Evaluation of the Heparin Binding Protein Levels in Sepsis
Evaluation of the Heparin Binding Protein Levels in Sepsis
Present criteria used to define sepsis are non-specific, making it difficult to both
 distinguish sepsis from other diseases and to predict which patients are likely to become
 more severely ill. In standard care, patients at risk of becoming more severely ill are
 neither identified nor indicated for resuscitative efforts until they develop hemodynamic
 insufficiency or organ failure; after progression to severe disease, mortality increases
 significantly. The identification of risk patients can lead to earlier initiation of
 resuscitation therapies and potentially lead to reduced morbidity and mortality. This study
 aims to determine whether Heparin-binding protein (HBP), which is secreted from neutrophils
 during infection and a mediator of vascular leakage, can act as a biomarker for the
 progression to severe sepsis with circulatory failure.

 The objective of this study is to validate the utility of HBP to predict the development of
 delayed onset organ dysfunction in sepsis in patients and to compare the performance of HBP
 relative to currently used prognostic biomarkers in sepsis.
Sepsis is a heterogeneous disorder caused by an invasive infection that results in host
 inflammatory response. The underlying pathogenesis is complex and dependent on the etiologic
 microorganism, site of infection, and host factors. Present criteria defining sepsis
 (including change of body temperature, increased heart and respiration rates, and
 leukocytosis/leukopenia) are non-specific making it difficult to distinguish sepsis from
 other diseases and in particular to predict which patients are likely to become more severely
 ill. The consensus definition of sepsis has been debated over the past years and one
 suggested approach is to focus more on the presence of organ dysfunction. In standard care,
 patients at risk of becoming more seriously ill are not identified nor indicated for
 resuscitative efforts until they develop hemodynamic insufficiency or organ failure. However,
 after progression to severe disease mortality increases significantly. A recent study showed
 that almost a quarter of patients presenting with uncomplicated sepsis in an Emergency
 Department (ED) developed severe sepsis or septic shock within 72 hours. Delayed in-hospital
 progression to increased organ dysfunction was associated with increased transfer to the
 intensive care unit (ICU) and increased hospital length of stay. The identification of risk
 patients can lead to earlier initiation of resuscitation therapies and potentially lead to
 reduced morbidity and mortality. There are also increasing evidence that a single episode of
 severe sepsis has negative impact on quality of life and mortality several years after the
 actual incident. Also, recent studies indicate that less severe organ dysfunction, such as
 small increases in serum creatinine, are associated with increased long-term mortality among
 sepsis survivors.

 Mechanisms that trigger the release of heparin-binding protein (HBP) from neutrophils in the
 presence of bacteria have previously been reported. HBP has several functions such as a
 chemo-attractant and as an activator of monocytes and macrophages. Also, it induces vascular
 leakage by interacting with the capillary endothelium and breaking cell barriers. In vivo
 studies have demonstrated that HBP released by the complex formed by the group A
 streptococcal M1 protein and fibrinogen induces a massive tissue edema contributing to severe
 organ damage. In clinical investigations, the release of HBP has been demonstrated in various
 infectious diseases caused by a wide array of bacteria. A recent single-center study of
 patients admitted for suspected infection and fever showed that plasma levels of HBP were
 significantly higher among patients who presented with or developed severe sepsis with
 circulatory failure.

 A prospective observational study in a tertiary care Emergency Department. Patients must be
 identified and enrolled within 72 hours of qualifying inclusion criteria. At this time,
 unused blood samples collected for routine testing will be examined and the plasma level of
 HBP will be recorded; only blood samples processed by the lab within 3 hours of collection
 will be used. In addition, physiologic variables detailed in the data elements section,
 including mental status, metabolic, renal, heme, hepatic, respiratory, cardiovascular,
 resuscitation, and vasopressor use will be recorded. Patients who meet the inclusion criteria
 will be identified. Researchers will collect and record a resuscitation summary for a span of
 4 hours; this data, outlined in the data elements section, will be linked to the quality
 improvement (QI) database of Sepsis Research. Additionally, the patient's HBP plasma levels
 will be measured from unused blood samples collected for routine lab testing time (T) 24, 48,
 and 72-hours (T24, T48, T72) after meeting the inclusion criteria (T0); resuscitation
 summaries will also be collected at T24, T48, T72. For patients meeting sepsis alert
 criteria, T0 will be defined as the time that the patient qualified; those enrolled based on
 Predisposition, Injury, Response, Organ dysfunction (PIRO) score will have T0 defined as the
 time hospital admission was ordered. Patients will be followed throughout their time in the
 hospital and their outcomes will be recorded.
Inclusion Criteria:

 -  Clinical diagnosis of a bacterial or viral infection

 -  18 years or older

 -  Meet the sepsis alert criterion (Hypotension (BP < 90 after 2 L of fluids or lactate ≥
 4) OR

 -  PIRO (Predispose, Infection, Response, Organ dysfunction ) score ≥ 15 .

 Exclusion Criteria:

 -  Minors (less than 18 years of age)

 -  Patients who do not meet sepsis criteria as described above