The Prevalence of Iron Overload and Relationship Between Blood Transfusion, Iron Overload and Hepatotoxicity in Children With Sickle Cell Disease at the Kenyatta National Hospital- a Cross Sectional Study.

Abstract

Background: Blood transfusion, essential in the management of sickle cell disease ultimately leads to the accumulation of exogeneous iron. Iron overload which is often undetected is pathological to the body. Serum ferritin can be used a means of evaluation of body iron stores. Study justification and utility : Children with SCD undergo repeated blood transfusions which exposes them to the risk of iron overload. Monitoring of iron levels enables preventive therapy as iron overload is treatable. There is a paucity of evidence on the magnitude of iron overload and its associated effects among children in long term care in our setting. Objectives: To determine the prevalence of iron overload among children aged 1-18 years with sickle cell disease receiving care in KNH, determine the association between blood transfusion iron overload, and liver function in these children. Study Design: This was a hospital based descriptive cross-sectional study . Methods: The study population comprised of 145 children recruited from the Kenyatta National Hospital Haematology clinic, the inclusion criteria being any child aged 1-18 years with sickle cell disease and whose consent and assent (where applicable) was obtained. The exclusion criteria was anyone with a history of recent crises in the preceding 4 weeks or exacerbation of acute illness on day of screening. Sampling was by consecutive recruitment and once screened and enrolled, history of blood transfusions received was obtained . A retrospective abstraction of the patient’s medical records was also carried out . A venous blood sample was delivered to the laboratory for ass essment of serum ferritin and alanine aminotransferase levels. The outcomes of interest were serum ferritin measurement as evaluation of iron overload, where iron overload was defined as serum ferritin levels >300ng/ml, the number and volume of blood transfusions over a three-year period as well as assessment of serum alanine aminotransferase (ALT) levels as indicator of hepatic dysfunction, with hepatic dysfunction defined as serum ALT >42 IU/L. Data management and analysis: All data was entered into a case record form. The prevalence of iron overload was computed by the number of children with xi elevated serum ferritin levels as the numerator and the total number of children as denominator and this was converted to percentage. Logistic regression as well as the Mann Whitney test in which medians between groups was compared was used to analyse the association between number of blood transfusions and serum ferritin levels as well as serum ferritin levels and ALT levels . Results: 145 children were enrolled into the study, 86 male and 59 female. The median age of the population was 8 years and the median duration of care in KNH was 7 years. The median number of blood transfusions was 2. The prevalence of iron overload as measured by serum ferritin was 64% (95% CI 407-584 IU/L), with 49 (39%), 27 (19%), 6 (4%) and 11 (8%) of the children having mild, moderate, high and severe overload respectively. The number of transfusions received influenced the level of ferritin in the serum and each additional unit of blood transfused conferred a 1.8-fold increased odds of iron overload (OR 1.8 95% CI 1.38,2.54.). Elevated serum ferritin conferred an 8.3-fold increased odds of hepatic dysfunction (OR 8.3 , 95% CI 1.05, 65.29). Serum ferritin was significantly associated with ALT levels (p value <0.01) and every 1 ng increase in serum ferritin increased the odds of elevated ALT level by 0.1% ( OR 1.001, CI 1.001, 1.002) Conclusions: Iron overload was highly prevalent in this population of children with SCD. Every additional unit of transfused blood increased the risk of iron overload by two-fold. There is a positive association between iron overload and hepatic dysfunction in these children with SCD Recommendations: We recommend that children with SCD have careful monitoring of number and volume of blood transfusions, and routine monitoring of serum ferritin should be done. Further studies can be done to study the correlation between elevated serum ferritin levels and hepatic iron concentration.