title: 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.
  
  
  RESULTS
  Patients demonstrated strong activation of the coagulation system, as reflected by high plasma levels of soluble tissue factor, the prothrombin fragment F(1+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-alpha2-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, F(1+2), tPA and PAPc and lower protein C and antithrombin levels on admission than patients who survived.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. w.j.wiersinga@amc.uva.nl
authors.forename: W J
authors.initials: WJ
authors.lastname: Wiersinga
authors.forename: J C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: M
authors.initials: M
authors.lastname: Levi
authors.forename: C
authors.initials: C
authors.lastname: Van 't Veer
authors.forename: N P
authors.initials: NP
authors.lastname: Day
authors.forename: S J
authors.initials: SJ
authors.lastname: Peacock
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D008554:Melioidosis / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D008875:Middle Aged; D011379:Prognosis; D018805:Sepsis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers