Dysregulation of Inflammatory and Hemostatic Markers In Disseminated Intravascular Coagulation.

Abstract 3656

Disseminated intravascular coagulation (DIC) represents a complex polypathologic syndrome where marked alterations in the hemostatic system are manifested. As a result several inflammatory mediators are upregulated through multiple mechanisms. The upregulation of inflammatory mediators such as anaphylatoxin C5a (C5a), procalcitonin (PCT), interleukin 6 (IL-6), interleukin 10 (IL-10), myeloperoxidase (MPO) and c reactive protein (CRP), and circulating levels of hemostatic markers including protein C inhibitor (PCI), plasminogen activator inhibitor 1 (PAI-1), prothrombin fragment1.2 (F1.2), thrombin antithrombin complex (TAT), antithrombin (AT), activated protein C (APC) and protein C (Pr C) were evaluated in the baseline samples of an initial cohort of provisionally diagnosed DIC and sepsis patients enrolled in an ongoing clinical trial designed to assess the safety and efficacy of r-thrombomodulin (ART-123) (n=100). The control group consisted of normal male and female volunteers (n=30). 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 normal volunteers, patients showed a 5–10 fold increase in the circulating level of most inflammatory markers, with the exception of PCT, IL-6 and CRP, where the increase was over 50 fold. PCI, Pr C and AT exhibited slight decreases. Wide individual variations were obvious. These results clearly indicate that inflammation, thrombin generation, impairment of fibrinolysis and impairment of endogenous anticoagulants play a key role in the pathogenesis of DIC.