Background: Sepsis is a complex, heterogeneous syndrome involving dysregulated inflammatory, haematopoietic, and coagulation pathways that collectively drive organ dysfunction. Evaluating a multi-pathway biomarker panel may provide a more comprehensive characterization of clinical severity. Methods: This retrospective, single-centre study included 228 adult patients with suspected sepsis evaluated at emergency department admission and categorized by SOFA score into High Risk (HR, SOFA ≥ 13; n = 78), Severe Risk (SR, SOFA 10–12; n = 52), Moderate Risk (MR, SOFA 7–9; n = 58), and Low Risk (LR, SOFA 0–6; n = 40). We assessed procalcitonin (PCT), presepsin (P-SEP), C-reactive protein (CRP), white blood cell count (WBC), immature granulocyte (IG%), platelet count (PLT), immature platelet fractions (IPF%, IPF#), and D-dimer (DD). Results: Blood cultures were positive in 65.4% of patients. PLT count and DD demonstrated the highest discriminative performance for distinguishing combined HR + SR from MR + LR groups, with areas under the ROC curve (AUCs) of 0.902 and 0.894, respectively. Among inflammatory markers, PCT achieved the highest AUC (0.835), followed by P-SEP (0.793) and CRP (0.726). WBC showed limited discrimination (0.582); immature lineage markers showed higher numerical discrimination, with both IG% and relative IPF% achieving AUCs of 0.796. Conclusions: Relative IPF% increased in parallel with severe thrombocytopenia in higher-SOFA groups, a pattern compatible with compensatory thrombopoietic activity, whereas absolute IPF# declined in HR cases. These findings highlight distinct multi-organ biomarker profiles across severity states and support an integrated biomarker framework, a multi-pathway approach incorporating bone marrow kinetics and coagulation markers to refine early severity characterization in emergency settings.