OC 67.5 - The Von Clauss Assay Does Not Accurately Measure Total Fibrinogen Levels After Traumatic Injury. Have We Been Thinking About Fibrinogen Replacement All Wrong?

Tuesday, July 12, 2022

3:45 PM – 4:00 PM

Location: ExCel Center, ICC Capital Suite Room 2-4

Presentation Format: In-Person

Presenting Author(s)

Margot DeBot, MD

Surgery Resident
University of Colorado
Denver, Colorado, United States

Co-Author(s)

IL

Ian Lacroix

PhD Student
University of Colorado
Aurora, Colorado, United States
AD

Angelo D'Alessandro

Associate Professor
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
EM

Ernest E Moore, MD

Director of Research
Ernest E Moore Shock Trauma Center atDenver Health
Denver, Colorado, United States
CS

Christopher Silliman

Professor
University of Colorado
Aurora, Colorado, United States
AS

Angela Sauaia

Professor
University of Colorado
Aurora, Colorado, United States
Terry R. Schaid, Jr., MD

Surgery Resident
University of Colorado
Denver, Colorado, United States
CE

Christopher Erickson

Post Doctoral Fellow
University of Colorado
Aurora, Colorado, United States
Alexis Cralley, MD

Research Fellow
University of Colorado
Aurora, Colorado, United States
MC

Mitchell J Cohen

Surgeon
University of Colorado
Aurora, Colorado, United States
KH

Kirk Hansen

Professor
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States

Background: The Von Clauss assay (FbVC), which estimates fibrinogen concentration based on the rate of thrombin-induced fibrin polymerization, is the standard clinical fibrinogen measurement. During acute physiological stress, oxidation alters the capacity of fibrinogen for fibrin polymerization and thus decreases the accuracy of FbVC. To date, there are no reports on the accuracy of FbVC after trauma.

Aims: Our aim was to evaluate the accuracy of FbVC versus total fibrinogen levels measured via mass spectrometry (FbMS). We hypothesized that severe injury reduces the accuracy of FbVC, and that fibrinogen repletion increases total fibrinogen levels without improving fibrin polymerization.

Methods: Blood was collected from injured patients at a level I trauma center in the ED, and at 6 and 24hr after hospital arrival. Fibrinogen levels were measured via targeted liquid chromatography coupled with mass spectrometry and analyzed with clinical data, treatments, outcomes, and FbVC.

Results: At 6hr after injury, patients who received cryoprecipitate showed a 13% increase in FbMS while patients who did not receive cryoprecipitate showed no change in FbMS (p=0.03, figure 1). No significant difference was seen in FbVC between patients who did and did not receive cryoprecipitate. Patients with minor trauma (NISS < 15, BE >-10 or INR < 1.4) showed correlations between FbMS and FbVC which were similar to healthy controls (Figure 2); whereas severely injured patients with shock or coagulopathy had poor correlations between FbMS and FbVC.

Conclusion(s): The Von Clauss Assay underestimates fibrinogen levels in hemorrhagic shock. Decreases in FbVC may reflect impaired fibrinogen polymerization rather than decreased availability and therefore FbVC may not respond to fibrinogen replacement. FbVC should be used with caution to guide fibrinogen replacement during resuscitation and correcting shock and the oxidative milieu of trauma may be more effective at improving fibrin polymerization than fibrinogen repletion alone.