PB0485 - Assessment of Trauma-Induced Coagulopathy Using a Microfluidic Model of Injury at Venous and Arterial Shear Regimes

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Susan M. Shea, MSME, PhD

Assistant Professor
Trauma and Transfusion Medicine Research Center, Department of Surgery and Department of Bioengineering, University of Pittsburgh
Pittsburgh, Pennsylvania, United States

Co-Author(s)

RR

Rassam M.G. Rassam

Senior Research Laboratory Specialist
Trauma and Transfusion Medicine Research Center, Department of Surgery, University of Pittsburgh
Pittsburgh, Pennsylvania, United States
RF

Ricardo Fonseca

Postdoctoral Research Associate
Department of Surgery, Washington University in St. Louis
St. Louis, Missouri, United States
MC

Melissa Canas

Postdoctoral Research Associate
Department of Surgery, Washington University in St. Louis
St. Louis, Missouri, United States
KT

Kimberly Thomas

Instructor
Department of Pediatrics, Washington University in St. Louis
St. Louis, Missouri, United States
KB

Kelly Bochicchio

Senior Research Administrator
Department of Surgery, Washington University in St. Louis
St. Louis, Missouri, United States
GB

Grant Bochicchio

Edison Professor of Surgery
Department of Surgery, Washington University in St. Louis
St. Louis, Missouri, United States
PS

Philip C. Spinella

Professor, Surgery and Critical Care Medicine
University of Pittsburgh School of Medicine
SEWICKLEY, Pennsylvania, United States

Background: Trauma is the leading cause of death in young individuals. 25% of trauma patients present with trauma-induced-coagulopathy (TIC), which increases mortality 400%. The underlying mechanisms of TIC are not fully understood.

Aims: We aimed to characterize flow-dependent hemostatic function of trauma patient samples in a microfluidic model of injury.

Methods: Whole blood collected from Level I trauma patients at admission (N=19) was perfused at venous and arterial shear through a microfluidic model of injury comprising an injury-site (IS) and a collagen/tissue-factor-coated extravascular space. Hemostasis at the IS generates a clot seal, yielding endpoints of bleeding time (BT) and IS closure frequency (CF). A random subset of samples (N=7) were stained with a fluorescent CD41 antibody to label platelets and mean fluorescence intensity (MFI) measured throughout perfusion. Trauma samples were compared to healthy controls (N=2) via t-test. Data are reported as mean (standard error of the mean(SEM)).

Results: Patients were 78% male, majority blunt injury (61%), and ISS was median 14 (interquartile range 5-27). BT and CF for all groups are shown in Fig1. At low shear, control BT was 222s(48s), while trauma BT was 803s(83s) (p=0.04). At high shear, control BT was 642s(33s), while trauma BT was 1011s(67s) (p=0.09). There was a bimodal distribution in the trauma population, suggesting a possible division between those with hemostatic function and those without (Fig1). The CF was 100% in both controls, 63% for trauma in low shear, and 33% for trauma in high shear. Trauma samples demonstrated decreased platelet incorporation at low shear, yet increased platelet incorporation at high shear (Fig2).

Conclusion(s): We found delayed bleeding times in trauma samples at venous shear supported by a concomitant lack of platelet deposition. Bleeding times were delayed at high shear, despite substantial platelet deposition. Further characterization of TIC can optimize treatment approaches and identify novel therapeutics.