The Efficacy of Fibrinogen Concentrates in Relation to Cryoprecipitate in Restoring Clot Integrity and Stability against Lysis

Claire S. Whyte, Akriti Rastogi, Ellis Ferguson, Michela Donnarumma, Nicola J. Mutch* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
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Abstract

Loss of fibrinogen is a feature of trauma-induced coagulopathy (TIC), and restoring this clotting factor is protective against hemorrhages. We compared the efficacy of cryoprecipitate, and of the fibrinogen concentrates RiaSTAP® and FibCLOT® in restoring the clot integrity in models of TIC. Cryoprecipitate and FibCLOT® produced clots with higher maximal absorbance and enhanced resistance to lysis relative to RiaSTAP®. The fibrin structure of clots, comprising cryoprecipitate and FibCLOT®, mirrored those of normal plasma, whereas those with RiaSTAP® showed stunted fibers and reduced porosity. The hemodilution of whole blood reduced the maximum clot firmness (MCF) as assessed by thromboelastography. MCF could be restored with the inclusion of 1 mg/mL of fibrinogen, but only FibCLOT® was effective at stabilizing against lysis. The overall clot strength, measured using the Quantra® hemostasis analyzer, was restored with both fibrinogen concentrates but not cryoprecipitate. α2antiplasmin and plasminogen activator inhibitor-1 (PAI-1) were constituents of cryoprecipitate but were negligible in RiaSTAP® and FibCLOT®. Interestingly, cryoprecipitate and FibCLOT® contained significantly higher factor XIII (FXIII) levels, approximately three-fold higher than RiaSTAP®. Our data show that 1 mg/mL fibrinogen, a clinically achievable concentration, can restore adequate clot integrity. However, FibCLOT®, which contained more FXIII, was superior in normalizing the clot structure and in stabilizing hemodiluted clots against mechanical and fibrinolytic degradation.
Original languageEnglish
Article number2944
Number of pages14
JournalInternational Journal of Molecular Sciences
Volume23
Issue number6
Early online date9 Mar 2022
DOIs
Publication statusPublished - 9 Mar 2022

Bibliographical note

Funding: This work was supported in part by Tenovus Scotland Grampian (G17.03) and Friends of Anchor (SC025332). C.S.W. and N.J.M. were supported by the British Heart Foundation (PG/15/82/31721and PG/20/17/35050).

Acknowledgments: We thank the NHS Grampian Haematology department for kindly performing the Clauss assay to measure the fibrinogen concentration in the cryoprecipitate. We thank the University of Aberdeen Microscopy and Histology facility for their advice and the use of their facilities. We thank Linda Robertson and Megan Simpson for their technical assistance.

Keywords

  • fibrinogen
  • fibrinolysis
  • coagulation
  • trauma
  • cryoprecipitate

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