Avanços e perspectivas em biomarcadores de prognóstico na anemia falciforme
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May 14, 2025
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Resumo
Objetivo: Explorar os avanços mais recentes de biomarcadores de prognóstico da Anemia Falciforme (AF). Métodos: A busca foi conduzida no PubMed Central com artigos em inglês publicados entre os anos de 2020 e 2024. Após a triagem dos títulos e resumos, foram selecionados artigos experimentais que abordassem a temática a partir dos descritores “biomarkers” e “Sickle Cell Anemia”. Foram excluídos da pesquisa, revisões de literatura, cartas de editores, editoriais, livros, capítulos de livros, relatos de caso, ou qualquer outro artigo que não se adequasse a proposta do trabalho ou fora do período estipulado. Resultados: Foram identificados 212 artigos, mas apenas 26 atenderam a todos os critérios de inclusão. Os biomarcadores encontrados no estudo foram: cf-mtDNA, sE-selectina, dilatação mediada pelo fluxo da artéria braquial, Fluxo Sanguíneo Cerebral, viscosidade do sangue total, PON1, IL-6, miR-199a-5p e miR-144, SOD2V16A, cortisol capilar, PLSCR4, NRG-1β, gene TGFBR3, uNGAL, Copeptina, entre outros. Considerações finais: Esses achados podem abrir caminhos para o desenvolvimento de estudos que possam contribuir para o aprimoramento e manejo da AF, entretanto, mais pesquisas são necessárias para validar sua utilidade clínica.
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Como Citar
GomesM. J. P., PinheiroN. M. L., SampaioT. L., & LemesR. P. G. (2025). Avanços e perspectivas em biomarcadores de prognóstico na anemia falciforme. Revista Eletrônica Acervo Saúde, 25(5), e20227. https://doi.org/10.25248/reas.e20227.2025
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Referências
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2. AYOOLA OO. et al. Association between Endothelial Dysfunction, Biomarkers of Renal Function, and Disease Severity in Sickle Cell Disease. Kidney360, 2020; 1(2): 79–85.
3. BATTE A. et al. Mineral bone disorders and kidney disease in hospitalized children with sickle cell anemia. Frontiers in Pediatrics, 2023; 10(1): 1078853.
4. BATTE A. et al. Neutrophil gelatinase-associated lipocalin is elevated in children with acute kidney injury and sickle cell anemia, and predicts mortality, Kidney International, 2022; 102(4): 885–893.
5. CHAMBLISS C. et al. Elevated neuregulin-1β levels correlate with plasma biomarkers of cerebral injury and high stroke risk in children with sickle cell anemia. Endocrine and Metabolic Science, 2021; 3(1): e100088.
6. CONRAN N e BELCHER JD. Inflammation in sickle cell disease, Clinical Hemorheology and Microcirculation, 2018; 68(2-3): 263-299.
7. DELGADINHO M. et al. Differential expression of adhesion molecules in sickle cell anemia and gut microbiome effect. Annals of Hematology, 2024; 103(2): 409–419.
8. DELGADINHO M. et al. How Hydroxyurea Alters the Gut Microbiome: A Longitudinal Study Involving Angolan Children with Sickle Cell Anemia. International Journal of Molecular Sciences. 2022; 23(16): 9061.
9. DEVECI OS. et al. Increased Circulating Copeptin Levels Are Associated with Vaso-Occlusive Crisis and Right Ventricular Dysfunction in Sickle Cell Anemia. Medical Principles and Practice, 2022; 31(1): 47–53.
10. DOSUNMU-OGUNBI A. et al. SOD2 V16A amplifies vascular dysfunction in sickle cell patients by curtailing mitochondria complex IV activity, Blood, 2022; 139(11): 1760–1765.
11. FEUGRAY G. et al. Lipid and hemolysis parameters predicting acute chest syndrome in adulthood with sickle cell disease. Lipids in Health and Disease, 2024; 23(1): 140.
12. FEUGRAY, G. et al. Lactate dehydrogenase and hemolysis index to predict vaso-occlusive crisis in sickle cell disease. Sci Rep, 13(1), 21198, 2023.
13. HOLLISTER BM. et al. Lower hair cortisol among patients with sickle cell disease may indicate decreased adrenal reserves. American Journal of Blood Research, 2021; 11(2): 140–148.
14. JONES RS. et al. Silent infarction in sickle cell disease is associated with brain volume loss in excess of infarct volume. Frontiers in Neurology, 2023; 14(1): e1112865.
15. KNISELY MR. et al. Severe Persistent Pain and Inflammatory Biomarkers in Sickle Cell Disease: An Exploratory Study. Biological Research For Nursing, 2021; 24(1): 24–30.
16. KUCUKAL E. et al. Whole blood viscosity and red blood cell adhesion: Potential biomarkers for targeted and curative therapies in sickle cell disease, American Journal of Hematology, 2020; 95(11): 1246–1256.
17. LAURENTINO MR. Avaliação de biomarcadores inovadores no diagnóstico precoce de lesão renal e endotelial em pacientes com anemia falciforme em uso ou não de hidroxiuréia. Tese de Doutorado (Doutorado em Ciências Farmacêuticas) – Faculdade de Farmácia, Odontologia e Enfermagem da Universidade Federal do Ceará, Fortaleza, 2020; 59p.
18. MANGLA, A. et al. Sickle Cell Anemia, In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
19. MENEZES JF. et al. Role of paraoxonase 1 activity and PON1 gene polymorphisms in sickle cell disease, Scientific Reports, 2023; 13(1): 7215.
20. NADER E, et al. The red blood cell – inflammation vicious circle in sickle cell disease, Frontiers in Immunology, 2020; 11(454): 1-11.
21. NISS O. et al. Progression of albuminuria in patients with sickle cell anemia: a multicenter, longitudinal study, Blood Advances, 2020; 4(7): 1501–1511.
22. NOURAIE M. et al. Tricuspid regurgitation velocity and other biomarkers of mortality in children, adolescents, and young adults with sickle cell disease in the United States: The PUSH study. American Journal of Hematology, 2020; 95(7): 766–774.
23. PICCIN A. et al. Insight into the complex pathophysiology of sickle cell anaemia and possible treatment, European Journal of Haematology, 2019; 102 (1): 319-330.
24. RINCÓN-LÓPEZ EM. et al. Interleukin 6 as a marker of severe bacterial infection in children with sickle cell disease and fever: A case–control study. BMC Infectious Diseases, 2021; 21(1): 741.
25. SADAF A. et al. Automated Oxygen Gradient Ektacytometry: A Novel Biomarker in Sickle Cell Anemia, Frontiers in Physiology, 2021; 12(1): 636609.
26. SANTIAGO RP. et al. TGFBR3 polymorphisms (rs1805110 and rs7526590) are associated with laboratory biomarkers and clinical manifestations in sickle cell anemia. Disease Markers, 2020; 2020(1): 8867986.
27. SANTOS EC. et al. A description of the hemolytic component in sickle leg ulcer: The role of circulating miR-199a-5p, miR-144, and miR-126, Biomolecules, 2022; 12(2): 317.
28. SECRETARIA DE ESTADO DE SAÚDE DO MATO GROSSO DO SUL. Anemia falciforme: desconhecimento sobre a doença tem evitado diagnóstico precoce em MS, 2021. Disponível em: < https://www.saude.ms.gov.br/anemia-falciforme-desconhecimento-sobre-a-doenca-tem-evitado-diagnostico-precoce-em-ms/>. Acessado em: 09 ago. 2024.
29. SILVA-JUNIOR AL. et al. Immunological Hallmarks of Inflammatory Status in Vaso-Occlusive Crisis of Sickle Cell Anemia Patients. Frontiers in Immunology, 2021; 12(1): e559925.
30. SOP D. et al. Association of Cerebral Hemodynamics and Anemia on Processing Speed in Adults with Sickle Cell Disease, Journal of Neurology and Experimental Neural Science, 2023; 5(1): 150.
31. STOTESBURY H. et al. Quantification of Silent Cerebral Infarction on High-Resolution FLAIR and Cognition in Sickle Cell Anemia. Frontiers in Neurology, 2022, 13(1): 867329.
32. SUNDD P, et al. Pathophysiology of sickle cell disease, Annual Review of Pathology: Mechanisms of Disease, 2019; 14(1): 263-292.
33. TALL FG. et al. Influence of Oxidative Stress Biomarkers and Genetic Polymorphisms on the Clinical Severity of Hydroxyurea-Free Senegalese Children with Sickle Cell Anemia, Antioxidants (Basel), 2020; 9(9): 863.
34. TUMBURU L. et al. Circulating mitochondrial DNA is a proinflammatory DAMP in sickle cell disease, Blood, 2021; 137(22): 3116–3126.
35. WILLIAMS TN, THEIN SL. Sickle cell anemia and its phenotypes, Annual Review of Genomics and Human Genetic, 2018; 19(1): 113-147.
36. YASARA N, et al. A comprehensive review of hydroxyurea for β-haemoglobinopathies: the role revisited during COVID-19 pandemic, Orphanet Journal of Rare Diseases, 2021; 16(114): 1-12.
37. Zamora-Obando HR. et al. Biomarcadores moleculares de doenças humanas: conceitos fundamentais, modelos de estudo e aplicações clínicas. Química Nova. 2022;45(9):1098–1113.
38. ZÚÑIGA P et al. Enfermedad de células falciformes: un diagnóstico para tener presente, Revista Chilena de Pediatría, 2018; 89(4): 1-5.
2. AYOOLA OO. et al. Association between Endothelial Dysfunction, Biomarkers of Renal Function, and Disease Severity in Sickle Cell Disease. Kidney360, 2020; 1(2): 79–85.
3. BATTE A. et al. Mineral bone disorders and kidney disease in hospitalized children with sickle cell anemia. Frontiers in Pediatrics, 2023; 10(1): 1078853.
4. BATTE A. et al. Neutrophil gelatinase-associated lipocalin is elevated in children with acute kidney injury and sickle cell anemia, and predicts mortality, Kidney International, 2022; 102(4): 885–893.
5. CHAMBLISS C. et al. Elevated neuregulin-1β levels correlate with plasma biomarkers of cerebral injury and high stroke risk in children with sickle cell anemia. Endocrine and Metabolic Science, 2021; 3(1): e100088.
6. CONRAN N e BELCHER JD. Inflammation in sickle cell disease, Clinical Hemorheology and Microcirculation, 2018; 68(2-3): 263-299.
7. DELGADINHO M. et al. Differential expression of adhesion molecules in sickle cell anemia and gut microbiome effect. Annals of Hematology, 2024; 103(2): 409–419.
8. DELGADINHO M. et al. How Hydroxyurea Alters the Gut Microbiome: A Longitudinal Study Involving Angolan Children with Sickle Cell Anemia. International Journal of Molecular Sciences. 2022; 23(16): 9061.
9. DEVECI OS. et al. Increased Circulating Copeptin Levels Are Associated with Vaso-Occlusive Crisis and Right Ventricular Dysfunction in Sickle Cell Anemia. Medical Principles and Practice, 2022; 31(1): 47–53.
10. DOSUNMU-OGUNBI A. et al. SOD2 V16A amplifies vascular dysfunction in sickle cell patients by curtailing mitochondria complex IV activity, Blood, 2022; 139(11): 1760–1765.
11. FEUGRAY G. et al. Lipid and hemolysis parameters predicting acute chest syndrome in adulthood with sickle cell disease. Lipids in Health and Disease, 2024; 23(1): 140.
12. FEUGRAY, G. et al. Lactate dehydrogenase and hemolysis index to predict vaso-occlusive crisis in sickle cell disease. Sci Rep, 13(1), 21198, 2023.
13. HOLLISTER BM. et al. Lower hair cortisol among patients with sickle cell disease may indicate decreased adrenal reserves. American Journal of Blood Research, 2021; 11(2): 140–148.
14. JONES RS. et al. Silent infarction in sickle cell disease is associated with brain volume loss in excess of infarct volume. Frontiers in Neurology, 2023; 14(1): e1112865.
15. KNISELY MR. et al. Severe Persistent Pain and Inflammatory Biomarkers in Sickle Cell Disease: An Exploratory Study. Biological Research For Nursing, 2021; 24(1): 24–30.
16. KUCUKAL E. et al. Whole blood viscosity and red blood cell adhesion: Potential biomarkers for targeted and curative therapies in sickle cell disease, American Journal of Hematology, 2020; 95(11): 1246–1256.
17. LAURENTINO MR. Avaliação de biomarcadores inovadores no diagnóstico precoce de lesão renal e endotelial em pacientes com anemia falciforme em uso ou não de hidroxiuréia. Tese de Doutorado (Doutorado em Ciências Farmacêuticas) – Faculdade de Farmácia, Odontologia e Enfermagem da Universidade Federal do Ceará, Fortaleza, 2020; 59p.
18. MANGLA, A. et al. Sickle Cell Anemia, In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
19. MENEZES JF. et al. Role of paraoxonase 1 activity and PON1 gene polymorphisms in sickle cell disease, Scientific Reports, 2023; 13(1): 7215.
20. NADER E, et al. The red blood cell – inflammation vicious circle in sickle cell disease, Frontiers in Immunology, 2020; 11(454): 1-11.
21. NISS O. et al. Progression of albuminuria in patients with sickle cell anemia: a multicenter, longitudinal study, Blood Advances, 2020; 4(7): 1501–1511.
22. NOURAIE M. et al. Tricuspid regurgitation velocity and other biomarkers of mortality in children, adolescents, and young adults with sickle cell disease in the United States: The PUSH study. American Journal of Hematology, 2020; 95(7): 766–774.
23. PICCIN A. et al. Insight into the complex pathophysiology of sickle cell anaemia and possible treatment, European Journal of Haematology, 2019; 102 (1): 319-330.
24. RINCÓN-LÓPEZ EM. et al. Interleukin 6 as a marker of severe bacterial infection in children with sickle cell disease and fever: A case–control study. BMC Infectious Diseases, 2021; 21(1): 741.
25. SADAF A. et al. Automated Oxygen Gradient Ektacytometry: A Novel Biomarker in Sickle Cell Anemia, Frontiers in Physiology, 2021; 12(1): 636609.
26. SANTIAGO RP. et al. TGFBR3 polymorphisms (rs1805110 and rs7526590) are associated with laboratory biomarkers and clinical manifestations in sickle cell anemia. Disease Markers, 2020; 2020(1): 8867986.
27. SANTOS EC. et al. A description of the hemolytic component in sickle leg ulcer: The role of circulating miR-199a-5p, miR-144, and miR-126, Biomolecules, 2022; 12(2): 317.
28. SECRETARIA DE ESTADO DE SAÚDE DO MATO GROSSO DO SUL. Anemia falciforme: desconhecimento sobre a doença tem evitado diagnóstico precoce em MS, 2021. Disponível em: < https://www.saude.ms.gov.br/anemia-falciforme-desconhecimento-sobre-a-doenca-tem-evitado-diagnostico-precoce-em-ms/>. Acessado em: 09 ago. 2024.
29. SILVA-JUNIOR AL. et al. Immunological Hallmarks of Inflammatory Status in Vaso-Occlusive Crisis of Sickle Cell Anemia Patients. Frontiers in Immunology, 2021; 12(1): e559925.
30. SOP D. et al. Association of Cerebral Hemodynamics and Anemia on Processing Speed in Adults with Sickle Cell Disease, Journal of Neurology and Experimental Neural Science, 2023; 5(1): 150.
31. STOTESBURY H. et al. Quantification of Silent Cerebral Infarction on High-Resolution FLAIR and Cognition in Sickle Cell Anemia. Frontiers in Neurology, 2022, 13(1): 867329.
32. SUNDD P, et al. Pathophysiology of sickle cell disease, Annual Review of Pathology: Mechanisms of Disease, 2019; 14(1): 263-292.
33. TALL FG. et al. Influence of Oxidative Stress Biomarkers and Genetic Polymorphisms on the Clinical Severity of Hydroxyurea-Free Senegalese Children with Sickle Cell Anemia, Antioxidants (Basel), 2020; 9(9): 863.
34. TUMBURU L. et al. Circulating mitochondrial DNA is a proinflammatory DAMP in sickle cell disease, Blood, 2021; 137(22): 3116–3126.
35. WILLIAMS TN, THEIN SL. Sickle cell anemia and its phenotypes, Annual Review of Genomics and Human Genetic, 2018; 19(1): 113-147.
36. YASARA N, et al. A comprehensive review of hydroxyurea for β-haemoglobinopathies: the role revisited during COVID-19 pandemic, Orphanet Journal of Rare Diseases, 2021; 16(114): 1-12.
37. Zamora-Obando HR. et al. Biomarcadores moleculares de doenças humanas: conceitos fundamentais, modelos de estudo e aplicações clínicas. Química Nova. 2022;45(9):1098–1113.
38. ZÚÑIGA P et al. Enfermedad de células falciformes: un diagnóstico para tener presente, Revista Chilena de Pediatría, 2018; 89(4): 1-5.