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01-05-2019 | Original Article

Post-mortem in situ stability of serum markers of cerebral damage and acute phase response

Authors: Benjamin Ondruschka, Lina Woydt, Michael Bernhard, Heike Franke, Holger Kirsten, Sabine Löffler, Dirk Pohlers, Niels Hammer, Jan Dreßler

Published in: International Journal of Legal Medicine | Issue 3/2019

Abstract

The aim of the given study was to test the in situ stability of biochemical markers of cerebral damage and acute phase response in the early post-mortem interval to assess their usability for forensic pathology. A monocentric, prospective study investigated post-mortem femoral venous blood samples at four time points obtained within 48 h post-mortem starting at the death of 20 deceased, using commercial immunoassays for the ten parameters: S100 calcium-binding protein B (S100B), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), ferritin, soluble tumor necrosis factor receptor type 1 (sTNFR1), and lactate dehydrogenase (LDH). Significant changes in serum levels were observed only later than 2 h after death for all markers. Inter-laboratory comparability was high, and intra-assay precision was sufficient for most markers. Most of the biomarker levels depended on the severity of hemolysis and lipemia but were robust against freeze-thaw cycles. Serum levels increased with longer post-mortem intervals for S100B, NSE, ferritin, sTNFR1, and LDH (for all p < 0.001) but decreased over this period for CRP (p = 0.089) and PCT (p < 0.001). Largely unchanged median values were found for GFAP (p = 0.139), BDNF (p = 0.106), and IL-6 (p = 0.094). Serum levels of CRP (p = 0.059) and LDH (p = 0.109) did not differ significantly between the final ante-mortem (resuscitation) and the first post-mortem sample (moment of death). Collecting the post-mortem blood sample as soon as possible will reduce the influence of post-mortem blood changes. Serum GFAP for detection of cerebral damage as well as serum IL-6 and CRP as proof of acute phase response seemed to be preferable due to their in situ stability in the first 2 days after death.

Coe J (1993) Post-mortem chemistry update. Emphasis on forensic application. Am J Forensic Med Pathol 14:91–111PubMed

Palmiere C, Mangin P (2012a) Post-mortem chemistry update part I. Int J Legal Med 126:187–198PubMed

Palmiere C, Mangin P (2012b) Post-mortem chemistry update part II. Int J Legal Med 126:199–215PubMed

Maeda H, Zhu BL, Ishikawa T, Quan L, Michiue T (2009) Significance of post-mortem biochemistry in determining the cause of death. Legal Med 11:46–49

Luna A (2009) Is post-mortem biochemistry really useful? Why is it not widely used in forensic pathology? Legal Med 11:27–30

Ondruschka B, Schuch S, Pohlers D, Franke H, Dreßler J (2018) Acute phase response after fatal traumatic brain injury. Int J Legal Med 132:531–539.PubMed

Ondruschka B, Sieber M, Kirsten H; Franke H, Dreßler J (2018) Measurement of cerebral biomarkers proving traumatic brain injuries in post-mortem body fluids. J Neurotrauma 35:2044–2055.PubMed

Sieber M, Dreßler J, Franke, Pohlers D, Ondruschka B (2018) Post-mortem biochemistry of NSE and S100B. A supplemental tool for detecting a lethal traumatic brain injury? J Forensic Legal Med 55:65–73.

Woodcock T, Morganti-Kossmann MC (2013) The role of markers of inflammation in traumatic brain injury. Front Neurol 4:18PubMedPubMedCentral

10.

Tsokos M, Reichelt U, Jung R, Nierhaus A, Püschel K (2001) Interleukin-6 and C-reactive protein serum levels in sepsis-related fatalities during the early postmortem period. Forensic Sci Int 119:47–56.PubMed

11.

Tsokos M, Reichelt U, Nierhaus A, Püschel K (2001) Serum procalcitonin (PCT): a valuable biochemical parameter for the post-mortem diagnosis of sepsis. Int J Legal Med 114:237–243.PubMed

12.

Soar J, Nolan JP, Böttiger BW, Perkins GD, Loot C, Carli P, Pellis T, Sandroni C, Skrifvars MB, Smith GB, Sunde K, Deakin CD et al (2015) European resuscitation council guidelines for resuscitation 2015. Section 3. Adult advanced life support. Resuscitation 95:100–147PubMed

13.

Hess C, Krueger L, Unger M, Madea B (2017) Freeze- and -thaw stability and long-term-stability of 84 synthetic cannabinoids in serum. Drug Test Anal 9:1506–1511PubMed

14.

German Medical Assocation (2015) Revision of the “Guideline of the German Medical Association on quality assurance in medical laboratory examinations - Rili-BAEK”. J Lab Med 39:26–69

15.

Ishikawa T, Hamel M, Zhu B-L, Li D-R, Zhao D, Michiue T, Maeda H (2008) Comparative evaluation of postmortem serum concentrations of neopterin and C-reactive protein. Forensic Sci Int 179:135–143PubMed

16.

Palmiere C, Bardy D, Mangin P, Augsburger M (2013) Value of sTREM-1, procalcitonin and CRP as laboratory parameters for postmortem diagnosis of sepsis. J Inf Secur 67:545–555

17.

Bode-Jänisch S, Schütz S, Schmidt A, Tschernig T, Debertin AS, Fieguth A, Hagemeier L, Teske J, Suerbaum S, Klintschar M, Bange FC (2013) Serum procalcitonin levels in the postmortem diagnosis of sepsis. Forensic Sci Int 226:266–272PubMed

18.

Majdan M, Plancikova D, Brazinova A, Rusnak M, Nieboer D, Feigin V, Maas A (2016) Epidemiology of traumatic brain injuries in Europe: a cross-sectional analysis. Lancet Public Health 1:e76–e83PubMed

19.

Blennow K, Brody DL, Kochanek PM, Levin H, McKee A, Ribbers GM, Yaffe K, Zetterberg H (2016) Traumatic brain injuries. Nat Rev Dis Primers 2:16084PubMed

20.

Chirica VI (2017) Useful markers to assess traumatic and hypoxic brain injury. Rom J Legal Med 25:146–151

21.

Wang KK, Yang Z, Zhu T, Shi Y, Rubenstein R, Tyndall JA, Manley GT (2018) An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Rev Mol Diagn 18:165–180PubMedPubMedCentral

22.

Li DR, Zhu BL, Ishikawa T, Zhao D, Michiue T, Maeda H (2006a) Postmortem serum protein S100B levels with regard to the cause of death involving brain damage in medicolegal autopsy cases. Legal Med 8:71–77PubMed

23.

Li DR, Zhu BL, Ishikawa T, Zhao D, Michiue T, Maeda H (2006b) Immunohistochemical distribution of S-100 protein in the cerebral cortex with regard to the cause of death in forensic autopsy. Legal Med 8:78–85PubMed

24.

Goede A, Dreßler J, Sommer G, Schober K, Franke H, Ondruschka B (2015) Wundalterdiagnostik nach letalem Schädel-Hirn-Trauma. Rechtsmedizin 25:261–267

25.

Ondruschka B, Pohlers D, Sommer G, Schober K, Teupser D, Franke H, Dreßler J (2013) S100B and NSE as useful postmortem biochemical markers of traumatic brain injury in autopsy cases. J Neurotrauma 30:1862–1871

26.

Osuna E, Perez-Carceles MD, Luna A, Pounder DJ (1992) Efficacy of cerebro-spinal fluid biochemistry in the diagnosis of brain insult. Forensic Sci Int 52:193–198PubMed

27.

Raabe A, Kopetsch O, Groß U, Zimmermann M, Gebhart P (2003) Measurements of serum S-100B protein: effects of storage time and temperature on pre-analytical stability. Clin Chem Lab Med 41:700–703PubMed

28.

Beaudeux JL, Léger P, Dequen L, Gandjbakhch I, Coriat P, Foglietti MJ (2000) Influence of hemolysis on the measurement of S-100 protein and neuron-specific enolase plasma concentrations during coronary artery bypass grafting. Clin Chem 46:989–990PubMed

29.

Missler U, Wiesmann M, Wittmann G (1999) Measurement of glial fibrillary acidic protein in human blood: analytical method and preliminary clinical results. Clin Chem 45:138–141PubMed

30.

Ramont L, Thoannes H, Volondat, Chastang F, Millet MC, Maquart FX (2005) Effects of hemolysis and storage condition on neuron-specific enolase (NSE) in cerebrospinal fluid and serum: implications in clinical practice. Clin Chem Lab Med 43:1215–1217PubMed

31.

Verfaillie CJ, Delanghe JR (2010) Hemolysis correction factor in the measurement of serum neuron-specific enolase. Clin Chem Lab Med 48:891–892PubMed

32.

Korley FK, Diaz-Arrastia R, Wu AH, Yue JK, Manley GT, Sair HI, Van Eyk J, Everett AD et al (2016) Circulating brain-derived neurotrophic factor has diagnostic and prognostic value in traumatic brain injury. J Neurotrauma 33:215–225PubMedPubMedCentral

33.

Failla MD, Conley YP, Wagner AK (2016) Brain-derived neurotrophic factor (BDNF) in traumatic brain injury-related mortality: interrelationships between genetics and acute systemic and central nervous system BDNF profiles. Neurorehabil Neural Repair 30:83–93PubMed

34.

Tsokos M (2007) Postmortem diagnosis of sepsis. Forensic Sci Int 165:155–164PubMed

35.

Mimasaka S, Funayama M, Hashiyada M, Nata M, Tsunenari S (2007) Significance of levels of IL-6 and IL-8 after trauma. A study of 11 cytokines post-mortem using multiplex immunoassay. Injury 38:1047–1051PubMed

36.

Schrag B, Roux-Lombard P, Schneiter D, Vaucher P, Mangin P, Palmiere C (2012) Evaluation of C-reactive protein, procalcitonin, tumor necrosis factor alpha, interleukin-6, and interleukin-8 as diagnostic parameters in sepsis-related fatalities. Int J Legal Med 126:505–512PubMed

37.

Fujita MQ, Zhu B-L, Ishida K, Quan L, Oritani S, Maeda H (2002) Serum C-reactive protein levels in postmortem blood—an analysis with special reference to the cause of death and survival time. Forensic Sci Int 130:160–166PubMed

38.

Astrup BS, Thomsen JL (2007) The routine use of C-reactive protein in forensic investigations. Forensic Sci Int 172:49–55PubMed

39.

Maeda H, Zhu B-L, Bessho Y, Ishikawa T, Quan L, Michiue T, Zhao D, Li D-R, Komatsu A (2008) Postmortem serum nitrogen compounds and C-reactive protein levels with special regard to investigation of fatal hyperthermia. Forensic Sci Med Pathol 4:175–180PubMed

40.

Uhlin-Hansen L (2001) C-reactive protein (CRP), a comparison of pre- and post-mortem blood levels. Forensic Sci Int 124:32–35PubMed

41.

Palmiere C, Augsburger M (2014) Markers for sepsis diagnosis in the forensic setting. State of the art. Croat Med J 55:103–114PubMed

42.

Schmidt S, Windgassen M, Nofer J-R, Pfeiffer H, Ribbecke S, Schmeling A (2015) Procalcitonin as a postmortem sepsis marker. A comparison of the validity of results obtained from blood serum, aqueous humour and cerebrospinal fluid. Int J Legal Med 129:117–123PubMed

43.

Ramsthaler F, Kettner M, Mall G, Bratzke H (2008) The use of rapid diagnostic test of procalcitonin serum levels for the postmortem diagnosis of sepsis. Forensic Sci Int 178:139–145PubMed

44.

Meisner M, Tschaikowsky K, Schnabel S, Schmidt J, Katalinic A, Schüttler J (1997) Procalcitonin - influence of temperature, storage, anticoagulation and arterial or venous asservation of blood samples on procalcitonin concentrations. Clin Chem Lab Med 35:597–602.

45.

Madea B, Musshoff F (2007) Post-mortem biochemistry. Forensic Sci Int 165:165–171PubMed

46.

Flanagan RJ (2017) Post-mortem biochemistry and toxicology. Arab J For Sci For Med 1:540–552

47.

Hanrieder J, Wetterhall M, Enblad P, Hillered L, Bergquist J (2009) Temporally resolved differential proteomic analysis of human ventricular CSF for monitoring traumatic brain injury biomarker candidates. J Neurosci Methods 177:469–478PubMed

Title: Post-mortem in situ stability of serum markers of cerebral damage and acute phase response
Authors: Benjamin Ondruschka
Lina Woydt
Michael Bernhard
Heike Franke
Holger Kirsten
Sabine Löffler
Dirk Pohlers
Niels Hammer
Jan Dreßler
Publication date: 01-05-2019
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Legal Medicine / Issue 3/2019
Print ISSN: 0937-9827
Electronic ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-018-1925-2

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Springer Medicine

Post-mortem in situ stability of serum markers of cerebral damage and acute phase response

Abstract

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Abstract

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