Reversal of Apixaban Induced Alterations in Hemostasis by Different Coagulation Factor Concentrates: Significance of Studies In Vitro with Circulating Human Blood

作者: Gines Escolar , Victor Fernandez-Gallego , Eduardo Arellano-Rodrigo , Jaume Roquer , Joan Carles Reverter

DOI: 10.1371/JOURNAL.PONE.0078696

关键词:

摘要: Apixaban is a new oral anticoagulant with specific inhibitory action on FXa. No information available the reversal of antihemostatic apixaban in experimental or clinical settings. We have evaluated effectiveness different factor concentrates at reversing modifications hemostatic mechanisms induced by moderately elevated concentrations (200 ng/ml) added vitro to blood from healthy donors (n = 10). Effects thrombin generation (TG) and thromboelastometry (TEM) parameters were assessed. Modifications platelet adhesive, aggregating procoagulant activities studies circulating through damaged vascular surfaces, shear rate 600 s(-1). The potential prothrombin complex (PCCs; 50 IU/kg), activated (aPCCs; 75 recombinant VII (rFVIIa; 270 μg/kg), actions apixaban, investigated. interfered TG kinetics. Delayed lag phase, prolonged time peak reduced values, improved concentrates, though patterns diversely affected depending activating reagents. significantly clotting times (CTs) TEM studies. Prolongations CTs corrected variable efficacies (rFVIIa≥aPCC>PCC). fibrin interactions surfaces perfusion (p<0.05 p<0.01, respectively). Impairments formation normalized concentrates. Only rFVIIa restored levels deposition. Alterations hemostasis variably compensated However, effects these not homogeneous all tests, PCCs showing more efficacy TG, being effective Our results indicate that rFVIIa, aPCCs restore components previously altered apixaban.

参考文章(38)
Ana M. Galan, Miguel Lozano, Patricia Molina, Fulgencio Navalon, Sussane Marschner, Raymond Goodrich, Ginés Escolar, IMPACT OF PATHOGEN REDUCTION TECHNOLOGY AND STORAGE IN PLATELET ADDITIVE SOLUTIONS ON PLATELET FUNCTION Transfusion. ,vol. 51, pp. 808- 815 ,(2011) , 10.1111/J.1537-2995.2010.02914.X
Charles Frost, Jessie Wang, Sunil Nepal, Alan Schuster, Yu Chen Barrett, Rogelio Mosqueda‐Garcia, Richard A. Reeves, Frank LaCreta, Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects British Journal of Clinical Pharmacology. ,vol. 75, pp. 476- 487 ,(2013) , 10.1111/J.1365-2125.2012.04369.X
K. G. MANN, Is there value in kinetic modeling of thrombin generation? Yes. Journal of Thrombosis and Haemostasis. ,vol. 10, pp. 1463- 1469 ,(2012) , 10.1111/J.1538-7836.2012.04799.X
H. C. HEMKER, S. KERDELO, R.M.W. KREMERS, Is there value in kinetic modeling of thrombin generation? No (unless…) Journal of Thrombosis and Haemostasis. ,vol. 10, pp. 1470- 1477 ,(2012) , 10.1111/J.1538-7836.2012.04802.X
I. PRAGST, S. H. ZEITLER, B. DOERR, F. J. KASPEREIT, E. HERZOG, G. DICKNEITE, J. van RYN, Reversal of dabigatran anticoagulation by prothrombin complex concentrate (Beriplex P/N) in a rabbit model Journal of Thrombosis and Haemostasis. ,vol. 10, pp. 1841- 1848 ,(2012) , 10.1111/J.1538-7836.2012.04859.X
Luciano Crippa, Anna Falanga, Guido Finazzi, Francesco Marongiu, Gualtiero Palareti, Daniela Poli, Sophie Testa, Eros Tiraferri, Alberto Tosetto, Armando Tripodi, Cesare Manotti, Vittorio Pengo, Questions and answers on the use of dabigatran and perpectives on the use of other new oral anticoagulants in patients with atrial fibrillation: A consensus document of the Italian Federation of Thrombosis Centers (FCSA) Thrombosis and Haemostasis. ,vol. 106, pp. 868- 876 ,(2011) , 10.1160/TH11-05-0358
Chiara Marchesi, Matteo Pierfranceschi, Mark Crowther, David Garcia, Elaine Hylek, Daniel Witt, Nathan Clark, Alessandro Squizzato, Davide Imberti, Walter Ageno, Francesco Dentali, Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists Thrombosis and Haemostasis. ,vol. 106, pp. 429- 438 ,(2011) , 10.1160/TH11-01-0052
Raphael Marlu, Enkelejda Hodaj, Adeline Paris, Pierre Albaladejo, Jean Crackowski, Gilles Pernod, Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thrombosis and Haemostasis. ,vol. 108, pp. 217- 224 ,(2012) , 10.1160/TH12-03-0179
K. Varadi, P. L. Turecek, H. P. Schwarz, Thrombin generation assay and other universal tests for monitoring haemophilia therapy. Haemophilia. ,vol. 10, pp. 17- 21 ,(2004) , 10.1111/J.1365-2516.2004.00936.X