Cryoprecipitate transfusion in trauma patients attenuates hyperfibrinolysis and restores normal clot structure and stability: results from a laboratory sub-study of the FEISTY trial.

Morrow, Gael B.; Feller, Timea; McQuilten, Zoe; Wake, Elizabeth; Ariëns, Robert A. S.; Winearls, James; Mutch, Nicola J.; Laffan, Mike A.; Curry, Nicola

Abstract

Fibrinogen is the first coagulation protein to reach critical levels during traumatic haemorrhage. This laboratory study compares paired plasma samples pre- and post-fibrinogen replacement from the Fibrinogen Early In Severe Trauma studY (FEISTY; NCT02745041). FEISTY is the first randomised controlled trial to compare the time to administration of cryoprecipitate (cryo) and fibrinogen concentrate (Fg-C; Riastap) in trauma patients. This study will determine differences in clot strength and fibrinolytic stability within individuals and between treatment arms. Clot lysis, plasmin generation, atomic force microscopy and confocal microscopy were utilised to investigate clot strength and structure in FEISTY patient plasma. Fibrinogen concentration was significantly increased post-transfusion in both groups. The rate of plasmin generation was reduced 1.5-fold post-transfusion of cryo but remained unchanged with Fg-C transfusion. Plasminogen activator inhibitor 1 activity and antigen levels and Factor XIII antigen were increased post-treatment with cryo, but not Fg-C. Confocal microscopy analysis of fibrin clots revealed that cryo transfusion restored fibrin structure similar to those observed in control clots. In contrast, clots remained porous with stunted fibres after infusion with Fg-C. Cryo but not Fg-C treatment increased individual fibre toughness and stiffness. In summary, our data indicate that cryo transfusion restores key fibrinolytic regulators and limits plasmin generation to form stronger clots in an ex vivo laboratory study. This is the first study to investigate differences in clot stability and structure between cryo and Fg-C and demonstrates that the additional factors in cryo allow formation of a stronger and more stable clot.

Citation

MORROW, G.B., FELLER, T., MCQUILTEN, Z., WAKE, E., ARIËNS, R.A.S., WINEARLS, J., MUTCH, N.J., LAFFAN, M.A. and CURRY, N. 2022. Cryoprecipitate transfusion in trauma patients attenuates hyperfibrinolysis and restores normal clot structure and stability: results from a laboratory sub-study of the FEISTY trial. Critical care [online], 26, article number 290. Available from: https://doi.org/10.1186/s13054-022-04167-x

• Journal Article Type: Article
• Acceptance Date: Sep 13, 2022
• Online Publication Date: Sep 26, 2022
• Publication Date: Dec 31, 2022
• Deposit Date: Jul 25, 2023
• Publicly Available Date: Jul 25, 2023
• Journal: Critical care
• Print ISSN: 1364-8535
• Electronic ISSN: 1466-609X
• Publisher: Springer
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Article Number: 290
• DOI: https://doi.org/10.1186/s13054-022-04167-x
• Keywords: Fibrinogen; Cryoprecipitate; Trauma coagulopathy; Fibrinolysis; Clot structure
• Public URL: https://rgu-repository.worktribe.com/output/2010430
• Additional Information: This article has been published with separate supporting information. This supporting information has been incorporated into a single file on this repository and can be found at the end of the file associated with this output.