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Semin Vasc Med 2001; 01(1): 089-096
DOI: 10.1055/s-2001-14545
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Deep Venous Thrombosis and Thrombophilia: Indications for Testing and Clinical Implications

Philippe de Moerloose1 , Martine Alhenc-Gelas2 , Françoise Boehlen1 , Henri Bounameaux1 , Martine Aiach2
  • 1Division of Angiology and Haemostasis, University Hospital Geneva, Geneva, Switzerland
  • 2Haematology Service, Georges Pompidou Hospital, Paris, France
Further Information

Publication History

Publication Date:
31 December 2001 (online)

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ABSTRACT

In the past 3 decades, numerous biological abnormalities linked with deep venous thrombosis have been described. Among the different possibilities, it is crucial to order tests that can modify the therapeutic attitude towards the patient and/or his family. A combined clinical and laboratory approach taking into account the history of the patient and his family, the prevalence of the defects, and also the accuracy of the tests should allow tailoring a laboratory testing program to each patient. It is essential to keep in mind that the more difficult task is not to perform the tests but to consider who will benefit from testing both for prevention and therapy of venous thromboembolism. This article provides answers to some of these issues. These answers should, however, be considered as tentative and provisional because new findings and study results will certainly modify them in the near future.

KEYWORD

Thrombophilia - deep vein thrombosis - pulmonary embolism - guidelines

REFERENCES

  • 1 British Society for Haematology. Guidelines on the investigation and management of thrombophilia.  J Clin Pathol . 1990;  43 703-710
    PubMedGoogle Scholar
  • 2 Alhenc-Gelas M, Aiach M, de Moerloose P. Venous thromboembolic disease: risk factors and laboratory investigations.  Semin Vasc Med . 2001;  1 81-88
    PubMedGoogle Scholar
  • 3 Lane D, Mannucci P M, Bauer K A. Inherited thrombophilia: Part 2.  Thromb Haemost . 1996;  76 824-834
    PubMedGoogle Scholar
  • 4 De Stefano V, Finazzi G, Mannucci P M. Inherited thrombophilia: pathogenesis, clinical syndromes and management.  Blood . 1996;  87 3531-3544
    PubMedGoogle Scholar
  • 5 Adcock D M, Fink L, Marlar R A. A laboratory approach to the evaluation of hereditary hypecoagulability.  Am J Clin Pathol . 1997;  108 434-449
    PubMedGoogle Scholar
  • 6 Laffan M, Tuddenham E. Assessing thrombotic risk.  BMJ . 1998;  317 520-523
    PubMedGoogle Scholar
  • 7 de Moerloose P, Mannucci P, Bounameaux H. Screening tests for thrombophilic patients: which test, for which patient, by whom, when and why?.  Semin Thromb Hemost . 1998;  24 321-327
    PubMedGoogle Scholar
  • 8 Huisman M V, Rosendaal F R. Thrombophilia.  Curr Opin Hematol . 1999;  6 291-297
    CrossrefPubMedGoogle Scholar
  • 9 Samama M M, Gerotziafas G, Conard J, Horellou M H, Elalamy I. Clinical aspects and laboratory problems in hereditary thrombophilia.  Haemostasis . 1999;  29 76-99
    PubMedGoogle Scholar
  • 10 Kearon C, Crowther M, Hirsh J. Management of patients with hereditary hypercoagulable disorders.  Annu Rev Med . 2000;  51 169-185
    CrossrefPubMedGoogle Scholar
  • 11 Baglin T. Thrombophilia testing: what do we think the tests mean and what should we do with the results?.  J Clin Pathol . 2000;  53 167-170
    CrossrefPubMedGoogle Scholar
  • 12 Middeldorp S, Büller H R, Prins M H, Hirsh J. Approach to the thrombophilic patient. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN, eds. Hemostasis and Thrombosis Basic Principles and Clinical Practice, 4th ed Philadelphia: Lippincott Williams & Wilkins 2001: 1085-1100
    Google Scholar
  • 13 Rosendaal F R. Thrombosis in the young: epidemiology and risk factors. A focus on venous thrombosis.  Thromb Haemost . 1997;  78 1-6
    PubMedGoogle Scholar
  • 14 Ridker P M, Hennekens C H, Lindpainter K, Stampfer M J, Eisenberg R P, Miletich J P. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke and venous thrombosis in apparently healthy men.  N Engl J Med . 1995;  332 912-917
    CrossrefPubMedGoogle Scholar
  • 15 Brenner B. Inherited thrombophilia and fetal loss.  Curr Opin Hematol . 2000;  7 290-295
    CrossrefPubMedGoogle Scholar
  • 16 de Moerloose P, Wutschert R, Heinzmann M, Perneger T h, Reber G, Bounameaux H. Superficial vein thrombosis of lower limbs: influence of factor V Leiden, factor II G20210A and overweight.  Thromb Haemost . 1998;  80 239-241
    PubMedGoogle Scholar
  • 17 Zoller B, Garcia de Frutos P, Hillarp A, Dahlback B. Thrombophilia as a multigenic disease.  Haematologica . 1999;  84 59-70
    PubMedGoogle Scholar
  • 18 den Heijer M. Homocysteine and venous thrombosis. In: Robinson K, ed. Homocysteine and Vascular Disease. Dordrecht, The Netherlands: Kluwer Academic; 2000: 239-252
    Google Scholar
  • 19 O'Donnel J O, Mumford A D, Manning R A, Laffan M. Elevation of factor VIII C in venous thromboembolism is persistent and independent of the acute phase response.  Thromb Haemost . 2000;  83 10-13
    PubMedGoogle Scholar
  • 20 van Hylckama A, van der Linden I, Bertina R M, Rosendaal F R. High levels of factor IX increase the risk of venous thrombosis.  Blood . 2000;  95 3678-3682
    PubMedGoogle Scholar
  • 21 Meijers J C, Tekelenburg W L, Bouma B N, Bertina R M, Rosendaal F R. High levels of factor XI as a risk factor for venous thrombosis.  N Eng J Med . 2000;  542 696-701
    PubMedGoogle Scholar
  • 22 van der Belt G M A, Hutten B A, Prins M H, Bossuyt P M. Duration of oral anticoagulant treatment in patients with venous thromboembolism and a deficiency of antithrombin, protein C or protein S-a decision analysis.  Thromb Haemost . 2000;  84 758-763
    PubMedGoogle Scholar
  • 23 Schulman S, Rhedin A-S, Lindmarker P. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism.  N Engl J Med . 1995;  332 1661-1665
    CrossrefPubMedGoogle Scholar
  • 24 Schulman S, Granqvist S, Holmstrom M. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism.  N Engl J Med . 1997;  336 393-398
    CrossrefPubMedGoogle Scholar
  • 25 Levine M N, Hirsh J, Gent M. Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis.  Thromb Haemost . 1995;  74 606-611
    PubMedGoogle Scholar
  • 26 Hyers T, Agnelli G, Hull R. Antithrombotic therapy for venous thromboembolic disease.  Chest . 2001;  119 1765-1935
    PubMedGoogle Scholar
  • 27 Prins M H, Hutten B A, Koopman M M, Büller H R. Long-term treatment of venous thromboembolic disease.  Thromb Haemost . 1999;  82 892-828
    PubMedGoogle Scholar
  • 28 Kearon C, Gent M, Hirsh J. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism.  N Engl J Med . 1999;  340 901-907
    PubMedGoogle Scholar
  • 29 Palareti G, Leali N, Coccheri S. Bleeding complications of oral anticoagulant treatment: an inception cohort, prospective collaborative study (ISCOAT).  Lancet . 1996;  348 423-428
    CrossrefPubMedGoogle Scholar
  • 30 De Stefano V, Leone G, Mastrangelo S. Clinical manifestations and management of inherited thrombophilia: retrospective analysis and follow-up after diagnosis of 238 patients with congenital deficiency of antithrombin, protein C, protein S.  Thromb Haemost . 1994;  72 352-358
    PubMedGoogle Scholar
  • 31 van der Belt G M A, Sanson B J, Simioni P. Recurrence of venous thromboembolism in patients with familial thrombophilia.  Arch Intern Med . 1997;  157 2227-2232
    CrossrefPubMedGoogle Scholar
  • 32 Schulman S, Svenungsson E, Granqvist S. Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Duration of Anticoagulation Study Group.  Am J Med . 1998;  104 332-338
    CrossrefPubMedGoogle Scholar
  • 33 Greaves M, Cohen H, Machin S J, Mackie I. Guidelines on the investigation and management of the antiphospholipid syndrome.  Br J Haematol . 2000;  109 704-715
    CrossrefPubMedGoogle Scholar
  • 34 Simioni P, Prandoni P, Lensing A W. The risk of recurrent venous thromboembolism in patients with an Arg506Gln mutation in the gene for factor V (factor V Leiden).  N Engl J Med . 1997;  336 399-403
    CrossrefPubMedGoogle Scholar
  • 35 Ridker P M, Miletich J P, Stampfer M J. Factor V Leiden and risks of recurrent idiopathic venous thromboembolism.  Circulation . 1995;  92 2800-2802
    CrossrefPubMedGoogle Scholar
  • 36 Eichinger S, Pabinger I, Stumpflen A. The risk of recurrent venous thromboembolism in patients with or without factor V Leiden.  Thromb Haemost . 1997;  77 624-628
    PubMedGoogle Scholar
  • 37 Eichinger S, Minar E, Hirschl M. The risk of early recurrent venous thromboembolism after oral anticoagulant therapy in patients with the G20210A transition in the prothrombin gene.  Thromb Haemost . 1999;  81 14-17
    PubMedGoogle Scholar
  • 38 De Stefano V, Martinelli I, Mannucci P M. The risk of recurrent deep venous thrombosis among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation.  N Engl J Med . 1999;  341 801-806
    CrossrefPubMedGoogle Scholar
  • 39 de Moerloose P, Reber G, Perrier A, Pernegger T, Bounameaux H. Prevalence of factor V Leiden and prothrombin G20210A mutations in unselected patients with venous thromboembolism.  Br J Haematol . 2000;  110 125-129
    CrossrefPubMedGoogle Scholar
  • 40 Sarasin F, Bounameaux H. Decision analysis model of prolonged anticoagulation in factor V Leiden carriers with a first episode of deep vein thrombosis.  BMJ . 1998;  316 95-99
    PubMedGoogle Scholar
  • 41 Marchetti M, Pistorio A, Barosi G. Extended anticoagulation for prevention of recurrent venous thromboembolism in carriers of factor V Leiden: cost-effectiveness analysis.  Thromb Haemost . 2000;  84 752-757
    PubMedGoogle Scholar
  • 42 Ridker P M. Long-term, low-dose warfarin among venous thrombosis patients with and without factor V Leiden mutation: rationale and design for the prevention of recurrent venous thromboembolism (PREVENT) trial.  Vasc Med . 1998;  3 67-73
    CrossrefPubMedGoogle Scholar
  • 43 Malinow M R, Nieto F J, Kruger W D. The effects of folic acid supplementation on plasma total homocysteine are modulated by multivitamin use and methylenetetrahydrofolate reductase genotypes.  Arterioscler Thromb Vasc Biol . 1997;  17 1157-1162
    CrossrefPubMedGoogle Scholar
  • 44 Vandenbroucke J P, Koster T, Briet E. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation.  Lancet . 1994;  344 1453-1457
    CrossrefPubMedGoogle Scholar
  • 45 Pabinger I, Schneider B. Thrombotic risk of women with hereditary antithrombin III, protein C and protein S deficiency taking oral contraceptive medication.  Thromb Haemost . 1994;  71 548-552
    PubMedGoogle Scholar
  • 46 Hulley S, Grady D, Bush T. Randomised trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women.  JAMA . 1998;  280 605-613
    CrossrefPubMedGoogle Scholar
  • 47 Martinelli I, Sacchi E, Landi G. High risk of cerebral vein thrombosis in carriers of a prothrombin gene mutation and in users of oral contraceptives.  N Engl J Med . 1998;  338 1793-1797
    CrossrefPubMedGoogle Scholar
  • 48 Lahita R G. Hormonal contraception and replacement and the use of androgens in the antiphospholipid syndrome.  J Autoimmunity . 2000;  15 213-216
    CrossrefPubMedGoogle Scholar
  • 49 Wahl D, Bounameaux H, de Moerloose P, Sarasin F. Prophylactic antithrombotic therapy for patients with systemic lupus erythematosus: do the benefits outweigh the risks?.  <~>A decision analysis. Arch Intern Med . 2000;  160 2042-2048
    PubMedGoogle Scholar
  • 50 Walker I D. Congenital thrombophilia.  Baillières Clin Obstet Gynaecol . 1997;  11 431-445
    PubMedGoogle Scholar
  • 51 Kutteh W H, Rote N S, Silver R. Antiphospholipid antibodies and reproduction: the antiphospholipid antibody syndrome.  Am J Reprod Immunol . 1999;  41 133-152
    CrossrefPubMedGoogle Scholar
  • 52 Rai R. Obstetric management of antiphospholipid syndrome.  J Autoimmunity . 2000;  15 203-208
    CrossrefPubMedGoogle Scholar
  • 53 Vandebroucke J P, van der Meer J F, Helmerhorst F M, Rosendaal F R. Factor V Leiden: should we screen oral contraceptives users and pregnant women?.  Br Med J . 1996;  313 1127-1130
    PubMedGoogle Scholar
  • 54 Gonzalez Ordonez J A, Medina Rodriguez M J, Martin L, Alvarez V, Coto E. The O blood group protects against venous thromboembolism in individuals with the factor V Leiden but not the prothrombin (factor II G20210A) mutation.  Blood Coagul Fibrinolysis . 1999;  10 303-307
    PubMedGoogle Scholar
  • 55 Arnaud E, Nicaud V, Poirier O. Protective effect of a thrombin receptor (protease-activated receptor 1) gene polymorphism towards venous thromboembolism.  Arterioscler Thromb Vasc Biol . 2000;  20 585-592
    PubMedGoogle Scholar