Extension of anticoagulation after venous thromboembolism

Summary

Whereas every clinician agrees on the need for anticoagulation initially after the diagnosis of venous thromboembolism (VTE), the opinions regarding optimal duration of secondary prophylaxis differ. The decision is complicated by the large number of identified risk factors associated with the risk of recurrence. In addition consideration has to be taken to the risk factors for bleeding and individual patient preferences. Data from long-term follow-up studies up to a decade indicate that some risk factors for recurrence decline and others seem to gain importance with time. In this review data has been extracted from the most illustrative trials to highlight controversies but also where there is consensus in order to give the clinician some support for the individual decisions on extension of anticoagulation after VTE.

Zusammenfassung

Während unter den Ärzten dahingehend Konsens herrscht, dass sofort eine Antikoagulanzientherapie einzuleiten ist, wenn eine venöser Thromboembolie (VTE) diagnostiziert wird, gehen die Meinungen bezüglich der optimalen Dauer der sekundären Thromboseprophylaxe auseinander. Die Entscheidung wird durch die große Anzahl nachgewiesener Risikofaktoren erschwert, die das Rezidivrisiko bedingen. Darüber hinaus sind die Risikofaktoren für das Auftreten von Blutungen und die Präferenzen der Patienten zu berücksichtigen. Daten aus Langzeitstudien, deren Follow-up bis zu zehn Jahren betrug, weisen darauf hin, dass bestimmte Rezidivrisikofaktoren mit der Zeit an Bedeutung verlieren, während andere im Laufe der Zeit größeres Gewicht erlangen. Dieser Überblick enthält Daten aus den aussagekräftigsten Studien. Es soll gezeigt werden, wo gegensätzliche Ansichten vorliegen und wo Konsens besteht. Der Arzt erhält damit eine Entscheidungshilfe bei der Festlegung der Dauer der Antikoagulanzientherapie nach VTE. Verlängerung der antikoagulativen Behandlung nach venöser Thromboembolie Entscheidungsrelevante Risikofaktoren

Keywords

Venous thromboembolism - risk factors - recurrence - bleeding

Schlüsselwörter

Venöse Thromboembolie - Risikofaktoren - Rückfall - Blutung

• References

• 1 Lindhagen A, Bergqvist D, Hallböök T. Deep venous insufficiency after postoperative thrombosis diagnosed with 125I-labelled fibrinogen uptake test. Br J Surg 1984; 71: 511-515.
• 2 Prandoni P, Lensing AW, Cogo A. et al. The longterm clinical course of acute deep venous thrombosis. Ann Intern Med 1996; 125: 1-7.
• 3 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.
• 4 Heit JA, Rooke TW, Silverstein MD. et al. Trends in the incidence of venous stasis syndrome and venous ulcer: a 25-year population-based study. J Vasc Surg 2001; 33: 1022-1027.
• 5 Pengo V, Lensing A, Prins MH. et al. for the Thromboembolic Pulmonary Hypertension Study Group. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004; 350: 2257-2264.
• 6 Büller HR, Agnelli G, Hull RD. et al. Antithrombotic therapy for venous thromboembolic disease. Chest 2004; 126 Suppl 401S-428S.
• 7 Pinedé L, Ninet J, Duhaut P. et al. Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Circulation 2001; 103: 2453-2460.
• 8 Schulman S, Wahlander K, Lundstrom T. et al. Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran. N Engl J Med 2003; 349: 1713-1721.
• 9 Schulman S, Rhedin AS, Lindmarker P. et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group. N Engl J Med 1995; 332: 1661-1665.
• 10 Boutitie F, Schulman S, Kearon C. et al. Factors at baseline influencing the risk of recurrence in venous thromboembolism: results of a meta-analysis on individual patient data. Blood 2003; 102: 730.
• 11 Douketis JD, Crowther MA, Foster GA. et al. Does the location of thrombosis determine the risk of disease recurrence in patients with proximal deep vein thrombosis?. Am J Med 2001; 110: 515-519.
• 12 Douketis JD, Gu CS, Schulman S. et al. The risk for fatal pulmonary embolism after discontinuing anticoagulant therapy for venous thromboembolism. Ann Intern Med 2007; 147: 766-774.
• 13 Lane DA, Mannucci PM, Bauer KA. et al. Inherited thrombophilia: Part 2. Thromb Haemost 1996; 76: 824-834.
• 14 Baglin T, Luddington R, Brown K. et al. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet 2003; 362: 523-526.
• 15 Schulman S, Granqvist S, Holmström M. et al. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. The Duration of Anticoagulation Trial Study Group. N Engl J Med 1997; 336: 393-398.
• 16 Ridker PM, Goldhaber SZ, Danielson E. et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003; 348: 1425-1434.
• 17 Heit JA, Mohr DN, Silverstein MD. et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 2000; 160: 761-768.
• 18 Young L, Ockelford P, Milne D. et al. Post treatment residual thrombus is associated with an increased risk of DVT recurrence, mortality and a trend towards increased vascular death. J Thromb Haemost 2005; 3 (Suppl. 01) OR365.
• 19 Prandoni P, Lensing AW, Prins MH. et al. Residual venous thrombosis as a predictive factor of recurrent venous thromboembolism. Ann Intern Med 2002; 137: 955-960.
• 20 Piovella F, Crippa L, Barone M. et al. Normalization rates of compression ultrasonography in patients with a first episode of deep vein thrombosis of the lower limbs: association with recurrence and new thrombosis. Haematologica 2002; 87: 515-522.
• 21 Cosmi B, Legnani C, Cini M. et al. D-dimer levels in combination with residual venous obstruction and the risk of recurrence after anticoagulation withdrawal for a first idiopathic deep vein thrombosis. Thromb Haemost 2005; 94: 969-774.
• 22 Kniffin Jr WD, Baron JA, Barrett J. et al. The epidemiology of diagnosed pulmonary embolism and deep venous thrombosis in the elderly. Arch Intern Med 1994; 154: 861-866.
• 23 Ögren M, Eriksson H, Bergqvist D. et al. Subcutaneous fat accumulation and BMI associated with risk for pulmonary embolism in patients with proximal deep vein thrombosis: a population study based on 23 796 consecutive autopsies. J Intern Med 2005; 258: 166-711.
• 24 Heit JA, Silverstein MD, Mohr DN. et al. The epidemiology of venous thromboembolism in the community. Thromb Haemost 2001; 86: 452-463.
• 25 White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107: 14-18.
• 26 Gore I, Hirst AE, Tanaka K. Myocardial infarction and thromboembolims: a comparative study in Boston and in Kyushu, Japan. Arch Intern Med 1964; 113: 323-330.
• 27 Mok CK, Hoaglund FT, Rogoff SM. et al. The incidence of deep vein thrombosis in Hong Kong Chinese after hip surgery for fracture of the proximal femur. Br J Surg 1979; 66: 640-642.
• 28 Silverstein MD, Heit JA, Mohr DN. et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158: 585-593.
• 29 Piovella F, Wang CJ, Lu H. et al. Deep-vein thrombosis rates after major orthopedic surgery in Asia. An epidemiological study based on postoperative screening with centrally adjudicated bilateral venography. J Thromb Haemost 2005; 3: 2664-2670.
• 30 McRae S, Tran H, Schulman S. et al. Effect of patient’s sex on risk of recurrent venous thromboembolism: a meta-analysis. Lancet 2006; 368: 371-378.
• 31 Goldhaber SZ, Grodstein F, Stampfer MJ. et al. A prospective study of risk factors for pulmonary embolism in women. JAMA 1997; 277: 642-645.
• 32 Goldhaber SZ, Savage DD, Garrison RJ. et al. Risk factors for pulmonary embolism. The Framingham Study. American Journal of Medicine 1983; 74: 1023-1028.
• 33 Blaszyk H, Wollan PC, Witkiewicz AK. et al. Death from pulmonary thromboembolism in severe obesity: lack of association with established genetic and clinical risk factors. Virchows Archiv 1999; 434: 529-532.
• 34 Blaszyk H, Bjornsson J. Factor V leiden and morbid obesity in fatal postoperative pulmonary embolism. Arch Surg 2000; 135: 1410-1413.
• 35 Samama MM. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Intern Med 2000; 160: 3415-3420.
• 36 Tryba M, Wedel DJ. Central neuraxial block and low molecular weight heparin (enoxaparine): lessons learned from different dosage regimes in two continents. Acta Anaesthesiol Scand Suppl 1997; 111: 100-104.
• 37 Abdollahi M, Cushman M, Rosendaal FR. Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. Thromb Haemost 2003; 89: 493-498.
• 38 Eriksson H, Lundstrom T, Wahlander K. et al. Prognostic factors for recurrence of venous thromboembolism (VTE) or bleeding during long-term secondary prevention of VTE with ximelagatran. Thromb Haemost 2005; 94: 522-527.
• 39 Van den Belt AG, Sanson BJ, Simioni P. et al. Recurrence of venous thromboembolism in patients with familial thrombophilia. Arch Intern Med 1997; 157: 2227-2232.
• 40 Simioni P, Sanson BJ, Prandoni P. et al. Incidence of venous thromboembolism in families with inherited thrombophilia. Thromb Haemost 1999; 81: 198-202.
• 41 Ho WK, Hankey GJ, Quinlan DJ. et al. Risk of recurrent venous thromboembolism in patients with common thrombophilia: a systematic review. Arch Intern Med 2006; 166: 729-736.
• 42 Koster T, Blann AD, Briet E. et al. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-155.
• 43 Kyrle PA, Minar E, Hirschl M. et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000; 343: 457-462.
• 44 Legnani C, Cosmi B, Cini M. et al. High plasma levels of factor VIII and risk of recurrence of venous thromboembolism. Br J Haematol 2004; 124: 504-510.
• 45 O’Donnell J, Mumford AD, Manning RA. et al. Elevation of FVIII: C in venous thromboembolism is persistent and independent of the acute phase response. Thromb Haemost 2000; 83: 10-13.
• 46 Wahl DG, Guillemin F, de Maistre E. et al. Metaanalysis of the risk of venous thrombosis in individuals with antiphospholipid antibodies without underlying autoimmune disease or previous thrombosis. Lupus 1998; 7: 15-22.
• 47 Kearon C, Gent M, Hirsh J. et al. 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.
• 48 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.
• 49 Den Heijer M, Rosendaal FR, Blom HJ. et al. Hyperhomocysteinemia and venous thrombosis: a metaanalysis. Thromb Haemost 1998; 80: 874-877.
• 50 Ray JG. Meta-analysis of hyperhomocysteinemia as a risk factor for venous thromboembolic disease. Arch Intern Med 1998; 158: 2101-2106.
• 51 Eichinger S, Stümpflen A, Hirschl M. et al. Hyperhomocysteinemia is a risk factor of recurrent venous thromboembolism. Thromb Haemost 1998; 80: 566-569.
• 52 Christiansen SC, Cannegieter SC, Koster T. et al. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 2005; 293: 2352-2361.
• 53 Palareti G, Legnani C, Cosmi B. et al. Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thromb Haemost 2002; 87: 7-12.
• 54 Eichinger S, Minar E, Bialonczyk C. et al. D-dimer levels and risk of recurrent venous thromboembolism. JAMA 2003; 290: 1071-1074.
• 55 Palareti G, Legnani C, Cosmi B. et al. Predictive value of D-dimer test for recurrent venous thromboembolism after anticoagulation withdrawal in subjects with a previous idiopathic event and in carriers of congenital thrombophilia. Circulation 2003; 108: 313-318.
• 56 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.
• 57 Hron G, Eichinger S, Weltermann A. et al. Prediction of recurrent venous thromboembolism by the activated partial thromboplastin time. J Thromb Haemost 2006; 4: 752-756.
• 58 Eichinger S, Hron G, Hirschl M. et al. Prediction of recurrent venous thromboembolism by measuring ProC Global. Thromb Haemost 2007; 98: 1232-1236.
• 59 Heit JA, O’Fallon WM, Petterson TM. et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population- based study. Arch Intern Med 2002; 162: 1245-1248.
• 60 Baron JA, Gridley G, Weiderpass E. et al. Venous thromboembolism and cancer. Lancet 1998; 351: 1077-1080.
• 61 Sørensen HT, Mellemkjaer L, Steffensen FH. et al. The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism. N Engl J Med 1998; 338: 1169-1173.
• 62 Hutten BA, Prins MH, Gent M. et al. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol 2000; 18: 3078-3083.
• 63 Palareti G, Legnani C, Lee A. et al. A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic dis-ease in patients with or without malignancy. Thromb Haemost 2000; 84: 805-810.
• 64 Prandoni P, Lensing AW, Piccioli A. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100: 3484-348.
• 65 Llach F, Arieff AI, Massry SG. Renal vein thrombosis and nephrotic syndrome. A prospective study of 36 adult patients. Ann Intern Med 1975; 83: 8-14.
• 66 Hoyer PF, Gonda S, Barthels M. et al. Thromboembolic complications in children with nephrotic syndrome. Risk and incidence. Acta Paediatr Scand 1986; 75: 804-810.
• 67 Hillmen P, Lewis SM, Bessler M. et al. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med 1995; 333: 1253-1258.
• 68 Tefferi A. JAK2 mutations and clinical practice in myeloproliferative neoplasms. Cancer J 2007; 13: 366-371.
• 69 Danese S, Papa A, Saibeni S. et al. Inflammation and coagulation in inflammatory bowel disease: The clot thickens. Am J Gastroenterol 2007; 102: 174-186.
• 70 Sjoberg HE, Blomback M, Granberg PO. Thromboembolic complications, heparin treatment in increase in coagulation factors in Cushing’s syndrome. Acta Med Scand 1976; 199: 95-98.
• 71 Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3: 692-694.
• 72 Levine MN, Raskob G, Beyth RJ. et al. Hemorrhagic complications of anticoagulant treatment: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 287S-310S.
• 73 Gage BF, Yan Y, Milligan PE. et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151: 713-719.
• 74 Shireman TI, Mahnken JD, Howard PA. et al. Development of a contemporary bleeding risk model for elderly warfarin recipients. Chest 2006; 130: 1390-1396.
• 75 Kearon C, Ginsberg JS, Kovacs MJ. et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for longterm prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349: 631-639.
• 76 Kyrle PA, Minar E, Bialonczyk C. et al. The risk of recurrent venous thromboembolism in men and women. N Engl J Med 2004; 350: 2558-2563.