Practical issues with vitamin K antagonists: Elevated INRs, low time-in-therapeutic range, and warfarin failure

Journal of Thrombosis and Thrombolysis

Volumn 31, Issue 3, 2011, Pages 249-258

  Lee, Andrea ^a   Crowther, Mark ^a  

^a ST JOSEPH S HOSPITAL   (Canada)

Author keywords

Anticoagulation; Bleeding; INR; Vitamin K; Warfarin

Indexed keywords

ACENOCOUMAROL; ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; ANTIVITAMIN K; HEPARIN; LOW MOLECULAR WEIGHT HEPARIN; PHENPROCOUMON; PLACEBO; VITAMIN K GROUP; WARFARIN;

BLEEDING; CARDIOVASCULAR DISEASE; CONFERENCE PAPER; DEEP VEIN THROMBOSIS; DISEASE ASSOCIATION; DISEASE SEVERITY; DOSE TIME EFFECT RELATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG INDICATION; DRUG MECHANISM; DRUG METABOLISM; DRUG QUALITY; DRUG SAFETY; DRUG TREATMENT FAILURE; EVIDENCE BASED MEDICINE; HIGH RISK PATIENT; HUMAN; INTERNATIONAL NORMALIZED RATIO; LOW DRUG DOSE; LUNG EMBOLISM; MEDICAL LITERATURE; NONHUMAN; OUTCOME ASSESSMENT; PREDICTION; PRIORITY JOURNAL; PROTHROMBIN TIME; RECURRENT DISEASE; RISK ASSESSMENT; RISK FACTOR; RISK REDUCTION; STEADY STATE; THROMBOEMBOLISM; VENOUS THROMBOEMBOLISM;

ANTICOAGULANTS; DRUG INTERACTIONS; HEMORRHAGE; HUMANS; INTERNATIONAL NORMALIZED RATIO; MONITORING, PHYSIOLOGIC; RISK FACTORS; THROMBOSIS; VITAMIN K; WARFARIN;

EID: 79958180601     PISSN: 09295305     EISSN: 1573742X     Source Type: Journal    
DOI: 10.1007/s11239-011-0555-z     Document Type: Conference Paper

References (112)

1. Wardrop D, Keeling D (2008) The story of the discovery of heparin and warfarin. Br J Haematol 141(6):757-763 (Pubitemid 351724858)
2. Wittkowsky AK (2003) Warfarin and other coumarin derivatives: pharmacokinetics, pharmacodynamics, and drug interactions. Semin Vasc Med 3(3):221-230
3. O'Reilly RA, Aggeler PM, Leong LS (1963) Studies on the coumarin anticoagulant drugs: the pharmacodynamics of warfarin in man. J Clin Invest 42:1542-1551
4. Yacobi A, Stoll RG, Di Santo AR, Levy G (1976) Intersubject variation of warfarin binding to protein in serum of normal subjects. Res Commun Chem Pathol Pharmacol 14(4):743-746
5. Yacobi A, Udall JA, Levy G (1976) Serum protein binding as a determinant of warfarin body clearance and anticoagulant effect. Clin Pharmacol Ther 19(5 Pt 1):552-558
6. Weiss P, Soff GA, Halkin H, Seligsohn U (1987) Decline of proteins C and S and factors II, VII, IX and X during the initiation of warfarin therapy. Thromb Res 45(6):783-790 (Pubitemid 17053699)
7. Harrison L, Johnston M, Massicotte MP, Crowther M, Moffat K, Hirsh J (1997) Comparison of 5-mg and 10-mg loading doses in initiation of warfarin therapy. Ann Intern Med 126(2):133-136 (Pubitemid 27058587)
8. Chan E, McLachlan AJ, Pegg M, MacKay AD, Cole RB, Rowland M (1994) Disposition of warfarin enantiomers and metabolites in patients during multiple dosing with rac-warfarin. Br J Clin Pharmacol 37(6):563-569 (Pubitemid 24197150)
9. Ufer M (2005) Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet 44(12):1227-1246
10. Jahnchen E, Meinertz T, Gilfrich HJ, Groth U, Martini A (1976) The enantiomers of phenprocoumon: pharmacodynamic and pharmacokinetic studies. Clin Pharmacol Ther 20(3):342-349
11. Thijssen HH, Drittij MJ, Vervoort LM, de Vries-Hanje JC (2001) Altered pharmacokinetics of R- and S-acenocoumarol in a subject heterozygous for CYP2C9*3. Clin Pharmacol Ther 70(3):292-298 (Pubitemid 32868494)
12. Hewick DS, McEwen J (1973) Plasma half-lives, plasma metabolites and anticoagulant efficacies of the enantiomers of warfarin in man. J Pharm Pharmacol 25(6):458-465
13. Kelly JG, O'Malley K (1979) Clinical pharmacokinetics of oral anticoagulants. Clin Pharmacokinet 4(1):1-15 (Pubitemid 9087267)
14. Schmitt L, Speckman J, Ansell J (2003) Quality assessment of anticoagulation dose management: comparative evaluation of measures of time-in-therapeutic range. J Thromb Thrombolysis 15(3):213-216 (Pubitemid 38213191)
15. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G (2008) Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133(6 Suppl):160S-198S
16. Veeger NJ, Piersma-Wichers M, Tijssen JG, Hillege HL, van der Meer J (2005) Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation, predictor of clinical outcome. A retrospective study of 2300 consecutive patients with venous thromboembolism. Br J Haematol 128(4):513-519 (Pubitemid 40283170)
17. Wan Y, Heneghan C, Perera R, Roberts N, Hollowell J, Glasziou P, Bankhead C, Xu Y (2008) Anticoagulation control and prediction of adverse events in patients with atrial fibrillation: a systematic review. Circ Cardiovasc Qual Outcomes 1(2):84-91
18. Cannegieter SC, Rosendaal FR, Wintzen AR, van der Meer FJ, Vandenbroucke JP, Briet E (1995) Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 333(1):11-17
19. Palareti G, Legnani C, Cosmi B, Guazzaloca G, Cini M, Mattarozzi S (2005) Poor anticoagulation quality in the first 3 months after unprovoked venous thromboembolism is a risk factor for long-term recurrence. J Thromb Haemost 3(5):955-961 (Pubitemid 41632826)
20. Connolly SJ, Pogue J, Eikelboom J, Flaker G, Commerford P, Franzosi MG, Healey JS, Yusuf S (2008) Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation 118(20):2029-2037
21. No Authors Listed. (1996) Bleeding during antithrombotic therapy in patients with atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. Arch Intern Med 156(4):409-416
22. No Authors Listed. (1994) Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 154(13):1449-1457
23. Linkins LA, Choi PT, Douketis JD (2003) Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med 139(11):893-900
24. Gottlieb LK, Salem-Schatz S (1994) Anticoagulation in atrial fibrillation. Does efficacy in clinical trials translate into effectiveness in practice? Arch Intern Med 154(17):1945-1953
25. Evans A, Kalra L (2001) Are the results of randomized controlled trials on anticoagulation in patients with atrial fibrillation generalizable to clinical practice? Arch Intern Med 161(11):1443-1447
26. Palareti G, Hirsh J, Legnani C, Manotti C, D'Angelo A, Pengo V, Moia M, Guazzaloca G, Musolesi S, Coccheri S (2000) Oral anticoagulation treatment in the elderly: a nested, prospective, case-control study. Arch Intern Med 160(4):470-478 (Pubitemid 30112270)
27. Fang MC, Chang Y, Hylek EM, Rosand J, Greenberg SM, Go AS, Singer DE (2004) Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med 141(10):745-752
28. Poli D, Antonucci E, Grifoni E, Abbate R, Gensini GF, Prisco D (2009) Bleeding risk during oral anticoagulation in atrial fibrillation patients older than 80 years. J Am Coll Cardiol 54(11):999-1002
29. Launbjerg J, Egeblad H, Heaf J, Nielsen NH, Fugleholm AM, Ladefoged K (1991) Bleeding complications to oral anticoagulant therapy: multivariate analysis of 1010 treatment years in 551 outpatients. J Intern Med 229(4):351-355
30. Beyth RJ, Quinn LM, Landefeld CS (1998) Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 105(2):91-99 (Pubitemid 28405230)
31. Landefeld CS, Beyth RJ (1993) Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. Am J Med 95(3):315-328 (Pubitemid 23270290)
32. Palareti G, Leali N, Coccheri S, Poggi M, Manotti C, D'Angelo A, Pengo V, Erba N, Moia M, Ciavarella N, Devoto G, Berrettini M, Musolesi S (1996) Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT) Italian Study on Complications of Oral Anticoagulant Therapy. Lancet 348(9025):423-428 (Pubitemid 26267872)
33. Aithal GP, Day CP, Kesteven PJ, Daly AK (1999) Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 353(9154):717-719 (Pubitemid 29103806)
34. Higashi MK, Veenstra DL, Kondo LM, Wittkowsky AK, Srinouanprachanh SL, Farin FM, Rettie AE (2002) Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA 287(13):1690-1698 (Pubitemid 34289221)
35. Schalekamp T, Klungel OH, Souverein PC, de Boer A (2008) Effect of oral antiplatelet agents on major bleeding in users of coumarins. Thromb Haemost 100(6):1076-1083
36. Hart RG, Benavente O, Pearce LA (1999) Increased risk of intracranial hemorrhage when aspirin is combined with warfarin: a meta-analysis and hypothesis. Cerebrovasc Dis 9(4):215-217 (Pubitemid 29308806)
37. Hansen ML, Sorensen R, Clausen MT, Fog-Petersen ML, Raunso J, Gadsboll N, Gislason GH, Folke F, Andersen SS, Schramm TK, Abildstrom SZ, Poulsen HE, Kober L, Torp-Pedersen C (2010) Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 170(16):1433-1441
38. Shorr RI, Ray WA, Daugherty JR, Griffin MR (1993) Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Arch Intern Med 153(14):1665-1670 (Pubitemid 23217872)
39. Battistella M, Mamdami MM, Juurlink DN, Rabeneck L, Laupacis A (2005) Risk of upper gastrointestinal hemorrhage in warfarin users treated with nonselective NSAIDs or COX-2 inhibitors. Arch Intern Med 165(2):189-192
40. Cheetham TC, Levy G, Niu F, Bixler F (2009) Gastrointestinal safety of nonsteroidal antiinflammatory drugs and selective cyclooxygenase-2 inhibitors in patients on warfarin. Ann Pharmacother 43(11):1765-1773
41. Knijff-Dutmer EA, Van der Palen J, Schut G, Van de Laar MA (2003) The influence of cyclo-oxygenase specificity of non-steroidal anti-inflammatory drugs on bleeding complications in concomitant coumarine users. QJM 96(7):513-520 (Pubitemid 36850167)
42. Wittkowsky AK, Boccuzzi SJ, Wogen J, Wygant G, Patel P, Hauch O (2004) Frequency of concurrent use of warfarin with potentially interacting drugs. Pharmacotherapy 24(12):1668-1674 (Pubitemid 39578956)
43. Gasse C, Hollowell J, Meier CR, Haefeli WE (2005) Drug interactions and risk of acute bleeding leading to hospitalisation or death in patients with chronic atrial fibrillation treated with warfarin. Thromb Haemost 94(3):537-543 (Pubitemid 41300849)
44. Hauta-Aho M, Tirkkonen T, Vahlberg T, Laine K (2009) The effect of drug interactions on bleeding risk associated with warfarin therapy in hospitalized patients. Ann Med 41(8):619-628
45. Schulman S, Kearon C (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3(4):692-694 (Pubitemid 41647882)
46. Leissinger CA, Blatt PM, Hoots WK, Ewenstein B (2008) Role of prothrombin complex concentrates in reversing warfarin anticoagulation: a review of the literature. Am J Hematol 83(2):137-143
47. Ostermann H, Haertel S, Knaub S, Kalina U, Jung K, Pabinger I (2007) Pharmacokinetics of Beriplex P/N prothrombin complex concentrate in healthy volunteers. Thromb Haemost 98(4):790-797 (Pubitemid 47555071)
48. Lankiewicz MW, Hays J, Friedman KD, Tinkoff G, Blatt PM (2006) Urgent reversal of warfarin with prothrombin complex concentrate. J Thromb Haemost 4(5):967-970
49. Garcia D, Crowther MA, Ageno W (2010) Practical management of coagulopathy associated with warfarin. BMJ 340:c1813
50. Demeyere R, Gillardin S, Arnout J, Strengers PF (2010) Comparison of fresh frozen plasma and prothrombin complex concentrate for the reversal of oral anticoagulants in patients undergoing cardiopulmonary bypass surgery: a randomized study. Vox Sang 99(3):251-260
51. Makris M, Greaves M, Phillips WS, Kitchen S, Rosendaal FR, Preston EF (1997) Emergency oral anticoagulant reversal: the relative efficacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy. Thromb Haemost 77(3):477-480 (Pubitemid 27121012)
52. Fredriksson K, Norrving B, Stromblad LG (1992) Emergency reversal of anticoagulation after intracerebral hemorrhage. Stroke 23(7):972-977
53. Deveras RA, Kessler CM (2002) Reversal of warfarin-induced excessive anticoagulation with recombinant human factor VIIa concentrate. Ann Intern Med 137(11):884-888 (Pubitemid 35416624)
54. Brody DL, Aiyagari V, Shackleford AM, Diringer MN (2005) Use of recombinant factor VIIa in patients with warfarin-associated intracranial hemorrhage. Neurocrit Care 2(3):263-267 (Pubitemid 41112397)
55. Rowe AS, Turner RM (2010) Coagulation factor VIIa (recombinant) for warfarin-induced intracranial hemorrhage. Am J Health Syst Pharm 67(5):361-365
56. Bartal C, Freedman J, Bowman K, Cusimano M (2007) Coagulopathic patients with traumatic intracranial bleeding: defining the role of recombinant factor VIIa. J Trauma 63(4):725-732 (Pubitemid 350287285)
57. Lindley CM, Sawyer WT, Macik BG, Lusher J, Harrison JF, Baird-Cox K, Birch K, Glazer S, Roberts HR (1994) Pharmacokinetics and pharmacodynamics of recombinant factor VIIa. Clin Pharmacol Ther 55(6):638-648 (Pubitemid 24212264)
58. Tanaka KA, Szlam F, Dickneite G, Levy JH (2008) Effects of prothrombin complex concentrate and recombinant activated factor VII on vitamin K antagonist induced anticoagulation. Thromb Res 122(1):117-123 (Pubitemid 351601847)
59. Ratnaweera M, Janowski W, Simmons D (2007) Multiple thrombotic events following warfarin reversal. Intern Med J 37(8):580-581 (Pubitemid 47084183)
60. Ehrlich HJ, Henzl MJ, Gomperts ED (2002) Safety of factor VIII inhibitor bypass activity (FEIBA): 10-year compilation of thrombotic adverse events. Haemophilia 8(2):83-90 (Pubitemid 35238060)
61. Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T (2005) Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 352(8):777-785
62. Taberner DA, Thomson JM, Poller L (1976) Comparison of prothrombin complex concentrate and vitamin K1 in oral anticoagulant reversal. Br Med J 2(6027):83-85
63. Yasaka M, Sakata T, Minematsu K, Naritomi H (2002) Correction of INR by prothrombin complex concentrate and vitamin K in patients with warfarin related hemorrhagic complication. Thromb Res 108(1):25-30 (Pubitemid 36197658)
64. Lubetsky A, Yonath H, Olchovsky D, Loebstein R, Halkin H, Ezra D (2003) Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study. Arch Intern Med 163(20):2469-2473 (Pubitemid 37385789)
65. Dentali F, Ageno W, Crowther M (2006) Treatment of coumarin-associated coagulopathy: a systematic review and proposed treatment algorithms. J Thromb Haemost 4(9):1853-1863 (Pubitemid 44226758)
66. Crowther MA, Ageno W, Garcia D, Wang L, Witt DM, Clark NP, Blostein MD, Kahn SR, Vesely SK, Schulman S, Kovacs MJ, Rodger MA, Wells P, Anderson D, Ginsberg J, Selby R, Siragusa S, Silingardi M, Dowd MB, Kearon C (2009) Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med 150(5):293-300
67. Crowther MA, Donovan D, Harrison L, McGinnis J, Ginsberg J (1998) Low-dose oral vitamin K reliably reverses over-anticoagulation due to warfarin. Thromb Haemost 79(6):1116-1118 (Pubitemid 28297157)
68. Crowther MA, Douketis JD, Schnurr T, Steidl L, Mera V, Ultori C, Venco A, Ageno W (2002) Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy. A randomized, controlled trial. Ann Intern Med 137(4):251-254
69. Pengo V, Banzato A, Garelli E, Zasso A, Biasiolo A (1993) Reversal of excessive effect of regular anticoagulation: low oral dose of phytonadione (vitamin K1) compared with warfarin discontinuation. Blood Coagul Fibrinolysis 4(5):739-741 (Pubitemid 23343397)
70. Crowther MA, Garcia D, Ageno W, Wang L, Witt DM, Clark NP, Blostein MD, Kahn SR, Schulman S, Kovacs M, Rodger MA, Wells P, Anderson D, Ginsberg J, Selby R, Siragusa S, Silingardi M, Dowd MB, Kearon C (2010) Oral vitamin K effectively treats international normalised ratio (INR) values in excess of 10 Results of a prospective cohort study. Thromb Haemost 104(1):118-121
71. Fondevila CG, Grosso SH, Santarelli MT, Pinto MD (2001) Reversal of excessive oral anticoagulation with a low oral dose of vitamin K1 compared with acenocoumarine discontinuation A prospective, randomized, open study. Blood Coagul Fibrinolysis 12(1):9-16 (Pubitemid 32150246)
72. Ageno W, Crowther M, Steidl L, Ultori C, Mera V, Dentali F, Squizzato A, Marchesi C, Venco A (2002) Low dose oral vitamin K to reverse acenocoumarol-induced coagulopathy: a randomized controlled trial. Thromb Haemost 88(1):48-51 (Pubitemid 34759875)
73. Penning-van Beest FJ, Rosendaal FR, Grobbee DE, van Meegen E, Stricker BH (1999) Course of the international normalized ratio in response to oral vitamin K1 in patients overanticoagulated with phenprocoumon. Br J Haematol 104(2):241-245 (Pubitemid 29083329)
74. Nee R, Doppenschmidt D, Donovan DJ, Andrews TC (1999) Intravenous versus subcutaneous vitamin K1 in reversing excessive oral anticoagulation. Am J Cardiol 83(2):86-288 A286-287
75. Dezee KJ, Shimeall WT, Douglas KM, Shumway NM, O'Malley PG (2006) Treatment of excessive anticoagulation with phytonadione (vitamin K): a meta-analysis. Arch Intern Med 166(4):391-397
76. Hung A, Singh S, Tait RC (2000) A prospective randomized study to determine the optimal dose of intravenous vitamin K in reversal of over-warfarinization. Br J Haematol 109(3):537-539 (Pubitemid 30415179)
77. Crowther MA, Julian J, McCarty D, Douketis J, Kovacs M, Biagoni L, Schnurr T, McGinnis J, Gent M, Hirsh J, Ginsberg J (2000) Treatment of warfarin-associated coagulopathy with oral vitamin K: a randomised controlled trial. Lancet 356(9241):1551-1553
78. Lubetsky A, Shasha Y, Olchovsky D, Loebstein R, Halkin H, Ezra D (2003) Impact of pre-treatment INR level on the effect of intravenous low dose vitamin K in patients with excessive anticoagulation. Thromb Haemost 90(1):71-76 (Pubitemid 36873861)
79. Ford SK, Misita CP, Shilliday BB, Malone RM, Moore CG, Moll S (2007) Prospective study of supplemental vitamin K therapy in patients on oral anticoagulants with unstable international normalized ratios. J Thromb Thrombolysis 24(1):23-27 (Pubitemid 46831560)
80. Sconce E, Avery P, Wynne H, Kamali F (2007) Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood 109(6):2419-2423 (Pubitemid 46425883)
81. Sconce E, Khan T, Mason J, Noble F, Wynne H, Kamali F (2005) Patients with unstable control have a poorer dietary intake of vitamin K compared to patients with stable control of anticoagulation. Thromb Haemost 93(5):872-875 (Pubitemid 40691544)
82. de Assis MC, Rabelo ER, Avila CW, Polanczyk CA, Rohde LE (2009) Improved oral anticoagulation after a dietary vitamin k-guided strategy: a randomized controlled trial. Circulation 120(12):1115-1122 1113 p following 1122
83. Rombouts EK, Rosendaal FR, Van Der Meer FJ (2007) Daily vitamin K supplementation improves anticoagulant stability. J Thromb Haemost 5(10):2043-2048 (Pubitemid 47450022)
84. No Authors Listed. (1997) Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. The Columbus Investigators. N Engl J Med 337(10):657-662
85. Prandoni P, Lensing AW, Cogo A, Cuppini S, Villalta S, Carta M, Cattelan AM, Polistena P, Bernardi E, Prins MH (1996) The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 125(1):1-7
86. Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R, Iotti M, Tormene D, Simioni P, Pagnan A (2007) The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 92(2):199-205
87. Schulman S, Rhedin AS, Lindmarker P, Carlsson A, Larfars G, Nicol P, Loogna E, Svensson E, Ljungberg B, Walter H (1995) 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 332(25):1661-1665
88. Hansson PO, Sorbo J, Eriksson H (2000) Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors. Arch Intern Med 160(6):769-774 (Pubitemid 30165237)
89. Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen JG, Buller HR (2000) 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 18(17):3078-3083
90. Schulman S, Svenungsson E, Granqvist S (1998) 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 104(4):332-338 (Pubitemid 28211022)
91. de Godoy JM, de Godoy MF, Braile DM (2006) Recurrent thrombosis in patients with deep vein thrombosis and/or venous thromboembolism associated with anticardiolipin antibodies. Angiology 57(1):79-83
92. De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A, Leone G (2006) The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. Haematologica 91(5):695-698 (Pubitemid 43799473)
93. Kearon C, Julian JA, Kovacs MJ, Anderson DR, Wells P, Mackinnon B, Weitz JI, Crowther MA, Dolan S, Turpie AG, Geerts W, Solymoss S, van Nguyen P, Demers C, Kahn SR, Kassis J, Rodger M, Hambleton J, Gent M, Ginsberg JS (2008) Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial. Blood 112(12):4432-4436
94. Santamaria MG, Agnelli G, Taliani MR, Prandoni P, Moia M, Bazzan M, Guazzaloca G, Ageno W, Bertoldi A, Silingardi M, Tomasi C, Ambrosio GB (2005) Thrombophilic abnormalities and recurrence of venous thromboembolism in patients treated with standardized anticoagulant treatment. Thromb Res 116(4):301-306 (Pubitemid 40994912)
95. Quinlan DJ, McQuillan A, Eikelboom JW (2004) Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials. Ann Intern Med 140(3):175-183
96. Louzada ML, Majeed H, Wells PS (2009) Efficacy of low-molecular-weight- heparin versus vitamin K antagonists for long term treatment of cancer-associated venous thromboembolism in adults: a systematic review of randomized controlled trials. Thromb Res 123(6):837-844
97. Akl EA, Barba M, Rohilla S, Terrenato I, Sperati F, Muti P, Schunemann HJ (2008) Anticoagulation for the long term treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev (2):CD006650
98. Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M (2003) Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349(2):146-153
99. Lyman GH, Khorana AA, Falanga A, Clarke-Pearson D, Flowers C, Jahanzeb M, Kakkar A, Kuderer NM, Levine MN, Liebman H, Mendelson D, Raskob G, Somerfield MR, Thodiyil P, Trent D, Francis CW (2007) American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 25(34):5490-5505
100. Cunningham MS, Gilmore R, O'Donnell D, O'Donnell JS (2009) Management of refractory venous thrombosis associated with malignancy using a supra-therapeutic enoxaparin regimen. Ir J Med Sci 178(3):339-341
101. Luk C, Wells PS, Anderson D, Kovacs MJ (2001) Extended outpatient therapy with low molecular weight heparin for the treatment of recurrent venous thromboembolism despite warfarin therapy. Am J Med 111(4):270-273 (Pubitemid 32885621)
102. Carrier M, Le Gal G, Cho R, Tierney S, Rodger M, Lee AY (2009) Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients. J Thromb Haemost 7(5):760-765
103. White RH, Ginsberg JS (2003) Low-molecular-weight heparins: are they all the same? Br J Haematol 121(1):12-20
104. Wells PS, Anderson DR, Rodger MA, Forgie MA, Florack P, Touchie D, Morrow B, Gray L, O'Rourke K, Wells G, Kovacs J, Kovacs MJ (2005) A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism. Arch Intern Med 165(7):733-738 (Pubitemid 40569425)
105. Pillai AR, Olujohungbe A, Evans MR, Main NJ, Hunt BJ (2010) The management of recurrent VTE in cancer patients receiving therapeutic anticoagulation: the use of dual anticoagulant therapy combined with an IVC filter. Blood Coagul Fibrinolysis 21(8):766-769
106. Crowther MA, Ginsberg JS, Julian J, Denburg J, Hirsh J, Douketis J, Laskin C, Fortin P, Anderson D, Kearon C, Clarke A, Geerts W, Forgie M, Green D, Costantini L, Yacura W, Wilson S, Gent M, Kovacs MJ (2003) A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 349(12):1133-1138 (Pubitemid 37122325)
107. Finazzi G, Marchioli R, Brancaccio V, Schinco P, Wisloff F, Musial J, Baudo F, Berrettini M, Testa S, Angelo A, Tognoni G, Barbui T (2005) A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS). J Thromb Haemost 3(5):848-853 (Pubitemid 41632808)
108. Dentali F, Manfredi E, Crowther M, Ageno W (2005) Long-duration therapy with low molecular weight heparin in patients with antiphospholipid antibody syndrome resistant to warfarin therapy. J Thromb Haemost 3(9):2121-2123 (Pubitemid 43086081)
109. Levine SR, Brey RL, Tilley BC, Thompson JL, Sacco RL, Sciacca RR, Murphy A, Lu Y, Costigan TM, Rhine C, Levin B, Triplett DA, Mohr JP (2004) Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA 291(5):576-584 (Pubitemid 38500311)
110. van Es RF, Jonker JJ, Verheugt FW, Deckers JW, Grobbee DE (2002) Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet 360(9327):109-113 (Pubitemid 34786198)
111. Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H (2002) Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 347(13):969-974
112. No Authors Listed. (2005) Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study. Circulation 112(3): 416-422