Assay of clotting ability accurately predicts need for transfusion in trauma patients
CHICAGO (May 15, 2017): By combining a conventional laboratory measurement of blood clotting time (known as the International Normalized Ratio or INR) with a new test of blood clot strength, based upon thrombelastography (TEG®), researchers at the University of Colorado's Department of Surgery, Denver, are able to quickly and efficiently assess the overall ability of blood to clot and identify trauma patients who were most in need of a massive blood transfusion. The investigators believe that in the not too distant future these tests, when used in combination, will be able to personalize trauma care, help surgeons save lives, and make better use of scarce blood bank resources. The ability of the tests to predict the need for massive transfusion was described in an "article in press" published on the Journal of the American College of Surgeons website in advance of print publication.
More than 80 percent of deaths in the operating room and 50 percent of deaths in the first 24 hours after injury are due to massive blood loss and impaired coagulation. While only 3 percent of civilian trauma patients receive a massive transfusion in the first day of treatment after trauma, these patients account for 70 percent of all blood transfused in a trauma center.1
"When someone is massively bleeding, you need to give certain blood products early, and the blood bank has to mobilize blood products that are resource scarce, such as platelets, which have only a five-day shelf life. You want to quickly identify patients who will require a large quantity of blood products to save lives and mobilize the blood bank only when you need it," according to lead study author, Hunter B. Moore, MD.
However, clinical scoring systems for predicting the need for massive transfusion are problematic. Some rely on vital signs, such as blood pressure and heart rate, which are subjective and highly variable; others require multiple diagnostic imaging and laboratory tests.2
Dr. Moore and his colleagues at the University of Colorado's Department of Surgery developed a new test to predict which patients would require massive transfusion. This test modifies a currently available test of blood clot strength, thrombelastography (TEG®), by adding tissue plasminogen activator (tPA) to a patient's blood sample. Thrombelastography is a point-of-care assay of coagulation that measures the viscoelastic properties of whole blood and determines the ability of blood to clot. Tissue plasminogen activator is a protein involved in the breakdown of blood clots.
"When patients go into hemorrhagic shock, they activate the blood's fibrinolysis or clot degradation system at the local or organ level so organs continue to be perfused with blood. At the systemic level, there are backup inhibitors–platelets and proteins–that prevent clot degradation from affecting the whole body. Activators of fibrinolysis include tissue plasminogen activator. As patients progress toward hemorrhagic shock, clot degradation intensifies, and their tPA levels increase. We can unmask this process in the early stages by giving extra tPA to blood samples and forecast if the patient is at high risk of progression to hyperfibrinolysis," Dr. Moore said.
Dr. Moore and associates studied more than 300 patients who were treated for trauma between 2014 and 2016. Seventeen percent of the patients required a massive transfusion, and one third of deaths were due to uncontrolled hemorrhage. The investigators assessed how effectively each clinical score could determine the need for massive transfusion, and compared their effectiveness to their new developed test.
The analysis showed that this tPA-challenged TEG assay was highly sensitive and specific and took only a few minutes to provide results–up to 30 minutes faster than existing tests. Moreover, when the tPA-challenged TEG assay, was used in combination with the INR, it improved the predictive value of identifying patients who needed transfusion by roughly 40 percent. Additionally, the two-test combination identified 97 percent of patients who did not require blood products, thereby preventing unnecessary transfusions. The researchers therefore propose that trauma teams use the INR as a screening test to determine if someone is at risk for bleeding and then follow up with tPA-challenged TEG to ensure that this result is accurate.
The tPA-challenged TEG assays currently require trained technicians to conduct the testing. However, newly available fully automated TEG instruments will streamline this process, according to Dr. Moore.
"The fully automated assays will have a standardized methodology for obtaining samples and may be used as a point-of-care test by prehospital providers to screen for the risk of massive transfusion before patients enter the trauma center. These assays will help us move one step closer to the time when the trauma team can tailor or personalize resuscitation to each patient," Dr. Moore said.
In addition to Dr. Moore, other study authors include Ernest E. Moore, MD, FACS; Michael P. Chapman, MD; Benjamin R. Huebner, MD; Peter M. Einersen, MD; Solimon Oushy, BA; Christopher C. Silliman, MD, PhD; Anirban Banerjee, PhD; and Angela Sauaia, MD, PhD.
"FACS" designates that a surgeon is a Fellow of the American College of Surgeons
Citation: Viscoelastic Tissue Plasminogen Activator Challenge Predicts Massive Transfusion in 15 Minutes. Journal of American College of Surgeons. DOI: http://dx.doi.org/10.1016/j.jamcollsurg.2017.02.018.
This study was supported in part by National Institute of General Medical Sciences grants T32-GM008315 and P50-GM49222; National Heart Lung and Blood Institute grant UM 1HL120877; and Department of Defense Contract Number USAMRAA, W81XWH-12-2-0028. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences, National Heart Lung and Blood Institute, National Institutes of Health, or the Department of Defense.
Disclaimer: Drs. H. Moore, E. Moore, and Chapman have shared intellectual property with Haemonetics. There is no direct financial relationship. Haemonetics provided reagents and devices to run viscoelastic assays, but has no involvement with data analysis, interpretation, or any contribution to this manuscript.
1 American College of Surgeons Trauma Quality Improvement Program: ACS TQIP Massive Transfusion in Trauma Guidelines. Available at https://www.facs.org/~/media/files/quality%20programs/trauma/tqip/massive%20transfusion%20in%20trauma%20guildelines.ashx. Accessed May 11, 2017. 2 Brockamp T et al. Predicting on-goin hemorrhage and transfusion requirement after severe trauma: a validation of six scoring systems and algorithm on the TraumaRegister DGU. Critical Care. 2012; 16(4):R129.
About the American College of Surgeons
The American College of Surgeons is a scientific and educational organization of surgeons that was founded in 1913 to raise the standards of surgical practice and improve the quality of care for surgical patients. The College is dedicated to the ethical and competent practice of surgery. Its achievements have significantly influenced the course of scientific surgery in America and have established it as an important advocate for all surgical patients. The College has more than 80,000 members and is the largest organization of surgeons in the world. For more information, visit http://www.facs.org.