OC 11.1 - Cryoprecipitate transfusion in trauma patients attenuates hyperfibrinolysis and restores normal clot structure and strength; results from a sub-study of the FEISTY trial

Sunday, July 10, 2022

10:45 AM – 11:00 AM

Location: ExCel Center, ICC Auditorium

Presentation Format: In-Person

Presenting Author(s)

Gael B. Morrow, PhD

Postdoctoral Research Fellow
University of Oxford
Aberdeen, Scotland, United Kingdom

Co-Author(s)

Timea Feller, PhD

Postdoctoral research fellow
University of Leeds
Leeds, England, United Kingdom
Zoe McQuilten, MBBS, PhD

Associate Professor
Monash University
Melbourne, Victoria, Australia
EW

Elizabeth Wake

Trauma Research Co-ordinator
Gold Coast University Hospital
Gold Coast, Queensland, Australia
Robert A. S. Ariens, PhD

Professor
Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
Leeds, England, United Kingdom
JW

James Winearls

Clinician
Gold Coast University Hospital
Gold Coast, Queensland, Australia
Nicola J. J. Mutch, PhD

Professor
Aberdeen Cardiovascular & Diabetes Centre, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen
Aberdeen, Scotland, United Kingdom
Michael A. Laffan, MD

Professor
Centre for Haematology, Imperial College London, London, UK
London, England, United Kingdom
Nicola Curry, MD

Consultant Haematologist
Oxford University Hospitals NHS Foundation Trust
Oxford, England, United Kingdom

Background: Fibrinogen rapidly reaches critically low levels during traumatic haemorrhage. Hyperfibrinolysis is common and exacerbates hypofibrinogenaemia. The Fibrinogen Early in Severe Trauma studY (FEISTY;NCT02745041) is the first randomised controlled trial comparing the clinical effects of cryoprecipitate and fibrinogen concentrate (Fg-C) during traumatic haemorrhage.

Aims: To compare the effect of Fg-C or cryoprecipitate supplementation on clot structure, strength and fibrinolysis in severely injured patients enrolled to FEISTY.

Methods: Paired plasma samples pre- and post-fibrinogen replacement were examined for PAI-1 and FXIII antigen and activity levels and plasmin generation. Fibrin clot structure was analysed using confocal microscopy and mechanical properties of individual fibres investigated using atomic force microscopy (AFM). Healthy donor plasma was used as a control.

Results: Plasmin generation was significantly reduced in patients treated with cryoprecipitate, but did not change with Fg-C. PAI-1 activity and antigen levels were increased post-cryoprecipitate treatment, but not Fg-C. There was a significant increase in FXIII post-cryoprecipitate, whereas a significant decrease was observed in the Fg-C cohort. FXIII activity analysis revealed trauma patients had significantly lower levels than controls. Upon hospital admission trauma patients formed clots with significantly fewer fibrin fibres, that were shorter in length and reduced cross-links compared to controls. Cryoprecipitate transfusion restored the fibrin network, with fibres comparable to those observed in normal plasma, whereas Fg-C did not restore normal clot structure. AFM analysis confirmed that fibres formed after cryoprecipitate transfusion required more energy to rupture than their Fg-C counterparts.

Conclusion(s): In severely injured, bleeding trauma patients, cryoprecipitate supplementation attenuated plasmin generation and increased PAI-1 and FXIII levels. Patients given cryoprecipitate showed a homogeneous fibrin network with increased fibres than those with Fg-C. Moreover, these fibres showed increased resistance to mechanical stress. Our data indicate that cryoprecipitate is a superior source of fibrinogen to manage bleeding in trauma coagulopathy by increasing stability against mechanical disruption and fibrinolysis.