DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

The Pathogenesis of Post-Traumatic Pulmonary Embolism: A Prospective Multi-center Investigation by the CLOTT Study Group

Principal Investigator: KNUDSON, MARY M.
Institution Receiving Award: NATIONAL TRAUMA INSTITUTE D/B/A COALITION FOR NATIONAL TRAUMA RESEARCH
Program: DMRDP
Proposal Number: BA160400
Award Number: W81XWH-17-1-0673
Funding Mechanism: Broad Agency Announcement for Extramural Medical Research
Partnering Awards:
Award Amount: $4,262,854.00


TECHNICAL ABSTRACT

Background: Venous thromboembolism, which includes both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common and potentially mortal complication after injury in both civilian and military settings. To date, there are no methods that have been definitively demonstrated to prevent post-traumatic PE, which carries a mortality of 11% and is the third leading cause of death following injury. PE is particularly common among combat casualties due to the prevalence of certain risk factors such as multiple amputations, traumatic brain injury, the need for transfusions, and prolonged immobilization during evacuation. However, due to the liberal use of computed tomography following injury, many patients are found to have small clots in the chest that may not be PE at all and may in fact not need to be treated. Additionally, recent laboratory investigations suggest that some severally injured patients develop a hypercoagulable state due to failure to break down clot once formed and that platelets contribute to the strength of the clot. This failure of clot lysis may set the stage for true PE events.

Objectives/Hypotheses: This study is designed to address two major aims. The first aim will explore the hypothesis that small, peripheral, asymptomatic clots seen on computed tomography scans of the chest are not embolic events (PE) from DVT but are instead thrombi associated with inflammation and can be safely observed without specific treatment. The second aim is designed to identify patients with fibrinolytic shutdown/failure of clot lysis and to test the hypothesis that these patients are at increased risk for post-traumatic PE.

Study Design: This is a multi-center, prospective, observational study. For Aim 1, patients aged 18-40 years who are admitted to any of 17 major trauma centers will be considered eligible for enrollment. Data will be collected on all patients who develop PE in order to characterize the risk factors for those with symptomatic, central PE versus those with asymptomatic, peripheral thrombi. The safety of observing patients with peripheral thrombi versus treatment (full-dose anticoagulation or placement of a vena cava filter) will be compared. For Aim 2, five trauma centers with existing research teams focused on coagulation after injury will enroll a cohort of patients admitted to their intensive care unit and collect blood samples that can be subjected to thromboelastography (TEG) in order to identify patients with failure of clot lysis (fibrinolytic shutdown). The association between fibrinolytic shutdown and the subsequent development of PE will be explored.

Relevance: Due to the increasing number of patients who are found to have occult thrombi on imaging studies in both the combat and civilian trauma settings, demonstrating the safety of simple observation of these clots would have a major impact on practice patterns while protecting patients from the complications of anticoagulation and from the morbidity associated with placement of a vena cava filter. Secondly, if we establish an association between failure of clot lysis and PE, we can then address fibrinolytic shutdown with agents such as aspirin and other anti-platelet agents as a novel method of preventing post-traumatic PE.