PB1274 - Trauma Induces Intravascular Hemolysis, which is Associated with Adverse Clinical Outcomes: Potential Role of Released Arginase-1, Depletion of L-arginine, and Reduced Production of Nitric Oxide

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Terry R. Schaid, Jr., MD

Surgery Resident
University of Colorado
Denver, Colorado, United States

Co-Author(s)

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
Margot DeBot, MD

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

Christopher Erickson

Post Doctoral Fellow
University of Colorado
Aurora, Colorado, United States
IL

Ian Lacroix

PhD Student
University of Colorado
Aurora, Colorado, United States
Alexis Cralley, MD

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

Anirban Banerjee

Professor
University of Colorado, Department of Surgery
Aurora, Colorado, United States
KJ

Kenneth Jones

Associate Professor
University of Colorado, Department of Surgery
Aurora, Colorado, United States
AG

Arsen Ghasabyan

Study Coordinator
University of Colorado, Department of Surgery
Denver, Colorado, United States
SM

Sanchayita Mitra

Senior Researcher
University of Colorado, Department of Surgery
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: Severe injury may induce hemolysis, releasing intracellular RBC proteins, such as arginase-1. Transfused RBC’s can lyse in the trauma-associated, thromboinflammatory milieu, which may have serious clinical implications given the frequency of blood transfusion after trauma. There are currently no studies examining the relationship between trauma-induced hemolysis and clinical outcomes.

Aims: Use comprehensive proteomics to link trauma-induced hemolysis to outcomes and unmask potential mechanisms of post-injury organ dysfunction.

Methods: Blood was collected from injured patients at a Level I Trauma Center. Proteomics were performed using targeted liquid chromatography coupled with mass spectrometry. Intracellular RBC proteins as well as haptoglobin, L-arginine, and ornithine were measured at multiple timepoints. Unpaired t-tests and multiple linear regression were used to analyze association between injury, hemolysis, and outcomes.

Results: Intracellular RBC proteins were elevated on emergency department (ED) arrival through 24hr versus healthy controls. Haptoglobin decreased over 24hr in those severely injured with shock (NISS >25, base excess <-6 mEq/L). Severe injury and shock were associated with elevated arginase-1 on ED arrival that decreased over 24hr but remained elevated, reduced L-arginine on ED arrival that continued decreasing over 24hr, and elevated ornithine on ED arrival that decreased over 24hr (Fig.1). Over 24hr, RBC transfusions were negatively correlated with haptoglobin concentrations. Additionally, elevated hemolysis proteins and increased arginine conversion to ornithine were associated with mortality and adverse outcomes (Table1).

Conclusion(s): Trauma and shock result in intravascular hemolysis, which is exacerbated by RBC transfusions and associated with worse outcomes. Arginase-1 release with depletion of L-arginine necessary for nitric oxide production may contribute to organ dysfunction. This study raises important questions about how the trauma milieu causes hemolysis, which may be exacerbated by exogenous RBC’s given during resuscitation. Additional investigation is needed on endogenous versus transfused RBC lysis in trauma, which may unveil critical implications for resuscitation.

Research was supported by NIH 1RM1GM131968-01.