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Early Fibrinolytic Inhibition is Associated with DVT after Injury

Mark H. Meissner and Wayne Chandler, MD
University of Washington, Surgery, Seattle, WA

Objectives: Seriously injured patients are at high risk for the development of deep venous thrombosis (DVT). The purpose of this study was to evaluate the early coagulation and fibrinolytic changes after serious injury and their relationship to the development of DVT.
Methods: Plasma prothrombin fragment 1+2 (F 1+2), D-dimer (DD), antithrombin (AT), protein C (PC), tissue factor (TF), plasmin-antiplasmin complex (PAP), t-PA antigen (TPANT) and t-PA activity (TPACT) levels and the ultrasound development of DVT were determined 1 and 7 days after injury in 101 trauma patients with an injury severity score ≥ 15.
Results: DVT developed in 22 (21.8%) patients during the first week after injury. Activated coagulation (F 1+2) and intravascular fibrin formation (D-Dimer) were evident in most patients on day 1. These findings were associated with mildly decreased AT and PC levels. Among patients having coagulation and fibrinolytic variables measured at both 1 and 7 days, ongoing activation of coagulation was suggested by sustained elevation of F1+2 and increasing D-Dimer levels, despite normalization of the natural anticoagulants, antithrombin and protein C. (Table) Fibrinolytic activity increased during this time as indicated by rising t-PA activity and plasmin generation (PAP complex) and declining fibrinolytic inhibition (t-PA antigen). Although DVT was not associated with early changes in activated coagulation (F 1 + 2, D-Dimer), natural anticoagulants (antithrombin, protein C), or fibrinolytic activity (t-PA activity, PAP complex), it was associated with increased fibrinolytic inhibition Mean t-PA antigen levels increased among those with early DVT (mean change + 2.4 ѱ 5.6 ng/ml) and decreased among those without DVT (- 5.3 ѱ 9.3 ng / ml, p = 0.001).
Conclusions: Major trauma is associated with significant changes in coagulation and fibrinolysis over the first week following injury. The risk of DVT is high during this period and is associated with ongoing fibrinolytic inhibition (rising t-PA antigen)