A selection of important academic publications on sepsis and Heparin Binding Protein are shown below along with a summary of their conclusions.


Heparin-binding protein: a key player in the pathophysiology of organ dysfunction in sepsis
Fisher J, Linder A
J Intern Med. 2017 Mar 28
“During sepsis, there is a significant increase in plasma HBP, and levels correlate with the development of hypotension and organ dysfunction. The rapid assessment of HBP concentration could prove to be a valuable tool for the early diagnosis of severe sepsis; however, this remains to be confirmed further in larger and more heterogeneous populations”


Heparin-Binding Protein (HBP): A Causative Marker and Potential Target for Heparin Treatment of Human Sepsis-Induced Acute Kidney Injury
Fisher J et al
Shock 2017 Mar;17
“Elevated plasma HBP is associated with development of sepsis-induced AKI and HBP is involved in its pathophysiology. Our studies suggest that heparin(s) could be tested for efficacy and safety of prevention of sepsis-induced AKI”


Elevated plasma Heparin-Binding Protein is associated with early death after resuscitation from cardiac arrest
Ristagno G et al
Critical Care 2016 20:251
“Elevated plasma levels of HBP at ICU admission were independently associated with early death in ICU “


Heparin-binding protein is important for vascular leak in sepsis
Bentzer P et al
Intensive Care Med Exp 2016 Dec; 4:33
“HBP is a potential mediator of sepsis-induced acute lung injury through enhanced endothelial permeability. HBP increases permeability through an interaction with luminal GAGs and activation of the PKC and Rho-kinase pathways. Heparins are potential inhibitors of HBP-induced increases in permeability.”


Suilysin Stimulates the Release of Heparin Binding Protein from Neutrophils and Increases Vascular Permeability in Mice
Chen S et al
Frontiers in Microbiology August 2016
“In summary, we reported for the first time in this study that SLY from the highly virulent S. suis strain 05ZYH33 induced the release of HBP from PMNs in a Ca2 influx-dependent manner and increased vascular leakage in mice.”


Increased Plasma Levels of Heparin-Binding Protein on Admission to Intensive Care Are Associated with Respiratory and Circulatory Failure
Tyden J et al
PLOS One March 2016
“A high concentration of HBP in plasma on admission to the ICU is associated with respiratory and circulatory failure later during the ICU care period. It is also associated with increased 30-day mortality.”


Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department
Linder A et al
Crit Care Med 2015 Nov;43(11):2378-86
“In 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”


Increased plasma levels of heparin-binding protein in patients with acute respiratory distress syndrome
Qionghua Lin et al
Critical Care 2013 17:R155
“Patients with ALI/ARDS had significantly higher median levels of HBP compared to patients with CPE. HBP levels of non-survivors were significantly higher than survivors. HBP was the independent predictor for 30-day mortaility inpatients with ALI/ARDS”


Heparin-binding protein: An early indicator of critical illness and predictor of outcome in cardiac arrest
Dankiewicz J et al
Resuscitation 2013 Jan 11
“Elevated HBP is an early indicator of organ failure and poor neurological outcome after CA, independent of microbial infection, and should be further evaluated in prospective trials. The temporal profile of HBP is suggestive of a role in the pathogenesis of critical illness after CA”


Sepsis biomarkers: a review
Pierrakos C and Vincent J-L
Crit Care 2010, 14:R15
“Many biomarkers have been evaluated for use in sepsis. Most of the biomarkers had been tested clinically, primarily as prognostic markers in sepsis; relatively few have been used for diagnosis. None has sufficient specificity or sensitivity to be routinely employed in clinical practice. PCT and CRP have been most widely used, but even these have limited ability to distinguish sepsis from other inflammatory conditions or to predict outcome”


Heparin Binding Protein: An Early Marker of Circulatory Failure in Sepsis
Linder A et al
Clin Inf Dis 2009:49;1044-1050
“Twenty-six patients were diagnosed with severe sepsis and septic shock, 44 patients had severe sepsis without septic shock, 100 patients had sepsis, 43 patients had an infection without sepsis, and 20 patients had an inflammatory response caused by a noninfectious disease. A plasma HBP level >15 ng/mL was a better indicator of severe sepsis (with or without septic shock) than any other laboratory parameter investigated (sensitivity, 87.1%; specificity, 95.1%; positive predictive value, 88.4%; negative predictive value, 94.5%). Thirty-two of the 70 patients with severe sepsis were sampled for up to 12 h before signs of circulatory failure appeared, and in 29 of these patients, HBP plasma concentrations were already elevated. In febrile patients, high plasma levels of HBP help to identify patients with an imminent risk of developing sepsis with circulatory failure”


Elevated plasma levels of heparin-binding protein in intensive care unit patients with severe sepsis and septic shock
Linder A et al
Crit Care 2012 May 21;16(3):R90
“Plasma HBP levels were significantly higher in patients with severe sepsis or septic shock compared to patients with a non-septic illness in the ICU. HBP was associated with severity of disease and an elevated HBP at admission was associated with an increased risk of death. HBP that rises over time may identify patients with a deteriorating prognosis. Thus, repeated HBP measurement in the ICU may help monitor treatment and predict outcome in patients with severe infections”


Should heparin-binding protein levels be routinely monitored in patients with severe sepsis and septic shock?
Holub M, Beran O
Crit Care, 2012 Jun 28;16(3):133
“In the present issue of Critical Care, Linder and colleagues demonstrate new aspects of HBP daily monitoring in ICU patients. The authors observed that high HBP plasma levels are associated with an increased mortality rate in both septic and nonseptic critically ill patients, indicating that HBP may be a reliable prognostic biomarker…if the results of the present study are validated in large clinical trials in different ICU populations and cost-effectiveness data become available, the serial HBP measurements will have a promising future”


Heparin-binding protein: a diagnostic marker of acute bacterial meningitis
Linder A et al
Crit Care Med 2011 Apr;39(4):812-7
“Elevated cerebrospinal fluid levels of heparin-binding protein distinguish between patients with acute bacterial meningitis and patients with other central nervous system infections”


Increased plasma levels of heparin-binding protein in patients with shock: a prospective, cohort study
Chew MS et al
Inflamm Res. 2012 Apr;61(4):375-9
“HBP is elevated in patients with shock from septic and non-septic etiologies. Future investigations are required to define the functional role of HBP in patients with shock”



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