Thromboinflammatory and Pharmacological Effects of Low-Molecular-Weight Heparins in Acute Venous Thromboembolism: An Integrated Clinical and In Silico Analysis

Background: Venous thromboembolism (VTE) is a thromboinflammatory disorder involving coordinated activation of coagulation, endothelial dysfunction, and inflammatory signaling. Low-molecular-weight heparins (LMWHs) may exert pharmacological effects beyond anticoagulation. This study compared enoxaparin, bemiparin, and tinzaparin and explored potential multi-target mechanisms using molecular docking, network pharmacology, and enrichment analyses. Methods: In this retrospective cohort study, patients with acute VTE treated with therapeutic-dose LMWHs were analyzed. Stabilized IPTW based on multinomial propensity scores was used to reduce baseline imbalance between treatment groups. Clinical recovery was assessed using the Clinical Severity Score (CSS). Thromboinflammatory biomarkers (MPV, hs-CRP, NLR, fibrinogen) were evaluated during follow-up. Molecular docking, STRING/Cytoscape-based protein–protein interaction, and enrichment analyses were performed. Results: Median time to symptom resolution was 31 days with enoxaparin, 28 days with bemiparin, and 24 days with tinzaparin (log-rank p < 0.001). Recovery was faster with bemiparin (HR 1.28, 95% CI 1.05–1.56) and tinzaparin (HR 1.72, 95% CI 1.41–2.10). Tinzaparin showed greater reductions in hs-CRP, MPV, NLR, and fibrinogen (all p < 0.05) and less analgesic use beyond 10 days (19.7% vs. 27.0% and 33.2%; p < 0.001). Docking analyses identified plausible conformations (root-mean-square deviation, RMSD ≤ 2 Å). Given the structural flexibility and heterogeneous chain length of LMWHs, rigid docking algorithms may not fully capture biologically relevant conformations. Therefore, docking results should be interpreted as qualitative interaction mapping rather than quantitative binding affinity estimation. Network analysis highlighted F3, TNF, IL6, and VWF, while enrichment analyses suggested involvement of cytokine signaling, leukocyte migration, and thromboinflammatory pathways. Conclusions: LMWH therapy was associated with improved thromboinflammatory markers and clinical recovery, with tinzaparin showing comparatively more favorable thromboinflammatory biomarker trajectories and recovery dynamics within the limitations of this observational analysis. Integrated clinical and in silico findings provide hypothesis-generating insights into potential multi-target pharmacological effects beyond anticoagulation; however, these observations should be interpreted cautiously and require experimental validation.