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Elevated Tissue Plasminogen Activator and Reduced Plasminogen Activator Inhibitor Promote Hyperfibrinolysis in Trauma Patients

Cardenas, Jessica C.; Matijevic, Nena; Baer, Lisa A.; Holcomb, John B.; Cotton, Bryan A.; Wade, Charles E.


Table 4 in the article beginning on page 514 in the June 2014 issue contained a number of errors in the notations of significance. The authors regret the error. The corrected table appears below.

Shock. 43(4):424, April 2015.

doi: 10.1097/SHK.0000000000000161
Clinical Science Aspects

ABSTRACT: Severe hyperfibrinolysis after trauma is a poorly understood phenomenon associated with profound shock, serious anatomic injuries, increased transfusions, and high mortality rates. Molecular mechanisms driving hyperfibrinolysis in trauma have not been completely delineated. The authors aimed to determine the relationship between severe hyperfibrinolysis and outcomes in trauma patients and characterize the role of the plasminogen activator (PA) system in this condition. A prospective observational study was performed in 163 adult level I trauma patients admitted between April and August 2012. Blood was collected on admission, and fibrinolysis was determined by plasmin-α2 antiplasmin (PAP) levels. Tissue-derived and urokinase PA (tPA and uPA, respectively), PA inhibitor (PAI-1), fibrinogen, and antithrombin levels were also measured. Patient demographics, vital signs, laboratory values, mechanisms and severity of injuries, transfusions, and outcomes were collected at admission or from patient records. Moderate fibrinolysis was defined as PAP level 1,500 to 20,000 μg/L and severe hyperfibrinolysis as PAP level more than 20,000 μg/L. Severe hyperfibrinolysis was observed in 10% of patients and associated with increased injury severity, greater transfusions, fewer ventilator and hospital-free days, and higher mortality. Plasmin-α2 antiplasmin level was directly correlated with tPA level and inversely correlated with PAI-1 level. Patients with both elevated tPA and reduced PAI-1 were more severely injured, received more transfusions, and experienced fewer ventilator and hospital-free days. In conclusion, Severe hyperfibrinolysis is observed in a small percentage of trauma patients and is associated with severe injuries, greater transfusions, and worse outcomes. This condition is mediated, in part, by excessive upregulation of profibrinolytic tPA in the absence of concomitant increases in antifibrinolytic PAI-1.

Department of Surgery and The Center for Translational Injury Research, The University of Texas Health Science Center at Houston, Houston, Texas

Received 16 Dec 2013; first review completed 2 Jan 2014; accepted in final form 20 Feb 2014

Address reprint requests to Jessica C. Cardenas, PhD, 6431 Fannin St, MSB 5.030, The University of Texas Health Science Center at Houston, Houston, TX 77030. E-mail:

This work was supported by NIGMS T32GM008792, by The State of Texas Emerging Technology Fund, and by the University of Texas Health Science Center’s Center for Translational Injury Research.

© 2014 by the Shock Society