Prothrombin complex concentrates as reversal agents for new oral anticoagulants: Lessons from preclinical studies with beriplex

Clinics in Laboratory Medicine

Volumn 34, Issue 3, 2014, Pages 623-635

  Dickneite, Gerhard ^a  

^a CSL BEHRING GMBH   (Germany)

Author keywords

Anticoagulant reversal; Beriplex; New oral anticoagulants; Prothrombin complex concentrate

Indexed keywords

ANTICOAGULANT AGENT; APIXABAN; DABIGATRAN; EDOXABAN; PROTHROMBIN COMPLEX; RIVAROXABAN; THROMBIN; ANTITHROMBIN; BLOOD CLOTTING FACTOR 10; BLOOD CLOTTING FACTOR 10A INHIBITOR; BLOOD CLOTTING FACTOR 7; BLOOD CLOTTING FACTOR 9; DRUG COMBINATION; FACTOR IX, FACTOR VII, FACTOR X, PROTHROMBIN DRUG COMBINATION; HEMOSTATIC AGENT; PROTHROMBIN;

ANTICOAGULATION; ANTICOAGULATION REVERSAL; BLEEDING; BLEEDING TIME; BLOOD CLOTTING TIME; BRAIN HEMORRHAGE; DISEASE MODEL; DOSE RESPONSE; DRUG EFFECT; DRUG EFFICACY; DRUG SCREENING; EX VIVO STUDY; HEMOSTASIS; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MURINE MODEL; NONHUMAN; PARTIAL THROMBOPLASTIN TIME; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTHROMBIN TIME; RABBIT MODEL; REVIEW; THROMBIN TIME; TREATMENT DURATION; VALIDATION PROCESS; ANIMAL; BIOLOGICAL MODEL; BLOOD CLOTTING; CHEMICALLY INDUCED; CHEMISTRY; COMPARATIVE STUDY; DRUG COMBINATION; DRUG EFFECTS; HEMORRHAGE; ORAL DRUG ADMINISTRATION;

ADMINISTRATION, ORAL; ANIMALS; ANTICOAGULANTS; ANTITHROMBINS; BLOOD COAGULATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG COMBINATIONS; DRUG EVALUATION, PRECLINICAL; FACTOR IX; FACTOR VII; FACTOR X; FACTOR XA INHIBITORS; HEMORRHAGE; HEMOSTASIS; HEMOSTATICS; HUMANS; MODELS, BIOLOGICAL; PROTHROMBIN;

EID: 84906936308     PISSN: 02722712     EISSN: 15579832     Source Type: Journal    
DOI: 10.1016/j.cll.2014.06.001     Document Type: Review

References (46)

1. Nutescu E.A., Shapiro N.L., Chevalier A., et al. Apharmacologic overview of current and emerging anticoagulants. Cleve Clin J Med 2005, 72(Suppl 1):S2-S6.
2. Ahrens I., Peter K., Lip G.Y., et al. Development and clinical applications of novel oral anticoagulants. Part II. Drugs under clinical investigation. Discov Med 2012, 13(73):445-450.
3. Moser M., Bode C. Anticoagulation in atrial fibrillation: a new era has begun. Hamostaseologie 2012, 32(1):37-39. [in German].
4. Eriksson B.I., Quinlan D.J., Eikelboom J.W. Novel oral factor Xa and thrombin inhibitors in the management of thromboembolism. Annu Rev Med 2011, 62:41-57.
5. Ahrens I., Peter K., Lip G.Y., et al. Development and clinical applications of novel oral anticoagulants. Part I. Clinically approved drugs. Discov Med 2012, 13(73):433-443.
6. Samama M.M. The mechanism of action of rivaroxaban-an oral, direct factor Xa inhibitor-compared with other anticoagulants. Thromb Res 2011, 127(6):497-504.
7. Budnitz D.S., Lovegrove M.C., Shehab N., et al. Emergency hospitalizations for adverse drug events in older Americans. NEngl J Med 2011, 365(21):2002-2012.
8. Budnitz D.S., Shehab N., Kegler S.R., et al. Medication use leading to emergency department visits for adverse drug events in older adults. Ann Intern Med 2007, 147(11):755-765.
9. Huhtakangas J., Tetri S., Juvela S., et al. Effect of increased warfarin use on warfarin-related cerebral hemorrhage: a longitudinal population-based study. Stroke 2011, 42(9):2431-2435.
10. Rosand J., Eckman M.H., Knudsen K.A., et al. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004, 164(8):880-884.
11. Wysowski D.K., Nourjah P., Swartz L. Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arch Intern Med 2007, 167(13):1414-1419.
12. Holbrook A., Schulman S., Witt D.M., et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012, 141(2 Suppl):e152S-e184S.
13. Kalina U., Bickhard H., Schulte S. Biochemical comparison of seven commercially available prothrombin complex concentrates. Int J Clin Pract 2008, 62(10):1614-1622.
14. Sarode R., Milling T.J., Refaai M.A., et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation 2013, 128(11):1234-1243.
15. Sarode R. Four-factor prothrombin complex concentrate versus plasma for urgent VKA reversal: what's new? Clin Lab Med, in press.
16. Eerenberg E.S., Kamphuisen P.W., Sijpkens M.K., et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 2011, 124(14):1573-1579.
17. Diaz M.Q., Borobia A.M., Nunez M.A., et al. Use of prothrombin complex concentrates for urgent reversal of dabigatran in the emergency department. Haematologica 2013, 98(11):e143-e144.
18. Pabinger I., Brenner B., Kalina U., et al. Prothrombin complex concentrate (Beriplex P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial. JThromb Haemost 2008, 6(4):622-631.
19. Dickneite G., Hoffman M. Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence?. Thromb Haemost 2013, 111(2):189-198. Availabe at:. http://www.ncbi.nlm.nih.gov/pubmed/24136202.
20. Pragst I., Zeitler S.H., Doerr B., et al. Reversal of dabigatran anticoagulation by prothrombin complex concentrate (Beriplex P/N) in a rabbit model. JThromb Haemost 2012, 10(9):1841-1848.
21. Hoffman M., Volovyk Z., Monroe D. Partial reversal of dabigatran effect by a prothrombin complex concentrate in a model of thrombin generation (2012 ASH abstracts). Blood 2012, 120:3420.
22. Pillitteri D., Pilgrimm-Thorp A.K., Krause M., et al. Antidotal effects of non-specific reversal agents on anticoagulant-induced inhibition of thrombin generation (2013 ISTH abstracts). JThromb Haemost 2013, 11(Suppl s2):562-563.
23. Galan A.M., Arellano-Rodrigo E., Sanz V., et al. Reversal of the antithrombotic action of rivaroxaban and dabigatran: a clinical study in healthy volunteers. (2012 ASH abstracts). Blood 2012, 120(21):2261.
24. Galan A.M., Arellano-Rodrigo E., Sanz V., et al. Effects of rivaroxaban and dabigatran on hemostasis and reversion of their antithrombotic effects by different coagulation factors. Evidence raised from a clinical study in healthy volunteers (2013 ISTH abstracts). JThromb Haemost 2013, 11(Suppl s2):418-419.
25. Zhou W., Schwarting S., Illanes S., et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke 2011, 42(12):3594-3599.
26. van Ryn J., Schurer J., Kink-Eiband M., et al. The successful reversal of dabigatran-induced bleeding by coagulation factor concentrates in a rat tail bleeding model do not correlate with exvivo markers of anticoagulation (2011 ASH abstracts). Blood 2011, 118:2316.
27. Herzog E, Kaspereit F, Krege W, etal. Pre-clinical safety aspects on the use of Beriplex P/N for reversal of Dabigatran anticoagulation [abstract P5-1]. Paper presented at: 57th Annual Meeting of the German Thrombosis and Haemostasis Research Society. Munich, Germany, February 20-23, 2013.
28. Herzog E., Kaspereit F., Krege W., et al. Non-clinical safety and efficacy of prothrombin complex concentrates (PCC) for the reversal of dabigatran mediated anticoagulation (2013 ISTH abstracts). JThromb Haemost 2013, 11(Suppl s2):693.
29. van Ryn J, Schurer J, Kink-Eiband M, etal. Successful reversal of dabigatran-induced bleeding by 3-factor coagulation concentrates in a rat tail bleeding model: lack of correlation with exvivo markers of anticoagulation. Paper presented at: AHA Scientific Sessions and Resuscitation Science Symposium. Los Angeles, USA, November 3-5, 2012.
30. Arellano-Rodrigo E., Galan A.M., Sanz V., et al. Alterations induced by rivaroxaban on hemostasis can be reversed by different coagulation factor concentrates: invitro experimental studies with steady and circulating human blood (2013 ISTH abstracts). JThromb Haemost 2013, 11(Suppl s2):953-954.
31. Zhou W., Zorn M., Nawroth P., et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with rivaroxaban. Stroke 2013, 44(3):771-778.
32. Perzborn E., Gruber A., Tinel H., et al. Reversal of rivaroxaban anticoagulation by haemostatic agents in rats and primates. Thromb Haemost 2013, 110(1):162-172.
33. Levi M., Moore T., Castillejos C.F., et al. Effects of three-factor and four-factor prothrombin complex concentrates on the pharmacodynamics of rivaroxaban (2013 ISTH abstracts). JThromb Haemost 2013, 11(Suppl s2):167.
34. Escolar G., Fernandez-Gallego V., Arellano-Rodrigo E., et al. Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies invitro with circulating human blood. PLoS One 2013, 8(11):e78696.
35. Herzog E., Kaspereit F., Krege W., et al. Four-factor prothrombin complex concentrate (4-PCC) effectively reverses edoxaban induced bleeding in a rabbit model of acute injury (2013 ASH abstracts). Blood 2013, 122:1133.
36. Sorensen B., Spahn D.R., Innerhofer P., et al. Clinical review: prothrombin complex concentrates-evaluation of safety and thrombogenicity. Crit Care 2011, 15(1):201.
37. Baglin T., Hillarp A., Tripodi A., et al. Measuring Oral Direct Inhibitors (ODIs) of thrombin and factor Xa: a recommendation from the Subcommittee on Control of Anticoagulation of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. JThromb Haemost 2013, 11(4):756-760.
38. Samama M.M., Mendell J., Guinet C., et al. Invitro study of the anticoagulant effects of edoxaban and its effect on thrombin generation in comparison to fondaparinux. Thromb Res 2012, 129(4):e77-e82.
39. Lambourne M.D., Eltringham-Smith L.J., Gataiance S., et al. Prothrombin complex concentrates reduce blood loss in murine coagulopathy induced by warfarin, but not in that induced by dabigatran etexilate. JThromb Haemost 2012, 10(9):1830-1840.
40. Holland L., Warkentin T.E., Refaai M., et al. Suboptimal effect of a three-factor prothrombin complex concentrate (Profilnine-SD) in correcting supratherapeutic international normalized ratio due to warfarin overdose. Transfusion 2009, 49(6):1171-1177.
41. Godier A., Miclot A., Le Bonniec B., et al. Evaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit model. Anesthesiology 2012, 116(1):94-102.
42. Turpie A.G., Kreutz R., Llau J., et al. Management consensus guidance for the use of rivaroxaban-an oral, direct factor Xa inhibitor. Thromb Haemost 2012, 108(5):876-886.
43. Ahmad Y., Lip G.Y. Anticoagulation in atrial fibrillation. Arrhythmia & Electrophysiology Review 2012, 1:12-16.
44. Lu G., DeGuzman F.R., Hollenbach S.J., et al. Aspecific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med 2013, 19(4):446-451.
45. van Ryn J, Litzenburger T, Waterman A, etal. An antibody selective to dabigatran safely neutralizes both dabigatran-induced anticoagulant and bleeding activity in invitro and invivo models [Abstract P-MO-166]. Paper presented at: 57th Annual Meeting of the International Society on Thrombosis and Haemostasis. Kyoto, Japan, July 23-28, 2011.
46. van Ryn J, Litzenburger T, Schurer J. Reversal of anticoagulant activity of dabigatran and dabigatran-induced bleeding in rats by a specific antidote (antibody fragment) [abstract 9928]. Paper presented at: American Heart Association Scientific Sessions and Resuscitation Science Symposium. Los Angeles, USA, November 3-7, 2012.