Hemolysis correction factor in the reporting of serum neuron-specific enolase – Clinical utility in neuroprognostication after cardiac arrest

Abstract

Background

Neuron-specific enolase (NSE) from 48 h after cardiac arrest is the only biomarker of brain injury with recommended cut-offs for use in neuroprognostication. Hemolysis elevates levels of NSE and may result in false outcome predictions.

Methods

A correction-factor for hemolysis in reporting of levels of NSE was established and evaluated in (1) incoming routine samples and (2) biobank samples from 48 h after cardiac arrest from the SweCrit biobank. Comparisons were made with three methods for handling hemolysis: Hemolysis Index (HI) 30 mg/dL or HI 50 mg/dL as the highest acceptable level of hemolysis, or a graded approach.

Results

Five-hundred and fifty-six routine samples and 263 biobank samples were analyzed. A correction factor of 0.33 µg/L per HI significantly increased the number of reported routine samples, when compared to the three other methods for handling hemolysis (HI 30 mg/dL or HI 50 mg/dL as the highest acceptable level of hemolysis, or a graded approach). Use of the correction factor did not affect the number of reported biobank samples. The prognostic accuracy of NSE was unaffected by use of the correction factor compared to the other tested methods for handling hemolysis: area under the curve (AUC) 0.88 (95 % Cl 0.84–0.92) vs 0.87 (95 % Cl 0.83–0.92) at HI ≤ 30 mg/dL, 0.87 (95 % Cl 0.83–0.92) at HI ≤ 50 mg/dL and 0.87 (95 % CI 0.83–0.92) with the graded approach. Levels of hemolysis were low in the biobank samples.

Conclusion

Due to the low levels of hemolysis in the biobank samples, the effects of a correction factor on neuroprognostication after cardiac arrest in routine samples remains uncertain. Clinical use of a correction factor may lead to more reported samples but risks over-correction.