RECOMBINANT FACTOR VIII, FAMILY HISTORY, AND HIGH-TITER INHIBITOR RISK IN SEVERE HEMOPHILIA A

@article{lima2026recombinant,
  title = {{RECOMBINANT FACTOR VIII, FAMILY HISTORY, AND HIGH-TITER INHIBITOR RISK IN SEVERE HEMOPHILIA A}},
  author = {Victória Gomes De França LIMA and Alexsandro Pedro DA SILVA and Madi Veiga DINIZ and Gabriel Lúcio Guimarães DOS SANTOS and Matheus Gomes Marques DA SILVA and Ednayran Da Silva GALDINO and Gabriela Da Silva ARCANJO and Marcos André Cavalcanti BEZERRA and Betânia Lucena Domingues HATZLHOFER},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.108041},
  url = {https://doi.org/10.1016/j.htct.2026.108041},
  note = {CC BY},
}

TY  - JOUR
TI  - RECOMBINANT FACTOR VIII, FAMILY HISTORY, AND HIGH-TITER INHIBITOR RISK IN SEVERE HEMOPHILIA A
AU  - Victória Gomes De França LIMA
AU  - Alexsandro Pedro DA SILVA
AU  - Madi Veiga DINIZ
AU  - Gabriel Lúcio Guimarães DOS SANTOS
AU  - Matheus Gomes Marques DA SILVA
AU  - Ednayran Da Silva GALDINO
AU  - Gabriela Da Silva ARCANJO
AU  - Marcos André Cavalcanti BEZERRA
AU  - Betânia Lucena Domingues HATZLHOFER
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.108041
UR  - https://doi.org/10.1016/j.htct.2026.108041
AB  - Introduction: Severe hemophilia A is a hereditary coagulopathy whose chronic treatment with factor VIII (FVIII) concentrates can be complicated by the development of anti-FVIII inhibitors, compromising therapeutic efficacy. Among the factors associated with this outcome, family history of inhibitors and the type of replacement product used, recombinant (rFVIII) or plasma-derived (pFVIII), stand out as a question still debated in the literature. Objective: This study aimed to analyze the association between these variables and inhibitor development in patients with severe hemophilia A followed at the Pernambuco Foundation of Hematology and Hemotherapy (HEMOPE), Recife unit. Methodology: This is an observational, cross-sectional, retrospective study, conducted between June and July 2025, with 47 adult patients, whose clinical, laboratory, and therapeutic data were extracted from medical records and analyzed using chi-square, Fisher's exact test, and the Mann-Whitney test, with odds ratio calculation and p < 0.05. Results and discussion: High-titer inhibitors were identified in 37.5% of the sample. A statistically significant association was observed between product type and this outcome, with 36% of patients treated with rFVIII developing inhibitors versus 13% of those treated with pFVIII; and between positive family history and inhibitor development, present in 77.8% of these patients versus 5.6% among those with unknown history, both with odds roughly three to four times higher, although without significance in the isolated comparison. These findings align with post-hoc analyses from the SIPPET study, which identified a higher inhibitor risk within the first ten days of FVIII exposure, this risk being, within the first five days, three to four times higher with recombinant than with plasma-derived products. Mechanistically, plasma-derived FVIII carries von Willebrand factor and immunomodulatory proteins that may reduce its immunogenicity, whereas recombinant products, derived from non-human mammalian cell lines, undergo post-translational modifications that generate neoantigens. Studies show a gene-environment interaction whereby genetically low-risk patients are not protected from this greater immunogenicity when exposed to rFVIII, reaching 43% inhibitor development in this group, versus no cases among those treated with pFVIII. Conclusion: It is concluded that both family history and product type are relevant factors in high-titer inhibitor formation, reinforcing the importance of considering them in individualized therapeutic selection, especially in previously untreated patients.
SN  - 2531-1379
SN  - 2531-1387
ER  -