Human Fibrinogen Concentrate for Bleeding Prophylaxis During Surgery in Paediatric Patients with Congenital Fibrinogen Deficiency

Objective Congenital fibrinogen deficiency (CFD) is a rare disorder which predisposes patients to thromboembolic complications, both with and without fibrinogen supplementation. Treatment with human fibrinogen concentrate (HFC) can prevent blood loss in surgical treatment in patients with CFD. Herein we report data from paediatric patients receiving HFC as surgical prophylaxis during two Phase 3 studies.

Material and Methods Patients were enrolled in two multinational, multicentre, prospective, open-label, uncontrolled Phase 3 clinical trials (FORMA-02 and FORMA-04) for the use of HFC in adult and paediatric patients with CFD. Efficacy of HFC (Fibryga® Octapharma) in surgical prophylaxis was assessed at the end of surgery by the surgeon and post-operatively by the haematologist using a four-point objective scale (Excellent, Good, Moderate, None), and by an Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC).

Results Haemostatic efficacy of HFC in the prevention of bleeding during and after surgery was assessed in four patients (FORMA-02 [n = 1, 12 years old], and FORMA-04 [n = 3, <6 years old]) for a total of four surgeries, one of which was major (splenectomy) and three were minor (circumcision, pulpectomy for two teeth, and extraction of tooth). The median total dose per surgery was 85.8 mg/kg for the FORMA-02 patient and 108 mg/kg for the three FORMA-04 patients. Only one infusion was required for each of the three minor surgeries. The patient undergoing major surgery received a total of six infusions. For all surgeries, overall intra-operative and post-operative haemostatic efficacy was rated 100 % excellent by both the investigator and IDMEAC. In vivo recovery (IVR) for the loading dose for the FORMA-02 patient was 0.82 mg/dL/(mg/kg). Mean (±SD) IVR value for the loading dose of the first infusion for each of the three surgeries for the FORMA-04 patients was 1.3 mg/dL/[mg/kg] (±0.22) with a median (range) of 1.3 mg/dL/[mg/kg] (1.0–1.4). No allergic/hypersensitivity reactions or deaths were observed.

Conclusion HFC administration for bleeding prophylaxis during surgery was efficacious for this ultra-rare disease in a paediatric population with congenital afibrinogenemia and showed a favourable safety profile.

Tab 1. Efficacy assessments after HFC treatment

Publication History

Article published online:
18 June 2021