Temporal changes in factors associated with neutrophil elastase and coagulation in intensive care patients with a biphasic waveform and disseminated intravascular coagulation

Abstract

The biphasic waveform is an early marker of disseminated intravascular coagulation (DIC). Neutrophil elastase (NE) cleaves coagulation factors; thus, elevated elastase levels or its dysregulation by α-1-protease inhibitor (A1PI) may be linked to DIC. Time courses over a period were determined for factors associated with NE and coagulation in 14 Intensive Care Unit patients with a biphasic waveform who developed DIC. The data were analyzed using a random coefficient linear regression model to predict the variables' mean values on day 0 and their mean rates of change over the period in which the biphasic waveform appeared. The biphasic waveform was normal on day 0, maximized on day 1, and approached normal again by day 4. A1PI/NE complex levels were 2.5-fold greater than normal for the entire period. The A1PI activity, antigen, and specific activity levels were normal on day 0 and increased thereafter by 21.0, 10.5, and 8.9% of normal per day, respectively. Factor II, V, VII, IX, and X activity levels were, respectively, 57, 46, 46, 77, and 46% of normal on day 0, whereas factor VIII and fibrinogen levels were normal. All coagulation factor levels trended upward with time but not significantly. The prothrombin time, but not the activated partial thromboplastin time, was prolonged, and the platelet counts and hematocrits were below normal on day 0 and remained so thereafter. We conclude that events associated with neutrophil activation, elastase release, and perturbations of coagulation precede both the appearance of the biphasic waveform and the diagnosis of DIC in these patients. © 2004 International Society on Thrombosis and Haemostasis.