Factor XIa-specific IgG and a reversal agent to probe factor XI function in thrombosis and hemostasis

Science Translational Medicine

Volumn 8, Issue 353, 2016, Pages

  David, Tovo ^a   Kim, Yun Cheol ^b   Ely, Lauren K ^b   Rondon, Isaac ^b   Gao, Huilan ^b   O'Brien, Peter ^b   Bolt, Michael W ^b   Coyle, Anthony J ^b   Garcia, Jorge L ^c   Flounders, Eric A ^c   Mikita, Thomas ^b   Coughlin, Shaun R ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b PFIZER INC   (United States)

^c PMI PreClinical   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATED PROTEIN C; ANTISENSE OLIGONUCLEOTIDE; APIXABAN; BENZYLSULFONYL FLUORIDE; BLOOD CLOTTING FACTOR 11; BLOOD CLOTTING FACTOR 11A; BLOOD CLOTTING FACTOR 11A INHIBITOR; CYCLIC AMP DEPENDENT PROTEIN KINASE; ENOXAPARIN; ENZYME PRECURSOR; FERROUS CHLORIDE; IMMUNOGLOBULIN; IMMUNOGLOBULIN B11; IMMUNOGLOBULIN C24; IMMUNOGLOBULIN D4; IMMUNOGLOBULIN DEF; IMMUNOGLOBULIN G; IMMUNOGLOBULIN G1; PREKALLIKREIN; RIVAROXABAN; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; THROMBIN; UNCLASSIFIED DRUG; BLOCKING ANTIBODY; MONOCLONAL ANTIBODY;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTICOAGULATION; ARTERY THROMBOSIS; ARTICLE; BINDING AFFINITY; BINDING KINETICS; BLEEDING; BLOOD CLOTTING; BLOOD CLOTTING FACTOR 11 DEFICIENCY; BLOOD SAMPLING; CAROTID ARTERY OBSTRUCTION; CEREBROVASCULAR ACCIDENT; CONTROLLED STUDY; CUTICLE; DEEP VEIN THROMBOSIS; DISSOCIATION CONSTANT; DOSE RESPONSE; DRUG HALF LIFE; ENZYME ACTIVATION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME LINKED IMMUNOSORBENT ASSAY; HEART INFARCTION; HEMOSTASIS; LIMB ISCHEMIA; LUNG EMBOLISM; MOUSE; NONHUMAN; OPTICAL DENSITY; PARTIAL THROMBOPLASTIN TIME; POLYMERASE CHAIN REACTION; POSITIVE FEEDBACK; PRIORITY JOURNAL; PROTEIN BINDING; RAT; STOICHIOMETRY; SURFACE PLASMON RESONANCE; THROMBIN TIME; THROMBOSIS; VEIN THROMBOSIS; ANIMAL; ANTAGONISTS AND INHIBITORS; ANTIBODY SPECIFICITY; BLOOD; HUMAN; IMMUNOLOGY; IN VITRO STUDY; KINETICS; LEPORIDAE; MACACA FASCICULARIS; METABOLISM; PHYSIOLOGY;

ANIMALS; ANTIBODIES, BLOCKING; ANTIBODIES, MONOCLONAL; ANTIBODY SPECIFICITY; FACTOR XI; FACTOR XIA; HEMOSTASIS; HUMANS; IMMUNOGLOBULIN G; IN VITRO TECHNIQUES; KINETICS; MACACA FASCICULARIS; MICE; RABBITS; THROMBOSIS;

EID: 84983445525     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aaf4331     Document Type: Article

References (47)

1. V. Marder, W. C. Aird, J. S. Bennett, S. Schulman, G. C. White II, Hemostasis and Thrombosis: Basic Principles and Clinical Practice (Lipincott Williams & Wilkins, Philadelphia, 2013).
2. G. E. Raskob, P. Angchaisuksiri, A. N. Blanco, H. Buller, A. Gallus, B. J. Hunt, E. M. Hylek, A. Kakkar, S. V. Konstantinides, M. McCumber, Y. Ozaki, A. Wendelboe, J. I. Weitz; ISTH Steering Committee for World Thrombosis Day, Thrombosis: A major contributor to global disease burden. Arterioscler. Thromb. Vasc. Biol. 34, 2363-2371 (2014).
3. R. De Caterina, S. Husted, L. Wallentin, F. Andreotti, H. Arnesen, F. Bachmann, C. Baigent, K. Huber, J. Jespersen, S. D. Kristensen, G. Y. H. Lip, J. Morais, L. H. Rasmussen, A. Siegbahn, F. W. A. Verheugt, J. I. Weitz, General mechanisms of coagulation and targets of anticoagulants (Section I). Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease. Thromb. Haemost. 109, 569-579 (2013).
4. C. H. Yeh, K. Hogg, J. I. Weitz, Overview of the new oral anticoagulants: Opportunities and challenges. Arterioscler. Thromb. Vasc. Biol. 35, 1056-1065 (2015).
5. B. Furie, B. C. Furie, The molecular basis of blood coagulation. Cell 53, 505-518 (1988).
6. D. Gailani, Future prospects for contact factors as therapeutic targets. Hematology Am. Soc. Hematol. Educ. Program 2014, 52-59 (2014).
7. T. H. Bugge, Q. Xiao, K. W. Kombrinck, M. J. Flick, K. Holmbäck, M. J. Danton, M. C. Colbert, D. P. Witte, K. Fujikawa, E. W. Davie, J. L. Degen, Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulation. Proc. Natl. Acad. Sci. U.S.A. 93, 6258-6263 (1996).
8. P. Carmeliet, V. Ferreira, G. Breier, S. Pollefeyt, L. Kieckens, M. Gertsenstein, M. Fahrig, A. Vandenhoeck, K. Harpal, C. Eberhardt, C. Declercq, J. Pawling, L. Moons, D. Collen, W. Risau, A. Nagy, Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380, 435-439 (1996).
9. E. D. Rosen, J. C. Y. Chan, E. Idusogie, F. Clotman, G. Vlasuk, T. Luther, L. R. Jalbert, S. Albrecht, L. Zhong, A. Lissens, L. Schoonjans, L. Moons, D. Collen, F. J. Castellino, P. Carmeliet, Mice lacking factor VII develop normally but suffer fatal perinatal bleeding. Nature 390, 290-294 (1997).
10. L. Bi, A. M. Lawler, S. E. Antonarakis, K. A. High, J. D. Gearhart, H. H. Kazazian Jr., Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A. Nat. Genet. 10, 119-121 (1995).
11. L. Wang, M. Zoppe, T. M. Hackeng, J. H. Griffin, K.-F. Lee, I. M. Verma, A factor IX-deficient mouse model for hemophilia B gene therapy. Proc. Natl. Acad. Sci. U.S.A. 94, 11563-11566 (1997).
12. M. Dewerchin, Z. Liang, L. Moons, P. Carmeliet, F. J. Castellino, D. Collen, E. D. Rosen, Blood coagulation factor X deficiency causes partial embryonic lethality and fatal neonatal bleeding in mice. Thromb. Haemost. 83, 185-190 (2000).
13. W. Y. Sun, D. P. Witte, J. L. Degen, M. C. Colbert, M. C. Burkart, K. Holmbäck, Q. Xiao, T. H. Bugge, S. J. F. Degen, Prothrombin deficiency results in embryonic and neonatal lethality in mice. Proc. Natl. Acad. Sci. U.S.A. 95, 7597-7602 (1998).
14. F. Peyvandi, R. Palla, M. Menegatti, S. M. Siboni, S. Halimeh, B. Faeser, H. Pergantou, H. Platokouki, P. Giangrande, K. Peerlinck, T. Celkan, N. Ozdemir, C. Bidlingmaier, J. Ingerslev, M. Giansily-Blaizot, J. F. Schved, R. Gilmore, A. Gadisseur, M. Benedik-Dolničar, L. Kitanovski, D. Mikovic, K. M. Musallam, F. R. Rosendaal; European Network Of Rare Bleeding Disorders (EN-RBD) Group, Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: Results from the European Network of Rare Bleeding Disorders. J. Thromb. Haemost. 10, 615-621 (2012).
15. D. Gailani, C. E. Bane, A. Gruber, Factor XI and contact activation as targets for anti-thrombotic therapy. J. Thromb. Haemost. 13, 1383-1395 (2015).
16. F. Müller, D. Gailani, T. Renné, Factor XI and XII as antithrombotic targets. Curr. Opin. Hematol. 18, 349-355 (2011).
17. J. H. Morrissey, S. A. Smith, Polyphosphate as modulator of hemostasis, thrombosis, and inflammation. J. Thromb. Haemost. 13 (Suppl. 1), S92-S97 (2015).
18. S. Massberg, L. Grahl, M. L. von Bruehl, D. Manukyan, S. Pfeiler, C. Goosmann, V. Brinkmann, M. Lorenz, K. Bidzhekov, A. B. Khandagale, I. Konrad, E. Kennerknecht, K. Reges, S. Holdenrieder, S. Braun, C. Reinhardt, M. Spannagl, K. T. Preissner, B. Engelmann, Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat. Med. 16, 887-896 (2010).
19. O. Salomon, U. Seligsohn, New observations on factor XI deficiency. Haemophilia 10 (Suppl. 4), 184-187 (2004).
20. D. Gailani, G. J. Broze Jr., Factor XI activation in a revised model of blood coagulation. Science 253, 909-912 (1991).
21. H. R. Büller, C. Bethune, S. Bhanot, D. Gailani, B. P. Monia, G. E. Raskob, A. Segers, P. Verhamme, J. I. Weitz; FXI-ASO TKA Investigators, Factor XI antisense oligonucleotide for prevention of venous thrombosis. N. Engl. J. Med. 372, 232-240 (2015).
22. M. L. Quan, C. P. Decicco, J. R. Corte, C. Wang, U. States, US Patent 9,079,918 (2015).
23. A. Matafonov, Q. Cheng, Y. Geng, I. M. Verhamme, O. Umunakwe, E. I. Tucker, M.-F. Sun, V. Serebrov, A. Gruber, D. Gailani, Evidence for factor IX-independent roles for factor XIa in blood coagulation. J. Thromb. Haemost. 11, 2118-2127 (2013).
24. A. Wilmen, J. Strassburger, F. Dittmer, M. Strerath, A. Buchmüller, J. Grudzinska-Goebel, R. Finnern, M. Schäfer, C. Gerdes, H. Jörißen, A. Itakura, P. Y. Leung, E. Tucker, Patent WO 2013167669 A1 (2013).
25. D. L. Pedicord, D. Seiffert, Y. Blat, Feedback activation of factor XI by thrombin does not occur in plasma. Proc. Natl. Acad. Sci. U.S.A. 104, 12855-12860 (2007).
26. E. D. Rosen, D. Gailani, F. J. Castellino, FXI is essential for thrombus formation following FeCl3-induced injury of the carotid artery in the mouse. Thromb. Haemost. 87, 774-776 (2002).
27. X. Wang, Q. Cheng, L. Xu, G. Z. Feuerstein, M.-Y. Hsu, P. L. Smith, D. A. Seiffert, W. A. Schumacher, M. L. Ogletree, D. Gailani, Effects of factor IX or factor XI deficiency on ferric chloride-induced carotid artery occlusion in mice. J. Thromb. Haemost. 3, 695-702 (2005).
28. Y. Geng, I. M. Verhamme, S. B. Smith, M.-F. Sun, A. Matafonov, Q. Cheng, S. A. Smith, J. H. Morrissey, D. Gailani, The dimeric structure of factor XI and zymogen activation. Blood 121, 3962-3969 (2013).
29. E. Perzborn, J. Strassburger, A. Wilmen, J. Pohlmann, S. Roehrig, K.-H. Schlemmer, A. Straub, In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939 - An oral, direct Factor Xa inhibitor. J. Thromb. Haemost. 3, 514-521 (2005).
30. D. J. P. Pinto, M. J. Orwat, S. Koch, K. A. Rossi, R. S. Alexander, A. Smallwood, P. C. Wong, A. R. Rendina, J. M. Luettgen, R. M. Knabb, K. He, B. Xin, R. R. Wexler, P. Y. S. Lam, Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa. J. Med. Chem. 50, 5339-5356 (2007).
31. P. C. Wong, E. J. Crain, B. Xin, R. R. Wexler, P. Y. S. Lam, D. J. Pinto, J. M. Luettgen, R. M. Knabb, Apixaban, an oral, direct and highly selective factor Xa inhibitor: In vitro, antithrombotic and antihemostatic studies. J. Thromb. Haemost. 6, 820-829 (2008).
32. H. Zhang, E. C. Löwenberg, J. R. Crosby, A. R. MacLeod, C. Zhao, D. Gao, C. Black, A. S. Revenko, J. C. M. Meijers, E. S. Stroes, M. Levi, B. P. Monia, Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: A novel antithrombotic strategy with lowered bleeding risk. Blood 116, 4684-4692 (2010).
33. D. Gailani, T. Renné, The intrinsic pathway of coagulation: A target for treating thromboembolic disease? J. Thromb. Haemost. 5, 1106-1112 (2007).
34. U. Seligsohn, Factor XI deficiency in humans. J. Thromb. Haemost. 7 (Suppl. 1), 84-87 (2009).
35. M. M. Bern, M. Sahud, O. Zhukov, K. Qu, W. Mitchell Jr., Treatment of factor XI inhibitor using recombinant activated factor VIIa. Haemophilia 11, 20-25 (2005).
36. T. Livnat, A. Zivelin, U. Martinowitz, O. Salomon, U. Seligsohn, Prerequisites for recombinant factor VIIa-induced thrombin generation in plasmas deficient in factors VIII, IX or XI. J. Thromb. Haemost. 4, 192-200 (2006).
37. T. Livnat, I. Tamarin, Y. Mor, H. Winckler, Z. Horowitz, Y. Korianski, B. Bar-Zakay, U. Seligsohn, O. Salomon, Recombinant activated factor VII and tranexamic acid are haemostatically effective during major surgery in factor XI-deficient patients with inhibitor antibodies. Thromb. Haemost. 102, 487-492 (2009).
38. D. M. Siegal, J. T. Curnutte, S. J. Connolly, G. Lu, P. B. Conley, B. L. Wiens, V. S. Mathur, J. Castillo, M. D. Bronson, J. M. Leeds, F. A. Mar, A. Gold, M. A. Crowther, Andexanet alfa for the reversal of factor Xa inhibitor activity. N. Engl. J. Med. 373, 2413-2424 (2015).
39. C. V. Pollack Jr., P. A. Reilly, J. Eikelboom, S. Glund, P. Verhamme, R. A. Bernstein, R. Dubiel, M. V. Huisman, E. M. Hylek, P. W. Kamphuisen, J. Kreuzer, J. H. Levy, F. W. Sellke, J. Stangier, T. Steiner, B. Wang, C.-W. Kam, J. I. Weitz, Idarucizumab for dabigatran reversal. N. Engl. J. Med. 373, 511-520 (2015).
40. P. C. Wong, E. J. Crain, C. A. Watson, W. A. Schumacher, A small-molecule factor XIa inhibitor produces antithrombotic efficacy with minimal bleeding time prolongation in rabbits. J. Thromb. Thrombolysis 32, 129-137 (2011).
41. A. Yamashita, K. Nishihira, T. Kitazawa, K. Yoshihashi, T. Soeda, K. Esaki, T. Imamura, K. Hattori, Y. Asada, Factor XI contributes to thrombus propagation on injured neointima of the rabbit iliac artery. J. Thromb. Haemost. 4, 1496-1501 (2006).
42. J. W. Yau, P. Liao, J. C. Fredenburgh, A. R. Stafford, A. S. Revenko, B. P. Monia, J. I. Weitz, Selective depletion of factor XI or factor XII with antisense oligonucleotides attenuates catheter thrombosis in rabbits. Blood 123, 2102-2107 (2014).
43. L. Wang, C. Miller, R. F. Swarthout, M. Rao, N. Mackman, M. B. Taubman, Vascular smooth muscle-derived tissue factor is critical for arterial thrombosis after ferric chloride-induced injury. Blood 113, 705-713 (2009).
44. S. M. Day, J. L. Reeve, B. Pedersen, D. M. Farris, D. D. Myers, M. Im, T. W. Wakefield, N. Mackman, W. P. Fay, Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall. Blood 105, 192-198 (2005).
45. A. Gruber, S. R. Hanson, Factor XI-dependence of surface- and tissue factor-initiated thrombus propagation in primates. Blood 102, 953-955 (2003).
46. X. Wang, L. Xu, An optimized murine model of ferric chloride-induced arterial thrombosis for thrombosis research. Thromb. Res. 115, 95-100 (2005).
47. I. Cornelissen, D. Palmer, T. David, L. Wilsbacher, C. Concengco, P. Conley, A. Pandey, S. R. Coughlin, Roles and interactions among protease-activated receptors and P2ry12 in hemostasis and thrombosis. Proc. Natl. Acad. Sci. U.S.A. 107, 18605-18610 (2010).