Fibrinogen-to-Platelet Ratio and Hematologic Inflammatory Indexes in Spondylarthritis

Background/Objectives: Spondylarthritis (SA) is characterized by high clinical heterogeneity, often resulting in a discrepancy between systemic inflammation and patient-reported symptoms. While hematologic indices are emerging as cost-effective biomarkers, their role in phenotypic differentiation remains unclear. We investigated the utility of traditional inflammatory markers, including the novel fibrinogen-to-platelet ratio (FPR), in differentiating SA subtypes and predicting patient-reported disease activity. Methods: This cross-sectional study included 64 patients with spondylarthritis: axial SA (n = 32), peripheral SA (n = 8), and psoriatic SA (n = 24). Clinical assessments included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Functional Index (BASFI). Systemic inflammation was evaluated via C-reactive protein (CRP), fibrinogen, and calculated ratios (NLR, PLR, MLR, and FPR). Principal Component Analysis (PCA) was employed to map the inflammatory architecture, while Receiver Operating Characteristic (ROC) curves evaluated the predictive power for high disease activity (BASDAI ≥ 4). Results: Significant phenotypic differences were observed with the FPR demonstrating superior discriminative capacity (p = 0.003). Patients with peripheral SA exhibited significantly higher FPR (median 1.88) compared to axial (1.33) and psoriatic (1.32) subtypes, and the dedicated ROC analysis for phenotypic discrimination yielded an AUC of 0.866 (95% CI: 0.745–0.987) (1.36, p = 0.039). HLA-B27 prevalence was low overall (31.3%) and in psoriatic SA (4.2%, p = 0.012). Correlation analysis revealed strong associations between BASDAI and BASFI (ρ = 0.79), NLR and MLR (ρ = 0.78), and CRP and fibrinogen (ρ = 0.66). PCA identified two independent inflammatory dimensions explaining 74.8% of variance: neutrophil-hypercoagulable axis (41.4%, driven by NLR, PLR, and MLR), and an acute-phase/fibrinogen axis (33.4%, driven by CRP, fibrinogen, and FPR). Notably, FPR clustered with acute-phase reactants rather than leukocyte-derived ratios, supporting its role as a marker of systemic inflammatory burden. Although fibrinogen is involved in the coagulation cascade, the absence of direct coagulation markers precludes definitive characterization of this component as hypercoagulable. ROC analysis revealed that fibrinogen showed the highest discriminative ability for disease activity (BASDAI ≥ 4), with an AUC of 0.690 (95% CI: 0.519–0.861), followed by NLR (0.621), MLR (0.592), and FPR (0.583). However, overall discriminative performance remained modest, with most 95% confidence intervals crossing 0.5. Conclusions: FPR emerges as a robust phenotypic biomarker capable of discriminating against SA subtypes, particularly identifying peripheral SA with high accuracy and excellent negative predictive value. In contrast, its ability to predict patient-reported disease activity remains limited, reinforcing the distinction between trait and state biomarkers. Exploratory PCA revealed that FPR clusters with acute-phase reactants rather than leukocyte-derived ratios, supporting its biological link to systemic inflammatory burden. These findings advocate for a dual-purpose biomarker approach in SA: FPR for phenotypic stratification and fibrinogen for activity assessment, while clinical indices remain indispensable for symptom monitoring. Validation in larger, prospective cohorts is warranted.