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01-04-2021 | Leg Ulcer | Original Article

Alpha thalassemia, but not β^S-globin haplotypes, influence sickle cell anemia clinical outcome in a large, single-center Brazilian cohort

Authors: Betânia Lucena Domingues Hatzlhofer, Diego Antonio Pereira-Martins, Igor de Farias Domingos, Gabriela da Silva Arcanjo, Isabel Weinhäuser, Diego Arruda Falcão, Isabela Cristina Cordeiro Farias, Jéssica Vitória Gadelha de Freitas Batista, Luana Priscilla Laranjeira Prado, Jéssica Maria Florencio Oliveira, Thais Helena Chaves Batista, Marcondes José de Vasconcelos Costa Sobreira, Rodrigo Marcionilo de Santana, Amanda Bezerra de Sá Araújo, Manuela Albuquerque de Melo, Bruna Vasconcelos de Ancântara, Juan Luiz Coelho-Silva, Ana Beatriz Lucas de Moura Rafael, Danízia Menezes de Lima Silva, Flávia Peixoto Albuquerque, Magnun Nueldo Nunes Santos, Ana Cláudia dos Anjos, Fernando Ferreira Costa, Aderson da Silva Araújo, Antonio Roberto Lucena-Araújo, Marcos André Cavalcanti Bezerra

Published in: Annals of Hematology | Issue 4/2021

Abstract

Alpha thalassemia and beta-globin haplotype are considered classical genetic disease modifiers in sickle cell anemia (SCA) causing clinical heterogeneity. Nevertheless, their functional impact on SCA disease emergence and progression remains elusive. To better understand the role of alpha thalassemia and beta-globin haplotype in SCA, we performed a retrospective study evaluating the clinical manifestations of 614 patients. The univariate analysis showed that the presence of alpha-thalassemia −3.7-kb mutation (αα/-α and -α/-α) decreased the risk of stroke development (p = 0.046), priapism (p = 0.033), and cholelithiasis (p = 0.021). Furthermore, the cumulative incidence of stroke (p = 0.023) and cholelithiasis (p = 0.006) was also significantly lower for patients carrying the alpha thalassemia −3.7-kb mutation. No clinical effects were associated with the beta-globin haplotype analysis, which could be explained by the relatively homogeneous haplotype composition in our cohort. Our results reinforce that alpha thalassemia can provide protective functions against hemolysis-related symptoms in SCA. Although, several genetic modifiers can impact the inflammatory state of SCA patients, the alpha thalassemia mutation remains one of the most recurrent genetic aberration and should therefore always be considered first.

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Title: Alpha thalassemia, but not βS-globin haplotypes, influence sickle cell anemia clinical outcome in a large, single-center Brazilian cohort
Authors: Betânia Lucena Domingues Hatzlhofer
Diego Antonio Pereira-Martins
Igor de Farias Domingos
Gabriela da Silva Arcanjo
Isabel Weinhäuser
Diego Arruda Falcão
Isabela Cristina Cordeiro Farias
Jéssica Vitória Gadelha de Freitas Batista
Luana Priscilla Laranjeira Prado
Jéssica Maria Florencio Oliveira
Thais Helena Chaves Batista
Marcondes José de Vasconcelos Costa Sobreira
Rodrigo Marcionilo de Santana
Amanda Bezerra de Sá Araújo
Manuela Albuquerque de Melo
Bruna Vasconcelos de Ancântara
Juan Luiz Coelho-Silva
Ana Beatriz Lucas de Moura Rafael
Danízia Menezes de Lima Silva
Flávia Peixoto Albuquerque
Magnun Nueldo Nunes Santos
Ana Cláudia dos Anjos
Fernando Ferreira Costa
Aderson da Silva Araújo
Antonio Roberto Lucena-Araújo
Marcos André Cavalcanti Bezerra
Publication date: 01-04-2021
Publisher: Springer Berlin Heidelberg
Keywords: Leg Ulcer
Stroke
Thalassemia
Priapism
Cholelithiasis
Sickle Cell Anemia
Published in: Annals of Hematology / Issue 4/2021
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-021-04450-x

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Alpha thalassemia, but not β^S-globin haplotypes, influence sickle cell anemia clinical outcome in a large, single-center Brazilian cohort

Abstract

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Abstract

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