Background and Goal of Study: Patients with congenital afibrinogenaemia and hypofibrinogenaemia frequently experience severe bleeding episodes after minor trauma or surgical intervention, starting at birth or early childhood. Therapeutic substitution with human fibrinogen concentrate (HFC) corrects the haemostatic defect and arrests bleeding in these patients. Here, we investigate the safety and efficacy of Octafibrin (Octapharma OPG, Vienna, Austria), a new plasma-derived, highly purified, lyophilized fibrinogen concentrate with two dedicated virus inactivation/removal steps, in the on-demand treatment of bleeding (BE) and surgical prophylaxis. 

Materials and Methods: This was a prospective, open-label, multinational study in adult and adolescent a- or hypofibrinogenemic patients. This planned interim analysis comprised data from 11 adult and 2 adolescent patients. Efficacy was assessed using a 4-point objective scale by the investigator and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC). 

Results and Discussion: Eleven of the 13 patients experienced a total of 23 minor BEs. Sixteen BEs (69.6%) were spontaneous and 7 (30.4%) traumatic. The majority of BEs (21/23) required 1 HFC infusion (91.3%) and 2 (8.7%) required 2 infusions. The median (range) dose of HFC administered for all BEs was 57.5 mg/kg (33.9-71.4 mg/kg) per infusion and 58.8 mg/kg (33.9-101.7 mg/kg) per BE.
The success rate (efficacy rating excellent or good) for all BEs was 100% (90% CI: 0.88, 1.00).
Maximum clot firmness (MCF) using thromboelastometry (ROTEM®) performed in plasma was also determined for the first infusion administered for the treatment of all 23 BEs. The mean (±SD) change in MCF from baseline (MCF 0) to 1 h after the first infusion of HFC was 6.5 mm (±2.0) (95% CI: 5.65, 7.40; p< 0.0001).
Four patients underwent 4 surgeries (3 major 1 minor). The postoperative success rate (haemostatic efficacy excellent or good) was 100% (90% CI 0.5, 1.0).
There have been no reports of serious adverse events related to infusion of the HFC. 

Conclusions: This study showed 100% haemostatic efficacy in on-demand treatment with HFC in bleeding patients with congenital fibrinogen deficiency. Haemostatic efficacy in surgical prophylaxis was rated excellent/good in 100% of surgeries. MCF increased significantly post-infusion in all patients after HFC administration, reflecting the successful treatment of bleeding events. There were no safety concerns relating to HFC.

Efficacy of human fibrinogen concentrate for on-demand treatment of acute bleeding and to prevent bleeding during and after surgery in subjects with congenital fibrinogen deficiency