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A study of the geographic distribution and associated risk factors of leg ulcers within an international cohort of sickle cell disease patients: the CASiRe group analysis

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Abstract

Vasculopathy is a hallmark of sickle cell disease ultimately resulting in chronic end organ damage. Leg ulcer is one of its sequelae, occurring in ~ 5–10% of adult sickle cell patients. The majority of leg ulcer publications to date have emanated from single center cohort studies. As such, there are limited studies on the geographic distribution of leg ulcers and associated risk factors worldwide. The Consortium for the Advancement of Sickle Cell Research (CASiRe) was formed to improve the understanding of the different phenotypes of sickle cell disease patients living in different geographic locations around the world (USA, UK, Italy, Ghana). This cross-sectional cohort sub-study of 659 sickle cell patients aimed to determine the geographic distribution and risk factors associated with leg ulcers. The prevalence of leg ulcers was 10.3% and was associated with older age, SS genotype, male gender, and Ghanaian origin. In fact, the highest prevalence (18.6%) was observed in Ghana. Albuminuria, proteinuria, increased markers of hemolysis (lower hemoglobin, higher total bilirubin), lower oxygen saturation, and lower body mass index were also associated with leg ulceration. Overall, our study identified a predominance of leg ulcers within male hemoglobin SS patients living in sub-Saharan Africa with renal dysfunction and increased hemolysis.

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Acknowledgments

The authors acknowledge the contributions of the study participants. We would like to thank the following individuals for their contributions to this work: students of the University of Michigan Minority Health and Health Disparities International Research Training (MHIRT) program.

Funding

(Funding support: Grant No. NIMHD T37MD001425),Funding support: Grant No. NIMHD T37MD001425), Ahmed Owda, Duna Buttner, Biana D. Oteng, Sophia Akatue, Ashya Smith, Austin Novarra, Clementine Fu, Fitz Tavernier, Samuel Wilson, Tulana Kpadenou, Lewis Graham, Rose Bamfo, Esther Kim, Haikel, Halle, Rebekah Urbonya, Fatimah Farooq, Sheri Van Omen, and Marianna Yamamoto. Thanks to Sasia-Marie Jones from the University of Connecticut for her research assistance to Biree Andemariam. Thanks to Adetola Kassim and Vishwas Sakhalkar for their help in developing the questionnaire and protocol.

Author information

Authors and Affiliations

  1. Department of Physiology, University of Ghana Medical School, Accra, Ghana

    Charles Antwi-Boasiako & Gifty Dankwah Boatemaa

  2. New England Sickle Cell Institute, Division of Hematology-Oncology, Neag Comprehensive Cancer Center, UCONN Health, University of Connecticut, Farmington, CT, USA

    Biree Andemariam

  3. Clinic of Pediatric Hematology Oncology, Department of Women’s and Child Health, Azienda Ospedaliera-Università di Padova, Padova, Italy

    Raffaella Colombatti & Laura Sainati

  4. Department of Hematology, Korle-Bu Teaching Hospital, Accra, Ghana

    Eugenia Vicky Asare

  5. ProMedica Russell J. Ebeid Children’s Hospital, Toledo, OH, USA

    Crawford Strunk

  6. Pediatric Hematology/Oncology, Rainbow Babies and Children’s Hospital, Cleveland, OH, USA

    Connie M. Piccone

  7. Department of Pediatrics, Albert Einstein College of Medicine, Children’s Hospital at Montefiore, Bronx, NY, USA

    Deepa Manwani

  8. Department of Pediatrics, Connecticut Children’s Medical Center, Hartford, CT, USA

    Donna Boruchov & William Zempsky

  9. Division of Pediatric Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA

    Fatimah Farooq, Rebekah Urbonya, Samuel Wilson & Andrew D. Campbell

  10. Department of Women, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy

    Silverio Perrotta & Immacolata Tartaglione

  11. Division of Pediatric Hematology/Oncology, University of Illinois- Chicago, Chicago, IL, USA

    Angela Rivers

  12. Department of Child Health, Korle Bu Teaching Hospital, Accra, Ghana

    Sudha Rao

  13. Department of Haematology, University of Cape Coast, Cape Coast, Ghana

    Ivy Ekem

  14. Ghana Institute of Clinical Genetics, Korle Bu Teaching Hospital, Accra, Ghana

    Fredericka Sey

  15. Department of Child Health, Korle Bu Teaching Hospital, University of Ghana Medical School, Accra, Ghana

    Catherine Segbefia

  16. Department of Pediatric Haematology, Evelina Children’s Hospital, Guy’s and St. Thomas NHS Trust, London, UK

    Baba Inusa

  17. Division of Hematology, Center for Cancer & Blood Disorders, Children’s National Medical Center, George Washington University School of Medicine & Health Sciences, 111 Michigan Avenue NW, Washington, DC, 20010, USA

    Andrew D. Campbell

Authors
  1. Charles Antwi-Boasiako
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  2. Biree Andemariam
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  4. Eugenia Vicky Asare
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  5. Crawford Strunk
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  6. Connie M. Piccone
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  7. Deepa Manwani
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  8. Donna Boruchov
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  9. Fatimah Farooq
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  11. Samuel Wilson
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  12. Gifty Dankwah Boatemaa
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  13. Silverio Perrotta
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  14. Laura Sainati
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  15. Angela Rivers
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  16. Sudha Rao
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  17. William Zempsky
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  18. Ivy Ekem
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  19. Fredericka Sey
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  20. Catherine Segbefia
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  21. Baba Inusa
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  22. Immacolata Tartaglione
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  23. Andrew D. Campbell
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Contributions

AC, CAB, wrote the manuscript. BA, RC, CS (Ghana), IT, CP, DM, EVA, DB, AR, WZ, CS(US), BI, critically edited the manuscript. AC, RC, BA, CS (US), CP, IT, DM, DB, RU, WZ, BI, CAB helped design the study, performed the research, and analyzed the data. EVA, DB, FF, SW, GDB, SR, FS, CS (Ghana) performed the research and analyzed the data. AR, FS, LS helped design the study and analyzed the data. FS, LS, IE, SR reviewed the manuscript and analyzed the data.

Corresponding author

Correspondence to Andrew D. Campbell.

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Conflict of interest

A Campbell: Research Funding from Global Blood Therapeutics, Novartis, Cyclerion; Consultancy for Global Blood Therapeutics, Cyclerion and Bluebird Bio; D Manwani: Research funding from Grifols; Consultancy for Novartis, Pfizer, Blood Therapeutics; B Andemariam: Consultancy for Novartis, Pfizer, NovoNordisk, Emmaus, Cyclerion, Terumo, Sanofi; DSMB: Global Blood Therapeutics; Research Funding: Imara; B Inusa: Education Funding: Novartis Ast raZeneca, Global Blood Therapeutics, Celgene, Vertex; C. Strunk: Consultancy Global Blood Therapeutics and Novartis; C Piccone: Consultancy for Global Blood Therapeutics and Novartis; R Colombatti: Research Funding: Global Blood Therapeutics, Novartis.

Ethical approval

With the exception of Azienda Ospedaliera-Università di Padova, where there was a previously IRB-approved SCD Registry, IRB approval was obtained at all sites, and written informed consent was obtained from each patient and/or parent/guardian. Ethical approval for the study was sought from the Ethical and Protocol Review Committee of each participating site.

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Antwi-Boasiako, C., Andemariam, B., Colombatti, R. et al. A study of the geographic distribution and associated risk factors of leg ulcers within an international cohort of sickle cell disease patients: the CASiRe group analysis. Ann Hematol 99, 2073–2079 (2020). https://doi.org/10.1007/s00277-020-04057-8

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  • DOI: https://doi.org/10.1007/s00277-020-04057-8

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