Post-Injury Platelet Biology: Mechanisms and Outcomes

December 1, 2023 updated by: University of California, San Francisco

Trauma-induced coagulopathy is a central cause of preventable deaths from hemorrhage after injury. The contribution and impact of altered post injury platelet biology on trauma-induced coagulopathy is not well understood despite the pivotal contribution of platelets to normal coagulation and endothelial integrity. The central hypothesis for this study is that severe injury and shock drive altered platelet activation, platelet aggregation, and platelet-endothelial interactions that are associated with increased rates of transfusion, organ failure, and mortality. This study will investigate these causal pathways, mechanisms, and associated outcomes in a prospective observational trauma cohort through collection of biospecimens and detailed clinical data.

Study Overview

Status

Completed

Conditions

Detailed Description

This is a prospective cohort study of trauma patients on admission to the emergency department and for the subsequent 28 days. All adult patients meeting criteria for full trauma team activation and admitted to Zuckerberg San Francisco General Hospital and Trauma center, a level-1 trauma center, are eligible for enrollment. A 20-ml sample of blood will be drawn within 10 minutes of arrival in the emergency department (ED), processed in the central laboratory, and plasma stored at -80°C. Blood samples will be collected immediately on presentation via initial placement of a 16-gauge or larger peripheral intravenous line. Plasma biomarkers of endothelial injury will be measured by enzyme-linked immunosorbent assays (von Willebrand factor, syndecan-1, and angiopoietin-2). Cellular biomarkers of platelet activation will be measured by flow cytometry (platelet-monocyte aggregates, integrin αIIbβ3, P-selectin, and platelet microparticles). Platelet aggregation will be measured by whole blood multiple electrode impedance aggregometry. The effect of post-injury platelets on endothelial integrity will be quantified by in vitro assays of platelet-induced endothelial permeability. Comprehensive demographic data and medical history will be collected from chart review, interviews of patients and family members. Detailed clinical and outcome data is collected including transfusion timing and doses, the incidence of organ failure (Denver Postinjury Multiple Organ Failure Score), acute respiratory distress syndrome (Berlin Definition), infection, symptomatic thromboembolic complications, ventilator-free days, length of intensive care unit (ICU) and hospital stay, and mortality (6 hours, 24 hours, 30 days). In hospital mortality after 30 days will be assessed for all patients. Standard coagulation measures (international normalized ratio, prothrombin time, platelet count) and other laboratory measures will be collected to account and control for other distinct but highly integrated pathways implicated in trauma-induced coagulopathy. The Trauma Registry, a large database managed under guidelines from the American Trauma society, uses chart review to retrospectively assign Injury Severity Scores (ISS) and Abbreviated Injury Scores (AIS).

Study Type

Observational

Enrollment (Actual)

367

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- California
  - San Francisco, California, United States, 94110
    - Zuckerberg San Francisco General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Adult patients meeting criteria for full trauma team activation and admitted to Zuckerberg San Francisco General Hospital

Description

Inclusion Criteria:

Adult patients meeting criteria for full trauma team activation and admitted to Zuckerberg San Francisco General Hospital.

Exclusion Criteria:

Patients <18 years old
Patients transferred from other hospitals
Patients who are pregnant
Patients who are incarcerated
Patients will be retrospectively excluded if they were taking anticoagulant or anti-platelet medications, have moderate or severe liver disease, or a known bleeding diathesis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Severe Injury/Shock Severely injured trauma patients presenting with shock, as defined by an Injury Severity Score (ISS)>=25, and base deficit (BD)>=6.
Without Severe Injury/Shock Not severely injured trauma patients presenting without shock, as defined by an Injury Severity Score (ISS)<25, and base deficit (BD) <6.
Healthy Controls Uninjured healthy volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In Vitro Measurement of Endothelial Biomarkers Time Frame: 0 hour (within 10 minutes of arrival to the Emergency Department)	Plasma biomarkers of endothelial injury will be measured by enzyme-linked immunosorbent assays (von Willebrand factor, syndecan-1, and angiopoietin-2).	0 hour (within 10 minutes of arrival to the Emergency Department)
In Vitro Measurement Platelet Activation Biomarkers Time Frame: 0 hour (within 10 minutes of arrival to the Emergency Department)	Cellular biomarkers of platelet activation will be measured by flow cytometry (platelet-monocyte aggregates, integrin αIIbβ3, P-selectin, and platelet microparticles).	0 hour (within 10 minutes of arrival to the Emergency Department)
In Vitro Measurement of Platelet Aggregation Time Frame: 0 hour (within 10 minutes of arrival to the Emergency Department)	Platelet aggregation will be measured by whole blood multiple electrode impedance aggregometry.	0 hour (within 10 minutes of arrival to the Emergency Department)
In Vitro Assays of Platelet-Induced Endothelial Permeability Time Frame: 0 hour (within 10 minutes of arrival to the Emergency Department)	The effect of post-injury platelets on endothelial integrity will be quantified by in vitro assays of platelet-induced endothelial permeability using transendothelial permeability electrical resistance (TEER) assays.	0 hour (within 10 minutes of arrival to the Emergency Department)
Transfusion products received (red cell, plasma, platelet) Time Frame: in first 24 hours after arrival to the emergency department	Continuous units of red cell, plasma, platelet; transfused in 24 hours (yes/no); massive transfusion (>10units red cell/24 hour, yes/no)	in first 24 hours after arrival to the emergency department
Organ Failure Time Frame: Within 1 week of arrival to the emergency department	Rates of organ failure (yes/no) (Denver Postinjury Multiple Organ Failure Score)	Within 1 week of arrival to the emergency department
6-hour Mortality Time Frame: 6 hours after arrival to the emergency department		6 hours after arrival to the emergency department
24-hour Mortality Time Frame: 24 hours after arrival to the emergency department		24 hours after arrival to the emergency department
30-days Mortality Time Frame: 30 days after arrival to the emergency department		30 days after arrival to the emergency department
Hospital Discharge Mortality Time Frame: Through hospital discharge (an average of 13 days)		Through hospital discharge (an average of 13 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

University of Colorado, Denver

University of California, Berkeley

University of Utah

National Institute of General Medical Sciences (NIGMS)

Investigators

Principal Investigator: Lucy Kornblith, MD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 20, 2018

Primary Completion (Actual)

September 30, 2023

Study Completion (Actual)

September 30, 2023

Study Registration Dates

First Submitted

September 17, 2018

First Submitted That Met QC Criteria

September 21, 2018

First Posted (Actual)

September 25, 2018

Study Record Updates

Last Update Posted (Actual)

December 8, 2023

Last Update Submitted That Met QC Criteria

December 1, 2023

Last Verified