ReviewToxins2019
Hemolysis Derived Products Toxicity and Endothelium: Model of the Second Hit.
Review in Toxins, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 88 citations in OpenAlex.
- Haemolytic injury and cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Development of a hemolysis filter system for the selective removal of free hemoglobin, haem and iron from blood envisaged for use in extracorporeal circuits.Scientific reports · 2026Article
- Red blood cell damage defines the etiology of hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids.Acta pharmaceutica Sinica. B · 2026Article
- Regulatory interplay between nitric oxide and heme in redox signaling and inflammation.Redox biology · 2026Review
- Early Vascular Aging and Subclinical Myocardial Deformation in Children with β-Thalassemia Major: The Role of Asymmetric Dimethylarginine.Children (Basel, Switzerland) · 2026Article
- Hemoglobin binders reduce inflammation and tissue injury from hemolysis in venovenous extracorporeal circulation.Blood advances · 2026Article
- Free Fetal Haemoglobin in Severe Early-Onset Fetal Growth Restriction: A Prospective Multi-Centre Study.BJOG : an international journal of obstetrics and gynaecology · 2026Article
- Article
- Iron-driven secondary injury after intracranial hemorrhage: mitochondrial dysfunction and ferroptosis.Frontiers in neuroscience · 2026Review
- Human Protein Z as the Second Known Heme-Binding Protein from the Endogenous Blood Coagulation Inhibitor System.Chembiochem : a European journal of chemical biology · 2026Article
- Hemolysis-induced hepatic ferroptosis following xenotransfusion of genetically modified pig red blood cells.Scientific reports · 2025Article
- HCAR2 is a novel receptor for heme.Blood advances · 2025Article
- Podocyte dysfunction driven by heme in sickle-cell nephropathy.Scientific reports · 2025Article
- Review
- Artificial blood-hope and the challenges to combat tumor hypoxia for anti-cancer therapy.Medical & biological engineering & computing · 2025Review
- Hemoglobin homeostasis in abdominal aortic aneurysm: diagnostic and prognostic potential of hemoglobin/heme and scavenger molecules.BMC cardiovascular disorders · 2024Article
- Nonlinear optical and spectroscopic properties, thermal analysis, and hemolytic capacity evaluation of quinoline-1,3-benzodioxole chalcone.RSC advances · 2024Article
- Pregnancy as a susceptible state for thrombotic microangiopathies.Frontiers in medicine · 2024Review
- Ferroptosis as an emerging target in sickle cell disease.Current research in toxicology · 2024Article
- Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia.Clinical and translational science · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular diseases are multifactorial, often requiring multiple challenges, or 'hits', for their initiation. Intra-vascular hemolysis illustrates well the multiple-hit theory where a first event lyses red blood cells, releasing hemolysis-derived products, in particular cell-free heme which is highly toxic for the endothelium. Physiologically, hemolysis derived-products are rapidly neutralized by numerous defense systems, including haptoglobin and hemopexin which scavenge hemoglobin and heme, respectively. Likewise, cellular defense mechanisms are involved, including heme-oxygenase 1 upregulation which metabolizes heme. However, in cases of intra-vascular hemolysis, those systems are overwhelmed. Heme exerts toxic effects by acting as a damage-associated molecular pattern and promoting, together with hemoglobin, nitric oxide scavenging and ROS production. In addition, it activates the complement and the coagulation systems. Together, these processes lead to endothelial cell injury which triggers pro-thrombotic and pro-inflammatory phenotypes. Moreover, among endothelial cells, glomerular ones display a particular susceptibility explained by a weaker capacity to counteract hemolysis injury. In this review, we illustrate the 'multiple-hit' theory through the example of intra-vascular hemolysis, with a particular focus on cell-free heme, and we advance hypotheses explaining the glomerular susceptibility observed in hemolytic diseases. Finally, we describe therapeutic options for reducing endothelial injury in hemolytic diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.