Sub-Saharan Africa bears the highest burden of all Sickle Cell disease births worldwide. Chronic haemolysis in children with sickle cell disease (SCD) is known to cause multi-organ damage, increased risk of stroke, and cognitive impairment. This study sought to investigate haemolysis biomarkers in sickle cell disease (SCD) among sub-Saharan African children, aiming to improve individualized management through enhanced diagnostic and prognostic capabilities. Fifty children with SCD and 32 non-SCD children aged 2-17 years were evaluated using 5-part differential FBC and ELISA to profile haemolysis and haem cytoprotective proteins. Significantly elevated levels of bilirubin, free haemoglobin, haem oxygenase, ferritin, potassium ions, and AST activity in SCD participants was observed, while haptoglobin was significantly reduced. Hydroxyurea treatment was associated with increased haptoglobin and ferritin levels and decreased free haemoglobin and haem oxygenase activity. Male children with SCD exhibited higher haem oxygenase activity and free haemoglobin levels. A comparative analysis of machine learning algorithms revealed that the random forest model achieved 100% accuracy, sensitivity, specificity, predictive, and AUC values in classifying SCD. Direct bilirubin emerged as the most important classifier, followed by potassium, haptoglobin, free haemoglobin, haem oxygenase, total bilirubin, and ferritin. This research highlights the potential of machine learning-based classification using haemolysis biomarkers for improved SCD diagnosis and management. The findings from this sub-Saharan African cohort may have broader implications for SCD patient populations worldwide, potentially revolutionizing individualized treatment approaches and enhancing patient outcomes.

I have read the journal's policy and one author of this manuscript have the following competing interests: PWA has served on the advisory boards of K36 Therapeutics and CommBio Tx and serves as Chief Scientific Officer of Landcent.

The study was funded through a capacity building grant to KOD from the China Novartis Institutes of Biomedical Research, Shanghai, China. EAA was supported by a DELTAS Africa grant (DEL-15-007: Awandare). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS) Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (107755/Z/15/Z: Awandare) and the UK government. The views expressed in this publication are those of the author(s) and not necessarily those of Novartis, AAS, NEPAD Agency, Wellcome Trust or the UK government.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the Research Ethics Committee of the University of Health and Allied Sciences, Ho with protocol reference numbers UHAS-REC A.3 [1] 18-19 and UHAS-REC A.12 [42] 20-21.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors