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Hydroxyurea and fetal hemoglobin effect on leg ulcers in patients with sickle cell disease

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Abstract

The presence of leg ulcers in individuals with sickle cell disease often represents an early sign of vasculopathy and future end organ damage. Pathophysiological mechanisms of formation and evolution of leg ulcers are poorly understood; nevertheless, HbF has been associated with lower incidence of leg ulcers, while hydroxyurea has been correlated with high risk of leg ulcers. As a result, there is hesitation regarding hydroxyurea use in patients with SCD and leg ulcers. In this study, we aim to define (1) a target of HbF that offers protection against leg ulcer development and (2) the impact of hydroxyurea therapy on leg ulcer prevalence. Our study demonstrated that in order to reduce leg ulcer incidence by one-third, a HbF > 25% is needed, a threshold not commonly reached and maintained in the adult SCD population. Importantly, leg ulcer incidence appears to be independent of HU use (p = 0.50). Our interpretation of this data is that the use of HU in a patient with SCD and leg ulcers should be guided by a careful assessment of risks and benefits of this therapeutic modality.

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Author information

Authors and Affiliations

  1. Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, 111 East 210th street, Bronx, NY, 10467, USA

    Seda S. Tolu

  2. Department of Medicine, Division of Hematology, Albert Einstein College of Medicine, Bronx, NY, USA

    Andrew Crouch

  3. Department of Epidemiology and Public Health, Albert Einstein College of Medicine, Bronx, NY, USA

    Jaeun Choi & Qi Gao

  4. Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA

    Moramaya Reyes-Gil

  5. Department of Medicine, Division of Hematology/Center for Sickle Cell Disease, University of Tennessee Health Science Center, Memphis, TN, USA

    Ugochi Olivia Ogu

  6. Department of Family and Social Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA

    Giacomo Vinces

  7. Department of Medicine, Division of Hematology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA

    Caterina P. Minniti

Authors
  1. Seda S. Tolu
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  2. Andrew Crouch
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  3. Jaeun Choi
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  4. Qi Gao
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  5. Moramaya Reyes-Gil
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  6. Ugochi Olivia Ogu
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  7. Giacomo Vinces
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  8. Caterina P. Minniti
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Contributions

ST collected data, analyzed data, developed tables and graphs, and wrote the paper. AC collected data. JC and QG analyzed the data, developed tables and graphs. MR analyzed the data. GV and UO collected data. CM designed project idea and wrote the paper.

Corresponding author

Correspondence to Seda S. Tolu.

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This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

CM has consultancy with Novartis, GBT, Roche, Berhinger, bluebird Bio, Emmaus, Forma, and TeuTona. UO has consultancy with Vertex Pharmaceuticals.

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Tolu, S.S., Crouch, A., Choi, J. et al. Hydroxyurea and fetal hemoglobin effect on leg ulcers in patients with sickle cell disease. Ann Hematol 101, 541–548 (2022). https://doi.org/10.1007/s00277-021-04635-4

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  • DOI: https://doi.org/10.1007/s00277-021-04635-4

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