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Heparin-Binding Protein as a Prognostic Biomarker of Sepsis and Disease Severity at the Emergency Department

Kahn, Fredrik*,†; Tverring, Jonas*,‡; Mellhammar, Lisa*,†; Wetterberg, Nils*,†; Bläckberg, Anna*,†; Studahl, Erika*; Hadorn, Niklas*; Kahn, Robin§,||; Nueesch, Susanne; Jent, Philipp¶,#; Ricklin, Meret E.; Boyd, John**; Christensson, Bertil*,†; Sendi, Parham#,††; Åkesson, Per*,†; Linder, Adam*,†

doi: 10.1097/SHK.0000000000001332
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Objective: Rapid and early detection of patients at risk to develop sepsis remains demanding. Heparin-binding protein (HBP) has previously demonstrated good prognostic properties in detecting organ dysfunction among patients with suspected infections. This study aimed to evaluate the plasma levels of HBP as a prognostic biomarker for infection-induced organ dysfunction among patients seeking medical attention at the emergency department.

Design: Prospective, international multicenter, convenience sample study.

Setting: Four general emergency departments at academic centers in Sweden, Switzerland, and Canada.

Patients: All emergency encounters among adults where one of the following criteria were fulfilled: respiratory rate >25 breaths per minute; heart rate >120 beats per minute; altered mental status; systolic blood pressure <100 mm Hg; oxygen saturation <90% without oxygen; oxygen saturation <93% with oxygen; reported oxygen saturation <90%.

Intervention: None.

Measurements and Main Results: A total of 524 emergency department patients were prospectively enrolled, of these 236 (45%) were eventually adjudicated to have a noninfectious disease. Three hundred forty-seven patients (66%) had or developed organ dysfunction within 72 h, 54 patients (10%) were admitted to an intensive care unit, and 23 patients (4%) died within 72 h. For the primary outcome, detection of infected-related organ dysfunction within 72 h, the area under the receiver operating curve (AUC) for HBP was 0.73 (95% CI 0.68–0.78) among all patients and 0.82 (95% CI 0.76–0.87) among patients confidently adjudicated to either infection or no infection. Against the secondary outcome, infection leading to admittance to the ICU, death or a persistent high SOFA-score due to an infection (SOFA-score ≥5 at 12–24 h) HBP had an AUC of 0.87 (95% CI 0.79–0.95) among all patients and 0.88 (95% CI 0.77–0.99) among patients confidently adjudicated to either infection or noninfection.

Conclusions: Among patients at the emergency department, HBP demonstrated good prognostic and discriminatory properties in detecting the most severely ill patients with infection.

*Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden

Department of Infectious Diseases, Skåne University Hospital, Lund, Sweden

Department of Infectious Diseases, Helsingborg General Hospital, Helsingborg, Sweden

§Division of Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden

||Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden

Department of Emergency Medicine, Inselspital, University Hospital, Bern, Switzerland

#Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

**Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada

††Institute for Infectious Diseases, University of Bern, Bern, Switzerland

Address reprint requests to Fredrik Kahn, MD, PhD, Division of Infection Medicine, Department of Clinical Sciences, Lund University, BMC B14, Baravägen 27, 223 63 Lund, Sweden. E-mail: Fredrik.Kahn@med.lu.se

Received 4 December, 2018

Revised 21 December, 2018

Accepted 14 February, 2019

BC, PÅ, and AL are listed as inventors on a patent on the use of HBP as a diagnostic tool in sepsis filed by Hansa Medical AB. Axis Shield Ltd analyzed the PCT and distributed free of charge ELISA-kits for determining HBP.

Swedish Government Funds for Clinical Research (ALF), the Crafoord foundation, the Swedish Society of Medicine, the Thelma Zoégas foundation, the foundation of Petrus and Augusta Hedlund, the foundation of Magnus Bergvall, the Royal Physiographic Society, Lund, the Foundations of Skåne University Hospital, the foundation of Alfred Österlund, the foundation of Clas Groschinsky, and The Knut and Alice Wallenberg foundation are acknowledged for generous support.

The authors declares no conflicts of interest.

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© 2019 by the Shock Society