The human pharmacology of thrombin inhibition

Coronary Artery Disease

Volumn 7, Issue 12, 1996, Pages 911-918

  FitzGerald, Garret A ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

coagulation; platelets; thrombin; thrombosis

Indexed keywords

ANTITHROMBIN; ANTITHROMBIN III; ARGATROBAN; BLOOD CLOTTING FACTOR 5A; BLOOD CLOTTING FACTOR 8A; FIBRIN; FIBRINOGEN; FIBRINOGEN RECEPTOR; FIBRINOGEN RECEPTOR ANTAGONIST; HEPARIN; HIRUDIN; HIRULOG; NITRIC OXIDE; PLASMINOGEN ACTIVATOR INHIBITOR; PROSTACYCLIN; PROTEIN C; THROMBIN; TRIABAN; UNCLASSIFIED DRUG;

BLOOD CLOTTING; CLINICAL TRIAL; DRUG DELIVERY SYSTEM; DRUG MECHANISM; DRUG RESEARCH; FIBRINOLYTIC THERAPY; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; ORAL DRUG ADMINISTRATION; PHASE 2 CLINICAL TRIAL; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; REVIEW; SUBCUTANEOUS DRUG ADMINISTRATION; UNSTABLE ANGINA PECTORIS; VEIN THROMBOSIS;

EID: 0030498405     PISSN: 09546928     EISSN: None     Source Type: Journal    
DOI: 10.1097/00019501-199612000-00006     Document Type: Review

References (108)

1. Jaques LB: Heparins - anionic polyelectrolyte drugs. Pharmacol Rev 1980, 31:99-166.
2. Rosenberg RD: Role of heparin and heparin-like molecules in thrombosis and atherosclerosis. Fed Proc 1985, 44:404-409.
3. Badimon L, Merino A, Badimon J, Chesebro JH, Fuster V: Hirudin and other thrombin inhibitors: experimental results and potential clinical applications. Trends Cardiovasc Med 1991, 1:261-267.
4. Lefkovits J, Topol EJ: Direct thrombin inhibitors in cardiovascular medicine. Circulation 1994, 90:1522-1536.
5. Swords NA, Mann KG: The assembly of the prothrombinase complex on adherent platelets. Arterioscler Thromb 1993, 13:1602-1612.
6. Fitzgerald DJ, Catella F, FitzGerald GA: Platelet activation in unstable coronary disease. N Engl J Med 1986, 315:983-989.
7. Fitzgerald DJ, Catella F, Roy L, FitzGerald GA: Marked platelet activation in vivo after intravenous streptokinase in patients with acute myocardial infarction. Circulation 1988, 77:142-150.
8. Haskel EJ, Prager NA, Sobel BE, Abendschein DR: Relative efficacy of antithrombin compared with antiplatelet agents in accelerating coronary thrombolysis and preventing early reocclusion. Circulation 1991, 83:1048-1056.
9. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico: GISSI-2: a factorial randomised trial of alteplase versus streptokinase and heparin versus non heparin among 12,490 patients with acute myocardial infarction. Lancet 1990, 336: 65-71.
10. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group: ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin and of aspirin alone among 41,299 cases of suspected acute myocardial infarction. Lancet 1992, 339:754-770.
11. Delanty N, Fitzgerald DJ: Subcutaneous heparin during coronary thrombolysis. Too little, too late. Circulation 1992, 86:1636-1638.
12. Visentin GP, Ford SE, Scott JP, Aster RH: Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells. J Clin Invest 1994, 93:81-88.
13. Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, et al.: Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995, 332:1330-1335.
14. Dehmer GJ, Fisher M, Tate DA, Teo S, Bonnem EM: Reversal of heparin anticoagulation by recombinant platelet factor 4 in humans. Circulation 1995, 91:2188-2194.
15. Gao G, Goldfarb M: Heparin can activate a receptor tyrosine kinase. EMBO J 1995, 14:2183-2190.
16. 2 activity and prostacyclin synthesis in patients undergoing cardiac surgery. J Clin Invest 1995, 95:1062-1070.
17. 2+ is necessary for thrombin-induced platelet activation. J Biol Chem 1989, 264:19600-19606.
18. Heilmann E, Hourdillé P, Pruvost A, Paponneau A, Nurden AT: Thrombin-induced platelet aggregates have a dynamic structure. Arterioscler Thromb 1991, 11:704-718.
19. Eidt JF, Allison P, Noble S, Ashton J, Golino P, McNatt J, et al.: Thrombin is an important mediator of platelet aggregation in stenosed canine coronary arteries with endothelial injury. J Clin Invest 1989, 84:18-27.
20. Gast A, Tschopp TB, Baumgartner HR: Thrombin plays a key role in late platelet thrombus growth and/or stability. Arterioscler Thromb 1994, 14:1466-1474.
21. Davie EW, Fujikawa K, Kisiel W: The coagulation cascade: interaction, maintenance and regulation. Biochemistry 1991, 30:10363-10370.
22. Tsiang M, Jain AK, Dunn KE, Rojas ME, Leung LLK, Gibbs CS: Functional mapping of the surface residues of human thrombin. J Biol Chem 1995, 270:16854-16863.
23. Hackeng TM, van'tVeer C, Meijers JCM, Bouma BN: Human protein S inhibits prothrombinase complex activity on endothelial cells and platelets via direct interactions with factors Va and Xa. J Biol Chem 1994, 269:21051-21058.
24. R506Q by activated protein C. J Biol Chem 1995, 270:27852-27858.
25. Dang QD, Vindigni A, DiCera E: An allosteric switch controls the procoagulant and anticoagulant activities of thrombin. Proc Natl Acad Sci USA 1995, 92:5977-5981.
26. Leipold RJ, Bozarth TA, Racanelli AL, Dicker IB: Mathematical model of serine protease inhibition in the tissue factor pathway to thrombin. J Biol Chem 1995, 270:25383-25387.
27. Vu T-KH, Hung DT, Wheaton VI, Coughlin SR: Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor evolution. Cell 1991, 64:1057-1068.
28. Ishi K, Gerszten R, Zheng YW, Welsh JB, Turck CW, Coughlin SR: Determinants of thrombin receptor cleavage. J Biol Chem 1995, 270:16435-16440.
29. Jenkins AL, Bootman MD, Berridge MJ, Stone SR: Differences in intracellular calcium signaling after activation of the thrombin receptor by thrombin and agonist peptide in osteoblast-like cells. J Biol Chem 1994, 269:17104-17110.
30. 2) by thrombin and thrombin receptor agonist peptide in human platelets. J Biol Chem 1995, 270:14816-14823.
31. Kramer RM, Roberts EF, Strifler BA, Johnsonte EM: Thrombin induces activation of p38 MAP kinase in human platelets. J Biol Chem 1995, 270:27395-27398.
32. Vouret-Craviari V, Grall D, Chambard J-C, Rasmussen UB, Pouysségur J, Obberghen-Schilling EV: Post-translational and activation-dependent modifications of the G protein-coupled thrombin receptor. J Biol Chem 1995, 270:8367-8372.
33. Hung DT, Vu T-KH, Wheaton VI, Charo IF, Nelken NA, Esmon N, et al.: 'Mirror image' antagonists of thrombin-induced platelet activation based on thrombin receptor structure. J Clin Invest 1992, 89:444-450.
34. Chaikof EL, Cabans R, Yan C-N, Rao GN, Runge MS: Growth-related responses in arterial smooth muscle cells are arrested by thrombin receptor antisense sequences. J Biol Chem 1995, 270:7431-7436.
35. Santulli RJ, Derian CK, Darrow AL, Tomko KA, Eckardt AJ, Seiberg M, et al.: Evidence for the presence of a protease-activated receptor distinct from the thrombin receptor in human keratinocytes. Proc Natl Acad Sci USA 1995, 92:9151-9155.
36. Brass LF. Thrombin receptor antagonists: a work in progress. Coronary Artery Dis 1996 (in press).
37. Stubbs MT, Bode W: A player of many parts: the spotlight falls on thrombin's structure. Thromb Res 1993, 69:1-58.
38. Stone SR: Thrombin inhibitors. A new generation of antithrombotics. Trends Cardiovasc Med 1995, 5:134-140.
39. Kikumoto R, Tamao Y, Tezuka T, Tonomura S, Hara H, Nenomiyak, et al.: Selective inhibition of thrombin by (2R,4R)-4-methyl-1-[N2-[(3-methyl-1,2,3,4,-tetrahydro-8-quinolinyl)-sulfonyl]-L- arginyl]-2-piperidenecarboxylic acid. Biochemistry 1984, 23:85-90.
40. Fitzgerald D, Murphy N: Argatroban: a synthetic thrombin inhibitor of low relative molecular mass. Coronary Artery Dis 1996, 7:455-458.
41. Krstenansky JL, Broersma RJ, Owen TJ, Payne MH, Yates MT, Mao SJT: Development of MDL 28 050 a small stable antithrombin agent based on a functional domain of the leech protein, hirudin. Thromb Haemost 1990, 63:208-214.
42. Bock LC, Griffin LC, Latham JA, Vermaas EH, Tole JJ: Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature 1992, 35:564-566.
43. Li WX, Kaplan AV, Grant GW, Tolle JJ, Leung LLK: A novel nucleotide-based thrombin inhibitor inhibits clot-bound thrombin and reduces arterial platelet thrombus formation. Blood 1994, 83:677-682.
44. Noeske-Jungblut C, Haendler B, Donner P, Alagon A, Possani L, Schleuning W-D: Triabin, a highly potent exosite inhibitor of thrombin. J Biol Chem 1995, 270:28629-28634.
45. Arnaud E, Lafay M, Gaussem P, Picard V, Jandrot-Perrus M, Aiach M, et al.: An autoantibody directed against human thrombin anion-binding exosite in a patient with arterial thrombosis: effects on platelets, endothelial cells, and protein C activation. Blood 1994, 84:1843-1850.
46. The Global Use of Strategies to Open Occluded Arteries (GUSTO) IIa Investigators: Randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. Circulation 1994, 90:1631-1637.
47. Neuhaus K-L, v Essen R, Tebbe U, Jessel A, Heinrichs H, Maurer W, et al.: Safety observations from the pilot phase of the randomized r-hirudin for improvement of thrombolysis (HIT-III) study. Circulation 1994, 90:1638-1642.
48. Antman EM and TIMI 9A investigators: Hirudin in acute myocardial infarction. Circulation 1994, 90:1624-1630.
49. The Hirulog Angioplasty Study Investigators: Treatment with bivalirudin (hirulog) as compared with heparin during coronary angioplasty for unstable or postinfarction angina. N Engl J Med 1995, 333: 764-769.
50. Helvetica Investigators: A comparison of hirudin with heparin in the prevention of restenosis after coronary angioplasty. N Engl J Med 1995, 333:757-763.
51. Catella-Lawson F: Direct thrombin inhibitors in cardiovascular disease: narrow therapeutic range or poor study design? Coronary Artery Dis 1996 (in press).
52. Carteaux JP, Gast A, Tschorpp TB, Roux S: Activated clotting time as an appropriate test to compare heparin and direct thrombin inhibitors such as hirudin or Ro 46-6240 in experimental arterial thrombosis. Circulation 1995, 91:1568-1574.
53. Clarke RJ, Mayo G, FitzGerald GA, Fitzgerald DJ: Combined administration of aspirin and a specific thrombin inhibitor in man. Circulation 1991, 83:1510-1518.
54. Zoldhelyi P, Webster WI, Fuster V, Grill DE, Gaspar D, Edwards SJ, et al.: Recombinant hirudin in patients with chronic, stable coronary artery disease. Circulation 1993, 88:2015-2022.
55. Topol EJ, Bonan R, Jewitt D, Sigwart U, Kakkar VV, Rothman M, et al.: Use of a direct antithrombin, hirulog, in place of heparin during coronary angioplasty. Circulation 1993, 87:1622-1629.
56. Topol EJ, Fuster V, Harrington R, Califf RM, Kleiman NS, Kereiakes DJ, et al.: Recombinant hirudin for unstable angina pectoris. Circulation 1994, 89:1557-1566.
57. Fuchs J, Cannon CP and the TIMI 7 Investigators: Hirulog in the treatment of unstable angina. Circulation 1995, 92:727-733.
58. Théroux P, Pérez-Villa F, Waters D, Lesperance J, Shabani F, Bonan R: Randomized double-blind comparison of two doses of hirulog with heparin as adjunctive therapy to streptokinase to promote early patency of the infarct-related artery in acute myocardial infarction. Circulation 1995, 91:2132-2139.
59. Lidón R-M, Théroux P, Juneau M, Adelman B, Maraganore J: Initial experience with a direct antithrombin, hirulog, in unstable angina. Circulation 1993, 88:1495-1501.
60. Van den Bos AA, Deckers JW, Heynddrickx GR, Laarman G-J, Suryapranata H, Zijlstra F, et al.: Safety and efficacy of recombinant hirudin (CGP 39 393) versus heparin in patients with stable angina undergoing coronary angioplasty. Circulation 1993, 88:2058-2066.
61. Verstraete M, Nurmohamed M, Kienast J, Siebeck M, Silling-Engelhardt G, Buller H, et al.: Biologic effects of recombinant hirudin (CGP 39393) in human volunteers. J Am Coll Cardiol 1993, 22:1080-1088.
62. Eriksson BI, Kälebo P, Ekman S, Lindbratt S, Kerry R, Close P: Direct thrombin inhibition with rec-hirudin CGP 39393 as prophylaxis of thromboembolic complications after total hip replacement. Thromb Haemost 1994, 72:227-231.
63. Markwardt F, Nowak G, Stürzebecher J, Vogel G: Clinical pharmacological studies with recombinant hirudin. Thromb Res 1988, 52:393-400.
64. The European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group: Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995, 332:635-641.
65. Ridker PM, Hennekens CH, Cerkus A, Stampfer MJ: Plasma concentrations of cross-linked degradation product (D-dimer) and the risk of future myocardial infarction among apparently healthy men. Circulation 1994, 90:2236-2240.
66. Eichinger S, Wolzt M, Schneider B, Nieszpaur-Los M, Heinrichs H, Lechner K, et al.: Effects of recombinant hirudin (r-Hirudin, HBW 023) on coagulation and platelet activation in vivo. Arterioscler Thromb Vasc Biol 1995, 15:886-892.
67. Zoldhelyi P, Bichler J, Owen WG, Grill DE, Fuster V, Mruk JS, et al.: Persistent thrombin generation in humans during specific thrombin inhibition with hirudin. Circulation 1994, 90:2671-2678.
68. Sobel BE: Intracranial bleeding, fibrinolysis, and anticoagulation. Circulation 1994, 90:2147-2152.
69. Scott NA, Nunes GL, King SB, Harker LA, Hanson SR: Local delivery of an antithrombin inhibits platelet-dependent thrombosis. Circulation 1994, 90:1951-1955.
70. Meyer BJ, Fernádenz-Ortiz A, Mailhac A, Falk E, Badimon L, Michael AD, et al.: Local delivery of r-hirudin by a double-balloon perfusion catheter prevents mural thrombosis and minimizes platelet deposition after angioplasty. Circulation 1994, 90:2474-2480.
71. Nunes GL, Thomas CN, Hanson SR, Barry JJ, King SB, Scott NA: Inhibition of platelet-dependent thrombosis by local delivery of heparin with a hydrogel-coated balloon. Circulation 1995, 92:1697-1700.
72. Azrin MA, Mitchel JF, Fram DB, Pedersen CA, Cartun RW, Barry JJ, et al.: Decreased platelet deposition and smooth muscle cell proliferation after intramural heparin delivery with hydrogel-coated balloons. Circulation 1994, 90:433-441.
73. Bode C, Hudelmayer M, Mehwald P, Bauer S, Freitag M, v Hodenberg E, et al.: Fibrin-targeted recombinant hirudin inhibits fibrin deposition on experimental clots more efficiently than recombinant hirudin. Circulation 1994, 90:1956-1963.
74. Kiely J-M, Cybulsky MI, Luscinskas FW, Gimbrone MA: Immunoselective targeting of an anti-thrombin agent to the surface of cytokine-activated vascular endothelial cells. Arterioscler Thromb Vasc Biol 1995, 15:1211-1218.
75. Théroux P, Waters D, Lam J, Juneau M, McCans J: Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med 1992, 327:141-145.
76. Granger CB, Miller JM, Bovill EG, Griber A, Tracy RP, Krucoff MW, et al.: Rebound increase in thrombin generation and activity after cessation of intravenous heparin in patients with acute coronary syndromes. Circulation 1995, 91:1929-1935.
77. Fihn SD: Aiming for safe anticoagulation. N Engl J Med 1995, 333:54-55.
78. The European Atrial Fibrillation Trial Study Group: Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. N Engl J Med 1995, 333:5-10.
79. Cannegieter SC, Rosendaal FR, Wintzen AR, v der Meer FJM, Vandenbroucke JP, Briet E: Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 1995, 333:11-17.
80. 2 in reocclusion following coronary thrombolysis with tissue type plasminogen activator. Proc Natl Acad Sci USA 1989, 86: 7585-7589.
81. Kawai H, Tamao Y: The combination of thrombin inhibitor and thromboxane synthase inhibitor on experimental thrombosis and bleeding. Thromb Res 1995, 80:429-434.
82. Nicolini FA, Lee P, Rios G, Kotte-Marchant K, Topol EJ: Combination of platelet fibrinogen receptor antagonist and direct thrombin inhibitor at low doses markedly improves thrombolysis. Circulation 1994, 89:1802-1809.
83. The EPIC investigators: Randomized trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. Lancet 1994, 343:881-886.
84. Mills DCB, Puri R, Hu C-J, Miniiti C, Grana G, Freedman MD, et al.: Clopidogrel inhibits the binding of ADP analogues to the receptor mediating inhibition of platelet adenylate cyclase. Arterioscler Thromb Vasc Biol 1992, 12:430-436.
85. Prandoni P, Lensing AWA, Büller HR, Carta M, Cogo A, Vigo M, et al.: Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992, 339:441-445.
86. Agnelli G, Iorio A, Renga C, Boschetti E, Nenci GG, Ofosu FA, et al.: Prolonged antithrombln activity of low molecular weight heparins. Circulation 1995, 92:2819-2824.
87. Ahmed SS, Walsh PN: Platelet membrane-mediated coagulation protease complex assembly. Trends Cardiovasc Med 1994, 4:271-278.
88. Prager NA, Abendschein DR, McKenzie CR, Eisenberg PR: Role of thrombin compared with factor Xa in the procoagulant activity of whole blood clots. Circulation 1995, 92:962-967.
89. Stubbs MT, Bode W: Structure and specificity in coagulation and its inhibition. Trends Cardiovasc Med 1995, 5:157-166.
90. Cappello M, Vlasuk GP, Bergum PW, Huang S, Hotez PJ: Ancylostoma caninum anticoagulant peptide: a hookworm-derived inhibitor of human coagulation factor Xa. Proc Natl Acad Sci USA 1995, 92:6152-6156.
91. Kaiser B, Callas D, Hoppensteadt D, Mallinowska K, Fareed J: Comparative studies on the inhibitor spectrum of recombinant hirudin, DuP 714 and heparin on thrombin and factor Xa generation in biochemically defined systems. Thromb Res 1994, 73:327-335.
92. Yokohama T, Kelly AB, Marzec UM, Hanson SR, Kunitada S, Harker LA: Antithrombotic effects of orally active synthetic antagonist of activated factor X in nonhuman primates. Circulation 1995, 92:485-491.
93. Lawson JH, Kalafatis M, Stram S, Mann KG: A model for the tissue factor pathway to thrombin. I. An empirical study. J Biol Chem 1994, 269:23357-23366.
94. Jones KC, Mann KG: A model for the tissue factor pathway to thrombin. II. A mathematical simulation. J Biol Chem 1994, 269:23367-23373.
95. Kirchhofer D, Tschopp TB, Baumgartner HR: Active site-blocked factors VIIa and IXa differentially inhibit fibrin formation in a human ex vivo thrombosis model. Arterioscler Thromb Vasc Biol 1995, 15:1098-1106.
96. Barstad RM, Hamers MJAG, Kierulf P, Westvik Å-B., Sakariassen KS: Procoagulant human monocytes mediate tissue factor/factor VIIa-dependent platelet-thrombus formation when exposed to flowing nonanticoagulated human blood. Arterioscler Thromb Vasc Biol 1995, 15:11-16.
97. Ruf W, Edgington TS: Structural biology of tissue factor, the initiator of thrombogenesis in vivo. FASEB J 1994, 8:385-390.
98. Lindhal AK: Tissue factor pathway inhibitor in health and disease. Trends Cardiovasc Med 1995, 5:167-171.
99. Van't Veer C, Hackeng TM, Delahaye C, Sixma JJ, Bouma BN: Activated factor X and thrombin formation triggered by tissue factor on endothelial cell matrix in a flow model: effect of the tissue factor pathway inhibitor. Blood 1994, 84:1132-1142.
100. Castellino FJ: Human protein C and activated protein C. Components of the human anticoagulant system. Trends Cardiovasc Med 1995, 5:55-62.
101. Esmon CT, Schwarz HP: An update on clinical and basic aspects of the protein C anticoagulant pathway. Trends Cardiovasc Med 1995, 5:141-148.
102. Bajzar L, Manuel R, Nesheim ME: Purification and characterization of TAFI, a thrombin-activable fibrinolysis inhibitor. J Biol Chem 1995, 270:14477-14484.
103. Rezaie AR, Cooper ST, Church FC, Esmon CT: Protein C inhibitor is a potent inhibitor of the thrombin-thrombomodulin complex. J Biol Chem 1995, 270:25336-25339.
104. Dahlbäck B: Physiological anticoagulation. Resistance to activated protein C and venous thromboembolism. J Clin Invest 1994, 94:923-927.
105. Rydel TJ, Ravichandran KG, Tulinsky A, Bode W, Huber R, Roitsch C, et al.: The structure of a complex of recombinant hirudin and human α-thrombin. Science 1990, 249:277-280.
106. Van Zanten GH, Connolly TM, Schiphorst ME, deGraaf S, Slootweg PJ, Sixma JJ: Recombinant leech antiplatelet protein specifically blocks platelet deposition on collagen surfaces under flow conditions. Arterioscler Thromb Vasc Biol 1995, 15:1424-1431.
107. Silver MJ, Sutton JM, Hook S, Lee P, Malycky JL, Phillips ML, et al.: Adjunctive selectin blockade successful reduces infarct size beyond thrombolysis in the electrolytic canine coronary artery model. Circulation 1995, 92:492-499.
108. Toombs CF, deGraaf GL, Martin JP, Geng JG, Anderson DC, Shebuski RJ: Pretreatment with a blocking monoclonal antibody to P-selectin accelerates pharmacological thrombolysis in an primate model of arterial thrombosis. J Biol Chem 1995, 275:941-949.