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Summary   Background  The plasma protease factor  VII ‐activating protease ( FSAP ) can release nucleosomes from late apoptotic cells. Nucleosomes are markers of cell death, and extracellular cell‐free  DNA  has been suggested to play an important role in inflammation and has been demonstrated to correlate with severity and outcome in sepsis patients.    Objective  To investigate  FSAP  activation in patients suffering from  Burkholderia pseudomallei  infection (melioidosis), an important cause of Gram‐negative sepsis in Southeast Asia. As diabetes mellitus (DM) is the most important risk factor for both melioidosis and sepsis, we were also able to examine the role of DM in  FSAP  activation in this cohort of patients.    Methods  In a prospective observational study, complexes of  FSAP  with α 2 ‐antiplasmin (AP) were assayed in 44 patients with melioidosis, 34 of whom were classified as diabetic. Eighty‐two healthy subjects served as controls (52 with DM and 30 without).    Results  FSAP–AP complex levels were markedly elevated in patients as compared with controls. The FSAP level increased by 16.82 AU mL −1  in patients with melioidosis after adjustment for the effect of DM in the regression model. As expected, FSAP activation was correlated with nucleosome release (slope = 0.74). No difference in FSAP activation on admission was seen between survivors and non‐survivors, but the extent of FSAP activation correlated with stage of the disease; repeated testing during convalescence showed a return towards normal values (day 0 vs. day 28, 4.16 AU mL −1 , 95% confidence interval [CI] 1.42–12.22).    Conclusion  Patients with Gram‐negative sepsis caused by  B. pseudomallei  have abundant  FSAP  activation, which significantly correlates with stage of disease. The presence of DM, however, does not influence the extent of  FSAP  activation.

Diabetes‐independent increase of factor VII ‐activating protease activation in patients with Gram‐negative sepsis (melioidosis)