Proteins of the Hageman Factor System in an Inflammatory Reaction in the Acute Period of Severe Brain Injury

Abstract

Objective: to study the time course of changes and an association of contact factors and their inhibitors with the global values of hemocoagulation, fibrinolysis, and inflammatory reactants in acute severe brain injury (SBI) in order to deepen notions of Hageman factor system functioning. Subjects and methods. One hundred and thirteen patients with SBI were examined on 1 to 21 days of injury. The level of unconsciousness averaged a Glasgow coma score of 6.8±0.25. A control group included 23 healthy individuals. The investigators determined the activity of contact factors (prekallikrein, high-molecular-weight kininogen, factors XII, XI) and their inhibitors (total activity of the protein C system, the activity and quantity of antithrombin III, C1 esterase inhibitor, a^antitrypsin, fl^-antiplasmin, fl^-macroglobulin), hemostatic parameters (blood fibrinolytic activity by an euglobulin test; factor XII-kallikrein-dependent fibrinolysis, treptokinase induced fibrinolysis by calculating the plasminogen reserve index, activated partial thromboplastin time, fibrinogen, D-dimer, and soluble fibrin monomer complexes), and inflammatory reactants (C-reactive protein, IL10, IL2, IL4, IL5, IL6, IL8, IL10, IL12p70, TNF-a, and IFN-y). Results. The acute period of SBI was marked by significant deficiency and imbalance of contact factors and their physiological inhibitors. In SBI, prekallikrein rather than factor XII plays a central role in the function of the contact factor system due to inflammatory inhibition of Hageman factor synthesis, which disturbs its key role in the reactions of contact activation of homeostatic proteolytic systems. Out of the considered systems, the activation of which is associated with contact factors, the function of the internal mechanism of fibrinolysis is largely changed; at the same time the internal hemocoagulation activation pathway remains virtually intact. When an inflammatory reaction develops after SBI, normal Hageman factor system protein relationships are impaired. There is the inflammatory inhibition by cytokines, including IL12p70 that is of the greatest importance, which plays a significant role in reducing the level of contact factors and a number of their inhibitors. Key words: severe brain injury, Hageman factor system, antiproteases, inflammation, cytokines.