Effects of Hydroxyurea Treatment on Haemolysis in Patients with Sickle Cell Disease at Muhimbili National Hospital, Tanzania

Tanzania is one of the countries with a high burden of sickle cell disease (SCD). Haemolytic anaemia is a clinical feature of SCD, and has been linked to major complications leading to morbidity and mortality. Treatment with hydroxyurea (HU) has shown to induce foetal haemoglobin (HbF) which in turn decreases haemolysis in patients. This study aimed to investigate the effects of HU on haemolysis in SCD patients attending Muhimbili National Hospital, Tanzania by comparing their haemolytic parameters before and after therapy. Patients meeting the criteria were initiated on HU therapy for 3 months. Two haemolytic biomarkers: unconjugated plasma bilirubin levels and absolute reticulocyte counts were measured from patients’ blood samples at baseline and after 3 months of HU therapy and compared. Both absolute reticulocyte counts and indirect plasma bilirubin levels significantly declined after HU therapy. Median (IQR) plasma unconjugated bilirubin levels dropped significantly from 20.3 (12.7–34.4) μmol/L to 14.5 (9.6–24.1) μmol/L (p < 0.001) and mean (SD) absolute reticulocyte counts dropped significantly from 0.29 (0.1) x 109/L to 0.17 (0.1) x 109/L (p < 0.001) after therapy, thus, a decline in both haemolytic biomarkers after treatment was observed. This study found a potential for use of HU therapy in managing SCD patients in our settings evidenced by improvements in their haemolytic parameters. Clinical trials with a lager sample size conducted for a longer time period would be beneficial in guiding towards the inclusion of HU in treatment protocols for the Tanzanian population. Keywords: Sickle cell disease; hydroxyurea; haemolysis; foetal haemoglobin

FOETAL HAEMOGLOBIN AND DISEASE SEVERITY IN NIGERIAN CHILDREN WITH SICKLE CELL ANAEMIA.

Background: Foetal haemoglobin (HbF) is a major modifying factor influencing sickle cell disease (SCD) severity. Despite this, HbF estimation is not routinely done in Nigeria. Relationship between HbF and SCD severity among affected children is also poorly studied.Methods: In this descriptive cross-sectional study, we determined the relationship between steady state HbF levels and disease severity of Nigerian children aged 1 – 15 years with homozygous SCD. For each child, the socio-demographic characteristics and SCD clinical severity were determined. The latter was assessed based on the frequency of significant painful episodes, blood transfusion, and hospitalization in the preceding 12 months; lifetime cummulative incidence of SCD-related complications; degree of splenic and hepatic enlargement; current haematocrit and leucocyte count, as previously described. Foetal haemoglobin levels were quantified with high performance liquid chromatography.Results: The mean HbF level of the 105 children with SCA was 9.9 ± 6.0%. Male had significantly lower mean HbF levels than females, 8.0 ± 5.6% vs. 12.2 ± 5.8% (p < 0.001). None of the children had severe disease. However, those with moderate disease had significantly lower mean foetal haemoglobin levels than those with mild disease (7.7 ± 5.6% vs. 10.8 ± 6.0% respectively). The mean HbF level was also significantly lower in children who had history of acute chest syndrome and stroke compared to those without these complications, p = 0.002 and 0.010 respectively.Conclusion: Children with SCA who had moderate disease and those with history of life threatening complications such as stroke and acute chest syndrome had significantly low HbF. Therefore it is recommended that facilities for early quantification of foetal haemoglobin and HbF inducement be made available in order to reduce the morbidity and mortality among these children.