Surgery Websites
Kornblith Lab »  Research

Research

The goal of our research is to develop new treatments and identify optimal resuscitation strategies that can both treat and prevent the derangements in coagulation and inflammation that lead to morbidity and mortality in critically injured patients. We are working toward these objectives through 1) Translational research to identify new treatment targets for trauma induced coagulopathy and platelet dysfunction 2) Studies investigating novel therapeutics for trauma patients, and 3) Large observational studies to identify predictors of poor outcomes after trauma and improve resuscitation strategies.

Translational Research

Post-Injury Platelet Biology and Trauma-Induced Coagulopathy

Using a well-established, large scale translational research infrastructure, one of the research group’s primary aims is to decode the mechanisms of altered platelet biology that contribute to trauma-induced coagulopathy, a multifactorial disorder of coagulation and inflammation that is a major cause of morbidity and mortality in injured patients. Patients with the highest level trauma activation at Zuckerberg San Francisco General Hospital are enrolled into an ongoing prospective trial entitled “Activation of Coagulation and Inflammation (ACIT) - Precision Approaches to Resuscitation in Trauma (PART) III”.

From these patients, serial blood samples are collected for coagulation and platelet function assays. These assays include platelet aggregometry, flow cytometry, and viscoelastic assays to fully characterize platelet function, platelet surface receptor expression patterns, and coagulation profiles. Two additional important aspects of these investigations include phenotyping post-injury platelet behavior with platelet genomics and ultrastructural platelet imaging.

In collaboration with Dr. Roland Bainton at UCSF, platelet RNA is isolated and sequenced to understand the upstream changes in the platelet transcriptome that may underly the observed biological alterations in platelet function after trauma. Lastly, through an ongoing collaboration with Dr. Wah Chiu at Stanford University, platelet ultrastructure after trauma is being analyzed using cryogenic electron microscopy techniques.

Clinical Trial

Start Date: Sep 2018
Estimated Completion Date: Sep 2023
Condition(s): Wound and Injuries, Blood Platelets, Endothelium 

Acute Respiratory Distress Syndrome after Isolated Traumatic Brain Injury

The development of ARDS after TBI is common and is associated with worse neurological outcomes, but the biologic mechanisms driving this are poorly understood. Dr. Carolyn Hendrickson is addressing this gap in knowledge through biomarker studies and analysis of prospectively collected data in TBI patients to understand how activation of the vascular endothelium and platelets may be implicated. This study also aims to understand the contribution of non-protective mechanical ventilation strategies in the development of ARDS after TBI.

Changes of Gut and Blood Microbiota in Critically-Injured Trauma Patients

Emerging evidence from human microbial ecology has redefined our understanding of the critical relationship between health status and the microbial communities that inhabit multiple niches within human hosts. However, the time course, nature, and magnitude of microbiome alterations following trauma remain unknown. The research group is collaborating with Drs. Sarah Doernberg, Jennifer Mulliken, and Chaz Langelier, leaders in Infectious Disease and Antimicrobial Stewardship Research in a prospective study to characterize the changes in the human microbiome after severe trauma and understand how this is associated with clinical outcomes, including infectious complications, multi-organ failure, wound healing, and mortality.

Novel Therapeutics for Critically Injured Patients

Platelet Based Hemostatic Agents

Another focus of our research is on improving the efficacy of platelet transfusions and platelet based therapeutics. The research group is participating in a Department of Defense Congressionally Directed Medical Research Program in collaboration with the UCSF Department of Laboratory Medicine, and OHSU Division of Trauma, Critical Care, and Acute Care Surgery, for the study of “Freeze Dried Platelet Extracellular Vesicles as a Hemostatic Adjunct to Resuscitation for Prolonged Field Care.”

The DOD/CDMRP funded study is a multicenter, multi-investigator grant with primary investigators Dr. Shibani Pati and Dr. Martin Schreiber. This two year grant will explore how therapeutic product derived from platelets called platelet derived extracellular vesicles (PEVs) and lyophilized platelet derived extracellular vesicles (LPEVs) can act to stop bleeding trauma patients from bleeding to death or dying from organ failure.

Mesenchymal Stromal Cells for Acute Respiratory Distress Syndrome (STAT Trial)

The research group is a participating site in the STAT trial, a Department of Defense funded multicenter phase 2b clinical trial investigating the efficacy of mesenchymal stromal cells for the treatment of ARDS led by Dr. Michael Matthay at UCSF. This clinical trial is partnering with several collaborators including the Department of Defense, Harborview Injury Prevention and Research Center, Oregon Health and Science University, Vanderbilt University Medical Center, The University of Texas Health Science Center, and the University of Minnesota. Patients with both ARDS after major trauma as well as critically ill patients in the Medical Intensive Care Unit are eligible for enrollment.

Multicenter Observational Studies

The research group participates in a number of multicenter trials through the Western Trauma Association (WTA) and the Eastern Association for the Surgery of Trauma (EAST). The research group is currently the lead center for:

The Ultra-Massive Transfusions Study (EAST)

This multi-center retrospective study aims to advance our understanding of optimal resuscitation strategies and predictors of outcomes, both in trauma patients and across specialties for patients requiring greater than 20 units of blood transfused over 24 hours. 

Site Directory
    X