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

Jungar, Christina ; Alinder, Erik ; Becker, Charlotte LU ; Moseby-Knappe, Marion LU and Lybeck, Anna LU orcid (2026) In Resuscitation Plus 28.
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... (More)

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.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Resuscitation Plus
volume
28
article number
101208
publisher
Elsevier
external identifiers
  • pmid:41608738
  • scopus:105027682907
ISSN
2666-5204
DOI
10.1016/j.resplu.2025.101208
language
English
LU publication?
yes
additional info
© 2025 The Author(s).
id
69868a20-0a9c-4300-9156-6ae5ac5e7f89
date added to LUP
2026-08-24 08:59:02
date last changed
2026-09-08 05:35:50
@article{69868a20-0a9c-4300-9156-6ae5ac5e7f89,
  abstract     = {{<p>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.</p><p>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.</p><p>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.</p><p>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.</p>}},
  author       = {{Jungar, Christina and Alinder, Erik and Becker, Charlotte and Moseby-Knappe, Marion and Lybeck, Anna}},
  issn         = {{2666-5204}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Resuscitation Plus}},
  title        = {{Hemolysis correction factor in the reporting of serum neuron-specific enolase - Clinical utility in neuroprognostication after cardiac arrest}},
  url          = {{http://dx.doi.org/10.1016/j.resplu.2025.101208}},
  doi          = {{10.1016/j.resplu.2025.101208}},
  volume       = {{28}},
  year         = {{2026}},
}