Among pediatric patients with congenital fibrinogen deficiency (CFD), on-demand treatment with human fibrinogen concentrate appears to be effective for both bleeding episodes and surgical prophylaxis, according to an article published in Haemophilia.
CFD, which affects as many as 2 million individuals per year, is characterized by inadequate blood clot formation, and can result in bleeding episodes of variable severity and frequency. While fibrinogen replacement therapy with cryoprecipitate or fresh frozen plasma can be effective, several problems, including lack of virus inactivation and variable fibrinogen levels, can pose an issue.
Human fibrinogen concentrate, which has been shown to be effective in adults and adolescents in the CFD setting, undergoes virus inactivation and contains a defined level of fibrinogen. For this study, researchers evaluated the safety and efficacy of human fibrinogen concentrate among pediatric patients with CFD. Human fibrinogen concentrate was evaluated as an on-demand treatment for acute bleeding episodes, for surgical prophylaxis, and for single-dose pharmacokinetics.
Overall, of 15 patients screened for inclusion, 13 were included in the pharmacokinetics group, 8 in the bleeding group, and 3 in the surgical group. The median age was 6 years overall (range, 1-10).
By an Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC) 4-point efficacy scale, hemostatic efficacy was rated as 100% successful for both on-demand bleeding episode treatment (95% CI, 69.15-100) and surgical prophylaxis (95% CI, 29.24-100). Maximum clot firmness significantly increased at 1 hour after infusion in the bleeding episode group (3.3 mm; P =.0002).
The authors added that, among the 13 patients that underwent pharmacokinetic analysis, fibrinogen levels increased by a mean 106.1 mg/dL at 1 hour after infusion and by 101.5 mg/dL at 3 hours after infusion. At 1 week, mean fibrinogen levels had decreased to approximately baseline levels.
Ten adverse events were noted in 4 patients, 1 of which was severe portal vein thrombosis that led to treatment discontinuation, and which may have been therapy-related.
“This study of [human fibrinogen concentrate] efficacy, [pharmacokinetic] assessment and safety in [pediatric] patients with CFD demonstrated [human fibrinogen concentrate] to be 100% efficacious for on-demand treatment of bleeding and surgical prophylaxis,” the authors wrote. “There were no severe allergic/hypersensitivity reactions, or clinical evidence of [neutralizing] anti-fibrinogen antibodies.”
Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Djambas Khayat C, Lohade S, D’Souza F, et al. Efficacy and safety of fibrinogen concentrate for on-demand treatment of bleeding and surgical prophylaxis in paediatric patients with congenital fibrinogen deficiency. Haemophilia. Published online December 16, 2020. doi:10.1111/hae.14230