Reversal of dabigatran effects in models of thrombin generation and hemostasis by factor Viia and prothrombin complex concentrate

Anesthesiology

Volumn 122, Issue 2, 2015, Pages 353-362

  Hoffman, Maureane ^a   Volovyk, Zoya ^a   Monroe, Dougald M ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BLOOD CLOTTING FACTOR 10; BLOOD CLOTTING FACTOR 9; DABIGATRAN ETEXILATE; PROTHROMBIN; PROTHROMBIN COMPLEX; RECOMBINANT BLOOD CLOTTING FACTOR 7A; THROMBIN; ANTICOAGULANT AGENT; BENZIMIDAZOLE DERIVATIVE; BETA ALANINE; BLOOD CLOTTING FACTOR; BLOOD CLOTTING FACTOR 7A; DABIGATRAN; PROTHROMBIN COMPLEX CONCENTRATES;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTICOAGULATION; ARTICLE; BLEEDING; BLEEDING TIME; CONTROLLED STUDY; DRUG EFFECT; HEMOSTASIS; HUMAN; HUMAN CELL; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; SAPHENOUS VEIN; ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; CHEMICALLY INDUCED; DRUG EFFECTS; HEMORRHAGE; PATHOLOGY; THROMBOELASTOGRAPHY;

ANTICOAGULANTS; BENZIMIDAZOLES; BETA-ALANINE; BLOOD COAGULATION FACTORS; FACTOR VIIA; HEMORRHAGE; HEMOSTASIS; HUMANS; SAPHENOUS VEIN; THROMBELASTOGRAPHY; THROMBIN;

EID: 84922067059     PISSN: 00033022     EISSN: 15281175     Source Type: Journal    
DOI: 10.1097/ALN.0000000000000540     Document Type: Article

References (29)

1. Eisert WG, Hauel N, Stangier J, Wienen W, Clemens A, van Ryn J: Dabigatran: An oral novel potent reversible nonpeptide inhibitor of thrombin. Arterioscler Thromb Vasc Biol 2010; 30:1885-9
2. Camm AJ: The RE-LY study: Randomized Evaluation of Longterm anticoagulant therapY: Dabigatran vs. warfarin. Eur Heart J 2009; 30:2554-5
3. Blech S, Ebner T, Ludwig-Schwellinger E, Stangier J, Roth W: The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos 2008; 36:386-99
4. Stangier J, Clemens A: Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost 2009; 15(suppl 1):9S-16S
5. Bauer KA: Dabigatran, ROCKET atrial fibrillation, and beyond: Basic science, mechanisms of agents, monitoring, and reversal. Stroke 2013; 44(6, suppl 1):S38-40
6. Grottke O, van Ryn J, Spronk HM, Rossaint R: Prothrombin complex concentrates and a specific antidote to dabigatran are effective ex-vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model. Crit Care 2014; 18:R27
7. Schiele F, van Ryn J, Canada K, Newsome C, Sepulveda E, Park J, Nar H, Litzenburger T: A specific antidote for dabigatran: Functional and structural characterization. Blood 2013; 121:3554-62
8. Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski JL, Crackowski 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. 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
10. Zhou W, Schwarting S, Illanes S, Liesz A, Middelhoff M, Zorn M, Bendszus M, Heiland S, van Ryn J, Veltkamp R: Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke 2011; 42:3594-9
11. Dickneite G, Hoffman M: Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): What is the evidence? Thromb Haemost 2014; 111:189-98
12. Dargaud Y, Wolberg AS, Luddington R, Regnault V, Spronk H, Baglin T, Lecompte T, Ten Cate H, Negrier C: Evaluation of a standardized protocol for thrombin generation measurement using the calibrated automated thrombogram: An international multicentre study. Thromb Res 2012; 130:929-34
13. Pastoft AE, Lykkesfeldt J, Ezban M, Tranholm M, Whinna HC, Lauritzen B: A sensitive venous bleeding model in haemophilia A mice: Effects of two recombinant FVIII products (N8 and Advate(® )). Haemophilia 2012; 18:782-8
14. Buyue Y, Whinna HC, Sheehan JP: The heparin-binding exosite of factor IXa is a critical regulator of plasma thrombin generation and venous thrombosis. Blood 2008; 112:3234-41
15. McCord DM, Monroe DM, Smith KJ, Roberts HR: Characterization of the functional defect in factor IX Alabama. Evidence for a conformational change due to high affinity calcium binding in the first epidermal growth factor domain. J Biol Chem 1990; 265:10250-4
16. Hoffman M, Monroe DM, Oliver JA, Roberts HR: Factors IXa and Xa play distinct roles in tissue factor-dependent initiation of coagulation. Blood 1995; 86:1794-801
17. Machlus KR, Colby EA, Wu JR, Koch GG, Key NS, Wolberg AS: Effects of tissue factor, thrombomodulin and elevated clotting factor levels on thrombin generation in the calibrated automated thrombogram. Thromb Haemost 2009; 102:936-44
18. Lambourne MD, Eltringham-Smith LJ, Gataiance S, Arnold DM, Crowther MA, Sheffield WP: Prothrombin complex concentrates reduce blood loss in murine coagulopathy induced by warfarin, but not in that induced by dabigatran etexilate. J Thromb Haemost 2012; 10:1830-40
19. Petersen LC, Nørby PL, Branner S, Sørensen BB, Elm T, Stennicke HR, Persson E, Bjørn SE: Characterization of recombinant murine factor VIIa and recombinant murine tissue factor: A human-murine species compatibility study. Thromb Res 2005; 116:75-85
20. Tranholm M, Kristensen K, Kristensen AT, Pyke C, Røjkjaer R, Persson E: Improved hemostasis with superactive analogs of factor VIIa in a mouse model of hemophilia A. Blood 2003; 102:3615-20
21. Ivanciu L, Toso R, Margaritis P, Pavani G, Kim H, Schlachterman A, Liu JH, Clerin V, Pittman DD, Rose-Miranda R, Shields KM, Erbe DV, Tobin JF, Arruda VR, Camire RM: A zymogen-like factor Xa variant corrects the coagulation defect in hemophilia. Nat Biotechnol 2011; 29:1028-33
22. Kalina U, Bickhard H, Schulte S: Biochemical comparison of seven commercially available prothrombin complex concentrates. Int J Clin Pract 2008; 62:1614-22
23. Feng D, Whinna H, Monroe D, Stafford DW: FVIIa as used pharmacologically is not TF dependent in hemophilia B mice. Blood 2014; 123:1764-6
24. Vaezzadeh N, Ni R, Kim PY, Weitz JI, Gross PL: Comparison of the effect of coagulation and platelet function impairments on various mouse bleeding models. Thromb Haemost 2014; 112:412-8
25. Allen GA, Wolberg AS, Oliver JA, Hoffman M, Roberts HR, Monroe DM: Impact of procoagulant concentration on rate, peak and total thrombin generation in a model system. J Thromb Haemost 2004; 2:402-13
26. Allen GA, Hoffman M, Roberts HR, Monroe DM: Manipulation of prothrombin concentration improves response to highdose factor VIIa in a cell-based model of haemophilia. Br J Haematol 2006; 134:314-9
27. Gatt A, van Veen JJ, Woolley AM, Kitchen S, Cooper P, Makris M: Thrombin generation assays are superior to traditional tests in assessing anticoagulation reversal in vitro. Thromb Haemost 2008; 100:350-5
28. Xu Y, Wu W, Wang L, Chintala M, Plump AS, Ogletree ML, Chen Z: Differential profiles of thrombin inhibitors (heparin, hirudin, bivalirudin, and dabigatran) in the thrombin generation assay and thromboelastography in vitro. Blood Coagul Fibrinolysis 2013; 24:332-8
29. Hosokawa K, Ohnishi T, Sameshima H, Miura N, Koide T, Maruyama I, Tanaka KA: Comparative evaluation of direct thrombin and factor Xa inhibitors with antiplatelet agents under flow and static conditions: An in vitro flow chamber model. PLoS One 2014; 9:e86491