Nena Matijevic1, Yao-Wei W Wang2, Charles E Wade3, John B Holcomb4, Bryan A Cotton5, Martin A Schreiber6, Peter Muskat7, Erin E Fox8, Deborah J Del Junco9, Jessica C Cardenas10, Mohammad H Rahbar11, Mitchell Jay Cohen12. 1. Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Nena.Matijevic@uth.tmc.edu. 2. Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Yao-Wei.W.Wang@uth.tmc.edu. 3. Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Charles.E.Wade@uth.tmc.edu. 4. Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: John.Holcomb@uth.tmc.edu. 5. Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Bryan.A.Cotton@uth.tmc.edu. 6. Division of Trauma, Critical Care and Acute Care Surgery, School of Medicine, Oregon Health & Science University, 3181 Sam Jackson Rd SW, Mail Code L-611, Portland, OR 97035, USA. Electronic address: schreibm@ohsu.edu. 7. Division of Trauma/Critical Care, Department of Surgery, College of Medicine, University of Cincinnati, 222 Piedmont Ave., Suite 7000, Cincinnati, OH 45219, USA. Electronic address: muskatp@ucmail.uc.edu. 8. Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Erin.E.Fox@uth.tmc.edu. 9. Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Deborah.J.deljunco@uth.tmc.edu. 10. Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Jessica.C.Cardenas@uth.tmc.edu. 11. Division of Clinical and Translational Sciences, Department of Internal Medicine, Medical School, Biostatistics/Epidemiology/Research Design Core,Center for Clinical and Translational Sciences and Division of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, 1100 Fannin St. UPB 1100.21, Houston, TX 77030, USA. Electronic address: Mohammad.H.Rahbar@uth.tmc.edu. 12. Division of General Surgery, Department of Surgery, School of Medicine, University of California San Francisco, 1001 Potrero Ave. Room 3C-38, San Francisco, CA 94110, USA. Electronic address: mcohen@sfghsurg.ucsf.edu.
Abstract
BACKGROUND: Trauma-induced coagulopathy following severe injury is associated with increased bleeding and mortality. Injury may result in alteration of cellular phenotypes and release of cell-derived microparticles (MP). Circulating MPs are procoagulant and support thrombin generation (TG) and clotting. We evaluated MP and TG phenotypes in severely injured patients at admission, in relation to coagulopathy and bleeding. METHODS: As part of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, research blood samples were obtained from 180 trauma patients requiring transfusions at 5 participating centers. Twenty five healthy controls and 40 minimally injured patients were analyzed for comparisons. Laboratory criteria for coagulopathy was activated partial thromboplastin time (APTT) ≥ 35 sec. Samples were analyzed by Calibrated Automated Thrombogram to assess TG, and by flow cytometry for MP phenotypes [platelet (PMP), erythrocyte (RMP), leukocyte (LMP), endothelial (EMP), tissue factor (TFMP), and Annexin V positive (AVMP)]. RESULTS: 21.7% of patients were coagulopathic with the median (IQR) APTT of 44 sec (37, 53), and an Injury Severity Score of 26 (17, 35). Compared to controls, patients had elevated EMP, RMP, LMP, and TFMP (all p<0.001), and enhanced TG (p<0.0001). However, coagulopathic PROMMTT patients had significantly lower PMP, TFMP, and TG, higher substantial bleeding, and higher mortality compared to non-coagulopathic patients (all p<0.001). CONCLUSIONS: Cellular activation and enhanced TG are predominant after trauma and independent of injury severity. Coagulopathy was associated with lower thrombin peak and rate compared to non-coagulopathic patients, while lower levels of TF-bearing PMPs were associated with substantial bleeding.
BACKGROUND:Trauma-induced coagulopathy following severe injury is associated with increased bleeding and mortality. Injury may result in alteration of cellular phenotypes and release of cell-derived microparticles (MP). Circulating MPs are procoagulant and support thrombin generation (TG) and clotting. We evaluated MP and TG phenotypes in severely injured patients at admission, in relation to coagulopathy and bleeding. METHODS: As part of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, research blood samples were obtained from 180 traumapatients requiring transfusions at 5 participating centers. Twenty five healthy controls and 40 minimally injured patients were analyzed for comparisons. Laboratory criteria for coagulopathy was activated partial thromboplastin time (APTT) ≥ 35 sec. Samples were analyzed by Calibrated Automated Thrombogram to assess TG, and by flow cytometry for MP phenotypes [platelet (PMP), erythrocyte (RMP), leukocyte (LMP), endothelial (EMP), tissue factor (TFMP), and Annexin V positive (AVMP)]. RESULTS: 21.7% of patients were coagulopathic with the median (IQR) APTT of 44 sec (37, 53), and an Injury Severity Score of 26 (17, 35). Compared to controls, patients had elevated EMP, RMP, LMP, and TFMP (all p<0.001), and enhanced TG (p<0.0001). However, coagulopathic PROMMTT patients had significantly lower PMP, TFMP, and TG, higher substantial bleeding, and higher mortality compared to non-coagulopathicpatients (all p<0.001). CONCLUSIONS: Cellular activation and enhanced TG are predominant after trauma and independent of injury severity. Coagulopathy was associated with lower thrombin peak and rate compared to non-coagulopathicpatients, while lower levels of TF-bearing PMPs were associated with substantial bleeding.
Authors: Nena Matijevic; Yao-Wei W Wang; Vadim Kostousov; Charles E Wade; K Vinod Vijayan; John B Holcomb Journal: Thromb Res Date: 2011-03-21 Impact factor: 3.944
Authors: Nena Matijevic; Vadim Kostousov; Yao-Wei W Wang; Charles E Wade; Weiwei Wang; Phillip Letourneau; Elizabeth Hartwell; Rosemary Kozar; Tien Ko; John B Holcomb Journal: J Trauma Date: 2011-01
Authors: John R Hess; Karim Brohi; Richard P Dutton; Carl J Hauser; John B Holcomb; Yoram Kluger; Kevin Mackway-Jones; Michael J Parr; Sandro B Rizoli; Tetsuo Yukioka; David B Hoyt; Bertil Bouillon Journal: J Trauma Date: 2008-10
Authors: Hunter B Moore; Ernest E Moore; Eduardo Gonzalez; Gregory Wiener; Michael P Chapman; Monika Dzieciatkowska; Angela Sauaia; Anirban Banerjee; Kirk C Hansen; Christopher Silliman Journal: J Am Coll Surg Date: 2015-03-31 Impact factor: 6.113
Authors: Emily F Midura; Peter L Jernigan; Joshua W Kuethe; Lou Ann Friend; Rosalie Veile; Amy T Makley; Charles C Caldwell; Michael D Goodman Journal: J Surg Res Date: 2015-03-05 Impact factor: 2.192
Authors: Benjamin R Huebner; Ernest E Moore; Hunter B Moore; Gregory R Stettler; Geoffrey R Nunns; Peter Lawson; Angela Sauaia; Marguerite Kelher; Anirban Banerjee; Christopher C Silliman Journal: Shock Date: 2018-12 Impact factor: 3.454
Authors: Myung S Park; Ailing Xue; Grant M Spears; Timothy M Halling; Michael J Ferrara; Melissa M Kuntz; Sabtir K Dhillon; Donald H Jenkins; William S Harmsen; Karla V Ballman; Paul Harrison; John A Heit Journal: J Trauma Acute Care Surg Date: 2015-11 Impact factor: 3.313
Authors: Benjamin R Huebner; Ernest E Moore; Hunter B Moore; Eduardo Gonzalez; Marguerite R Kelher; Angela Sauaia; Anirban Banerjee; Christopher C Silliman Journal: J Surg Res Date: 2018-01-05 Impact factor: 2.192
Authors: Emily F Midura; Joshua W Kuethe; Teresa C Rice; Rosalie Veile; Lisa G England; Lou Ann Friend; Charles C Caldwell; Michael D Goodman Journal: Shock Date: 2016-01 Impact factor: 3.454
Authors: Kasiemobi E Pulliam; Bernadin Joseph; Mackenzie C Morris; Rosalie A Veile; Rebecca M Schuster; Amy T Makley; Timothy A Pritts; Michael D Goodman Journal: Thromb Res Date: 2020-07-01 Impact factor: 3.944
Authors: Young Kim; Michael D Goodman; Andrew D Jung; William A Abplanalp; Rebecca M Schuster; Charles C Caldwell; Alex B Lentsch; Timothy A Pritts Journal: Thromb Res Date: 2019-11-26 Impact factor: 3.944