XML Template (2014) [22.10.2014–12:53pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACBJ/Vol00000/140092/APPFile/SG-ACBJ140092.3d
(ACB)
[1–3] [PREPRINTER stage]
Ann Clin Biochem OnlineFirst, published on November 6, 2014 as doi:10.1177/0004563214554463
Short Report Annals of Clinical Biochemistry 0(0) 1–3 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0004563214554463 acb.sagepub.com
Specificity of elevated cerebrospinal fluid bilirubin in the investigation of subarachnoid haemorrhage Helen L Falconer, Susan A Walker and J Peter Ashby
Abstract Background: The spectrophotometric examination of cerebrospinal fluid for bilirubin is an established investigation in patients with suspected subarachnoid haemorrhage. This study assesses the diagnostic specificity of an elevated cerebrospinal fluid bilirubin and how this may be influenced by the presence of oxyhaemoglobin and the concentration of cerebrospinal fluid total protein. Methods: One thousand cerebrospinal fluid spectroscopy reports were reviewed. Electronic patient records were examined to determine the clinical outcome in patients with an elevated cerebrospinal fluid bilirubin. Results: Forty-four out of 1000 cerebrospinal fluid scans showed an increase in cerebrospinal fluid bilirubin unrelated to elevated serum bilirubin concentrations. This was associated with subarachnoid haemorrhage in 16 (36%) cases. Subarachnoid haemorrhage was confirmed in 5/17 (29%) patients positive for cerebrospinal fluid bilirubin alone and in 11/27 (41%) patients positive for both cerebrospinal fluid bilirubin and oxyhaemoglobin. At cerebrospinal fluid total protein concentrations 0.007 AU). NBA: net bilirubin absorbance, NOA: net oxyhaemoglobin absorbance, TP: total protein, OxyHb: oxyhaemoglobin, FP: false positive, TT: traumatic tap, CM: CNS malignancy. CI: CNS infection, UK: unknown.
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(ACB)
[1–3] [PREPRINTER stage]
Falconer et al.
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Table 1. CSF findings for 44 CSF reports with raised CSF bilirubin. CSF findings Bilirubin
OxyHb
Total protein (g/L)
N
Confirmed SAH
False positives
þve þve þve þve
þve þve ve ve
1 1
10 17 9 8
6 5 4 1
4 12 5 7
(60%) (29%) (44%) (13%)
Bilirubin: þve (positive) ¼ >0.007 AU, ve (negative) ¼ 40.007 AU. OxyHb (Oxyhaemoglobin): þve (positive) ¼ >0.02 AU, ve (negative) ¼ 40.02 AU. CSF total protein range (g/L): confirmed SAH, 0.42–15.0; False positives, 0.29–4.63.
but recommend reporting all such results as ‘consistent with SAH’. While this approach is undoubtedly safe and appropriate, consideration of the CSF protein concentration may be helpful when discussing the likelihood of SAH in individual patients, particularly if there is a more likely alternative explanation for the raised CSF total protein. The expert guidelines for the examination of CSF advise that ‘the final interpretation should take into account all available clinical information’. The present data endorse the view that specificity will improve if the results are interpreted by laboratory staff who are aware of the clinical circumstances of each case, including the CSF total protein concentration. Acknowledgements NA.
presence of bilirubin than those who present later. In the present study, 6/7 patients presenting within seven days showed an increase in both oxyhaemoglobin and bilirubin. However, 3/6 patients presenting later also showed an increase in both oxyhaemoglobin and bilirubin. The time of presentation was not established in the further three patients with confirmed SAH. In the presence of CSF oxyhaemoglobin, SAH was confirmed in 11/27 (41%) patients but this proportion increased to 60% (6/10 patients) with CSF total protein concentrations 1 g/L in the absence of oxyhaemoglobin. However, they do not specifically consider the CSF total protein when both bilirubin and oxyhaemoglobin are present
Declaration of conflicting interests None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Ethical approval Not applicable.
Guarantor SAW.
Contributorship HLF reviewed the CSF spectroscopy data. HLF and SAW reviewed the electronic patient records. SAW and JPA conceived the study. HLF drafted the manuscript and all authors were involved in reviewing and editing the manuscript.
References 1. Cruikshank A, Auld P, Beetham R, et al. Revised national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage. Ann Clin Biochem 2008; 45: 238–244. 2. Horstman P, Linn FHH, Voorbij HAM, et al. Chance of aneurysm in patients suspected of SAH who have a ‘negative’ CT scan but a ‘positive’ lumbar puncture. J Neurol 2012; 259: 649–652. 3. Alons I, Verheul RJ, Ponjee GAE, et al. Optimizing blood pigment analysis in cerebrospinal fluid for the diagnosis of subarachnoid haemorrhage – a practical approach. Eur J Neurol 2013; 20: 193–197.
Downloaded from acb.sagepub.com at Bobst Library, New York University on April 27, 2015
(ACB)
[1–3] [PREPRINTER stage]
Ann Clin Biochem OnlineFirst, published on November 6, 2014 as doi:10.1177/0004563214554463
Short Report Annals of Clinical Biochemistry 0(0) 1–3 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0004563214554463 acb.sagepub.com
Specificity of elevated cerebrospinal fluid bilirubin in the investigation of subarachnoid haemorrhage Helen L Falconer, Susan A Walker and J Peter Ashby
Abstract Background: The spectrophotometric examination of cerebrospinal fluid for bilirubin is an established investigation in patients with suspected subarachnoid haemorrhage. This study assesses the diagnostic specificity of an elevated cerebrospinal fluid bilirubin and how this may be influenced by the presence of oxyhaemoglobin and the concentration of cerebrospinal fluid total protein. Methods: One thousand cerebrospinal fluid spectroscopy reports were reviewed. Electronic patient records were examined to determine the clinical outcome in patients with an elevated cerebrospinal fluid bilirubin. Results: Forty-four out of 1000 cerebrospinal fluid scans showed an increase in cerebrospinal fluid bilirubin unrelated to elevated serum bilirubin concentrations. This was associated with subarachnoid haemorrhage in 16 (36%) cases. Subarachnoid haemorrhage was confirmed in 5/17 (29%) patients positive for cerebrospinal fluid bilirubin alone and in 11/27 (41%) patients positive for both cerebrospinal fluid bilirubin and oxyhaemoglobin. At cerebrospinal fluid total protein concentrations 0.007 AU). NBA: net bilirubin absorbance, NOA: net oxyhaemoglobin absorbance, TP: total protein, OxyHb: oxyhaemoglobin, FP: false positive, TT: traumatic tap, CM: CNS malignancy. CI: CNS infection, UK: unknown.
Downloaded from acb.sagepub.com at Bobst Library, New York University on April 27, 2015
XML Template (2014) [22.10.2014–12:53pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACBJ/Vol00000/140092/APPFile/SG-ACBJ140092.3d
(ACB)
[1–3] [PREPRINTER stage]
Falconer et al.
3
Table 1. CSF findings for 44 CSF reports with raised CSF bilirubin. CSF findings Bilirubin
OxyHb
Total protein (g/L)
N
Confirmed SAH
False positives
þve þve þve þve
þve þve ve ve
1 1
10 17 9 8
6 5 4 1
4 12 5 7
(60%) (29%) (44%) (13%)
Bilirubin: þve (positive) ¼ >0.007 AU, ve (negative) ¼ 40.007 AU. OxyHb (Oxyhaemoglobin): þve (positive) ¼ >0.02 AU, ve (negative) ¼ 40.02 AU. CSF total protein range (g/L): confirmed SAH, 0.42–15.0; False positives, 0.29–4.63.
but recommend reporting all such results as ‘consistent with SAH’. While this approach is undoubtedly safe and appropriate, consideration of the CSF protein concentration may be helpful when discussing the likelihood of SAH in individual patients, particularly if there is a more likely alternative explanation for the raised CSF total protein. The expert guidelines for the examination of CSF advise that ‘the final interpretation should take into account all available clinical information’. The present data endorse the view that specificity will improve if the results are interpreted by laboratory staff who are aware of the clinical circumstances of each case, including the CSF total protein concentration. Acknowledgements NA.
presence of bilirubin than those who present later. In the present study, 6/7 patients presenting within seven days showed an increase in both oxyhaemoglobin and bilirubin. However, 3/6 patients presenting later also showed an increase in both oxyhaemoglobin and bilirubin. The time of presentation was not established in the further three patients with confirmed SAH. In the presence of CSF oxyhaemoglobin, SAH was confirmed in 11/27 (41%) patients but this proportion increased to 60% (6/10 patients) with CSF total protein concentrations 1 g/L in the absence of oxyhaemoglobin. However, they do not specifically consider the CSF total protein when both bilirubin and oxyhaemoglobin are present
Declaration of conflicting interests None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Ethical approval Not applicable.
Guarantor SAW.
Contributorship HLF reviewed the CSF spectroscopy data. HLF and SAW reviewed the electronic patient records. SAW and JPA conceived the study. HLF drafted the manuscript and all authors were involved in reviewing and editing the manuscript.
References 1. Cruikshank A, Auld P, Beetham R, et al. Revised national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage. Ann Clin Biochem 2008; 45: 238–244. 2. Horstman P, Linn FHH, Voorbij HAM, et al. Chance of aneurysm in patients suspected of SAH who have a ‘negative’ CT scan but a ‘positive’ lumbar puncture. J Neurol 2012; 259: 649–652. 3. Alons I, Verheul RJ, Ponjee GAE, et al. Optimizing blood pigment analysis in cerebrospinal fluid for the diagnosis of subarachnoid haemorrhage – a practical approach. Eur J Neurol 2013; 20: 193–197.
Downloaded from acb.sagepub.com at Bobst Library, New York University on April 27, 2015
