BackgroundMajor trauma results in dramatic changes in platelet behavior. Newly-formed platelets are more reactive than older platelets, but their contributions to hemostasis and thrombosis after severe injury have not been previously evaluated.ObjectivesTo determine the relationship between immature platelet metrics and circulating drivers of platelet production with clinical outcomes after major injury.MethodsProspective observational cohort study of adult trauma patients. Platelet counts and the immature platelet fraction (IPF) were measured at admission, 24 hours, 72 hours and 7 days post-injury. Plasma proteins involved in thrombopoiesis were quantified at admission. The primary outcome was in-hospital mortality; secondary outcomes were venous thromboembolic events (VTE) and organ failure.ResultsAt two hours post-injury, immature platelet counts (IPC) were significantly lower in non-survivors (n=40) compared to survivors (n=236; 7.3x109/L vs 10.6x109/L, p=0.009). Similarly, impaired platelet function on thromboelastometry was associated with a lower admission IPC (9.1x109/L vs 11.9x109/L, p<0.001). However, at later timepoints we observed a significantly higher IPF and IPC in patients who developed VTE (21.0x109/L vs 11.1x109/L, p=0.02) and prolonged organ dysfunction (20.9 x109/L vs 11x109/L, p=0.003) compared to those who did not develop complications. Plasma levels of thrombopoietin at admission were significantly lower in in non-survivors (p<0.001), in patients with organ failure (p<0.001) and in those who developed VTE (p=0.04).ConclusionsImmature platelet depletion in the acute phase after major injury is associated with increased morality, whereas excessive immature platelet release at later timepoints may predispose to thrombosis and organ dysfunction.ESSENTIALS-Newly-formed platelets are highly active, but their role in outcomes after major trauma is unknown-Immature platelets were quantified in a cohort of 276 severely injured patients-Early depletion of immature platelets is associated with increased mortality and coagulopathy-Raised immature platelet at later timepoints increases the risk of thrombosis and organ failure