Clinical trial NCT03682757: Post-Injury Platelet Biology: Mechanisms and Outcomes
Official title: Post-Injury Platelet Biology: Mechanisms and Outcomes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Wound and Injuries
Blood Platelets
Endothelium
Keywords: Trauma
Platelets
Coagulopathy
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: University of Colorado, Denver
name: University of Utah
name: University of California, Berkeley
name: National Institute of General Medical Sciences (NIGMS)
First posted: 2018-09-25
Enrollment: 367
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients meeting criteria for full trauma team activation and admitted to Zuckerberg San Francisco General Hospital

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: In Vitro Measurement of Endothelial Biomarkers
timeFrame: 0 hour (within 10 minutes of arrival to the Emergency Department)
measure: In Vitro Measurement Platelet Activation Biomarkers
timeFrame: 0 hour (within 10 minutes of arrival to the Emergency Department)
measure: In Vitro Measurement of Platelet Aggregation
timeFrame: 0 hour (within 10 minutes of arrival to the Emergency Department)
measure: In Vitro Assays of Platelet-Induced Endothelial Permeability
timeFrame: 0 hour (within 10 minutes of arrival to the Emergency Department)
measure: Transfusion products received (red cell, plasma, platelet)
timeFrame: in first 24 hours after arrival to the emergency department
measure: Organ Failure
timeFrame: Within 1 week of arrival to the emergency department
measure: 6-hour Mortality
timeFrame: 6 hours after arrival to the emergency department
measure: 24-hour Mortality
timeFrame: 24 hours after arrival to the emergency department
measure: 30-days Mortality
timeFrame: 30 days after arrival to the emergency department
measure: Hospital Discharge Mortality
timeFrame: Through hospital discharge (an average of 13 days)
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital
state: California
Study officials:
affiliation: University of California, San Francisco
name: Lucy Kornblith, MD
role: PRINCIPAL_INVESTIGATOR
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