The disturbance of hemostasis in septic shock: role of neutrophil elastase and thrombin, effects of antithrombin III and plasma substitution*

Abstract

In 42 patients with septic shock, 29 of whom underwent substitution with antithrombin Ill concentrate and fresh frozen plasma for coagulation disorders, the proteinase-inhibitor complexes thrombin-antithrombin I11 and neutrophil elastasealpha, proteinase inhibitor, were elevated on admission. On admission, the elastase complex was significantly higher in the patients receiving substitution (p = 0.0039). but at the endpoint it was higher in the non-survivors (p = 0.0040). The elastase decrease was confined to the substitution group with the thrombin complex decreasing in both groups. Initially the thrombin complex correlated with prothrombin times and factor XIII, while the elastase complex correlated with creatinine, thrombocyte count and prothrombin times in the late stages. Hemostatic disturbance, thrombin generation and neutrophil elastase release were favorably influenced by substitution. Furthermore, in this uncontrolled pilot study, the survival rate was higher in the treated (16 of 29) than in the untreated (1 of 13) patients, although the treated patients initially had pronounced hemostatic disturbances.

Sepsis and Thrombosis

“…During severe inflammatory responses, antithrombin levels are markedly decreased because of consumption (as a result of ongoing thrombin generation), impaired synthesis (as a result of a negative acute phase response), and degradation by elastase from activated neutrophils. 36,37 A reduction in glycosaminoglycan availability at the endothelial surface (due to the influence of proinflammatory cytokines on endothelial synthesis) will also contribute to reduced antithrombin function, since glycosaminoglycans act as physiological heparin-like cofactors of antithrombin. Binding of glycosaminoglycans to antithrombin induces a conformational change at the reactive center of the antithrombin molecule, thereby rendering this protease inhibitor from a slow to a very efficient inhibitor of thrombin and other active coagulation factors.…”

Stabilized Infective Endocarditis and Altered Heparin Responsiveness During Cardiopulmonary Bypass

“…Previously reported predisposing factors of decreased heparin responsiveness include preoperative heparin use, old age, high platelet counts, and hypoalbuminemia [4,5]. Among them, AT III deficiency is thought to be the primary cause of altered heparin responsiveness [6,7] and is thought to be one of the main causes of decreased heparin responsiveness frequently encountered in patients with active infective endocarditis (IE).…”

Thrombosis in vasculitic disorders−clinical manifestations, pathogenesis and management

“…There is accumulating evidence suggesting that along with its central role in coagulation regulation, the protein C system also has an important function in modulating inflammation [43].In systemic inflammation, the decreased levels of protein C are attributed to impaired synthesis, degradation by neutrophil elastase and down-regulation of thrombomodulin [44]. In addition, in severe inflammatory responses, antithrombin levels are markedly reduced [45], favoring pro-thrombotic environment, as a result of increased consumption, impaired synthesis and degradation of antithrombin [44,45].…”