Participation and interactions of neutrophil elastase in haemostatic disorders of patients with severe infections

Abstract

The prognosis of septicaemia depends on the occurrence of complications such as shock and coagulation defects. The damage to haemostasis is usually explained by the action of the main coagulation and fibrinolysis enzymes, thrombin and plasmin. This paper presents data concerning the role of a third protease, granulocytic elastase. 82 patients who had been admitted to our hospital with suspected septicaemia were examined. Septicaemia was proven in 22 patients by the growth of microorganisms in blood cultures, and was clinically diagnosed in 9 patients. The plasma levels of neutrophil elastase-like protease complexed to a,antitrypsin (a,AT-ELP) were measured by zone immunoelectrophoresis assay (ZIA). The a,AT-ELP values were significantly increased in the 31 septic as compared to the 51 non-septic patients. In patients with complicated septicaemia, negative correlations of a,AT-ELP with factor XI11 and the coagulation inhibitor antithrombin 111 were demonstrable. Among the patients with septic complications, the 3 who survived exhibited a dramatic decrease of a,AT-ELP, whereas in the other 16 patients who died the levels remained elevated. It might be of therapeutic significance that in 9 patients receiving fresh plasma and AT IIIconcentrate substitution for DIC the a,AT-ELP levels dropped, whereas they remained high in the other septicaemia patients. There were no correlations between a,AT-ELP and the a,antiplasmin-plasmin complexes (a,AP-PI), but strong correlations with signs of coagulation. The data suggest an interaction of coagulation and elastase release, probably involving the Hageman factor.A severe complication of septicaemia, in most to as disseminated intravascular coagulation instances associated with septic shock, is haemor-(DIC) or consumption coagulopathy (13). The rhagic diathesis. The coagulation system is then consumption of coagulation factors is often decompensated a s a result of an enhanced pro-aggravated by hyperfibrinolysis due to plasmin tein turnover in haemostasis. Since enhanced clot-activation. ting can be demonstrated in this syndrome, it is As early as 1968 the possibility of neutral explained by the action of thrombin and referred granulocyte proteases had been considered as t

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