Increased mortality in systemic inflammatory response syndrome patients with high levels of coagulation factor VIIa

Abstract

The tissue factor (TF)- Factor VIIa (FVIIa) complex has a pivotal role in inflammatory and coagulation responses in patients with systemic inflammatory response syndrome (SIRS) and sepsis. Because zymogen FVII (FVII) and FVIIa compete for binding to TF, their plasma levels determine if a catalytically active TF-FVIIa complex will be formed. To study mortality in SIRS patients as a function of FVIIa and FVII levels in plasma. This was a cohort study of 275 patients presenting with SIRS, aged 18 years or older and with an anticipated Intensive Care Unit (ICU) stay of at least 24h. FVIIa was measured using a novel, quantitative assay that recognizes FVIIa, but not FVII. All-cause hospital mortality was followed over a period of 60days. The percentage of FVII measured as FVIIa was higher in non-survivors than survivors (2.8%, IQR=1-5.5% vs. 1.5%, IQR=0.6-3.3%; P=0.034). High levels of FVIIa were associated with decreased 60-day cumulative survival (62% vs. 81%, P=0.030); the opposite was observed for FVII (84% vs. 76%, P=0.039). Patients with high-FVIIa and low-FVII levels had a three-fold increased hazard ratio (HR) compared with the patients that had low-FVIIa and high-FVII levels (HR=3.24, 95% confidence interval [CI]=1.41-7.36). This association persisted after adjusting for the APACHE IV score (adjusted HR=2.75, 95% CI=1.2-6.27). SIRS patients with high-FVIIa and low-FVII on admission have an increased mortality risk, an association that is independent from the parameters included in the APACHE IV score.