ACTIVATION OF PROTEIN-C AND ITS DISTRIBUTION BETWEEN ITS INHIBITORS, PROTEIN-C INHIBITOR, ALPHA(1)-ANTITRYPSIN AND ALPHA(2)-MACROGLOBULIN, IN PATIENTS WITH DISSEMINATED INTRAVASCULAR COAGULATION

Activation and inactivation of protein C during the clinical course of disseminated intravascular coagulation (DIC) was studied in three pat ients by qualitative (Western blotting) and quantitative (ELISA) analy sis and the intensity of procoagulant activity monitored by the measur ement of thrombin and factor Xa antithrombin III complexes. In one pat ient, inhibitor complexes of APC with protein C inhibitor (PCI) and al pha1-antitrypsin (alpha1-AT) were observed and the latter predominated at presentation. Both disappeared during the development of remission but the loss of alpha1-AT complexes preceded PCI complexes which on W estern blotting appeared to increase in intensity prior to disappearan ce. The two other patients bled to- death from uncontrollable haemorrh age. In both cases, APC/inhibitor complexes with alpha2-macroglobulin (alpha2-M) in addition to PCI and alpha1-AT were detected and persiste d until death. Although PCI appeared to be the primary inhibitor in al l three cases, alpha1-antitrypsin and particularly alpha2-macroglobuli n appeared to assume greater roles in the two fatal cases. These data are similar to previous findings in an experimental animal model of DI C that suggested that alpha2-macroglobulin and alpha1-antitrypsin beco me more important inhibitors of APC as the primary inhibitor PCI is co nsumed in the face of a sustained procoagulant challenge.