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

Figures

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  Figure 1.. Multiomics analyses reveal distinct molecular signatures depended on VTE status. (A) The cohort comprised 145 patients, including 121 who did not develop VTE (green) and 24 who developed VTE (purple). Blood samples were collected from each patient at 8 time points, spanning from arrival to 8 days after admission. The plasma fraction of these samples was subjected to MS-based multiomics analyses. (B) LDA was performed on the metabolomic and proteomic profiles of the patients across the monitored time points. (C) Protein network detected by the LDA model, annotated with the top significantly enriched biological processes, highlighting the functional implications of the proteomic alterations.

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  Figure 2.. Multiomics profiling of enoxaparin never responders. (A) Twenty-six patients were identified as never responders to enoxaparin therapy. Among these, 18 patients did not develop VTE, whereas 8 patients developed VTE (purple). (B) Ranked log2-transformed median protein abundances for the never responders, grouped by VTE development status. (C) Similarly, ranked log2-transformed median metabolite abundances displayed for the never responders, grouped by VTE development status. (D) PLS-DA was used to classify the integrated metabolomic and proteomic signatures of patients based on VTE development status. (E) The top 25 molecular features identified by the PLS-DA model contributed to the differentiation between VTE development status groups. (F) Heat map depicting the top 50 molecular features that showed significant differences between the VTE development status groups, as determined by the t test. Feature names were colored according to key thromboinflammatory pathways of interest to this analysis. Orange, complement activation; red, blood coagulation; dark blue, immune response; light blue, acute phase response. The analysis incorporated data from all time points.

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  Figure 3.. Longitudinal protein abundances among never responders who do and do not develop VTE. Median plasma protein levels with standard error across monitored time points, categorized by VTE development status: no VTE and VTE (purple). The analysis specifically focused on patients who responded poorly to enoxaparin treatment. (A) Fibrinogen chain levels. (B) Carboxypeptidase N catalytic chain. (C) Coagulation factors. (D) Complement activators. (E) Complement proteins. (F) Acute phase proteins. (G) VWF.

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  Figure 4.. Day 5 multiomics signatures in never responders highlight key altered pathways in the VTE cohort. (A) Significant differences in protein and metabolite levels between VTE development status groups were assessed specifically for patients who responded poorly to enoxaparin, at each monitored time point. The day 5 time point exhibited the highest number of significantly different features. (B) Pairwise comparison of features detected in both VTE status groups, specifically for day 5 plasma samples. (C) PLS-DA of day 5 multiomic signatures, categorized by VTE status. (D) The top 25 molecular features identified by the PLS-DA model that contributed to the differentiation between VTE status. (E) Heat map presentation of the top 50 molecular features that showed significant differences between the VTE status groups at day 5, as determined by the t test. Feature names were colored according to key thromboinflammatory pathways of interest to this analysis. Orange, complement activation; red: blood coagulation; dark blue, immune response; light blue, acute phase response.