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DOI: 10.1055/s-2001-14545
Deep Venous Thrombosis and Thrombophilia: Indications for Testing and Clinical Implications
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
- 2 Alhenc-Gelas M, Aiach M, de Moerloose P. Venous thromboembolic disease: risk factors and laboratory investigations. Semin Vasc Med . 2001; 1 81-88
- 3 Lane D, Mannucci P M, Bauer K A. Inherited thrombophilia: Part 2. Thromb Haemost . 1996; 76 824-834
- 4 De Stefano V, Finazzi G, Mannucci P M. Inherited thrombophilia: pathogenesis, clinical syndromes and management. Blood . 1996; 87 3531-3544
- 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
- 6 Laffan M, Tuddenham E. Assessing thrombotic risk. BMJ . 1998; 317 520-523
- 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
- 8 Huisman M V, Rosendaal F R. Thrombophilia. Curr Opin Hematol . 1999; 6 291-297
- 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
- 10 Kearon C, Crowther M, Hirsh J. Management of patients with hereditary hypercoagulable disorders. Annu Rev Med . 2000; 51 169-185
- 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
- 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
- 13 Rosendaal F R. Thrombosis in the young: epidemiology and risk factors. A focus on venous thrombosis. Thromb Haemost . 1997; 78 1-6
- 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
- 15 Brenner B. Inherited thrombophilia and fetal loss. Curr Opin Hematol . 2000; 7 290-295
- 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
- 17 Zoller B, Garcia de Frutos P, Hillarp A, Dahlback B. Thrombophilia as a multigenic disease. Haematologica . 1999; 84 59-70
- 18 den Heijer M. Homocysteine and venous thrombosis. In: Robinson K, ed. Homocysteine and Vascular Disease. Dordrecht, The Netherlands: Kluwer Academic; 2000: 239-252
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 26 Hyers T, Agnelli G, Hull R. Antithrombotic therapy for venous thromboembolic disease. Chest . 2001; 119 1765-1935
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 48 Lahita R G. Hormonal contraception and replacement and the use of androgens in the antiphospholipid syndrome. J Autoimmunity . 2000; 15 213-216
- 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
- 50 Walker I D. Congenital thrombophilia. Baillières Clin Obstet Gynaecol . 1997; 11 431-445
- 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
- 52 Rai R. Obstetric management of antiphospholipid syndrome. J Autoimmunity . 2000; 15 203-208
- 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
- 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
- 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