Title: Real-World Utilization of Human Fibrinogen Concentrate in Managing Bleeding in Adult and Pediatric Patients: A Retrospective Study

Introduction: Fibrinogen deficiency can be either congenital, due to genetic mutations, or acquired. Acquired fibrinogen deficiency is more common and occurs in certain diseases, trauma, excessive surgical bleeding, or post-partum hemorrhage as a result of increased coagulation factor consumption and/or reduced factor production. Transfusion of human fibrinogen concentrate can potentially correct this deficiency, limiting, or even preventing hemorrhage, excessive blood loss, and transfusion. Human fibrinogen concentrate is a freeze-dried, pathogen-reduced substance that is often available in the operating room and can be administered immediately without the need for thawing or blood bank management. This observational, retrospective study assessed the use of human fibrinogen concentrate for controlling bleeding in patients with diverse clinical presentations. Methods: A retrospective investigation was undertaken at Vanderbilt University Medical Center that included 43 patients with acquired fibrinogen deficiency. The main objective of the study was to determine the specific circumstances in which human fibrinogen concentrate (Fibryga) was used in this real-world setting. The secondary objective was to assess the success of treatment, defined as the ability to effectively control or prevent bleeding. Data were gathered regarding the characteristics of the patients, indications for human fibrinogen concentrate use and dosage, pre-dose and post-dose laboratory evaluations (including hemoglobin and fibrinogen activity levels), and the resulting clinical outcomes. Treatment efficacy was assessed based on the management of bleeding and the maintenance of hemoglobin levels with hemostatic success being defined as hemoglobin within 20% of the initial values. Results: Among the 43 patients included in the study, there were 30 females (69.8%) and 13 males (30.2%). The median age was 33 years (range 0.5 to 72 years). Three patients (7.0%) were below the age of 18. Thirty patients (69.8%) received a single infusion of human fibrinogen concentrate while 13 (30.2%) patients received multiple infusions (2-3 infusions within a 24-hour period). Human fibrinogen concentrate was administered to 11 (25.6%) patients for surgical bleeding and 32 patients (74.4%) for nonsurgical bleeding. Surgical bleeding was assessed in cardiac (n=8 [18.6%]) and abdominal surgeries (n=3 [7.0%]). The category of nonsurgical bleeding was further classified into post-partum hemorrhage (n=25 [58.1%]), liver disease (n=3 [7.0%]), trauma (n=3 [7.0%]), and right pulmonary hemorrhage (n=1 [2.3%]). Hemostatic success was achieved in 91.7% of patients (n=36; patients with pre- and post-dose hemoglobin levels), resulting in effective bleeding control. Additionally, there was a considerable improvement in fibrinogen levels following administration of human fibrinogen concentrate, with mean pre-dose levels of 2.4 g/dL and mean post-dose levels of 3.1 g/dL after the first infusion (n=38 [88.4%]; patients with pre- and post-dose fibrinogen levels [Clauss]). The majority of patients demonstrated favorable responses, with rapid cessation of bleeding and normalization of their hemodynamic parameters. Conclusions: The results of this study demonstrate that human fibrinogen concentrate can successfully manage bleeding in patients with acquired fibrinogen deficiency. The existing findings provide justification for the adoption of human fibrinogen concentrate in many clinical scenarios, including both surgical and nonsurgical hemorrhage. The practical benefits and predictable effects of human fibrinogen concentrate in place of standard treatments highlight its potential to not only enhance patient outcomes but also provide for optimized clinical workflows.