Project Details

Early Career

Status: Funded - Open

Mechanisms and outcomes in children with acute traumatic coagulopathy

Alison Nair, MD

Summary

BACKGROUND: Acute traumatic coagulopathy (ATC) is an endogenous biologic response that occurs immediately after injury and is associated with key pathophysiology underlying trauma-related mortality and morbidity in children. Preliminary data from Benioff Children’s Hospital Oakland (BCHO) suggests pediatric ATC has an incidence of 16%, results in a 26% mortality, and leads to worsened morbidities.

GAP: Key epidemiology has yet to be prospectively defined in pediatric ATC. Further, while markers of coagulopathy and endothelial dysfunction have been associated with both adult ATC and poor outcomes in adults after injury, the mechanistic underpinnings of pediatric ATC may be significantly different because the hemostatic system does not reach maturity until adulthood.

HYPOTHESES:

• Hypothesis 1: Using a large prospective cohort of pediatric trauma patients, we hypothesize that constellations of clinical characteristics can be delineated into pediatric traumatic phenotypes to be used to risk-stratify and predict multiple organ dysfunction, mortality, and other morbidities.

• Hypothesis 2a: To understand coagulation dysfunction, we will evaluate the activated protein C (PC) pathway. We hypothesize that pediatric ATC patients will have elevated activated PC, elevated thrombomodulin, decreased factors V and VIII, and decreased plasminogen activator inhibitor-1, but all to a lesser degree than in adult ATC.

• Hypothesis 2b: To understand endothelial dysfunction, we will analyze several markers implicated in adult ATC. We hypothesize that pediatric ATC patients will have elevated syndecan-1 and Ang-1/Ang-2.

METHODS: In this prospective single center cohort study, we will consecutively enroll pediatric patients presenting to BCHO with traumatic injury over a 1.5-year period. In addition to gathering clinical characteristics and outcomes, included patients will have a blood sample drawn at presentation to measure the above markers of coagulopathy and endothelial dysfunction.

RESULTS: Pending

IMPACT: This project aims to understand causative indicators or associations between pediatric ATC, hemostatic abnormalities, and outcomes in pediatric trauma. We anticipate this knowledge will lead to pediatric-specific diagnostic decision support, identification of therapeutic targets, and personalized approaches for treating children following trauma.

Website Link: https://profiles.ucsf.edu/alison.nair