Traumatic injury is a medical nightmare. If the initial injury doesn’t kill patients, many still have to contend with a deadly bleeding syndrome called coagulopathy. A new five-year, $23.8 million grant will support research at OMRF and other institutes to understand the cause and find new therapies for coagulopathy.
OMRF scientist Charles Esmon, Ph.D., will serve as a part of the Trans-Agency Consortium for Trauma-Induced Coagulopathy, or TACTIC, which will examine why bleeding becomes an unmanageable problem for some trauma patients.
“A large number of severe trauma patients die in the hospital because their blood won’t clot,” said Esmon, who holds the Lloyd Noble Chair in Cardiovascular Biology at OMRF.
Trauma is the major cause of death in people under age 34 and the third leading cause of mortality in the U.S., with uncontrollable hemorrhage representing the major cause of preventable deaths, according to the National Institutes of Health. Each year there are nearly 50 million injuries in the U.S. that result in 170,000 deaths.
Little is known about the biological phenomena that lead to coagulopathy. When a person sustains a traumatic injury, whether on the battlefield or in a car accident, he typically suffers serious physical damage. Doctors treat the injuries and, if all goes well, the patient gradually heals. However, some patients, regardless of proper treatment, can suddenly suffer from uncontrolled bleeding and die. It is believed that the shock from the trauma induces a “storm” of coagulation and inflammatory problems that prevents blood from clotting.
“Those are the questions we’re asking: Why does the blood become unable to clot, and how can we fix it?” Esmon said.
Led by University of Vermont Professor Emeritus of Biochemistry Kenneth Mann, Ph.D., the TACTIC study is a cooperative effort funded by the National Heart, Lung and Blood Institute that establishes a unique collaboration between the NIH and the Department of Defense.
“There are no analytical tools that allow emergency department staff to conclude that coagulopathy is occurring in trauma victims—we’re starting from ‘ground zero,’” Mann said. “The physicians and staff are left without resources to guide an effective therapeutic approach.”
This trans-agency endeavor links the NHLBI-supported TACTIC program with Department of Defense clinical trauma research centers in a unique initiative that integrates laboratory, clinical and early translational, hypothesis-driven research by leading investigators across the country and enable the basic science investigative units to explore clinical specimens obtained from the DoD centers.
“We’ve gathered the leading minds in the field to attack a problem that has a serious and immediate impact on patients,” said Esmon. “To understand and address the issue of severe trauma, we need a multi-disciplinary approach. This project requires experts in clinical science, basic biology, laboratory science and animal research.”
Esmon’s portion of the project will look at DNA and histones that escape from cells in a traumatic injury and the role they play in coagulopathy.
In addition to Esmon and Mann, Stephen Wisniewski, Ph.D., senior associate dean and co-director of the Epidemiology Data Center at the University of Pittsburgh Graduate School of Public Health, will also be a principal investigator. The University of Pittsburgh serves as the Coordinating Center. Additional institutions involved in the research funded by the TACTIC grant include Massachusetts Institute of Technology, Mayo Clinic, Scripps Research Institute, University of California-San Francisco, University of Illinois, and University of Pennsylvania. DoD-supported institutions participating in the clinical component of the TACTIC grant include University of Colorado, University of Pittsburgh, and Virginia Commonwealth University.
This research is funded by NIH grant number UM1 HL120877-01.