Abstract
Objective
To find out whether changes within the hemostatic system are related to the severity of illness and organ failure in patients at the onset of clinically defined sepsis and to find some indications for the contribution of endothelial cell activation or perturbation to the patient's status. The following measurements were undertaken: Acute Physiology and Chronic Health Evaluation (APACHE) II score, multiple organ failure (MOF) score, plasma levels of thrombin—antithrombin III complexes (TAT), antithrombin III (AT III), protein C antigen, factor XII, and plasminogen activator inhibitor type 1 antigen (PAI-1), neopterin, and interleukin 6 (IL-6).
Design
A prospective case series study.
Setting
Intensive care unit (ICU) of the Department of Internal Medicine, Justus Liebig University, Giessen, Germany.
Patients
28 consecutive patients (11 females, 17 males; mean age 58 years) with clinically defined sepsis. Eleven patients were admitted from the surgical ICU (9 after elective surgery, 2 after trauma surgery). The operations were done 1–26 days (mean 14 days) prior to the onset of sepsis.
Main results
At the onset of sepsis we found elevated plasma levels of TAT, PAI-1, neopterin, and IL-6, and lowered plasma levels of AT III, factor XII, and protein Cantigen. Neopterin, PAI-1, IL-6, and factor XII showed a statistically significant correlation with the APACHE II score. The MOF score is significantly correlated with IL-6 and neopterin. The extent of hemostatic abnormalities was related to increasing levels of IL-6.
Conclusions
Clinical evidence of a septic process is most likely to be preceded by activation of the hemostatic system, the vascular endothelium, and the monocyte/macrophage system. IL-6 may have a regulatory function for hemostasis in inflammation. Laboratory monitoring could be helpful in deciding whether to start early intensive therapy in patients at risk for sepsis.
Similar content being viewed by others
References
Baue AE (1992) The horror autotoxicus and multiple organ failure. Arch Surg 127:1451–1462
Neuhof H (1991) Actions and interactions of mediator systems and mediators in the pathogenesis of ARDS and multiorgan failure. Acta Anaesthesiol Scand 35 [Suppl 95]:7–14
Levi M, ten Cate H, van der Poll T, van Deventer SJH (1993) New insights in pathogenesis of disseminated intravascular coagulation in sepsis. JAMA 270:975–979
Thijs LG, de Boer JP, de Groot MCM, Hack CE (1993) Coagulation disorders in septic shock. Intensive Care Med 19:S8-S15
Stern D, Kaiser E, Nawroth PP (1988) Regulation of the coagulation by vascular endothelial cells. Haemostasis 18: 202–214
Pober JS, Contran RS (1990) The role of endothelial cells in inflammation. Transplantation 50:537–544
Hack CE, Nuijens JH, Strack van Schijndel RJM, Abbink JJ, Eerenberg AJM, Thijs LG (1990) A model for the interplay of inflammatory mediators in sepsis — a study in 48 patients. Intensive Care Med 16:S187-S191
Dofferhoff ASM, Bom VJJ, de Vries-Hospers HG, van Ingen J, van der Meer J, Hazenberg BPC, Mulder POM, Weits J (1992) Patterns of cytokines, plasma endotoxin, plasminogen activator inhibitor, and acute-phase proteins during the treatment of severe sepsis in humans. Crit Care Med 20:185–192
Hack CE, De Groot ER, Felt-Bersma RJF, Nujens JH, Strack van Schijndel RJM, Eerenberg-Belmer AJM, Thijs LG, Aarden LA (1989) Increased plasma levels of interleukin-6 in sepsis. Blood 74:1704–1710
Huber C, Batchelor JR, Fuchs D, Hausen A, Lang A, Niederwieser D, Reibnegger G, Swetly P, Troppmaier J, Wachter H (1984) Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma. J Exp Med 160:310–316
Troppmaier J, Nachbaur K, Herold M, Aulitzky W, Tilg H, Gastl G, Bieling P, Kotlan B, Flener R, Mull B, Aulitzky WO, Rokos H, Huber C (1988) In-vitro and in-vivo studies on the induction of neopterin biosynthesis by cytokines, alloantigens, and lipopolysaccharide (LPS). Clin Exp Immunol 74:392–397
The Veterans Administration Systemic Sepsis Cooperative Study Group (1987) Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med 317:659–665
Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829
Goris RJA, te Boeckhorst TPA, Nuytinck JKS, Gimbrére JSF (1985) Multiple organ failure: generalized autodestructive inflammation? Arch Surg 120:1109–1115
Rowley G, Fielding K (1991) Reliability and accuracy of the Glasgow Coma Scale with experienced and inexperienced users. Lancet 337:535–538
Kluft C, Jie FH, Rijken DC, Verheijen JH (1988) Daytime fluctuations in blood of tissue-type plasminogen activator (t-PA) and its fast-acting inhibitor (PAI-1). Thromb Haemost 59:329–332
Montgomery DC, Peck EA (1982) Introduction to linear regression analysis. Wiley, New York
Esmon CT (1993) Cell mediated events that control blood coagulation and vascular injury. Annu Rev Cell Biol 9:1–26
Sironi M, Breviario F, Proserpio P, Biondi A, Vecchi A, van Damme J, Dejana E, Mantovani A (1989) IL-1 stimulates IL-6 production in endothelial cells. J Immunol 142:549–553
Jirik FR, Podor TJ, Hirano T, Kishimoto T, Loskutoff DJ, Carson DA, Lotz M (1989) Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. J Immunol 142:144–147
Billiau A (1988) Interleukin-6: structure, productions and actions. Prog Leukocyte Biol 8:3–13
Strohmaier W, Redl H, Schlag G, Inthorn D (1987) D-Erythro-neopterin plasma levels in intensive care patients with and without septic complications. Crit Care Med 15:757–760
Pacher R, Redl H, Frass M, Petzl DH, Schuster E, Woloszczuk W (1989) Relationship between neopterin and granulocyte elastase plasma levels and the severity of multiple organ failure. Crit Care Med 17:221–226
Voss R, Matthias FR, Borkowski G, Reitz D (1990) Activation and inhibition of fibrinolysis in septic patients in an internal intensive care unit. Br J Haematol 75:99–105
Loskutoff DJ, Sawdey M, Mimuro J (1989) Type 1 plasminogen activator inhibitor. Prog Hemost Thromb 9:87–115
Boer JP de, Abbink JJ, Brouwer MC, Meijer C, Roem D, Voorn GP, Lambers JWJ, Mourik JA van, Hack CE (1991) PAI-1 synthesis in the human hepatoma cell line Hep G2 is increased by cytokines — evidence that the liver contributes to acute phase behaviour of PAI-1. Thromb Haemost 65:181–185
Podor TJ, Hirsh J, Gelehrter TD, Zeheb R, Torry D, Guigoz Y, Sierra F, Gauldie J (1993) Type 1 plasminogen activator inhibitor is not an acute phase reactant in rats. Lack of IL-6 and hepatocyte-dependent synthesis. J Immunol 150:225–235
Hesselvik JF, Blombäck M, Brodin B, Maller R (1989) Coagulation, fibrinolysis, and kallikrein systems in sepsis: relation to outcome. Crit Care Med 17:724–733
Colman RW (1993) Factor XII activation and inhibition in inflammation. Agents Actions Suppl 42:125–143
van der Poll T, Levi M, Hack CE, ten Cate H, van Deventer SJH, Eerenberg AJM, de Groot ER, Jansen J, Gallati H, Büller HR, ten Cate JW, Aarden LA (1994) Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees. J Exp Med 179:1253–1259
Creasey AA, Chang ACK, Feigen L, Wün TC, Taylor FB, Hinshaw LB (1993) Tissue factor pathway inhibitor reduces mortality fromEscherichia coli septic shock. J Clin Invest 91:2850–2860
Edwards RL, Rickles FR, Bobrove AM (1979) Mononuclear cell tissue factor: cell of origin and requirements for activation. Blood 54:359–370
Okajima K, Yang WP, Okabe H, Inoue M, Takatsuki K (1991) Role of leukocytes in the activation of intravascular coagulation in patients with septicemia. Am J Hematol 36:265–271
Toossi Z, Sedor JR, Mettler M, Everson B, Young T, Ratnoff OD (1992) Induction of expression of monocyte interleukin 1 by Hageman factor (factor XII). Proc Natl Acad Sci USA 89:11969–11972
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Leithäuser, B., Matthias, F.R., Nicolai, U. et al. Hemostatic abnormalities and the severity of illness in patients at the onset of clinically defined sepsis. Intensive Care Med 22, 631–636 (1996). https://doi.org/10.1007/BF01709738
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01709738