Abstract

Chronic tramadol misuse represents a significant public health challenge, with emerging evidence suggesting sex-specific physiological impacts that remain insufficiently characterized. This investigation examined the haematological consequences of prolonged tramadol administration (100 mg/kg/day orally for 28 days) in mature Wistar albino rats, with particular emphasis on identifying potential sex-based variations. The experimental design employed twenty-eight rats (14 males, 14 females), systematically stratified by sex and subsequently divided into treatment and control cohorts (n = 7 per subgroup). Haematological analysis of blood samples quantified erythrocytic indices (RBC count, Hb concentration, PCV), total leukocyte count, and differential leukocyte profiles using automated analyzers complemented by microscopic verification. Statistical evaluation (Two-Way ANOVA with Tukey's HSD post-hoc test, p < 0.05) revealed significant sex-treatment interactions across multiple haematological parameters. The tramadol-exposed groups demonstrated marked alterations in erythrocytic parameters relative to respective controls. Male rats showed reductions in PCV (27%), RBC (25%), and Hb (27%), while female group displayed more pronounced decreases in PCV (38%) and Hb (38%), with moderate RBC decline (14%). Notably, female rats manifested distinct microcytic hypochromic anaemia, evidenced by significant decreases in MCV (44.90 ± 4.67 fL versus control 62.66 ± 2.84 fL) and MCH (14.91 ± 1.51 pg versus 21.09 ± 1.26 pg). Leukocyte profiling identified a consistent neutropenia (~16% reduction) across sexes, with female rats showing reactive lymphocytosis (22% increase). No significant alterations were observed in monocyte, eosinophil, or basophil. These findings indicate heightened female susceptibility to tramadol-induced haematopoietic suppression, potentially mediated through estrogen-enhanced opioid receptor sensitivity or hormonal modulation of erythropoietic pathways. The results corroborate clinical observations of tramadol-associated anaemia and immune dysregulation, emphasizing necessity for sex-specific therapeutic monitoring in chronic users. Public health initiatives should prioritize prevalent safety misconceptions, particularly among female populations, while future research should investigate underlying molecular mechanisms and potential recovery following cessation of use.

Key words: Anaemia, Opiod toxicity, Red Blood Cells, Tramadol, Wistar rats