Fibrinogen (Liminal BioSciences)

Internal hemorrhage remains a critical challenge requiring immediate intervention. Recent advances in biomaterials have positioned fibrin hemostatic patches (FHPs) as a promising therapeutic option through targeted fibrinogen-to-fibrin conversion at the injured organ; however, insufficient understanding of the stoichiometric coupling between active components of FHP may limit its coagulation performance. Here, we report a novel FHP (nFHP) through orthogonal optimization of fibrinogen, thrombin, and calcium chloride. Systematic screening identified fibrinogen concentration as the primary determinant of clotting time, with fibrinogen-to-thrombin and fibrinogen-to-calcium chloride ratios further impacting. nFHP, fabricated with the optimal formulation (17 mg/cm² fibrinogen, 40 IU/cm² thrombin, 115 μg/cm² calcium chloride), achieved rapid fibrin network formation and superior adhesive strength on the porcine aorta, surpassing commercial FHP (cFHP). In vivo evaluations across hepatic resection, cardiac stab wound, and arterial hemorrhage models demonstrated nFHP's universal efficacy, achieving the minimal blood loss compared to commercial products. Our work identifies stoichiometric proportion as a key factor in fibrin-based biomaterial rational design and provides a translatable solution for uncontrolled internal hemorrhage.

Postpartum hemorrhage is the leading cause of maternal mortality worldwide and is often complicated by hypofibrinogenemia, increasing the risk of severe hemorrhage. Fibrinogen concentrate may offer several advantages over cryoprecipitate for rapid fibrinogen replacement, but data on its availability and use in obstetric units are limited.

An IRB-approved electronic survey was distributed to all 70 Society for Obstetric Anesthesia and Perinatology (SOAP) Centers of Excellence (COE) in the United States and Canada. Responses were collected over six weeks, with three reminders.

Twenty-eight centers (40%) responded. Annual delivery volumes ranged from <2,500 (14%) to >6,000 (26%). Fibrinogen concentrate was available in 75% of the centers, but only 17 (61%) had it on the Labor and Delivery Unit. Delivery volume did not correlate with institutional (ρ = -0.11, P = 0.56) or Labor and Delivery Unit (ρ = 0.03, P = 0.89) availability of fibrinogen concentrate. In centers with availability on the Labor and delivery Unit, 94% incorporated it in their obstetric hemorrhage protocols. Preparation was most often performed by the anesthesia care team (82%), with 76% achieving readiness within 10 min. Barriers to its use included cost and unfamiliarity with reconstitution.

Although three-quarters of the SOAP COE responding institutions reported availability of fibrinogen concentrate, only 61% had it on the Labor and Delivery Unit. Availability of fibrinogen concentrate allows for a more rapid management of hypofibrinogenemia compared to cryoprecipitate in the setting of postpartum hemorrhage. Despite evidence of its effectiveness, inconsistent societal recommendations, dosing variability and educational gaps remain, highlighting the need for wider availability, greater awareness and training of personnel in its use in obstetrics.