Abstract

Abstract 2223

Disseminated intravascular coagulation (DIC) represents a complex pathophysiologic syndrome where marked alterations in the hemostatic system are manifested. As a result several inflammatory mediators are up regulated through multiple mechanisms. The up regulation of inflammatory mediators such as anaphylatoxin C5a (C5a), procalcitonin (PCT), interleukin 6 (IL-6), interleukin 10 (IL-10), myeloperoxidase (MPO), C reactive protein (CRP), and circulating levels of hemostatic markers including protein C inhibitor (PCI), plasminogen activator inhibitor 1 (PAI-1), and protein C (Pr C) were evaluated in 758 subjects enrolled in a randomized, double-blind, placebo-controlled, Phase-2B study evaluating the safety and efficacy of recombinant thrombomodulin (ART-123) in subjects with sepsis and suspected DIC. Thirty healthy male and female volunteers served as the control group. Commercially available ELISA methods were used to measure the various mediators. Marked deviations in the circulating levels of these markers, as compared to controls, were noted as shown in the following table. Compared with controls, subjects in DIC showed an increase in the circulating levels of most inflammatory markers. The levels of PCT, IL-6 and CRP, where considerably higher in the DIC subjects whereas PCI, Pr C and AT exhibited slight decreases. Wide individual variations were present. The PAI-1 levels were also increased in the DIC subjects. These results are tabulated below. These results clearly indicate that inflammation and impairment of fibrinolysis play a key role in the pathogenesis of DIC

ParameterNomal (NHP Mean+SEM)DIC (Baseline Mean+SEM)% Change
Protein C (% Ag) 82.5 ± 13.6 47.6 ± 23.7 −42.2% 
Functional Protein C (%) 83.4 ± 13.2 46.2 ± 29.8 −44.6% 
PCI (% Inhibition) 130.0 ± 24.6 79.4 ± 105.5 −38.9% 
PAI-1 (ng/ml) 35.4 ± 10.8 140.6 ± 165.6 297.1% 
CRP (ug/ml) 2.6 ± 0.4 48.0 ± 14.2 1736.9% 
C5a (ng/ml) 9.2 ± 3.2 17.2 ± 13.3 85.1% 
IL-6 (pg/ml) 9.3 ± 3.7 620.3 ± 1883.4 6583.9% 
IL-10 (pg/ml) 13.9 ± 13.1 130.2 ± 118.6 836.1% 
MPO (ng/ml) 16.0 ± 4.2 108.1 ± 68.6 574.6% 
PCT (ng/ml) 0.2 ± 0.13 21.9 ± 43.3 14514.5% 
ParameterNomal (NHP Mean+SEM)DIC (Baseline Mean+SEM)% Change
Protein C (% Ag) 82.5 ± 13.6 47.6 ± 23.7 −42.2% 
Functional Protein C (%) 83.4 ± 13.2 46.2 ± 29.8 −44.6% 
PCI (% Inhibition) 130.0 ± 24.6 79.4 ± 105.5 −38.9% 
PAI-1 (ng/ml) 35.4 ± 10.8 140.6 ± 165.6 297.1% 
CRP (ug/ml) 2.6 ± 0.4 48.0 ± 14.2 1736.9% 
C5a (ng/ml) 9.2 ± 3.2 17.2 ± 13.3 85.1% 
IL-6 (pg/ml) 9.3 ± 3.7 620.3 ± 1883.4 6583.9% 
IL-10 (pg/ml) 13.9 ± 13.1 130.2 ± 118.6 836.1% 
MPO (ng/ml) 16.0 ± 4.2 108.1 ± 68.6 574.6% 
PCT (ng/ml) 0.2 ± 0.13 21.9 ± 43.3 14514.5% 

Disclosures:

Osawa:Asahi Kasei Pharma America Corporation: Employment. Kaul:Asahi Kasei Pharma America Corporation: Employment.

Author notes

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Asterisk with author names denotes non-ASH members.