PB0617 - Kinetics of Clot Formation and Fibrinolysis in Severely Injured Trauma Patients

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Andrew R. Gosselin, BS (he/him/his)

PhD Student
Rutgers University
Springfield, New Jersey, United States

Co-Author(s)

CB

Christopher Bargoud

MD
Rutgers-Robert Wood Johnson Medical School
New Bru, New Jersey, United States
SM

Shane Mathew

Medical Student
Rutgers-Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States
AT

Ashley Toussaint

Medical Student
Rutgers-Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States
MM

Marie Macor

Nurse
Rutgers-Robert Wood Johnson Medical Center
New Brunswick, New Jersey, United States
SC

Susette Coyle

Nurse
Rutgers-Robert Wood Johnson Medical Center
New Brunswick, New Jersey, United States
Valerie Tutwiler, PhD

Assistant Professor
Rutgers-State University of New Jersey
Piscataway, New Jersey, United States
JH

Joseph Hanna

Assistant Professor
Rutgers-Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States

Background: Traumatic injury is a leading cause of death for those under 45 years old, with nearly 40% of occurring due to hemorrhage. Severe tissue injury and hypoperfusion lead to marked changes in coagulation, thereby preventing formation of a stable blood clot and increasing hemorrhage associated mortality.

Aims: We aimed to quantify changes in clot formation and mechanics which occur after traumatic injury and the relationship to coagulation factor concentration, kinetics, and fibrinolysis.

Methods: Following Rutgers University Institutional Review Board approval and informed consent, blood samples from injured patients were collected in 3.2% sodium citrate upon arrival to the emergency department (n=42). Coagulation kinetics and mechanics of healthy donor and subject plasma were compared with rheological and turbidity assays following activation with 20mM CaCl2 and 0.6U/mL thrombin. ELISA was performed to determine the concentration of tissue plasminogen activator (tPA) and D-dimer as fibrinolytic markers.

Results: Injured patient samples showed increased maximum clot stiffness and optical density, as well as a similarly increased fibrin polymerization rate when compared to healthy controls (Figure 1A-D). This polymerization increase was paired with a paradoxically higher percent lysis after one hour and higher tPA concentrations (Figure 1E,G). Samples from patients who died (n=12) exhibited an increase in lysis as compared to patients who survived (n=30)(Figure 1F). This lysis increase was mirrored by an associated increase in tPA and D-dimer concentration in patients that died (Figure 1G,H).

Conclusion(s): Injury patients appear to have increased rates of clot formation compared to healthy subjects along with an increase in tPA concentration and fibrinolysis. Consistent with this, the subgroup of patients who died prior to discharge exhibited higher tPA concentration and lysis when compared to survivors. These results suggest that hyperfibrinolysis driven by increased tPA concentration from tissue injury is a primary contributor to clot breakdown resulting in the increased mortality after severe trauma.