{
  "abstract": "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.",
  "abstract_shown": true,
  "affiliations": [
    "Universidade Federal de Pernambuco (UFPE), Recife, Brazil",
    "Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Victória Gomes De França LIMA"
    },
    {
      "affs": [
        0
      ],
      "name": "Alexsandro Pedro DA SILVA"
    },
    {
      "affs": [
        0
      ],
      "name": "Madi Veiga DINIZ"
    },
    {
      "affs": [
        0
      ],
      "name": "Gabriel Lúcio Guimarães DOS SANTOS"
    },
    {
      "affs": [
        0
      ],
      "name": "Matheus Gomes Marques DA SILVA"
    },
    {
      "affs": [
        0
      ],
      "name": "Ednayran Da Silva GALDINO"
    },
    {
      "affs": [
        1
      ],
      "name": "Gabriela Da Silva ARCANJO"
    },
    {
      "affs": [
        0
      ],
      "name": "Marcos André Cavalcanti BEZERRA"
    },
    {
      "affs": [
        0
      ],
      "name": "Betânia Lucena Domingues HATZLHOFER"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4dh0tahcpa52a.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.108041",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926017888",
  "id": "4dh0tahcpa52a",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.108041",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2720|Hemophilia Treatment and Research"
    ]
  ],
  "openalex": "W7223097582",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/4dh0tahcpa52a.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:27Z",
      "native_id": "bb47c853eb15402192ce67642df38828",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.108041"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC633-647.5",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "RECOMBINANT FACTOR VIII, FAMILY HISTORY, AND HIGH-TITER INHIBITOR RISK IN SEVERE HEMOPHILIA A",
  "title_text": "RECOMBINANT FACTOR VIII, FAMILY HISTORY, AND HIGH-TITER INHIBITOR RISK IN SEVERE HEMOPHILIA A",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:27Z",
  "url": "https://research.draconitic.com/paper/4dh0tahcpa52a",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}