Reversal of new, factor-specific oral anticoagulants by rFVIIa, prothrombin complex concentrate and activated prothrombin complex concentrate: A review of animal and human studies

Thrombosis Research

Volumn 133, Issue 5, 2014, Pages 705-713

  Lee, Frank M H ^a,b   Chan, Anthony K C ^a,c   Lau, Keith K ^d   Chan, Howard H ^a,c  

^a MCMASTER UNIVERSITY   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c MCMASTER UNIVERSITY   (Canada)

^d THE UNIVERSITY OF HONG KONG SHENZHEN HOSPITAL   (China)

Author keywords

anticoagulant; coagulation factor; factor VIIa; prothrombin complex concentrates

Indexed keywords

ANTICOAGULANT AGENT; BLOOD CLOTTING FACTOR; BLOOD CLOTTING FACTOR 7A; PROTHROMBIN COMPLEX CONCENTRATES; RECOMBINANT FVIIA; RECOMBINANT PROTEIN;

ANIMAL; DRUG INTERACTION; HUMAN; ORAL DRUG ADMINISTRATION;

ADMINISTRATION, ORAL; ANIMALS; ANTICOAGULANTS; BLOOD COAGULATION FACTORS; DRUG INTERACTIONS; FACTOR VIIA; HUMANS; RECOMBINANT PROTEINS;

EID: 84898784649     PISSN: 00493848     EISSN: 18792472     Source Type: Journal    
DOI: 10.1016/j.thromres.2014.01.031     Document Type: Review

References (65)

1. E. Investigators, R. Bauersachs, S.D. Berkowitz, B. Brenner, H.R. Buller, and H. Decousus et al. Oral rivaroxaban for symptomatic venous thromboembolism N Engl J Med 363 26 2010 2499 2510
2. S.J. Connolly, M.D. Ezekowitz, S. Yusuf, J. Eikelboom, J. Oldgren, and A. Parekh et al. Dabigatran versus warfarin in patients with atrial fibrillation N Engl J Med 361 12 2009 1139 1151
3. C.B. Granger, J.H. Alexander, J.J. McMurray, R.D. Lopes, E.M. Hylek, and M. Hanna et al. Apixaban versus warfarin in patients with atrial fibrillation N Engl J Med 365 11 2011 981 992
4. M.R. Patel, K.W. Mahaffey, J. Garg, G. Pan, D.E. Singer, and W. Hacke et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation N Engl J Med 365 10 2011 883 891
5. B.I. Eriksson, L.C. Borris, R.J. Friedman, S. Haas, M.V. Huisman, and A.K. Kakkar et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty N Engl J Med 358 26 2008 2765 2775
6. M.R. Lassen, W. Ageno, L.C. Borris, J.R. Lieberman, N. Rosencher, and T.J. Bandel et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty N Engl J Med 358 26 2008 2776 2786
7. M.R. Lassen, A. Gallus, G.E. Raskob, G. Pineo, D. Chen, and L.M. Ramirez et al. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement N Engl J Med 363 26 2010 2487 2498
8. M.R. Lassen, G.E. Raskob, A. Gallus, G. Pineo, D. Chen, and R.J. Portman Apixaban or enoxaparin for thromboprophylaxis after knee replacement N Engl J Med 361 6 2009 594 604
9. M. Crowther, M. Kitt, V. Mathur, G. Lu, A. Hutchaleelaha, and S. Hollenbach et al. A phase 2 randomized, double-blind, placebo-controlled trial of PRT064445, a novel, universal antidote for direct and indirect factor Xa inhibitors ISTH 2013 Conference: International Society of Thrombosis & Hemostasis 2013 [Available from: http://www.eventure-online.com/eventure/ publicAbstractView.do?id=214894&congressId=6839 ]
10. G. Lu, F.R. DeGuzman, S.J. Hollenbach, M.J. Karbarz, K. Abe, and G. Lee et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa Nat Med 19 4 2013 446 451
11. F. Schiele, J. van Ryn, K. Canada, C. Newsome, E. Sepulveda, and J. Park et al. A specific antidote for dabigatran: functional and structural characterization Blood 121 18 2013 3554 3562
12. M. Levi, J.H. Levy, H.F. Andersen, and D. Truloff Safety of recombinant activated factor VII in randomized clinical trials N Engl J Med 363 19 2010 1791 1800
13. A. Majeed, A. Eelde, A. Agren, S. Schulman, and M. Holmstrom Thromboembolic safety and efficacy of prothrombin complex concentrates in the emergency reversal of warfarin coagulopathy Thromb Res 129 2 2012 146 151
14. C. Wojcik, M.L. Schymik, and E.G. Cure Activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for the reversal of warfarin-induced coagulopathy Int J Emerg Med 2 4 2009 217 225
15. S. Schulman, C. Kearon, A.K. Kakkar, P. Mismetti, S. Schellong, and H. Eriksson et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism N Engl J Med 361 24 2009 2342 2352
16. J. Stangier, H. Stahle, K. Rathgen, and R. Fuhr Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects Clin Pharmacokinet 47 1 2008 47 59
17. J. van Ryn, J. Stangier, S. Haertter, K.H. Liesenfeld, W. Wienen, and M. Feuring et al. Dabigatran etexilate-a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity Thromb Haemost 103 6 2010 1116 1127
18. V. Gurewich Ximelagatran-promises and concerns JAMA 293 6 2005 736 739
19. J.N. Fiessinger, M.V. Huisman, B.L. Davidson, H. Bounameaux, C.W. Francis, and H. Eriksson et al. Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial JAMA 293 6 2005 681 689
20. S. Baathe, B. Hamren, M.O. Karlsson, M. Wollbratt, M. Grind, and U.G. Eriksson Population pharmacokinetics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, in atrial fibrillation patients receiving long-term anticoagulation therapy Clin Pharmacokinet 45 8 2006 803 819
21. M. Wolzt, M. Levi, T.C. Sarich, S.L. Bostrom, U.G. Eriksson, and M. Eriksson-Lepkowska et al. Effect of recombinant factor VIIa on melagatran-induced inhibition of thrombin generation and platelet activation in healthy volunteers Thromb Haemost 91 6 2004 1090 1096
22. G. Agnelli, A. Gallus, S.Z. Goldhaber, S. Haas, M.V. Huisman, and R.D. Hull et al. Treatment of proximal deep-vein thrombosis with the oral direct factor Xa inhibitor rivaroxaban (BAY 59-7939): the ODIXa-DVT (Oral Direct Factor Xa Inhibitor BAY 59-7939 in Patients With Acute Symptomatic Deep-Vein Thrombosis) study Circulation 116 2 2007 180 187
23. D. Kubitza, M. Becka, G. Wensing, B. Voith, and M. Zuehlsdorf 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 61 12 2005 873 880
24. W. Mueck, J. Stampfuss, D. Kubitza, and M. Becka Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban Clin Pharmacokinet 53 1 2014 1 16
25. G. Agnelli, H.R. Buller, A. Cohen, M. Curto, A.S. Gallus, and M. Johnson et al. Oral apixaban for the treatment of acute venous thromboembolism N Engl J Med 369 9 2013 799 808
26. C. Frost, J. Wang, S. Nepal, A. Schuster, Y.C. Barrett, and R. Mosqueda-Garcia et al. Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects Br J Clin Pharmacol 75 2 2013 476 487
27. V.V. Upreti, Y. Song, J. Wang, W. Byon, R.A. Boyd, and J.M. Pursley et al. Effect of famotidine on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor Clin Pharmacol 5 2013 59 66
28. R.P. Giugliano, C.T. Ruff, E. Braunwald, S.A. Murphy, S.D. Wiviott, and J.L. Halperin et al. Edoxaban versus warfarin in patients with atrial fibrillation N Engl J Med 369 22 2013 2093 2104
29. V.T.E.I. Hokusai, H.R. Buller, H. Decousus, M.A. Grosso, M. Mercuri, and S. Middeldorp et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism N Engl J Med 369 15 2013 1406 1415
30. K. Ogata, J. Mendell-Harary, M. Tachibana, H. Masumoto, T. Oguma, and M. Kojima et al. Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers J Clin Pharmacol 50 7 2010 743 753
31. J.I. Weitz, S.J. Connolly, I. Patel, D. Salazar, S. Rohatagi, and J. Mendell et al. Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation Thromb Haemost 104 3 2010 633 641
32. W. Zhou, S. Schwarting, S. Illanes, A. Liesz, M. Middelhoff, and M. Zorn et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran Stroke 42 12 2011 3594 3599
33. M.D. Lambourne, L.J. Eltringham-Smith, S. Gataiance, D.M. Arnold, M.A. Crowther, and W.P. Sheffield Prothrombin complex concentrates reduce blood loss in murine coagulopathy induced by warfarin, but not in that induced by dabigatran etexilate J Thromb Haemost 10 9 2012 1830 1840
34. W. Zhou, M. Zorn, P. Nawroth, U. Butehorn, E. Perzborn, and S. Heitmeier et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with rivaroxaban Stroke 44 3 2013 771 778
35. M. Elg, S. Carlsson, and D. Gustafsson Effects of agents, used to treat bleeding disorders, on bleeding time prolonged by a very high dose of a direct thrombin inhibitor in anesthesized rats and rabbits Thromb Res 101 3 2001 159 170
36. M. Elg, S. Carlsson, and D. Gustafsson Effect of activated prothrombin complex concentrate or recombinant factor VIIa on the bleeding time and thrombus formation during anticoagulation with a direct thrombin inhibitor Thromb Res 101 3 2001 145 157
37. T. Fukuda, Y. Honda, C. Kamisato, Y. Morishima, and T. Shibano Reversal of anticoagulant effects of edoxaban, an oral, direct factor Xa inhibitor, with haemostatic agents Thromb Haemost 107 2 2012 253 259
38. E. Perzborn, A. Gruber, H. Tinel, U.M. Marzec, U. Buetehorn, and A. Buchmueller et al. Reversal of rivaroxaban anticoagulation by haemostatic agents in rats and primates Thromb Haemost 110 1 2013 162 172
39. I. Pragst, S.H. Zeitler, B. Doerr, F.J. Kaspereit, E. Herzog, and G. Dickneite et al. Reversal of dabigatran anticoagulation by prothrombin complex concentrate (Beriplex P/N) in a rabbit model J Thromb Haemost 10 9 2012 1841 1848
40. A. Godier, A. Miclot, B. Le Bonniec, M. Durand, A.M. Fischer, and J. Emmerich et al. Evaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit model Anesthesiology 116 1 2012 94 102
41. J.D. Folts, E.B. Crowell Jr., and G.G. Rowe Platelet aggregation in partially obstructed vessels and its elimination with aspirin Circulation 54 3 1976 365 370
42. A.C. Martin, B. Le Bonniec, A.M. Fischer, C. Marchand-Leroux, P. Gaussem, and C.M. Samama et al. Evaluation of recombinant activated factor VII, prothrombin complex concentrate, and fibrinogen concentrate to reverse apixaban in a rabbit model of bleeding and thrombosis Int J Cardiol 168 4 2013 4228 4233
43. A. Gruber, S. Carlsson, H.F. Kotze, U. Marzec, T.C. Sarich, and S.R. Hanson Hemostatic effect of activated factor VII without promotion of thrombus growth in melagatran-anticoagulated primates Thromb Res 119 1 2007 121 127
44. E.S. Eerenberg, P.W. Kamphuisen, M.K. Sijpkens, J.C. Meijers, H.R. Buller, and M. Levi Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects Circulation 124 14 2011 1573 1579
45. R. Marlu, E. Hodaj, A. Paris, P. Albaladejo, J.L. Cracowski, and G. Pernod Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers Thromb Haemost 108 2 2012 217 224
46. J. van Ryn, A. Goss, N. Hauel, W. Wienen, H. Priepke, and H. Nar et al. The discovery of dabigatran etexilate Front Pharmacol 4 2013 12
47. CHMP Assessment Report for Xarelto 2008 European Medicines Agency [EMEA/543519/2008]
48. C. Weeterings, P.G. de Groot, J. Adelmeijer, and T. Lisman The glycoprotein Ib-IX-V complex contributes to tissue factor-independent thrombin generation by recombinant factor VIIa on the activated platelet surface Blood 112 8 2008 3227 3233
49. C. Weeterings, T. Lisman, and P.G. de Groot Tissue factor-independent effects of recombinant factor VIIa on hemostasis Semin Hematol 45 2 Suppl. 1 2008 S12 S15
50. D.M. Monroe, M. Hoffman, J.A. Oliver, and H.R. Roberts Platelet activity of high-dose factor VIIa is independent of tissue factor Br J Haematol 99 3 1997 542 547
51. J.W. Eikelboom, and J.I. Weitz New anticoagulants Circulation 121 13 2010 1523 1532
52. M. Hoffman, and D.M. Monroe Tissue factor in brain is not saturated with factor VIIa: implications for factor VIIa dosing in intracerebral hemorrhage Stroke 40 8 2009 2882 2884
53. T. Knudsen, O.H. Olsen, and L.C. Petersen Tissue factor and factor VIIa cross-species compatibility Front Biosci (Landmark Ed) 16 2011 3196 3215
54. R.T. NovoSeven, and Product Monograph Novo Nordisk 2013
55. T. Klitgaard, R. Tabanera y Palacios, K.D. Boffard, P.T. Iau, B. Warren, and S. Rizoli et al. Pharmacokinetics of recombinant activated factor VII in trauma patients with severe bleeding Crit Care 10 4 2006 R104
56. K.D. Boffard, B. Riou, B. Warren, P.I. Choong, S. Rizoli, and R. Rossaint et al. Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials J Trauma 59 1 2005 8 15
57. F.E. Preston, S.T. Laidlaw, B. Sampson, and S. Kitchen Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): efficacy and safety in 42 patients Br J Haematol 116 3 2002 619 624
58. Unactivated prothrombin complex concentrates (4 factors: II, VII, IX, and X with proteins C and S): Drug information UpToDate [Internet] 2014
59. M.W. Hilgartner, and G.L. Knatterud The use of factor eight inhibitor by-passing activity (FEIBA immuno) product for treatment of bleeding episodes in hemophiliacs with inhibitors Blood 61 1 1983 36 40
60. L.J. Sjamsoedin, L. Heijnen, E.P. Mauser-Bunschoten, J.L. van Geijlswijk, H. van Houwelingen, and P. van Asten et al. The effect of activated prothrombin-complex concentrate (FEIBA) on joint and muscle bleeding in patients with hemophilia A and antibodies to factor VIII. A double-blind clinical trial N Engl J Med 305 13 1981 717 721
61. H. Vinazzer Comparison between two concentrates with factor VIII inhibitor bypassing activity Thromb Res 26 1 1982 21 29
62. P.L. Turecek, K. Varadi, H. Gritsch, and H.P. Schwarz FEIBA: mode of action Haemophilia 10 Suppl. 2 2004 3 9
63. J. Astermark, S.M. Donfield, D.M. DiMichele, A. Gringeri, S.A. Gilbert, and J. Waters et al. A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study Blood 109 2 2007 546 551
64. G. Young, F.E. Shafer, P. Rojas, and S. Seremetis Single 270 microg kg(- 1)-dose rFVIIa vs. standard 90 microg kg(- 1)-dose rFVIIa and APCC for home treatment of joint bleeds in haemophilia patients with inhibitors: a randomized comparison Haemophilia 14 2 2008 287 294
65. Cofact: Product Monograph The Netherlands 2011