Impact of Hydroxyurea on Frequency of Blood Transfusion in Children With Sickle Cell Anaemia a Retrospective Quasi Experimental Study

Abstract

Study background: Sickle cell anaemia (SCA) is a red blood cell disorder that occurs commonly in Sub- Saharan Africa. Most of the children affected often have low haemoglobin levels as a result of increased destruction of these abnormal red blood cells and are subjected to several blood transfusions in an attempt to replace these red blood cells. Blood however is not always readily available and transfusions may result in undesired complications. Hydroxyurea (HU) is recommended for all children with SCA from the age of 9 months. HU changes the natural progression of the disease and sickle cell related complications. Although there is considerable use of hydroxyurea in Kenya there is no formal study on the impact of its use on the frequency of blood transfusions. Study Objective: The study’s main objective was to determine the impact of hydroxyurea use over a 6-month period on the frequency of blood transfusion among children aged 1-18 years with SCD on follow up at Kenyatta National Hospital (KNH) and Gertrude’s hospital. The study also aimed to describe dosage of hydroxyurea,adherence to hydroxyurea and factors affecting adherence and concurrent medication use in children with SCD on follow up at KNH and Gertrude’s hospital. Study design and sites: A retrospective quasi-experimental (single interrupted time series) design was employed to examine the frequency of blood transfusions in the 1 year period before initiating hydroxyurea (intervention) in comparison to the frequency in the 6 months - 1 year period after its introduction. The study was conducted in Kenyatta National Hospital and Gertrude’s Garden Children Hospital between February and May 2017. Participants and methods: Participants in the study were childrenaged 1 year to 18 years with a diagnosis of sickle cell anaemia confirmed by serum electrophoresis who had been on Hydroxyurea for at least 6

months and their caregivers. A questionnaire was used to collect data upon which the data were analysed to find any association between use of hydroxyurea and frequency of blood transfusions.Bivariate analyses were done using chi squares for categorical variables and also paired t-tests for the comparison of the means before and after initiation of hydroxyurea. A statistical comparison of time trends before and after the intervention was done. A Poisson regression analysis of the transfusion and admission counts while accounting for time periods was done to explore for any association between use of hydroxyurea (intervention) and frequency of blood transfusions and admissions. The results presented as Incidence Rate Ratios (IRR) with their respective 95% confidence intervals Results A total of 64 children participated in the study with a mean age of 7.6 years (SD= 3.7). Majority of the respondents were male 37(57.8%). The median age at diagnosis of Sickle Cell Anemia was 2.2 years (IQR= 0.7-3.5). Mean age when respondents started using Hydroxyurea was 4.8 years (SD=2.6), with median duration of use at 2.1 years (IQR=1.3-4). All hospital admissions were due to Sickle Cell Anemia complications with a median age of 2 years (IQR=1-4) at the first hospital admission. Majority of the respondents had received blood transfusion 57(89.1%) with a median age of 2 years (IQR=0.6-4) at the first transfusion. There was a statistically significant mean decrease of 0.9 (95%, CI 0.7 to 1.2)(P value <0.001) in the counts of blood transfusions in the 6-12 month period after adequate use of HU, that is from a mean of 1.2 (95% CI 0.9-1.4) to that of 0.2 (95% CI 0.1 - 0.4).The children had a statistically significant lower rate of transfusion after a 6 month period of having used HU with an IRR of 0.18 (95% CI 0.09 - 0.35). Majority of the participants wereunder dosed, with 51 (79.7%) receiving a daily dosage of < 20mg/kg/day. Most of the parents/caregivers ensured that the children took HU as prescribed with 50 (78.1%) reporting good compliance to the drug. Majority of the participants had not experienced any side effect with the use of Hydroxyurea 56(87.5%).

Conclusion This study suggests that Hydroxyurea significantly reduces thev number of blood transfusions in children aged between 1year and 18 years at KNH and Gertrude’s hospital. The application of Hydroxyurea in children with SCA in these two institutions should therefore be encouraged as it reduces morbidity.