A-155 HbS, HbF and HbA2 reference intervals in a sickle cell population with Senegal haplotype as the most prevalent sickle cell haplotype

Background In numerous textbooks and official documents on the management of sickle cell disease (SCD), the SS profile is characterized by the presence of hemoblobin S (HbS) (80 - 90%), HbF (2 - 20%) and HbA2 (2.5 - 3.5%); the S/beta(0)-thalassemia profile by the presence of HbS (80 - 95%), HbF (1 - 15%) and HbA2 (3.5 - 6%). These two profiles can be distinguished with the level of HbA2 which is higher than 3.5% in S/beta(0)-thalassemia. Senegal is a country whose name is associated with one of the five major haplotypes of SCD, the Senegal haplotype, which is present in at least 60% of the sickle cell population of the country. A presence of this haplotype attenuates the clinical severity of the disease by increasing the expression of HbF level. It seems like the official description of SS and S/beta(0)-thalassemia profiles did not take into account the specificity of the Senegal haplotype as the level of HbF is often noted in our practice to be higher than the level officially described. It is in this context that this study was decided. Its objective is to establish reference intervals of HbS, HbF and HbA2 in the Senegalese sickle cell population. Methods Data were collected from the records of SCD patients with SS or S-beta(0)-thalassemia profile free from hydroxyurea and aged 4 years or older. Patients were excluded when their capillary electrophoresis showed the presence of HbA or other Hb different from HbS, HbF and HbA2.. Patients were considered to have an SS profile when their HbA2 was = 3.5%. After a box-cox transformation, the normality of the distribution was checked using Kolmogorov-Smirnov test before applying Tukey*s method to eliminate outliers. The non-parametric method was applied to establish the reference intervals. Test significance was set at p-value < 0.05. Results A total of 471 patients, with a mean age of 10.05±5.18 years, were included. The female frequency was 50.11% (n = 236). The majority of the patients, 80.47% (n = 379), had a SS profile and 19.63% (n = 92) a S-beta(0)-thalassemia profile. HbF was between [1.2 - 15%[ in 62.63% (n = 295), [15-30%] in 34.82% (n = 164) and ]30 - 36.4%] in 2.55% (n = 12) of the population. HbS was between [62.1 - 80%[ in 27.18% (n = 129) and [80 - 95.6%[ in 72.82% (n = 342). HbS and HbF showed no outliers whereas values of HbA2 = 2.2% or HbA2 > 5.3% were found to be outliers. In the overall population, the reference intervals of HbS was (66.88 - 93.3%), HbF (2.96 - 30.48%) and HbA2 (2.38 - 4.4%). In SS patients, the reference intervals of HbS was (66.8 - 93.1%), HbF (3.5 - 31%) and HbA2 (2.3 - 3.5%). In S-beta(0)-thal patients, the reference intervals of HbS was (69.46 - 93.83%), HbF (1.9 - 25.20%) and HbA2 (3.6 - 5.15%). Conclusion The SS or S/beta(0)-thalassemia profile is characterized in the Senegalese population by a lower HbS lower limit reference intervals and a higher HbF upper limit reference intervals than those officially described. A level of HbA2 > 5.3% suggests a presence of an HbA2-raising factor associated with S/beta(0)-thalassemia. A level of HbA2 = 2.2% implies a presence of a HbA2-lowering factor associated with SS or S/beta(0)-thalassemia.