Abstract
The fact that thrombomodulin (TM) is released into the bloodstream from damaged vascular endothelial cells led us to hypothesize that plasma levels of soluble TM could be an indicator of the development of organ failure. In this study, we examined the changes in plasma levels of TM in 60 septic patients and 13 postsurgical patients, and investigated the circulating levels of interleukin 6 (IL-6) and polymorphonuclear leukocyte elastase (PMN-E) to determine the mechanism causing the excess liberation of TM. The arterial ketone body ratio (AKBR) was also measured as an indicator of the hepatocyte energy state. Of the 60 septic patients, 26 developed organ failure, 10 of whom died. In contrast, none of the postsurgical patients developed organ failure. The mean plasma level of TM was significantly higher in the septic patients who developed organ failure compared to those without organ failure (P<0.001) or the postsurgical patients (P<0.001). Furthermore, those patients whose plasma TM values became elevated over 6.0ng/ml frequently developed complications. A positive correlation was also observed between the plasma TM levels and the IL-6 (P<0.01) and PMNE levels (P<0.01). In contrast, a negative correlation was seen between the plasma TM levels and the AKBR (P<0.01). These findings show that plasma TM could be a useful indicator of impending organ failure during sepsis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Maruyama I (1992) Thrombomodulin: an endothelial anticoagulant; its structure, function and expression. Jpn Circ J 56:187–191
Maruyama I, Majerus PW (1985) The turnover of thrombin-thrombomodulin complex in cultured human umbilical vein endothelial cells and A549 lung cancer cells. J Biol Chem 260:15432–15438
Ishii H, Majerus PW (1985) Thrombomodulin is present in human plasma and urine. J Clin Invest 76:2178–2181
Kodama S, Uchijima E, Nagai M, Mikawatani K, Hayashi T, Suzuki K (1990) One-step sandwich enzyme immunoassay for soluble human thrombomodulin using monoclonal antibodies. Clinica Chimica Acta 192:191–200
Wada H, Ohiwa M, Kaneko T, Tamaki S, Tanigawa M, Shirakawa S, Koyama M, Hayashi T, Suzuki K (1992) Plasma thrombomodulin as a marker of vascular disorders in thrombotic thrombocytopenic purpura and disseminated intravascular coagulation. Am J Hematol 39:20–24
Iwashima Y, Sato T, Watanabe K, Ooshima E, Hiraishi S, Ishii H, Kazama M, Makino I (1990) Elevation of plasma thrombomodulin level in diabetic patients with early diabetic nephropathy. Diabetes 39:983–988
Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapeutics in sepsis. Crit Care Med 20:864–874
Kodama N, Maegawa T, Takada M, Tanaka H, Gonmori H (1987) Criteria for diagnosis of DIC based on the analysis of clinical and laboratory findings in 345 DIC patients collected by the research committee on DIC in Japan. Biol Haematol 49:265–275
Hayashi T, Suzuki K (1990) Monoclonal antibodies for human thrombomodulin which recognize binding sites for thrombin and protein C. J Biochem 108:874–878
Waage A, Halstensen A, Espevik T (1987) Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet 1:355–357
Schirmer WJ, Schirmer JM, Fry DE (1989) Recombinant human tumor necrosis factor produces hemodynamic changes characteristic of sepsis and endotoxemia. Arch Surg 124:445–448
Busund R, Lindsetmo RO, Rasmussen LT, Rokke O, Rekvig O, Revhaug A (1991) Tumor necrosis factor and interleukin-1 appearance in experimental gram-negative septic shock. Arch Surg 126:591–597
Hirokawa K, Aoki N (1991) Regulatory mechanism for thrombomodulin expression in human umbilical vein endothelial cells in vitro. J Cell Physiol 147:157–165
Lentz SR, Tsiang M, Sadler JE (1991) Regulation of thrombomodulin by tumor necrosis factor-α comparison of transcriptional and posttranscriptional mechanism. Blood 77:542–550
Archipoff G, Beretz A, Freyssinet JM, Klein-Soyer C, Brisson C, Cazenave JP (1991) Heterogeneous regulation of constitutive thrombomodulin or inducible tissue-factor activities on the surface of human saphenous-vein endothelial cells in culture following stimulation by interleukin-1, tumor necrosis factor, thrombin, or phorbol ester. Biochem J 273:679–684
Hack CE, DeGroot ER, Felt-Bersma JFF, Nuijens JH, Van Schijndel RJMS, Eerenberg-Belmer AJM, Thijs LG, Aarden LA (1989) Increased plasma levels of interleukin-6 in sepsis. Blood 74:1704–1710
Heese DG, Tracey KJ, Fong Y, Manogue KR, Palladino MA Jr, Cerami A, Shires GT, Lowry SF (1988) Cytokine appearance in human endotoxemia and primate bacteremia. Surg Gynecol Obstet 166:147–153
Waage A, Brandtzaeg P, Halstensen A, Kierulf P, Espevik T (1989) The complex pattern of cytokines in serum from patients meningococcal septic shock. J Exp Med 169:333–338
Kazama M (1988) Clinical evaluation of hemostatic molecular markers. Acta Haematol Jpn 51:1387–1394
Deguchi K, Zhao L, Shirakawa S (1991) Clinical application of laboratory diagnosis: leukemia and DIC. Jpn J Clin Pathol 39:736–742
Takano S, Kimura S, Ohdama S, Aoki N (1990) Plasma thrombomodulin in health and disease. Blood 76:2024–2029
Oida K, Takai H, Maeda H, Tamai T, Nakai T, Miyabo S, Ishii H (1989) Plasma thrombomodulin concentrations in diabetes mellitus. Thromb Haemost 62:276
Asakura H, Jokaji H, Saito M, Uotani C, Kumabashiri I, Morishita E, Yamazaki M, Matsuda T (1991) Plasma levels of soluble thrombomodulin increase in cases of disseminated intravascular coagulation with organ failure. Am J Hematol 38:281–287
Tanaka A, Morimoto T, Tani Y, Noguchi M, Nakatani T, Kamiyama Y, Yamaoka Y, Ozawa K (1987) The influence of hemodilution in normal and hepatectomized rats in relation to hepatic energy metabolism. Am J Med Sci 294:310–316
Higashiyama H, Yamaguchi M, Kumada K, Sasaki H, Yamaguchi T, Ozawa K (1992) Tolerance of the liver as measured by ketone body ratio and hepatocyte energy charge to 120 minutes acute venous congestion in dogs. Circ Shock 38:202–208
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Iba, T., Yagi, Y., Kidokoro, A. et al. Increased plasma levels of soluble thrombomodulin in patients with sepsis and organ failure. Surg Today 25, 585–590 (1995). https://doi.org/10.1007/BF00311430
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00311430