Clinical Outcome and Laboratory Parameters in Sickle Cell Anemia Patients of Pediatric Age Group Post Hydroxyurea Therapy

Background: Homozygous condition in Sickle cell disease (SCD) is called as sickle cell anemia(SCA). In sickle cell anemia patients clinically presents as hemolytic anemia, vaso-occlusive events, along with organ dysfunction and acute chest syndrome. Recently Hydroxyurea has shown promising results in treatment of sickle cell anemia. Hydroxyurea is the only approved drug by FDA which has shown disease modifying results. Aim: To determine the clinical outcome and laboratory parameters in SCA patients of pediatric age group post-hydroxyurea therapy. Methods: A total of 30 patients who were diagnosed as Sickle cell anemia (SCA) patients in Sickle cell anemia OPD of Pediatric department were included in the study. Results: Hydroxyurea therapy is expected to increase HbF% levels and improve the clinical outcome and laboratory parameters in sickle cell anemia patients of pediatric age group. Original Research Article Gupta et al.; JPRI, 33(63A): 65-70, 2021; Article no.JPRI.80029 66


INTRODUCTION
Homozygous condition in SCD is called as SCA. In sickle cell anemia(SCA) patients clinically presents as hemolytic anemia, vaso-occlusive events, along with organ dysfunction and acute chest syndrome. Overall quality of life in sickle cell anemia patients is poor and usually have early mortality [1,2].
In world more than 3,00,000 children in a year born with sickle cell disease, out of these almost 70% originate from Africa [3]. In India, incidence of sickle cell disease varies from region to region. Lehman & Cutbush in 1952 detected sickle cell gene for the first time among tribal of Nilgiri hills. Since then almost 300 tribal were screened for sickle cell gene and its prevalence varies from 0-35%. In few states like Chhattisgarh, Madhya Pradesh, Maharashtra, Gujrat, and Orissa; it remains as the major public health issue [4].
Bone marrow transplant remains the only known treatment for Sickle cell anemia. The availability of bone marrow transplant is greatly hampered as there is lack of matching donors, heavy costing of procedure and associated complication of bone marrow transplant [5]. Transcranial doppler is used to screen children for risk of stroke and also safe blood transfusion has reduced morbidity [6].
Recently Hydroxyurea has shown promising results in treatment of sickle cell anemia. Hydroxyurea is the only approved drug by FDA which has shown disease modifying results. In 1998 FDA approved use of Hydroxyurea for adult patients and in recent years it has been added in treatment of children as well [7]. National heart, lung and blood institute has also recommended hydroxyurea use in SCA as early as by 9 months of age [8].
In past years there were many studies which showed the effect of Hydroxyurea therapy in pediatric patients having SCA. In these studies, patients showed significant rise of HbF% and reduction in painful crises, number of days of hospitalization, number of blood transfusions and acute chest syndrome [9]. Our study is focused to demonstrate the experience of the use of Hydroxyurea at AVBRH in SCA pediatric patients and determining its beneficial effects and short term safety.

Research Question
What is the Clinical outcome and laboratory parameters of SCA patients of pediatric age group post hydroxyurea therapy? Population(P)-All pediatric patients diagnosed with Sickle cell anemia in sickle cell OPD.

Hypothesis
Hydroxyurea therapy in Sickle Cell Anemia patients of pediatric age group leads to improvement in Clinical outcome and laboratory parameters.

Aim
To determine the clinical outcome and laboratory parameters in SCA patients of pediatric age group post-hydroxyurea therapy.

EXPECTED RESULTS
Hydroxyurea therapy increases HbF%, decreases blood transfusions, days of hospitalization, incidence of acute chest syndrome. It is expected that Hydroxyurea therapy will overall improve clinical outcome and laboratory parameters in sickle cell anemia patients of pediatric age group.

DISCUSSION and CONCLUSION
SCD is a hemolytic anemia in which RBCs predominantly have HbS as a result of inheritance of β-globin mutation. β-globin mutation results from one amino acid substitution in β-globin chain of Hb, hence forming Sickle cell Hb(HbS). The amount of HbF is the most important parameter that influences the clinical outcome of sickle cell disease and also is an important predictor of early mortality in pediatric patients having sickle cell disease [12].
In past few years one approach has been taken into consideration, by induction of HbF even after newborn and fetal period. For this many agents have been used but then agent which has shown promise is use of Hydroxyurea. Hydroxyurea has been known for inducing HbF production in SCD patients. Hydroxyurea is used in a titrated dose and its dose is limited by peripheral blood counts mainly by neutropenia, and occasionally by reticulocytopenia and rarely by thrombocytopenia [7]. ZM Al Hawsawi et al in 2008 [11] conducted their study to demonstrate the use of hydroxyurea in SCD patients. Total 10 patients were considered in study out of them 04 were female and 06 were male. Age of patients range from 05-15 yrs. The study showed that clinical symptoms like ACS and Painful crises were reduced post hydroxyurea therapy.
Laboratory parameters showed significant rise in MCV and HbF% post hydroxyurea therapy. E Papadopoulou et al in 2015 [13] conducted a study on safety and efficacy of hydroxyurea in children and adolescents with sickle/betathalassemia. In the study total 13 pediatric patients with S/b-thalassemia were given hydroxyurea for 2 years and during that period the clinical and laboratory parameters were evaluated. The results showed reduction in ACS, Pain crises and days of hospitalization and also showed significant rise in HbF%, MCV, & MCH.
L Tshilolo et al in 2019 [14] conducted a study for Hydroxyurea in children with sickle cell anemia in sub-Saharan Africa. In this study total of 635 pediatric patients were included, amongst them 606 completed screening and they were started on hydroxyurea at a titrated dose. The results showed that hydroxyurea helped them in reducing clinical symptoms and improving Hb% and HbF%.
Akinyemi O.D. Ofakunrin et al in 2019 [15] conducted a study to evaluated the effectiveness of hydroxyurea in SCA pediatric patients. Total of 54 patients were enrolled in the study. A baseline clinical and laboratory parameters were recorded. Hydroxyurea therapy was given for 1 year. Post hydroxyurea therapy patients showed significant reduction in painful crises 27 (50%) to 2 (2.7%), and ACS6 (11.1%) to 0 (0.0%). There was also reduction in days of hospital stay and requirements of blood transfusion. Also there was raise in HbF% and HCT levels.

Scope
The study will make an attempt to accurately find the effect of Hydroxyurea on sickle cell anemia patients in reference to its effect on number of hospitalization, blood transfusions, onset of acute crisis and HbF levels. The change in HbF levels will be estimated before the starting of Hydroxyurea and post Hydroxyurea therapy with the help of HPLC.

Limitation
A triad consisting of proper hydroxyurea dosing, regular follow-up and compliance of patients to medication is a must while evaluating hydroxyurea effects on clinical and laboratory outcome in patients with sickle cell anemia. Lacunae in any of the above mentioned components can put negative impact on the desired results.

CONSENT
As per international standard or university standard, respondents' written consent has been collected and preserved by the author(s).

ETHICAL APPROVAL
It is not application.