IntroductionAlthough many sepsis biomarkers have shown promise in selected patient groups, only C-reactive protein and procalcitonin (PCT) have entered clinical practice. The aim of this study was to evaluate three promising novel sepsis biomarkers in unselected patients at admission to intensive care. We assessed the performance of pancreatic stone protein (PSP), soluble CD25 (sCD25) and heparin binding protein (HBP) in distinguishing patients with sepsis from those with a non-infective systemic inflammatory response and the ability of these markers to indicate severity of illness.MethodsPlasma levels of the biomarkers, PCT and selected inflammatory cytokines were measured in samples taken from 219 patients during the first six hours of admission to intensive or high dependency care. Patients with a systemic inflammatory response were categorized as having sepsis or a non-infective aetiology, with or without markers of severity, using standard diagnostic criteria.ResultsBoth PSP and sCD25 performed well as biomarkers of sepsis irrespective of severity of illness. For both markers the area under the receiver operating curve (AUC) was greater than 0.9; PSP 0.927 (0.887 to 0.968) and sCD25 0.902 (0.854 to 0.949). Procalcitonin and IL6 also performed well as markers of sepsis whilst in this intensive care unit (ICU) population, HBP did not: PCT 0.840 (0.778 to 0.901), IL6 0.805 (0.739 to 0.870) and HBP 0.607 (0.519 to 0.694). Levels of both PSP and PCT reflected severity of illness and both markers performed well in differentiating patients with severe sepsis from severely ill patients with a non-infective systemic inflammatory response: AUCs 0.955 (0.909 to 1) and 0.837 (0.732 to 0.941) respectively. Although levels of sCD25 did not correlate with severity, the addition of sCD25 to either PCT or PSP in a multivariate model improved the diagnostic accuracy of either marker alone.ConclusionsPSP and sCD25 perform well as sepsis biomarkers in patients with suspected sepsis at the time of admission to intensive or high dependency care. These markers warrant further assessment of their prognostic value. Whereas previously published data indicate HBP has clinical utility in the emergency department, it did not perform well in an intensive-care population.

Pancreatic stone protein and sCD25 perform well as infection and sepsis biomarkers, with a similar performance than PCT, in ED patients with suspected infection. Further larger studies investigating use of PSP and sCD25 are needed.

High factor VIII (FVIII) levels are known to be a risk factor for deep venous thrombosis, but the mechanisms responsible for high FVIII levels remain unclear. Here, a new phenotype "FVIII level residuum" (FVIII-R) was defined in order to eliminate the impact of common determinants on FVIII levels. We studied 13 families of patients with thrombosis and reproducibly high FVIII levels of unknown origin.