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

Int J Legal Med. 2019 May;133(3):871-881. doi: 10.1007/s00414-018-1925-2. Epub 2018 Aug 30.

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.

Keywords: Acute phase response; Intra-individual stability; Post-mortem biochemistry; Serum; Thanatochemistry; Traumatic brain injury.

MeSH terms

  • Acute-Phase Reaction*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood*
  • Brain Injuries / blood*
  • Brain-Derived Neurotrophic Factor / blood
  • C-Reactive Protein / analysis
  • Female
  • Ferritins / blood
  • Glial Fibrillary Acidic Protein / blood
  • Humans
  • Immunoassay
  • Interleukin-6 / blood
  • L-Lactate Dehydrogenase / blood
  • Male
  • Middle Aged
  • Phosphopyruvate Hydratase / blood
  • Postmortem Changes*
  • Procalcitonin / blood
  • Prospective Studies
  • Receptors, Tumor Necrosis Factor, Type I / blood
  • S100 Calcium Binding Protein beta Subunit / blood

Substances

  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Glial Fibrillary Acidic Protein
  • Interleukin-6
  • Procalcitonin
  • Receptors, Tumor Necrosis Factor, Type I
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • C-Reactive Protein
  • Ferritins
  • L-Lactate Dehydrogenase
  • Phosphopyruvate Hydratase