Hemolysis and cell-free hemoglobin drive an intrinsic mechanism for human disease
Open accessAbstract
Blood transfusion represents the first and most prescribed cell-based therapy; however, clinical safety and efficacy trials are lacking. Clinical cohort studies have suggested that massive transfusion and/or transfusion of aged stored blood may contribute to multiorgan dysfunction in susceptible patients. In this issue of the JCI, Baek and colleagues report that aged stored blood hemolyzes after massive transfusion in a guinea pig model. Hemolysis led to vascular and kidney injury that was mediated by cell-free plasma hemoglobin and prevented by coinfusion of the specific hemoglobin scavenger protein, haptoglobin. These studies support an expanding body of research indicating that intravascular hemolysis is a pathological mechanism in several human diseases, including multiorgan dysfunction after either massive red blood cell transfusion or hemoglobin-based blood substitute therapy, the hemoglobinopathies, malaria, and other acquired and genetic hemolytic conditions.
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In hemolytic anemia, release of free Hb may lead to systemic NO scavenging, affecting vascular tone.
“For example, in hemolytic anemia, release of free Hb may lead to systemic NO scavenging, affecting vascular tone (71, 152).”
From Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia (2017) · cites this paper as [71]
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- Authors
- Gladwin, M. T., Kanias, T., & Kim-Shapiro, D. B.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Gladwin, Mark T.
- Venue
- Journal of Clinical Investigation
- Published
- 2012-04-02
- Volume
- 122
- Issue
- 4
- Pages
- 1205-1208
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3314481
- OpenAlex
- W1978464782
- Cited by
- 196
- References
- 24
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 26 · 2023: 12 · 2022: 21 · 2021: 12 · 2020: 11 · 2019: 18 · 2018: 16 · 2017: 12 · 2016: 7 · 2015: 12 · 2014: 12 · 2013: 9 · 2012: 1
- FWCI
- 7.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (PO1-HL-103455)
- National Heart, Lung, and Blood Institute (R01HL096973, R37HL058091, P01HL103455, R01HL098032)
- Topics
- Health Sciences › Medicine › Biochemistry › Blood transfusion and management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
- Keywords
- intravascular hemolysis, free hemoglobin, haptoglobin, massive transfusion, multiple organ failure, hemoglobin-based blood substitutes, hemoglobinopathies, malaria, kidney injury, vascular injury, guinea pig model
- MeSH terms
- Animals, Blood Preservation, Haptoglobins, Hemoglobins, Hemolysis, Humans, Kidney, Male, Transfusion Reaction
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