316
W. Li et al.
82. Povsic TJ, Wargin WA, Alexander JH, Krasnow J, Krolick M, Cohen MG, Mehran R, Buller
CE, Bode C, Zelenkofske SL, Rusconi CP, Becker RC, Investigators RADAR (2011) Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients: RADAR
pharmacokinetic and pharmacodynamic substudy. Eur Heart J 32(19):2412–2419
83. Blake CM, Wang H, Laskowitz DT, Sullenger BA (2011) A reversible aptamer improves
outcome and safety in murine models of stroke and hemorrhage. Oligonucleotides 21(1):11–
19
84. Sullenger B, Woodruff R, Monroe DM (2012) Potent anticoagulant aptamer directed against
factor IXa blocks macromolecular substrate interaction. J Biol Chem 287(16):12779–12786
85. Mertens K, Bertina RM (1980) Pathways in the activation of human coagulation factor X.
Biochem J 185(3):647–658
86. Bom VJ, Bertina RM (1990) The contributions of Ca2+, phospholipids and tissue-factor
apoprotein to the activation of human blood-coagulation factor X by activated factor VII.
Biochem J 265(2):327–336
87. Hoffman M, Monroe DM 3rd (2001) A cell-based model of hemostasis. Thromb Haemost
85(6):958–965
88. Soule EE, Bompiani KM, Woodruff RS, Sullenger BA (2016) Targeting Two Coagulation Cascade Proteases with a Bivalent Aptamer Yields a Potent and Antidote-Controllable
Anticoagulant. Nucleic Acid Ther 26(1):1–9
89. Hirsh J, Warkentin TE, Raschke R, Granger C, Ohman EM, Dalen JE (1998) Heparin and lowmolecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations,
monitoring, efficacy, and safety. Chest 114(5 Suppl):489S-510S
90. Buddai SK, Layzer JM, Lu G, Rusconi CP, Sullenger BA, Monroe DM, Krishnaswamy S
(2010) An anticoagulant RNA aptamer that inhibits proteinase-cofactor interactions within
prothrombinase. J Biol Chem 285(8):5212–5223
91. Gunaratne R, Kumar S, Frederiksen JW, Stayrook S, Lohrmann JL, Perry K, Bompiani KM,
Chabata CV, Thalji NK, Ho MD, Arepally G, Camire RM, Krishnaswamy S, Sullenger BA
(2018) Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary
bypass. Nat Biotechnol 36(7):606–613
92. Emsley J, McEwan PA, Gailani D (2010) Structure and function of factor XI. Blood
115(13):2569–2577
93. Seligsohn U (2009) Factor XI deficiency in humans. J Thromb Haemost 7(Suppl 1):84–87
94. Büller HR, Bethune C, Bhanot S, Gailani D, Monia BP, Raskob GE, Segers A, Verhamme
P, Weitz JI, Investigators FXI-ASOTKA (2015) Factor XI antisense oligonucleotide for
prevention of venous thrombosis. N Engl J Med 372(3):232–240
95. Donkor DA, Bhakta V, Eltringham-Smith LJ, Stafford AR, Weitz JI, Sheffield WP (2017)
Selection and characterization of a DNA aptamer inhibiting coagulation factor XIa. Sci Rep
7(1):2102
96. Woodruff RS, Ivanov I, Verhamme IM, Sun MF, Gailani D, Sullenger BA (2017) Generation
and characterization of aptamers targeting factor XIa. Thromb Res 156:134–141
97. Stavrou E, Schmaier AH (2010) Factor XII: what does it contribute to our understanding of the
physiology and pathophysiology of hemostasis & thrombosis. Thromb Res 125(3):210–215
98. Samuel M, Pixley RA, Villanueva MA, Colman RW, Villanueva GB (1992) Human factor
XII (Hageman factor) autoactivation by dextran sulfate. Circular dichroism, fluorescence, and
ultraviolet difference spectroscopic studies. J Biol Chem 267(27): 19691–19697.
99. Renne T, Pozgajova M, Gruner S, Schuh K, Pauer H-U, Burfeind P, Gailani D, Nieswandt
B (2005) Defective thrombus formation in mice lacking coagulation factor XII. J Exp Med
202(2):271–281
100. Woodruff RS, Xu Y, Layzer J, Wu W, Ogletree ML, Sullenger BA (2013) Inhibiting the
intrinsic pathway of coagulation with a factor XII-targeting RNA aptamer. J Thromb Haemost
11(7):1364–1373
101. Paul A, Avci-Adali M, Neumann B, Guo K, Straub A, Dietz K, Ziemer G, Wendel HP (2010)
Aptamers influence the hemostatic system by activating the intrinsic coagulation pathway in
an in vitro Chandler-Loop model. Clin Appl Thromb Hemost 16(2):161–169
W. Li et al.
82. Povsic TJ, Wargin WA, Alexander JH, Krasnow J, Krolick M, Cohen MG, Mehran R, Buller
CE, Bode C, Zelenkofske SL, Rusconi CP, Becker RC, Investigators RADAR (2011) Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients: RADAR
pharmacokinetic and pharmacodynamic substudy. Eur Heart J 32(19):2412–2419
83. Blake CM, Wang H, Laskowitz DT, Sullenger BA (2011) A reversible aptamer improves
outcome and safety in murine models of stroke and hemorrhage. Oligonucleotides 21(1):11–
19
84. Sullenger B, Woodruff R, Monroe DM (2012) Potent anticoagulant aptamer directed against
factor IXa blocks macromolecular substrate interaction. J Biol Chem 287(16):12779–12786
85. Mertens K, Bertina RM (1980) Pathways in the activation of human coagulation factor X.
Biochem J 185(3):647–658
86. Bom VJ, Bertina RM (1990) The contributions of Ca2+, phospholipids and tissue-factor
apoprotein to the activation of human blood-coagulation factor X by activated factor VII.
Biochem J 265(2):327–336
87. Hoffman M, Monroe DM 3rd (2001) A cell-based model of hemostasis. Thromb Haemost
85(6):958–965
88. Soule EE, Bompiani KM, Woodruff RS, Sullenger BA (2016) Targeting Two Coagulation Cascade Proteases with a Bivalent Aptamer Yields a Potent and Antidote-Controllable
Anticoagulant. Nucleic Acid Ther 26(1):1–9
89. Hirsh J, Warkentin TE, Raschke R, Granger C, Ohman EM, Dalen JE (1998) Heparin and lowmolecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations,
monitoring, efficacy, and safety. Chest 114(5 Suppl):489S-510S
90. Buddai SK, Layzer JM, Lu G, Rusconi CP, Sullenger BA, Monroe DM, Krishnaswamy S
(2010) An anticoagulant RNA aptamer that inhibits proteinase-cofactor interactions within
prothrombinase. J Biol Chem 285(8):5212–5223
91. Gunaratne R, Kumar S, Frederiksen JW, Stayrook S, Lohrmann JL, Perry K, Bompiani KM,
Chabata CV, Thalji NK, Ho MD, Arepally G, Camire RM, Krishnaswamy S, Sullenger BA
(2018) Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary
bypass. Nat Biotechnol 36(7):606–613
92. Emsley J, McEwan PA, Gailani D (2010) Structure and function of factor XI. Blood
115(13):2569–2577
93. Seligsohn U (2009) Factor XI deficiency in humans. J Thromb Haemost 7(Suppl 1):84–87
94. Büller HR, Bethune C, Bhanot S, Gailani D, Monia BP, Raskob GE, Segers A, Verhamme
P, Weitz JI, Investigators FXI-ASOTKA (2015) Factor XI antisense oligonucleotide for
prevention of venous thrombosis. N Engl J Med 372(3):232–240
95. Donkor DA, Bhakta V, Eltringham-Smith LJ, Stafford AR, Weitz JI, Sheffield WP (2017)
Selection and characterization of a DNA aptamer inhibiting coagulation factor XIa. Sci Rep
7(1):2102
96. Woodruff RS, Ivanov I, Verhamme IM, Sun MF, Gailani D, Sullenger BA (2017) Generation
and characterization of aptamers targeting factor XIa. Thromb Res 156:134–141
97. Stavrou E, Schmaier AH (2010) Factor XII: what does it contribute to our understanding of the
physiology and pathophysiology of hemostasis & thrombosis. Thromb Res 125(3):210–215
98. Samuel M, Pixley RA, Villanueva MA, Colman RW, Villanueva GB (1992) Human factor
XII (Hageman factor) autoactivation by dextran sulfate. Circular dichroism, fluorescence, and
ultraviolet difference spectroscopic studies. J Biol Chem 267(27): 19691–19697.
99. Renne T, Pozgajova M, Gruner S, Schuh K, Pauer H-U, Burfeind P, Gailani D, Nieswandt
B (2005) Defective thrombus formation in mice lacking coagulation factor XII. J Exp Med
202(2):271–281
100. Woodruff RS, Xu Y, Layzer J, Wu W, Ogletree ML, Sullenger BA (2013) Inhibiting the
intrinsic pathway of coagulation with a factor XII-targeting RNA aptamer. J Thromb Haemost
11(7):1364–1373
101. Paul A, Avci-Adali M, Neumann B, Guo K, Straub A, Dietz K, Ziemer G, Wendel HP (2010)
Aptamers influence the hemostatic system by activating the intrinsic coagulation pathway in
an in vitro Chandler-Loop model. Clin Appl Thromb Hemost 16(2):161–169