• Anesthesia and analgesia · Sep 2023

    Influence of Fibrinogen Concentrate on Neonatal Clot Structure When Administered Ex Vivo After Cardiopulmonary Bypass.

    • Nina Moiseiwitsch, Kimberly A Nellenbach, Laura A Downey, David Boorman, Ashley C Brown, and Nina A Guzzetta.
    • From the Joint Department of Biomedical Engineering of University of North Carolina - Chapel Hill and North Carolina State University, Raleigh, North Carolina.
    • Anesth. Analg. 2023 Sep 1; 137 (3): 682690682-690.

    BackgroundBleeding is a serious complication of cardiopulmonary bypass (CPB) in neonates. Blood product transfusions are often needed to adequately restore hemostasis, but are associated with significant risks. Thus, neonates would benefit from other effective, and safe, hemostatic therapies. The use of fibrinogen concentrate (FC; RiaSTAP, CSL Behring, Marburg, Germany) is growing in popularity, but has not been adequately studied in neonates. Here, we characterize structural and degradation effects on the neonatal fibrin network when FC is added ex vivo to plasma obtained after CPB.MethodsAfter approval by the institutional review board and parental consent, blood samples were collected from neonates undergoing cardiac surgery and centrifuged to yield platelet poor plasma. Clots were formed ex vivo from plasma obtained at several time points: (1) baseline, (2) immediately post-CPB, and (3) post-transfusion of cryoprecipitate. In addition, we utilized post-CPB plasma to construct the following conditions: (4) post-CPB +0.5 mg/mL FC, and (5) post-CPB +0.9 mg/mL FC. The resultant fibrin networks were imaged using confocal microscopy to analyze overall structure, fiber density, and alignment. Clots were also analyzed using a microfluidic degradation assay. Fibrinogen content was quantified for all plasma samples.ResultsThe addition of 0.5 or 0.9 mg/mL FC to post-CPB samples significantly enhanced the median fiber density when compared to untreated post-CPB samples (post-CPB = 0.44 [interquartile range {IQR}: 0.36-0.52], post-CPB +0.5 mg/mL FC = 0.69 [0.56-0.77], post-CPB +0.9 mg/mL FC = 0.87 [0.59-0.96]; P = .01 and P = .006, respectively). The addition of 0.9 mg/mL FC to post-CPB samples resulted in a greater fiber density than that observed after the in vivo transfusion of cryoprecipitate (post-transfusion = 0.54 [0.45-0.77], post-CPB +0.9 mg/mL FC = 0.87 [0.59-0.96]; P = .002). Median fiber alignment did not differ significantly between post-CPB samples and samples treated with FC. Degradation rates were not statistically significant from baseline values with either 0.5 or 0.9 mg/mL FC. In addition, we found a significant correlation between the difference in the baseline and post-CPB fibrinogen concentration with patient age ( P = .033) after controlling for weight.ConclusionsOur results show that clots formed ex vivo with clinically relevant doses of FC (0.9 mg/mL) display similar structural and degradation characteristics compared to the in vivo transfusion of cryoprecipitate. These findings suggest that FC is effective in restoring structural fibrin clot properties after CPB. Future studies after the administration of FC in vivo are needed to validate this hypothesis.Copyright © 2023 International Anesthesia Research Society.

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