Efficacy and safety of fibrinogen concentrate for on-demand treatment of bleeding and surgical prophylaxis in paediatric patients with congenital fibrinogen deficiency

Claudia Djambas Khayat, Sunil Lohade, Fulton D’Souza, Latha Gowda Shamanur, Omid Reza Zekavat, Irina Kruzhkova, Bruce Schwartz, Cristina Solomon, Sigurd Knaub, Flora Peyvandi

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Congenital fibrinogen deficiency (CFD) is a rare, inherited disorder affecting normal blood clotting function, where patients can experience severe and/or frequent bleeding episodes (BEs). Treatment with human fibrinogen concentrate (HFC) can prevent/arrest bleeding. There is a need for more data on the efficacy, pharmacokinetics (PK) and safety of HFC treatment in paediatric patients with CFD. Methods: Haemostatic efficacy of HFC (Fibryga®, Octapharma AG) for on-demand treatment of bleeding and surgical prophylaxis in patients <12 years old was assessed by investigators and an Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC) based on an objective 4-point efficacy scale. Maximum clot firmness (MCF; surrogate marker of haemostatic efficacy), single-dose PK and safety were also assessed. Results: Of 14 patients receiving HFC (median [range] age 6.0 years [1.0–10.0]), eight received HFC for 10 BEs, three for surgical prophylaxis and 13 for PK. The IDMEAC rated haemostatic efficacy as 100% successful for on-demand BE treatment (95% CI 69.15–100.00) and surgical prophylaxis (95% CI 29.24–100.00). After a mean first dose of 70.78 mg/kg for BEs, mean (±SD) MCF significantly increased from pre-treatment to 1-hour post-infusion (3.3 mm [±1.77]; P = 0.0002), coinciding with haemostatic efficacy. PK parameters were favourable. Two possibly related adverse events occurred, including one serious (portal vein thrombosis). No allergic/hypersensitivity reactions or deaths were observed. Conclusion: HFC treatment for on-demand treatment of BEs and surgical prophylaxis was efficacious for this ultra-rare paediatric population with congenital afibrinogenaemia and showed a favourable PK and safety profile.

Original languageEnglish
Pages (from-to)283-292
Number of pages10
JournalHaemophilia
Volume27
Issue number2
DOIs
Publication statusPublished - Mar 2021

Keywords

  • afibrinogenaemia
  • fibrinogen
  • haemorrhage
  • haemostatics
  • paediatrics

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

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