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DOI: 10.1055/s-0037-1613858
Recurrent Venous Thrombosis and Markers of Inflammation
Publication History
Received
01 July 1999
Accepted after revision
24 November 1999
Publication Date:
08 December 2017 (online)
Summary
Inflammatory processes may play a key role in venous thrombosis, by inducing a procoagulant state through the action of cytokines and chemokines on monocytes and endothelial cells. Plasma concentrations of three inflammatory mediators, interleukin 6 (IL-6), interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1), that mediate the cross-talk between inflammation and coagulation, were measured in 182 subjects with recurrent venous thrombosis and 350 healthy subjects recruited through a general practice. Elevated levels of IL-6 (>90th percentile of the control group) were detected in 25.8% of the patients with venous thrombosis in comparison with 10% (by definition) of the controls [odds ratio 2.4 (95%CI 1.5-3.8)]. In 21.5% of the patients elevated plasma levels of IL-8 (>90th percentile) were determined [odds ratio 2.0 (95%CI 1.2-3.5)]. Elevated levels of MCP-1 (>90th percentile) were detected in 24.1% of the patients [odds ratio 1.9 (95%CI 1.2-3.2)]. This is the first large clinical study showing that an increase in inflammatory mediators is associated with venous thrombosis. Future prospective studies are necessary to clarify the causal nature of the inflammatory process with respect to venous thrombosis.
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References
- 1 Hirsh J, Hull RD, Raskob GE. Epidemiology and pathogenesis of venous thrombosis. J Am Coll Cardiol 1986; 08: 104B-13B.
- 2 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-8.
- 3 Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet 1993; 342: 1503-6.
- 4 Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
- 5 Koster T, Blann AD, Briët E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-5.
- 6 Den Heijer M, Koster T, Blom HJ, Bos GM, Briët E, Reitsma PH, Vandenbroucke JP, Rosendaal FR. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med 1996; 334: 759-62.
- 7 Den Heijer M, Rosendaal FR, Blom HJ, Gerrits WB, Bos GM. Hyperhomocysteinemia and venous thrombosis: a meta-analysis. Thromb Haemost 1998; 80: 874-7.
- 8 Van Deventer SJ, Büller HR, ten Cate JW, Aarden LA, Hack CE, Sturk A. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood 1990; 76: 2520-6.
- 9 Van der Poll T, Levi M, van Deventer SJ, ten Cate H, Haagmans BL, Biemond BJ, Büller HR, Hack CE, ten Cate JW. Differential effects of antitumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. Blood 1994; 83: 446-51.
- 10 Bauer KA, ten Cate H, Barzegar S, Spriggs DR, Sherman ML, Rosenberg RD. Tumor necrosis factor infusions have a procoagulant effect on the hemostatic mechanism of humans. Blood 1989; 74: 165-72.
- 11 Stouthard JM, Levi M, Hack CE, Veenhof CH, Romijn HA, Sauerwein HP, van der Poll T. Interleukin-6 stimulates coagulation, not fibrinolysis, in humans. Thromb Haemost 1996; 76: 738-42.
- 12 Dosquet C, Weill D, Wautier J. Cytokines and thrombosis. J Cardiovasc Pharmacol 1995; 25: S13-S9.
- 13 Levi M, Van der Poll T, Ten Cate H, Van Deventer SJH. The cytokinemediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia. Eur J Clin Invest 1997; 27: 3-9.
- 14 Ten Cate JW, van der Poll T, Levi M, ten Cate H, van Deventer SJ. Cytokines: triggers of clinical thrombotic disease. Thromb Haemost 1997; 78: 415-9.
- 15 Den Heijer M, Blom HJ, Gerrits WB, Rosendaal FR, Haak HL, Wijermans PW, Bos GM. Is hyperhomocysteinaemia a risk factor for recurrent venous thrombosis?. Lancet 1995; 345: 882-5.
- 16 Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-703.
- 17 Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353: 1167-73.
- 18 De Maat MP, Pietersma A, Kofflard M, Sluiter W, Kluft C. Association of plasma fibrinogen levels with coronary artery disease, smoking and inflammatory markers. Atherosclerosis 1996; 121: 185-91.
- 19 Taylor Jr FB, Chang A, Ruf W, Morrissey JH, Hinshaw L, Catlett R, Blick K, Edgington TS. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 1991; 33: 127-34.
- 20 Creasey AA, Chang AC, Feigen L, Wun TC, Taylor Jr FB, Hinshaw LB. Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. J Clin Invest 1993; 91: 2850-6.
- 21 Levi M, ten Cate H, Bauer KA, van der Poll T, Edgington TS, Büller HR, van Deventer SJ, Hack CE, ten Cate JW, Rosenberg RD. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest 1994; 93: 114-20.
- 22 Neumann FJ, Ott I, Marx N, Luther T, Kenngott S, Gawaz M, Kotzsch M, Schomig A. Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity. Arterioscler Thromb Vasc Biol 1997; 17: 3399-405.
- 23 Schecter AD, Rollins BJ, Zhang YJ, Charo IF, Fallon JT, Rossikhina M, Giesen PL, Nemerson Y, Taubman MB. Tissue factor is induced by monocyte chemoattractant protein-1 in human aortic smooth muscle and THP-1 cells. J Biol Chem 1997; 272: 28568-73.
- 24 Hirano T, Akira S, Taga T, Kishimoto T. Biological and clinical aspects of interleukin 6. Immunol Today 1990; 11: 443-9.
- 25 Luster AD. Chemokines – Chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338: 436-45.
- 26 Gerszten RE, Garcia-Zepeda EA, Lim Y, Yoshida M, Ding HA, Gimbrone Jr. MAADL, Luscinskas FW, Rosenzweig A. MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature 1999; 398: 718-23.
- 27 Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336: 973-9.
- 28 Kamphuisen PW, Eikenboom JCJ, Vos HL, Pablo R, Sturk A, Bertina RM, Rosendaal FR. Increased levels of factor VIII and fibrinogen in patients with venous thrombosis are not caused by acute phase reactions. Thromb Haemost 1999; 81: 680-3.
- 29 Wakefield TW, Strieter RM, Wilke CA, Kadell AM, Wrobleski SK, Burdick MD, Schmidt R, Kunkel SL, Greenfield LJ. Venous thrombosis-associated inflammation and attenuation with neutralizing antibodies to cytokines and adhesion molecules. Arterioscler Thromb Vasc Biol 1995; 15: 258-68.
- 30 Johnson K, Aarden L, Choi Y, De Groot E, Creasey A. The proinflammatory cytokine response to coagulation and endotoxin in whole blood. Blood 1996; 87: 5051-60.
- 31 Froehlich JB, Prince MR, Greenfield LJ, Downing LJ, Shah NL, Wakefield TW. “Bull’s-eye” sign on gadolinium-enhanced magnetic resonance venography determines thrombus presence and age: a preliminary study. J Vasc Surg 1997; 26: 809-16.
- 32 Senden NHM, Jeunhomme TMAA, Heemskerk JWM, Wagenvoord R, Van ’t Veer C, Hemker HC, Buurman WA. Factor Xa induces cytokine production and expression of adhesion molecules by human umbilical vein endothelial cells. J Immunol 1998; 161: 4318-24.
- 33 Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Muller-Berghaus G, Kroczek RA. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 391: 591-4.
- 34 Carr C, Bild GS, Chang AC, Peer GT, Palmier MO, Frazier RB, Gustafson ME, Wun TC, Creasey AA, Hinshaw LB. Recombinant E. coli-derived tissue factor pathway inhibitor reduces coagulopathic and lethal effects in the baboon gram-negative model of septic shock. Circ Shock 1994; 44: 126-37.
- 35 Hisama N, Yamaguchi Y, Okajima K, Uchiba M, Murakami K, Mori K, Yamada S, Ogawa M. Anticoagulant pretreatment attenuates production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion of rat liver. Dig Dis Sci 1996; 41: 1481-6.