Thromb Haemost 2005; 94(02): 362-365
DOI: 10.1160/TH05-04-0266
Review Article
Schattauer GmbH

The relationship between inflammation and venous thrombosis

A systematic review of clinical studies
Eric A. Fox
1   Faculty of Medicine, McGill University, Montreal, Canada
,
Susan R. Kahn
1   Faculty of Medicine, McGill University, Montreal, Canada
2   Center for Clinical Epidemiology and Community Studies, SMBD Jewish General Hospital, Montreal, Canada
› Author Affiliations
Financial support: Eric Fox was supported by a McGill University Faculty of Medicine Summer Research Bursary. Dr. Susan Kahn is the recipient of a Clinical Research Scholar Award from the Fonds de la Recherche en Santé du Québec.
Further Information

Publication History

Received: 18 April 2005

Accepted after major revision: 19 May 2005

Publication Date:
05 December 2017 (online)

Summary

During the past decade, the role of inflammation in the pathophysiology of arterial thrombosis has been elucidated. However, comparatively little is known about the relationship between inflammation and venous thrombosis. The aim of this study was to perform a systematic review of clinical studies that have examined the association between inflammation and venous thrombosis, specifically: (1) the value of inflammatory markers in predicting the future development of venous thrombosis; (2) test characteristics of markers of inflammation in the diagnosis of acute venous thrombosis; and (3) effect of venous thrombosis on blood levels of inflammatory markers. Using keywords venous thrombosis, venous thromboembolism, inflammation, acute phase markers, C-reactive protein (CRP), interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1, PubMed and Medline computerized databases were searched for English language articles published after 1980. Search results were restricted to clinical studies in humans that used study designs that were appropriate to address the above objectives. Results show that plasma CRP levels do not appear to predict risk of future venous thtwo (rombosis studies; N=41,308). Four studies (N=562) have examined the utility of plasma CRP in the diagnosis of venous thrombosis; pooled positive and negative predictive values were 53% (95% CI:47%,59%) and 85% (95% CI: 81%, 89%), respectively.A two- to six-fold increase in the risk of deep vein thrombosis (DVT) is associated with elevations in plasma levels of CRP, IL-6, IL-8, MCP-1 orTNF-α (three studies). We can conclude that the nature of the relationship between inflammation and clinical venous thrombosis is not yet established. CRP does not appear to be useful in predicting future venous thrombosis or in the diagnosis of acute venous thrombosis. While several markers of inflammation are elevated in acute venous thrombosis, further research is needed to determine the precise relationship between these markers and venous thrombosis. The identification and elucidation of inflammatory markers relevant to venous thrombosis could provide targets for future therapy.

 
  • References

  • 1 Ridker PM, Cushman M, Stampfer MJ. et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336: 973-9.
  • 2 Anderson FA, Jr. Spencer FA. Risk factors for venous thromboembolism. Circulation 2003; 107: I9-6.
  • 3 Silverstein MD, Heit JA, Mohr DN. et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158: 585-93.
  • 4 Wakefield TW, Strieter RM, Prince MR. et al. Pathogenesis of venous thrombosis: a new insight. Cardiovasc Surg 1997; 5: 6-15.
  • 5 van der PT, Buller HR, tenCate H. et al. Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 1990; 322: 1622-7.
  • 6 Cermak J, Key NS, Bach RR. et al. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993; 82: 513-20.
  • 7 Wakefield TW, Greenfield LJ, Rolfe MW. et al. Inflammatory and procoagulant mediator interactions in an experimental baboon model of venous thrombosis. Thromb Haemost 1993; 69: 164-72.
  • 8 Chooi CC, Gallus AS. Acute phase reaction, fibrinogen level and thrombus size. Thromb Res 1989; 53: 493-501.
  • 9 Verma S, Li SH, Badiwala MV. et al. Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic effects of C-reactive protein. Circulation 2002; 105: 1890-6.
  • 10 Tsai AW, Cushman M, Rosamond WD. et al. Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE). Am J Med 2002; 113: 636-42.
  • 11 Koster T, Blann AD, Briet E. et al. Role of clotting factor VIII in the effect of von Willebrand factor on occurrence of deep vein thrombosis. Lancet 1995; 345: 152-5.
  • 12 Kraaijenhagen RA, Anker PS, Koopman MMW. et al. High plasma concentration of factor VIII C: A major risk factor for venous thromboembolism. Blood 1998; 92 (Suppl. 10) pt.1 501a.
  • 13 O’Donnell J, Tuddenham EG, Manning R. et al. High prevalence of elevated factor VIII levels in patients referred for thrombophilia screening: role of increased synthesis and relationship to the acute phase reaction. Thromb Haemost 1997; 77: 825-8.
  • 14 O’Donnell J, Mumford AD, Manning RA. et al. Elevation of FVIII: C in venous thromboembolism is persistent and independent of the acute phase response. Thromb Haemost 2000; 83: 10-13.
  • 15 Kamphuisen PW, Eikenboom JC, Vos HL. et al. 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.
  • 16 Thomas EA, Cobby MJ, Rhys DE. et al. Liquid crystal thermography and C reactive protein in the detection of deep venous thrombosis. BMJ 1989; 299: 951-2.
  • 17 Wong NA, Laitt RD, Goddard PR. et al. Serum C reactive protein does not reliably exclude lower limb deep venous thrombosis. Thromb Haemost 1996; 76: 816-7.
  • 18 Maskell NA, Butland RJ. A normal serum CRP measurement does not exclude deep vein thrombosis. Thromb Haemost 2001; 86: 1582-3.
  • 19 Bucek RA, Reiter M, Quehenberger P. et al. C-reactive protein in the diagnosis of deep vein thrombosis. Br J Haematol 2002; 119: 385-9.
  • 20 van Aken BE, den Heijer M, Bos GM. et al. Recurrent venous thrombosis and markers of inflammation. Thromb Haemost 2000; 83: 536-9.
  • 21 van Aken BE, Reitsma PH, Rosendaal FR. Interleukin 8 and venous thrombosis: evidence for a role of inflammation in thrombosis. Br J Haematol 2002; 116: 173-7.
  • 22 Reitsma PH, Rosendaal FR. Activation of innate immunity in patients with venous thrombosis: the Leiden Thrombophilia Study. J Thromb Haemost 2004; 2: 619-22.
  • 23 Roumen-Klappe EM, den Heijer M, van Uum SH. et al. Inflammatory response in the acute phase of deep vein thrombosis. J Vasc Surg 2002; 35: 701-6.
  • 24 Downing LJ, Strieter RM, Kadell AM. et al. Lowdose low-molecular-weight heparin is anti-inflammatory during venous thrombosis. J Vasc Surg 1998; 28: 848-54.