Background: Hemorrhage is a leading cause of death after trauma, and coagulopathy contributes to death from hemorrhage. Platelet dysfunction plays a role in coagulopathy, and impaired platelet aggregation is associated with higher mortality. However, little is known about the cause underlying this platelet dysfunction. Proteomic analysis offers an unbiased approach to characterizing the changes in the plasma environment accompanying platelet dysfunction in trauma patients.

Aims: Characterize plasma protein changes in trauma patients with platelet dysfunction to generate a deeper understanding of the possible causes.

Methods: Blood was collected from severely injured trauma patients meeting full trauma team activation criteria at the time of Emergency Department (ED) arrival. Twelve patients with impaired platelet aggregation and twelve with normal aggregation were identified. Plasma samples underwent proteomics analysis by mass spectrometry. To account for different amounts of hemodilution prior to blood draw, individual protein concentrations were normalized to total protein concentration. Statistical comparisons were made by Wilcoxon rank-sum test with significance at p< 0.05.

Results: Compared to patients with normal platelet function, those with platelet dysfunction had lower gelsolin (median 1.21E6 vs. 1.83E6, p< 0.001), histidine-rich glycoprotein, alpha-2-HS-glycoprotein (31.1 vs. 2.3% positive, p< 0.001), and apolipoprotein A-IV (1.67E6 vs. 2.51E6, p=0.021). They also exhibited higher plasma VWF (19.7 vs. 12.2 µg/mL, p< 0.001) and TSP-1 levels (2,609 vs. 128 ng/mL, p< 0.001). One-third of patients showed a higher density of less-adhesive, low-molecular weight multimers, and half showed enhanced satellite bands, a characteristic of multimer cleavage.

Conclusions: Trauma patients show evidence of platelet activation, VWF release and cleavage, and TSP-1 release. These changes describe a complex alteration in the VWF-platelet adhesion axis with mixed effects on function. Patients with platelet dysfunction also show lower levels of four proteins known to modulate coagulation and platelet function. Future study should describe the role of these changes in platelet dysfunction after trauma.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/complex-changes-in-plasma-associated-with-platelet-dysfunction-in-trauma-patients/