Investigation of haematological, inflammatory parameters and the incidence of alloimmunization in multi-transfused sickle cell diseased patients

Abstract

Introduction: Sickle cell disease is a haemoglobinopathy caused by an aberrant mutation of the beta chain with the amino acid valine replacing glutamic acid at the 6th position. Patients with sickle cell disease suffer from complications including chronic inflammation and the development of allogeneic antibodies due to multiple blood transfusions. This study investigated the association between haematological, inflammatory markers and alloimmunization in multi-transfused patients with sickle cell disease. Methods: This was a cross-sectional study, that enrolled 100 participants; 50 young adults (18−48 years) with homozygous sickle cell disease (Sickle cell Group) from the Obafemi University Health Centre in Nigeria, and 50 age and sex matched individuals who did not have the disease (Control group) but who had also received blood transfusions. Complete blood counts and differentials were processed on an auto-analyser (SFRI H18 Light, France). Red cell antigen identification used the saline and anti-human globin method while the abnormal haemoglobinopathy was evaluated using electrophoresis. ABO and Rhesus blood groups were analysed using a direct method ontile, andthedetermination ofinflammatory markers including C-reactive protein, tumour necrosis factor-alpha, interleukin-6, and interleukin-1b was by the enzyme-linked immunosorbent assay technique. The data were statistically analysed using SPSS version 24.0 and GraphPad Prism. Additionally, the student t-test and Chi-square test were employed as appropriate. Data were presented as mean§standarddeviation, with ap-value <0.05 considered statistically significant. Result: As expected, the Sickle Cell group had an increased rate of alloimmunisation and significantly reduced haemoglobin and red cell parameters except for the mean cell volume. Although both groups had platelet counts within the reference range the Sickle Cell group had significantly higher counts than the Control group. The Sickle Cell group displayed evidence of inflammation with significantly increased levels (p-value = 0.001) of C-reactive protein and tumour necrosis factor-alpha. This was supported by higher white cell counts and neutrophilia. The majority of the antibodies detected in sickle cell disease were anti-Kell, Jka and Fya while the controls showed a higher prevalence of anti-M and Kell antibodies. Despite the elevated inflammatory markers, no significant correlation was observed between these and the rate of alloimmunization. Conclusion: In this study, the Sickle Cell group had an elevated rate of alloimmunization with higher levels of anti-kell, Jka and Fya as well as inflammatory markers. However, despite these findings, no significant correlation between inflammatory markers and alloimmunization could be detected. This suggests that elevated alloimmunization rates are multifactorial and involve other processes which require further investigation.