New oral anticoagulants and regional anaesthesia

British Journal of Anaesthesia

Volumn 111, Issue SUPPL.1, 2013, Pages

  Benzon, H T ^a   Avram, M J ^a   Green, D ^a   Bonow, R O ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

Author keywords

anaesthesia; anticoagulants; blood; drug; regional; safety

Indexed keywords

ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; APIXABAN; CARBAMAZEPINE; DABIGATRAN; DABIGATRAN ETEXILATE; ENOXAPARIN; HEPARIN; HISTAMINE H2 RECEPTOR ANTAGONIST; KETOCONAZOLE; LOW MOLECULAR WEIGHT HEPARIN; NAPROXEN; NONSTEROID ANTIINFLAMMATORY AGENT; PANTOPRAZOLE; PHENYTOIN; PRASUGREL; RIFAMPICIN; RITONAVIR; RIVAROXABAN; TICAGRELOR; WARFARIN;

ACUTE CORONARY SYNDROME; ANESTHESIST; ARTICLE; BLEEDING; BRAIN HEMORRHAGE; CATHETER REMOVAL; CEREBROVASCULAR ACCIDENT; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; DRUG WITHDRAWAL; EPIDURAL CATHETER; HEART ATRIUM FIBRILLATION; HEMOSTASIS; HIGH RISK PATIENT; HIP FRACTURE; HUMAN; JOINT SURGERY; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REGIONAL ANESTHESIA; RISK BENEFIT ANALYSIS; SPINAL HEMATOMA; THROMBOEMBOLISM; VEIN THROMBOSIS; VENOUS THROMBOEMBOLISM;

EID: 84890689245     PISSN: 00070912     EISSN: 14716771     Source Type: Journal    
DOI: 10.1093/bja/aet401     Document Type: Article

References (168)

1. Horlocker TT,Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving antithrombotic therapy or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine evidence-based guidelines (third edition). Reg Anesth Pain Med 2010; 35: 64-101
2. Gogarten W, Vandermeulen E, Van Aken H, Kozek S, Llau JV, Samama CM, European Society of Anaesthesiology. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol 2010; 27: 999-1015
3. Breivik H, Bang U, Jalonen J, Vigfusson G, Alahuhta S, Lagerkranser M. Nordic guidelines for neuraxial blocks in disturbed haemostasis from the Scandinavian Society of Anaesthesiology and Intensive Care Medicine. Acta Anaesthesiol Scand 2010; 54: 16-41
4. Green L, Machin SJ. Managing anticoagulated patients during neuraxial anaesthesia. Br J Hematol 2010; 149: 195-208
5. Levy JH, Key NS, Azran MS. Novel oral anticoagulants: implications in the perioperative setting. Anesthesiology 2010; 113: 726-45
6. Hall R, Mazer CD. Antiplatelet drugs: a review of their pharmacology and management in the perioperative period. Anesth Analg 2011; 112: 292-318
7. Horlocker TT. Regional anaesthesia in the patient receiving antithrombotic and antiplatelet therapy. Br J Anaesth 2011; 107 (Suppl. 1): i96-106
8. Gomez-Outez A, Terleira-Fernandez AI, Suarez-Gea ML, Vargas-Castrillon E. Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip orknee replacement: systematic review, meta-analysis, and indirect treatment comparisons. Br Med J 2012; 344: e3675
9. Kozek-Langenecker SA, Afshari A, Albaladejo P, et al.Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013; 30: 270-382
10. Sie P,SamamaCM, Godier A, et al. Surgeryand invasive procedures in patients on long-term treatment with direct oral anticoagulants: thrombin or factor-Xa inhibitors. Recommendations of the Working Group on Perioperative Hemostasis and the French Study Group on Thrombosis and Haemostasis. Arch Cardiovasc Dis 2011; 104: 669-76
11. Levy JH, Faraoni D, Spring JL, Douketis JD, Samana CM. Managing new oral anticoagulants in the perioperative and intensive care unit setting. Anesthesiology 2013; 118: 1466-74
12. Baron TH,Kamath PS, McBane RD.Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med 2013; 368: 2113-24
13. Connolly G, Spyropoulos AC. Practical issues, limitations, and periprocedural management of the NOAC's. J Thromb Thrombolysis 2013; 36: 212-22
14. Liew A, Douketis J. Perioperativemanagement of patientswhoare receiving a novel oral anticoagulant. Intern Emerg Med 2013; 8: 477-84
15. Tripodi A. The laboratory and the direct oral anticoagulants. Blood 2013; 121: 4032-5
16. Garcia D, Barrett YC,Ramaciotti E,Weitz JI. Laboratoryassessment of the anticoagulant effects of the nextgenerationoforal anticoagulants. J Thromb Haemost 2013; 11: 245-52
17. Siegal DM, Cuker A. Reversal of novel oral anticoagulants in patients with major bleeding. J Thromb Thrombolysis 2013; 35: 391-8
18. Siegal DM, Crowther MA. Acute management of bleeding in patients on novel oral anticoagulants. Eur Heart J 2013; 34: 489-500
19. Nitzki-George D,Wozniak I, Caprini JA. Current state of knowledge on oral anticoagulant reversal using procoagulant factors. Ann Pharmacother 2013; 47: 841-55
20. Baglin T. The role of the laboratory in treatment with new oral anticoagulants. J Thromb Haemost 2013; 11 (Suppl. 1): 122-8
21. del Zoppo GJ, Eliasziw M. New options in anticoagulation for atrial fibrillation. N Engl J Med 2011; 365: 952-3
22. Omran H, Bauersachs R, Rubenacker S, Goss F, Hammerstingl C. The HAS-BLED score predicts bleedings during bridging of chronic oral anticoagulation. Results from the multicenter BNK Online bRiDging Registry (BORDER). Thromb Haemost 2012; 108: 65-73
23. Gage BF, Yan Y, Milligan PE, et al. Clinical classification schemes for predictinghemorrhage: results fromthe NationalRegistry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151: 713-9
24. Douketis JD, SpyropoulosAC, Spencer FA, et al.AmericanCollege of Chest Physicians. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of ChestPhysicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2 Suppl.): e326-50S
25. Kearon C. Perioperative management of long-term anticoagulation. Semin Thromb Haemost 1998; 24 (Suppl. 1): 77-83
26. Ruff RL, Dougherty JH Jr. Complications of lumbar puncture followed by anticoagulation. Stroke 1981; 12: 879-81
27. Horlocker TT,Wedel DJ, Schroeder DR, et al. Preoperative antiplatelet therapy does not increase the risk of spinal hematoma associated with regional anesthesia. Anesth Analg 1995; 80: 303-9
28. Horlocker TT, Bajwa ZH, Ashraf Z, et al. Risk assessment of hemorrhagic complications associated with nonsteroidal antiinflammatorymedications inambulatorypainclinicpatientsundergoing epidural steroid injection. Anesth Analg 2002; 95: 1691-7
29. Benzon HT, Brunner EA, Vaisrub N. Bleeding time and nerve blocks in patients who had aspirin. Reg Anesth 1984; 9: 86-9
30. de Swiet M, Redman CW. Aspirin, extradural anaesthesia and the MRC Collaborative Low-dose Aspirin Study in Pregnancy. Br J Anaesth 1992; 69: 109-10
31. Liu SS, Mulroy MF. Neuraxial anesthesia and analgesia in the presence of standard heparin. Reg Anesth Pain Med 1998; 23: 157-63
32. Rosencher N, Bonnet MP, Sessler DI. Selected new antithrombotic agents and neuraxial anaesthesia for major orthopedic surgery: management strategies. Anaesthesia 2007; 62: 1154-60
33. Geerts WS, Berqvist D, Pineo GF, et al.; American College of Chest Physicians. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 2008; 133 (Suppl.): 381-453S
34. Benzon HT, Benzon HA, Kirby-Nolan M, Avram MJ, Nader A. Factor VII levels and risk factors for increased international normalized ratio in the early phase of warfarin therapy. Anesthesiology 2010; 112: 298-304
35. Benzon HT, McCarthy R, Benzon HA, et al. Determination of the residual antiplatelet activity of clopidogrel. Br J Anaesth 2011; 107: 966-71
36. Greenblatt DJ. Elimination half-life of drugs: value and limitations. Ann Rev Med 1985; 36: 421-7
37. Hylek EM. Therapeutic potential of oral factorXainhibitors.NEngl J Med 2010; 363: 2559-61
38. Laux V, Perzborn E, Kubitza D, Misselwitz F. Preclinical and clinical characteristics of rivaroxaban: a novel, oral, direct factor Xa inhibitor. Semin Thromb Hemost 2007; 33: 515-23
39. Olesen JB, Lip GY, Hansen ML, et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. Br Med J 2011; 342: d124.
40. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg 1994; 79: 1165-77
41. Horlocker TT. When to remove a spinal or epidural catheter in an anticoagulated patient. Reg Anesth 1993; 18: 264-5
42. Bouma BN, Mosnier LO. Thrombin activates fibrinolysis inhibitor (TAF)-how does thrombin regulate fibrinolysis? Ann Med 2006; 38: 378-88
43. IST-3 Collaborative Group. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroketrial [IST-3]):arandomizedtrial. Lancet 2012;379:2352-63
44. Fisher M, AlbersGW. Advanced imaging to extend the therapeutic window of ischemic stroke. Ann Neurol 2013; 73: 4-9
45. Tertri S, Hakal J, Juvela S, et al. Safety of low-dose subcutaneous enoxaparin for the prevention of venous thromboembolism after primary intracerebral haemorrhage. Thromb Res 2008; 123: 206-12
46. Gouya G, Palkovits S, Kapiotis S, et al. Bioactivity of enoxaparin in critically ill patients with normal renal function. Br J ClinPharmacol 2012; 74: 806-14
47. Di Nisio M, Middeldorp S, Buller HR. Direct thrombin inhibitors. N Engl J Med 2005; 353: 1028-40
48. Blech S, Ebner T, Ludwig-Schwellinger E, Stangier J, Roth W. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Disposition 2008; 36: 386-99
49. Ericksson BI, Quinlan DJ,Weitz JI. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor Xa inhibitors in development. Clin Pharmacokinet 2009; 48: 1-22
50. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet 2008; 47: 285-95
51. Stangier J, Clemens A. Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost 2009; 15 (Suppl. 1): 9-16S
52. Stangier J, Stahle H, Rathgen K, Fuhr R. Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin Pharmacokinet 2008; 47: 47-59
53. Eisert WG, Hauel N, Stangier J, Wienen W, Clemens A, Van Ryn J. Dabigatran: an oral novel potent reversible nonpeptide inhibitor of thrombin. Arterioscler Thromb Vasc Biol 2010; 30: 1885-9
54. Stangier J, Rathgen K, Stahle H, Gansser D, RothW. Thepharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, aneworal direct thrombininhibitor, in healthy male subjects. Br J Clin Pharmacol 2007; 64: 292-308
55. Stangier J, Rathgen K, Stahle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate. An open label, parallel-group, single-centre study. Clin Pharmacokinet 2010; 49: 259-68
56. Ezekowitz MD, Reilly PA, Nehmiz G, et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol 2007; 100: 1419-26
57. Wittkowsky AK. New oral anticoagulants: a practical guide to clinicians. J Thromb Thrombolysis 2010; 29: 182-91
58. Connolly SJ, Ezekowitz MD, Yusuf S. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-51
59. Schulman S, Kearon C, Kakkar AK, et al.; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361: 2342-52
60. Oldgren J, Budai A, Granger CB, et al.; RE-DEEMInvestigators. Dabigatran versus placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J 2011; 32: 2781-9
61. Fuji T, Fujita S, Ujihira T, Sato T. Dabigatran etexilate prevents venous thromboembolism after total knee arthroplasty in Japanese patients with safety profile comparable to placebo. J Arthroplasty 2010; 25: 1267-74
62. Ericksson BI, Dahl OE, Buller HR, et al.; BISTRO II Study Group. A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTROII randomized trial. J Thromb Haemost 2005; 3: 103-11
63. Ericksson BI, Dahl OE, Rosencher N, et al.; RE-MODEL Study Group. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J ThrombHaemost 2007; 5: 2178-85
64. Ericksson BI, Dahl OE, Rosencher N, et al.; RE-NOVATE Study Group. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomized, double-blind, non-inferiority trial. Lancet 2007; 370: 949-56
65. RE-MOBILIZE Writing Committee, Ginsberg JS, Davidson BL, Comp PC, et al. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty 2009; 24: 1-9
66. Wolowacz SE, Roskell NS, Plumb JM, Caprini JA, Ericksson BI. Efficacy and safety of dabigatran etaxilate for the prevention of venous thromboembolism following hip or knee arthroplasty. A meta-analysis. Thromb Haemost 2009; 101: 77-85
67. Ericksson BI, Dahl OE, Ahnfelt L, et al. Dose escalating safety study of a new direct thrombin inhibitor, dabigatran etexilate, in patients undergoing total hip replacement: BISTRO I. J Thromb Haemost 2004; 2: 1573-80
68. Bateman BT,Mhyre JM, Ehrenfeld J, et al. The risk and outcomes of epidural hematomas after perioperative and obstetric epidural catheterization: a report from the multicenter perioperative outcomes group research consortium. Anesth Analg 2013; 116: 1380-5
69. Harper P, Young L, Merriman E. Bleeding risk with dabigatran in the frail elderly. N Eng J Med 2012; 366: 864-6
70. SouthworthMR,ReichmanME,UngerEF.Dabigatranandpostmarketing reports of bleeding. N Engl J Med 2013; 368: 1272-4
71. Hawes EM, Deal AM, Funk-Adcock D, et al. Performance of coagulation tests in patientsontherapeuticdoses of dabigatran:acrosssectional pharmacodynamic study based on peak and trough plasma levels. J Thromb Haemost 2013; 11: 1493-502
72. Miyares MA,Davis K.Neweroral anticoagulants:areviewof laboratory monitoring options and reversal agents in the hemorrhagic patient. Am J Health Syst Pharm 2012; 69: 1473-84
73. van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate-a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103: 1116-27
74. Eerenberg ES, Kamphuisen PW, Sijkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 2011; 124: 1573-9
75. Hanke AA, Joch C, Gorlinger K. Long-term safety and efficacy of a pasteurizednanofiltrated prothrombincomplexconcentrate(Beriplex P/N): a pharmacovigilance study. Br J Anaesth 2013; 110: 764-72
76. Schiele F, van Ryn J, Canada K, et al. A specific antidote for dabigatran: functional and structural characterization. Blood 2013; 121: 3554-62
77. Kubitza D, Becka M, Wensing G, Voith B, Zuehlsdorf M. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939-an oral, direct factor Xa inhibitor-after multiple dosing in healthy male subjects. Eur J Clin Pharmacol 2005; 61: 873-80
78. Jiang J,HuY, ZhangJ, et al. Safety,pharmacokineticsandpharmacodynamics of single doses of rivaroxaban-an oral, direct factor Xa inhibitor-in elderly Chinese subjects. Thromb Haemost 2010; 103: 234-41
79. Kubitza D, Becka M, Roth A, Mueck W. Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. Curr Med Res Opin 2008; 24: 2757-65
80. Weitz JI, Eikelboom JW, Samama MM. New antithrombotic drugs. Chest 2012; 141S: e120-51S
81. Kubitza D, Becka M, Zueshlsdorf M, Mueck W. Body weight has limited influence on the safety, tolerability, pharmacokinetics, pharmacodynamics of rivaroxaban (BAY 59-7939) in healthy subjects. J Clin Pharmacol 2007; 47: 218-26
82. Kubitza D, BeckaM, MueckW, et al. Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct factor Xa inhibitor. Br J Clin Pharmacol 2010; 70: 703-12
83. Rivaroxaban Package Insert. Titusville,NJ: JanssenPharmaceuticals.
84. Kubitza D, Becka M, Mueck W, Zuelhsdorf M. Rivaroxaban (BAY 59-7939)-an oral, direct factor Xa inhibitor-has no clinically relevant interaction with naproxen. Br J Clin Pharmacol 2007; 63: 469-76
85. Becker EM, Perzborn E, Klipp A,, et al. Effects of rivaroxaban, acetylsalicylic acid and clopidogrel as monotherapy and in combination in a porcine model of stent thrombosis. J Thromb Haemost 2012; 10: 2470-80
86. EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363: 2499-510
87. Patel MR, Mahaffey KW, Garg J, et al.; ROCKETAF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-91
88. Mega JL, Braunwald E, Wiviott SD, et al.; ATLAS ACS 2-TIMI Investigators. Rivaroxaban in patients with recent acute coronary syndrome. N Engl J Med 2012; 366: 9-19
89. Roe MT, Ohman EM. A new era in secondary prevention after coronary artery syndrome. N Engl J Med 2012; 366: 85-7
90. Cohen AT, Spiro TE, Buller HR, et al.; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 2013; 368: 513-23
91. Eriksson BI, Borris LC, Friedman RJ, et al.; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008; 358: 2765-75
92. Kakkar AK, Brenner B, Dahl O, et al.; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomized controlled trial. Lancet 2008; 372: 31-9
93. Lassen MR, AgenoW, Borris LC, et al.; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008; 358: 2776-86
94. Turpie AG, Lassen MR, Davidson BL, et al.; RECORD4 Investigators. Rivaroxabanversusenoxaparin for thromboprophylaxisafter total knee arthroplasty (RECORD4): a randomized trial. Lancet 2009; 373: 1673-80
95. Ericksson BI, Kakkar AK, Turpie AG, et al. Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after elective hip and knee replacement. J Bone Joint Surg Br 2009; 91: 636-44
96. Rosencher N, Liau JV, Mueck W, Loewe A, Berkowitz SD, Homering M. Incidence of neuraxial haematoma after total hip or knee surgery: RECORDprogramme(rivaroxabanvs enoxaparin). Acta Anaesthesiol Scand 2013; 57: 565-72
97. MueckW, Erickson BI, Bauer KA, et al. Population pharmacokinetics and pharmacodynamics of rivaroxaban-an oral direct factor Xa inhibitor-in patients undergoing major orthopedic surgery. Clin Pharmacokinet 2008; 47: 203-16
98. Samama MM. Which test to use to measure the anticoagulant effect of rivaroxaban: the anti-factor Xa assay. J Thromb Haemost 2013; 11: 579-80
99. Raghavan N, Frost CE, Yu Z, et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos 2009; 37: 74-81
100. Frost C, Wang J, Nepal S, et al. Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy sbjects. Br J Pharmacol 2013; 75: 476-87
101. Frost C, Nepal S, Wang J, et al. Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects. Br J Clin Pharmacol 2013 Advance Access published on4 March 2013; doi: 10.1111/bcp.12106
102. Zhang D, He K, Raghavan N, et al. Comparative metabolism of 14C-labeled apixaban in mice, rats, rabbits, dogs, and humans. Drug Metab Dispos 2009; 37: 1738-48
103. Wang L, Zhang D, Raghavendra N, et al. In vitro assessment of metabolic drug-drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies. Drug Metab Dispos 2010; 38: 448-58
104. UpretiVV,Wang J, Barrett YC, et al. Extremesof bodyweighton the pharmacokinetics, pharmacodynamics, safety and tolerability of apixaban in healthy subjects. Br J Clin Pharmacol 2013 Advance Access published on 14 March 2013; doi: 10.1111/bcp.12114
105. Alexander JH, Lopes RD, James S, et al.; APPRAISE-2 Investigators. Apixaban with anitiplatelet therapy after coronary syndrome. N Engl J Med 2011; 365: 699-708
106. Goldhaber SZ, Leizorovicz A, Kakkar AJ, et al.; ADOPT Trial Investigators. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 2011; 365: 2167-77
107. Agnelli G, Buller HR, Cohen A, et al., for the AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369: 799-808
108. Agnelli G, Buller HR,CohenA, et al.; PFLIFY-EXT Investigators. Apixabanforextended treatmentof venous thromboembolism.NEngl J Med 2013; 368: 699-708
109. Connolly SJ, Eikebbom J, Joyner C, et al.; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364: 806-17
110. Granger CB, Alexander JH, McMurray JJ, et al.; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patient with atrial fibrillation. N Engl J Med 2011; 365: 981-92
111. Mega JL. A new era for anticoagulation in atrial fibrillation. N Engl J Med 2011; 365: 1052-3
112. Lassen MR, Davidson BL, Gallus A, Pineo G, Ansell J, Deitchman D. The efficacyandsafety of apixaban,an oral, direct factor Xainhibitor, as thromboprophylaxis in patients following total knee replacement. J Thromb Haemost 2007; 5: 2368-75
113. Lassen MR, Rasskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med 2009; 361: 594-604
114. Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P; ADVANCE-2 Investigators. Apixabanversus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomized double-blind trial. Lancet 2010; 375:807-15
115. Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM; ADVANCE-3 Investigators. Apixabanversus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 2010; 363: 2487-98
116. WongPC, Crain EJ, Xin RR, et al. Apixaban,anoral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies. J Throm Haemost 2008; 6: 820-9
117. Becker RC, Yang H, Barrett Y, et al. Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban-an oral, direct and selective factor Xa inhibitor. J Thromb Thrombolysis 2011; 32: 183-7
118. Barrett YC, Wang Z, Frost C, Shenker A. Clinical laboratory measurement of direct factor Xa inhibitors: anti Xa assay is preferable to prothrombin time assay. Thromb Haemost 2010; 104: 1263-71
119. Janssen PWA, ten Berg JM. Platelet function testing and tailored antiplatelet therapy. J Cardiovasc Trans Res 2013; 6: 316-28
120. Gorog DA, Fuster V. Platelet function tests in clinical cardiology. J Am Coll Cardiol 2013; 61: 2115-29
121. Wallentin L. P2y(12) inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. Eur Heart J 2009; 30: 1964-77
122. Capodanno D, Ferreiro JL, Angiolillo DJ. Antiplatelet therapy: new pharmacological agents and changing paradigms. J Thromb Haemost 2013; 11 (Suppl. 1): 316-29
123. Brandt JT, Payne CD, Wiviott SD, et al. A comparison of prasugrel and clopidogrel loading doses on platelet function: magnitude of platelet inhibition is related to active metabolite formation. Am Heart J 2007; 153: 66.e9-16
124. Dobesh PP. Pharmacokinetics and pharmacodynamics of prasugrel, a thienopyridine P2Y12 inhibitor. Pharmacotherapy 2009; 29: 1089-102
125. Farid NA, Smith RL, Gillespie TA, et al.The disposition of prasugrel,a novel thienopyridine, in humans. Drug Metab Dispos 2007; 35: 1096-104
126. Floyd CN, Passacquale G, Ferro A. Comparative pharmacokinetics and pharmacodynamics of platelet adenosine diphosphate receptor antagonists and their clinical implications. Clin Pharmacokinet 2012; 51: 429-42
127. Asai F, Jacubowski JA, Nagamura H, et al. Platelet inhibitory activity and pharmacokinetics of prasugrel (CS-747) a novel thienopyridine P2Y12 inhibitor: a single ascending dose study in healthy humans. Platelets 2006; 17: 209-17
128. Husted S, Emanuelsson H, Heptinstall S, Sandset PM, Wickens M, Peters G. Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J 2006; 27: 1038-47
129. Storey RF, Husted S, Harrington RA, et al. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol 2007; 50: 1852-6
130. Bhatt DL. Prasugrel in clinical practice. N Engl J Med 2009; 361: 940-2
131. PayneCD,LiYG,SmallDS, etal.Increasedactivemetaboliteexplains the greater platelet inhibition with prasugrel compared to highdose clopidogrel. J Cardiovasc Pharmacol 2007; 50: 555-62
132. Small DS, Wrishko RE, Ernest CS II, et al. Prasugrel pharmacokinetics and pharmacodynamics in subjects with moderate renal impairment and end-stage renal disease. J Clin Pharm Ther 2009; 34: 585-94
133. Small DS, Farid NA, Li YG, et al. Pharmacokinetics and pharmacodynamics of prasugrel in subjects with moderate liver disease. J Clin Pharm Ther 2009; 34: 575-83
134. Wiviott SD,AntmanEM, Winters KJ, et al.Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y12 antagonist, with clopidogrel in percutaneous coronary intervention: results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)-TIMI 26 trial. Circulation 2005; 111: 3366-73
135. Wiviott SD, Trenk D, Frelinger AL, et al. Prasugrel compared with high loading-and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 trial. Circulation 2007; 116: 2923-32
136. Kelly RP, Close SL, Farid NA, et al. Pharmacokinetics and pharmacodynamics following maintenance doses of prasugrel and clopidogrel in Chinese carriers of CYP2C19 variants. Br J Clin Pharmacol 2012; 73: 93-105
137. Brandt JT, Close SL, Iturria SJ, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost 2007; 5: 2429-36
138. MegaJL, Close SL, Wiviott SD, et al. CytochromeP450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation 2009; 119: 2553-60
139. SmallDS,FaridNA,PayneCD, etal. Effects oftheprotonpumpinhibitor lansoprazole onthe pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel. J Clin Pharmacol 2008; 48: 475-84
140. Teng R, Butler K.Pharmacokinetics,pharmacodynamics, tolerability and safety of single ascending doses of ticagrelor, a reversibly binding oral P2Y(12) receptor antagonist, in healthy subjects. Eur J Clin Pharmacol 2010; 66: 487-96
141. Teng R, Oliver S, Hayes MA, Butler K. Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos 2010; 38: 1514-21
142. GurbelPA,BlidenKP,Butler K, etal.Randomizeddouble-blindassessment of the ONSETandOFFSETof the antiplatelet effects of ticagrelor versus clopidogrel inpatientswith stablecoronaryarterydisease: the ONSET/OFFSET study. Circulation 2009; 120: 2577-85
143. Butler K, Teng R. Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with mild hepatic impairment. J Clin Pharmacol 2011; 51: 978-87
144. Latib A, Morici N, Cosgrave J, et al. Incidence of bleeding and compliance on prolonged dual antiplatelet therapy (aspirin+ thienopyridine) following drug eluting stent implantation. Am J Cardiol 2008; 102: 1477-81
145. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001; 23: 1296-310
146. Collyer TC, Reynolds HC, Truyens E, Kilshaw L, Corcoran T. Perioperative management of clopidogrel therapy: the effects on in-hospital cardiac morbidity in older patients with hip fractures. Br J Anaesth 2011; 107: 911-5
147. Akowuah E, Shrivastava V, Jamnadas B, et al. Comparison of two strategies for the management of antiplatelet therapy during urgent surgery. Ann Thorac Surg 2005; 80: 149-52
148. NewsomeLT,Weller RS, Gerancher JC, Kutcher MA,Royster RL.Coronary stents II. Perioperative considerations and management. Anesth Analg 2008; 107: 570-90
149. George JN. Platelets. Lancet 2000; 355: 1531-9
150. van Giezen J, Nilsson L, Berntsson P, et al. Ticagrelor binds to human P2Y(12) independently from ADP but antagonizes ADP-induced receptor signaling and platelet aggregation. J Thromb Haemost 2009; 7: 1556-65
151. Harrison P, Lordkipanidze M. Testing platelet function. Hematol Oncol Clin N Am 2013; 27: 411-41
152. Edwards A, Jakubowski JA, Rechner AR, Sugidachi A, Harrison P. Evaluation of the INNOVANCE PFA P2Y test cartridge: sensitivity to P2Y(12) blockade and influence of anticoagulant. Platelets 2012; 23: 106-15
153. Tsantes A, Ikonomidis I, Papadakis I, et al. Evaluation of the role of thenewINNOVANCEPFAP2Ytest cartridge in detection of clopidogrel resistance. Platelets 2012; 23: 481-9
154. Bouman HJ, Parlak E, vanWerkum JW, et al. Which platelet function test is suitable to monitorclopidogrel responsiveness?Apharmacokinetic analysis on the active metabolite of clopidogrel. J Thromb Haemost 2010; 8: 482-8
155. Bal Dit Sollier C, Berge N, Boval B, Dubar M, Drouet L. Differential sensitivity and kinetics of response of different ex vivo tests monitoring functional variability of platelet response to clopidogrel. Thromb Haemost 2010; 104: 571-81
156. Gaglia MA, Torguson R, Pakala R, et al. Correlation between light transmission aggregometry, VerifyNow P2Y12, and VASP-P platelet reactivity assays following percutaneous coronary intervention. J Interv Cardiol 2011; 24: 529-34
157. Mueller T, Dieplinger B, Poelz W, Haltmayer M. Utility of the PFA-100 insturment and the novel multiplate analyzer for the assessment of aspirin and clopidogrel effects on platelet function in patients with cardiovascular disease. Clin Appl Thromb Hemost 2009; 15: 652-9
158. Blais N, Pharand C, Lordkipanidzé M, Sia YK, Merhi Y, Diodati JG. Response to aspirin in healthy individuals. Cross-comparison of light transmission aggregometry, VerifyNow system, platelet count drop, thromboelastography (TEG) and urinary 11-dehydrothromboxane B(2). Thromb Haemost 2009; 102: 404-11
159. Scharbert G, Auer A, Kozek-Langenecker S. Evaluationof the Platelet Mapping Assayon rotational thromboelastometry ROTEM. Platelets 2009; 20: 125-30
160. Kaur J, Jones N, Mallett S. Thrombelastography platelet mapping is a useful preoperative tool in surgical patients taking antiplatelet medication (letter). Br J Anaesth 2009; 103: 304
161. Collyer TC, Gray DJ, Sandhu R, Berridge J, Lyons G. Assessment of platelet inhibition secondary to clopidogrel and aspirin therapy in preoperative acute surgical patients measured by Thrombelastography w Platelet MappingTM. Br J Anaesth 2009; 102: 492-8
162. Dyszkiewicz-Korpanty A, Olteaanu H, Frenkel EP, Sarode R. Clopidogrel anti-platelet effect: an evaluation by optical aggregometry, impedance aggregometry, and the platelet function analyzer (PFA-100). Platelets 2007; 18: 491-6
163. van Werkum JW, Harmsze AM, Elsenberg EH, Bouman HJ, ten Berg JM, Hackeng CM. The use of the VerifyNow system to monitor antiplatelet therapy: a review of the current evidence. Platelets 2008; 19: 479-88
164. Collet J-P, Cuisset T, Range G, et al.; ARCTIC Investigators. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2013; 367: 2100-9
165. Bonello L, Tantry US, Marcucci R, et al.; Working Group on High On-TreatmentPlateletReactivity.Consensusandfuturedirections on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 2010; 56: 919-33
166. Bonello L, Mancini J, Pansieri M, et al. Relationship between posttreatment platelet reactivity and ischemic and bleeding events at 1-year follow-up in patients receiving prasugrel. J Thromb Haemost 2012; 10: 1999-2005
167. Kozek-Langenecker SA, Fries D, Gutl M, et al. Locoregional anesthesia and coagulation inhibitors. Recommendations of the Task Force on Perioperative Coagulation of the Austrian Society for Anesthesiology and Intensive CareMedicine. Anaesthesist 2005; 54: 476-84
168. Mukerji N, Todd N. Spinal epiduralhaematoma; factors influencing outcome.