ReviewFrontiers in immunology2020
The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease.
Review in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Gut Bacteroides act in a microbial consortium to cause susceptibility to severe malaria.Nature communications · 2023Pooled it
- Effect of voxelotor on cerebral perfusion and cerebral oxygen metabolism and cardiac stress in adult patients with sickle cell disease.American journal of hematology · 2025Trial
- Phase I study of the safety and pharmacokinetics of CSL889 (hemopexin) in adults with sickle cell anemia.Haematologica · 2026Article
- Hemopexin Purification From Human Cohn Fraction IV Paste and Its Biophysical Characterization and Functional Evaluation in Sickle Cell Disease Mice.Biotechnology and bioengineering · 2026Article
- Haemolytic injury and cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Adaptive Immune Remodeling in Sickle Cell Disease: Linking Hemolysis-Driven Inflammation to Immune Dysfunction.Experimental hematology · 2026Review
- Augmenting hemopexin-mediated heme scavenging mitigates sepsis-induced acute kidney injury in humanized sickle cell mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Thrombocytosis and the generation of platelet-derived microparticles in the pathophysiology of sickle cell disease.British journal of haematology · 2026Review
- Elevated tricuspid regurgitation velocity in adults with sickle cell disease and HbAA controls in Kinshasa, Democratic Republic of the Congo: a comparative cross-sectional study.Annals of hematology · 2026Article
- Gene expression profiling identifies potential biomarkers for vaso-occlusive episodes in sickle cell disease.JCI insight · 2026Article
- Unravelling the Immunological Enigma of Sickle Cell Disease: Current Understanding and Future Directions.Immunology · 2026Review
- Assessing the Impact of Intravascular Hemolysis on Erythropoiesis in Sickle Cell Disease.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Interleukin-6 in hemolytic anemias: from inflammatory pathways to therapeutic targeting.Frontiers in immunology · 2026Review
- Plasma heme pool compartmentalization is linked to pathophysiology in Sickle Cell Disease.PloS one · 2026Article
- Article
- Mitochondrial retention and autophagy dysregulation drive oxidative stress in sickle cell disease erythrocytes.Experimental hematology · 2025Article
- Clinical Benefits and Risks of Haptoglobin Therapy in Hemolytic Disorders of Diverse Etiologies: A Systematic Review.Cureus · 2025Review
- Heme Modulates Bladder Contractility Through the HO-CO-sGC-cGMP Pathway: Insights into Sickle Cell Disease-Associated Bladder Dysfunction.Antioxidants (Basel, Switzerland) · 2025Article
- Combined haptoglobin and hemopexin therapy for the treatment of cardiopulmonary dysfunction in sickle cell disease.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Caveolin-1 Is a Central Mediator of Acute Lung Injury in an Animal Model of Sickle Cell Disease.Pulmonary circulation · 2025Article
12 more citing papers are in PubMed but not listed here.
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 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hemolysis is a pathological feature of several diseases of diverse etiology such as hereditary anemias, malaria, and sepsis. A major complication of hemolysis involves the release of large quantities of hemoglobin into the blood circulation and the subsequent generation of harmful metabolites like labile heme. Protective mechanisms like haptoglobin-hemoglobin and hemopexin-heme binding, and heme oxygenase-1 enzymatic degradation of heme limit the toxicity of the hemolysis-related molecules. The capacity of these protective systems is exceeded in hemolytic diseases, resulting in high residual levels of hemolysis products in the circulation, which pose a great oxidative and proinflammatory risk. Sickle cell disease (SCD) features a prominent hemolytic anemia which impacts the phenotypic variability and disease severity. Not only is circulating heme a potent oxidative molecule, but it can act as an erythrocytic danger-associated molecular pattern (eDAMP) molecule which contributes to a proinflammatory state, promoting sickle complications such as vaso-occlusion and acute lung injury. Exposure to extracellular heme in SCD can also augment the expression of placental growth factor (PlGF) and interleukin-6 (IL-6), with important consequences to enthothelin-1 (ET-1) secretion and pulmonary hypertension, and potentially the development of renal and cardiac dysfunction. This review focuses on heme-induced mechanisms that are implicated in disease pathways, mainly in SCD. A special emphasis is given to heme-induced PlGF and IL-6 related mechanisms and their role in SCD disease progression.
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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.