Decreased Protein C, Protein S and Antithrombin III Levels are predictive of poor outcome in Gram-negative sepsis caused by Burkholderia pseudomallei

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The acute septicemic form of Burkholderia pseudomallei infection or Melioidosis is associated with substantial release of endotoxin, TNF-α and IL-1. This inflammatory response leads to endothelial injury, activation of the extrinsic coagulation cascade, depletion of naturally occurring anticoagulants, microvascular thrombosis, organ failure and death. Plasma samples drawn at baseline and at time points during the illness from 30 patients with Melioidosis were assayed for D-dimer levels, Protein C and Protein S antigen levels and Antithrombin III functional activities. Results of samples drawn during the illness were averaged for each patient. Baseline and continued deficiencies of Protein C, Protein S and Antithrombin III were predictive of poor outcome in a statistically significant fashion by logistic regression.

Endothelial injury as a result of inflammatory response to Burkholderia pseudomallei infection leads to coagulopathy and depletion of the natural anticoagulants Protein C, Protein S and Antithrombin III. Early and continued deficiency of these factors is predictive of poor outcome. Replacement therapy of depleted factors to achieve normal levels may be a worthwhile strategy for patients with Gram-negative sepsis.

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