Whether free hemoglobin can be a severity’s marker of general condition of the patient with sepsis?

Y.P. Orlov1, 3, V.T. Dolgikh2, A.V. Glushchenko3

1 The Department of Anesthesiology and Intensive Care, Federal state budgetary educational institution higher education “Omsk State Medical University” Ministry of Health of Russian Federation, Omsk

2 The Department of Pathophysiology with course of clinical pathophysiology, Federal state budget educational institution higher education “Omsk State Medical University” Ministry of Health of Russian Federation, Omsk

3 BUZOO “City clinical emergency hospital N 1», Omsk, Russia

For correspondence: Orlov Yuriy Petrovich — MD, Professor of Anesthesiology and reanimatology, Russian “Omsk State Medical University” the Ministry of health of Russia; e-mail: orlov-up@mail.ru

For citation: Orlov YP, Dolgikh VT, Glushchenko AV. Whether Free Hemoglobin can be a Severity’s Marker of General Condition of the Patient with Sepsis? Alexander Saltanov Intensive Care Herald. 2018;1:48–54.

DOI: 10.21320/1818-474X-2018-1-48-54

Purpose of Research: to determine whether we can use free hemoglobin concentration as early prognostic marker and a predictor of mortality in sepsis. Materials and Methods. In a retrospective study in 60 patients aged 47,6 ± 7,2 years with sepsis (30,4 ± 2,1 points on the Mannheim’s scale for evaluation of the severity of peritonitis) modern methods of statistics (ROC-analysis) hypothesis was tested, whether level of free hemoglobin in the first 24 hours from the moment of admission can be used as a biomarker for diagnosis and prognosis for severe sepsis. Informative criterion was compared with the information of the procalcitonin test. Results. The present study had shown that the above average free hemoglobin concentration, measured on the first day of the heavy flow of sepsis, is directly connected with increased 30-days mortality, and the level of free hemoglobin in a first day of the disease has high sensitivity, specificity, and can determine the outcome of sepsis with accuracy up to 96,7 %. Conclusion. Free hemoglobin concentration above medium size identified on the first day of the currents of severe sepsis, is directly related to increased 30-day mortality, and researched level of free hemoglobin in day 1 of the disease has a high proportion of sensitivity and specificity. Level of free hemoglobin is Predictor outcome of sepsis in the first 24 hours after the start of therapy, but the results did not rule out the need to use the necessary test from septic patients, but rather the feasibility of combining the two dictates the criteria to assess the outcome of severe septic process that requires further research.

Keywords: free hemoglobin, procalcitonin, sepsis, ROC-analysis

Received: 15.01.2018


  1. Weis S., Carlos A.R., Moita M.R., et al. Metabolic Adaptation Establishes Disease Tolerance to Sepsis. Cell. 2017; 169(7): 1263–1275. e14. doi: 10.1016/j.cell.2017.05.031.
  2. Harbarth S., Holeckova K., Froidevaux C., et al. Geneva Sepsis Network. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am. J. Respir. Crit. Care Med. 2001; 164(3): 396–402.
  3. Selberg O., Hecker H., Martin M., et al. Discrimination of sepsis and systemic inflammatory response syndrome by determination of circulating plasma concentrations of procalcitonin, protein complement 3a, and interleukin-6. Crit. Care Med. 2000; 28(8): 2793–2798.
  4. Yu X., Ma X., Ai Y. Diagnostic value of serum procalcitonin for infection in the immunocompromised critically ill patients with suspected infection. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2015; 27(6): 477–483. doi: 10.3760/cma.j.issn.2095-4352.2015.06.012.
  5. Jordi Rello J., Francisco Valenzuela-Sánchez F., Ruiz-Rodriguez M., Moyano S. Sepsis: A Review of Advances in Management. Adv. Ther. 2017; 34(11): 2393–2411. doi: 10.1007/s12325-017-0622-8.
  6. Мчедлишвили Г.И. Гемореология в системе микроциркуляции: ее специфика и практическое значение. Тромбоз, гемостаз иреология. 2002; 4(12); 18–24. [Mchedlishvili G.I. Hemorheology in microcirculation system: its specificity and practical significance. Thrombosis, hemostasis and rheology. 2002; 4(12); 18–24. (In Russ)]
  7. Сторожук П.Г. Ферменты прямой и косвенной антирадикальной защиты эритроцитов и их роль в инициации процессов оксигенации гемоглобина, антибактериальной защите и делении клеток. Вестн. инт. терапии. 2000; 3: 8–13. [Storozhuk P.G. Enzymes direct and indirect antiradical protect red blood cells and their role in triggering processes of oxygenation of hemoglobin, antibacterial protection and cell division. Vestn. intensive therapy. 2000; 3: 8–13. (In Russ)]
  8. Huffman D.L., Bischof L.J., Griffitts J.S., Aroian R.V. Pore worms: using Caenorhabditis elegans to study how bacterial toxins interact with their target host. Int. J. Med. Microbiol. 2004; 293: 599–607. doi: 10.1078/1438-4221-00303.
  9. Aroian R., van der Goot F.G. Pore-forming toxins and cellular nonimmune defenses (CNIDs) Curr. Opin. Microbiol. 2007; 10: 57–61. doi: 10.1016/j.mib.2006.12.008.
  10. Gonzalez M.R., Bischofberger M., Pernot L., et al. Bacterial pore-forming toxins: the (w)hole story? Cell. Mol. Life Sci. 2008; 65: 493–507. doi: 10.1007/s00018-007-7434-y.
  11. Bull B.S., Kuhn I.N. The production of schistocytes by fibrin strands (a scanning electron microscope study). Blood. 1970; 35: 104–111.
  12. Heyes H., Köhle W., Slijepcevic B. The appearance of schistocytes in the peripheral blood in correlation to the degree of disseminated intravascular coagulation. An experimental study in rats. Haemostasis. 1976; 5: 66–73.
  13. Ehrnthaller C., Ignatius A., Gebhard F., Huber-Lang M. New insights of an old defense system: structure, function, and clinical relevance of the complement system. Mol. Med. 2011; 17: 317–329.
  14. Pöschl J.M., Leray C., Ruef P., et al. Endotoxin binding to erythrocyte membrane and erythrocyte deformability in human sepsis and in vitro. Crit. Care Med. 2003; 31: 924–928. doi: 10.1097/01.CCM.0000055366.24147.80.
  15. Lang F., Gulbins E., Lang P.A., et al. Ceramide in suicidal death of erythrocytes. Cell Physiol. Biochem. 2010; 26: 21–28. doi: 10.1159/000315102.
  16. Lang F., Qadri S.M. Mechanisms and Significance of Eryptosis, the Suicidal Death of Erythrocytes. Blood Purif. 2012; 33: 125–130. doi: 10.1159/000334163.
  17. Hod E.A., Zhang N., Sokol S.A., et al. Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation. Blood. 2010; 115: 4284–4292. doi: 10.1182/blood-2009-10-245001.
  18. Dutra F.F., Bozza M.T. Heme on innate immunity and inflammation. Front. Pharmacol. 2014; 5: 115. doi: 10.3389/fphar.2014.00115.
  19. Vinchi F., Tolosano E. Therapeutic approaches to limit hemolysis-driven endothelial dysfunction: scavenging free heme to preserve vasculature homeostasis. Oxid. Med. Cell. Longev. 2013; 2013: 396527. doi: 10.1155/2013/396527.
  20. Linder M.M., Wacha H., Feldmann U., et al. The Mannheim peritonitis index. An instrument for the intraoperative prognosis of peritonitis. Chirurg. 1987; 58(2): 84–92.
  21. Singer M., Deutschman C.S., Seymour C.W., et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315(8): 801–810. doi: 10.1001/jama.2016.0287.
  22. Vincent J.L., Ince C., Bakker J. Clinical review: Circulatory shock-an update: a tribute to Professor Max Harry Weil. Crit. Care. 2012; 16(6): 239. doi: 10.1186/cc11510.
  23. Савельев О.Н., Сухоруков В.П., Киселева А.В. Определение свободного гемоглобина плазмы крови гемоглобинцианидным методом. Лаб. дело. 1990; 10: 45–47. [Savelyev O.N., Sukhorukov V.P., Kiseleva A.V. Definition of free plasma hemoglobin gemoglobincianidnym method. Lab. case. 1990; 10: 45–47. (In Russ)]
  24. Мeisner M. PCT — procalcitonin. A new and innovative parameter in diagnosis of infections. Berlin: BRAHMS Diagnostica, 1996.
  25. Belcher J.D., Mahaseth H., Welch T.E., et al. Critical role of endothelial cell activation in hypoxia-induced vasoocclusion in transgenic sickle mice. American Journal of Physiology. 2005; 288(6): 2715–2725. doi: 10.1152/ajpheart.00986.2004.
  26. Belcher J.D., Mahaseth H., Welch T.E., et al. Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice. Journal of Clinical Investigation. 2006; 116(3): 808–816. doi: 10.1172/JCI26857.
  27. Jeney V., Balla J., Yachie A., et al. Pro-oxidant and cytotoxic effects of circulating heme. Blood. 2002; 100(3): 879–887.
  28. Kumar S., Bandyopadhyay U. Free heme toxicity and its detoxification systems in human. Toxicology Letters. 2005; 157(3): 175–188. doi: 10.1016/j.toxlet.2005.03.004.
  29. Weinberg E.D. Iron and infection. Microbiol. Rev. 1978; 42(1): 45–66.
  30. Cassat J.E., Skaar E.P. Iron in Infection and Immunity. Cell. Host. Microbe. 2013; 13(5): 509–519. doi: 10.1016/j.chom.2013.04.010.
  31. Brauckmann S., Effenberger-Neidnicht K., de Groot H., et al. Lipopolysaccharide-induced hemolysis: Evidence for direct membrane interactions. Sci.Rep. 2016; 6: 35508. doi: 10.1038/srep35508.