PROTEINASE-INHIBITOR COMPLEXES (PIC) IN SEPTIC AND NON-SEPTIC SHOCK. COAGULATION; LEUKOCYTE AND BACTERIAL PROTEASE INHIBITION BY MEANS OF PLASMA-INHIBITOR REPLACEMENT
In septic or cardiac shock antithrombin III-thrombin (AT III-Thr) and a1antitrypsin-elastase(a1AT-ELP) as well as a2antiplas-min-plasmin (a2AP-Pl) are found to be elevated to different extents. In cardiac shock AT III-Thr is predominantly increased, while in septic disorders a2AT-ELP as indicator of leukocyte stimulation is additionally found to be elevated. Stimuli for leukocyte activation are bacterial endotoxins, immune complexes, factor Xlla and others. The possible action of bacterial proteases during septic infections is only known in animal models. To stop hemorrhagic complications in disseminated intravascular coagulation (DIC) following septic (n=24) or non-septic (n=15) shock, we treated the patients with AT III concentrate and FFP in relatively high amounts containing a2macroglobulin (a2M), a1antitrypsin (a1AT) and others which are not available as concentrates. Subsequent to the procedure PIC's decreased, coagulation factors and inhibitors as well as thrombocyte counts increased. In in vitro models bacterial proteases have been shown to destroy a1AT, activate prothrombin and others. Only a2M may inhibit proteolytic activity of Staph aureus, N. meningitidis, P. aeroginosa and K1. pneumoniae and E. coli as our in vitro studies, using fibrin plates containing a2M, demonstrated. Not only bleeding or microthrombotic complications might be influenced by plasma derivative substitution, but also proteases released from bacteria