Elevated cell-free hemoglobin: A novel early biomarker following traumatic injury

BACKGROUND Cell-free hemoglobin (CFH) and free heme are potent mediators of endotheliopathy and organ injury in sepsis, but their roles in other hemolytic pathologies are not well-defined. A prime example is trauma where early hemolysis may initiate damage and predict outcome. Here, we investigated the presence of plasma CFH, heme, and their major scavengers after traumatic injury. METHODS Adult patients who presented as highest-level activations were prospectively enrolled at a level 1 trauma center between 2021 and 2023. Venous blood was collected upon arrival (pretransfusion) and 6, 12, and 24 hours after admittance for quantification of CFH, haptoglobin, heme, and hemopexin. RESULTS We studied 119 mostly male subjects (101:18) with a median age of 48 years (interquartile range [IQR], 31–64 years) and an Injury Severity Score of 22 (IQR, 11–29); the majority had suffered blunt force trauma. The 28-day mortality rate was 11%. Cell-free hemoglobin was high upon emergency department arrival (10.9 μM; IQR, 6.8–17.6) and then declined but remained elevated compared with normative levels during the monitoring period (>5 vs. ~0.2 μM). The initial drop in CFH was attributed to haptoglobin binding and clearance. Notably, there was a subgroup of patients with two- to threefold higher levels of CFH on emergency department arrival (median, 25 μM). Patients with these highest CFH levels had longer hospital stays and more frequent complications. CONCLUSION Cell-free hemoglobin is elevated in trauma patients very early after injury and may impact outcome. While further work is needed, early correction of hemolysis could provide benefit. LEVEL OF EVIDENCE Prognostic/Epidemiological Study; Level III.