Download PDF
Semin intervent Radiol 2012; 29(01): 003-009
DOI: 10.1055/s-0032-1302445
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Medical Management of Venous Thromboembolism: What the Interventional Radiologist Needs to Know

Raj S. Kasthuri
1   Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
,
Nigel S. Key
1   Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
› Author Affiliations
Further Information

Publication History

Publication Date:
16 April 2012 (online)

Also available at
    Permissions and Reprints

Abstract

Deep vein thrombosis and pulmonary embolism are considered manifestations of the same pathophysiological process and are together referred to as venous thromboembolism (VTE). VTE is a common disorder with an incidence of 1 to 3 in 1000 in the general population. It is estimated that the incidence of VTE is likely to increase as the average life expectancy of the U.S. population increases. Treatment of VTE consists of anticoagulation; the duration of anticoagulation is largely determined by the circumstances surrounding development of the thrombotic event. Vitamin K antagonists, the only oral anticoagulants approved for treatment of VTE in the United States, have several drawbacks and therefore new oral anticoagulants are currently in various stages of development. This review focuses on the risk factors for VTE and the approach to determining the duration of anticoagulation in patients with VTE. Results of clinical trials on the new oral anticoagulants that may soon be licensed for the treatment of VTE are also discussed.

Keywords

venous thromboembolism - thrombophilia testing - anticoagulation - medical management
 

  • References

  • 1 Heit JA. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol 2008; 28 (3) 370-372
    CrossrefPubMedGoogle Scholar
  • 2 White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107 (23, Suppl 1) I4-I8
    PubMedGoogle Scholar
  • 3 The surgeon general's call to action to prevent deep vein thrombosis and pulmonary embolism. 2008 http://www.surgeongeneral.gov/topics/deepvein/calltoaction/call-to-action-on-dvt-2008.pdf . Accessed October 16, 2011
    PubMedGoogle Scholar
  • 4 Juul K, Tybjaerg-Hansen A, Schnohr P, Nordestgaard BG. Factor V Leiden and the risk for venous thromboembolism in the adult Danish population. Ann Intern Med 2004; 140 (5) 330-337
    CrossrefPubMedGoogle Scholar
  • 5 Moll S. Thrombophilias—practical implications and testing caveats. J Thromb Thrombolysis 2006; 21 (1) 7-15
    CrossrefPubMedGoogle Scholar
  • 6 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 (10) 3698-3703
    CrossrefPubMedGoogle Scholar
  • 7 Demers C, Ginsberg JS, Hirsh J, Henderson P, Blajchman MA. Thrombosis in antithrombin-III-deficient persons. Report of a large kindred and literature review. Ann Intern Med 1992; 116 (9) 754-761
    CrossrefPubMedGoogle Scholar
  • 8 Allaart CF, Poort SR, Rosendaal FR, Reitsma PH, Bertina RM, Briët E. Increased risk of venous thrombosis in carriers of hereditary protein C deficiency defect. Lancet 1993; 341 (8838) 134-138
    CrossrefPubMedGoogle Scholar
  • 9 Tait RC, Walker ID, Reitsma PH , et al. Prevalence of protein C deficiency in the healthy population. Thromb Haemost 1995; 73 (1) 87-93
    PubMedGoogle Scholar
  • 10 Makris M, Leach M, Beauchamp NJ , et al. Genetic analysis, phenotypic diagnosis, and risk of venous thrombosis in families with inherited deficiencies of protein S. Blood 2000; 95 (6) 1935-1941
    PubMedGoogle Scholar
  • 11 Dykes AC, Walker ID, McMahon AD, Islam SI, Tait RC. A study of protein S antigen levels in 3788 healthy volunteers: influence of age, sex and hormone use, and estimate for prevalence of deficiency state. Br J Haematol 2001; 113 (3) 636-641
    CrossrefPubMedGoogle Scholar
  • 12 Martinelli I, Bucciarelli P, Margaglione M, De Stefano V, Castaman G, Mannucci PM. The risk of venous thromboembolism in family members with mutations in the genes of factor V or prothrombin or both. Br J Haematol 2000; 111 (4) 1223-1229
    CrossrefPubMedGoogle Scholar
  • 13 Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 1995; 85 (6) 1504-1508
    PubMedGoogle Scholar
  • 14 Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost 2005; 3 (2) 292-299
    CrossrefPubMedGoogle Scholar
  • 15 Den Heijer M, Willems HP, Blom HJ , et al. Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial. Blood 2007; 109 (1) 139-144
    CrossrefPubMedGoogle Scholar
  • 16 Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158 (6) 585-593
    CrossrefPubMedGoogle Scholar
  • 17 Tormene D, Ferri V, Carraro S, Simioni P. Gender and the risk of venous thromboembolism. Semin Thromb Hemost 2011; 37 (3) 193-198
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Kyrle PA, Minar E, Bialonczyk C, Hirschl M, Weltermann A, Eichinger S. The risk of recurrent venous thromboembolism in men and women. N Engl J Med 2004; 350 (25) 2558-2563
    CrossrefPubMedGoogle Scholar
  • 19 McRae S, Tran H, Schulman S, Ginsberg J, Kearon C. Effect of patient's sex on risk of recurrent venous thromboembolism: a meta-analysis. Lancet 2006; 368 (9533) 371-378
    CrossrefPubMedGoogle Scholar
  • 20 Pomp ER, le Cessie S, Rosendaal FR, Doggen CJ. Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations. Br J Haematol 2007; 139 (2) 289-296
    CrossrefPubMedGoogle Scholar
  • 21 Severinsen MT, Kristensen SR, Johnsen SP, Dethlefsen C, Tjønneland A, Overvad K. Smoking and venous thromboembolism: a Danish follow-up study. J Thromb Haemost 2009; 7 (8) 1297-1303
    CrossrefPubMedGoogle Scholar
  • 22 Holst AG, Jensen G, Prescott E. Risk factors for venous thromboembolism: results from the Copenhagen City Heart Study. Circulation 2010; 121 (17) 1896-1903
    CrossrefPubMedGoogle Scholar
  • 23 Lutsey PL, Virnig BA, Durham SB , et al. Correlates and consequences of venous thromboembolism: the Iowa Women's Health Study. Am J Public Health 2010; 100 (8) 1506-1513
    CrossrefPubMedGoogle Scholar
  • 24 Key NS, Kasthuri RS. Current treatment of venous thromboembolism. Arterioscler Thromb Vasc Biol 2010; 30 (3) 372-375
    CrossrefPubMedGoogle Scholar
  • 25 Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (6 Suppl) 454S-545S
    CrossrefPubMedGoogle Scholar
  • 26 Kyrle PA, Rosendaal FR, Eichinger S. Risk assessment for recurrent venous thrombosis. Lancet 2010; 376 (9757) 2032-2039
    CrossrefPubMedGoogle Scholar
  • 27 Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med 2002; 346 (10) 752-763
    CrossrefPubMedGoogle Scholar
  • 28 Rodger MA, Kahn SR, Wells PS , et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ 2008; 179 (5) 417-426
    CrossrefPubMedGoogle Scholar
  • 29 Siragusa S, Malato A, Anastasio R , et al. Residual vein thrombosis to establish duration of anticoagulation after a first episode of deep vein thrombosis: the Duration of Anticoagulation based on Compression UltraSonography (DACUS) study. Blood 2008; 112 (3) 511-515
    CrossrefPubMedGoogle Scholar
  • 30 Prandoni P, Prins MH, Lensing AW , et al; AESOPUS Investigators. Residual thrombosis on ultrasonography to guide the duration of anticoagulation in patients with deep venous thrombosis: a randomized trial. Ann Intern Med 2009; 150 (9) 577-585
    CrossrefPubMedGoogle Scholar
  • 31 Palareti G, Cosmi B, Legnani C , et al. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 2006; 355 (17) 1780-1789
    CrossrefPubMedGoogle Scholar
  • 32 Moll S. Who should be tested for thrombophilia?. Genet Med 2011; 13 (1) 19-20
    CrossrefPubMedGoogle Scholar
  • 33 Eikelboom JW, Weitz JI. New anticoagulants. Circulation 2010; 121 (13) 1523-1532
    CrossrefPubMedGoogle Scholar
  • 34 Van Es J, Eerenberg ES, Kamphuisen PW, Büller HR. How to prevent, treat, and overcome current clinical challenges of VTE. J Thromb Haemost 2011; 9 (Suppl. 01) 265-274
    CrossrefPubMedGoogle Scholar
  • 35 Castellone DD, Van Cott EM. Laboratory monitoring of new anticoagulants. Am J Hematol 2010; 85 (3) 185-187
    PubMedGoogle Scholar
  • 36 Samama MM, Guinet C. Laboratory assessment of new anticoagulants. Clin Chem Lab Med 2011; 49 (5) 761-772
    CrossrefPubMedGoogle Scholar
  • 37 Blech S, Ebner T, Ludwig-Schwellinger E, Stangier J, Roth W. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos 2008; 36 (2) 386-399
    CrossrefPubMedGoogle Scholar
  • 38 Stangier J, Eriksson BI, Dahl OE , et al. Pharmacokinetic profile of the oral direct thrombin inhibitor dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement. J Clin Pharmacol 2005; 45 (5) 555-563
    CrossrefPubMedGoogle Scholar
  • 39 Eriksson BI, Dahl OE, Huo MH , et al; RE-NOVATE II Study Group. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial. Thromb Haemost 2011; 105 (4) 721-729
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Eriksson BI, Dahl OE, Rosencher N , et al; RE-MODEL Study Group. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 2007; 5 (11) 2178-2185
    CrossrefPubMedGoogle Scholar
  • 41 Eriksson BI, Dahl OE, Rosencher N , et al; RE-NOVATE Study Group. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007; 370 (9591) 949-956
    CrossrefPubMedGoogle Scholar
  • 42 Schulman S, Kearon C, Kakkar AK , et al; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361 (24) 2342-2352
    CrossrefPubMedGoogle Scholar
  • 43 Connolly SJ, Ezekowitz MD, Yusuf S , et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151
    CrossrefPubMedGoogle Scholar
  • 44 Kubitza D, Becka M, Wensing G, Voith B, Zuehlsdorf M. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939—an oral, direct factor Xa inhibitor—after multiple dosing in healthy male subjects. Eur J Clin Pharmacol 2005; 61 (12) 873-880
    CrossrefPubMedGoogle Scholar
  • 45 Eriksson BI, Borris LC, Friedman RJ , et al; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008; 358 (26) 2765-2775
    CrossrefPubMedGoogle Scholar
  • 46 Kakkar AK, Brenner B, Dahl OE , et al; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 2008; 372 (9632) 31-39
    CrossrefPubMedGoogle Scholar
  • 47 Bauersachs R, Berkowitz SD, Brenner B , et al; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363 (26) 2499-2510
    CrossrefPubMedGoogle Scholar
  • 48 Ahrens I, Lip GY, Peter K. What do the RE-LY, AVERROES and ROCKET-AF trials tell us for stroke prevention in atrial fibrillation?. Thromb Haemost 2011; 105 (4) 574-578
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Raghavan N, Frost CE, Yu Z , et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos 2009; 37 (1) 74-81
    CrossrefPubMedGoogle Scholar
  • 50 Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM ; ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 2010; 363 (26) 2487-2498
    CrossrefPubMedGoogle Scholar
  • 51 Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P ; ADVANCE-2 investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 2010; 375 (9717) 807-815
    CrossrefPubMedGoogle Scholar
  • 52 Connolly SJ, Eikelboom J, Joyner C , et al; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364 (9) 806-817
    CrossrefPubMedGoogle Scholar