{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:12:04Z","timestamp":1789053124321,"version":"build-2803163510"},"reference-count":255,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Sickle cell disease (SCD) is the most common inherited clinically relevant blood disorder. Although a deceptively simple monogenetic disorder, the associated complications have multiple downstream effects. In this review, we explore the many facets of SCD, with a particular focus on its impact on the vascular system. Despite progress in understanding the underlying mechanisms of SCD, including Hemoglobin S polymerization, microvascular occlusion, and inflammation, there are still many questions surrounding the condition, especially predicting which affected individuals will acquire specific complications in order to personalize treatments. While current standard of care treatments, including hydroxyurea and chronic red blood cell transfusions, have been proven to be disease-modifying, newer therapies like crizanlizumab and voxelotor have only proven to manage symptoms. Newer gene therapies have been approved; however, it is not clear what impact these will have long-term on the end-organ complications of SCD. There is still a significant need to understand how we optimize and personalize therapies to improve outcomes for patients. This review highlights the importance of recognizing SCD as a vascular disease to understand its multi-organ complications and heterogeneity of effects.<\/jats:p>","DOI":"10.3390\/cells15040326","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T12:07:06Z","timestamp":1770725226000},"page":"326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Rethinking Sickle Cell Disease as a Systemic Vasculopathy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7986-3383","authenticated-orcid":false,"given":"Mariana","family":"DuPont","sequence":"first","affiliation":[{"name":"Department of Health Sciences and Human Performance, The University of Tampa, Tampa, FL 33606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6853-5023","authenticated-orcid":false,"given":"Najibah A.","family":"Galadanci","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, 1808 7th Avenue South BDB321, Birmingham, AL 35294, USA"},{"name":"Lifespan Comprehensive Sickle Cell Center, The University of Alabama at Birmingham, 1808 7th Avenue South BDB321, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2856-6271","authenticated-orcid":false,"given":"Rushil V.","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, 1808 7th Avenue South BDB321, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Lebensburger","sequence":"additional","affiliation":[{"name":"Lifespan Comprehensive Sickle Cell Center, The University of Alabama at Birmingham, 1808 7th Avenue South BDB321, Birmingham, AL 35294, USA"},{"name":"Division of Pediatric Hemato-Oncology, Department of Pediatrics, Heersink School of Medicine, The University of Alabama at Birmingham, 1808 7th Avenue South BDB321, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7002-8891","authenticated-orcid":false,"given":"Julie","family":"Kanter","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, 1808 7th Avenue South BDB321, Birmingham, AL 35294, USA"},{"name":"Lifespan Comprehensive Sickle Cell Center, The University of Alabama at Birmingham, 1808 7th Avenue South BDB321, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"ref_1","unstructured":"Ashorobi, D., Ramsey, A., Killeen, R.B., and Bhatt, R. (2025). Sickle Cell Trait. StatPearls, StatPearls Publishing."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1365-2141.2010.08419.x","article-title":"One hundred years of sickle cell disease","volume":"151","author":"Serjeant","year":"2010","journal-title":"Br. J. Haematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/ajh.24134","article-title":"Critical Reviews: How we treat sickle cell patients with leg ulcers","volume":"91","author":"Minniti","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/bjh.19523","article-title":"The Clinical Spectrum of Hemoglobin SC Sickle Cell Disease-Not a Benign Condition","volume":"205","author":"Nelson","year":"2024","journal-title":"Br. J. Haematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1001\/jama.2022.10233","article-title":"Sickle cell disease: A review","volume":"328","author":"Kavanagh","year":"2022","journal-title":"JAMA"},{"key":"ref_6","first-page":"572","article-title":"Prevalence and risk factors for sickle retinopathy in a sub-Saharan comprehensive Sickle Cell Center","volume":"38","author":"Toure","year":"2017","journal-title":"Rev. Med. Interne"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1146\/annurev-pathmechdis-012418-012838","article-title":"Pathophysiology of sickle cell disease","volume":"14","author":"Sundd","year":"2019","journal-title":"Annu. Rev. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1056\/NEJM200001133420203","article-title":"Prediction of adverse outcomes in children with sickle cell disease","volume":"342","author":"Miller","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_9","first-page":"4","article-title":"Differences in the clinical and genotypic presentation of sickle cell disease around the world","volume":"15","author":"Saraf","year":"2014","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1002\/ajh.23683","article-title":"Factors associated with survival in a contemporary adult sickle cell disease cohort","volume":"89","author":"Elmariah","year":"2014","journal-title":"Am. J. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.trsl.2021.03.007","article-title":"Pain in sickle cell disease: Current and potential translational therapies","volume":"234","author":"Sagi","year":"2021","journal-title":"Transl. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1001\/jama.2011.235","article-title":"Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: A randomized controlled trial","volume":"305","author":"Gladwin","year":"2011","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.blre.2006.07.001","article-title":"Deconstructing sickle cell disease: Reappraisal of the role of hemolysis in the development of clinical subphenotypes","volume":"21","author":"Kato","year":"2007","journal-title":"Blood Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15018","DOI":"10.1073\/pnas.1922004117","article-title":"Allosteric control of hemoglobin S fiber formation by oxygen and its relation to the pathophysiology of sickle cell disease","volume":"117","author":"Henry","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1182\/blood-2017-02-765891","article-title":"Treating sickle cell disease by targeting HbS polymerization","volume":"129","author":"Eaton","year":"2017","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1182\/blood.V77.7.1405.1405","article-title":"Vascular occlusion in sickle cell disease: Current concepts and unanswered questions","volume":"77","author":"Francis","year":"1991","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/ejh.13430","article-title":"The vaso-occlusive pain crisis in sickle cell disease: Definition, pathophysiology, and management","volume":"105","author":"Darbari","year":"2020","journal-title":"Eur. J. Haematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.pcl.2013.09.006","article-title":"Sickle cell disease in childhood: From newborn screening through transition to adult medical care","volume":"60","author":"Quinn","year":"2013","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1182\/blood-2013-05-498311","article-title":"Vaso-occlusion in sickle cell disease: Pathophysiology and novel targeted therapies","volume":"122","author":"Manwani","year":"2013","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1172\/JCI89741","article-title":"Intravascular hemolysis and the pathophysiology of sickle cell disease","volume":"127","author":"Kato","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1161\/CIRCULATIONAHA.110.008698","article-title":"Nitric oxide scavenging by red blood cell microparticles and cell-free hemoglobin as a mechanism for the red cell storage lesion","volume":"124","author":"Donadee","year":"2011","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"18010","DOI":"10.1038\/nrdp.2018.10","article-title":"Sickle cell disease","volume":"4","author":"Kato","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1161\/ATVBAHA.110.211615","article-title":"P-selectin-mediated platelet-neutrophil aggregate formation activates neutrophils in mouse and human sickle cell disease","volume":"30","author":"Wallace","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5010","DOI":"10.1182\/blood-2010-06-290643","article-title":"Adenosine A2A receptors induced on iNKT and NK cells reduce pulmonary inflammation and injury in mice with sickle cell disease","volume":"116","author":"Wallace","year":"2010","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/nm.2507","article-title":"Ischemia and reperfusion\u2014From mechanism to translation","volume":"17","author":"Eltzschig","year":"2011","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1001\/jama.293.13.1653","article-title":"The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: A novel mechanism of human disease","volume":"293","author":"Rother","year":"2005","journal-title":"JAMA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1016\/j.freeradbiomed.2008.01.008","article-title":"Sickle cell disease vasculopathy: A state of nitric oxide resistance","volume":"44","author":"Wood","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"L314","DOI":"10.1152\/ajplung.00252.2014","article-title":"Vasculopathy and pulmonary hypertension in sickle cell disease","volume":"308","author":"Potoka","year":"2015","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1056\/NEJM199505183322001","article-title":"Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia","volume":"332","author":"Charache","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1056\/NEJMoa1715971","article-title":"A Phase 3 Trial of l-Glutamine in Sickle Cell Disease","volume":"379","author":"Niihara","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1056\/NEJMoa1611770","article-title":"Crizanlizumab for the prevention of pain crises in sickle cell disease","volume":"376","author":"Ataga","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1056\/NEJMoa1903212","article-title":"A phase 3 randomized trial of voxelotor in sickle cell disease","volume":"381","author":"Vichinsky","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_33","unstructured":"American Society of Hematology (2024, April 03). ASH Statement on FDA\u2019s Approval of New Sickle Cell Disease Gene Therapy\u2014Hematology.org. Available online: https:\/\/www.hematology.org\/newsroom\/press-releases\/2023\/ash-statement-on-fda-approval-of-new-sickle-cell-disease-gene-therapies."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.3324\/haematol.2010.023325","article-title":"Hydroxyurea therapy requires HbF induction for clinical benefit in a sickle cell mouse model","volume":"95","author":"Lebensburger","year":"2010","journal-title":"Haematologica"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0006-291X(68)90266-0","article-title":"Effect of hydroxyurea on ribonucleotide reductase","volume":"33","author":"Elford","year":"1968","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/1096-8652(200011)65:3<227::AID-AJH9>3.0.CO;2-V","article-title":"Mechanism for fetal hemoglobin induction by hydroxyurea in sickle cell erythroid progenitors","volume":"65","author":"Baliga","year":"2000","journal-title":"Am. J. Hematol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1172\/JCI200316672","article-title":"Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase","volume":"111","author":"Cokic","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s12288-013-0261-4","article-title":"Hydroxyurea in sickle cell disease: Drug review","volume":"30","author":"Agrawal","year":"2014","journal-title":"Indian J. Hematol. Blood Transfus."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"L\u00f3pez Rubio, M., and Arg\u00fcello Marina, M. (2024). The current role of hydroxyurea in the treatment of sickle cell anemia. J. Clin. Med., 13.","DOI":"10.3390\/jcm13216404"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1001\/jama.2014.10517","article-title":"Management of sickle cell disease: Summary of the 2014 evidence-based report by expert panel members","volume":"312","author":"Yawn","year":"2014","journal-title":"JAMA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e26","DOI":"10.1016\/S2352-3026(21)00368-9","article-title":"Hydroxyurea for primary stroke prevention in children with sickle cell anaemia in Nigeria (SPRING): A double-blind, multicentre, randomised, phase 3 trial","volume":"9","author":"Abdullahi","year":"2022","journal-title":"Lancet Haematol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1182\/blood.2022016620","article-title":"Hydroxyurea for secondary stroke prevention in children with sickle cell anemia in Nigeria: A randomized controlled trial","volume":"141","author":"Abdullahi","year":"2023","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1358\/dot.2020.56.4.3110575","article-title":"L-Glutamine in sickle cell disease","volume":"56","author":"Cox","year":"2020","journal-title":"Drugs Today"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Niihara, Y., Matsui, N.M., Shen, Y.M., Akiyama, D.A., Johnson, C.S., Sunga, M.A., Magpayo, J., Embury, S.H., Kalra, V.K., and Cho, S.H. (2005). L-glutamine therapy reduces endothelial adhesion of sickle red blood cells to human umbilical vein endothelial cells. BMC Blood Disord., 5.","DOI":"10.1186\/1471-2326-5-4"},{"key":"ref_45","unstructured":"U.S. Food and Drug Adminstration (2024, April 02). FDA Approves Drug to Treat Sickle Cell Disease in Patients Aged 4 up to 11 Years|FDA, Available online: https:\/\/www.fda.gov\/drugs\/news-events-human-drugs\/fda-approves-drug-treat-sickle-cell-disease-patients-aged-4-11-years#:%E2%88%BC:text=FDA%20has%20granted%20accelerated%20approval,older%20with%20sickle%20cell%20disease."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s40265-020-01262-7","article-title":"Voxelotor: First Approval","volume":"80","author":"Blair","year":"2020","journal-title":"Drugs"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/bjh.14214","article-title":"GBT440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half-life in a murine model of sickle cell disease","volume":"175","author":"Oksenberg","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_48","unstructured":"U.S. Food and Drug Administration (2026, January 18). Available online: https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-alerting-patients-and-health-care-professionals-about-voluntary-withdrawal-oxbryta-market-due."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"q2147","DOI":"10.1136\/bmj.q2147","article-title":"Sickle cell drug is withdrawn over safety concerns just months after rollout","volume":"387","author":"Mahase","year":"2024","journal-title":"BMJ"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1182\/asheducation-2013.1.439","article-title":"Transfusion therapy for sickle cell disease: A balancing act","volume":"2013","author":"Chou","year":"2013","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0140-6736(17)30193-9","article-title":"Sickle cell disease","volume":"390","author":"Ware","year":"2017","journal-title":"Lancet"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.hoc.2016.01.011","article-title":"Management of Patients with Sickle Cell Disease Using Transfusion Therapy: Guidelines and Complications","volume":"30","author":"Chou","year":"2016","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/0002-9343(78)90772-6","article-title":"The natural history of stroke in sickle cell disease","volume":"65","author":"Powars","year":"1978","journal-title":"Am. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1056\/NEJM199807023390102","article-title":"Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography","volume":"339","author":"Adams","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1182\/asheducation-2013.1.370","article-title":"Allogeneic transplantation strategies including haploidentical transplantation in sickle cell disease","volume":"2013","author":"Gluckman","year":"2013","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1182\/blood-2007-03-079665","article-title":"SFGM-TC Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease","volume":"110","author":"Bernaudin","year":"2007","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1182\/blood.2019003776","article-title":"Gene therapy for sickle cell disease: Moving from the bench to the bedside","volume":"138","author":"Abraham","year":"2021","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1056\/NEJMoa2117175","article-title":"Biologic and clinical efficacy of lentiglobin for sickle cell disease","volume":"386","author":"Kanter","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1056\/NEJMoa2031054","article-title":"CRISPR-Cas9 Gene Editing for Sickle Cell Disease and \u03b2-Thalassemia","volume":"384","author":"Frangoul","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.jtha.2022.10.016","article-title":"Treatment with recombinant ADAMTS13, alleviates hypoxia\/reoxygenation-induced pathologies in a mouse model of human sickle cell disease","volume":"21","author":"Rossato","year":"2023","journal-title":"J. Thromb. Haemost."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/ajh.25384","article-title":"Critical role of C5a in sickle cell disease","volume":"94","author":"Vercellotti","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/s40265-024-02032-5","article-title":"Crovalimab: First Approval","volume":"84","author":"Dhillon","year":"2024","journal-title":"Drugs"},{"key":"ref_63","first-page":"725","article-title":"Targeting P-selectin and interleukin-1\u03b2 in mice with sickle cell disease: Effects on vaso-occlusion, liver injury and organ iron deposition","volume":"110","author":"Gotardo","year":"2025","journal-title":"Haematologica"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.jped.2022.01.001","article-title":"Omega 3 fatty acids\u2014Potential modulators for oxidative stress and inflammation in the management of sickle cell disease","volume":"98","author":"Khan","year":"2022","journal-title":"J. Pediatr."},{"key":"ref_65","first-page":"1918","article-title":"Epeleuton, a novel synthetic \u03c9-3 fatty acid, reduces hypoxia\/reperfusion stress in a mouse model of sickle cell disease","volume":"109","author":"Federti","year":"2024","journal-title":"Haematologica"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Kirkham, F.J., and Lagunju, I.A. (2021). Epidemiology of stroke in sickle cell disease. J. Clin. Med., 10.","DOI":"10.3390\/jcm10184232"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1182\/blood-2016-01-694562","article-title":"Silent cerebral infarcts and cerebral aneurysms are prevalent in adults with sickle cell anemia","volume":"127","author":"Kassim","year":"2016","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1002\/ajh.21476","article-title":"The excess burden of stroke in hospitalized adults with sickle cell disease","volume":"84","author":"Strouse","year":"2009","journal-title":"Am. J. Hematol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e463","DOI":"10.1161\/STROKEAHA.122.038651","article-title":"Hemorrhagic Stroke in Children and Adults with Sickle Cell Anemia: The Post-STOP Cohort","volume":"53","author":"Fox","year":"2022","journal-title":"Stroke"},{"key":"ref_70","unstructured":"Unnithan, A.K.A., Das, J.M., and Mehta, P. (2025). Hemorrhagic Stroke. StatPearls, StatPearls Publishing."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1007\/s00415-014-7291-1","article-title":"Progressing haemorrhagic stroke: Categories, causes, mechanisms and managements","volume":"261","author":"Chen","year":"2014","journal-title":"J. Neurol."},{"key":"ref_72","unstructured":"Rupareliya, C., and Lui, F. (2025). Moyamoya Disease. StatPearls, StatPearls Publishing."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5117","DOI":"10.1182\/blood-2009-05-220921","article-title":"Sickle cell disease and stroke","volume":"114","author":"Verduzco","year":"2009","journal-title":"Blood"},{"key":"ref_74","first-page":"e763","article-title":"Clinical features, course, and outcomes of a UK cohort of pediatric moyamoya","volume":"90","author":"Thompson","year":"2018","journal-title":"Neurology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"bcr2014203727","DOI":"10.1136\/bcr-2014-203727","article-title":"Moyamoya syndrome in sickle cell anaemia: A cause of recurrent stroke","volume":"2014","author":"Soares","year":"2014","journal-title":"BMJ Case Rep."},{"key":"ref_76","first-page":"e49039","article-title":"Moyamoya Syndrome in Children with Sickle Cell Disease in Saudi Arabia: A Single-Center Experience","volume":"15","author":"Zayed","year":"2023","journal-title":"Cureus"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1136\/neurintsurg-2014-011572","article-title":"Intracranial aneurysms in sickle cell anemia: Clinical and imaging findings","volume":"8","author":"Nabavizadeh","year":"2016","journal-title":"J. Neurointerv. Surg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1161\/STROKEAHA.116.012664","article-title":"Intracranial Aneurysms in Sickle-Cell Disease Are Associated with the Hemoglobin SS Genotype but Not with Moyamoya Syndrome","volume":"47","author":"Birkeland","year":"2016","journal-title":"Stroke"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/ajh.20033","article-title":"Embolization of intracranial aneurysms and sickle cell disease","volume":"76","author":"Vicari","year":"2004","journal-title":"Am. J. Hematol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S0140-6736(15)01041-7","article-title":"Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD with Transfusions Changing to Hydroxyurea (TWiTCH): A multicentre, open-label, phase 3, non-inferiority trial","volume":"387","author":"Ware","year":"2016","journal-title":"Lancet"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1182\/blood-2017-06-789842","article-title":"Red cell exchange transfusions lower cerebral blood flow and oxygen extraction fraction in pediatric sickle cell anemia","volume":"131","author":"Guilliams","year":"2018","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1182\/blood-2018-09-876318","article-title":"Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia","volume":"133","author":"Fields","year":"2019","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1002\/jmri.26213","article-title":"Differential cerebral hemometabolic responses to blood transfusions in adults and children with sickle cell anemia","volume":"49","author":"Juttukonda","year":"2019","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e1062","DOI":"10.1097\/MPH.0000000000002103","article-title":"Transcranial doppler screening in a current cohort of children with sickle cell anemia: Results from the DISPLACE study","volume":"43","author":"Kanter","year":"2021","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"E247","DOI":"10.1002\/ajh.25900","article-title":"Moderate fixed-dose hydroxyurea for primary prevention of strokes in Nigerian children with sickle cell disease: Final results of the SPIN trial","volume":"95","author":"Galadanci","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0022-3476(95)70204-0","article-title":"Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions","volume":"126","author":"Pegelow","year":"1995","journal-title":"J. Pediatr."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.jacc.2011.10.900","article-title":"Cardiovascular abnormalities in sickle cell disease","volume":"59","author":"Gladwin","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1111\/j.1365-2141.2012.09143.x","article-title":"Sickle-cell disease and the heart: Review of the current literature","volume":"157","author":"Voskaridou","year":"2012","journal-title":"Br. J. Haematol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1002\/ajh.27279","article-title":"Mortality in adults with sickle cell disease: Results from the sickle cell disease implementation consortium (SCDIC) registry","volume":"99","author":"Njoku","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.3324\/haematol.2021.280480","article-title":"Factors associated with left ventricular hypertrophy in children with sickle cell disease: Results from the DISPLACE study","volume":"107","author":"Galadanci","year":"2022","journal-title":"Haematologica"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.jacc.2006.09.038","article-title":"Diastolic dysfunction is an independent risk factor for death in patients with sickle cell disease","volume":"49","author":"Sachdev","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1378\/chest.98.5.1169","article-title":"Cardiac abnormalities in children with sickle cell anemia","volume":"98","author":"Lester","year":"1990","journal-title":"Chest"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/ajh.21016","article-title":"Relative systemic hypertension in patients with sickle cell disease is associated with risk of pulmonary hypertension and renal insufficiency","volume":"83","author":"Gordeuk","year":"2008","journal-title":"Am. J. Hematol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1182\/blood-2017-02-767624","article-title":"Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia","volume":"130","author":"Niss","year":"2017","journal-title":"Blood"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1016\/j.jacc.2007.09.011","article-title":"Joint ESC\/ACCF\/AHA\/WHF Task Force for the Redefinition of Myocardial Infarction Universal definition of myocardial infarction","volume":"50","author":"Thygesen","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1007\/s12265-012-9426-z","article-title":"Myocardial infarction in sickle cell disease: Use of translational imaging to diagnose an under-recognized problem","volume":"6","author":"Chacko","year":"2013","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_97","first-page":"448","article-title":"Myocardial infarction in sickle cell disease","volume":"94","author":"Mansi","year":"2002","journal-title":"J. Natl. Med. Assoc."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e029024","DOI":"10.1161\/JAHA.122.029024","article-title":"Revised definition of pulmonary hypertension and approach to management: A clinical primer","volume":"12","author":"Maron","year":"2023","journal-title":"J. Am. Heart Assoc."},{"key":"ref_99","unstructured":"Manek, G., and Bhardwaj, A. (2025). Pulmonary Hypertension. StatPearls, StatPearls Publishing."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/j.1365-2141.2011.08777.x","article-title":"NT-pro brain natriuretic peptide levels and the risk of death in the cooperative study of sickle cell disease","volume":"154","author":"Machado","year":"2011","journal-title":"Br. J. Haematol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1182\/blood-2005-06-2373","article-title":"Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease","volume":"107","author":"Kato","year":"2006","journal-title":"Blood"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1365-2141.2006.06417.x","article-title":"Severity of pulmonary hypertension during vaso-occlusive pain crisis and exercise in patients with sickle cell disease","volume":"136","author":"Machado","year":"2007","journal-title":"Br. J. Haematol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1182\/blood-2006-08-039438","article-title":"Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability","volume":"109","author":"Hsu","year":"2007","journal-title":"Blood"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1182\/blood-2010-02-268193","article-title":"Pulmonary hypertension and nitric oxide depletion in sickle cell disease","volume":"116","author":"Bunn","year":"2010","journal-title":"Blood"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1182\/blood-2015-08-618561","article-title":"Pathophysiology and treatment of pulmonary hypertension in sickle cell disease","volume":"127","author":"Gordeuk","year":"2016","journal-title":"Blood"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1900585","DOI":"10.1183\/13993003.00585-2019","article-title":"Clinical phenotypes and outcomes of precapillary pulmonary hypertension of sickle cell disease","volume":"54","author":"Savale","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1513\/AnnalsATS.201408-405CME","article-title":"American Thoracic Society Implementation Task Force Pulmonary hypertension in sickle cell disease","volume":"11","author":"Hayes","year":"2014","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_108","unstructured":"Mangla, A., Agarwal, N., and Maruvada, S. (2025). Sickle Cell Anemia. StatPearls, StatPearls Publishing."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1164\/rccm.201401-0065ST","article-title":"An official American Thoracic Society clinical practice guideline: Diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease","volume":"189","author":"Klings","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1800272","DOI":"10.1183\/13993003.00272-2018","article-title":"Chronic blood exchange transfusions in the management of pre-capillary pulmonary hypertension complicating sickle cell disease","volume":"52","author":"Turpin","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1182\/blood-2010-09-306167","article-title":"Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity","volume":"118","author":"Machado","year":"2011","journal-title":"Blood"},{"key":"ref_112","unstructured":"(2024, April 30). Sickle Cell Disease and CardiovAscular Risk\u2014Red Cell Exchange Trial (SCD-CARRE)\u2014Full Text View\u2014ClinicalTrials.gov, Available online: https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT04084080."},{"key":"ref_113","first-page":"1089","article-title":"Clitoral priapism: A rare condition presenting as a cause of vulvar pain","volume":"100","author":"Medina","year":"2002","journal-title":"Obstet. Gynecol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S0022-5347(17)45549-2","article-title":"The ultrastructure of the erectile tissue in priapism","volume":"135","author":"Spycher","year":"1986","journal-title":"J. Urol."},{"key":"ref_115","unstructured":"Silberman, M., and Hu, E.W. (2017). Priapism. StatPearls, StatPearls Publishing."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1182\/hematology.2021000275","article-title":"Treatment dilemmas: Strategies for priapism, chronic leg ulcer disease, and pulmonary hypertension in sickle cell disease","volume":"2021","author":"Azbell","year":"2021","journal-title":"Hematol. Am. Soc. Hematol Educ. Program"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1182\/hematology.2022000380","article-title":"Epidemiology and treatment of priapism in sickle cell disease","volume":"2022","author":"Idris","year":"2022","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/j.1743-6109.2006.00270.x","article-title":"Nitric oxide in the penis\u2014Science and therapeutic implications from erectile dysfunction to priapism","volume":"3","author":"Burnett","year":"2006","journal-title":"J. Sex. Med."},{"key":"ref_119","unstructured":"(2024, May 01). Treating Low-Flow Priapism\u2014Patient Information. Available online: https:\/\/patients.uroweb.org\/treatments\/low-flow-priapism\/."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.amjmed.2014.03.019","article-title":"Randomized controlled trial of sildenafil for preventing recurrent ischemic priapism in sickle cell disease","volume":"127","author":"Burnett","year":"2014","journal-title":"Am. J. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.urology.2005.11.045","article-title":"Long-term oral phosphodiesterase 5 inhibitor therapy alleviates recurrent priapism","volume":"67","author":"Burnett","year":"2006","journal-title":"Urology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1182\/blood-2014-09-551887","article-title":"How I treat priapism","volume":"125","author":"Anele","year":"2015","journal-title":"Blood"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e54376db","DOI":"10.1097\/01.HS9.0000967984.54376.db","article-title":"S268: Interim analysis of a phase 2 trial to assess the efficacy and safety of crizanlizumab in sickle cell disease patients with priapism (spartan)","volume":"7","author":"Anderson","year":"2023","journal-title":"HemaSphere"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Inusa, B.P.D. (2016). Leg ulceration in sickle cell disease: An early and visible sign of end-organ disease. Sickle Cell Disease\u2014Pain and Common Chronic Complications, InTech.","DOI":"10.5772\/62012"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1097\/01.ASW.0000755924.12513.40","article-title":"Common, but neglected: A comprehensive review of leg ulcers in sickle cell disease","volume":"34","author":"Sahu","year":"2021","journal-title":"Adv. Skin Wound Care"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1365-2141.2008.07115.x","article-title":"Venous incompetence, poverty and lactate dehydrogenase in Jamaica are important predictors of leg ulceration in sickle cell anaemia","volume":"142","author":"Cumming","year":"2008","journal-title":"Br. J. Haematol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1042\/cs0920153","article-title":"Postural vasoconstriction and leg ulceration in homozygous sickle cell disease","volume":"92","author":"Mohan","year":"1997","journal-title":"Clin. Sci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1042\/cs0980667","article-title":"Abnormal venous function in patients with homozygous sickle cell (SS) disease and chronic leg ulcers","volume":"98","author":"Mohan","year":"2000","journal-title":"Clin. Sci."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1002\/ajh.21838","article-title":"Leg ulcers in sickle cell disease","volume":"85","author":"Minniti","year":"2010","journal-title":"Am. J. Hematol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1097\/01.ASW.0000419408.37323.0c","article-title":"Sickle cell disease and leg ulcers","volume":"25","author":"Ladizinski","year":"2012","journal-title":"Adv. Skin Wound Care"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/ajh.22065","article-title":"Laboratory and echocardiography markers in sickle cell patients with leg ulcers","volume":"86","author":"Minniti","year":"2011","journal-title":"Am. J. Hematol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/0035-9203(87)90049-6","article-title":"Topical antibiotics in chronic sickle cell leg ulcers","volume":"81","author":"Baum","year":"1987","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s00277-021-04635-4","article-title":"Hydroxyurea and fetal hemoglobin effect on leg ulcers in patients with sickle cell disease","volume":"101","author":"Tolu","year":"2022","journal-title":"Ann. Hematol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.4081\/hr.2009.e22","article-title":"Best practices for transfusion for patients with sickle cell disease","volume":"1","author":"Wun","year":"2010","journal-title":"Hematol. Rep."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.jbspin.2006.01.025","article-title":"Pathophysiology and natural history of avascular necrosis of bone","volume":"73","author":"Lafforgue","year":"2006","journal-title":"Jt. Bone Spine"},{"key":"ref_136","unstructured":"Matthews, A.H., Davis, D.D., Fish, M.J., and Stitson, D. (2025). Avascular Necrosis. StatPearls, StatPearls Publishing."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"217","DOI":"10.4103\/1117-1936.180339","article-title":"Avascular necrosis of the femoral head in sickle cell disease in Nigeria: A retrospective study","volume":"14","author":"Akinyoola","year":"2007","journal-title":"Niger. Postgrad. Med. J."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"500","DOI":"10.2106\/00004623-200303000-00016","article-title":"The natural history of symptomatic osteonecrosis in adults with sickle-cell disease","volume":"85","author":"Hernigou","year":"2003","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Sanders, W.J. (2018). A rare case of avascular necrosis in sickle cell trait: A case report. BMC Hematol., 18.","DOI":"10.1186\/s12878-018-0098-z"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S0030-5898(05)70020-1","article-title":"Indications, technique, and results of shoulder arthroplasty in osteonecrosis","volume":"29","author":"Hattrup","year":"1998","journal-title":"Orthop. Clin. N. Am."},{"key":"ref_141","first-page":"CD004344","article-title":"Treatment for avascular necrosis of bone in people with sickle cell disease","volume":"12","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1159\/000534865","article-title":"Sickle cell disease and CKD: An update","volume":"55","author":"Zahr","year":"2024","journal-title":"Am. J. Nephrol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41581-022-00540-9","article-title":"The nephropathy of sickle cell trait and sickle cell disease","volume":"18","author":"Ataga","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_144","first-page":"450","article-title":"Nature of concentrating defect in sickle-cell nephropathy","volume":"1","year":"1970","journal-title":"Microradioangiographic studies. Lancet"},{"key":"ref_145","unstructured":"Aeddula, N.R., Bardhan, M., and Baradhi, K.M. (2023). Sickle Cell Nephropathy. StatPearls, StatPearls Publishing."},{"key":"ref_146","unstructured":"Goyal, A., Daneshpajouhnejad, P., Hashmi, M.F., and Bashir, K. (2025). Acute Kidney Injury. StatPearls, StatPearls Publishing."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1002\/pbc.24100","article-title":"Effect of hydroxyurea treatment on renal function parameters: Results from the multi-center placebo-controlled BABY HUG clinical trial for infants with sickle cell anemia","volume":"59","author":"Alvarez","year":"2012","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1097\/01.md.0000189089.45003.52","article-title":"Outcome of sickle cell anemia: A 4-decade observational study of 1056 patients","volume":"84","author":"Powars","year":"2005","journal-title":"Medicine"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"614","DOI":"10.7326\/0003-4819-115-8-614","article-title":"Chronic renal failure in sickle cell disease: Risk factors, clinical course, and mortality","volume":"115","author":"Powars","year":"1991","journal-title":"Ann. Intern. Med."},{"key":"ref_150","first-page":"619","article-title":"End Stage Kidney Disease Outcomes in Children and Young Adults with Sickle Cell Disease in the United States Renal Data System","volume":"39","author":"Zahr","year":"2023","journal-title":"Res. Sq."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"E143","DOI":"10.1002\/ajh.26115","article-title":"Hyperuricemia and abnormal nocturnal dipping impact glomerular filtration rate in patients with sickle cell anemia","volume":"96","author":"Lebensburger","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s00467-019-04432-2","article-title":"Hyperuricemia is associated with a lower glomerular filtration rate in pediatric sickle cell disease patients","volume":"35","author":"Kaspar","year":"2020","journal-title":"Pediatr. Nephrol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/pbc.24843","article-title":"Blood pressure abnormalities in children with sickle cell anemia","volume":"61","author":"Becker","year":"2014","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1182\/blood-2016-09-738104","article-title":"Severe anemia early in life as a risk factor for sickle-cell kidney disease","volume":"129","author":"Aban","year":"2017","journal-title":"Blood"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/ajh.25390","article-title":"Hyperfiltration during early childhood precedes albuminuria in pediatric sickle cell nephropathy","volume":"94","author":"Lebensburger","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1053\/j.ajkd.2018.12.027","article-title":"Progressive decline in estimated GFR in patients with sickle cell disease: An observational cohort study","volume":"74","author":"Derebail","year":"2019","journal-title":"Am. J. Kidney Dis."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1002\/ajh.25263","article-title":"Clinical and metabolomic risk factors associated with rapid renal function decline in sickle cell disease","volume":"93","author":"Xu","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.1111\/bjh.18494","article-title":"Patients with sickle cell disease who develop end-stage kidney disease continue to experience poor survival\u2014A 19-year United States renal data system study","volume":"199","author":"Winer","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1056\/NEJMra1214243","article-title":"Acute kidney injury and chronic kidney disease as interconnected syndromes","volume":"371","author":"Chawla","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1182\/blood-2018-05-853929","article-title":"HMOX1 and acute kidney injury in sickle cell anemia","volume":"132","author":"Saraf","year":"2018","journal-title":"Blood"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"E198","DOI":"10.1002\/ajh.25140","article-title":"Acute Kidney Injury during Parvovirus B19-Induced Transient Aplastic Crisis in Sickle Cell Disease","volume":"93","author":"Oakley","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_162","first-page":"1044","article-title":"Hemopexin deficiency promotes acute kidney injury in sickle cell disease","volume":"135","author":"Hazra","year":"2020","journal-title":"Blood"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1007\/s00467-014-2821-8","article-title":"Albuminuria correlates with hemolysis and NAG and KIM-1 in patients with sickle cell anemia","volume":"29","author":"Hamideh","year":"2014","journal-title":"Pediatr. Nephrol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/ajh.22045","article-title":"Biomarkers for early detection of sickle nephropathy","volume":"86","author":"Sundaram","year":"2011","journal-title":"Am. J. Hematol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"E27","DOI":"10.1002\/ajh.25329","article-title":"Hydroxyurea prevents onset and progression of albuminuria in children with sickle cell anemia","volume":"94","author":"Zahr","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1681\/ASN.2014111126","article-title":"Six Months of Hydroxyurea Reduces Albuminuria in Patients with Sickle Cell Disease","volume":"27","author":"Bartolucci","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"3867","DOI":"10.1182\/bloodadvances.2019000916","article-title":"American Society of Hematology 2019 guidelines for sickle cell disease: Cardiopulmonary and kidney disease","volume":"3","author":"Liem","year":"2019","journal-title":"Blood Adv."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"407","DOI":"10.2215\/CJN.02720320","article-title":"Mortality and Access to Kidney Transplantation in Patients with Sickle Cell Disease-Associated Kidney Failure","volume":"16","author":"Bae","year":"2021","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s40942-022-00419-8","article-title":"Risk factors associated with sickle cell retinopathy: Findings from the Cooperative Study of Sickle Cell Disease","volume":"8","author":"Nawaiseh","year":"2022","journal-title":"Int. J. Retin. Vitr."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/0002-9394(71)90429-6","article-title":"Classification and pathogenesis of proliferative sickle retinopathy","volume":"71","author":"Goldberg","year":"1971","journal-title":"Am. J. Ophthalmol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1001\/archopht.1971.00990050430006","article-title":"Natural history of untreated proliferative sickle retinopathy","volume":"85","author":"Goldberg","year":"1971","journal-title":"Arch. Ophthalmol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s00417-019-04294-2","article-title":"Sickle cell retinopathy. A focused review","volume":"257","author":"Mura","year":"2019","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"335","DOI":"10.2147\/JMDH.S90630","article-title":"Sickle cell retinopathy: Improving care with a multidisciplinary approach","volume":"10","author":"Menaa","year":"2017","journal-title":"J. Multidiscip. Healthc."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.ophtha.2019.02.023","article-title":"Prevalence and onset of pediatric sickle cell retinopathy","volume":"126","author":"Li","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_175","first-page":"150","article-title":"Incidence of ocular abnormalities in patients with sickle hemoglobinopathies","volume":"18","author":"Friberg","year":"1986","journal-title":"Ann. Ophthalmol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1097\/IIO.0000000000000255","article-title":"The role of retinal imaging in sickle cell retinopathy: A review","volume":"59","author":"Wang","year":"2019","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0002-9394(78)90013-2","article-title":"Retinal depression sign indicating a small retinal infarct","volume":"86","author":"Goldbaum","year":"1978","journal-title":"Am. J. Ophthalmol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/0002-9394(72)91213-5","article-title":"Ocular findings in hemoglobin SC disease in Jamaica","volume":"74","author":"Condon","year":"1972","journal-title":"Am. J. Ophthalmol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1136\/bjo.74.3.172","article-title":"Risk factors for proliferative sickle retinopathy","volume":"74","author":"Fox","year":"1990","journal-title":"Br. J. Ophthalmol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1016\/j.ophtha.2005.05.026","article-title":"Incidence and natural history of proliferative sickle cell retinopathy: Observations from a cohort study","volume":"112","author":"Downes","year":"2005","journal-title":"Ophthalmology"},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Scott, I.U., Regillo, C.D., Flynn, H.W., and Brown, G.C. (2018). Sickle Retinopathy. Vitreoretinal Disease: Diagnosis, Management, and Clinical Pearls, Thieme. Chapter 21.","DOI":"10.1055\/b-0037-149079"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/74651","article-title":"Mechanisms of angiogenesis and arteriogenesis","volume":"6","author":"Carmeliet","year":"2000","journal-title":"Nat. Med."},{"key":"ref_183","first-page":"574","article-title":"Vascular endothelial growth factor\/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model","volume":"145","author":"Miller","year":"1994","journal-title":"Am. J. Pathol."},{"key":"ref_184","first-page":"469","article-title":"Differential roles of vascular endothelial growth factor receptor-1 and receptor-2 in angiogenesis","volume":"39","author":"Shibuya","year":"2006","journal-title":"J. Biochem. Mol. Biol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"212532","DOI":"10.7573\/dic.212532","article-title":"The role of anti-vascular endothelial growth factor (anti-VEGF) in the management of proliferative diabetic retinopathy","volume":"7","author":"Zhao","year":"2018","journal-title":"Drugs Context"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1023\/A:1007657109012","article-title":"Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys","volume":"17","author":"Drolet","year":"2000","journal-title":"Pharm. Res."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"623.e1","DOI":"10.1016\/j.ophtha.2006.01.027","article-title":"Tolerability and efficacy of multiple escalating doses of ranibizumab (Lucentis) for neovascular age-related macular degeneration","volume":"113","author":"Rosenfeld","year":"2006","journal-title":"Ophthalmology"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nrd1381","article-title":"Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer","volume":"3","author":"Ferrara","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/bjh.12238","article-title":"Protection from sickle cell retinopathy is associated with elevated HbF levels and hydroxycarbamide use in children","volume":"161","author":"Estepp","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1136\/bjo.64.6.404","article-title":"Behaviour of untreated proliferative sickle retinopathy","volume":"64","author":"Condon","year":"1980","journal-title":"Br. J. Ophthalmol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/eye.1988.62","article-title":"Patterns of visual loss in untreated sickle cell retinopathy","volume":"2","author":"Moriarty","year":"1988","journal-title":"Eye"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S0161-6420(91)32246-2","article-title":"A randomized clinical trial of feeder vessel photocoagulation of sickle cell retinopathy. A long-term follow-up","volume":"98","author":"Jacobson","year":"1991","journal-title":"Ophthalmology"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/S0161-6420(83)34537-1","article-title":"A randomized clinical trial of feeder vessel photocoagulation of proliferative sickle cell retinopathy. I. Preliminary results","volume":"90","author":"Jampol","year":"1983","journal-title":"Ophthalmology"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.4103\/ijo.IJO_1446_18","article-title":"Central retinal artery occlusion","volume":"66","author":"Hayreh","year":"2018","journal-title":"Indian J. Ophthalmol."},{"key":"ref_195","unstructured":"Tripathy, K., Shah, S.S., and Waymack, J.R. (2025). Central retinal artery occlusion. StatPearls, StatPearls Publishing."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1002\/pbc.21152","article-title":"Sudden-onset blindness in sickle cell disease due to retinal artery occlusion","volume":"50","author":"Liem","year":"2008","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1001\/jamaophthalmol.2013.5047","article-title":"Acute, bilateral, concurrent central retinal artery occlusion in sickle cell disease after use of tadalafil (Cialis)","volume":"131","author":"Murthy","year":"2013","journal-title":"JAMA Ophthalmol."},{"key":"ref_198","first-page":"221","article-title":"Central retinal-artery occlusion in proliferative sickle-cell retinopathy after retrobulbar injection","volume":"20","author":"Roth","year":"1988","journal-title":"Ann. Ophthalmol."},{"key":"ref_199","first-page":"23247096211028390","article-title":"Concurrent bilateral central retinal artery occlusion secondary to sickle cell crisis","volume":"9","author":"Renganathan","year":"2021","journal-title":"J. Investig. Med. High Impact Case Rep."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00247-008-1049-9","article-title":"The spleen in the sickling disorders: An update","volume":"39","author":"Khatib","year":"2009","journal-title":"Pediatr. Radiol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0022-3476(85)80125-6","article-title":"Acute splenic sequestration in homozygous sickle cell disease: Natural history and management","volume":"107","author":"Emond","year":"1985","journal-title":"J. Pediatr."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0022-3468(92)90315-X","article-title":"Acute splenic sequestration crisis in sickle cell disease: Early detection and treatment","volume":"27","author":"Powell","year":"1992","journal-title":"J. Pediatr. Surg."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1136\/adc.56.10.765","article-title":"Acute splenic sequestration and hypersplenism in the first five years in homozygous sickle cell disease","volume":"56","author":"Topley","year":"1981","journal-title":"Arch. Dis. Child."},{"key":"ref_204","first-page":"67","article-title":"Management of acute splenic sequestration crisis in sickle cell disease","volume":"1","author":"Grover","year":"1990","journal-title":"J. Assoc. Acad. Minor. Phys."},{"key":"ref_205","first-page":"864257","article-title":"Splenic complications of sickle cell anemia and the role of splenectomy","volume":"2011","year":"2011","journal-title":"ISRN Hematol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/0002-9343(86)90649-2","article-title":"Acute splenic sequestration crises in adults with sickle cell disease","volume":"80","author":"Solanki","year":"1986","journal-title":"Am. J. Med."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"375","DOI":"10.3109\/03630269.2015.1072550","article-title":"Acute splenic sequestration crisis in adult sickle cell disease: A report of 16 cases","volume":"39","author":"Naymagon","year":"2015","journal-title":"Hemoglobin"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1064.e5","DOI":"10.1016\/j.ajem.2008.02.031","article-title":"Acute splenic sequestration in an adult with hemoglobin S-C disease","volume":"26","author":"Varon","year":"2008","journal-title":"Am. J. Emerg. Med."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1056\/NEJM196910232811703","article-title":"Functional asplenia in sickle-cell anemia","volume":"281","author":"Pearson","year":"1969","journal-title":"N. Engl. J. Med."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1002\/ajh.23154","article-title":"Hyposplenism: Comparison of different methods for determining splenic function","volume":"87","author":"Lammers","year":"2012","journal-title":"Am. J. Hematol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/ajh.23888","article-title":"Clinical outcomes of splenectomy in children: Report of the splenectomy in congenital hemolytic anemia registry","volume":"90","author":"Rice","year":"2015","journal-title":"Am. J. Hematol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1007\/s00259-001-0738-5","article-title":"Scintigraphic follow-up of the effects of therapy with hydroxyurea on splenic function in patients with sickle cell disease","volume":"29","author":"Santos","year":"2002","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/pbc.21271","article-title":"Preservation of spleen and brain function in children with sickle cell anemia treated with hydroxyurea","volume":"50","author":"Hankins","year":"2008","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1067\/mpd.2001.119590","article-title":"A two-year pilot trial of hydroxyurea in very young children with sickle-cell anemia","volume":"139","author":"Wang","year":"2001","journal-title":"J. Pediatr."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1182\/blood.V88.6.1951.bloodjournal8861951","article-title":"First report of reversal of organ dysfunction in sickle cell anemia by the use of hydroxyurea: Splenic regeneration","volume":"88","author":"Claster","year":"1996","journal-title":"Blood"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/00043426-199801000-00004","article-title":"Hydroxyurea in children with sickle cell disease: Impact on splenic function and compliance with therapy","volume":"20","author":"Olivieri","year":"1998","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_217","first-page":"209","article-title":"Reversibility of splenic function by transfusion in two young adults with sickle cell anemia","volume":"9","author":"Wethers","year":"1987","journal-title":"Am. J. Pediatr. Hematol. Oncol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1056\/NEJM197008132830703","article-title":"Transfusion-reversible functional asplenia in young children with sickle-cell anemia","volume":"283","author":"Pearson","year":"1970","journal-title":"N. Engl. J. Med."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/S0022-3476(89)80282-3","article-title":"Splenic phagocytic function in children with sickle cell anemia receiving long-term hypertransfusion therapy","volume":"115","author":"Buchanan","year":"1989","journal-title":"J. Pediatr."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1182\/blood-2013-12-542076","article-title":"How we treat sickle hepatopathy and liver transplantation in adults","volume":"123","author":"Gardner","year":"2014","journal-title":"Blood"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1177\/0033354919839072","article-title":"Improving an administrative case definition for longitudinal surveillance of sickle cell disease","volume":"134","author":"Snyder","year":"2019","journal-title":"Public Health Rep."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"S376","DOI":"10.1016\/j.amepre.2011.09.007","article-title":"Sickle cell disease: The need for a public health agenda","volume":"41","author":"Yusuf","year":"2011","journal-title":"Am. J. Prev. Med."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"S28","DOI":"10.1016\/j.annemergmed.2020.08.009","article-title":"Trends in Sickle Cell Disease-Related Mortality in the United States, 1979 to 2017","volume":"76","author":"Payne","year":"2020","journal-title":"Ann. Emerg. Med."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1056\/NEJMra1510865","article-title":"Sickle Cell Disease","volume":"376","author":"Piel","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_225","unstructured":"GBD 2021 Sickle Cell Disease Collaborators (2023). Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000\u20132021: A systematic analysis from the Global Burden of Disease Study 2021. Lancet Haematol., 10, e585\u2013e599."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1182\/blood-2016-05-716910","article-title":"Survival in adults with sickle cell disease in a high-income setting","volume":"128","author":"Gardner","year":"2016","journal-title":"Blood"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.ss7109a1","article-title":"Surveillance for Sickle Cell Disease\u2014Sickle Cell Data Collection Program, Two States, 2004\u20132018","volume":"71","author":"Snyder","year":"2022","journal-title":"MMWR Surveill. Summ."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"e1915374","DOI":"10.1001\/jamanetworkopen.2019.15374","article-title":"Estimated life expectancy and income of patients with sickle cell disease compared with those without sickle cell disease","volume":"2","author":"Lubeck","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1002\/ajh.20685","article-title":"Circumstances of death in adult sickle cell disease patients","volume":"81","author":"Darbari","year":"2006","journal-title":"Am. J. Hematol."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"626","DOI":"10.3324\/haematol.2016.153791","article-title":"Risk factors for mortality in adult patients with sickle cell disease: A meta-analysis of studies in North America and Europe","volume":"102","author":"Maitra","year":"2017","journal-title":"Haematologica"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1182\/blood-2018-10-880575","article-title":"Decreased median survival of adults with sickle cell disease after adjusting for left truncation bias: A pooled analysis","volume":"133","author":"DeBaun","year":"2019","journal-title":"Blood"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.3324\/haematol.2014.120030","article-title":"Environmental determinants of severity in sickle cell disease","volume":"100","author":"Tewari","year":"2015","journal-title":"Haematologica"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00277-008-0598-1","article-title":"The effects of air quality on haematological and clinical parameters in children with sickle cell anaemia","volume":"88","author":"Mittal","year":"2009","journal-title":"Ann. Hematol."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/ajh.24281","article-title":"Secondhand smoke is associated with more frequent hospitalizations in children with sickle cell disease","volume":"91","author":"Sadreameli","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Inusa, B.P.D., Hsu, L.L., Kohli, N., Patel, A., Ominu-Evbota, K., Anie, K.A., and Atoyebi, W. (2019). Sickle cell disease-genetics, pathophysiology, clinical presentation and treatment. Int. J. Neonatal Screen., 5.","DOI":"10.3390\/ijns5020020"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"666","DOI":"10.3324\/haematol.2016.154245","article-title":"Associations between environmental factors and hospital admissions for sickle cell disease","volume":"102","author":"Piel","year":"2017","journal-title":"Haematologica"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1080\/20469047.2021.1936393","article-title":"Co-existing sickle cell anaemia and inflammatory bowel disease: Case report and review of the literature","volume":"42","author":"Adepoju","year":"2022","journal-title":"Paediatr. Int. Child Health"},{"key":"ref_238","doi-asserted-by":"crossref","unstructured":"Ramsey, S.D., Bender, M.A., Li, L., Johnson, K.M., Jiao, B., Devine, B., and Basu, A. (2022). Prevalence of comorbidities associated with sickle cell disease among non-elderly individuals with commercial insurance-A retrospective cohort study. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0278137"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1097\/01.rhu.0000158549.92844.96","article-title":"Coexisting systemic lupus erythematosus and sickle cell disease: A diagnostic and therapeutic challenge","volume":"11","author":"Khalidi","year":"2005","journal-title":"J. Clin. Rheumatol."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neulet.2019.04.011","article-title":"Psychosocial and affective comorbidities in sickle cell disease","volume":"705","author":"Pecker","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_241","first-page":"378","article-title":"Co-existince of sickle cell disease and hemidiaphragm paralysis","volume":"54","author":"Melek","year":"2006","journal-title":"Tuberk. Toraks"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1590\/1984-0462\/;2018;36;4;00010","article-title":"Socioeconomic and nutritional characteristics of children and adolescents with sickle cell anemia: A systematic review","volume":"36","author":"Jesus","year":"2018","journal-title":"Rev. Paul. Pediatr."},{"key":"ref_243","first-page":"57","article-title":"The influence of socio-economic status on the severity of sickle cell disease","volume":"22","author":"Okany","year":"1993","journal-title":"Afr. J. Med. Med. Sci."},{"key":"ref_244","doi-asserted-by":"crossref","unstructured":"Phillips, S., Chen, Y., Masese, R., Noisette, L., Jordan, K., Jacobs, S., Hsu, L.L., Melvin, C.L., Treadwell, M., and Shah, N. (2022). Perspectives of individuals with sickle cell disease on barriers to care. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0265342"},{"key":"ref_245","first-page":"61","article-title":"Treatment of sickle cell disease\u2014Options and perspective","volume":"13","author":"Sheikh","year":"2023","journal-title":"Am. J. Blood Res."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.pcl.2018.01.005","article-title":"Treatment options for sickle cell disease","volume":"65","author":"Meier","year":"2018","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1126\/science.aba3827","article-title":"Treating sickle cell anemia","volume":"367","author":"Tisdale","year":"2020","journal-title":"Science"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1182\/asheducation-2007.1.482","article-title":"Limitations of clinical trials in sickle cell disease: A case study of the Multi-center Study of Hydroxyurea (MSH) trial and the Stroke Prevention (STOP) trial","volume":"2007","author":"Debaun","year":"2007","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1182\/blood.2023021220","article-title":"The challenge of clinical end points in sickle cell disease","volume":"142","author":"Ataga","year":"2023","journal-title":"Blood"},{"key":"ref_250","first-page":"e44780","article-title":"The effectiveness of common interventions in the management of sickle cell disease in primary care settings: A review","volume":"15","author":"Mbaezue","year":"2023","journal-title":"Cureus"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0033-3549(04)50214-5","article-title":"Rural\/urban differences in access to and utilization of services among people in Alabama with sickle cell disease","volume":"118","author":"Telfair","year":"2003","journal-title":"Public Health Rep."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"e2013062","DOI":"10.4084\/mjhid.2013.062","article-title":"Sickle cell disease: Management options and challenges in developing countries","volume":"5","author":"Ansong","year":"2013","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1182\/bloodadvances.2021006281","article-title":"Lifetime medical costs attributable to sickle cell disease among nonelderly individuals with commercial insurance","volume":"7","author":"Johnson","year":"2023","journal-title":"Blood Adv."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/ajh.21408","article-title":"The cost of health care for children and adults with sickle cell disease","volume":"84","author":"Kauf","year":"2009","journal-title":"Am. J. Hematol."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s10903-020-01102-6","article-title":"Effective Recruitment Strategies for a Sickle Cell Patient Registry Across Sites from the Sickle Cell Disease Implementation Consortium (SCDIC)","volume":"23","author":"Masese","year":"2021","journal-title":"J. Immigr. Minor. Health"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/4\/326\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T12:20:48Z","timestamp":1770726048000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/4\/326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,10]]},"references-count":255,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["cells15040326"],"URL":"https:\/\/doi.org\/10.3390\/cells15040326","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,10]]}}}