Post-Injury Platelet Biology: Mechanisms and Outcomes
| Status: | Recruiting |
|---|---|
| Conditions: | Hospital, Hematology |
| Therapuetic Areas: | Hematology, Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 9/27/2018 |
| Start Date: | September 20, 2018 |
| End Date: | September 2023 |
| Contact: | Lucy Kornblith, MD |
| Email: | Lucy.Kornblith@ucsf.edu |
| Phone: | 415-206-6946 |
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.
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.
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).
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).
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.
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