Post-Injury Platelet Biology: Mechanisms and Outcomes

Blood Platelets Clinical Trial

Official title:

Post-Injury Platelet Biology: Mechanisms and Outcomes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03682757
• Other study ID #: P0528296
• Secondary ID: 5K23GM130892
• Status: Completed
• Start date: September 20, 2018
• Est. completion date: September 30, 2023

Study information

• Verified date: December 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 367
• Est. completion date: September 30, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Blood Platelets
• Endothelium
• Wound and Injuries
• Wounds and Injuries

Locations

Country	Name	City	State
United States	Zuckerberg San Francisco General Hospital	San Francisco	California

Sponsors (5)

Lead Sponsor	Collaborator
University of California, San Francisco	National Institute of General Medical Sciences (NIGMS), University of California, Berkeley, University of Colorado, Denver, University of Utah

Country where clinical trial is conducted

United States, 

References & Publications (53)

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* Note: There are 53 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In Vitro Measurement of Endothelial Biomarkers	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)
Primary	In Vitro Measurement Platelet Activation Biomarkers	Cellular biomarkers of platelet activation will be measured by flow cytometry (platelet-monocyte aggregates, integrin aIIbß3, P-selectin, and platelet microparticles).	0 hour (within 10 minutes of arrival to the Emergency Department)
Primary	In Vitro Measurement of Platelet Aggregation	Platelet aggregation will be measured by whole blood multiple electrode impedance aggregometry.	0 hour (within 10 minutes of arrival to the Emergency Department)
Primary	In Vitro Assays of Platelet-Induced Endothelial Permeability	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)
Primary	Transfusion products received (red cell, plasma, platelet)	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
Primary	Organ Failure	Rates of organ failure (yes/no) (Denver Postinjury Multiple Organ Failure Score)	Within 1 week of arrival to the emergency department
Primary	6-hour Mortality		6 hours after arrival to the emergency department
Primary	24-hour Mortality		24 hours after arrival to the emergency department
Primary	30-days Mortality		30 days after arrival to the emergency department
Primary	Hospital Discharge Mortality		Through hospital discharge (an average of 13 days)