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. 2022 Oct 20:13:951802.
doi: 10.3389/fneur.2022.951802. eCollection 2022.

Measurement of D-dimer in cerebrospinal fluid using a luminescent oxygen channeling immunoassay

Konstantin Kohlhase  1 , Jan Hendrik Schaefer  1 , Wolfgang Miesbach  2 , Gudrun Hintereder  3 , Konstantin Kirchmayr  4 , Birga Zwinge  2 , Yavor Yalachkov  1 , Christian Foerch  1 , Martin A Schaller-Paule  1
Affiliations

Measurement of D-dimer in cerebrospinal fluid using a luminescent oxygen channeling immunoassay

Konstantin Kohlhase et al. Front Neurol. .

Abstract

Background: Measurement of D-dimer in cerebrospinal fluid (CSF) allows insight into coagulation system activation in the central nervous system and can be utilized to monitor intracranial hemorrhage as well as acute phase processes beyond hemostasis in inflammatory and neoplastic diseases. So far, the measurability of D-dimer in low and very low concentrations in CSF was limited in conventional immunoassays. Novel high-sensitivity chemiluminescent immunoassays such as the luminescent oxygen channeling immunoassay (LOCI®) are getting increasingly available but have not been validated in CSF. The aim of this study was to investigate the accuracy and linearity of the LOCI® in assessing D-dimer in CSF.

Methods: INNOVANCE LOCI hs D-dimer reagent cartridge was used for the measurement of D-dimer in CSF of patients with different neurological diseases. For the evaluation of linearity, dilution series were performed in a pooled CSF sample with the determination of intra-assay precision (CV, coefficient of variation) in 3 individual samples with 20 replicates. Furthermore, D-dimer concentrations measured by LOCI® were compared with the respective results of a routinely available clinical latex-enhanced immunoassay (HemosiIL D-Dimer HS 500).

Results: Linear regression analysis of the LOCI® method revealed a r 2 of 1.00 (p < 0.001) with a regression coefficient B of 1.012 ± 0.003 (CI: 1.005-1.019, p < 0.001) and an intercept of -1.475 ± 1.309 (CI: -4.493 to 1.543); the median intra-assay CV was 0.69% (range: 0.68-0.75). In total, 185 CSF samples were measured by LOCI® technology, showing a mean concentration of 204.84 ± 2,214.93 ng/ml. D-dimer concentration between LOCI and latex-enhanced immunoassay differed by a factor of 10.6 ± 13.6 on average with a maximum deviation by a factor of 61.3; the maximum deviation was found at low concentrations.

Conclusion: D-dimer in CSF of patients with neurological disease can be reliably measured by the LOCI® method with high linearity and accuracy at low concentrations.

Keywords: biomarker; coagulation; diagnostics; immunoassay; laboratory.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Linearity curves of D-dimer in cerebrospinal fluid (CSF) measured with luminescent oxygen channeling immunoassay (LOCI®) INNOVANCE LOCI hs D-dimer assay.
Figure 2
Figure 2
Calibration curve of D-dimer measurement in cerebrospinal fluid (CSF) using luminescent oxygen channeling immunoassay (LOCI®) INNOVANCE LOCI hs D-dimer assay.
Figure 3
Figure 3
Linearity assessment of D-dimer measurement in cerebrospinal fluid (CSF) using HemosIL HS 500 reagent latex-enhanced immunoassay. The measurement was performed on two different ACL TOP 700 analyzers [Linearity (1) and Linearity (2)].
Figure 4
Figure 4
Scatterplot of D-dimer concentrations in cerebrospinal fluid measured using luminescent oxygen channeling immunoassay (LOCI, y-axis) and latex-enhanced turbidimetric immunoassays (HemosIL HS 500 reagent) on the ACL TOP 700 (x-axis).
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