HA enrolled: 39 (22.8%) developed an inhibitor, 30 (17.5%) developed a high-titer inhibitor, and 9 (5.3%) developed a low-titer inhibitor; 82.1% within 20 EDs. Product exposure at <1 month (hazard ratio [HR], 2.57; 95% confidence interval [CI], 1.22-5.44), large structural changes (HR,16.59; 95% CI, 1.94-142.20), and nonsense variants (HR, 12.53; 95% CI, 1.41-111.49) were associated with inhibitor development. Overall, inhibitor development remains a significant CFC complication especially in the first 10 to 20 EDs. Further study should evaluate the impact of new treatments on inhibitor rates and age at inhibitor development and identify strategies to reduce inhibitor development.http://www.sciencedirect.com/science/article/pii/S2950327225000397 |
| spellingShingle | Courtney D. Thornburg H. Marijke van den Berg Martin Chandler Lynn Malec Matthew Manuel Carrie O’Neill Michael Recht Elizabeth Taggart Shannon L. Carpenter Christine Knoll Lynn Malec Michael Wang Michael Guerrera Cristina Tarango Robert Sidonio Nidra Rodriguez Kenneth D. Friedman Amy Shapiro Hassan Yaish Shannon Carpenter Maissaa Janbain Eric Grabowski Rajiv Pruthi Kristina Haley Courtney Thornburg Sanjay Ahuja Mindy Simpson Ulrike Reiss Tiffany Lucas Vinod Balasa Allison Wheeler Inhibitor development and clinical characteristics in children with severe hemophilia A in the ATHN 8 US cohort study Blood Vessels, Thrombosis & Hemostasis |
| title | Inhibitor development and clinical characteristics in children with severe hemophilia A in the ATHN 8 US cohort study |
| title_full | Inhibitor development and clinical characteristics in children with severe hemophilia A in the ATHN 8 US cohort study |
| title_fullStr | Inhibitor development and clinical characteristics in children with severe hemophilia A in the ATHN 8 US cohort study |
| title_full_unstemmed | Inhibitor development and clinical characteristics in children with severe hemophilia A in the ATHN 8 US cohort study |
| title_short | Inhibitor development and clinical characteristics in children with severe hemophilia A in the ATHN 8 US cohort study |
| title_sort | inhibitor development and clinical characteristics in children with severe hemophilia a in the athn 8 us cohort study |
| url | http://www.sciencedirect.com/science/article/pii/S2950327225000397 |
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