Thrombin as a multi-functional enzyme: Focus on in vitro and in vivo effects

Thrombosis and Haemostasis

Volumn 106, Issue 6, 2011, Pages 1020-1033

  Siller Matula, Jolanta M ^a   Schwameis, Michael ^a   Blann, Andrew ^b   Mannhalter, Christine ^a   Jilma, Bernd ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b UNIVERSITY OF BIRMINGHAM   (United Kingdom)

Author keywords

Animal studies; Coagulation; PAR; Pleiotropic; Thrombin

Indexed keywords

ANTICOAGULANT AGENT; ARGATROBAN; ATOPAXAR; DABIGATRAN; HEPARIN; HIRULOG; LEPIRUDIN; LOW MOLECULAR WEIGHT HEPARIN; MESSENGER RNA; PROTHROMBIN; SCH 205831; SCH 602539; THROMBIN; UNCLASSIFIED DRUG; VASCULOTROPIN; VORAPAXAR;

ACUTE CORONARY SYNDROME; ANTICOAGULATION; BINDING AFFINITY; BLOOD CLOTTING; BLOOD CLOTTING DISORDER; BLOOD VESSEL PERMEABILITY; BRAIN ISCHEMIA; CARDIOVASCULAR EFFECT; CELL PROLIFERATION; DEEP VEIN THROMBOSIS; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MEGADOSE; ENZYME BINDING; ENZYME STRUCTURE; ENZYME SYNTHESIS; GENE MUTATION; HEMOSTASIS; HEPARIN INDUCED THROMBOCYTOPENIA; HUMAN; LIMB ISCHEMIA; LUNG EMBOLISM; NONHUMAN; PHARMACOLOGICAL BLOCKING; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; STROKE; THROMBIN TIME; THROMBOCYTOPENIA; THROMBOEMBOLISM; THROMBOPLASTIN TIME; THROMBOSIS; VENOUS THROMBOEMBOLISM;

ANGIOGENESIS INDUCING AGENTS; ANIMALS; BLOOD COAGULATION; CAPILLARY PERMEABILITY; CELL PROLIFERATION; ENDOTHELIAL CELLS; HUMANS; INFLAMMATION; MYOCYTES, SMOOTH MUSCLE; THROMBIN;

EID: 82555195545     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH10-11-0711     Document Type: Review

References (165)

1. Gamgee A. On some old and new experiments on the fibrin-ferment. J Physiol 1879; 2: 145-163.
2. Krem MM, Di Cera E. Evolution of enzyme cascades from embryonic development to blood coagulation. Trends Biochem Sci 2002; 27: 67-74.
3. Di Cera E. Thrombin as procoagulant and anticoagulant. J Thromb Haemost 2007; 5 (Suppl 1): 196-202.
4. Krarup A, et al. Simultaneous activation of complement and coagulation by MBLassociated serine protease 2. PLoS One 2007; 2: e623.
5. Krem MM, Di Cera E. Molecular markers of serine protease evolution. Embo J 2001; 20: 3036-3045.
6. Krem MM, et al. Sequence determinants of function and evolution in serine proteases. Trends Cardiovasc Med 2000; 10: 171-176.
7. Banfield DK, MacGillivray RT. Partial characterization of vertebrate prothrombin cDNAs: amplification and sequence analysis of the B chain of thrombin from nine different species. Proc Natl Acad Sci USA 1992; 89: 2779-2783.
8. Davie EW, Kulman JD. An overview of the structure and function of thrombin. Semin Thromb Hemost 2006; 32 (Suppl 1): 3-15.
9. Yagi K, et al. Reciprocal regulation of prothrombin secretion and tyrosine aminotransferase induction in hepatocytes. Eur J Biochem 1995; 227: 753-756.
10. Bode W. The structure of thrombin: a janus-headed proteinase. Semin Thromb Hemost 2006; 32 (Suppl 1): 16-31.
11. Bukys MA, et al. The structural integrity of anion binding exosite I of thrombin is required and sufficient for timely cleavage and activation of factor V and factor VIII. J Biol Chem 2006; 281: 18569-18580.
12. Bukys MA, et al. The interaction of fragment 1 of prothrombin with the membrane surface is a prerequisite for optimum expression of factor Va cofactor activity within prothrombinase. Thromb Haemost 2008; 99: 511-522.
13. Matafonov A, et al. Activation of factor XI by products of prothrombin activation. Blood 2011; 118: 437-445.
14. He S, et al. The direct thrombin inhibitors (argatroban, bivalirudin and lepirudin) and the indirect Xa-inhibitor (danaparoid) increase fibrin network porosity and thus facilitate fibrinolysis. Thromb Haemost 2010; 103: 1076-1084.
15. Chung N, et al. Safety of edoxaban, an oral factor Xa inhibitor, in Asian patients with non-valvular atrial fibrillation. Thromb Haemost 2011; 105: 535-544.
16. Yegneswaran S, et al. Prothrombin amino terminal region helps protect coagulation factor Va from proteolytic inactivation by activated protein C. Thromb Haemost 2009; 101: 55-61.
17. de Amorim HL, et al. Thrombin allosteric modulation revisited: a molecular dynamics study. J Mol Model 2010; 16: 725-735.
18. Huntington JA. How Na+ activates thrombin--a review of the functional and structural data. Biol Chem 2008; 389: 1025-1035.
19. Ratnoff OD. An accelerating property of plasma for the coagulation of fibrinogen by thrombin. J Clin Invest 1954; 33: 1175-1182.
20. Wolberg AS, Aleman MM. Influence of cellular and plasma procoagulant activity on the fibrin network. Thromb Res 2010; 125 (Suppl 1): S35-37.
21. Tyler HM. Studies on the activation of purified human factor XIII. Biochim Biophys Acta 1970; 222: 396-404.
22. Bereczky Z, Muszbek L. Factor XIII and Venous Thromboembolism. Semin Thromb Hemost 2011; 37: 305-314.
23. Komaromi I, et al. Factor XIII: novel structural and functional aspects. J Thromb Haemost 2011; 9: 9-20.
24. Anand K, et al. The crystal structure of thrombin-activable fibrinolysis inhibitor (TAFI) provides the structural basis for its intrinsic activity and the short half-life of TAFIa. J Biol Chem 2008; 283: 29416-29423.
25. Walker JB, et al. Proteolytic cleavage of carboxypeptidase N markedly increases its antifibrinolytic activity. J Thromb Haemost 2008; 6: 848-855.
26. Kim PY, Nesheim ME. Down regulation of prothrombinase by activated protein C during prothrombin activation. Thromb Haemost 2010; 104: 61-70.
27. Van Walderveen MC, et al. Covalent antithrombin-heparin effect on thrombinthrombomodulin and activated protein C reaction with factor V/Va. Thromb Haemost 2010; 103: 910-919.
28. Schrör K, et al. Thrombin receptors in vascular smooth muscle cells - function and regulation by vasodilatory prostaglandins. Thromb Haemost 2010;103: 884-890.
29. Verkleij CJ, et al. The effects of hyperglycaemia on thrombin-activatable fibrinolysis inhibitor. Thromb Haemost 2009; 102: 460-468.
30. Adams TE, et al. Molecular basis of thrombomodulin activation of slow thrombin. J Thromb Haemost 2009; 7: 1688-1695.
31. Muszbek L, et al. Antithrombin deficiency and its laboratory diagnosis. Clin Chem Lab Med 2010; 48 (Suppl 1): S67-78.
32. Bereczky Z, et al. Protein C and protein S deficiencies: similarities and differences between two brothers playing in the same game. Clin Chem Lab Med 2011; 48 (Suppl 1): S53-66.
33. Hurtado B, et al. Expression of the vitamin K-dependent proteins GAS6 and protein S and the TAM receptor tyrosine kinases in human atherosclerotic carotid plaques. Thromb Haemost 2011; 105: 873-882.
34. Wu CC, et al. Combined blockade of thrombin anion binding exosite-1 and PAR4 produces synergistic antiplatelet effect in human platelets. Thromb Haemost 2011; 105: 88-95.
35. Spiel AO, et al. Increased platelet aggregation and in vivo platelet activation after granulocyte colony-stimulating factor administration. A randomised controlled trial. Thromb Haemost 2011; 105: 655-662.
36. Siller-Matula JM, et al. Pharmacokinetic, pharmacodynamic and clinical profile of novel antiplatelet drugs targeting vascular disease. Br J Pharmacol 2009; 159: 502-517.
37. Lin JH, et al. Identification of human thrombin-activatable fibrinolysis inhibitor in vascular and inflammatory cells. Thromb Haemost 2011; 105: 999-1009.
38. Vorjohann S, et al. Hypodysfibrinogenaemia due to production of mutant fibrinogen alpha-chains lacking fibrinopeptide A and polymerisation knob 'A'. Thromb Haemost 2010; 104: 990-997.
39. Chen D, Dorling A. Critical roles for thrombin in acute and chronic inflammation. J Thromb Haemost 2009; 7 (Suppl 1): 122-126.
40. Schuepbach RA, et al. Protection of vascular barrier integrity by activated protein C in murine models depends on protease-activated receptor-1. Thromb Haemost 2009; 101: 724-733.
41. Rex S, et al. Immune versus thrombotic stimulation of platelets differentially regulates signalling pathways, intracellular protein-protein interactions, and alpha-granule release. Thromb Haemost 2009; 102: 97-110.
42. Martorell L, et al. Thrombin and protease-activated receptors (PARs) in atherothrombosis. Thromb Haemost 2008; 99: 305-315.
43. Miyamoto M, et al. TRA-418, a thromboxane A2 receptor antagonist and prostacyclin receptor agonist, inhibits platelet-leukocyte interaction in human whole blood. Thromb Haemost 2010; 104: 788-795.
44. Rickles FR, et al. Tissue factor, thrombin, and cancer. Chest 2003; 124 (3 Suppl): 58S-68S.
45. Verkleij CJ, et al. The role of thrombin-activatable fibrinolysis inhibitor in diabetic wound healing. Thromb Res 2010; 126: 442-446.
46. Garcia PS, et al. The role of thrombin and protease-activated receptors in pain mechanisms. Thromb Haemost 2010; 103: 1145-1151.
47. Coughlin SR. Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost 2005; 3: 1800-1814.
48. Coughlin SR. Protease-activated receptors in vascular biology. Thromb Haemost 2001; 86: 298-307.
49. Coughlin SR. Thrombin signalling and protease-activated receptors. Nature 2000; 407: 258-264.
50. Camerer E, et al. Roles of protease-activated receptors in a mouse model of endotoxemia. Blood 2006; 107: 3912-3921.
51. Jennings LK. Mechanisms of platelet activation: need for new strategies to protect against platelet-mediated atherothrombosis. Thromb Haemost 2009; 102: 248-257.
52. Hosokawa K, et al. M-AAA-thrombin: potent anticoagulant and antiplatelet thrombin derivative with differential affinity for factor VIII and PAR1. Thromb Res 2010; 126: 447-453.
53. Goto S, et al. Phase II trial of the novel antiplatelet agent, SCH 530348, in Japanese patients with non-ST segment elevation acute coronary syndromes (NSTE ACS). Eur Heart J 2008; 29 (Suppl): Abstract P4767.
54. Wu CC, et al. Combined blockade of thrombin anion binding exosite-1 and PAR4 produces synergistic antiplatelet effect in human platelets. Thromb Haemost 2011; 105: 88-95.
55. Lova P, et al. Thrombin induces platelet activation in the absence of functional protease activated receptors 1 and 4 and glycoprotein Ib-IX-V. Cell Signal 2010; 22: 1681-1687.
56. Ruggeri ZM, et al. Unravelling the mechanism and significance of thrombin binding to platelet glycoprotein Ib. Thromb Haemost 2010; 104: 894-902.
57. Tsopanoglou NE, Maragoudakis ME. Role of thrombin in angiogenesis and tumor progression. Semin Thromb Hemost 2004; 30: 63-69.
58. Zhang P, et al. Sequential binding of alphaVbeta3 and ICAM-1 determines fibrinmediated melanoma capture and stable adhesion to CD11b/CD18 on neutrophils. J Immunol 2011; 186: 242-254.
59. Rukoyatkina N, et al. Phosphatidylserine surface expression and integrin alpha IIb beta 3 activity on thrombin/convulxin stimulated platelets/particles of different sizes. Br J Haematol 2009; 144: 591-602.
60. Diebold I, et al. Reciprocal regulation of Rac1 and PAK-1 by HIF-1alpha: a positive- feedback loop promoting pulmonary vascular remodeling. Antioxid Redox Signal 2010; 13: 399-412.
61. Diebold I, et al. Rac-1 promotes pulmonary artery smooth muscle cell proliferation by upregulation of plasminogen activator inhibitor-1: role of NFkappaBdependent hypoxia-inducible factor-1alpha transcription. Thromb Haemost 2008; 100: 1021-1028.
62. Petaja J. Inflammation and coagulation. An overview. Thromb Res 2011; 127 (Suppl 2): S34-37.
63. Kumar P, et al. Molecular mechanisms of endothelial hyperpermeability: implications in inflammation. Expert Rev Mol Med 2009; 11: e19.
64. Franchini M, et al. The bidirectional relationship of cancer and hemostasis and the potential role of anticoagulant therapy in moderating thrombosis and cancer spread. Semin Thromb Hemost 2009; 35: 644-653.
65. Shirvaikar N, et al. Hyaluronic acid and thrombin upregulate MT1-MMP through PI3K and Rac-1 signaling and prime the homing-related responses of cord blood hematopoietic stem/progenitor cells. Stem Cells Dev 2011; 20: 19-30.
66. Momi S, et al. Low molecular weight heparins prevent thrombin-induced thrombo- embolism in mice despite low anti-thrombin activity. Evidence that the inhibition of feed-back activation of thrombin generation confers safety advantages over direct thrombin inhibition. Haematologica 2001; 86: 297-302.
67. Ballabeni V, et al. Effects of subacute treatment with benzopyranopyrimidines in hemostasis and experimental thrombosis in mice. Life Sci 2004; 74: 1851-1859.
68. Gresele P, et al. Activated human protein C prevents thrombin-induced thromboembolism in mice. Evidence that activated protein c reduces intravascular fibrin accumulation through the inhibition of additional thrombin generation. J Clin Invest 1998; 101: 667-676.
69. Margaretten W, et al. Production of the Generalized Shwartzman Reaction in Pregnant Rats by Intravenous Infusion of Thrombin. Lab Invest 1964; 13: 552-559.
70. Kaplan JE, et al. Influence of plasma fibronectin on the response to infusion of thrombin and adenosine diphosphate. Thromb Haemost 1983; 49: 217-223.
71. Witte S, Schricker KT. The behavior of the blood vessels in experimental hemostasis]. Z Gesamte Exp Med 1960; 133: 361-374.
72. Siller-Matula JM, et al. An experimental model to study isolated effects of thrombin in vivo. Thromb Res 2010; 126: 454-461.
73. Gorog P, Kovacs IB. Increase in bronchial resistance during infusion of thrombin into the venous circulation of guinea pigs. Improved model for experimental pulmonary microembolism. Angiologica 1973; 10: 164-172.
74. Colucci M, et al. Thrombin infusion in endotoxin-treated rabbits reduces the plasma levels of plasminogen activator inhibitor: evidence for a protein-C-mediated mechanism. Blood 1989; 74: 1976-1982.
75. Davis RB, Palmer MJ. Thrombocytopenia and release of platelet amines induced by thrombin and bacterial lipopolysaccharide. Observations after infusion of low molecular weight dextran. Br J Exp Pathol 1965; 46: 554-563.
76. Burchardi H, et al. Adult respiratory distress syndrome (ARDS): experimental models with elastase and thrombin infusion in pigs. Adv Exp Med Biol 1984; 167: 319-333.
77. Bennett JM, et al. The effects of infusing thrombin and its acetylated derivative. II. Observations on intravascular hemolysis with pathologic correlations. Thromb Diath Haemorrh 1968; 20: 469-476.
78. Nordstrom S, Zetterqvist E. Effects of thrombin infusions upon 131-I-labelled fibrinogen in dogs. Acta Physiol Scand 1968; 72: 85-99.
79. Whitaker AN, McKay DG. Induction of hypotension in rhesus monkeys and rabbits by intravenous thrombin infusion. Lab Invest 1969; 20: 79-86.
80. Lentz SR, et al. Impaired anticoagulant response to infusion of thrombin in atherosclerotic monkeys associated with acquired defects in the protein C system. Arterioscler Thromb Vasc Biol 1999; 19: 1744-1750.
81. Arfors KE, et al. Pulmonary insufficiency following intravenous infusion of thrombin and AMCA (tranexamic acid) in the dog. Acta Chir Scand 1972; 138: 445-452.
82. Girolami A, et al. Hemorrhagic syndrome in dogs induced by intravenous thrombin. Thromb Diath Haemorrh 1966; 16: 243-256.
83. Lee L. Reticuloendothelial clearance of circulating fibrin in the pathogenesis of the generalized Shwartzman reaction. J Exp Med 1962; 115: 1065-1082.
84. Quick AJ, et al. Occult intravascular clotting by means of intravenous injection of thrombin. Am J Physiol 1959; 197: 791-794.
85. Delin A, et al. Vasodilatation in the canine leg caused by intraarterial infusion of thrombin and tissue thromboplastin. Cardiovasc Res 1967; 1: 371-378.
86. Monkhouse FC, Milojevic S. Changes in fibrinogen level after infusion of thrombin and thromboplastin. Am J Physiol 1960; 199: 1165-1168.
87. Ro JS, Flatmark A. Studies on thrombin infusion in dogs. Scand J Haematol 1972; 9: 293-304.
88. Kowalski E, et al. Circulating Fibrinogen Degradation Products (Fdp) in Dog Blood after Intravenous Thrombin Infusion. Thromb Diath Haemorrh 1965; 13: 12-24.
89. Jastrzebski J, et al. Thrombin-induced disseminated intravascular coagulation in the dog. I: Demonstration of microthrombi in lung. Br J Anaesth 1975; 47: 654-657.
90. Nagase H, et al. Antithrombin III-independent effect of depolymerized holothurian glycosaminoglycan (DHG) on acute thromboembolism in mice. Thromb Haemost 1997; 77: 399-402.
91. Soulier JP, et al. In vivo attempt to consume antithrombin III by i.v. injection of a thrombin-heparin mixture. Thromb Res 1984; 34: 255-262.
92. Hoie J, Schenk WG, Jr. Experimental intravascular coagulation: impairment of renal blood flow following thrombin infusion in the dog. J Trauma 1972; 12: 302-308.
93. Margaretten W, et al. An electron microscopic study of thrombin-induced disseminated intravascular coagulation. Blood 1967; 29: 169-181.
94. Collins RD, et al. Studies on the pathogenesis of the generalized Shwartzman reaction. Production of glomerular thrombosis and renal cortical necrosis by intraaortic thrombin infusion in normal and leucopenic rabbits. Johns Hopkins Med J 1968; 122: 375-379.
95. Berthelsen LO, et al. Purified thromboplastin causes haemostatic abnormalities but not overt DIC in an experimental rabbit model. Thromb Res 2010; 126: 337-344.
96. Hanson SR, et al. Antithrombotic effects of thrombin-induced activation of endogenous protein C in primates. J Clin Invest 1993; 92: 2003-2012.
97. Jastrzebski J, et al. Thrombin-induced disseminated intravascular coagulation in the dog. II. Cardiorespiratory changes during spontaneous and controlled ventilation. Br J Anaesth 1975; 47: 658-665.
98. Kumada T, et al. A role for thrombomodulin in the pathogenesis of thrombin-induced thromboembolism in mice. Blood 1988; 71: 728-733.
99. Radegran K, et al. The effect of regional thrombin infusion on the renal vascular resistance. Eur Surg Res 1970; 2: 460-470.
100. Vogel SM, et al. Abrogation of thrombin-induced increase in pulmonary microvascular permeability in PAR-1 knockout mice. Physiol Genomics 2000; 4: 137-145.
101. Chen B, et al. Thrombin Mediates Severe Neurovascular Injury During Ischemia. Stroke 2010; 41: 2348-2352.
102. Busch C, et al. Effect of reptilase on respiratory insufficiency induced by intravenous infusion of thrombin and AMCA (tranexamic acid) in the dog. Bibl Anat 1973; 12: 254-259.
103. Stafford BT, et al. The effects of infusion of thrombin or endotoxin in rabbits treated with cortisone. Thromb Diath Haemorrh 1975; 34: 159-168.
104. Meeks SL, Abshire TC. Abnormalities of prothrombin: a review of the pathophysiology, diagnosis, and treatment. Haemophilia 2008; 14: 1159-1163.
105. Lancellotti S, De Cristofaro R. Congenital prothrombin deficiency. Semin Thromb Hemost 2009; 35: 367-381.
106. Moser M, Patterson C. Thrombin and vascular development: a sticky subject. Arterioscler Thromb Vasc Biol 2003; 23: 922-930.
107. Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med 2005; 353: 1028-1040.
108. Krishnaswamy A, et al. The use and limitations of unfractionated heparin. Crit Pathw Cardiol 2010; 9: 35-40.
109. Schaden E, Kozek-Langenecker SA. Direct thrombin inhibitors: pharmacology and application in intensive care medicine. Intensive Care Med 2010; 36: 1127-1137.
110. Warkentin TE, et al. Bivalirudin. Thromb Haemost 2008; 99: 830-839.
111. Hochtl T, Huber K. New anticoagulants for the prevention of stroke in atrial fibrillation. Fundam Clin Pharmacol 2011; epub ahead of print.
112. De Luca G, et al. Bivalirudin as compared to unfractionated heparin among patients undergoing coronary angioplasty: A meta-analyis of randomised trials. Thromb Haemost 2009; 102: 428-436.
113. Pernerstorfer T, et al. Lepirudin blunts endotoxin-induced coagulation activation. Blood 2000; 95: 1729-1734.
114. Gajra A, et al. Lepirudin in the management of heparin-induced thrombocytopenia. Expert Opin Drug Metab Toxicol 2008; 4: 1131-1141.
115. Chong BH, Isaacs A. Heparin-induced thrombocytopenia: what clinicians need to know. Thromb Haemost 2009; 101: 279-283.
116. Jeske WP, Fet al. Pharmacology of argatroban. Expert Rev Hematol 2010; 3: 527-539.
117. Ahrens I, et al. New oral anticoagulant drugs in cardiovascular disease. Thromb Haemost 2010; 104: 49-60.
118. van Ryn J, et al. Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103: 1116-1127.
119. Wolowacz SE, et al. Economic evaluation of dabigatran etexilate for the prevention of venous thromboembolism in patients aged over 75 years or with moderate renal impairment undergoing total knee or hip replacement. Thromb Haemost 2010; 103: 360-371.
120. Wolowacz SE, et al. Efficacy and safety of dabigatran etexilate for the prevention of venous thromboembolism following total hip or knee arthroplasty. A metaanalysis. Thromb Haemost 2009; 101: 77-85.
121. Eriksson BI, et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, doubleblind, non-inferiority trial. Thromb Haemost 2011; 105: 721-729.
122. Roskell NS, et al. Treatments for stroke prevention in atrial fibrillation: a network meta-analysis and indirect comparisons versus dabigatran etexilate. Thromb Haemost 2010; 104: 1106-1115.
123. Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
124. Kogushi M, et al. Effects of E5555, a protease-activated receptor-1 antagonist, on the inflammatory markers in vitro. J Thromb Haemost 2007;5 (Suppl 2): Abstract P-M-059.
125. Peng CY, et al. The indazole derivative YD-3 specifically inhibits thrombin-induced angiogenesis in vitro and in vivo. Shock 2010; 34: 580-585.
126. Zania P, et al. Parstatin, the cleaved peptide on proteinase-activated receptor 1 activation, is a potent inhibitor of angiogenesis. J Pharmacol Exp Ther 2009; 328: 378-389.
127. Siller-Matula JM, et al. Interspecies differences in coagulation profile. Thromb Haemost 2008; 100: 397-404.
128. Suzuki H, et al. Factor V C2 domain contains a major thrombin-binding site responsible for thrombin-catalyzed factor V activation. J Thromb Haemost 2006; 4: 1354-1360.
129. Fritsch P, et al. Thrombin generation in factor VIII-depleted neonatal plasma: nearly normal because of physiologically low antithrombin and tissue factor pathway inhibitor. J Thromb Haemost 2006; 4: 1071-1077.
130. von dem Borne PA, et al. Factor XI enhances fibrin generation and inhibits fibrinolysis in a coagulation model initiated by surface-coated tissue factor. Blood Coagul Fibrinolysis 2006; 17: 251-257.
131. Ponce RA, et al. Preclinical safety and pharmacokinetics of recombinant human factor XIII. Toxicol Pathol 2005; 33: 495-506.
132. Lundblad RL, White GC, 2nd. The interaction of thrombin with blood platelets. Platelets 2005; 16: 373-385.
133. Ozuyaman B, et al. Endothelial nitric oxide synthase plays a minor role in inhibition of arterial thrombus formation. Thromb Haemost 2005; 93: 1161-1167.
134. Cleator JH, et al. Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP. Blood 2006; 107: 2736-2744.
135. George JN, Torres MM. Thrombin decreases von Willebrand factor binding to platelet glycoprotein Ib. Blood 1988; 71: 1253-1259.
136. Valnickova Z, et al. Post-translational modifications of human thrombin-activatable fibrinolysis inhibitor (TAFI): evidence for a large shift in the isoelectric point and reduced solubility upon activation. Biochemistry 2006; 45: 1525-1535.
137. Brogren H, et al. Platelets synthesize large amounts of active plasminogen activator inhibitor 1. Blood 2004; 104: 3943-3948.
138. Peterson EA, et al. Thrombin induces endothelial cell-surface exposure of the plasminogen receptor annexin 2. J Cell Sci 2003; 116: 2399-2408.
139. Esmon CT. The interactions between inflammation and coagulation. Br J Haematol 2005; 131: 417-430.
140. Seybold J, et al. Tumor necrosis factor-alpha-dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability. Blood 2005; 105: 3569-3576.
141. Zimmerman GA, et al. Platelet-activating factor (PAF): signalling and adhesion in cell-cell interactions. Adv Exp Med Biol 1996; 416: 297-304.
142. Fan Y, et al. Thrombin and PAR-1-AP increase proinflammatory cytokine expression in C6 cells. J Surg Res 2005; 129: 196-201.
143. Cakmak H, et al. Progestin suppresses thrombin- and interleukin-1beta-induced interleukin-11 production in term decidual cells: implications for preterm delivery. J Clin Endocrinol Metab 2005; 90: 5279-5286.
144. Naldini A, et al. Thrombin-mediated IL-10 up-regulation involves protease-activated receptor (PAR)-1 expression in human mononuclear leukocytes. J Leukoc Biol 2005; 78: 736-744.
145. Marklund M, et al. Bradykinin and thrombin stimulate release of arachidonic acid and formation of prostanoids in human periodontal ligament cells. Eur J Orthod 1994; 16: 213-221.
146. Razin E, Marx G. Thrombin-induced degranulation of cultured bone marrowderived mast cells. J Immunol 1984; 133: 3282-3285.
147. Miho N, et al. Role of the JNK pathway in thrombin-induced ICAM-1 expression in endothelial cells. Cardiovasc Res 2005; 68: 289-298.
148. Szaba FM, Smiley ST. Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo. Blood 2002; 99: 1053-1059.
149. Birukova AA, et al. Novel role of microtubules in thrombin-induced endothelial barrier dysfunction. Faseb J 2004; 18: 1879-1890.
150. Caunt M, et al. Growth-regulated oncogene is pivotal in thrombin-induced angiogenesis. Cancer Res 2006; 66: 4125-4132.
151. Lampugnani MG, et al. Thrombin induces c-fos expression in cultured human endothelial cells by a Ca2(+)-dependent mechanism. Blood 1990; 76: 1173-1180.
152. Marsden PA, et al. Regulated expression of endothelin 1 in glomerular capillary endothelial cells. Am J Physiol 1991; 261: F117-125.
153. Sarno JL, et al. Thrombin and interleukin-1beta regulate HOXA10 expression in human term decidual cells: implications for preterm labor. J Clin Endocrinol Metab 2006; 91: 2366-2372.
154. Bluteau G, et al. The modulation of gene expression in osteoblasts by thrombin coated on biphasic calcium phosphate ceramic. Biomaterials 2006; 27: 2934-2943.
155. Cao H, et al. Thrombin induces expression of FGF-2 via activation of PI3K-Akt- Fra-1 signaling axis leading to DNA synthesis and motility in vascular smooth muscle cells. Am J Physiol Cell Physiol 2006; 290: C172-182.
156. Beckett CS, et al. Activation of MAPKs in thrombin-stimulated ventricular myocytes is dependent on Ca2+-independent PLA2. Am J Physiol Cell Physiol 2006; 290: C1350-1354.
157. Tang H, et al. Thrombin induces endocytosis of endoglin and type-II TGF-beta receptor and down-regulation of TGF-beta signaling in endothelial cells. Blood 2005; 105: 1977-1985.
158. Kanda Y, Watanabe Y. Thrombin-induced glucose transport via Src-p38 MAPK pathway in vascular smooth muscle cells. Br J Pharmacol 2005; 146: 60-67.
159. Gorlach A, et al. Thrombin activates the p21-activated kinase in pulmonary artery smooth muscle cells. Role in tissue factor expression. Thromb Haemost 2005; 93: 1168-1175.
160. Kastl SP, et al. Thrombin induces the expression of oncostatin M via AP-1 activation in human macrophages: a link between coagulation and inflammation. Blood 2009; 114: 2812-2818.
161. Shankar H, et al. P2Y12 receptor-mediated potentiation of thrombin-induced thromboxane A2 generation in platelets occurs through regulation of Erk1/2 activation. J Thromb Haemost 2006; 4: 638-647.
162. Unruh M, et al. Systemic coagulation parameters in mice after treatment with vascular targeting agents. Thromb J 2005; 3: 21.
163. Geier B, et al. Laparoscopic ligation of the infrarenal vena cava in combination with transfemoral thrombin infusion: a new animal model of chronic deep venous thrombosis. Eur J Vasc Endovasc Surg 2005; 29: 542-548.
164. Lindquist O, Malmberg P. Heart lymph flow and aspartate aminotransferase activity after infusion of thrombin and tranexamic acid in the dog. Scand J Clin Lab Invest 1972; 30: 145-151.
165. Siller-Matula JM, et al. Continuous thrombin infusion leads to a bleeding phenotype in sheep. Thromb Res 2011; in press.