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静脉血栓栓塞患者无限期抗凝治疗的基本原则和指征

Authors
Gregory YH Lip, MD, FRCPE, FESC, FACC
Russell D Hull, MBBS, MSc
Section Editors
Jess Mandel, MD
Lawrence LK Leung, MD
Deputy Editor
Geraldine Finlay, MD
Translators
叶絮, 主任医师

引言

静脉血栓栓塞(venous thromboembolism, VTE)包括有两种表现形式，即深静脉血栓形成(deep vein thrombosis, DVT)和急性肺栓塞(pulmonary embolism, PE)。抗凝治疗是VTE患者的主要治疗手段。大多数VTE患者在VTE首次发作后，接受的是有限期的抗凝治疗(3-12个月)。在常规治疗疗程后，某些复发性血栓形成风险高的患者可能受益于无限期的抗凝治疗。在此情况下给予抗凝治疗，是为了减少复发性血栓形成和VTE相关死亡的终生风险。

本专题将讨论在一次VTE发作后进行治疗性无限期抗凝(而非预防性抗凝)的有关内容。可能和不大可能受益于无限期抗凝治疗的人群及其决定因素也将一并讨论。下肢DVT初始治疗和长期治疗的指征以及针对DVT和PE患者的其他治疗方法将单独详细讨论。 (参见“下肢深静脉血栓治疗概述”和“成人急性肺栓塞的治疗、预后和随访概述”和“静脉血栓栓塞症：初始抗凝治疗(最初10日)”和“静脉血栓栓塞的初始处理后抗凝”)

术语解释

在本文的讨论中，我们将采用如下术语：

●无诱因的VTE(DVT和/或PE)是指没有可识别的VTE的病因或诱发事件(也被称为自发性或特发性VTE)。相比之下，有诱因的VTE通常指由某种已知事件(如手术、住院)引起的VTE。导致VTE的诱发事件和危险因素可以是暂时的(即临时性的且可逆的，如雌激素治疗)或持久的。持久的危险因素包括可逆的情况(如手术后长时间制动、妊娠或可治愈的恶性肿瘤)，以及不可逆的情况(如遗传性血栓形成倾向和转移性终末期恶性肿瘤)。 (参见“静脉血栓形成病因概述”)

●近端DVT指位于腘静脉、股静脉或髂静脉的血栓。孤立性远端DVT患者没有近端血栓，其血栓位于膝以下，局限于小腿静脉(腓静脉、胫后静脉、胫前静脉和肌静脉)(表 1)。

                                   

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Literature review current through: 2017-06 . | This topic last updated: 2017-04-24.
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References
Top
  1. Husted S, de Caterina R, Andreotti F, et al. Non-vitamin K antagonist oral anticoagulants (NOACs): No longer new or novel. Thromb Haemost 2014; 111:781.
  2. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e419S.
  3. Baglin T, Bauer K, Douketis J, et al. Duration of anticoagulant therapy after a first episode of an unprovoked pulmonary embolus or deep vein thrombosis: guidance from the SSC of the ISTH. J Thromb Haemost 2012; 10:698.
  4. Nicolaides AN, Fareed J, Kakkar AK, et al. Prevention and treatment of venous thromboembolism--International Consensus Statement. Int Angiol 2013; 32:111.
  5. Iorio A, Kearon C, Filippucci E, et al. Risk of recurrence after a first episode of symptomatic venous thromboembolism provoked by a transient risk factor: a systematic review. Arch Intern Med 2010; 170:1710.
  6. Boutitie F, Pinede L, Schulman S, et al. Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants' data from seven trials. BMJ 2011; 342:d3036.
  7. Baglin T, Douketis J, Tosetto A, et al. Does the clinical presentation and extent of venous thrombosis predict likelihood and type of recurrence? A patient-level meta-analysis. J Thromb Haemost 2010; 8:2436.
  8. Agnelli G, Prandoni P, Santamaria MG, et al. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators. N Engl J Med 2001; 345:165.
  9. Douketis JD, Crowther MA, Foster GA, Ginsberg JS. Does the location of thrombosis determine the risk of disease recurrence in patients with proximal deep vein thrombosis? Am J Med 2001; 110:515.
  10. Kovacs MJ, Kahn SR, Wells PS, et al. Patients with a first symptomatic unprovoked deep vein thrombosis are at higher risk of recurrent venous thromboembolism than patients with a first unprovoked pulmonary embolism. J Thromb Haemost 2010; 8:1926.
  11. Couturaud F, Sanchez O, Pernod G, et al. Six Months vs Extended Oral Anticoagulation After a First Episode of Pulmonary Embolism: The PADIS-PE Randomized Clinical Trial. JAMA 2015; 314:31.
  12. Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013; 368:699.
  13. Middeldorp S, Prins MH, Hutten BA. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev 2014; :CD001367.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. Farraj RS. Anticoagulation period in idiopathic venous thromboembolism. How long is enough? Saudi Med J 2004; 25:848.
  20. Kearon C, Ginsberg JS, Kovacs MJ, et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349:631.
  21. Schulman S, Wåhlander K, Lundström T, et al. Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran. N Engl J Med 2003; 349:1713.
  22. EINSTEIN Investigators, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363:2499.
  23. EINSTEIN–PE Investigators, Büller HR, Prins MH, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366:1287.
  24. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369:799.
  25. Schulman S, Kearon C, Kakkar AK, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013; 368:709.
  26. Becattini C, Agnelli G, Schenone A, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012; 366:1959.
  27. Brighton TA, Eikelboom JW, Mann K, et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med 2012; 367:1979.
  28. Warkentin TE. Aspirin for dual prevention of venous and arterial thrombosis. N Engl J Med 2012; 367:2039.
  29. Simes J, Becattini C, Agnelli G, et al. Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration. Circulation 2014; 130:1062.
  30. Castellucci LA, Cameron C, Le Gal G, et al. Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: systematic review and network meta-analysis. BMJ 2013; 347:f5133.
  31. Hansson PO, Sörbo J, Eriksson H. Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors. Arch Intern Med 2000; 160:769.
  32. van der Hulle T, Tan M, den Exter PL, et al. Recurrence risk after anticoagulant treatment of limited duration for late, second venous thromboembolism. Haematologica 2015; 100:188.
  33. Wells PS, Forgie MA, Rodger MA. Treatment of venous thromboembolism. JAMA 2014; 311:717.
  34. Kearon C, Akl EA. Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism. Blood 2014; 123:1794.
  35. Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med 2003; 139:893.
  36. van Korlaar I, Vossen C, Rosendaal F, et al. Quality of life in venous disease. Thromb Haemost 2003; 90:27.
  37. Bauer KA. Low intensity warfarin: is it clinically useful in venous thromboembolism management? Br J Haematol 2004; 127:155.
  38. Locadia M, Bossuyt PM, Stalmeier PF, et al. Treatment of venous thromboembolism with vitamin K antagonists: patients' health state valuations and treatment preferences. Thromb Haemost 2004; 92:1336.
  39. Aujesky D, Smith KJ, Roberts MS. Oral anticoagulation strategies after a first idiopathic venous thromboembolic event. Am J Med 2005; 118:625.
  40. de Jong PG, Coppens M, Middeldorp S. Duration of anticoagulant therapy for venous thromboembolism: balancing benefits and harms on the long term. Br J Haematol 2012; 158:433.
  41. Rodger MA, Kahn SR, Wells PS, et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ 2008; 179:417.
  42. Eichinger S, Heinze G, Jandeck LM, Kyrle PA. Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation 2010; 121:1630.
  43. Tosetto A, Iorio A, Marcucci M, et al. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost 2012; 10:1019.
  44. 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.
  45. 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.
  46. Louzada ML, Carrier M, Lazo-Langner A, et al. Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism. Circulation 2012; 126:448.
  47. Christiansen SC, Lijfering WM, Helmerhorst FM, et al. Sex difference in risk of recurrent venous thrombosis and the risk profile for a second event. J Thromb Haemost 2010; 8:2159.
  48. Baglin T, Luddington R, Brown K, Baglin C. High risk of recurrent venous thromboembolism in men. J Thromb Haemost 2004; 2:2152.
  49. Christiansen SC, Cannegieter SC, Koster T, et al. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 2005; 293:2352.
  50. 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.
  51. Baglin T, Palmer CR, Luddington R, Baglin C. Unprovoked recurrent venous thrombosis: prediction by D-dimer and clinical risk factors. J Thromb Haemost 2008; 6:577.
  52. Kearon C, Spencer FA, O'Keeffe D, et al. D-dimer testing to select patients with a first unprovoked venous thromboembolism who can stop anticoagulant therapy: a cohort study. Ann Intern Med 2015; 162:27.
  53. Agnelli G, Becattini C, Prandoni P. Recurrent venous thromboembolism in men and women. N Engl J Med 2004; 351:2015.
  54. Cosmi B, Legnani C, Tosetto A, et al. Sex, age and normal post-anticoagulation D-dimer as risk factors for recurrence after idiopathic venous thromboembolism in the Prolong study extension. J Thromb Haemost 2010; 8:1933.
  55. Lijfering WM, Veeger NJ, Middeldorp S, et al. A lower risk of recurrent venous thrombosis in women compared with men is explained by sex-specific risk factors at time of first venous thrombosis in thrombophilic families. Blood 2009; 114:2031.
  56. Cushman M, Glynn RJ, Goldhaber SZ, et al. Hormonal factors and risk of recurrent venous thrombosis: the prevention of recurrent venous thromboembolism trial. J Thromb Haemost 2006; 4:2199.
  57. Kévorkian JP, Halimi C, Segrestaa JM, et al. Monitoring of patients with deep-vein thrombosis during and after anticoagulation with D-dimer. Lancet 1998; 351:571.
  58. 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.
  59. Eichinger S, Minar E, Bialonczyk C, et al. D-dimer levels and risk of recurrent venous thromboembolism. JAMA 2003; 290:1071.
  60. Shrivastava S, Ridker PM, Glynn RJ, et al. D-dimer, factor VIII coagulant activity, low-intensity warfarin and the risk of recurrent venous thromboembolism. J Thromb Haemost 2006; 4:1208.
  61. Poli D, Antonucci E, Ciuti G, et al. Combination of D-dimer, F1+2 and residual vein obstruction as predictors of VTE recurrence in patients with first VTE episode after OAT withdrawal. J Thromb Haemost 2008; 6:708.
  62. Bruinstroop E, Klok FA, Van De Ree MA, et al. Elevated D-dimer levels predict recurrence in patients with idiopathic venous thromboembolism: a meta-analysis. J Thromb Haemost 2009; 7:611.
  63. Verhovsek M, Douketis JD, Yi Q, et al. Systematic review: D-dimer to predict recurrent disease after stopping anticoagulant therapy for unprovoked venous thromboembolism. Ann Intern Med 2008; 149:481.
  64. Douketis J, Tosetto A, Marcucci M, et al. Patient-level meta-analysis: effect of measurement timing, threshold, and patient age on ability of D-dimer testing to assess recurrence risk after unprovoked venous thromboembolism. Ann Intern Med 2010; 153:523.
  65. Cosmi B, Legnani C, Tosetto A, et al. Usefulness of repeated D-dimer testing after stopping anticoagulation for a first episode of unprovoked venous thromboembolism: the PROLONG II prospective study. Blood 2010; 115:481.
  66. Palareti G, Cosmi B, Legnani C, et al. D-dimer to guide the duration of anticoagulation in patients with venous thromboembolism: a management study. Blood 2014; 124:196.
  67. Levine MN, Hirsh J, Gent M, et al. 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.
  68. 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.
  69. Young L, Ockelford P, Milne D, et al. Post-treatment residual thrombus increases the risk of recurrent deep vein thrombosis and mortality. J Thromb Haemost 2006; 4:1919.
  70. 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; 112:511.
  71. Prandoni P, Prins MH, Lensing AW, et al. Residual thrombosis on ultrasonography to guide the duration of anticoagulation in patients with deep venous thrombosis: a randomized trial. Ann Intern Med 2009; 150:577.
  72. LE Gal G, Carrier M, Kovacs MJ, et al. Residual vein obstruction as a predictor for recurrent thromboembolic events after a first unprovoked episode: data from the REVERSE cohort study. J Thromb Haemost 2011; 9:1126.
  73. Hamadah A, Alwasaidi T, LE Gal G, et al. Baseline imaging after therapy for unprovoked venous thromboembolism: a randomized controlled comparison of baseline imaging for diagnosis of suspected recurrence. J Thromb Haemost 2011; 9:2406.
  74. Tan M, Mos IC, Klok FA, Huisman MV. Residual venous thrombosis as predictive factor for recurrent venous thromboembolim in patients with proximal deep vein thrombosis: a sytematic review. Br J Haematol 2011; 153:168.
  75. Carrier M, Rodger MA, Wells PS, et al. Residual vein obstruction to predict the risk of recurrent venous thromboembolism in patients with deep vein thrombosis: a systematic review and meta-analysis. J Thromb Haemost 2011; 9:1119.
  76. Cosmi B, Legnani C, Cini M, et al. D-dimer and residual vein obstruction as risk factors for recurrence during and after anticoagulation withdrawal in patients with a first episode of provoked deep-vein thrombosis. Thromb Haemost 2011; 105:837.
  77. Tripodi A, Legnani C, Chantarangkul V, et al. High thrombin generation measured in the presence of thrombomodulin is associated with an increased risk of recurrent venous thromboembolism. J Thromb Haemost 2008; 6:1327.
  78. Hron G, Kollars M, Binder BR, et al. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA 2006; 296:397.
  79. Stain M, Schönauer V, Minar E, et al. The post-thrombotic syndrome: risk factors and impact on the course of thrombotic disease. J Thromb Haemost 2005; 3:2671.
  80. Castellucci LA, Le Gal G, Rodger MA, Carrier M. Major bleeding during secondary prevention of venous thromboembolism in patients who have completed anticoagulation: a systematic review and meta-analysis. J Thromb Haemost 2014; 12:344.
  81. Wells PS, Forgie MA, Simms M, et al. The outpatient bleeding risk index: validation of a tool for predicting bleeding rates in patients treated for deep venous thrombosis and pulmonary embolism. Arch Intern Med 2003; 163:917.
  82. Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998; 105:91.
  83. Scherz N, Méan M, Limacher A, et al. Prospective, multicenter validation of prediction scores for major bleeding in elderly patients with venous thromboembolism. J Thromb Haemost 2013; 11:435.
  84. Poli D, Antonucci E, Testa S, et al. The predictive ability of bleeding risk stratification models in very old patients on vitamin K antagonist treatment for venous thromboembolism: results of the prospective collaborative EPICA study. J Thromb Haemost 2013; 11:1053.
  85. Riva N, Bellesini M, Di Minno MN, et al. Poor predictive value of contemporary bleeding risk scores during long-term treatment of venous thromboembolism. A multicentre retrospective cohort study. Thromb Haemost 2014; 112:511.
  86. Schulman S. Tossing a coin or using common sense. J Thromb Haemost 2013; 11:432.
  87. Garcia DA, Baglin TP, Weitz JI, et al. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e24S.