R. L. Ball1,2, M. C. Bravo3, T. Orfeo3, L. T. Moffatt1,4, K. E. Brummel-Ziedins3, J. W. Shupp1,2,4,5 1MedStar Health Research Institute,Firefighters’ Burn And Surgical Research Laboratory,Washington, DC, USA 2MedStar Washington Hospital Center,The Burn Center,Washington, DC, USA 3University Of Vermont College Of Medicine / Fletcher Allen Health Care,Department Of Biochemistry,Burlington, VT, USA 4Georgetown University School of Medicine,Department Of Biochemistry,Washington, DC, USA 5Georgetown University School of Medicine,Department Of Surgery,Washington, DC, USA
Introduction: Activated thrombin activatable fibrinolysis inhibitor (TAFIa) is a carboxypeptidase whose primary physiological substrate is plasmin-modified fibrin. TAFIa removes C-terminal lysine and arginine residues generated by plasmin, thus reducing the rate of plasminogen activation, resulting in transient dampening of fibrinolysis. Expression of TAFIa/ai associated with major thermal burn injury (MThBI) has not been previously reported. For the first time, circulating levels of TAFIa/ai following thermal injury were investigated in order to advance the understanding of burn-induced coagulopathy.
Methods: In a prospective observational study, admission blood samples were collected within 6 hours of injury from 15 patients with MThBI greater than 20% total body surface area (TBSA) per protocol approved by the Institutional Review Board. Citrate plasma was prepared within 15 minutes of blood collection. TAFIa/ai levels were quantified with ELISA. Hemostatic activation in MThBI patients was established by measuring d-dimer and plasmin-antiplasmin complex (PAP). Chart review was conducted to determine demographics, TBSA, and 30-day mortality. Comparisons were made between patients that died (n = 10) versus survived (n = 5). Statistical significance was determined using Mann-Whitney U tests.
Results: In this study, MThBI patients had significantly higher levels of TAFIa/ai (49.8±25.9 ng/mL, range: 18.9-105.4 ng/mL) compared to the mean of 60 healthy individuals (15.3±6.8 ng/mL; p=<0.001). 80% of these patients showed coordinated increases above the upper limit of the normal range for d-dimer, PAP, and TAFIa/ai. Among the group of patients that survived, mean TAFIa/ai was 45.5±29.2 ng/mL compared to 58.4±17.1 in patients who died (p = 0.21).
Conclusion: On admission, MThBI patients have increased expression of TAFIa/ai. This suggests that this group of patients exhibited inhibition of fibrinolysis early after injury coinciding with evidence of hemostatic activation. Taken together, this potentially represents a mechanism to increased clot stability following MThBI.