Impaired Anticoagulant Activity Of Protein C And Activation Of Neutrophils In Extensive Lung Cancer

Lung cancer is associated with an increased incidence of thrombosis. An 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 degrading inhibitory proteins. We assessed antigen level, amidolytic activity, and clotting activity of the plasma anticoagulant protein C and the activation markers thrombin-antithrombin complex (TAT) and neutrophil elastase-alpha(1)-antitrypsin complex (EAT) in 67 lung cancer patients before antineoplastic treatment was begun. The protein C clotting activity was lower (p = 0.010) in the patients with extensive than in those with limited disease. However, the median levels remained within the normal range in both groups (91 vs. 108% of normal). The median 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 groups. There was no significant correlation of protein C measurements with TAT levels, but there were significant negative correlations between EAT and protein C clotting activity and antigen level. The data suggest that in patients with lung cancer, there may be an alteration of the protein C molecule, which reduces antigen level and impairs clotting activity without affecting amidolytic activity. The negative correlation with EAT levels might point to limited degradation of protein C by neutrophil enzymes, leading to partial loss of epitopes detected by the immunologic determination and of structures necessary for the biologic effect of protein C upon clotting time. Further studies should clarify whether such a modification of protein C could contribute to the increased incidence of thrombosis in lung cancer patients.