Four-factor prothrombin complex concentrate reverses apixaban-associated bleeding in a rabbit model of acute hemorrhage

Journal of Thrombosis and Haemostasis

Volumn 13, Issue 12, 2015, Pages 2220-2226

  Herzog, E ^a   Kaspereit, F ^a   Krege, W ^a   Mueller Cohrs, J ^a   Doerr, B ^a   Niebl, P ^a   Dickneite, G ^a  

^a CSL BEHRING GMBH   (Germany)

Author keywords

Anticoagulants; Apixaban; Drug evaluation; Hemorrhage; Preclinical study; Prothrombin complex concentrates

Indexed keywords

PROTHROMBIN COMPLEX; ANTIDOTE; APIXABAN; BLOOD CLOTTING FACTOR; HEMOSTATIC AGENT; PROTHROMBIN COMPLEX CONCENTRATES; PYRAZOLE DERIVATIVE; PYRIDONE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLEEDING; BLEEDING TIME; BLOOD CLOTTING TIME; CONTROLLED STUDY; DOSE RESPONSE; DRUG DOSE COMPARISON; HEMOSTASIS; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; PRIORITY JOURNAL; PROTHROMBIN TIME; RABBIT; ACUTE DISEASE; ANIMAL; BLOOD; BLOOD CLOTTING; BLOOD CLOTTING TEST; CHEMICALLY INDUCED; DISEASE MODEL; DRUG EFFECTS; HEMORRHAGE; TIME FACTOR;

ACUTE DISEASE; ANIMALS; ANTIDOTES; BLOOD COAGULATION; BLOOD COAGULATION FACTORS; BLOOD COAGULATION TESTS; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; HEMORRHAGE; HEMOSTASIS; HEMOSTATICS; PYRAZOLES; PYRIDONES; RABBITS; TIME FACTORS;

EID: 84958818867     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.13165     Document Type: Article

References (28)

1. Bristol-Myers Squibb Company. Eliquis highlights of prescribing information. 2014. http://packageinserts.bms.com/pi/pi_eliquis.pdf. Accessed 12 June 2015.
2. Bristol-Myers Squibb/Pfizer EEIG. Eliquis summary of product characteristics. 2014. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf. Accessed 12 June 2015.
3. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e44S-88S.
4. Spahn DR, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Filipescu D, Hunt BJ, Komadina R, Nardi G, Neugebauer E, Ozier Y, Riddez L, Schultz A, Vincent JL, Rossaint R. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care 2013; 17: R76.
5. Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. European Heart J 2013; 34: 2094-106.
6. Lu G, DeGuzman FR, Hollenbach SJ, Karbarz MJ, Abe K, Lee G, Luan P, Hutchaleelaha A, Inagaki M, Conley PB, Phillips DR, Sinha U. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med 2013; 19: 446-51.
7. Eerenberg ES, Kamphuisen PW, Sijpkens 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.
8. Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski JL, Pernod G. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost 2012; 108: 217-24.
9. Levi M, Moore KT, Castillejos CF, Kubitza D, Berkowitz SD, Goldhaber SZ, Raghoebar M, Patel MR, Weitz JI, Levy JH. Comparison of three-factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers. J Thromb Haemost 2014; 12: 1428-36.
10. Masotti L, Lorenzini G, Seravalle C, Panigada G, Landini G, Cappelli R, Schulman S. Management of new oral anticoagulants related life threatening or major bleedings in real life: a brief report. J Thromb Thrombolysis 2015; 39: 427-33.
11. Pragst I, Zeitler SH, Doerr B, Kaspereit FJ, Herzog E, Dickneite G, van Ryn J. Reversal of dabigatran anticoagulation by prothrombin complex concentrate (Beriplex P/N) in a rabbit model. J Thromb Haemost 2012; 10: 1841-8.
12. Herzog E, Kaspereit F, Krege W, Doerr B, Mueller-Cohrs J, Pragst I, Morishima Y, Dickneite G. Effective reversal of edoxaban-associated bleeding with four-factor prothrombin complex concentrate in a rabbit model of acute hemorrhage. Anesthesiology 2015; 122: 387-98.
13. Herzog E, Kaspereit F, Krege W, Mueller-Cohrs J, Doerr B, Niebl P, Dickneite G. Correlation of coagulation markers and 4F-PCC-mediated reversal of rivaroxaban in a rabbit model of acute bleeding. Thromb Res 2015; 135: 554-60.
14. Gouin-Thibault I, Flaujac C, Delavenne X, Quenet S, Horellou MH, Laporte S, Siguret V, Lecompte T. Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays. A multicentre French GEHT study. Thromb Haemost 2014; 111: 240-8.
15. ® highlights of prescribing information. 2013. http://labeling.cslbehring.com/PI/US/Kcentra/EN/Kcentra-Prescribing-Information.pdf. Accessed 12 June 2015.
16. Cui Y, Song Y, Wang J, Yu Z, Schuster A, Barrett YC, Frost C. Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects. Clin Pharmacol 2013; 5: 177-84.
17. Yamahira N, Frost C, Fukase H, Yu Z, Wang J, Pursley J, LaCreta F, Hiraoka M. Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of apixaban in healthy Japanese male subjects. Int J Clin Pharmacol Ther 2014; 52: 564-73.
18. Martin AC, Le Bonniec B, Fischer AM, Marchand-Leroux C, Gaussem P, Samama CM, Godier A. 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 2013; 168: 4228-33.
19. Wong PC, Crain EJ, Xin B, Wexler RR, Lam PY, Pinto DJ, Luettgen JM, Knabb RM. Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies. J Thromb Haemost 2008; 6: 820-9.
20. Frost C, Yu Z, Moore K, Nepal S, Barrett Y, Mosqueda-Garcia R, Shenker A. An oral direct factor Xa inhibitor: multiple-dose safety, pharmacokinetics, and pharmacodynamics in healthy subjects. J Thromb Haemost 2007; 5: P-M-664.
21. Frost C, Yu Z, Nepal S, Mosqueda-Garcia R, Shenker A. Factor Xa inhibitor: single-dose safety, pharmacokinetics and pharmacodynamics in healthy subjects. J Thromb Haemost 2007; 5: P-M-665.
22. Zhou W, Zorn M, Nawroth P, Butehorn U, Perzborn E, Heitmeier S, Veltkamp R. Hemostatic therapy in experimental intracerebral hemorrhage associated with rivaroxaban. Stroke 2013; 44: 771-8.
23. Zahir H, Brown KS, Vandell AG, Desai M, Maa JF, Dishy V, Lomeli B, Feussner A, Feng W, He L, Grosso MA, Lanz HJ, Antman EM. Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate. Circulation 2015; 131: 82-90.
24. Wong PC, Pinto DJ, Zhang D. Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor. J Thromb Thrombolysis 2011; 31: 478-92.
25. Furugohri T, Isobe K, Honda Y, Kamisato-Matsumoto C, Sugiyama N, Nagahara T, Morishima Y, Shibano T. DU-176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo pharmacological profiles. J Thromb Haemost 2008; 6: 1542-9.
26. Perzborn E, Strassburger J, Wilmen A, Pohlmann J, Roehrig S, Schlemmer KH, Straub A. In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939 - an oral, direct Factor Xa inhibitor. J Thromb Haemost 2005; 3: 514-21.
27. Wienen W, Stassen JM, Priepke H, Ries UJ, Hauel N. In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate. Thromb Haemost 2007; 98: 155-62.
28. CSL Behring. Beriplex P/N 1000 IU summary of product characteristics. 2014. http://www.medicines.org.uk/emc/medicine/27570. Accessed 12 June 2015.