Importance of the preanalytical phase: Elevation of protein levels in cerebrospinal fluid samples due to inappropriate containers

Abstract

Background: Biomarkers in cerebrospinal fluid (CSF) are crucial for diagnosing, monitoring, and prognosing neurological disorders.

Purpose: This study evaluates the impact of preanalytical variables, particularly container choice, on CSF protein measurements.

Analysis: Using 30 CSF samples, we compared sterile, additive-free tubes and lithium heparin tubes without separator gel.

Results: Protein levels were significantly elevated higher in heparin tubes (mean difference: 230.71 mg/dL, P < .001).

Conclusions: This overestimation underscores the necessity of adhering to preanalytical protocols to avoid erroneous clinical interpretations and ensure accurate diagnostic outcomes.

Keywords

Laboratory methods proteins analytes neurological disorders clinical studies

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References

Plebani

. Errors in clinical laboratories or errors in laboratory medicine? Clin Chem Lab Med 2006; 44(6): 750–759. DOI: 10.1515/CCLM.2006.123.

Vos

SJB

Visser

Verhey

, et al. Variability of CSF Alzheimer’s disease biomarkers: implications for clinical practice. PLoS One 2014; 9: e100784. DOI: 10.1371/journal.pone.0100784.

Shaw

Arias

, et al. Cerebrospinal fluid biomarker measures: preanalytical variables and handling. Alzheimer’s Dementia 2018; 14(6): 913–924. DOI: 10.1016/j.jalz.2018.04.002.

Zetterberg

Blennow

. Fluid biomarkers for mild traumatic brain injury and related conditions. Nat Rev Neurol 2016; 12(10): 563–574. DOI: 10.1038/nrneurol.2016.127.

Rifai

Horvath

Wittwer

. Principles and applications of clinical mass spectrometry: small molecules, peptides, and pathogens. Amsterdam: Elsevier, 2018.

Yang

J-Y

Chien

T-I

J-Y

, et al. Heparin interference in the cerebrospinal fluid protein assay measured with a pyrogallol red–molybdate complex. Clin Chim Acta 2009; 408(Issues 1–2): 75–78. DOI: 10.1016/j.cca.2009.07.011.

Cabanillas

da Silva

Marinsaldi

, et al. Interferencia de heparina en la determinación de proteínas totales por el método de Bradford. Revista Científica ANMAT 2023; 4: e40. DOI: 10.62035/rca.4.40.

Petzold

. CSF biomarkers for improved prognostic accuracy in acute CNS disease. Neurol Res 2007; 29(7): 691–708. DOI: 10.1179/016164107X240080.

CLSI . Collection, transport, and processing of blood specimens for testing plasma-based coagulation assays and molecular hemostasis assays; approved guideline—fifth edition. Wayne, PA: CLSI, 2008. CLSI Document H21-A5.

10.

Zhao

Gao

. Changes of proteins induced by anticoagulants can be more sensitively detected in urine than in plasma. Sci China Life Sci 2014; 57: 649–656. DOI: 10.1007/s11427-014-4661-y.

11.

Hansson

Mikulskis

Fagan

, et al. The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer’s disease diagnosis: a review. Alzheimers Dement 2018; 14(10): 1313–1333. DOI: 10.1016/j.jalz.2018.05.008.

12.

Cicognola

Chiasserini

Parnetti

. Preanalytical confounding factors in the analysis of cerebrospinal fluid biomarkers for Alzheimer’s disease: the issue of diurnal variation. Front Neurol 2015; 6: 143. DOI: 10.3389/fneur.2015.00143.