The Role of Platelet-to-Neutrophil Ratio as a Biomarker for Pulmonary Hypertension in Sickle Cell Disease Patients: A Retrospective Cohort Study

Background and Objectives: Pulmonary hypertension (PH) is a major contributor to morbidity and mortality in sickle cell disease (SCD), yet reliable and accessible biomarkers for cardiopulmonary risk stratification remain limited. This study aimed to evaluate whether the platelet-to-neutrophil ratio (PNR) is independently associated with echo-estimated PH (ePH) in adolescents and adults with SCD and to compare its predictive value with hemoglobin composition and genotype. Materials and Methods: A retrospective cohort study was conducted at King Fahd Hospital of the University, Al Khobar, Saudi Arabia (January 2019–January 2025). Clinical, laboratory, and echocardiographic data from 114 patients with confirmed SCD who underwent transthoracic echocardiography (TTE) were analyzed. ePH was defined as tricuspid regurgitant velocity (TRV) ≥ 2.5 m/s or pulmonary artery acceleration time (PAAT) ≤ 105 ms. Multivariable logistic and linear regression models were used to assess associations between PNR, hemoglobin fractions, genotype, and pulmonary pressure estimates. Results: Overall, 43% of patients met the criteria for ePH. PNR was not independently associated with ePH or TRV in adjusted analyses. In contrast, higher fetal hemoglobin (HbF) levels were independently associated with lower odds of ePH (adjusted OR 0.92 per 1% increase, 95% CI 0.86–0.98) and lower TRV values. The HbS/β⁰ genotype was significantly associated with increased odds of ePH (adjusted OR 5.44, 95% CI 1.37–24.0). Exploratory analyses demonstrated an inverse association between PNR and lactate dehydrogenase, suggesting that PNR reflects hemolytic activity rather than pulmonary vascular involvement. Conclusions: In this retrospective cohort of patients with SCD, PNR was not independently associated with ePH or TRV after multivariable adjustment. In contrast, hemoglobin composition and genotype, particularly higher HbF and the HbS/β⁰ genotype, were significantly associated with pulmonary pressure estimates.