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Recombinant factor IX Fc for major surgery in hemophilia B: factor IX plasma activity levels and effective hemostasis

BACKGROUND: Major surgical procedures are associated with significant bleeding risk and infectious complications in patients with hemophilia, which may be minimized by factor replacement. Monitoring perioperative factor levels guides dosing to maintain adequate levels for hemostatic control. OBJECTI...

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Autores principales: Shapiro, Amy D., Chambost, Hervé, Ozelo, Margareth C., Falk, Aletta, Ahlin, Helena, Casiano, Sandra, Santagostino, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491823/
https://www.ncbi.nlm.nih.gov/pubmed/37694269
http://dx.doi.org/10.1016/j.rpth.2023.102169
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author Shapiro, Amy D.
Chambost, Hervé
Ozelo, Margareth C.
Falk, Aletta
Ahlin, Helena
Casiano, Sandra
Santagostino, Elena
author_facet Shapiro, Amy D.
Chambost, Hervé
Ozelo, Margareth C.
Falk, Aletta
Ahlin, Helena
Casiano, Sandra
Santagostino, Elena
author_sort Shapiro, Amy D.
collection PubMed
description BACKGROUND: Major surgical procedures are associated with significant bleeding risk and infectious complications in patients with hemophilia, which may be minimized by factor replacement. Monitoring perioperative factor levels guides dosing to maintain adequate levels for hemostatic control. OBJECTIVES: We report prospectively collected post hoc surgical data in patients with hemophilia B who underwent major surgery with extended half-life recombinant factor IX Fc fusion protein (rFIXFc) in phase 3 studies (B-LONG/Kids B-LONG and B-YOND). METHODS: Achieved FIX plasma levels were described for those who underwent major surgeries with ≥1 peak and/or predose FIX assessment available on the day of surgery (Day 0 [D0]) from the central laboratory. Dosing, injection frequency, adverse events, and hemostatic responses were assessed. Two representative cases were described further including blood loss, transfusions, and concomitant medication assessment. RESULTS: Of 35 major surgeries, 17 (N = 16 subjects) with sufficient FIX measurements were included in this analysis; 13 of 17 surgeries were orthopedic. On D0, a median loading (preoperative) dose of 101.1 International Units (IU)/kg/injection achieved a median peak FIX of 103.3 IU/dL. Across postoperative Days 1 to 3, 4 to 6, and 7 to 14, the median predose levels were 75.1 IU/dL with 1 injection/d, 71.6 IU/dL with 0 to 1 injection/d, and 43.2 IU/dL with 0 to 1 injection/d, respectively. Hemostasis was rated excellent (14 of 16) or good (2 of 16) across surgeries. Both case studies (knee arthroscopy and ankle fusion) illustrate measured FIX levels with rFIXFc. CONCLUSION: The aggregate analysis and representative cases of major surgeries demonstrate that rFIXFc can achieve FIX levels for effective hemostasis during invasive high-risk procedures.
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spelling pubmed-104918232023-09-10 Recombinant factor IX Fc for major surgery in hemophilia B: factor IX plasma activity levels and effective hemostasis Shapiro, Amy D. Chambost, Hervé Ozelo, Margareth C. Falk, Aletta Ahlin, Helena Casiano, Sandra Santagostino, Elena Res Pract Thromb Haemost Brief Report BACKGROUND: Major surgical procedures are associated with significant bleeding risk and infectious complications in patients with hemophilia, which may be minimized by factor replacement. Monitoring perioperative factor levels guides dosing to maintain adequate levels for hemostatic control. OBJECTIVES: We report prospectively collected post hoc surgical data in patients with hemophilia B who underwent major surgery with extended half-life recombinant factor IX Fc fusion protein (rFIXFc) in phase 3 studies (B-LONG/Kids B-LONG and B-YOND). METHODS: Achieved FIX plasma levels were described for those who underwent major surgeries with ≥1 peak and/or predose FIX assessment available on the day of surgery (Day 0 [D0]) from the central laboratory. Dosing, injection frequency, adverse events, and hemostatic responses were assessed. Two representative cases were described further including blood loss, transfusions, and concomitant medication assessment. RESULTS: Of 35 major surgeries, 17 (N = 16 subjects) with sufficient FIX measurements were included in this analysis; 13 of 17 surgeries were orthopedic. On D0, a median loading (preoperative) dose of 101.1 International Units (IU)/kg/injection achieved a median peak FIX of 103.3 IU/dL. Across postoperative Days 1 to 3, 4 to 6, and 7 to 14, the median predose levels were 75.1 IU/dL with 1 injection/d, 71.6 IU/dL with 0 to 1 injection/d, and 43.2 IU/dL with 0 to 1 injection/d, respectively. Hemostasis was rated excellent (14 of 16) or good (2 of 16) across surgeries. Both case studies (knee arthroscopy and ankle fusion) illustrate measured FIX levels with rFIXFc. CONCLUSION: The aggregate analysis and representative cases of major surgeries demonstrate that rFIXFc can achieve FIX levels for effective hemostasis during invasive high-risk procedures. Elsevier 2023-08-07 /pmc/articles/PMC10491823/ /pubmed/37694269 http://dx.doi.org/10.1016/j.rpth.2023.102169 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Brief Report
Shapiro, Amy D.
Chambost, Hervé
Ozelo, Margareth C.
Falk, Aletta
Ahlin, Helena
Casiano, Sandra
Santagostino, Elena
Recombinant factor IX Fc for major surgery in hemophilia B: factor IX plasma activity levels and effective hemostasis
title Recombinant factor IX Fc for major surgery in hemophilia B: factor IX plasma activity levels and effective hemostasis
title_full Recombinant factor IX Fc for major surgery in hemophilia B: factor IX plasma activity levels and effective hemostasis
title_fullStr Recombinant factor IX Fc for major surgery in hemophilia B: factor IX plasma activity levels and effective hemostasis
title_full_unstemmed Recombinant factor IX Fc for major surgery in hemophilia B: factor IX plasma activity levels and effective hemostasis
title_short Recombinant factor IX Fc for major surgery in hemophilia B: factor IX plasma activity levels and effective hemostasis
title_sort recombinant factor ix fc for major surgery in hemophilia b: factor ix plasma activity levels and effective hemostasis
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491823/
https://www.ncbi.nlm.nih.gov/pubmed/37694269
http://dx.doi.org/10.1016/j.rpth.2023.102169
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