Victims of Lethal Hypothermia Have Decreased Levels of Thrombomodulin in Myocardium and Urine

Overview

Journal Int J Legal Med

Specialty Forensic Sciences

Date 2014 Dec 29

PMID 25543320

Citations 5

Authors

Lasse Pakanen

Helena Kaija

Marja-Leena Kortelainen

Terttu Sarkioja

Katja Porvari

Affiliations

Soon will be listed here.

Abstract

Severe cold stress has been shown to cause changes in the expression and secretion of thrombomodulin (TM), an endothelial protein regulating haemostasis and inflammation. To further evaluate TM as a cold stress indicator, relative TM mRNA and TM protein levels in the myocardium and the concentrations of TM in serum and urine were analysed in different causes of death (hypothermia main cause, n = 80; hypothermia contributory cause, n = 26; cardiovascular disease (CVD) main cause, n = 94; trauma main cause, n = 45; other main cause, n = 25). Urinary catecholamine concentrations and myocardial heat shock factor 1 (HSF1) transcript levels were also studied. The TM mRNA and the TM protein levels in myocardium and urine were significantly lower in hypothermia deaths than those in the controls. Post-mortem interval did not correlate with urinary TM concentration. The sensitivity and specificity of urinary TM assay to detect hypothermia deaths were 70.8 and 70.3 %, respectively. Catecholamine concentrations in urine correlated significantly with TM concentration in urine and TM mRNA levels in all groups excluding CVD deaths. There were no differences in the HSF1 transcript levels and no correlation to TM levels. These findings provide further evidence that cold stress and hypothermia affect TM expression and secretion and that they are possibly linked to catecholamine action. Thus, measuring post-mortem TM levels may provide additional support to diagnosing hypothermia in medico-legal examination. The results may also provide additional knowledge for the treatment of hypothermic patients and the use of hypothermia for medical purposes.

Citing Articles

Immunohistochemical insights into hypothermia-related deaths: a systematic review.

Tomassini L, Lancia M, Gambelunghe C, Ricchezze G, Fedeli P, Cingolani M Forensic Sci Med Pathol. 2025; .

PMID: 39786671 DOI: 10.1007/s12024-024-00934-0.

Reduced Production of JAK2V617F-positive Microparticles at Mild Hypothermia.

Hekimoglu H, Demirtas E, Sozer S In Vivo. 2023; 37(4):1680-1687.

PMID: 37369465 PMC: 10347929. DOI: 10.21873/invivo.13254.

Postmortem diagnosis of fatal hypothermia/hyperthermia by spectrochemical analysis of plasma.

Lin H, Zou D, Luo Y, Wang L, Zhang Z, Zhang J Forensic Sci Med Pathol. 2019; 15(3):332-341.

PMID: 31054024 DOI: 10.1007/s12024-019-00111-8.

RNU6B, a frequent reference in miRNA expression studies, differentiates between deaths caused by hypothermia and chronic cardiac ischemia.

Kaija H, Pakanen L, Porvari K Int J Legal Med. 2019; 134(1):159-162.

PMID: 30904931 PMC: 6949321. DOI: 10.1007/s00414-019-02041-0.

Biochemical detection of fatal hypothermia and hyperthermia in affected rat hypothalamus tissues by Fourier transform infrared spectroscopy.

Lin H, Deng K, Zhang J, Wang L, Zhang Z, Luo Y Biosci Rep. 2019; 39(3).

PMID: 30824563 PMC: 6418404. DOI: 10.1042/BSR20181633.

References

Keatinge W, Coleshaw S, Cotter F, Mattock M, Murphy M, Chelliah R . Increases in platelet and red cell counts, blood viscosity, and arterial pressure during mild surface cooling: factors in mortality from coronary and cerebral thrombosis in winter. Br Med J (Clin Res Ed). 1984; 289(6456):1405-8. PMC: 1443679. DOI: 10.1136/bmj.289.6456.1405. View

Hirvonen J, Huttunen P . Increased urinary concentration of catecholamines in hypothermia deaths. J Forensic Sci. 1982; 27(2):264-71. View

Boldt J, Knothe C, Welters I, Dapper F, Hempelmann G . Normothermic versus hypothermic cardiopulmonary bypass: do changes in coagulation differ?. Ann Thorac Surg. 1996; 62(1):130-5. DOI: 10.1016/0003-4975(96)00239-1. View

Huang J, Fu G, Yao Q, Cheng G . Relation of thrombomodulin, TFPI and plasma antioxidants in healthy individuals and patients with coronary heart disease. Acta Cardiol. 2008; 63(3):341-6. DOI: 10.2143/AC.63.3.1020311. View

Rajagopalan S, Mascha E, Na J, Sessler D . The effects of mild perioperative hypothermia on blood loss and transfusion requirement. Anesthesiology. 2007; 108(1):71-7. DOI: 10.1097/01.anes.0000296719.73450.52. View

Palmiere C, Mangin P . Postmortem biochemical investigations in hypothermia fatalities. Int J Legal Med. 2012; 127(2):267-76. DOI: 10.1007/s00414-012-0738-y. View

Esmon C, Owen W . Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. Proc Natl Acad Sci U S A. 1981; 78(4):2249-52. PMC: 319322. DOI: 10.1073/pnas.78.4.2249. View

Sakurada M, Asano M, Takahashi M, Kuse A, Morichika M, Nakagawa K . Estimates of exposure to cold before death from immunohistochemical expression patterns of HSP70 in glomerular podocytes. Int J Legal Med. 2012; 127(4):783-90. DOI: 10.1007/s00414-012-0806-3. View

Maruyama I, Bell C, MAJERUS P . Thrombomodulin is found on endothelium of arteries, veins, capillaries, and lymphatics, and on syncytiotrophoblast of human placenta. J Cell Biol. 1985; 101(2):363-71. PMC: 2113687. DOI: 10.1083/jcb.101.2.363. View

10.

Rohrer M, NATALE A . Effect of hypothermia on the coagulation cascade. Crit Care Med. 1992; 20(10):1402-5. DOI: 10.1097/00003246-199210000-00007. View

11.

Boldt J, Papsdorf M, Kumle B, Piper S, Hempelmann G . Influence of angiotensin-converting enzyme inhibitor enalaprilat on endothelial-derived substances in the critically ill. Crit Care Med. 1998; 26(10):1663-70. DOI: 10.1097/00003246-199810000-00018. View

12.

Ishikawa T, Michiue T, Zhao D, Komatsu A, Azuma Y, Quan L . Evaluation of postmortem serum and cerebrospinal fluid levels of thyroid-stimulating hormone with special regard to fatal hypothermia. Leg Med (Tokyo). 2009; 11 Suppl 1:S228-30. DOI: 10.1016/j.legalmed.2009.02.049. View

13.

Nayha S . Environmental temperature and mortality. Int J Circumpolar Health. 2006; 64(5):451-8. DOI: 10.3402/ijch.v64i5.18026. View

14.

Mercer J, Osterud B, Tveita T . The effect of short-term cold exposure on risk factors for cardiovascular disease. Thromb Res. 1999; 95(2):93-104. DOI: 10.1016/s0049-3848(99)00028-6. View

15.

Keatinge W, Donaldson G, Bucher K, Jendritzky G, Cordioli E, Martinelli M . Winter mortality in relation to climate. Int J Circumpolar Health. 2001; 59(3-4):154-9. View

16.

Zhu B, Ishikawa T, Michiue T, Li D, Zhao D, Quan L . Postmortem serum catecholamine levels in relation to the cause of death. Forensic Sci Int. 2007; 173(2-3):122-9. DOI: 10.1016/j.forsciint.2007.02.013. View

17.

He W, Hu Y, Zhang X, Hong M, Guo T, Wei W . Activated protein C ratio, plasma tissue factor activity and activated factor VII in Chinese patients with coronary heart disease. Eur J Med Res. 2008; 13(2):47-51. View

18.

Obama H, Obama K, Takemoto M, Soejima Y, Shirahama T, Ohi Y . Expression of Thrombomodulin in the epithelium of the urinary bladder: a possible source of urinary thrombomodulin. Anticancer Res. 1999; 19(2A):1143-7. View

19.

Kaija H, Pakanen L, Uusitalo J, Nikkila S, Kortelainen M, Porvari K . Changes in cardiac thrombomodulin and heat shock transcription factor 1 expression and peripheral thrombomodulin and catecholamines during hypothermia in rats. Stress. 2014; 17(6):504-11. DOI: 10.3109/10253890.2014.953477. View

20.

Nagelkirk P, Hogan K, Hoare J . Ambient temperature affects thrombotic potential at rest and following exercise. Thromb Res. 2011; 130(2):248-52. DOI: 10.1016/j.thromres.2011.10.015. View