Comparative Biochemical and Functional Characterization of a Novel Human Fibrinogen Concentrate (BT524) and Established Plasma-Derived Fibrinogen Concentrates

Abstract

Human fibrinogen concentrate is used as replacement therapy for congenital and acquired fibrinogen deficiencies. Despite similar manufacturing principles, compositional differences among products may affect clot quality and hemostatic efficacy. BT524 (Biotest) is a newly developed human fibrinogen concentrate with proven clinical safety and efficacy.

The objective of this study was to compare the biochemical composition and in vitro functional characteristics of BT524 with those of two commercially available plasma-derived fibrinogen concentrates (Products I and II).

Three independent batches of each human fibrinogen concentrate were analyzed for the total and clottable protein, fibrinogen antigen, fibrinogen activity by Clauss, clotting factors, degradation markers (fibrinopeptide A and D-dimer), sub-visible particles, and aggregates. Maximum clot firmness and dynamics were assessed using rotational thromboelastometry (fibrin-based thromboelastometry). Fibrinogen deficient plasma with low factor XIII content was spiked each fibrinogen concentrate and increasing concentrations of factor XIII (0–0.8 U/mL).

BT524 showed consistent fibrinogen content but contained no active factor VIII, factor XIII, or von Willebrand factor, indicating a precisely defined composition. Levels of degradation markers, aggregates, and sub-visible particles were markedly lower than in comparator products, reflecting the superior biochemical purity of BT524. BT524 achieved significantly higher maximum clot firmness than Product I (p<0.0001) and demonstrated comparable performance with Product II. Spiking of factor XIII resulted in an additional increase in maximum clot firmness in BT524 and Product II, but not in Product I, proving functional factor XIII susceptibility of BT524.

BT524 demonstrates high biochemical purity and robust functional clot formation. These findings highlight that fibrinogen concentrates differ in composition, functionality and molecular integrity, which determines clot quality and hemostatic performance.