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

Abstract

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.