Leukocyte Differential Distribution and Creatine Kinase Elevations as Indicators of Tissue Stress and Inflammation in Sickle Cell Disease

Abstract

Aims: To evaluate leukocyte subset distribution and serum creatine kinase (CK) activity, considered jointly, as indicators of tissue stress and low-grade inflammation in Nigerian patients with sickle cell anaemia. Study Design: A hospital-based, cross-sectional comparative study. Setting and Duration: Department of Haematology Laboratory, University College Hospital, Ibadan, Oyo State, Nigeria; data were collected over a twelve-month postgraduate research period (July 2025 to July 2026) as part of a wider investigation of this patient cohort. Methodology: The analysis drew on 150 clinically stable, confirmed HbSS patients and 100 apparently healthy HbAA controls (N = 250), assembled as part of a larger parent study of this population. Total and five-part differential leukocyte counts were obtained on an automated haematology analyser, and serum CK activity was assayed by kinetic spectrophotometry on an automated chemistry analyser. The neutrophil-to-lymphocyte ratio (NLR) was derived from the differential count as a composite index of physiological stress. Between-group differences were tested using the independent-samples t-test and one-way analysis of variance across CK tertiles, and associations between CK and the differential leukocyte parameters were examined using Pearson correlation, with significance set at p < 0.05. Results: Patients carried a significantly heavier total leukocyte load than controls (7,736 ± 3,406 versus 6,232 ± 1,744 cells/µL, p < 0.001), while the proportional differential counts and the derived NLR were closely similar between groups (NLR 0.99 versus 0.95), and mean CK did not differ significantly (169.32 ± 7.04 versus 171.14 ± 6.41 U/L, p = 0.116). Stratifying patients by CK tertile, however, uncovered a graded, dose-dependent shift: neutrophil percentage and NLR rose from 52.3% and 1.51 in the low tertile to 70.2% and 2.80 in the high tertile, lymphocyte percentage fell from 34.6% to 25.1% (all p ≤ 0.002), and CK correlated inversely with basophil percentage (r = -0.261, p = 0.009) but not with the other differential parameters. Conclusion: A simple comparison against healthy controls masked what a within-patient, CK-stratified analysis revealed: a consistent, dose-dependent shift toward a neutrophil-predominant, lymphocyte-depleted leukocyte profile, mirrored by a rising NLR, as CK activity increased. Interpreting the leukocyte differential count and CK jointly, rather than each in isolation against reference values, may add practical value to the assessment of tissue stress and low-grade inflammation in sickle cell disease.