{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:56:27Z","timestamp":1791510987582,"version":"4.3.4"},"reference-count":33,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020648","name":"Universidade Estadual de Santa Cruz","doi-asserted-by":"publisher","award":["073.11006.2019.0009828-54"],"award-info":[{"award-number":["073.11006.2019.0009828-54"]}],"id":[{"id":"10.13039\/501100020648","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematology Reports"],"abstract":"<jats:p>Sickle cell disease (SCD) is characterized by the presence of the variant S hemoglobin (HbS). The homozygous genotype (HbSS) is sickle cell anemia (SCA), while the double heterozygous of HbS and HbC (HbSC) is defined as SC hemoglobinopathy. The pathophysiology is based on chronic hemolysis, inflammation, endothelial dysfunction, and vaso-occlusion, which results in vasculopathy and serious clinical manifestations. Sickle leg ulcers (SLUs) are cutaneous lesions around the malleoli frequent in 20% of Brazilian patients with SCD. SLUs present a variable clinical and laboratory pattern modulated by several characteristics that are not fully understood. Hence, this study aimed to investigate laboratory biomarkers and genetic and clinical parameters associated with the development of SLUs. This descriptive cross-sectional study included 69 SCD patients, 52 without SLU (SLU\u2212) and 17 with active or previous SLU history (SLU+). The results showed a higher incidence of SLU in SCA patients and there was no observed association of \u03b1-3.7 Kb thalassemia in SLU occurrence. Alterations in NO metabolism and hemolysis were associated with clinical evolution and severity of SLU, in addition to hemolysis modulating the etiology and recurrence of SLU. Our multifactorial analyses demonstrate and extend the role of hemolysis driving the pathophysiological mechanism of SLU.<\/jats:p>","DOI":"10.3390\/hematolrep15010013","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T04:47:24Z","timestamp":1676436444000},"page":"119-129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Leg Ulcers in Sickle Cell Disease: A Multifactorial Analysis Highlights the Hemolytic Profile"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-1544","authenticated-orcid":false,"given":"Edvan do Carmo","family":"Santos","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Patologia Aplicada e Gen\u00e9tica, Departamento de Ci\u00eancias Biol\u00f3gicas, Universidade Estadual de Santa Cruz, Ilh\u00e9us 45662-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Vin\u00edcius Bispo","family":"Santana","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Patologia Aplicada e Gen\u00e9tica, Departamento de Ci\u00eancias Biol\u00f3gicas, Universidade Estadual de Santa Cruz, Ilh\u00e9us 45662-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"La\u00edne Lopes Silva de","family":"Jesus","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Patologia Aplicada e Gen\u00e9tica, Departamento de Ci\u00eancias Biol\u00f3gicas, Universidade Estadual de Santa Cruz, Ilh\u00e9us 45662-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Imbassahy Valentim","family":"Melo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Patologia Aplicada e Gen\u00e9tica, Departamento de Ci\u00eancias Biol\u00f3gicas, Universidade Estadual de Santa Cruz, Ilh\u00e9us 45662-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4219-1311","authenticated-orcid":false,"given":"S\u00e8tondji Cocou Modeste Alexandre","family":"Yahou\u00e9d\u00e9hou","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00e3o em Gen\u00e9tica e Hematologia Translacional, Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador 40296-710, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Concei\u00e7\u00e3o da","family":"Guarda","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00e3o em Gen\u00e9tica e Hematologia Translacional, Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador 40296-710, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayra Pereira","family":"Santiago","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00e3o em Gen\u00e9tica 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dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancia e Tecnologia em Energia e Sustentabilidade, Universidade Federal do Rec\u00f4ncavo da Bahia, Feira de Santana 44042-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elis\u00e2ngela Vit\u00f3ria","family":"Adorno","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Anemias, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal da Bahia, Salvador 40170-115, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2340-860X","authenticated-orcid":false,"given":"Augusto Cezar Magalh\u00e3es","family":"Aleluia","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Naturais, Universidade Estadual do Sudoeste da Bahia, Vit\u00f3ria da Conquista 45031-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5962-661X","authenticated-orcid":false,"given":"Luciene Cristina Gastalho Campos","family":"Luiz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Patologia Aplicada e Gen\u00e9tica, Departamento de Ci\u00eancias Biol\u00f3gicas, Universidade Estadual de Santa Cruz, Ilh\u00e9us 45662-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa Cristina Cardoso","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias da Sa\u00fade, Universidade Estadual de Santa Cruz, Ilh\u00e9us 45662-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilda de Souza","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00e3o em Gen\u00e9tica e Hematologia Translacional, Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador 40296-710, Brazil"},{"name":"Centro de Ci\u00eancia e Tecnologia em Energia e Sustentabilidade, Universidade Federal do Rec\u00f4ncavo da Bahia, Feira de Santana 44042-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6928-824X","authenticated-orcid":false,"given":"Milena Magalh\u00e3es","family":"Aleluia","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Patologia Aplicada e Gen\u00e9tica, Departamento de Ci\u00eancias Biol\u00f3gicas, Universidade Estadual de Santa Cruz, Ilh\u00e9us 45662-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"ref_1","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. 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