Post-Injury Platelet Aggregation and Venous Thromboembolism.

INTRODUCTION: Posttraumatic venous thromboembolism (VTE) remains prevalent in severely injured patients despite chemoprophylaxis. Importantly, although platelets are central to thrombosis, they are not routinely targeted in prevention of posttraumatic VTE. Further, platelets from injured patients show ex-vivo evidence of increased activation yet impaired aggregation, consistent with functional exhaustion. However, the relationship of this platelet functional phenotype with development of posttraumatic VTE is unknown. We hypothesized that following injury impaired ex-vivo platelet aggregation (PA) is associated with the development of posttraumatic VTE.
METHODS: We performed a secondary analysis of 133 severely injured patients from a prospective observational study investigating coagulation and inflammation (2011-2019). PA in response to stimulation with adenosine diphosphate (ADP), collagen, and thrombin was measured at presentation (pre-resuscitation) and 24 h (post-resuscitation). Viscoelastic clot strength and lysis were measured in parallel by thromboelastography. Multivariable regression examined relationships between PA at presentation, 24 h, and the delta between presentation and 24 h with development of VTE.
RESULTS: The 133 patients were severely injured (median injury severity score 25) and 14% developed VTE (all >48 hours after admission). At presentation, platelet count and PA were not significantly different between those with and without incident VTE. However, at 24 h, those who subsequently developed VTE had significantly lower platelet counts (126 x109/L vs 164 x109/L, p = 0.01), and lower PA in response to ADP (p < 0.05), collagen (p < 0.05), and thrombin (p = 0.06). Importantly, the magnitude of decrease in PA (Delta) from presentation to 24 h was independently associated with development of VTE (adjusted odds ratios per 10 aggregation unit decrease: Delta-ADP 1.31, p = 0.03; Delta-collagen 1.36, p = 0.01, Delta-thrombin 1.41, p < 0.01).
CONCLUSION: Severely injured patients with decreasing ex-vivo measures of platelet aggregation despite resuscitation have an increased risk of developing VTE. This may have implications for predicting development of VTE and for studying platelet targeted chemoprophylaxis regimens. LEVEL OF EVIDENCE: level III, prognostic.