The Dynamics of Heparin-Binding Protein in Cardiothoracic Surgery—A Pilot Study

Sterner, Niklas; Fisher, Jane; Thelaus, Louise; Ketteler, Carolin; Lemež, Špela; Dardashti, Alain; Nilsson, Johan; Linder, Adam; Zindovic, Igor

doi:10.1053/j.jvca.2020.12.033

Cited by 7 publications

(14 citation statements)

References 27 publications

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“…We found that HBP circulates in the blood for a short time, with a distribution half-life below 10 minutes and an elimination half-life between 1-2 hours. This nding is in line with previous observations in humans [12,13] and in mice [14] which indicated that plasma HBP levels change rapidly between measurements. HBP has pro-in ammatory and vascular permeability-inducing effects that can be dangerous in situations such as sepsis [6], and therefore rapid removal of HBP from the circulation is likely a protective mechanism against these detrimental effects.…”

Section: Discussionsupporting

confidence: 93%

“…In the setting of surgery it is advantageous to have a biomarker that rapidly normalizes following the temporary in ammatory stimulus of surgery, making post-surgical measurements less likely to be confounded by falsely elevated results. This was found to be particularly important in cardiac surgery with cardiopulmonary bypass which has particularly high levels of neutrophil activation and in ammation [13]. On the other hand the combination of rapid clearance and rapid release from neutrophils could cause values to uctuate greatly between measurements, as was observed in a previous study [12] and could therefore affect their interpretability.…”

Section: Implications For Hbp As a Biomarkermentioning

confidence: 80%

“…Serial measurements of HBP every four hours in septic shock patients indicated that HBP levels uctuate widely between measurements [12]. Repeated measurements of HBP in patients undergoing cardiac surgery with cardiopulmonary bypass showed that HBP levels were reduced 3-fold in only ve minutes after protamine reversal at the end of the surgery [13]. In mice, HBP plasma levels were measured at the end of an experiment following intravenous HBP infusion and only 1% of the administered HBP remained after 1 hour [14].…”

Section: Introductionmentioning

confidence: 99%

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The dynamics of circulating heparin-binding protein (HBP) - implications for its use as a biomarker

Fisher¹,

Kahn

Wiebe

et al. 2021

Preprint

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Background Heparin Binding Protein (HBP) is a promising new biomarker for the development and severity of sepsis. To guide the use of HBP as a biomarker it is important to understand the factors that may lead to false positive or negative results. The mechanisms that could lead to falsely elevated HBP levels include inappropriate release and inadequate clearance of HBP by the responsible cells and organs. HBP is presumably released only by neutrophils and the organs responsible for its elimination are unknown. Therefore, in this study we aimed to determine whether non-neutrophil cells can be a source of HBP in the circulation and which organs are responsible for its removal.Results We measured HBP in two cohorts of neutropenic patients and found that 12% and 19% of patients in each cohort respectively had detectable HBP levels. In vitro, we found that three leukemia-derived monocytic cell lines and healthy CD14 + monocytes constitutively released detectable levels of HBP. Next we injected HBP intravenously in rats found that plasma levels of HBP decreased rapidly, with a distribution half-life below 10 minutes and an elimination half-life of 1–2 hours. We measured HBP levels in the liver, spleen, kidneys, lungs, and urine using both ELISA and immunofluorescence quantitation and found that the majority of HBP was present in the liver and a small amount was present in the spleen. Immunofluorescence imaging indicated that HBP is associated mainly with hepatocytes in the liver and monocytes/macrophages in the spleen.Conclusions HBP can be found in some neutropenic patients. Other than neutrophils, malignant myeloid cells and monocytic cells may be an additional source of HBP. HBP disappears rapidly from the circulation and distributes primarily to liver hepatocytes and spleen monocytes/macrophages. The impact of hematologic malignancies and liver diseases on plasma HBP levels should be explored further in clinical studies.

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Section: Discussionsupporting

confidence: 93%

Section: Implications For Hbp As a Biomarkermentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The dynamics of circulating heparin-binding protein (HBP) - implications for its use as a biomarker

Fisher¹,

Kahn

Wiebe

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…We found that HBP circulates in the blood for a short time, with a distribution half-life below 10 min and an elimination half-life between 1 and 2 h. This finding is in line with previous observations in humans [ 12 , 13 ] and in mice [ 14 ], which indicated that plasma HBP levels change rapidly between measurements. HBP has pro-inflammatory and vascular permeability-inducing effects that can be dangerous in situations such as sepsis [ 6 ], and therefore, rapid removal of HBP from the circulation is likely a protective mechanism against these detrimental effects.…”

Section: Discussionsupporting

confidence: 92%

“…Serial measurements of HBP every four hours in septic shock patients indicated that HBP levels fluctuate widely between measurements [ 12 ]. Repeated measurements of HBP in patients undergoing cardiac surgery with cardiopulmonary bypass showed that HBP levels were reduced 3-fold in only five minutes after protamine reversal at the end of the surgery [ 13 ]. In mice, HBP plasma levels were measured at the end of an experiment following intravenous HBP infusion, and only 1% of the administered HBP remained after 1 h [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

The Dynamics of Circulating Heparin-Binding Protein: Implications for Its Use as a Biomarker

et al. 2021

Self Cite

View full text Add to dashboard Cite

Heparin-binding protein (HBP) is a promising biomarker for the development and severity of sepsis. To guide its use, it is important to understand the factors that could lead to false-positive or negative results, such as inappropriate release and inadequate clearance of HBP. HBP is presumably released only by neutrophils, and the organs responsible for its elimination are unknown. In this study, we aimed to determine whether non-neutrophil cells can be a source of circulating HBP and which organs are responsible for its removal. We found that in two cohorts of neutropenic patients, 12% and 19% of patients in each cohort, respectively, had detectable plasma HBP levels. In vitro, three leukemia-derived monocytic cell lines and healthy CD14+ monocytes constitutively released detectable levels of HBP. When HBP was injected intravenously in rats, we found that plasma levels of HBP decreased rapidly, with a distribution half-life below 10 min and an elimination half-life of 1–2 h. We measured HBP levels in the liver, spleen, kidneys, lungs, and urine using both ELISA and immunofluorescence quantitation, and found that the majority of HBP was present in the liver, and a small amount was present in the spleen. Immunofluorescence imaging indicated that HBP is associated mainly with hepatocytes in the liver and monocytes/macrophages in the spleen. The impact of hematologic malignancies and liver diseases on plasma HBP levels should be explored further in clinical studies.

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The effect of heparins on plasma concentration of heparin-binding protein: a pilot study

Halldorsdottir,

Lindbom,

Ebberyd

et al. 2024

BJA Open

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The Dynamics of Heparin-Binding Protein in Cardiothoracic Surgery—A Pilot Study

Cited by 7 publications

References 27 publications

The dynamics of circulating heparin-binding protein (HBP) - implications for its use as a biomarker

The dynamics of circulating heparin-binding protein (HBP) - implications for its use as a biomarker

The Dynamics of Circulating Heparin-Binding Protein: Implications for Its Use as a Biomarker

The effect of heparins on plasma concentration of heparin-binding protein: a pilot study

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