Impact of Hydroxyurea Therapy on Clinical Outcomes in Children with Sickle Cell Anemia: A 5-year Study at Benue State University Teaching Hospital, Makurdi

Authors

  • Michael A Benue State University image/svg+xml Author
  • Ogiator ABC Benue State University image/svg+xml Author
  • Bandin SK Benue State University Teaching Hospital Makurdi Author
  • Agbedeh AA Benue State University Teaching Hospital Makurdi. Author
  • Ochoga MO Federal University of Health Sciences, Otukpo image/svg+xml Author
  • Okpe ES Federal University of Health Sciences, Otukpo image/svg+xml Author

Keywords:

Clinical outcomes, Hydroxyurea, Nigeria, Peadiatric, Sickle cell anaemia, Vaso-occlusive crises

Abstract

Sickle cell anaemia (SCA) is a chronic, debilitating condition prevalent in Nigeria. Hydroxyurea therapy has been shown to reduce the frequency and severity of disease complications. However, its uptake in Nigeria has been limited due to concerns about safety, accessibility, and awareness. This study aimed to evaluate the clinical and laboratory outcomes of children with SCA on hydroxyurea therapy at the Benue State University Teaching Hospital, Makurdi, Nigeria. A total of 43 children diagnosed with SCA were followed after initiation of hydroxyurea therapy. Data on socio- demographic characteristics, frequency of SCA-related events and laboratory parameters were collected and analyzed using SPSS version 23. Paired t-tests were used to compare pre- and post-treatment outcomes, and adverse effects were recorded. The majority (65.1%) of the children were diagnosed with SCA by age two, and 60.5% started hydroxyurea within two years of diagnosis. Hydroxyurea therapy significantly reduced the frequency of vaso-occlusive crises (mean reduction from 7.70 to 1.91, p = .000), hospital admissions (mean reduction from 2.60 to 0.84, p = .000), and blood transfusions (mean reduction from 1.51 to 0.40, p = .005). Hospital stay duration also decreased significantly (p = .001). Laboratory findings showed significant reductions in WBC count (p = .001) and increases in MCV, while hemoglobin levels remained stable. Mild skin pigmentation and dizziness were observed as adverse effects. Low-dose hydroxyurea therapy in children with SCA resulted in substantial clinical benefits, including reduced disease complications and improved laboratory markers, with minimal adverse effects.

Author Biographies

  • Michael A, Benue State University

    Department of Pediatrics, Benue State University/Benue State University Teaching Hospital Makurdi.

  • Ogiator ABC, Benue State University

    Department of Pediatrics, Benue State University Teaching Hospital Makurdi.

  • Bandin SK, Benue State University Teaching Hospital Makurdi

    Department of Pediatrics, Benue State University Teaching Hospital Makurdi

  • Agbedeh AA, Benue State University Teaching Hospital Makurdi.

    Department of Pediatrics, Benue State University Teaching Hospital Makurdi.

  • Ochoga MO, Federal University of Health Sciences, Otukpo

    Department of Pediatrics, Federal University of Health Sciences Otukpo.

  • Okpe ES, Federal University of Health Sciences, Otukpo

    Department of Pediatrics, Federal University of Health Sciences Otukpo.

References

1. Ware RE, de Montalembert M, Tshilolo L, Abboud MR. Sickle cell disease. Lancet 2017; 390: 311-23.

2. National guideline for the control and management of sickle cell disease. Federal Ministry of Health Nigeria Abuja 2014. https://www.health.gov.ng/doc/scdguideline.pdf. accessed 27th July 2020.

3. Piel FB, Patil AP, Howes RE, Nyangiri OA, Gething PW, Dewi M. et al. Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates. Lancet 2013; 381: 142-51.

4. Ojewumi OO, Adeyemo TA, Ayinde OC, Iwalokun B, Adekile A. Current perspectives of Sickle cell disease in Ngeria: changing the narratives. Expert review of hematology. 2019;12(8):609-620. Doi:10.1080/17474086.2019.1631155

5. Omotade OO, Kayode CM, Falade SL, Ikpeme S, Adeyemo AA, Akinkugbe FM. Routine screening for sickle cell haemoglobinopathy by electrophoresis in an infant welfare clinic. West Afri J Med. 1998;17(2): 91-94.

6. Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN. Global burden of Sickle cell anemia in children under five, 2010-2050: Modelling based on demographics, excess mortality and interventions. PloS Med 2013;10(7): e1001484. Doi: 10.1371/journal.pmed.1001484.

7. National Heart, Lung, and Blood Institute: Evidence-Based Management of Sickle Cell Disease: Expert Panel Report. 2014. https://www.nhlbi.nih.gov/health-topics/evidence-based-management-sickle-cell-disease. Accessed 31st July 2020.

8. Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, et al. Management of sickle cell disease: Summary of the 2014 Evidence-Based Report by Export Panel Members. JAMA 2014;312(10):1033-1048. Doi:10.1001/jama.2014.10517

9. Ware RE. How I use hydroxyurea to treat young patients with sickle cell anemia. Blood. 2010;115(26):5300-5311. Doi:10.1182/blood-2009-04-146852.

10. Grosse SD, Odame I, Atrash HK, Amendah DD, Piel FB, Williams TN. Sickle cell disease in Africa: a neglected cause of early childhood mortality. Am J Prev Med 2011; 41: Suppl 4: S398-S405.

11. Inusa BP, Daniel Y, Lawson JO, Dada J, Matthews CE, Momi S. et al. Sickle Cell Disease Screening in Northern Nigeria: The Co-Existence of Β-Thalassemia Inheritance. Pediat Therapeut 2015; 5(3):1-4. Doi:10.4172/2161-0665.1000262.

12. Quinn C, Roger Z, Mc Cavit T, Buchanan G. Improved survival of children and adolescent with sickle cell disease. Blood 2010;115(17): 3447- 3452.

13. Muoghalu CO. Sickle Cell Disease Child Mortality-A Silent Epidemic in Nigeria: Issues in Political Economy. Blood Res Transfus J. 2018;2(2):555584. DOI:10.19080/OABTJ.2018.02.555584.

14. Aneni EC, Hamer DH, Gill CJ. Systematic review of current and emerging strategies for reducing morbidity from malaria in sickle cell disease. Trop Med Int Health. 2013;18(3):313-327.

15. Makani J, Sangeda RZ, Nnodu O, Nembaware V, Osei-Akoto A, Paintsil V, et al. SickleInAfrica. Lancet Haematol 2020;7(2): e98–e99.

16. Hankins JS, Ware RE, Rogers ZR, Wynn LW, Lane PA, Scott JP, et al. Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study. Blood 2005;106(7):2269-2275.

17. Steinberg MH, Mccarthy WF, Castro O, Ballas SK, Armstrong FD, Smith W, et al. The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5-year follow-up and Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia and MSH Patients' Follow-Up. Am J Hematol. 2010; 85:403–408.

18. Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV. et al. 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.1995;332(20)1317-1322.

19. Galadanci NA, Abdullahi SU, Abubakar SA, Jibir BW, Aminu H, Tijjani A et al. Moderate-Dose Hydroxyurea for Primary Prevention of Strokes in Nigerian Children with Sickle Cell Disease: Final Results of the SPIN Trial. Am J Hematol. 2020.doi:10.1002/ajh.25900.

20. Hankins JS, Aygun B, Nottage K, Thornburg C, Smeltzer MP, Ware RE, et al. From Infancy to Adolescence: Fifteen Years of Continuous Treatment with Hydroxyurea in Sickle Cell Anemia. Medicine 2014;93(28): e215 DOI:10.1097/MD.0000000000000215.

21. Chide OE, Gyamfi J, Ryan N, Oluwatoyin B, Eno-Abasi E, Chianumba R, et al. Barriers to Therapeutic Use of Hydroxyurea for Sickle Cell Disease in Nigeria: A Cross-sectional Survey. Research Square Immunology. 2020; 1:1-16 Doi:10.21203/rs.3.rs-33381/v1.

22. Adeyemo TA, Diaku-Akinwunmi IN, Ojewunmi OO, Bolarinwa AB, Adekile AD. Barriers to the use of hydroxyurea in the management of sickle cell disease in Nigeria. Hemoglobin 2019;43(3):188-192 Doi:10.1080/03630269.2019.1649278.

23. Ofakunrin AOD, Adekola K, Okpe ES, Oguche S, Afolaranmi T, Kanhu P. et al. Level of Utilization and Provider-related barriers to hydroxyurea use in the treatment of sickle cell disease in Jos, Nigeria. Blood 2019;1349(1)1029. Doi:10.1182/blood-2019-128185.

24. Ofakunrin AOD, Oguche S, Adeola K, Okpeh ES, Afolaranmi TO, Akinwunmi IN.et al. Effectiveness and safety of Hydroxyurea in the treatment of Sickle Cell Anaemia children in Jos, North Central Nigeria. J. Trop. Pediatr.2020;66: 290-298. Doi:10.1093/tropej/fmz070.

25. Tshilolo L, Tomlinson G, Williams TN, Santos B, Olupot-Olupot P, Lane A.et al. Hydroxyurea for children with sickle cell anemia in sub-Saharan Africa. N Engl J Med 2019; 380:121–31. DOI:10.1056/NEJMoa1813598

26. Opoka RO, Ndugwa CM, Latham TS, Lane A, Hume HA, Kasirye P, et al. Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia. Blood. 2017;130(24):2585-93 Doi:10.1182/blood-2017-06.

27. Zimmerman SA, Schultz WH, Davis JS, Pickens CV, Mortier NA, Howard TA. et al. Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease. Blood 2004; 103:2039-2045

28. Akingbola TS, Tayo B, Ezekekwu CA, Sonubi O, Saraf SL, Hsu LL. et al. Maximum Tolerated Dose Versus Fixed Low-Dose Hydroxyurea for Treatment of Adults with Sickle Cell Anemia-Retrospective Comparison of Two Studies. Blood 2018;132(1):3656 Doi:10.1182/blood-2018-99-114990.

29. Tayo BO, Akingbola TS, Saraf SL, Shah BN, Ezekekwu CA, Sonubi O, et al. Fixed Low-Dose Hydroxyurea for the Treatment of Adults with Sickle Cell Anemia in Nigeria. Am J Hematol 2018;93: e193-196.

30. Inusa BPD, Wale A, Hassan AA, Idhate T, Dogara L, Ijei I, Qin Y, et al. Low-dose hydroxycarbamide therapy may offer similar benefit as maximum tolerated dose for children and young adults with sickle cell disease in low-middle-income settings. F1000Research 2018; 7:1–9 Doi:10.12688/f1000research.14589.

31. Platt OS. Hydroxyurea for the Treatment of Sickle Cell Anemia. N Engl J Med 2008; 358:1362-9.

32. Segbefia CI, Goka B, Welbeck J, Amegan-Aho K, Dwuma-Badu D, Rao S, et al. Implementing newborn screening for sickle cell disease in Korle Bu Teaching Hospital, Accra: Results and lessons learned. Pediatr Blood Cancer. 2021;68(7): e29068 Doi:10.1002/pbc.29068.

33. Olaniyan HS, Briscoe C, Santos B, Pascoal R, Armando A, McGann PT. Comparison of Sickle SCAN and Hemotype SC As Point-of-Care Newborn Screening Diagnostics for Sickle Cell Disease in Luanda, Angola. Blood. 2021; 138:913–914. Doi:10.1182/blood-2021-151028.

34. Akodu SO, Diaku-Akinwumi IN, Njokanma OF. Age at diagnosis of sickle cell anaemia in lagos, Nigeria. Mediterr J Hematol Infect Dis. 2013;5(1): e2013001. Doi:10.4084/MJHID.2013.001.

35. Nnodu OE, Sopekan A, Nnebe-Agumadu U, Ohiaeri C, Adeniran A, Shedul G, et al. Implementing newborn screening for sickle cell disease as part of immunisation programmes in Nigeria: a feasibility study. Lancet Haematol. 2020;7: e534–40.

36. Isa H, Adegoke S, Madu A, Hassan AA, Ohiaeri C, Chianumba R, et al. Sickle cell disease clinical phenotypes in Nigeria: A preliminary analysis of the Sickle Pan Africa Research Consortium Nigeria database. Blood cells Mol Dis 2020; 84:102438. Doi: 10.1016/j.bcmd.2020.102438.

37. Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, et al. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011;377(9778):1663-72. Doi: 10.1016/S0140-6736(11)60355-3.

38. Kinney TR, Helms RW, O'Branski EE, Ohene-Frempong K, Wang W, Daeschner C, et al. Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyurea Group. Blood. 1999;94(5):1550-4.

Published

2025-02-13