Thrombelastography (TEG) fibrinolysis shutdown after trauma is associated with increased mortality due to hypercoagulability-associated organ failure. However, a lack of mechanistic data has precluded the development of novel interventions to treat shutdown.
To define the pathophysiology of TEG shutdown in severely injured, bleeding patients through secondary analysis of the PROPPR trial.
Fibrinolysis was characterized in PROPPR subjects using admission TEG lysis at 30 min (LY30) or plasmin-antiplasmin (PAP) levels. LY30 categories were low (<0.9%), moderate (0.9–2.9%), or high (≥ 3%). PAP was classified as low (<1,500 μg/L), moderate (1,500–20,000 μg/L), or high (>20,000 μg/L). Demographics, outcomes, admission TEG values, platelet count and function, standard coagulation tests, and coagulation proteins were compared.
Five hundred forty-seven patients had TEG data and 549 patients had PAP data available. Low LY30 was associated with reduced platelet count and aggregation, poorer TEG clot formation, prolonged clotting times, and reduced fibrinogen and alpha2 antiplasmin. Compared to moderate PAP, low PAP subjects had similar platelet parameters, TEG values, fibrinogen, and alpha2 antiplasmin, but reduced tPA, and elevated PAI-1. D-Dimer values increased as PAP increased, however patients with low LY30 had elevated D-Dimer compared with moderate LY30 patients. Most low LY30 deaths were due to TBI (45%) and hemorrhage (42%) versus one of each cause (TBI, hemorrhage, MOF) in low PAP patients.
Low TEG LY30 does not reflect shutdown of enzymatic fibrinolysis with hypercoagulability, but rather a coagulopathic state of moderate fibrinolysis with fibrinogen consumption and platelet dysfunction that is associated with poor outcomes.
*Division of Acute Care Surgery, Department of Surgery, The University of Texas Health Science Center and the McGovern School of Medicine, Houston, Texas
†Center for Translational Injury Research, Houston, Texas
‡Division of Trauma, Critical Care, and Acute Care Surgery, Oregon Health and Science University, Portland, Oregon
§The University of Washington Department of Emergency Medicine, Harborview Medical Center, Seattle, Washington
Address reprint requests to Jessica C. Cardenas, PhD, 6431 Fannin St. MSB 5.214, Houston, TX 77030. E-mail: Jessica.C.Cardenas@uth.tmc.edu
Received 6 March, 2018
Revised 27 March, 2018
Accepted 10 April, 2018
The Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial was sponsored by the U.S. National Heart, Lung, and Blood Institute (U01HL077863), the U.S. Department of Defense, as well as Defense Research and Development Canada in partnership with the Canadian Institutes for Health Research (CIHR), Institute of Circulatory and Respiratory Health (CRR-120612).
The authors report no conflicts of interest.