When someone is traumatically injured, giving them blood products before they arrive at the hospital – such as at the scene or during emergency transport – can improve their likelihood of survival and recovery. But patients with certain traumatic injuries have better outcomes when administered specific blood components.
University of Pittsburgh School of Medicine and UPMC scientist-surgeons announced today in Cell Reports Medicine that giving plasma that has been separated from other parts of donated blood improves outcomes in patients with traumatic brain injury (TBI) or shock, whereas giving unseparated or "whole" blood may be best for patients with traumatic bleeding.
Together, Pitt and UPMC have become home to the largest clinical trials research consortium for early trauma care in the U.S., with significant funding from the U.S. Department of Defense , allowing the research to benefit both soldiers and civilians.
"We've heard about precision medicine – giving the right care to the right patient at the right time. This is precision transfusion – giving the right blood product to the right patient at the right time," said senior author Timothy Billiar, M.D. , George Vance Foster Professor and Chair of Pitt's Department of Surgery and chief scientific officer at UPMC. "We're not just replacing the blood – it's almost like a drug where we're maximizing its benefits and minimizing side effects."
The discovery was made with the Shock, Whole Blood, and Assessment of TBI (SWAT) multicenter study, co-led by co-senior author Jason Sperry, M.D., M.P.H., section chief of trauma surgery at Pitt, as well as co-authors Francis X. Guyette, M.D., professor of emergency medicine at Pitt and medical director for STAT MedEvac , and Stephen R. Wisniewski, Ph.D., epidemiology professor and associate vice chancellor for clinical trials coordination at Pitt.
SWAT enrolled over 1,000 traumatically injured patients with a high probability of needing emergency surgery and sampled their blood at set timepoints. A subset of 134 patients with multiple blunt or penetrating injuries who received at least one unit of blood product (red blood cells, plasma, platelets or whole blood) before hospital admission were further studied.
After applying computational methods to ensure that their findings were not skewed by age, gender or other confounding factors, the team found that receiving a higher proportion of plasma – alone or in conjunction with whole blood – before arriving at the hospital was associated with improved coagulation in patients with severe shock and TBI markers, and reduced post-admission transfusion volumes in patient with TBI.
"To me, that was the 'Eureka!' moment," Billiar said. "Because, hey, wait a minute, plasma is part of whole blood, so why is just giving plasma better?"
Plasma is the protein-rich portion of blood, so the team then took a deep dive into proteomics – the study of proteins, which are complex molecules produced by cells that are essential for the structure and function of organs and tissues. They tested for more than 7,500 proteins in healthy donor blood and that of the trauma patients as they progressed through recovery and found clear differences. They then narrowed their list of proteins to 198 with well-known roles in inflammatory and clotting processes following traumatic injury.
Patients who received plasma had a distinct proteomic profile compared to those who did not, suggesting that receiving plasma had an impact on the proteins that help with inflammation and clotting. In particular, plasma recipients had higher levels of proteins associated with later stages of clot formation, neuron survival, platelet function, wound repair and inflammation mediation.
However, since the amount of plasma in a unit of whole blood is approximately the same as the amount of plasma that would be given individually as a separate blood product, it is still unclear why patients who received the separated plasma fared better and had proteomic profiles more conducive to healing.
"There are differences in the storage time of whole blood and plasma – whole blood can be kept for 21 days, whereas plasma alone has a five-day shelf life. Perhaps when kept in whole blood the proteins in the plasma change over time, possibly because the blood cells release enzymes that act on the plasma proteins," said Sperry, who is also the Andrew B. Peitzman Professor of Surgery at Pitt. "The proteomic profile of different donors likely varies as well from person-to-person. As we consider a strategy to leverage our findings to improve patient outcomes, it will be important to untangle this mystery."
Sperry noted that it isn't practical for most ambulances to carry plasma, since it expires so quickly and would result in a lot of wasted plasma for all but the busiest ambulance services, and must be kept refrigerated, making it logistically difficult to transport.
"Our findings indicate that it is worthwhile to overcome these challenges," Sperry said. "Getting the right blood products to the right patient at the right time is a life-saving endeavor and I'm confident we'll continue to lead innovations that make it possible."
Additional authors on this research are Hamed Moheimani, M.D., M.P.H., Xuejing Sun, M.D., Mehves Ozel, M.D., Jennifer L. Darby, M.D., Erika P. Ong, M.D., Tunde Oyebamiji, M.D., Upendra K. Kar, Ph.D., Mark H. Yazer, M.D., Matthew D. Neal, M.D., and Jishnu Das, Ph.D., all of Pitt; Bryan A. Cotton, M.D., M.P.H., of the University of Texas Health Science Center; Jeremy W. Cannon, M.D., of the University of Pennsylvania; Martin A. Schreiber, M.D., of the Uniformed Services University of the Health Sciences; Ernest E. Moore, M.D., of the University of Colorado Health Sciences Center; Nicholas Namias, M.D., of the University of Miami; Joseph P. Minei, M.D., of the University of Texas Southwestern Medical Center; and Christopher D. Barrett, M.D., of the University of Nebraska Medical Center.
This research was supported by Department of Defense contract no. W81XWH-16-D-0024, task order W81XWH-16-D-0024-0002.
