The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Haptoglobin therapy has differential effects depending on severity of canine septic shock and cell‐free hemoglobin level
Open accessAbstract
BACKGROUND: During sepsis, higher plasma cell-free hemoglobin (CFH) levels portend worse outcomes. In sepsis models, plasma proteins that bind CFH improve survival. In our canine antibiotic-treated Staphylococcus aureus pneumonia model, with and without red blood cell (RBC) exchange transfusion, commercial human haptoglobin (Hp) concentrates bound and compartmentalized CFH intravascularly, increased CFH clearance, and lowered iron levels, improving shock, lung injury, and survival. We now investigate in our model how very high CFH levels and treatment time affect Hp's beneficial effects. MATERIALS AND METHODS: Two separate canine pneumonia sepsis Hp studies were undertaken: one with exchange transfusion of RBCs after prolonged storage to raise CFH to very high levels and another with rapidly lethal sepsis alone to shorten time to treat. All animals received continuous standard intensive care unit supportive care for 96 hours. RESULTS: Older RBCs markedly elevated plasma CFH levels and, when combined with Hp therapy, created supraphysiologic CFH-Hp complexes that did not increase CFH or iron clearance or improve lung injury and survival. In a rapidly lethal bacterial challenge model without RBC transfusion, Hp binding did not increase clearance of complexes or iron or show benefits seen previously in the less lethal model. DISCUSSION: High-level CFH-Hp complexes may impair clearance mechanisms and eliminate Hp's beneficial effect during sepsis. Rapidly lethal sepsis narrows the therapeutic window for CFH and iron clearance, also decreasing Hp's beneficial effects. In designing clinical trials, dosing and kinetics may be critical factors if Hp infusion is used to treat sepsis.
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In a canine Staphylococcus aureus pneumonia-induced septic shock model, human haptoglobin infusions enhanced hemoglobin clearance and reduced circulating iron, which in turn led to improved survival.
“In a canine Staphylococcus aureus pneumonia induced septic shock model, human haptoglobin infusions enhanced hemoglobin clearance and reduced circulating iron, which in turn led to an improved survival”
From Iron in immune cell function and host defense (2021) · cites this paper as [98]
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Cites
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“Hemolysis with elevated cell-free hemoglobin (CFH) levels has been documented during bacterial sepsis, and higher CFH levels are associated with a worse outcome.(5,6) Preclinical studies have found that infusing plasma proteins that bind to sites on the CFH molecule improve outcomes.”
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Haptoglobin improves shock, lung injury, and survival in canine pneumonia
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Iron in immune cell function and host defense
Haschka, D., Hoffmann, A., & Weiss, G. (2021) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2020.12.005 · Cited by 188
Metadata
- Authors
- Remy, K. E., Cortés‐Puch, I., Sun, J., Feng, J., Lertora, J. J., Risoleo, T., Katz, J., Basu, S., Liu, X., Perlegas, A., Kim‐Shapiro, D. B., Klein, H. G., Natanson, C., & Solomon, S. B.
- Affiliations
- National Institutes of Health (US)
- Pennington Biomedical Research Center (US)
- Wake Forest University Health Sciences (US)
- Wake Forest University (US)
- Corresponding author
- Solomon, Steven B.
- ORCID
- Venue
- Transfusion
- Publisher
- Wiley
- Published
- 2019-10-22
- Volume
- 59
- Issue
- 12
- Pages
- 3628-3638
- ISSN
- 0041-1132 (ISSN-L)
- 1537-2995
- PMC
- PMC8216248
- OpenAlex
- W2982044354
- Cited by
- 14
- References
- 23
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 3
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Transfusion (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (1R01HL125886, 2R01HL098032, 5P01HL103455, T32 HL110849)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
- Keywords
- septic shock, free hemoglobin, Staphylococcus aureus pneumonia, red blood cell exchange transfusion, iron clearance, lung injury, survival, therapeutic window, plasma protein binding
- MeSH terms
- Animals, Disease Models, Animal, Dogs, Haptoglobins, Hemoglobins, Pneumonia, Staphylococcal, Shock, Septic, Erythrocyte Transfusion, Sepsis
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