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Thromb Haemost 2014; 111(06): 1031-1040
DOI: 10.1160/TH13-11-0931
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

The predictive value of markers of fibrinolysis and endothelial dysfunction in the post thrombotic syndrome

A systematic review
Anat Rabinovich
1   Center for Clinical Epidemiology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
,
Jacqueline M. Cohen
1   Center for Clinical Epidemiology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
2   Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
,
Susan R. Kahn
1   Center for Clinical Epidemiology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
2   Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
3   Division of Internal Medicine and Department of Medicine, McGill University, Montreal, Canada
› Author Affiliations
Further Information

Publication History

Received: 13 November 2013

Accepted after minor revision: 05 January 2014

Publication Date:
21 November 2017 (online)

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Summary

The post thrombotic syndrome (PTS) develops in 20–40% of deep venous thrombosis (DVT) patients. Risk factors for PTS have not been well elucidated. Identification of risk factors would facilitate individualised risk assessment for PTS. We conducted a systematic review to determine whether biomarkers of fibrinolysis or endothelial dysfunction can predict the risk for PTS among DVT patients. Studies were identified by searching the electronic databases PubMed, EMBASE, Scopus and Web of science. We included studies published between 1990 and 2013, measured biomarker levels in adult DVT patients, and reported rates of PTS development. Fourteen studies were included: 11 investigated the association between D-dimer and PTS; three examined fibrinogen; two measured von Willebrand factor; one measured plasminogen activator inhibitor-1; one assessed ADAMTS-13 (A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats) and one measured factor XIII activity. Studies varied with regards to inclusion criteria, definition of PTS, time point and method of biomarker measurement. We were unable to meta-analyse results due to marked clinical heterogeneity. Descriptively, a significant association with PTS was found for D-dimer in four studies and factor XIII in one study. Further prospective research is needed to elucidate whether these markers might be useful to predict PTS development.

Keywords

Post thrombotic syndrome - deep vein thrombosis - D-dimer - risk factors - fibrinolysis

 

  • References

  • 1 Kahn SR. The postthrombotic syndrome: progress and pitfalls. Br J Haematol 2006; 134: 357-365.
    CrossrefPubMedSearch in Google Scholar
  • 2 Kurz X, Kahn SR, Abenhaim L. et al. Chronic venous disorders of the leg: epidemiology, outcomes, diagnosis and management - Summary of an evidence-based report of the VEINES task force. Int Angiol 1999; 18: 83-102.
    PubMedSearch in Google Scholar
  • 3 Phillips II LJ, Sarkar R. Molecular characterization of postthrombotic syndrome. J Vasc Surg 2007; 45: 116A-122A.
    CrossrefPubMedSearch in Google Scholar
  • 4 Johnson BF, Manzo RA, Bergelin RO. et al. Relationship between changes in the deep venous system and the development of the postthrombotic syndrome after an acute episode of lower limb deep vein thrombosis: a one- to six-year follow-up. J Vasc Surg 1995; 21: 307-312.
    CrossrefPubMedSearch in Google Scholar
  • 5 Raju S. Regarding ‘‘The development of the postthrombotic syndrome in relationship to venous reflux and calf muscle pump dysfunction at 2 years after the onset of deep vein thrombosis’’ [letter]. J Vasc Surg 2002; 35: 1297-1298.
    CrossrefPubMedSearch in Google Scholar
  • 6 Prandoni P, Frulla M, Sartor D. et al. Venous abnormalities and the postthrombotic syndrome. J Thromb Haemost 2005; 03: 401-402.
    CrossrefPubMedSearch in Google Scholar
  • 7 Palareti G, Cosmi B, Legnani C. et al. D dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 2006; 355: 1780-1789.
    CrossrefPubMedSearch in Google Scholar
  • 8 Verhovsek M, Douketis JD, Yi Q. et al. Systematic review: D-dimer to predict recurrent disease after stopping anticoagulation therapy for unprovoked venous thromboembolism. Ann Intern Med 2008; 149: 481-490.
    CrossrefPubMedSearch in Google Scholar
  • 9 Aird WC. Phenotypic heterogeneity of the endothelium, I. Structure, function, and mechanisms. Circ Res 2007; 100: 158-173.
    CrossrefPubMedSearch in Google Scholar
  • 10 Deatrick KB, Eliason JL, Lynch EM. et al. Vein wall remodeling after deep vein thrombosis involves matrix metalloproteinases and late fibrosis in a mouse model. J Vasc Surg 2005; 42: 140-148.
    CrossrefPubMedSearch in Google Scholar
  • 11 Zhu T, Martinez I, Emmerich J. Venous thromboembolism: risk factors for recurrence. Arterioscler Thromb Vasc Biol 2009; 29: 298-310.
    CrossrefPubMedSearch in Google Scholar
  • 12 Rabinovich A, Cohen JM, Prandoni P. et al. Association between thrombophilia and the post thrombotic syndrome: a systematic review and meta-analysis. J Thromb Haemost 2014; 12: 14-23.
    CrossrefPubMedSearch in Google Scholar
  • 13 Villalta S, Bagatella P, Piccioli A. et al. Assessment of validity and reproducibility of a clinical scale for the postthrombotic syndrome [abstract]. Haemostasis 1994; 24: 158A
    PubMedSearch in Google Scholar
  • 14 Kahn SR, Hirsch A, Shrier I. Effect of postthrombotic syndrome on health-related quality of life after deep venous thrombosis. Arch Intern Med 2002; 162: 1144-1148.
    CrossrefPubMedSearch in Google Scholar
  • 15 Porter JM, Moneta GL. Reporting standards in venous disease: an update. International consensus committee on chronic venous disease. J Vasc Surg 1995; 21: 635-645.
    CrossrefPubMedSearch in Google Scholar
  • 16 Wells GA, Shea B, O’Connell D. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. Available at: URL: http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm
    PubMed
  • 17 Galanaud JP, Holcroft CA, Rodger MA. et al. Predictors of Post-Thrombotic Syndrome in a Population with a First Deep Vein Thrombosis and No Primary Venous Insufficiency. J Thromb Haemost 2013; 11: 474-480.
    CrossrefPubMedSearch in Google Scholar
  • 18 Mazetto BM, Orsi FL, Barnabé A. et al. Increased ADAMTS13 activity in patients with venous thromboembolism. Thromb Res 2012; 130: 889-893.
    CrossrefPubMedSearch in Google Scholar
  • 19 Schulman S, Lindmarker P, Holmstrom M. et al. Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months. J Thromb Haemost 2006; 04: 734-742.
    CrossrefPubMedSearch in Google Scholar
  • 20 Gabriel F, Labiós M, Portolés O. et al. Incidence of postthrombotic syndrome and its association with various risk factors in a cohort of Spanish patients after one year of follow-up following acute deep venous thrombosis. Thromb Haemost 2004; 92: 328-336.
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Roberts LN, Patel RK, Chitongo P. et al. Presenting D-dimer and early symptom severity are independent predictors of post thrombotic syndrome following a first deep vein thrombosis. Br J Haematol 2013; 160: 817-824.
    CrossrefPubMedSearch in Google Scholar
  • 22 Bellmunt-Montoya S, Gonzalez-Canas E, Solanich-Valldaura T. et al. What awaits the patient following a diagnosis of deep vein thrombosis? A study of the factors predicting mortality, postthrombotic syndrome and quality of life [in spanish; English abstract]. Angiologia 2006; 58: 39-49.
    CrossrefPubMedSearch in Google Scholar
  • 23 Marchena Yglesias PJ, Nieto Rodriguez JA, Serrano Martinez S. et al. Acute-phase reactants and markers of inflammation in venous thromboembolic disease: correlation with clinical and evolution parameters [in Spanish; English abstract]. An Med Interna 2006; 23: 105-110.
    PubMedSearch in Google Scholar
  • 24 Lopez-Azkarreta I, Reus S, Marco P. et al. Prospective study of the risk factors for the development of postthrombotic syndrome after proximal deep venous thrombosis [in spanish; English abstract]. Med Clin 2005; 125: 1-4.
    PubMedSearch in Google Scholar
  • 25 Latella J, Desmarais S, Miron MJ. et al. Relation between D-dimer level, venous valvular reflux and the development of postthrombotic syndrome after deep vein thrombosis. J Thromb Haemost 2010; 08: 2169-2175.
    CrossrefPubMedSearch in Google Scholar
  • 26 Bouman AC, Smits JJM, ten Cate H. et al. Markers of coagulation, fibrinolysis and inflammation in relation to postthrombotic syndrome. J Thromb Haemost 2012; 10: 1532-1538.
    CrossrefPubMedSearch in Google Scholar
  • 27 Stain M, Schonauer V, Minar E. et al. The postthrombotic syndrome: risk factors and impact on the course of thrombotic disease. J Thromb Haemost 2005; 03: 2671-2676.
    CrossrefPubMedSearch in Google Scholar
  • 28 Krieger E, Van Der Loo B, Amann-Vesti BR. et al. C-reactive protein and red cell aggregation correlate with late venous function after acute deep venous thrombosis. J Vasc Surg 2004; 40: 644-649.
    CrossrefPubMedSearch in Google Scholar
  • 29 Wik HS, Jacobsen AF, Sandvik L. et al. Prevalence and predictors for postthrombotic syndrome 3 to 16 years after pregnancy-related venous thrombosis: a population-based, cross-sectional, case-control study. J Thromb Haemost 2012; 10: 840-847.
    CrossrefPubMedSearch in Google Scholar
  • 30 Vanscheidt W, Hasler K, Wokalek H. et al. Factor XIII-deficiency in the blood of venous leg ulcer patients. Acta Derm Venereol 1991; 71: 55-57.
    PubMedSearch in Google Scholar
  • 31 Kahn SR, Partsch H, Vedantham S. et al. Definition of postthrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization. J Thromb Haemost 2009; 07: 879-883.
    CrossrefPubMedSearch in Google Scholar
  • 32 Monreal M, Martorell A, Callejas J. et al. Venographic assessment of deep vein thrombosis and risk of developing postthrombotic syndrome: a prospective study. J Intern Med 1993; 233: 233-238.
    CrossrefPubMedSearch in Google Scholar
  • 33 Meissner MH, Caps MT, Zierler BK. et al. Determinants of chronic venous disease after acute deep venous thrombosis. J Vasc Surg 1998; 28: 826-833.
    CrossrefPubMedSearch in Google Scholar
  • 34 Mohr DN, Silverstein MD, Heit JA. et al. The venous stasis syndrome after deep venous thrombosis or pulmonary embolism: a population-based study. Mayo Clin Proc 2000; 75: 1249-1256.
    CrossrefPubMedSearch in Google Scholar
  • 35 Asbeutah AM, Riha AZ, Cameron JD. et al. Five-year outcome study of deep vein thrombosis in the lower limbs. J Vasc Surg 2004; 40: 1184-1189.
    CrossrefPubMedSearch in Google Scholar
  • 36 Kahn SR, Shrier I, Julian JA. et al. Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med 2008; 149: 698-707.
    CrossrefPubMedSearch in Google Scholar
  • 37 Prandoni P, Lensing AW, Cogo A. et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996; 125: 1-7.
    CrossrefPubMedSearch in Google Scholar
  • 38 Prandoni P, Lensing AWA, Prins MH. et al. Below-Knee Elastic Compression Stockings To Prevent the Post-Thrombotic Syndrome. A Randomized, Controlled Trial. Ann Intern Med 2004; 141: 249-256.
    CrossrefPubMedSearch in Google Scholar
  • 39 Van Dongen CJ, Prandoni P, Frulla M. et al. Relation between quality of anticoagulant treatment and the development of the postthrombotic syndrome. J Thromb Haemost 2005; 03: 939-942.
    CrossrefPubMedSearch in Google Scholar
  • 40 Kahn SR. How I treat postthrombotic syndrome. Blood 2009; 114: 4624-4631.
    CrossrefPubMedSearch in Google Scholar
  • 41 Kahn SR. The post thrombotic syndrome. Thromb Res 2011; 127: S89-S92.
    CrossrefPubMedSearch in Google Scholar
  • 42 Khorana AA. Cancer-associated thrombosis: updates and controversies. Hematology Am Soc Hematol Educ Program 2012; 2012: 626-630.
    PubMedSearch in Google Scholar
  • 43 Tas F, Karabulut S, Bilgin E. et al. Clinical Significance of Coagulation Assays in Metastatic Pancreatic Adenocarcinoma. J Gastrointest Cancer. 2013 Epub ahead of print
    PubMedSearch in Google Scholar
  • 44 Granziera S, Rechichi A, De Rui M. et al. A new D-dimer cut-off in bedridden hospitalized elderly patients. Blood Coagul Fibrinolysis 2013; 24: 109-112.
    PubMedSearch in Google Scholar
  • 45 Davalos D, Akassoglou K. Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol 2012; 34: 43-62.
    CrossrefPubMedSearch in Google Scholar
  • 46 Prandoni P, Villalta S, Bagatella P. et al. The clinical course of Deep-vein thrombosis. Prospective long-term follow-up of 528 symptomatic patients. Haematologica 1997; 82: 423-428.
    PubMedSearch in Google Scholar
  • 47 Marcucci M, Iorio A, Douketis J. Management of Patients With Unprovoked Venous Thromboembolism: An Evidence-Based and Practical Approach. Curr Treat Options Cardiovasc Med 2013; 15: 224-239.
    CrossrefPubMedSearch in Google Scholar