Multiomics reveal plasma constituents associated with thrombosis among trauma patients who do not respond to enoxaparin Open Access

• Poor responsiveness to low molecular weight heparin (LMWH) is prevalent in the surgical trauma population.

• Coagulation, innate immunity, and endothelial activation distinguish VTE development in patients who do not respond to LMWH.

Venous thromboembolism (VTE) is among the most common complications affecting patients with severe injuries. While enoxaparin resistance is common, predicting which patients among this subgroup will develop VTE remains a clinical challenge. The goal of this study was to utilize multi-omics to identify plasma constituents associated with VTE development among trauma patients exhibiting poor responses to enoxaparin. We conducted a secondary analysis of trauma patients at high risk of VTE based on injury characteristics. Plasma was collected daily for the first 8 hospital days. Patients who never responded to enoxaparin were defined as not achieving an anti–factor Xa (FXa) level of ≥ 0.2 IU/mL during the sampling period. A total of 145 patients were included in the analysis, of whom 24 (16.6%) developed VTE. Proteomics analyses identified increased proteins involved in coagulation, complement activation, and immune response pathways among VTE patients compared to non-VTE patients. A subset of patients (n=26) never responded to enoxaparin, among whom 8 (30.8%) developed VTE. Partial least squares discriminant analysis (PLS-DA) on multi-omics of never responders revealed clear separation based on VTE status. The top 25 differentially abundant proteins were involved in coagulation, fibrin cross-linking, inflammation, and acute phase responses. Differences were particularly robust on hospital day 5, at which we observed significant increases in FV, FXI, fibrinogen, complement, and C-reactive protein. In conclusion, proteomics signatures distinguish VTE development among trauma patients who do not respond to enoxaparin. These findings implicate novel pathways in postinjury VTE pathogenesis and new candidate proteins for future therapeutic intervention.