Skip to main content
SpringerLink
Log in

The Effect of Hydroxyurea Therapy in Bahraini Sickle Cell Disease Patients

  • Original Article
  • Published:
Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

Abstract

Hydroxyurea (HU) is used as a disease-modifying agent in sickle cell disease (SCD). Its beneficial effects have been ascribed to inhibition of the sickling process through increase of fetal hemoglobin (HbF) levels and influence on multiple factors affecting adhesion of erythrocytes to vascular endothelium. The present study investigates the effect of HU in SCD patients who were grouped on the basis of association with α- and β-thalassemia using routine laboratory methods. A retrospective cross-sectional chart-review was done of 51 adult Bahraini SCD patients attending Salmaniya Medical Complex, Bahrain. Four sub-groups of cases were identified: (i) homozygous sickle cell anemia, 24 cases; (ii) SCD with microcytosis, 16 cases; (iii) sickle α-thalassemia, seven cases; and (iv) sickle β thalassemia, four cases. Documented laboratory and clinical data included hemoglobin level (Hb), hematocrit (Hct), red cell indices, hemoglobin fractions, hospital admissions (frequency), number of inpatient-days, pain episodes (frequency) and red cell transfusion requirement (number of units). Pre- and post-treatment data were compared. Hydroxyurea treatment led to highly significant reduction of HbS % and pain crisis episodes in all patient groups. Other changes such as increases of total hemoglobin, Hct and HbF and reduction of hospital admissions, inpatient days and red cell units transfused also occurred but with less consistent levels of significance within patient sub-groups. Treatment with HU is beneficial for all subgroups of Bahraini SCD patients, without or with α- and β-thalassemia interactions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wang WC (2009) Sickle cell anemia and other sickling syndromes. In: Greer JP, Foerster G, Rodgers GM, Paraskevas F, Glader B, Arber DA, Means RT (eds) Wintrobe’s clinical hematology, 12th edn. Wolters Kluwer, Philadelphia, pp 1038–1082

    Google Scholar 

  2. Serjeant GR, Serjeant BE (2001) Pathophysiology of sickle cell disease. Sickle cell disease, 3rd edn. Oxford University Press, Oxford, pp 56–75

    Google Scholar 

  3. Fathallah H, Atweh GF (2006) Induction of fetal hemoglobin in the treatment of sickle cell disease. Hematology Am Soc Hematol Educ Program 2006:58–62

    Article  Google Scholar 

  4. Platt OS, Orkin SH, Dover G, Beardsley GP, Miller B, Nathan DG (1984) Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. J Clin Invest 74:652–656

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR (1995) Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the multicenter study of hydroxyurea in sickle cell anemia. N Engl J Med 332:1317–1322

    Article  CAS  PubMed  Google Scholar 

  6. Vichinsky EP (1997) Hydroxyurea in children: present and future. Semin Hematol 34(3 Suppl 3):22–29

    CAS  PubMed  Google Scholar 

  7. Styles LA, Lubin B, Vichinsky E, Lawrence S, Hua M, Test S, Kuypers F (1997) Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea. Blood 89:2554–2559

    CAS  PubMed  Google Scholar 

  8. Johnson C, Telen MJ (2008) Adhesion molecules and hydroxyurea in the pathophysiology of sickle cell disease. Haematologica 93:481–485

    Article  PubMed  Google Scholar 

  9. Charache S (1997) Mechanism of action of hydroxyurea in the management of sickle cell anemia in adults. Semin Hematol 34(3 Suppl 3):15–21

    CAS  PubMed  Google Scholar 

  10. Mellouli F, Bejaoui M (2008) The use of hydroxyurea in severe forms of sickle cell disease: study of 47 Tunisian paediatric cases. Arch Pediatr 15:24–28

    Article  CAS  PubMed  Google Scholar 

  11. Odièvre MH, Bony V, Benkerrou M et al (2008) Modulation of erythroid adhesion receptor expression by hydroxyurea in children with sickle cell disease. Haematologica 93:502–510

    Article  PubMed  Google Scholar 

  12. Halsey C, Roberts IA (2003) The role of hydroxyurea in sickle cell disease. Br J Haematol 120:177–186

    Article  CAS  PubMed  Google Scholar 

  13. Sheehan VA, Luo Z, Flanagan JM, Howard TA, Thompson BW, Wang WC, Kutlar A, Ware RE, BABY HUG Investigators (2013) Genetic modifiers of sickle cell anemia in the BABY HUG cohort: influence on laboratory and clinical phenotypes. Am J Hematol 88:571–576

    Article  CAS  PubMed  Google Scholar 

  14. Hamamy HA, Al-Allawi NAS (2013) Epidemiological profile of common haemoglobinopathies in Arab countries. J Community Genet 4:147–167

    Article  PubMed Central  PubMed  Google Scholar 

  15. Darbari DS, Onyekwere O, Nouraie M et al (2012) Markers of severe vaso-occlusive painful episode frequency in children and adolescents with sickle cell anemia. J Pediatr 160:286–290

    Article  PubMed Central  PubMed  Google Scholar 

  16. Al-Jam’a AH, Al-Dabbous IA (2002) Hydroxyurea in sickle cell disease patients from Eastern Saudi Arabia. Saudi Med J 23:277–281

    PubMed  Google Scholar 

  17. El-Hazmi MA, Warsy AS, Al-Momen A, Harakati M (1992) Hydroxyurea for the treatment of sickle cell disease. Acta Haematol 88:170–174

    Article  CAS  PubMed  Google Scholar 

  18. Fathallah H, Taher A, Bazarbachi A, Atweh GF (2009) Differences in response to fetal hemoglobin induction therapy in beta-thalassemia and sickle cell disease. Blood Cells Mol Dis 43:58–62

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. WHO (2011) Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and mineral nutrition information system (WHO/NMH/NHD/MNM/11.1). World Health Organization, Geneva. http://www.who.int/vmnis/indicators/haemoglobin.pdf. Accessed 26 November 2014

  20. Steinberg MH, Lu ZH, Barton FB, Terrin ML, Charache S, Dover GJ (1997) Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea. Multicenter study of hydroxyurea. Blood 89:1078–1088

    CAS  PubMed  Google Scholar 

  21. Rogers ZR (1997) Hydroxyurea therapy for diverse pediatric populations with sickle cell disease. Semin Hematol 34(3 Suppl 3):42–47

    CAS  PubMed  Google Scholar 

  22. Loukopoulos D, Voskaridou E, Kalotychou V, Schina M, Loutradi A, Theodoropoulos I (2000) Reduction of the clinical severity of sickle cell/beta-thalassemia with hydroxyurea: the experience of a single center in Greece. Blood Cells Mol Dis 26:453–466

    Article  CAS  PubMed  Google Scholar 

  23. Zimmerman SA, Schultz WH, Davis JS, Pickens CV, Mortier NA, Howard TA, Ware RE (2004) Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease. Blood 103:2039–2045

    Article  CAS  PubMed  Google Scholar 

  24. Italia K, Jain D, Gattani S, Jijina F, Nadkarni A, Sawant P, Nair S, Mohanty D, Ghosh K, Colah R (2009) Hydroxyurea in sickle cell disease- a study of clinico-pharmacological efficacy in the Indian haplotype. Blood Cells Mol Dis 42:25–31

    Article  CAS  PubMed  Google Scholar 

  25. Higgs DR, Aldridge BE, Lamb J, Clegg JB, Weatherall DJ, Hayes RJ, Grandison Y, Lowrie Y, Mason KP, Serjeant BE, Serjeant GR (1982) The interaction of alpha-thalassemia and homozygous sickle-cell disease. N Engl J Med 306:1441–1446

    Article  CAS  PubMed  Google Scholar 

  26. Vasavda N, Woodley C, Allman M, Drašar E, Awogbade M, Howard J, Thein SL (2012) Effects of co-existing α-thalassaemia in sickle cell disease on hydroxycarbamide therapy and circulating nucleic acids. Br J Haematol 157:249–252

    Article  PubMed  Google Scholar 

  27. Ware RE, Eggleston B, Redding-Lallinger R, Wang WC, Smith-Whitley K, Daeschner C, Gee B, Styles LA, Helms RW, Kinney TR, Ohene-Frempong K (2002) Predictors of fetal hemoglobin response in children with sickle cell anemia receiving hydroxyurea therapy. Blood 99:10–14

  28. Lanzkron S, Strouse JJ, Wilson R, Beach MC, Haywood C, Park H, Witkop C, Bass EB, Segal JB (2008) Systematic review: hydroxyurea for the treatment of adults with sickle cell disease. Ann Intern Med 148:939–955

    Article  PubMed Central  PubMed  Google Scholar 

  29. Segal JB, Strouse JJ, Beach MC, Haywood C, Witkop C, Park H, Wilson RF, Bass EB, Lanzkron S (2008) Hydroxyurea for the treatment of sickle cell disease. Evid Rep Technol Assess (Full Rep) 165:1–95

    Google Scholar 

Download references

Acknowledgments

The study has been approved by the institutional research ethics committee, Ministry of Health, Kingdom of Bahrain and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Conflict of interest

Authors Durjoy K. Shome, Abdulla Al Ajmi, Ameera A. Radhi, Eman J. Mansoor and Kameela S. Majed declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pathology, College of Medicine and Medical Sciences, Arabian Gulf University, P.O. Box 26671, Manama, Kingdom of Bahrain

    Durjoy K. Shome

  2. Department of Pathology, Salmaniya Medical Complex, P.O. Box 12, Manama, Kingdom of Bahrain

    Durjoy K. Shome, Ameera A. Radhi, Eman J. Mansoor & Kameela S. Majed

  3. Department of Hematology and Oncology, Salmaniya Medical Complex, P.O. Box 12, Manama, Kingdom of Bahrain

    Abdulla Al Ajmi

Authors
  1. Durjoy K. Shome
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdulla Al Ajmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ameera A. Radhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eman J. Mansoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kameela S. Majed
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Durjoy K. Shome.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shome, D.K., Al Ajmi, A., Radhi, A.A. et al. The Effect of Hydroxyurea Therapy in Bahraini Sickle Cell Disease Patients. Indian J Hematol Blood Transfus 32, 104–109 (2016). https://doi.org/10.1007/s12288-015-0529-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12288-015-0529-y

Keywords

Search

Navigation