Review article| Volume 19, ISSUE 7, P476-481, November 2008

Venous and arterial thrombosis: Different sides of the same coin?

  • Massimo Franchini
    Transfusion and Hemophilia Center, City Hospital of Verona, Italy
    Search for articles by this author
  • Pier Mannuccio Mannucci
    Corresponding author. Via Pace 9, 20122 Milano, Italy. Tel.: +0039 02 55035423; fax: +0039 02 50320723.
    Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialities, University of Milan and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy
    Search for articles by this author
Published:March 25, 2008DOI:


      Until recently venous and arterial thrombosis were considered mechanistically distinct entities. However, their separate nature has been challenged by several studies showing that these conditions share a number of risk factors such as age, obesity, infections and the metabolic syndrome. The existence of an association is further supported by the finding that patients with venous thromboembolism are at higher risk of arterial events and vice versa. This review article addresses the association between venous and arterial thrombosis and its clinical and therapeutic implications. We conclude that arterial and venous thrombosis are mechanistically different, but that common risk factors are more relevant and frequent than previously thought.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Walker I.D.
        • Greaves M.
        • Preston F.E.
        Investigation and management of heritable thrombophilia.
        Br J Haematol. 2001; 114: 512-528
        • Prandoni P.
        Links between arterial and venous disease.
        J Intern Med. 2007; 262: 341-350
        • Jeries-Sanchez C.
        Venous and arterial thrombosis: a continuous spectrum of the same disease?.
        Eur Heart J. 2005; 26: 3-4
        • Agnelli G.
        • Becattini C.
        Venous thromboembolism and atherosclerosis: common denominators or different diseases?.
        J Thromb Haemost. 2006; 4: 1886-1890
        • Lowe G.D.O.
        Arterial disease and venous thrombosis: are they related, and if so, what should we do about it?.
        J Thromb Haemost. 2006; 4: 1882-1885
        • Prandoni P.
        Venous thromboembolism and atherosclerosis: is there a link?.
        J Thromb Haemost. 2007; 5: 270-275
        • Heit J.
        Venous thromboembolism epidemiology: implications for prevention and management.
        Semin Thromb Haemost. 2002; 28: 3-13
        • Marmot M.
        Social determinants of health inequalities.
        Lancet. 2005; 365: 1099-1104
        • Yusuf S.
        • Hawken S.
        • Ounpuu S.
        • et al.
        Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
        Lancet. 2004; 364: 937-952
        • Lowe G.D.O.
        • Rumley A.
        • Woodward M.
        • et al.
        Epidemiology of coagulation factors, inhibitors and activation markers: the Third Glasgow MONICA Survey. I. Illustrative reference ranges by age, sex and hormone use.
        Br J Haematol. 1997; 97: 775-784
        • Rumley A.
        • Emberson J.R.
        • Wannamethee S.G.
        • Lennon L.
        • Whincup P.H.
        • Lowe G.D.
        Effects of older age on fibrin D-dimer, C-reactive protein, and other hemostatic and inflammatory variables in men aged 60–79 years.
        J Thromb Haemost. 2006; 4: 982-987
        • Hansson P.O.
        • Eriksson H.
        • Welin L.
        • Svardsudd K.
        • Wilhelmsen L.
        Smoking and abdominal obesity. Risk factors for VTE among middle aged men: “The study of men born in 1913”.
        Arch Intern Med. 1999; 159: 1886-1890
        • Goldhaber S.Z.
        • Grodstein F.
        • Stampfer M.J.
        • et al.
        A prospective study of risk factors for pulmonary embolism in women.
        JAMA. 1997; 277: 642-645
        • Deguchi H.
        • Pecheniuk N.
        • Elias D.
        • Averell P.
        • Griffin J.
        High-density lipoprotein deficiency and dyslipoproteinemia associated with venous thrombosis in men.
        Circulation. 2005; 112: 893-899
        • Eichinger S.
        • Pecheniuk N.M.
        • Hron G.
        • et al.
        High-density lipoprotein and the risk of recurrent venous thromboembolism.
        Circulation. 2007; 115: 1609-1614
        • Vaya A.
        • Mira Y.
        • Ferrando F.
        • et al.
        Hyperlipidaemia and venous thromboembolism in patients lacking thrombophilic risk factors.
        Br J Haematol. 2002; 118: 255-259
        • Marcucci R.
        • Liotta A.A.
        • Cellai A.P.
        • et al.
        Increased plasma levels of lipoprotein(a) and the risk of idiopathic and recurrent venous thromboembolism.
        Am J Med. 2003; 115: 601-605
        • Doggen C.J.
        • Smith N.L.
        • Lemaitre R.N.
        • Heckbert S.R.
        • Rosendaal F.R.
        • Psaty B.M.
        Serum lipid levels and the risk of venous thrombosis.
        Arterioscler Thromb Vasc Biol. 2004; 24: 1070-1075
        • Stein P.D.
        • Beemath A.
        • Olson R.E.
        Obesity as a risk factor in venous thromboembolism.
        Am J Med. 2005; 118: 978-980
        • Hong C.
        • Zhu F.
        • Du D.
        • Pilgram T.K.
        • Sicard G.A.
        • Bae K.T.
        Coronary artery calcification and risk factors for atherosclerosis in patients with venous thromboembolism.
        Atherosclerosis. 2005; 183: 169-174
        • Ageno W.
        • Prandoni P.
        • Romualdi E.
        • et al.
        The metabolic syndrome and the risk of venous thrombosis: a case-control study.
        J Thromb Haemost. 2006; 4: 1914-1918
        • Ay C.
        • Tengler T.
        • Vormittag R.
        • et al.
        Venous thromboembolism — a manifestation of the metabolic syndrome.
        Haematologica. 2007; 92: 374-380
        • Wannamethee S.G.
        • Lowe G.D.
        • Shaper A.G.
        • Rumley A.
        • Lennon L.
        • Whincup P.H.
        The metabolic syndrome and insulin resistance: relationship to haemostatic and inflammatory markers in older non-diabetic men.
        Atherosclerosis. 2005; 181: 101-108
        • Smeeth L.
        • Thomas S.L.
        • Hall A.J.
        • Hubbard R.
        • Farrington P.
        • Vallance P.
        Risk of myocardial infarction and stroke after acute infection or vaccination.
        N Engl J Med. 2004; 351: 2611-2618
        • Smeeth L.
        • Cook C.
        • Thomas S.
        • Hall A.J.
        • Hubbard R.
        • Vallance P.
        Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting.
        Lancet. 2006; 367: 1075-1079
        • Kim R.J.
        • Becker R.C.
        Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies.
        Am Heart J. 2003; 146: 948-957
        • Ye Z.
        • Liu A.H.C.
        • Higgins J.P.T.
        • et al.
        Seven hemostatic gene polymorphisms in coronary disease: meta-analysis of 66155 cases and 91307 controls.
        Lancet. 2006; 367: 651-658
        • Smith A.
        • Patterson C.
        • Yarnell J.
        • Rumley A.
        • Ben-Schlomo
        • Lowe G.
        Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study.
        Circulation. 2005; 112: 3080-3087
        • Vormittag R.
        • Vukovich T.
        • Stain M.
        • Lehr S.
        • Minar E.
        • Pabinger I.
        Lipoprotein(a) in patients with spontaneous venous thromboembolism.
        Thromb Res. 2007; 120: 15-20
        • Tsai A.W.
        • Cushman M.
        • Rosamond W.D.
        • Heckbert S.R.
        • Polak J.F.
        • Folsom A.R.
        Cardiovascular risk factors and venous thromboembolism incidence.
        Arch Intern Med. 2002; 162: 1182-1189
        • Glynn R.J.
        • Rosner B.
        Comparison of risk factors for the competing risks of coronary heart disease, stroke, and venous thromboembolism.
        Am J Epidemiol. 2005; 162: 975-982
        • Libertiny G.
        • Hands L.
        Deep venous thrombosis in peripheral vascular disease.
        Br J Surg. 1999; 86: 907-910
        • Eliasson A.
        • Bergqvist D.
        • Bjorck M.
        • Acosta S.
        • Sternby N.H.
        • Orgen M.
        Incidence and risk of venous thromboembolism in patients with verified arterial thrombosis: a population study based on 23,796 consecutive autopsies.
        J Thromb Haemost. 2006; 4: 1897-1902
        • Reich L.M.
        • Folsom A.R.
        • Key N.S.
        • et al.
        Prospective study of subclinical atherosclerosis as a risk factor for venous thromboembolism.
        J Thromb Haemost. 2006; 4: 1909-1913
        • van der Hagen P.B.
        • Folsom A.R.
        • Jenny N.S.
        • et al.
        Subclinical atherosclerosis and the risk of future venous thrombosis in the Cardiovascular Health Study.
        J Thromb Haemost. 2006; 4: 1903-1908
        • Prandoni P.
        • Bilora F.
        • Marchiori A.
        • et al.
        An association between atheroslerosis and venous thrombosis.
        N Engl J Med. 2003; 348: 1435-1441
        • Becattini C.
        • Agnelli G.
        • Prandoni P.
        • et al.
        A prospective study on cardiovascular events after acute pulmonary embolism.
        Eur Heart J. 2005; 26: 77-83
        • Prandoni P.
        • Ghirarduzzi A.
        • Prins M.H.
        • et al.
        Venous thromboembolism and the risk of subsequent symptomatic atherosclerosis.
        J Thromb Haemost. 2006; 4: 1891-1896
        • Bova C.
        • Marchiori A.
        • Noto A.
        • et al.
        Incidence of arterial cardiovascular events in patients with idiopathic venous thromboembolism. A retrospective cohort study.
        Thromb Haemost. 2006; 96: 132-136
        • 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; 4: 734-742
        • Sorensen H.T.
        • Horvath-Puko E.
        • Pedersen L.
        • Baron J.A.
        • Prandoni P.
        Venous thromboembolism and subsequent hospitalization due to acute arterial cardiovascular events: a 20 year cohort study.
        Lancet. 2007; 370: 1773-1779
        • Lowe G.D.O.
        Fibrin D-dimer and risk of cardiovascular events.
        Semin Vasc Med. 2005; 5: 387-398
        • Ray J.G.
        • Mamdani M.
        • Tsuyuki R.T.
        • Anderson D.R.
        • Yeo E.L.
        • Laupacis A.
        Use of statins and the subsequent development of deep vein thrombosis.
        Arch Intern Med. 2001; 161: 1405-1410
      1. Collaborative overview of randomised trials of antiplatelet therapy — III: reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. Antiplatelet Trialists' Collaboration.
        BMJ. 1994; 308: 235-246
        • The ESPS 2 Group
        European Stroke prevention study 2. Efficacy and safety data. Secondary endpoints.
        J Neurol Sci. 1997; 151: S27-S37
      2. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Antithrombotic Trialists' Collaboration.
        BMJ. 2002; 324: 71-86
        • Landolfi R.
        • Marchioli R.
        • Kutti J.
        • et al.
        Efficacy and safety of low-dose aspirin in polycythemia vera.
        N Engl J Med. 2004; 350: 114-124
        • De Caterina R.
        • Husted S.
        • Wallentin L.
        • et al.
        Anticoagulants in heart disease: current status and perspectives.
        Eur Heart J. 2007; 28: 880-913
        • Phillips D.R.
        • Conley P.B.
        • Sinha U.
        • Andre P.
        Therapeutic approaches in arterial thrombosis.
        J Thromb Haemost. 2005; 3: 1577-1589
        • Andreotti F.
        • Testa L.
        • Biondi-Zoccai G.G.
        • Crea F.
        Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25,307 patients.
        Eur Heart J. 2006; 27: 519-526
        • Anand S.
        • Yusuf S.
        Oral anticoagulants in patients with coronary artery disease.
        JACC. 2003; 41: 62S-69S
      3. The medical research council's general practice research framework. Thrombosis prevention trial: randomized trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischemic heart disease in men at increased risk.
        Lancet. 1998; 351: 233-241
        • Cannon C.P.
        Evolving management of ST-segment elevation myocardial infarction: update on recent data.
        Am J Cardiol. 2006; 98 (Suppl): Q10-Q21
        • Popma J.J.
        • Berger P.
        • Ohman E.M.
        • Harrington R.A.
        • Grines C.
        • Weitz J.I.
        Antithrombotic therapy during percutaneous coronary intervention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.
        Chest. 2004; 126: 576S-599S
        • Gubitz G.
        • Sandercock P.
        • Counsell C.
        Anticoagulants for acute ischaemic stroke.
        Cochrane Database Syst Rev. 2004; 3: CD000024
        • Paciaroni M.
        • Agnelli G.
        • Micheli S.
        • Caso V.
        Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke: a meta-analysis of randomized controlled trials.
        Stroke. 2007; 38: 423-430
        • Aguilar R.I.
        • Hart R.
        • Pearce L.A.
        Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks.
        Cochrane Database Syst Rev. 2007; 3: CD006186
        • Adams H.P.
        • Del Zoppo G.
        • Alberts M.J.
        • et al.
        • American Heart Association
        • American Stroke Association Stroke Council
        • Clinical Cardiology Council
        • Cardiovascular Radiology and Intervention Council
        • Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups
        Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists.
        Stroke. 2007; 28: 1655-1711
        • WAVE Investigators
        The effects of oral anticoagulants in patients with peripheral arterial disease: rationale, design, and baseline characteristics of the Warfarin and Antiplatelet Vascular Evaluation (WAVE) trial, including a meta-analysis of trials.
        Am Heart J. 2006; 151: 1-9
        • WAVE Investigators
        Oral anticoagulant and antiplatelet therapy and peripheral arterial disease.
        N Engl J Med. 2007; 357: 217-227