Plasma levels of granulocyte elastase‐α₁‐proteinase inhibitor complex in patients with disseminated intravascular coagulation: Pathophysiologic implications

Abstract

To investigate the role of neutrophil activation in the pathophysiology and sequelae of disseminated intravascular coagulation (DIC), we measured plasma levels of granulocyte elastase-alpha 1-proteinase inhibitor complex (GEPIC) in 41 patients with DIC and 27 patients with similar underlying conditions but without DIC. Mean GEPIC levels were significantly higher in patients with DIC (421.0 +/- 45.6 ng/ml) than in patients without DIC (246.1 +/- 41.9 ng/ml, P < 0.01). Significant differences were also noted in DIC patients with or without infection (474.7 +/- 61.2 ng/ml vs. 302.4 +/- 48.9 ng/ml, P < 0.04), with or without organ dysfunction (546.6 +/- 72.7 ng/ml vs. 305.6 +/- 42 ng/ml, P < 0.01), and with or without respiratory failure (640.0 +/- 91.2 ng/ml vs. 328.1 +/- 55.1 ng/ml, P < 0.01). No significant difference was found in mean GEPIC levels in DIC patients with or without renal failure, heart failure, hepatic failure, or gastrointestinal bleeding. The frequency of respiratory failure correlated with rising plasma levels of GEPIC. Mortality was higher in patients with GEPIC levels > 500 ng/ml (53.8%) than in patients with GEPIC levels < 500 ng/ml (28.6%). This correlation was particularly strong in patients with DIC, infection, and respiratory failure. Based on these data, we suggest that neutrophil activation, triggered by the coagulation cascade and perhaps augmented by endotoxin or cytokine release with infection, significantly contributes to respiratory failure and mortality in patients with DIC.

Heterogeneity in the incidence and clinical manifestations of disseminated intravascular coagulation: A study of 204 cases

“…Plasma levels of PAI-1 have been shown to be increased in patients with infections [29] and may contribute to the development of organ failure by inhibiting microthrombus dissolution in patients with infections. Consistent with this hypothesis is our previous report showing that plasma levels of neutrophil elastase-␣ 1 -proteinase inhibitor complex, a reflection of neutrophil activation, are significantly increased in DIC patients with infections who experience organ failure [15]. Furthermore, these cytokines activate neutrophils, thereby releasing inflammatory mediators such as neutrophil proteases and oxygen free radicals that are capable of damaging endothelial cells [10].…”

“…The presence of organ failure was diagnosed according to the following criteria [15]: respiratory failure, patients who required mechanical ventilation; renal failure, urine output <500 ml/day, serum urea nitrogen >50 mg/ dl, or serum creatinine >2 mg/dl; hepatic failure, total serum bilirubin >3 mg/dl or transaminases (AST and ALT) >100 IU/ml; heart failure, cardiac arrest, arrhythmia (atrial-ventricular block or evidence for acute myocardial infarction), central venous pressure >20 cm H 2 O …”

Nafamostat Mesilate

“…Consistent with this notion is the finding that neutrophil activation contributes to the respiratory failure and death of patients with DIC and serious infection (Fig. 4) (47). Granulocyte proteases and hydrogen peroxide synergistically damage the endothelial cell membranes and detach the endothelial cells from the matrix (71).…”

Effects of Inter- α -inhibitor in Experimental Endotoxic Shock and Disseminated Intravascular Coagulation

“…Septic shock is frequently associated with an uncontrolled activation of the coagulation and fibrinolytic systems (2)(3)(4)(5) that results in the syndrome of disseminated intravascular coagulation (DIC). DIC is closely linked to the development of the multiple-organ failure syndrome and contributes to the poor prognosis of sepsis.…”