Activation of coagulation with concurrent impairment of anticoagulant mechanisms correlates with a poor outcome in severe melioidosis

Abstract

Background: Melioidosis, which is caused by infection with the Gram-negative bacterium Burkholderia pseudomallei, is an important cause of sepsis in South-East Asia with a mortality of up to 40%. Knowledge of the involvement of coagulation and fibrinolysis in the pathogenesis of melioidosis is highly limited. Objective: To define the involvement of the coagulation and fibrinolytic systems in patients with severe melioidosis. Methods: Parameters of coagulation and fibrinolysis were measured in 34 patients with culture proven septic melioidosis and 32 healthy controls. Rasults: Patients demonstrated strong activation of the coagulation system, as reflected by high plasma levels of soluble tissue factor, the prothrombin fragment F1+2 and thrombin-antithrombin complexes (TATc), and consumption of coagulation factors resulting in a prolonged prothrombin time and activated partial thromboplastin time. Concurrently, anticoagulant pathways were downregulated in patients: protein C, protein S, and antithrombin levels were all decreased when compared to controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis, as reflected by elevated concentrations of tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1, plasmin-α2-antiplasmin complexes (PAPc) and D-dimer. High TATc/PAPc ratios in patients pointed to a predominance of the prothrombotic pathway in melioidosis. Furthermore, soluble thrombomodulin levels were increased. The extent of coagulation activation correlated with mortality; patients who went on to die had higher TATc, F1+2, tPA and PAPc and lower protein C and antithrombin levels on admission than patients who survived. Conclusion: The coagulation system is strongly activated during melioidosis. A high degree of activation of the coagulation system is an indicator of poor outcome in patients with melioidosis. © 2007 International Society on Thrombosis and Haemostasis.