|Year : 2017 | Volume
| Issue : 2 | Page : 70-73
Effect of hydroxyurea on clinical and laboratory parameters of sickle cell anaemia patients in North–West Nigeria
Abdulaziz Hassan MBBS, FMCPath , Sani Awwalu, Lucky Okpetu, Aliyu D Waziri
Department of Haematology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
|Date of Submission||20-Oct-2016|
|Date of Acceptance||17-Nov-2016|
|Date of Web Publication||6-Oct-2017|
Department of Haematology, Ahmadu Bello University Teaching Hospital, Zaria, 810001
Source of Support: None, Conflict of Interest: None
Background Patients with sickle cell anaemia (SCA) are routinely managed with folic acid and paludrine in Nigeria. However, since the licensing of hydroxyurea (HU) by Food and Drug Administration in the USA in 1998, there has been a gradual but cautious use of HU in Nigeria, especially for SCA patients with severe disease.
Aim The aim of this study was to determine the effects of HU on the frequency of hospital admissions, blood transfusion and haematological parameters among SCA patients in Zaria, Nigeria.
Materials and methods This was a retrospective analytic study of patients with SCA on HU therapy at the haematology clinic of a teaching hospital in North–West Nigeria. The frequency of hospital admissions, blood units transfused per annum, haematocrit level and white blood cell (WBC) and platelet counts before and 1 year after commencing HU treatment were compared using paired sample t-test. P value lower to 0.05 was considered significant.
Results In total, 18 of 689 (2.6%) registered SCA patients were on HU, and the mean age of patients was 26.5 years. The median (interquartile range) pre-HU and post-HU frequency of hospital admissions and units of blood transfused yearly were 4.5 (6) versus 1 (6) (P=0.003) and 2.5 (1) versus 0 (2) (P=0.001), respectively. Pre-HU and post-HU mean±SD haemocrit (%), WBC (×109/l) and platelet (×109/l) counts were 22.6 versus 26.6% (P<0.001), 14.8 versus 9.8 (P=0.002) and 468.3 versus 360.2 (P=0.144), respectively.
Conclusion HU significantly reduced the frequency of hospital admissions and units of blood transfused with increase in haematocrit and reduction in WBC and platelet counts in patients with SCA. HU should be encouraged in patients with severe disease.
Keywords: anaemia, hydroxyurea, sickle cell
|How to cite this article:|
Hassan A, Awwalu S, Okpetu L, Waziri AD. Effect of hydroxyurea on clinical and laboratory parameters of sickle cell anaemia patients in North–West Nigeria. Egypt J Haematol 2017;42:70-3
|How to cite this URL:|
Hassan A, Awwalu S, Okpetu L, Waziri AD. Effect of hydroxyurea on clinical and laboratory parameters of sickle cell anaemia patients in North–West Nigeria. Egypt J Haematol [serial online] 2017 [cited 2020 Sep 30];42:70-3. Available from: http://www.ehj.eg.net/text.asp?2017/42/2/70/216116
| Introduction|| |
Sickle cell disease (SCD) is a relatively common disease in Nigeria with an annual birth of over 150 000 children with haemoglobin S (HbS) . Nigeria is said to have the highest burden of the disease with a prevalence rate of HbS estimated at 2–3%; currently, about three to five million people are living with the disease in Nigeria . Persons who inherit HbS from both parents (HbSS) are said to have sickle cell anaemia (SCA), even though the patients live relatively normal lives. However, patients may suffer recurrent exacerbation of signs and symptoms referred to as crises. These crises may occur in the form of painful vaso-occlusive episodes (VOE), sequestration crises, hyperhaemolytic crises or hypoplastic crises. During these crises, most patients suffer severe pain that may require medical attention and admission to hospital with attendant loss of school and work time, which translates to loss of income ,,. They are usually treated with analgesics, intravenous fluids, antibiotics and various forms of blood transfusion depending on their Hb levels and other indications. These forms of treatment require hospital admission at remarkable financial burden on the parents or other caregivers .
In Nigeria, the current management of SCA patients involves counselling, routine regular clinic follow-up visits at 12- to 16-week intervals, drug therapy in the form of daily oral folic acid supplementation and daily oral proguanil for malarial prophylaxis. However, some other medications are also given depending on the need. Patients with SCA are also encouraged to take the pneumococcal vaccine in addition to the routine immunisation received by the general public. This is because of the autosplenectomy that occurs in SCA patients between the ages of 7 and 11 years ,,.
In the past decade, there has been a gradual introduction of the agent hydroxyurea (HU) in the management of patients with SCA. HU, also called hydroxycarbamide, was first synthesised by Dressler and Stein in 1869 in Germany and licensed for the treatment of cancers in 1967 . However, in 1984, HU was tested for SCD where it was found to increase the levels of foetal Hb and to ameliorate the signs and symptoms of the disease. Hence, by 1998 it was licensed for use by the US Food and Drug Administration for the prevention of sickle cell crises .
HU is a hydroxamic acid that binds to metals and is able to inhibit ribonucleotide reductase. The cytotoxic effect of HU reduces the number of red blood corpuscles that contains HbS; it also increases the level of HbF and when metabolised leads to the production of nitric oxide. HU reduces white blood cell (WBC) and platelet count, as well as reducing the expression of vascular and endothelial adhesion molecules such as vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and P-selectin ,. It has also been shown to significantly reduce the rate of crises and need for blood transfusion in a US study . Other studies similarly confirm the remarkable reduction in the frequency of painful crises, acute chest syndrome (ACS) and requirements for transfusion, and most importantly an improvement in the quality of life and possibly survival of SCA patients compared with HU-naive patients ,.
This study was conducted to determine the effect of HU on the clinical and laboratory features of SCA patients attending the haematology clinic of Ahmadu Bello University Teaching Hospital, Zaria, Nigeria.
| Materials and methods|| |
This was a retrospective study involving the review of patients’ case note and duplicate copies of HU consent forms to ascertain the number of patients with SCA on HU therapy and the impact of HU on clinical and laboratory variables. The SCA patients’ register was used to determine the number of registered adult (≥18 years) SCA patients attending the clinic. The number of adult patients with SCA on HU therapy, sex, age, number of hospital admission and number of blood units transfused per annum before the commencement of HU therapy and thereafter the same parameters after 1 year on HU therapy were extracted. Similarly, the haematocrit level, WBC count, platelet and reticulocyte counts before and 1 year after HU therapy were extracted and entered into Epi Info 7.0 (CDC USA) statistical software and analysed. Descriptive statistics and paired sample t-test was used to compare the means of normally distributed quantitative variables. Where variables are not normally distributed, Wilcoxon’s rank sum test was used and level of significance was set at P value lower to 0.05. Ethical approval for this study was obtained from the Hospitals Health Research Ethics Committee.
| Results|| |
There were only 18 (2.6%) patients with SCA on HU therapy out of the 689 registered SCA patients in our centre, of whom only 14 had complete medical records . There were eight (57%) male and six (43%) female patients. The mean age of the patients was 25.6±6.1 years. The median hospital admissions yearly before and after HU therapy were 4.5 (6) and 1 (6) (P=0.003), respectively ([Figure 1]), whereas the median number of blood units transfused per annum before and after HU therapy were 2.5 (1) and 0 (2) (P=0.001) ([Figure 2]).
|Figure 1 Box column scatter diagram of hospital admissions pre- and post-HU therapy.|
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|Figure 2 Box column scatter diagram of number of blood units transfused per annum pre- and post-HU therapy.|
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Most of the patients, 12 (86%), have up to three admission per annum, indicating a severe disease. However, only two had less than three admissions and were enrolled on HU therapy because of ACS and sickle cell cerebral syndrome each. The pre-HU and post-HU hospital admissions ranged from 1–12 to 0–6, respectively.
The number of blood units transfused in the 12 months before HU therapy ranged from 0 to 4 U, whereas the haematological parameters before and 1 year after HU therapy are depicted in [Table 1].
|Table 1 Haematological parameters of SCA patients before and after HU therapy|
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There were only two SCA patients on HU therapy who developed hyperpigmentation of the nails, one of whom developed the hyperpigmentation after 8 weeks, whereas the other at 12 weeks after commencement of HU therapy. One other patient presented with alopecia areata at 6 weeks of HU therapy. However, the alopecia resolved by the 10th week of HU therapy. Only one patient discontinued therapy on account of nonreduction in the number of hospital admissions despite increased haematocrit and reduction in WBC and platelet counts.
| Discussion|| |
With routine oral daily folic acid and proguanil therapy, SCA patients in Nigeria have been documented to have lived up to the age of 90 years . There is a need to introduce HU therapy for patients with frequent hospital admissions because of recurrent painful crises, ACS and other life-threatening presentations in SCD. In our centre, patients who have up to three hospital admissions per annum and frequent blood transfusions are counselled for HU therapy . The finding of only 2.6% of patients on HU therapy is considerably low but may be explained by the fact that only the patients with severe disease or a frequency of crisis of up to 3  are counselled to commence HU therapy in our centre as against its universal use in the USA and other western countries. Similarly, poor understanding of its mechanisms of action and the notion that it is a cytotoxic agent may prevent most SCA patients from accepting the medication for routine care ,.
There was a remarkable (73%) statistically significant reduction in the number of hospital admissions per annum by all patients on HU therapy. This finding is in keeping with earlier reports by Charache et al.  in the USA, who reported a comparatively lower number of crises of 2.5 in SCA patients on HU therapy versus 4.5 in those not on HU therapy. Similarly, Al-Hawsawi and Turkistani  in Saudi Arabia reported a reduction in the total number of crises from 70 to 25 per year. This reduction in the number of crises can be attributed to the decrease in counts of WBCs, platelets and reticulocytes, as these contribute to the pathogenesis of vaso-occlusion and an increase in HbF levels . HU also leads to reduction in the expression of adhesion molecules and thus reduces the chances of vaso-occlusive events .
Similarly, there was a statistically significant reduction (83%) in the number of blood units transfused per annum 12 after post-HU therapy ([Table 1]). This is also in agreement with the earlier reports by workers such as Silva-Pinto  in Brazil, who reported a reduction of the number of hospital admissions per annum from 1.63 to 0.53. This remarkable reduction may be explained by the reduction in the number of VOE experienced by the SCA patients on HU therapy, thus reducing the need for hospital visits.
There were reductions in the haematological parameters of WBC count, reticulocyte count and platelet count. These reductions were statistically significant in all except the platelet count. On the other hand, the PCV was raised significantly. The reduction in the counts of WBC, platelets and reticulocytes may be explained by the cytoreductive action of HU, whereas the increase in PCV is likely due to increased red cell hydration and deformability and, thus, reduced haemolysis .
Even though safety and toxicity concerns are the main reasons most SCA patients avoid HU therapy, only two (14%) of the patients presented with hyperpigmentation of the nails, whereas one (7%) developed reversible alopecia areata, which resolved without treatment and may be a coincidental finding. This study did not record any haematological or hepatic toxicity, as the liver function tests were within normal limits. These findings further emphasize the Multicenter Study of Hydroxyurea by Steinberg et al.  who studied patients on HU for 17 years and reported its safety.
| Conclusion|| |
HU therapy in adult SCA patients shows a remarkable reduction in the transfusion rate and hospital admission with increase in PCV but a reduction in WBC, reticulocytes and platelets. HU therapy is relatively safe and thus should be encouraged for all SCA patients in our environment.
Limitations of this study
The levels of HbF were not determined because of nonavailability in our centre, the short duration of the study and the limited number of patients on HU therapy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts for interest.
| References|| |
Aliyu Z, Tumblin A, Kato G. Current therapy of sickle cell disease. Haematologica
Steinberg M. Hydroxyurea treatment for sickle cell disease. Sci World J
Nebor D, Bowers A, Hardy-Dessources M, Knight-Madden J, Romana M, Reid H et al.
Frequency of pain crises in sickle cell anemia and its relationship with the sympathovagal balance, blood viscosity and inflammation. Haematologica
Isoa E. Current trends in the management of sickle cell disease: an overview. Benin J Postgrad Med
Federal Ministry of Health. National Guideline for the Control and Management of Sickle Cell Disease
Inati A, Chabtini L, Mounayar M, Taher A. Current understanding in the management of sickle cell disease. Hemoglobin
Segal J, Strouse J, Beach MC, Haywood C, Witkop C, Park H et al. Hydroxyurea for the treatment of sickle cell disease, evidence report/technology assessment no. 165–John Hopkins University Evidence-Based Practice Centre
. Rockville; 2008.
Brawley OW, Cornelius LJ, Edwards LR, Northington GV, Green BL, Inturrisi G et al.
NIH state-of-the-science conference statement on hydroxyurea treatment for sickle cell disease. Ann Intern Med
Platt O. Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med
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. N Engl J Med
Haematology Department. Sickle cell anaemia register
. Zaria: ABUTH; 2016.
TheCable. Profile: Asiata, 90 year sickler with 5 children. News
. 4 December 2015.
Haematology Department. Protocol for the use of hydroxyurea in adult sickle cell disease
. Zaria: ABUTH; 2012.
Abdulazizi F. The role of hydroxyurea in the management in sickle cell anaemia in the UK. Sick Cell Aid Found
Al-Hawsawi M, Turkistani W. Effect of hydroxyurea in children with sickle cell disease in Saudi Arabia. J Taibah Univ Med Sci
Johnson C, Telen M. Adhesion molecules and hydroxyurea in the pathophysiology of sickle cell disease. Hematologica
Silva-Pinto AC, Angulo IL, Brunetta DM, Neves FI, Bassi SC, Santis GC et al.
Clinical and hematological effects of hydroxyurea therapy in sickle cell patients: a single-center experience in Brazil. Sao Paulo Med J
Steinberg M, 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. Am J Hematol
[Figure 1], [Figure 2]
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