Abstract
Quantification of foetal haemoglobin (HbF) via high-performance liquid chromatography (HPLC) remains a critical parameter for monitoring therapeutic response to hydroxyurea (HU) in patients with sickle cell disease (SCD). However, its routine application is constrained in low-income settings such as Nigeria due to limited accessibility. The platelet-to-neutrophil ratio (PNR), an emerging inflammatory biomarker, has demonstrated prognostic relevance in several disease conditions. This study investigates the potential utility of PNR as a surrogate monitoring tool in SCD patients receiving HU therapy. This was a retrospective analysis of data derived from the Children's National Hospital Natural History Study of Sickle Cell Disease, conducted in Washington, D.C., USA. Medical records of patients with SCD were reviewed from 1 September 2013 to 14 September 2023. Associations between PNR, HU use, HbF concentration, and reticulocyte count were evaluated. T-tests was used for continuous variables and chi-square tests for categorical variables. Regression analysis was used to evaluate the predictors of hydroxyurea use. A p-value of < 0.05 was considered statistically significant. Of 437 patient records reviewed, 222 (50.8%) were male, and 312 (71.4%) were receiving HU. The majority (81%) had no history of transfusion. Patients on HU exhibited significantly higher platelet counts, HbF levels, and PNR values (p = 0.0008, p < 0.0001, and p < 0.0001, respectively). In multivariate logistic regression, both HbF (OR: 1.121; 95% CI: 1.051-1.196; p < 0.001) and PNR (OR: 1.014; 95% CI: 1.005-1.024; p = 0.0022) were independently associated with HU use. No significant associations were observed between HU use and age group, haemoglobin phenotype, transfusion history, or BMI (p > 0.05). The PNR demonstrates a significant association with HU use and HbF levels, indicating its potential as a low-cost, accessible biomarker for monitoring HU therapy in SCD. Although this analysis was based on data from a high-resource setting, the findings underscore the relevance of PNR as a feasible monitoring alternative in resource-constrained environments. Further validation in low-income contexts is warranted to establish population-specific reference intervals and inform clinical practice.