PMID- 33957709
OWN - NLM
STAT- MEDLINE
DCOM- 20220314
LR  - 20220705
IS  - 1437-4331 (Electronic)
IS  - 1434-6621 (Linking)
VI  - 59
IP  - 10
DP  - 2021 Sep 27
TI  - Cerebrospinal fluid hemoglobin levels as markers of blood contamination: 
      relevance for alpha-synuclein measurement.
PG  - 1653-1661
LID - 10.1515/cclm-2020-1521 [doi]
AB  - OBJECTIVES: Cerebrospinal fluid alpha-synuclein (CSF alpha-syn) represents a possible 
      biomarker in Parkinson's disease (PD) diagnosis. CSF blood contamination can 
      introduce a bias in alpha-syn measurement. To date, CSF samples with a red blood 
      cells (RBC) count >50 RBC x 10(6)/L or haemoglobin (Hb) concentration >200 mug/L 
      are excluded from biomarker studies. However, investigations for defining 
      reliable cut-off values are missing. METHODS: We evaluated the effect of blood 
      contamination on CSF alpha-syn measurement by a systematic approach in a cohort of 42 
      patients with different neurological conditions who underwent lumbar puncture 
      (LP) for diagnostic reasons. CSF samples were spiked with whole blood and 
      serially diluted to 800, 400, 200, 100, 75, 50, 25, 5, 0 RBC x 10(6)/L. CSF alpha-syn 
      and Hb levels were measured by ELISA. RESULTS: In neat CSF, the average 
      concentration of alpha-syn was 1,936 +/- 636 ng/L. This value increased gradually in 
      spiked CSF samples, up to 4,817 +/- 1,456 ng/L (+149% alpha-syn variation) in samples 
      with 800 RBC x 10(6)/L. We established different cut-offs for discriminating 
      samples with alpha-syn level above 5, 10, and 20% variation, corresponding to a Hb 
      (RBC) concentration of 1,569 mug/L (37 RBC x 10(6)/L), 2,082 mug/L (62 
      RBC x 10(6)/L), and 3,118 mug/L (87 RBC x 10(6)/L), respectively. CONCLUSIONS: Our 
      data show the high impact of CSF blood contamination on CSF alpha-syn levels, 
      highlighting the measurement of Hb concentration as mandatory when assessing CSF 
      alpha-syn. The thresholds we calculated are useful to classify CSF samples for blood 
      contamination, considering as reliable only those showing a Hb concentration 
      <1,569 mug/L.
CI  - (c) 2021 Walter de Gruyter GmbH, Berlin/Boston.
FAU - Paciotti, Silvia
AU  - Paciotti S
AD  - Laboratory of Clinical Neurochemistry, Section of Neurology, Department of 
      Medicine and Surgery, University of Perugia, Perugia, Italy.
FAU - Stoops, Erik
AU  - Stoops E
AD  - ADx NeuroSciences, Gent, Belgium.
FAU - Francois, Cindy
AU  - Francois C
AD  - ADx NeuroSciences, Gent, Belgium.
FAU - Bellomo, Giovanni
AU  - Bellomo G
AD  - Laboratory of Clinical Neurochemistry, Section of Neurology, Department of 
      Medicine and Surgery, University of Perugia, Perugia, Italy.
FAU - Eusebi, Paolo
AU  - Eusebi P
AD  - Regional Health Authority of Umbria, Epidemiology Department, Perugia, Italy.
FAU - Vanderstichele, Hugo
AU  - Vanderstichele H
AD  - Biomarkable bv, Gent, Belgium.
FAU - Chiasserini, Davide
AU  - Chiasserini D
AUID- ORCID: 0000-0002-1169-3258
AD  - Department of Medicine and Surgery, Section of Physiology and Biochemistry, 
      University of Perugia, Perugia, Italy.
FAU - Parnetti, Lucilla
AU  - Parnetti L
AUID- ORCID: 0000-0001-5722-3967
AD  - Laboratory of Clinical Neurochemistry, Section of Neurology, Department of 
      Medicine and Surgery, University of Perugia, Perugia, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210507
PL  - Germany
TA  - Clin Chem Lab Med
JT  - Clinical chemistry and laboratory medicine
JID - 9806306
RN  - 0 (Biomarkers)
RN  - 0 (Hemoglobins)
RN  - 0 (alpha-Synuclein)
SB  - IM
MH  - Biomarkers
MH  - Erythrocytes
MH  - Hemoglobins
MH  - Humans
MH  - *Parkinson Disease/cerebrospinal fluid/diagnosis
MH  - *alpha-Synuclein/cerebrospinal fluid
OTO - NOTNLM
OT  - biomarkers
OT  - blood contamination
OT  - cerebrospinal fluid (CSF)
OT  - hemoglobin
OT  - alpha-synuclein
EDAT- 2021/05/07 06:00
MHDA- 2022/03/15 06:00
CRDT- 2021/05/06 20:53
PHST- 2020/10/13 00:00 [received]
PHST- 2021/04/26 00:00 [accepted]
PHST- 2021/05/07 06:00 [pubmed]
PHST- 2022/03/15 06:00 [medline]
PHST- 2021/05/06 20:53 [entrez]
AID - cclm-2020-1521 [pii]
AID - 10.1515/cclm-2020-1521 [doi]
PST - epublish
SO  - Clin Chem Lab Med. 2021 May 7;59(10):1653-1661. doi: 10.1515/cclm-2020-1521. 
      Print 2021 Sep 27.