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NCT Number: NCT03682757

Post-Injury Platelet Biology: Mechanisms and Outcomes

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.

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Key information

Conditions

Wound and Injuries Blood Platelets Cardiovascular Diseases Endothelium Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Vascular Diseases Wounds and Injuries

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Primary outcomes

  1. 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).

  2. 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).

  3. 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.

  4. 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.

  5. 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)

  6. 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)

  7. 6-hour Mortality

    Time frame: 6 hours after arrival to the emergency department

  8. 24-hour Mortality

    Time frame: 24 hours after arrival to the emergency department

  9. 30-days Mortality

    Time frame: 30 days after arrival to the emergency department

  10. Hospital Discharge Mortality

    Time frame: Through hospital discharge (an average of 13 days)

Sponsors and collaborators

Lead sponsor

University of California, San Francisco

Other

Collaborators

  • National Institute of General Medical Sciences (NIGMS)
  • University of California, Berkeley
  • University of Colorado, Denver
  • University of Utah

Registry information

Important dates

Study start
2018
Primary completion
2023
Study completion
2023
First posted
Sep 25, 2018
Registry last updated
Dec 8, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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