When and how to use antidotes for the reversal of direct oral anticoagulants: Guidance from the SSC of the ISTH

Journal of Thrombosis and Haemostasis

Volumn 14, Issue 3, 2016, Pages 623-627

  Levy, J H ^a   Ageno, W ^b   Chan, N C ^c   Crowther, M ^d   Verhamme, P ^e   Weitz, J I ^d  

^a DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF INSUBRIA   (Italy)

^c MONASH UNIVERSITY   (Australia)

^d MCMASTER UNIVERSITY   (Canada)

^e UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANDEXANET ALFA; ANTICOAGULANT AGENT; ANTIDOTE; APIXABAN; CIRAPARANTAG; DABIGATRAN; EDOXABAN; IDARUCIZUMAB; RIVAROXABAN; ARGININE; BLOOD CLOTTING FACTOR 10A; COAGULATING AGENT; MONOCLONAL ANTIBODY; PIPERAZINE DERIVATIVE; RECOMBINANT PROTEIN;

ANTICOAGULATION; ARTICLE; BLEEDING; DRUG BINDING; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG CONTRAINDICATION; DRUG COST; DRUG EFFICACY; DRUG HALF LIFE; DRUG INDICATION; DRUG MECHANISM; DRUG SAFETY; DRUG STORAGE; DRUG USE; HUMAN; LABORATORY TEST; PARTIAL THROMBOPLASTIN TIME; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTHROMBIN TIME; THROMBIN TIME; ANALOGS AND DERIVATIVES; BLOOD CLOTTING; CHEMICALLY INDUCED; DRUG EFFECTS; HEMORRHAGE; ORAL DRUG ADMINISTRATION; PRACTICE GUIDELINE;

ADMINISTRATION, ORAL; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTICOAGULANTS; ANTIDOTES; ARGININE; BLOOD COAGULATION; COAGULANTS; FACTOR XA; HEMORRHAGE; HUMANS; PIPERAZINES; RECOMBINANT PROTEINS;

EID: 84975770227     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.13227     Document Type: Article

References (14)

1. Weitz JI. Anticoagulation therapy in 2015: where we are and where we are going. J Thromb Thrombolysis 2015; 39: 264-72.
2. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383: 955-62.
3. Majeed A, Hwang HG, Connolly SJ, Eikelboom JW, Ezekowitz MD, Wallentin L, Brueckmann M, Fraessdorf M, Yusuf S, Schulman S. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation 2013; 128: 2325-32.
4. Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, Mathur VS, Castillo J, Bronson MD, Leeds JM, Mar FA, Gold A, Crowther MA. Andexanet alfa for the reversal of factor xa inhibitor activity. N Engl J Med 2015; 373: 2413-24.
5. Glund S, Stangier J, Schmohl M, Gansser D, Norris S, van Ryn J, Lang B, Ramael S, Moschetti V, Gruenenfelder F, Reilly P, Kreuzer J. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet 2015; 386: 680-90.
6. Pollack CV Jr, Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kamphuisen PW, Kreuzer J, Levy JH, Sellke FW, Stangier J, Steiner T, Wang B, Kam CW, Weitz JI. Idarucizumab for dabigatran reversal. N Engl J Med 2015; 373: 511-20.
7. Pollack CV Jr, Reilly PA, Bernstein R, Dubiel R, Eikelboom J, Glund S, Huisman MV, Hylek E, Kam CW, Kamphuisen PW, Kreuzer J, Levy JH, Sellke F, Stangier J, Steiner T, Wang B, Weitz JI. Design and rationale for RE-VERSE AD: a phase 3 study of idarucizumab, a specific reversal agent for dabigatran. Thromb Haemost 2015; 114: 198-205.
8. Crowther M, Crowther MA. Antidotes for novel oral anticoagulants: current status and future potential. Arterioscler Thromb Vasc Biol 2015; 35: 1736-45.
9. Crowther M, Levy G, Lu G, Leeds J, Barron L, Conley P, Connolly S, Curnutte J. A phase 2 randomized, double-blind, placebo-controlled trial demonstrating reversal of edoxaban-induced anticoagulation in healthy subjects by andexanet alfa (PRT064445), a universal antidote for factor Xa (fXa) inhibitors. Blood 2014; 124: 4269. abstract.
10. Sullivan DW Jr, Gad SC, Laulicht B, Bakhru S, Steiner S. Nonclinical safety assessment of PER977: a small molecule reversal agent for new oral anticoagulants and heparins. Int J Toxicol 2015; 34: 308-17.
11. Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso M, Brown K, Dishy V, Noveck RJ, Costin JC. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med 2014; 371: 2141-2.
12. van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, Clemens A. Dabigatran etexilate - a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103: 1116-27.
13. Samama MM, Contant G, Spiro TE, Perzborn E, Guinet C, Gourmelin Y, Le Flem L, Rohde G, Martinoli JL; Rivaroxaban Anti-Factor Xa Chromogenic Assay Field Trial L. Evaluation of the anti-factor Xa chromogenic assay for the measurement of rivaroxaban plasma concentrations using calibrators and controls. Thromb Haemost 2012; 107: 379-87.
14. Cuker A, Siegal DM, Crowther MA, Garcia DA. Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants. J Am Coll Cardiol 2014; 64: 1128-39.