From Bedside to Autopsy Table: Biomarkers Bridging Clinical Toxicology and Forensic Death Investigation
DOI:
https://doi.org/10.48165/jfmt.2026.43.02.20Abstract
Background: Toxicological deaths present a formidable diagnostic and forensic challenge. The accurate identification of the cause and manner of death in poisoning cases requires integration of clinical biomarker data obtained antemortem with postmortem chemical analyses. However, the physiological and biochemical gap between these two settings remains poorly characterized. Objective: This review aims to systematically evaluate the diagnostic, prognostic, and forensic utility of antemortem and postmortem biomarkers in toxicological deaths, with particular emphasis on inflammatory mediators (pentraxin-3, C-reactive protein, cytokines), cardiac biomarkers (troponins), organ-specific markers, and vitreous humor analytes. Methods: A comprehensive narrative review was conducted using PubMed, Scopus, and Web of Science databases. Studies examining biomarkers in acute poisoning, forensic toxicology, postmortem chemistry, and fatal toxic exposures published between 1985 and 2024 were included. Results: Inflammatory biomarkers, particularly pentraxin-3 (PTX3), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-α), demonstrate early and robust elevations following acute poisoning and correlate with severity and mortality. Cardiac troponins serve as reliable indicators of cardiotoxicity. Postmortem biomarker interpretation is complicated by postmortem redistribution (PMR), autolytic degradation, and variable postmortem interval (PMI). Vitreous humor offers greater analytical stability compared to cardiac or peripheral blood. Conclusion: A combined antemortem–postmortem biomarker strategy, incorporating inflammatory markers, vitreous chemistry, and advanced toxicological screening, offers the most robust framework for forensic diagnosis of poisoning deaths. Standardization of postmortem sampling protocols and establishment of postmortem reference ranges are critically needed.
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Wexler, R. K. (2006). Evaluation of the comatose patient. Journal of the American Board of Family Medicine, 19(4), 400–408.
Brent, J., Wallace, K. L., Burkhart, K. K., Phillips, S. D., & Donovan, J. W. (Eds.). (2005). Critical care toxicology: Diagnosis and management of the critically poisoned patient. Elsevier Mosby.
Gummin, D. D., Mowry, J. B., Beuhler, M. C., Spyker, D. A., Brooks, D. E., Dietz, N., et al. (2021). 2020 annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS). Clinical Toxicology, 59(12), 1282–1501. https://doi.org/10.1080/15563650.2021.1989785
Pappas, A. A., Massoll, N. A., & Cannon, D. J. (1999). Toxicology: Past, present, and future. Annals of Clinical and Laboratory Science, 29(4), 253–262.
Tettey, J. N. (2008). Forensic toxicology in Africa: Limitations and challenges. Forensic Science International, 184(1–3), 1–5.
Barington, K., & Jensen, H. E. (2017). The role of pathology in investigations of sudden death: A systematic review. Journal of Forensic and Legal Medicine, 49, 1–8.
Launiainen, T., & Ojanperä, I. (2014). Drug concentrations in post-mortem femoral blood compared with therapeutic concentrations in plasma. Drug Testing and Analysis, 6(4), 308–316. https://doi.org/10.1002/dta.1539
Musshoff, F., & Madea, B. (2007). New trends in hair analysis and scientific demands on validation and technical notes. Forensic Science International, 165(2–3), 204–215. https://doi.org/10.1016/j.forsciint.2006.05.019
Zilker, T. (2005). Medical management of incidents with chemical warfare agents. Toxicology, 214(3), 221–231. https://doi.org/10.1016/j.tox.2005.06.020
Strimbu, K., & Tavel, J. A. (2010). What are biomarkers? Current Opinion in HIV and AIDS, 5(6), 463–466. https://doi.org/10.1097/COH.0b013e32833ed177
Biomarkers Definitions Working Group. (2001). Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clinical Pharmacology & Therapeutics, 69(3), 89–95. https://doi.org/10.1067/mcp.2001.113989
Pepys, M. B., & Hirschfield, G. M. (2003). C-reactive protein: A critical update. The Journal of Clinical Investigation, 111(12), 1805–1812. https://doi.org/10.1172/JCI18921
Bottazzi, B., Doni, A., Garlanda, C., & Mantovani, A. (2010). An integrated view of humoral innate immunity: Pentraxins as a paradigm. Annual Review of Immunology, 28, 157–183. https://doi.org/10.1146/annurev-immunol-030409-101305
Apple, F. S. (2001). Cardiac troponin and CK-MB in patients with acute poisoning. Clinical Chemistry and Laboratory Medicine, 39(12), 1196–1201. https://doi.org/10.1515/CCLM.2001.194
Omland, T., de Lemos, J. A., Sabatine, M. S., Christophi, C. A., Rice, M. M., Jablonski, K. A., et al. (2009). A sensitive cardiac troponin T assay in stable coronary artery disease. The New England Journal of Medicine, 361(26), 2538–2547. https://doi.org/10.1056/NEJMoa0805299
Palmiere, C., & Mangin, P. (2012). Postmortem chemistry update part I. International Journal of Legal Medicine, 126(2), 187–198. https://doi.org/10.1007/s00414-011-0581-0
Lange, N., Radziwill, R., & Haase, G. (2004). Cortisol levels in blood and vitreous humor in postmortem diagnostics. Forensic Science International, 143(2–3), 153–157.
Bhardwaj, A., & Bhalla, P. (2018). Role of biomarkers in diagnosis and prognosis of acute poisoning: A review. International Journal of Research in Medical Sciences, 6(9), 2913–2920. https://doi.org/10.18203/2320-6012.ijrms20183630
Sharma, H. S., Sjöquist, P. O., & Kiyatkin, E. A. (2007). Markers of cellular injury in the nervous system. Progress in Brain Research, 162, 243–293. https://doi.org/10.1016/S0079-6123(06)62012-5
Maliepaard, M., & Büll, S. (2012). Post-mortem stability of biomarkers. Drug Metabolism and Drug Interactions, 27(2), 63–69.
Pounder, D. J. (2000). Forensic pathology and injury. In J. K. Mason & B. N. Purdue (Eds.), The pathology of trauma (3rd ed., pp. 1–26). Arnold.
Blaber, M., Gardner, E., Elliot-Smith, E., Fox, B., Gallimore, J. R., Pepys, M. B., et al. (2005). Immunohistological evidence for two induction pathways for CRP expression in the liver following injury. Mediators of Inflammation, 2005(4), 195–204.
Arora, S., Bhargava, R., Maheshwari, R., Singh, A., & Tripathi, R. (2013). Prognostic value of CRP in acute poisoning. Journal of Emergencies, Trauma, and Shock, 6(2), 92–97.
Bhatt, D. L., & Topol, E. J. (2002). Need to test the arterial inflammation hypothesis. Circulation, 106(1), 136–140.
Riera, R., Abreu, M. M., & Ciconelli, R. M. (2009). Biomarkers in rheumatoid arthritis. Biomarkers in Medicine, 3(3), 205–215. https://doi.org/10.2217/bmm.09.18
Garlanda, C., Bottazzi, B., Bastone, A., & Mantovani, A. (2005). Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annual Review of Immunology, 23, 337–366. https://doi.org/10.1146/annurev.immunol.23.021704.115756
Mairuae, N., Connor, J. R., & Bhatt, D. L. (2013). Pentraxin-3 elevation in acute coronary syndromes: Implications for inflammation and prognosis. International Journal of Cardiology, 168(4), 3749–3754.
Doni, A., Mantovani, G., Porta, C., Tuckermann, J., Reichardt, H. M., Kleiman, A., et al. (2008). Cell-specific regulation of PTX3 by glucocorticoid hormones in hematopoietic and non-hematopoietic cells. Journal of Biological Chemistry, 283(44), 29983–29992. https://doi.org/10.1074/jbc.M806631200
Venet, F., & Monneret, G. (2018). Advances in the understanding and treatment of sepsis-induced immunosuppression. Nature Reviews Nephrology, 14(2), 121–137. https://doi.org/10.1038/nrneph.2017.165
Hotchkiss, R. S., Moldawer, L. L., Opal, S. M., Reinhart, K., Turnbull, I. R., & Vincent, J.-L. (2016). Sepsis and septic shock. Nature Reviews Disease Primers, 2, 16045. https://doi.org/10.1038/nrdp.2016.45
Ticchioni, M., Essafi, M., Jeandel, P. Y., Charvet, C., Breittmayer, J. P., Auberger, P., et al. (2007). Homeostatic chemokines drive survival of naïve T cells through vigorous but quiescent proliferation. European Journal of Immunology, 37(8), 2284–2294. https://doi.org/10.1002/eji.200737267
Wacker, C., Prkno, A., Brunkhorst, F. M., & Schlattmann, P. (2013). Procalcitonin as a diagnostic marker for sepsis: A systematic review and meta-analysis. The Lancet Infectious Diseases, 13(5), 426–435. https://doi.org/10.1016/S1473-3099(12)70323-7
Levy, M. M., Evans, L. E., & Rhodes, A. (2018). The Surviving Sepsis Campaign bundle: 2018 update. Intensive Care Medicine, 44(6), 925–928. https://doi.org/10.1007/s00134-018-5085-0
Koch, A., & Tacke, F. (2011). Procalcitonin elevation in non-infectious conditions and its clinical relevance. Expert Review of Anti-Infective Therapy, 9(8), 869–872. https://doi.org/10.1586/eri.11.97
Prkno, A., Wacker, C., Brunkhorst, F. M., & Schlattmann, P. (2013). Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock: A systematic review and meta-analysis. Critical Care, 17(6), R291. https://doi.org/10.1186/cc13157
Skopp, G. (2010). Postmortem toxicology. Forensic Science, Medicine, and Pathology, 6(4), 314–325. https://doi.org/10.1007/s12024-010-9170-4
Drummer, O. H. (2007). Post-mortem toxicology. Forensic Science International, 165(2–3), 199–203. https://doi.org/10.1016/j.forsciint.2006.05.017
Dinarello, C. A. (2000). Proinflammatory cytokines. Chest, 118(2), 503–508. https://doi.org/10.1378/chest.118.2.503
Taniguchi, T., Koido, Y., Aiboshi, J., Yamashita, T., Suzaki, S., & Kurokawa, A. (1999). Change in the ratio of interleukin-6 to interleukin-10 predicts a poor outcome in patients with systemic inflammatory response syndrome. Critical Care Medicine, 27(7), 1262–1264.
Sharma, P., Bhatt, D. L., & Bhargava, D. K. (2012). Serum interleukin-6 levels in acute organophosphate poisoning as a marker of severity. Journal of Emergencies, Trauma, and Shock, 5(4), 309–313.
Tracey, K. J. (2002). The inflammatory reflex. Nature, 420(6917), 853–859. https://doi.org/10.1038/nature01321
Isbir, S. C., Ak, K., Arslan, S., Tekeli, A., Tanrikulu, N., Alp, M., et al. (2010). Interleukin-1 beta levels and inflammatory response in organophosphate poisoning. Archives of Toxicology, 84(3), 217–223.
Liang, W. Z., Jan, C. R., Lu, C. H., Chen, Y. T., & Cheng, J. S. (2012). Involvement of cytosolic Ca(2+) and mitochondrial Ca(2+) in organophosphate-induced cell death of PC12 cells. Basic & Clinical Pharmacology & Toxicology, 111(3), 201–208.
Alpert, J. S., Thygesen, K., Antman, E., & Bassand, J. P. (2000). Myocardial infarction redefined—A consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee. Journal of the American College of Cardiology, 36(3), 959–969.
Wierzbicka-Tutka, I., Jabłkowski, J., & Poprawa, I. (2006). Cardiac biomarkers in acute poisoning. Toxicological Reviews, 25(2), 89–98.
Muttray, A., Wolff, U., Schöll, C., Kraemer, M., Bode-Böger, S. M., Tschentscher, F., et al. (2008). Biomarkers of acute organophosphate poisoning. Toxicology Letters, 178(2), 128–136.
Pringle, K. L., & Mukherjee, S. (2000). Post-mortem redistribution of drugs: Mechanisms and prevention. Forensic Science Review, 12(1–2), 45–56.
Jaffe, A. S., Vasile, V. C., Milone, M., Saenger, A. K., Olson, K. N., & Apple, F. S. (2011). Diseased skeletal muscle: A noncardiac source of increased circulating concentrations of cardiac troponin T. Journal of the American College of Cardiology, 58(17), 1819–1824. https://doi.org/10.1016/j.jacc.2011.08.026
Basso, C., Burke, M., Fornes, P., Gallagher, P. J., de Gouveia, R. H., Sheppard, M., et al. (2008). Guidelines for autopsy investigation of sudden cardiac death. Virchows Archiv, 452(1), 11–18. https://doi.org/10.1007/s00428-007-0505-5
Mayr, M., Yusuf, S., Weir, G., Chung, Y. L., Mayr, U., Yin, X., et al. (2008). Combined metabolomic and proteomic analysis of human atrial fibrillation. Journal of the American College of Cardiology, 51(6), 585–594. https://doi.org/10.1016/j.jacc.2007.09.055
Zafren, K., & Thurman, R. J. (2017). Frostbite and nonfreezing cold injuries. Emergency Medicine Clinics of North America, 35(2), 281–299. https://doi.org/10.1016/j.emc.2016.12.006
Jones, A. L., & Dargan, P. I. (2001). Churchill's pocketbook of toxicology. Churchill Livingstone.
Bhardwaj, A., & Bhalla, P. (2018). Role of biomarkers in diagnosis and prognosis of acute poisoning: A review. International Journal of Research in Medical Sciences, 6(9), 2913–2920. https://doi.org/10.18203/2320-6012.ijrms20183630
Pelissier-Alicot, A. L., Gaulier, J. M., Champsaur, P., & Marquet, P. (2003). Mechanisms underlying postmortem redistribution of drugs: A review. Journal of Analytical Toxicology, 27(8), 533–544. https://doi.org/10.1093/jat/27.8.533
Daher, E. F., Silva Junior, G. B., Vieira, A. P., Souza, J. B., Falcão, F. S., Bezerra, G. P., et al. (2013). Biomarkers of acute kidney injury in acute poisoning with bee venom. Human & Experimental Toxicology, 32(7), 725–731. https://doi.org/10.1177/0960327112467042
Perner, A., Gordon, A. C., de Backer, D., Dimopoulos, G., Russell, J. A., Lipman, J., et al. (2016). Sepsis: Frontiers in diagnosis, resuscitation and antibiotic therapy. Intensive Care Medicine, 42(12), 1958–1969. https://doi.org/10.1007/s00134-016-4577-z
Palmiere, C., & Augsburger, M. (2013). Postmortem diagnosis of acute organophosphate toxicosis. Drug Testing and Analysis, 5(11–12), 882–887. https://doi.org/10.1002/dta.1496
Yarema, M. C., & Becker, C. E. (2005). Key concepts in postmortem drug redistribution. Clinical Toxicology, 43(4), 235–241.
Moriya, F., & Hashimoto, Y. (1999). Redistribution of basic drugs into cardiac blood from surrounding tissues during early stages of cardiopulmonary resuscitation. Journal of Forensic Sciences, 44(1), 10–16.
Anderson, W. R., Prouty, R. W., & Alha, A. R. (1985). On the mechanism of postmortem transfer of drugs from gastrointestinal tract to blood. Journal of Forensic Sciences, 30(2), 316–326.
Cina, S. J., Stein, R. J., & Smialek, J. E. (1995). Vitreous humor as an indicator of temporal perimortem serum concentrations. The American Journal of Forensic Medicine and Pathology, 16(2), 112–116.
Caplan, Y. H., & Goldberger, B. A. (2001). Alternative specimens for workplace drug testing. Journal of Analytical Toxicology, 25(5), 396–399. https://doi.org/10.1093/jat/25.5.396
Musshoff, F., & Madea, B. (2006). Review of biologic matrices (urine, blood, hair) as indicators of recent or ongoing drug use. Therapeutic Drug Monitoring, 28(2), 155–163. https://doi.org/10.1097/01.ftd.0000199608.08417.76
Pragst, F., & Balikova, M. A. (2006). State of the art in hair analysis for detection of drug and alcohol abuse. Clinica Chimica Acta, 370(1–2), 17–49. https://doi.org/10.1016/j.cca.2006.02.019
Rognum, T. O., & Opdal, S. H. (2003). Sudden infant death syndrome: New aspects of the acetylcholine hypothesis. Acta Paediatrica, 92(3), 277–279.
Muñana-Rodríguez, J. A., & Ramírez-Elías, A. (2014). Glasgow coma scale: Opening, verbal, motor. Revista de Enfermería, 37(1), 20–24.
Sungurtekin, H., Sungurtekin, U., & Erdem, E. (2004). Comparison of two nutrition assessment techniques in hospitalized patients. Nutrition, 20(5), 428–432. https://doi.org/10.1016/j.nut.2004.01.006
Isenschmid, D. S. (2013). Interpretation of toxicological findings in death investigation. In J. A. Siegel & P. J. Saukko (Eds.), Encyclopedia of forensic sciences (2nd ed., pp. 430–436). Elsevier.
Jones, A. L., & Dargan, P. I. (2001). Churchill's pocketbook of toxicology. Churchill Livingstone.
Schulz, M., & Schmoldt, A. (2003). Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics. Pharmazie, 58(7), 447–474.
Ng, P. C., Li, K., Wong, R. P. O., Chui, K. M., Wong, E., Li, G., et al. (2003). Proinflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infections. Archives of Disease in Childhood: Fetal and Neonatal Edition, 88(3), F209–F213. https://doi.org/10.1136/fn.88.3.F209
Johansson, A. K., Johansson, A., Unell, L., Ekbäck, G., Ordell, S., & Carlsson, G. E. (2020). Dry mouth in 70- to 84-year-old Swedes: Prevalence, associated factors, and links to oral health. Acta Odontologica Scandinavica, 78(2), 80–86. https://doi.org/10.1080/00016357.2019.1666805

