Comparison of fibrinogen concentrates to cryoprecipitate in restoring clot integrity and stability against fibrinolytic degradation

Authors: Whyte, C; Rastogi, A; Ferguson, E; Donnarumma, M; Mutch, N Affiliations: University of Aberdeen, Aberdeen, United Kingdom

Publication: Research and Practice in Thrombosis and Haemostasis ; 2022 ; 6

Abstract: BACKGROUND: Fibrinogen depletion is a critical feature in trauma induced coagulopathy (TIC). Cryoprecipitate or fibrinogen concentrates can be administered to restore levels of this clotting factor. Aims: To compare equivalent fibrinogen concentrations of cryoprecipitate and the fibrinogen concentrates, RiaSTAP® (CSL Behring) and FibCLOT® (LFB Biotechnologies), in their ability to restore clot integrity in models of TIC. Methods: Fibrinogen depleted plasma (FDP) and 40 % haemodilution were used to recapitulate TIC. FDP clot formation and tissue plasminogen activator-mediated lysis were monitored as change in absorbance at 405 nm. Clot structure were observed using fluorescently-labelled fibrinogen and confocal microscopy. The influence on the viscoelastic properties using both models was investigated using rotational thromboelastometry. Chandler model thrombi were used to establish changes to clot stability after haemodilution. Factor XIII (FXIII) and alpha2 antiplasmin (α2AP) were measured by ELISA. Results: Supplementation with all fibrinogen sources (≥1 mg/ml) increased maximum absorbance in FDP clot lysis with cryoprecipitate and FibCLOT giving similar A405. Clots formed with RiaSTAP consisted of stunted fibres whereas cryoprecipitate and FibCLOT produced fibres closely representing those formed with normal plasma. Maximum clot firmness (MCF) showed a concentration dependent increase with both fibrinogen concentrates being superior to cryoprecipitate. Haemodilution reduced the MCF of a clot but this was normalised with supplementation ≥1 mg/ml of any fibrinogen source. Only FibCLOT significantly increased the lysis onset time as measured by ROTEM. Haemodilution reduced thrombus stability against fibrinolytic degradation but this was normalised by supplementation ≥1 mg/ml of any fibrinogen source. Cryoprecipitate contained α2AP whilst the fibrinogen concentrates contained minimal levels. Cryoprecipitate and FibCLOT contained approximately 3-fold more FXIII/mg of fibrinogen than RiaSTAP. Conclusion(s): Addition of 1 mg/ml fibrinogen, a clinically achievable concentration, restored adequate clot integrity. FibCLOT, which contained more FXIII, was superior to RiaSTAP in normalising clot structure and stabilising haemodiluted clots against fibrinolysis.