• Adam Linder, Ryan Arnold, John H Boyd, Marko Zindovic, Igor Zindovic, Anna Lange, Magnus Paulsson, Patrik Nyberg, James A Russell, David Pritchard, Bertil Christensson, and Per Åkesson.
• 1Department of Clinical Sciences, Division of Infection Medicine, Klinikgatan 1, Skåne University Hospital, Lund University, Lund, Sweden. 2Value Institute and Department of Emergency Medicine, Christiana Care Health System, Newark, DE. 3Centre for Heart Lung Innovation, Division of Critical Care Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada. 4Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden. 5Department of Translational Medicine, Lund University, Lund, Sweden. 6Department of Emergency Medicine, Linköping University Hospital, Linköping, Sweden. 7Axis-Shield Diagnostics, Dundee, GB, United Kingdom.
• Crit. Care Med. 2015 Nov 1;43(11):2378-86.

ObjectivesEarly identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting.DesignA prospective international multicenter cohort study.SettingSeven different emergency departments in Sweden, Canada, and the United States.PatientsAdult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count).InterventionNone.Measurements And Main ResultsPlasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12-24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (>30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve=0.80). The performance of heparin-binding protein was confirmed in the validation cohort.ConclusionIn patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours.

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