IMPAIRED ANTICOAGULANT ACTIVITY OF PROTEIN-C AND ACTIVATION OF NEUTROPHILS IN EXTENSIVE LUNG-CANCER

Lung cancer is associated with an increased incidence of thrombosis. A n activation of coagulation is demonstrable in lung cancer patients by sensitive activation markers, as well as a stimulation of neutrophil granulocytes, which are known to interfere with hemostasis, e.g., by d egrading inhibitory proteins. We assessed antigen level, amidolytic ac tivity, and clotting activity of the plasma anticoagulant protein C an d the activation markers thrombin-antithrombin complex (TAT) and neutr ophil elastase-alpha(1)-antitrypsin complex (EAT) in 67 lung cancer pa tients before antineoplastic treatment was begun. The protein C clotti ng activity was lower (p = 0.010) in the patients with extensive than in those with limited disease. However, the median levels remained wit hin the normal range in both groups (91 vs. 108% of normal). The media n amidolytic activity levels (110 vs. 117% of normal; NS) were higher than the protein C antigen levels (82 vs. 77% of normal; NS) in both g roups. There was no significant correlation of protein C measurements with TAT levels, but there were significant negative correlations betw een EAT and protein C clotting activity and antigen level. The data su ggest that in patients with lung cancer, there may be an alteration of the protein C molecule, which reduces antigen level and impairs clott ing activity without affecting amidolytic activity. The negative corre lation with EAT levels might point to limited degradation of protein C by neutrophil enzymes, leading to partial loss of epitopes detected b y the immunologic determination and of structures necessary for the bi ologic effect of protein C upon clotting time. Further studies should clarify whether such a modification of protein C could contribute to t he increased incidence of thrombosis in lung cancer patients.