Comparison of the Responses of Global Tests of Coagulation with Molecular Markers of Neutrophil, Endothelial, and Hemostatic System Perturbation in the Baboon Model of E. coli Sepsis

Hideo Wada; Miho Yamamuro; Akiko Inoue; Hiroshi Shiku; Nobuo Sakuragawa; Heinz Redl; Glenn Peer; Fletcher B. Taylor Jr.

doi:10.1055/s-0037-1616753

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 86(06): 1489-1494
DOI: 10.1055/s-0037-1616753

Review Article

Schattauer GmbH

Comparison of the Responses of Global Tests of Coagulation with Molecular Markers of Neutrophil, Endothelial, and Hemostatic System Perturbation in the Baboon Model of E. coli Sepsis

Toward a Distinction between Uncompensated Overt DIC and Compensated Non-overt DIC

Hideo Wada

¹Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan

,

Miho Yamamuro

¹Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan

,

Akiko Inoue

¹Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan

,

Hiroshi Shiku

¹Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan

,

Nobuo Sakuragawa

²Clinical Laboratory Medicine, Toyama Medical and Pharmaceutical University, Toyama-City, Japan

,

Heinz Redl

³Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria

,

Glenn Peer

⁴Cardiovascular Biology Research, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

,

Fletcher B. Taylor Jr.

⁴Cardiovascular Biology Research, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

› Author Affiliations

Abstract

Summary

This study correlates changes in neutrophilic activity and endothelial injury with markers of hemostatic activity following the infusion of increasing concentrations of E. coli organisms. It focuses on the hemostatic response as a marker of microvascular injury and uses the response to increasing concentrations of E. coli to refine our definition of disseminated intravascular coagulation (DIC) and distinguish between a compensated (non-overt DIC) and uncompensated (overt DIC) response. We observed that the global coagulation tests reflected activation of the hemostatic system in a dose dependent manner (overt DIC) in the early phases (T+2 to 6 h) of the response to increasing concentrations of E. coli, but that they failed to do so in the late phases (T+ 24 to 48 h). We observed that molecular markers, soluble thrombomodulin and elastase, unlike thrombin/antithrombin and plasmin/antiplasmin complexes, remained elevated out to T+24 to 48 h indicating endothelial injury that persists beyond the initial inflammatory insult in compensated as well as uncompensated DIC.

Keywords

Endothelium - baboon - E. coli - hemostasis - sepsis - disseminated intravascular coagulation

Full Text

References

References
1 Bick RL. Disseminated intravascular coagulation and related syndromes: A clinical review. Semi Thromb Hemost 1988; 14: 299-338.
2 Muller-Berghaus G. Pathophysiologic and biochemical events in disseminated intravascular coagulation: Dysregulation of procoagulant and anticoagulant pathways. Semi Thromb Hemost 1989; 15: 58-98.
3 Kobayashi N, Maegawa K, Takada M, Tanaka H, Gonmori H. 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. Bibl Haematol 1987; 49: 265-75.
4 Wada H, Wakita Y, Nakase T, Shimura M, Hiyoyama K, Nagaya S, Mori Y, Shiku H, the Mie DIC. study group. Outcome of disseminated intravascular coagulation in relation to the score when treatment was begun. Thromb Hemost 1995; 74: 848-52.
5 Wada H, Minamikawa K, Wakita Y, Nakase T, Kaneko T, Ohiwa M, Tamaki S, Deguchi A, Mori Y, Deguchi K, Shirakawa S, Suzuki K. Hemostatic study before onset of disseminated intravascular coagulation. Am J Hematol 1993; 43: 190-4.
6 Takahasi H, Tatewaki W, Wada K, Hanano M, Shibata A. Thrombin versus plasmin generation in disseminated intravascular coagulation associated with various disorders. Am J Hematol 1990; 33: 90-5.
7 Wada H, Wakita Y, Nakase T, Shimura M, Hiyoyama K, Nagaya S, Deguchi H, Mori Y, Kaneko T, Deguchi K, Fujii J, Shiku H. Increased plasma soluble fibrin monomer levels in patients with disseminated intravascular coagulation. Am J Hematol 1998; 51: 255-60.
8 Wada H, Ohiwa M, Kaneko T, Tamaki S, Tanigawa M, Shirakawa S, Koyama M, Hayashi T, Suzuki K. Plasma thrombomodulin as a marker of vascular disorders in thrombotic thrombocytopenic purpura. Am J Hematol 1992; 39: 20-4.
9 Redl H, Schlag G, SchieBer A, Davies J. Thrombomodulin release in baboon sepsis: Its dependence on the dose of Escherichia coli and the presence of tumor necrosis factor. J Infect Dis 1995; 171: 1522-7.
10 Wada H, Mori Y, Shimura M, Hiyoyama K, Ioka M, Nakasaki T, Nishikawa M, Nakano M, Kumeda K, Kaneko T, Nakamura S, Shiku H. Poor outcome in disseminated intravascular coagulation or thrombotic thrombocytopenic purpura patients with severe vascular endothelial cell injuries. Am J Hematol 1998; 58: 189-94.
11 Taylor Jr FB. Studies of the natural history of the mechanism of the primate (baboon) response to Escherichia coli . In: Ryan JL, Morrison DC. (eds). Bacterial endotoxic lipopolysaccharides, volume II Immunopharmacology and Pathophysiology. Boca Raton, FL: CRC Press; 1992. p 239.
12 Ekberg M, Nilsson IM, Denneberg T. Coagulation studies in hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Acta Med Scand 1974; 196: 373-82.
13 Taylor Jr FB, Chang ACK, Ferrell G, Mather T, Catlett T, Blick K, Esmon CT. C4b-binding protein exacerbates the host response to Escherichia coli . Blood 1991; 78: 357-63.
14 Taylor Jr FB, Coller BS, Chang ACK, Peer G, Jordan R, Engellener W, Esmon CT. 7E3F(ab’)₂, a monoclonal antibody to the platelet GPIIb/IIIa receptor, protects against microangiopathic hemolytic anemia and micro-vascular thrombotic renal failure in baboons treated with C4b binding protein and a sublethal infusion of Escherichia coli . Blood 1997; 89: 4078-84.
15 Taylor Jr FB, Kosanke S, Randolph M, Emerson T, Hinshaw LB, White GL, Chang ACK, Peer GT, Blick K. Retrospective description and experimental reconstitution of three different responses of the baboon to lethal E. coli . Circ Shock 1994; 42: 92-103.
16 Redl H, Schlag G, Bahrami S. Endotoxemia in primate models. In: Brade H, Opal SM, Vogel SN, Morrison DC. (eds). Endotoxin in Health and Diseases. New York, Basel: Marcel Dekker, Inc.; 1999. pp 795-808.
17 Hinshaw LB, Bracker DJ, Archer LT, Beller L, Wilson MF. Detection of the “hyperdynamic state” of sepsis in the baboon during lethal E. coli infusion. J Trauma 1983; 23 (Suppl. 05) 361-5.
18 Hougie C. Method for estimating fibrinogen concentration – thrombin time test. In: Williams WJ, Beutler E, Erslev AJ, Lichtman MA. (eds). Hematology. Third edition. New York: McGraw-Hill; 1983. p 1667.
19 Wellcome Research Laboratories: Fibrinogen degradation products. Thrombo-Wellcotest (rapid latex kit) Purley, Surrey, UK: Southern Press; 1984
20 Technical Information in Test Methodologies. Rochester, NY: Eastman Kodak Co.; 1985
21 Nuijens JH, Abbink JJ, Wachtfogel YT, Colman RW, Eerenberg AJM, Dors D. et al. Plasma elastase alpha, -antitrypsin and lactoferrin in sepsis: Evidence for neutrophils as mediators in fatal sepsis. J Lab Clin Med 1992; 119: 159.
22 Morrissey JH, Macik BG, Neuenschwander PF, Comp PC. Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation. Blood 1993; 81 (Suppl. 03) 734-44.
23 Kinasewitz GT, Chang ACK, Peer GT, Hinshaw LB, Taylor Jr FB. Peritonitis in the baboon: A Primate Model that Simulates Human Sepsis. Shock 2000; 13 (Suppl. 82) 100-9.