Article
Licensed
Unlicensed Requires Authentication

An improved laboratory protocol to assess subarachnoid haemorrhage in patients with negative cranial CT scan

  • , , and
Published/Copyright: July 31, 2006
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 44 Issue 8

Abstract

Background: The laboratory analysis of cerebrospinal fluid (CSF) plays a key role in considering subarachnoid haemorrhage (SAH) in patients with clinical suspicion, but negative CT scan. Although the determination of the CSF bilirubin concentration generally provides high sensitivity, it was recently shown that specificity and positive predictive value are unacceptably low, limiting its use as a diagnostic tool.

Methods: We intended to design and evaluate an improved laboratory protocol, which fulfills the requirement of better specificity without losing sensitivity. We present a procedure in which a “bili-excess” concentration is determined, which is the surplus CSF bilirubin measured after subtraction of an estimated upper limit for the individual patient. The latter is calculated from [bilirubin]serum, [albumin]serum and [albumin]CSF, taking into account the propagation of analytical errors in the individual analyses. We investigated the applicability of direct absorption vs. derivative spectroscopy, thereby addressing the influence of various calibration methods. We evaluated our procedure in 92 CSF samples drawn from patients with (n=37) and without (n=55) clinical suspicion of SAH.

Results: In our study population, we show that specificity increases from 0.83 (95% CI, 0.74–0.91) to 1.00 (95% CI, 0.96–1.00) using the bili-excess concept, with an established upper limit for bili-excess of 0.11μmol/L instead of the recommended use of an “uncorrected” CSF bilirubin upper limit of 0.20 μmol/L. Sensitivity in both cases is 1.00 (95% CI, 0.66–1.00). We demonstrate the merit of allowing for analytical imprecision in the bili-excess concept.

Conclusions: We provide a quantitative procedure to explore the likelihood of (CT-negative) SAH independent of the absolute CSF bilirubin concentration by considering the “bili-excess” concentration per individual, using derivative spectroscopy to determine CSF bilirubin. This procedure led to an increase in specificity to 1.00 (95% CI, 0.96–1.00) in our study population.

Clin Chem Lab Med 2006;44:938–48.

Keywords: bili-excess; bilirubin; blood pigments; cerebrospinal fluid; subarachnoid haemorrhage
Corresponding author: Joke J. Apperloo, PhD, Laboratory of Clinical Chemistry, Máxima Medical Centre, De Run 4600, 5500 MB Veldhoven, The Netherlands Phone: +31-40-8888900, Fax: +31-40-8888909,

References

1. Morgenstern LB, Luna-Gonzales H, Huber JC Jr, Wong SS, Uthman MO, Gurian JH, et al. Worst headache and subarachnoid haemorrhage: prospective, modern computed tomography and spinal fluid analysis. Ann Emerg Med 1998; 32:297–304.Search in Google Scholar

2. Wood MJ, Dimeski G, Nowitzke AM. CSF spectrophotometry in the diagnosis and exclusion of spontaneous subarachnoid haemorrhage. J Clin Neurosci 2005; 12:142–6.10.1016/j.jocn.2004.05.009Search in Google Scholar PubMed

3. Kassell NF, Torner JC, Haley EC Jr, Jane JA, Adams HP, Kongable GL. The international cooperative study on the timing of aneurysmal surgery. Part 1: overall management results. J Neurosurg 1990; 73:18–36.10.3171/jns.1990.73.1.0018Search in Google Scholar PubMed

4. Vermeulen M, van Gijn J. The diagnosis of subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 1990; 53:367–72.10.1136/jnnp.53.5.365Search in Google Scholar PubMed PubMed Central

5. Beetham R, Fahie-Wilson MN, Park D. What is the role of CSF spectrophotometry in the diagnosis of subarachnoid haemorrhage. Ann Clin Biochem 1998; 35:1–4.10.1177/000456329803500101Search in Google Scholar PubMed

6. UK National External Quality Assessment Scheme for Immunochemistry Working Group. National guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage. Ann Clin Biochem 2003;40:481–8.10.1258/000456303322326399Search in Google Scholar PubMed

7. O'Connell DM, Watson ID. Definitive angiographic detection of subarachnoid haemorrhage compared with laboratory assessment of intracranial bleed in CT-negative patients. Ann Clin Biochem 2003; 40:269–73.10.1258/000456303321610592Search in Google Scholar PubMed

8. Cruickshank AM. CSF spectrophotometry in the diagnosis of subarachnoid haemorrhage. J Clin Pathol 2001; 54:827–30.10.1136/jcp.54.11.827Search in Google Scholar PubMed PubMed Central

9. Fishman RA. Cerebrospinal fluid in diseases of the nervous system. London: WB Saunders, 1980.Search in Google Scholar

10. Jacobsson KE, Saveland H, Hillman J, Edner G, Zygmunt S, Pellettieri L. Warning leak and management outcome in aneurysmal subarachnoid haemorrhage. J Neurosurg 1996; 85:995–9.10.3171/jns.1996.85.6.0995Search in Google Scholar PubMed

11. Widjicks E, Kerkhoff H, van Gijn J. Long-term follow-up of 71 patients with thunderclap headache mimicking subarachnoid haemorrhage. Lancet 1988; 2:1247–8.Search in Google Scholar

12. Markus H. A prospective follow-up of thunderclap headache mimicking subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 1991; 54:1117–8.10.1136/jnnp.54.12.1117Search in Google Scholar PubMed PubMed Central

13. Heiserman J, Hodak J, Flom R, Bird R, Drayer B, Fram E. Neurologic complications of cerebral angiography. Am J Neuroradiol 1994; 15:1401–7.Search in Google Scholar

14. Cruickshank A, Beetham R, Holbrook I, Watson I, Wenham P, Keir G, et al. Spectrophotometry of cerebrospinal fluid in suspected subarachnoid haemorrhage. Br Med J 2005; 330:138.10.1136/bmj.330.7483.138Search in Google Scholar PubMed PubMed Central

15. Petzold MD, Keir G, Sharpe LT. Spectrophotometry for xanthochromia. N Engl J Med 2004; 351:1695–6.10.1056/NEJM200410143511627Search in Google Scholar

16. Kortbeek LH, Booij AC. Bilirubin excess, erythrophages and siderophages in differentiation of blood in cerebrospinal fluid. Clin Neurol Neurosurg 1979; 81:265–79.10.1016/0303-8467(79)90031-3Search in Google Scholar

17. Chalmers AH, Kiley M. Detection of xanthochromia in cerebrospinal fluid. Clin Chem 1998; 44:1740–2.10.1093/clinchem/44.8.1740Search in Google Scholar

18. Chalmers AH. Cerebrospinal fluid xanthochromia testing simplified. Clin Chem 2001; 47:338–41.10.1093/clinchem/47.1.147Search in Google Scholar

19. Prahl S. Tabulated molar extinction coefficients for hemoglobin in water. http://www.seas.upenn.edu/courses/belab/ReferenceFiles/Chemicals/hgbextdata.txt or http://omlc.ogi.edu/spectra/hemoglobin/moaveni.html.Search in Google Scholar

20. Burtis CA, Ashwood ER, editors. Tietz textbook of clinical chemistry, 2nd ed. Philadelphia, PA: WB Saunders, 1999:1171.Search in Google Scholar

21. Apperloo JJ, van der Graaf F, Scharnhorst V, Vader HL. Do we measure bilirubin correctly anno 2005? Clin Chem Lab Med 2005; 43:531–5.10.1515/CCLM.2005.092Search in Google Scholar PubMed

22. Gunawardena H, Beetham R, Scolding N, Lhatoo SD. Is cerebrospinal fluid spectrophotometry useful in CT scan-negative suspected subarachnoid haemorrhage? Eur Neurol 2004; 52:226–9.10.1159/000082162Search in Google Scholar PubMed

23. See for example http://webche.ent.ohiou.edu/che408/Error_Prop.PDF or http://www.rit.edu/~uphysics/uncertainties/Uncertaintiespart1.html#top.Search in Google Scholar

24. Marshall WJ. Clinical Chemistry, 4th ed. London: Mosby, 2000:6.Search in Google Scholar

25. Burtis CA, Ashwood ER, editors. Tietz textbook of clinical chemistry, 2nd ed. Philadelphia, PA: WB Saunders, 1999:1385.Search in Google Scholar

26. Viljoen A, Walker SW, Walker KS, Twomey PJ. Imprecision of cerebrospinal fluid net bilirubin absorbance. Clin Chem 2004; 50:1266–8.10.1373/clinchem.2004.034306Search in Google Scholar PubMed

27. Shah K, Richard K, Nicholas S, Edlow J. Incidence of traumatic lumbar puncture. Acad Emerg Med 2003; 10:151–4.10.1197/aemj.10.2.151Search in Google Scholar

28. O'Connell DM, Watson ID. Precision of computed spectrophotometric scans for heme pigments in subarachnoid hemorrhage makes interpretation reliable. Clin Chem 2005; 51:793–4.10.1373/clinchem.2004.043380Search in Google Scholar PubMed

29. Stroes JW, van Rijn HJ. Quantitative measurement of blood pigments in cerebrospinal fluid by derivative spectrophotometry. Ann Clin Biochem 1987; 24:189–97.10.1177/000456328702400213Search in Google Scholar PubMed

Received: 2005-11-3
Accepted: 2006-5-3
Published Online: 2006-7-31
Published in Print: 2006-8-1

©2006 by Walter de Gruyter Berlin New York

Articles in the same Issue

  1. Laboratory medicine in the 2000s: programmed death or rebirth?
  2. Polymorphisms of the inflammatory system and risk of ischemic cerebrovascular events
  3. Haptoglobin polymorphism in patients with preeclampsia
  4. Fifteen polymorphisms in endothelin-1, endothelin-2 and endothelin-receptor-A genotyped by four duplex assays and seven simple assays on a LightCycler using hybridization probes
  5. Optimization of an enzymatic method for the determination of lysosomal N-acetyl-β-D-hexosaminidase and β-glucuronidase in synovial fluid
  6. An improved laboratory protocol to assess subarachnoid haemorrhage in patients with negative cranial CT scan
  7. Association of aminothiols with the clinical outcome in hemodialysis patients: comparison of chromatography and immunoassay for homocysteine determination
  8. Poor prognosis indicated by nucleated red blood cells in peripheral blood is not associated with organ failure of the liver or kidney
  9. Detection of citrate overdose in critically ill patients on citrate-anticoagulated venovenous haemofiltration: use of ionised and total/ionised calcium
  10. Unchanged androgen-binding properties of sex hormone-binding globulin in male patients with liver cirrhosis
  11. Relationship between serum uric acid, creatinine, albumin and gestational diabetes mellitus
  12. Aminothiols in human brain tumors
  13. Measurement of carnitine in hemodialysis patients – adaptation of an enzymatic photometric method for an automatic analyzer
  14. A robust liquid chromatography tandem mass spectrometry method for total plasma homocysteine determination in clinical practice
  15. Establishment of reference distributions and decision values for thyroid antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and the thyrotropin receptor (TRAb)
  16. Effects of a long-distance run on cardiac markers in healthy athletes
  17. α-Tocopherol supplementation reduces the elevated 8-hydroxy-2-deoxyguanosine blood levels induced by training in basketball players
  18. Influence of the needle bore size used for collecting venous blood samples on routine clinical chemistry testing
  19. The ratio of apoB/apoAI, apoB and lipoprotein(a) are the best predictors of stable coronary artery disease
  20. Evaluation of the analytical performance of the advanced method for cardiac troponin I for the AxSYM platform: comparison with the old method and the Access system
  21. Preliminary performance evaluation of blood gas analyzers
  22. A cost-effectiveness evaluation of reticulocyte measurement in new outpatients with or without hematologic disorders
  23. Guidelines for setting up an External Quality Assessment Scheme for blood smear interpretation. Part II: survey preparation, statistical evaluation and reporting
  24. Free light chain testing in follow-up of multiple myeloma
  25. Blood reactive oxygen metabolites (ROMs) and total antioxidant status (TAS) in patients with laryngeal squamous cell carcinoma after surgical treatment
  26. SIBioC 2006 38th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology, Turin, Italy, September 19–22, 2006
  27. Third Santorini Biologie Prospective Conference 2006: From Human Genetic Variations to Prediction of Risks and Responses to Drugs and the Environment, Santorini Island, Greece, September 29 - October 2, 2006
https://doi.org/10.1515/CCLM.2006.171
Keywords for this article
bili-excess; bilirubin; blood pigments; cerebrospinal fluid; subarachnoid haemorrhage

Articles in the same Issue

  1. Laboratory medicine in the 2000s: programmed death or rebirth?
  2. Polymorphisms of the inflammatory system and risk of ischemic cerebrovascular events
  3. Haptoglobin polymorphism in patients with preeclampsia
  4. Fifteen polymorphisms in endothelin-1, endothelin-2 and endothelin-receptor-A genotyped by four duplex assays and seven simple assays on a LightCycler using hybridization probes
  5. Optimization of an enzymatic method for the determination of lysosomal N-acetyl-β-D-hexosaminidase and β-glucuronidase in synovial fluid
  6. An improved laboratory protocol to assess subarachnoid haemorrhage in patients with negative cranial CT scan
  7. Association of aminothiols with the clinical outcome in hemodialysis patients: comparison of chromatography and immunoassay for homocysteine determination
  8. Poor prognosis indicated by nucleated red blood cells in peripheral blood is not associated with organ failure of the liver or kidney
  9. Detection of citrate overdose in critically ill patients on citrate-anticoagulated venovenous haemofiltration: use of ionised and total/ionised calcium
  10. Unchanged androgen-binding properties of sex hormone-binding globulin in male patients with liver cirrhosis
  11. Relationship between serum uric acid, creatinine, albumin and gestational diabetes mellitus
  12. Aminothiols in human brain tumors
  13. Measurement of carnitine in hemodialysis patients – adaptation of an enzymatic photometric method for an automatic analyzer
  14. A robust liquid chromatography tandem mass spectrometry method for total plasma homocysteine determination in clinical practice
  15. Establishment of reference distributions and decision values for thyroid antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and the thyrotropin receptor (TRAb)
  16. Effects of a long-distance run on cardiac markers in healthy athletes
  17. α-Tocopherol supplementation reduces the elevated 8-hydroxy-2-deoxyguanosine blood levels induced by training in basketball players
  18. Influence of the needle bore size used for collecting venous blood samples on routine clinical chemistry testing
  19. The ratio of apoB/apoAI, apoB and lipoprotein(a) are the best predictors of stable coronary artery disease
  20. Evaluation of the analytical performance of the advanced method for cardiac troponin I for the AxSYM platform: comparison with the old method and the Access system
  21. Preliminary performance evaluation of blood gas analyzers
  22. A cost-effectiveness evaluation of reticulocyte measurement in new outpatients with or without hematologic disorders
  23. Guidelines for setting up an External Quality Assessment Scheme for blood smear interpretation. Part II: survey preparation, statistical evaluation and reporting
  24. Free light chain testing in follow-up of multiple myeloma
  25. Blood reactive oxygen metabolites (ROMs) and total antioxidant status (TAS) in patients with laryngeal squamous cell carcinoma after surgical treatment
  26. SIBioC 2006 38th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology, Turin, Italy, September 19–22, 2006
  27. Third Santorini Biologie Prospective Conference 2006: From Human Genetic Variations to Prediction of Risks and Responses to Drugs and the Environment, Santorini Island, Greece, September 29 - October 2, 2006
Downloaded on 8.4.2026 from https://www.degruyterbrill.com/document/doi/10.1515/CCLM.2006.171/html
Scroll to top button