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Venous and arterial thrombosis – pathogenesis and the rationale for anticoagulation

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Issue: 2011: 105/4 (Apr) pp. 571-741
Pages: 586-596

  1. Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133: 630S-669S. DOI:10.1378/chest.08-0720
  2. Harrington RA, Becker RC, Cannon CP, et al. Antithrombotic therapy for non-ST-segment elevation acute coronary syndromes: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133: 670S-707S. DOI:10.1378/chest.08-0691
  3. Kearon C. Natural history of venous thromboembolism. Circulation 2003; 107: I22-I30.
  4. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133: 381S-453S. DOI:10.1378/chest.08-0656
  5. Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133: 160S-198S. DOI:10.1378/chest.08-0670
  6. Hirsh J, Guyatt G, Albers GW, et al. Antithrombotic and thrombolytic therapy: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133: 110S-112S. DOI:10.1378/chest.08-0652
  7. Weitz JI, Hirsh J, Samama MM. New antithrombotic drugs: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133: 234S-256S. DOI:10.1378/chest.08-0673
  8. Furie B, Furie BC. Mechanisms of thrombus formation. N Engl J Med 2008; 359: 938-949. DOI:10.1056/NEJMra0801082
  9. Seré KM, Hackeng TM. Basic mechanisms of hemostasis. Semin Vasc Med 2003; 3: 3-12. DOI:10.1055/s-2003-38328
  10. Chou J, Mackman N, Merrill-Skoloff G, et al. Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood 2004; 104: 3190-3197. DOI:10.1182/blood-2004-03-0935
  11. Mann KG. The biochemistry of coagulation. Clin Lab Med 1984; 4: 207-220.
  12. Monroe DM, Hoffman M. What does it take to make the perfect clot? Arterioscler Thromb Vasc Biol 2006; 26: 41-48. DOI:10.1161/01.ATV.0000193624.28251.83
  13. Weitz JI, Bates SM. New anticoagulants. J Thromb Haemost 2005; 3: 1843-1853. DOI:10.1111/j.1538-7836.2005.01374.x
  14. Bates SM, Weitz JI. Coagulation assays. Circulation 2005; 112: e53-e60. DOI:10.1161/CIRCULATIONAHA.104.478222
  15. Kannemeier C, Shibamiya A, Nakazawa F, et al. Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation. Proc Natl Acad Sci USA 2007; 104: 6388-6393. DOI:10.1073/pnas.0608647104
  16. Xu J, Zhang X, Pelayo R, et al. Extracellular histones are major mediators of death in sepsis. Nat Med 2009; 15: 1318-1321. DOI:10.1038/nm.2053
  17. Lopez JA, Kearon C, Lee AY. Deep venous thrombosis. Hematology Am Soc Hematol Educ Program 2004; 439-456.
  18. Tanaka KA, Key NS, Levy JH. Blood coagulation: hemostasis and thrombin regulation. Anesth Analg 2009; 108: 1433-1446. DOI:10.1213/ane.0b013e31819bcc9c
  19. Esmon CT. Crosstalk between inflammation and thrombosis. Maturitas 2008; 61: 122-131. DOI:10.1016/j.maturitas.2008.11.008
  20. Licari LG, Kovacic JP. Thrombin physiology and pathophysiology. J Vet Emerg Crit Care (San Antonio) 2009; 19: 11-22. DOI:10.1111/j.1476-4431.2009.00383.x
  21. Sarangi PP, Lee HW, Kim M. Activated protein C action in inflammation. Br J Haematol 2010; 148: 817-833. DOI:10.1111/j.1365-2141.2009.08020.x
  22. Esmon CT. Coagulation inhibitors in inflammation. Biochem Soc Trans 2005; 33: 401-405. DOI:10.1042/BST0330401
  23. Conway EM, Rosenberg RD. Tumor necrosis factor suppresses transcription of the thrombomodulin gene in endothelial cells. Mol Cell Biol 1988; 8: 5588-5592.
  24. Esmon CT. Inflammation and the activated protein C anticoagulant pathway. Semin Thromb Hemost 2006; 32 (Suppl. 1): 49-60. DOI:10.1055/s-2006-939554
  25. Fisher CJ, Jr. , Yan SB. Protein C levels as a prognostic indicator of outcome in sepsis and related diseases. Crit Care Med 2000; 28: S49-S56. DOI:10.1097/00003246-200009001-00011
  26. Isermann B, Vinnikov IA, Madhusudhan T, et al. Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis. Nat Med 2007; 13: 1349-1358. DOI:10.1038/nm1667
  27. Cheng T, Liu D, Griffin JH, et al. Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective. Nat Med 2003; 9: 338-342. DOI:10.1038/nm826
  28. Van Sluis GL, Niers TM, Esmon CT, et al. Endogenous activated protein C limits cancer cell extravasation through sphingosine-1-phosphate receptor 1-mediated vascular endothelial barrier enhancement. Blood 2009; 114: 1968-1973. DOI:10.1182/blood-2009-04-217679
  29. Han MH, Hwang SI, Roy DB, et al. Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets. Nature 2008; 451: 1076-1081. DOI:10.1038/nature06559
  30. Loubele ST, Spek CA, Leenders P, et al. Activated protein C protects against myocardial ischemia/reperfusion injury via inhibition of apoptosis and inflammation. Arterioscler Thromb Vasc Biol 2009; 29: 1087-1092. DOI:10.1161/ATVBAHA.109.188656
  31. Mizutani A, Okajima K, Uchiba M, et al. Activated protein C reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation. Blood 2000; 95: 3781-3787.
  32. Kroegel C, Reissig A. Principle mechanisms underlying venous thromboembolism: epidemiology, risk factors, pathophysiology and pathogenesis. Respiration 2003; 70: 7-30. DOI:10.1159/000068427
  33. Lowe GD. Virchow's triad revisited: abnormal flow. Pathophysiol Haemost Thromb 2003; 33: 455-457. DOI:10.1159/000083845
  34. Sevitt S. The structure and growth of valve-pocket thrombi in femoral veins. J Clin Pathol 1974; 27: 517-528. DOI:10.1136/jcp.27.7.517
  35. Chirinos JA, Heresi GA, Velasquez H, et al. Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. J Am Coll Cardiol 2005; 45: 1467-1471. DOI:10.1016/j.jacc.2004.12.075
  36. Esmon CT. Basic mechanisms and pathogenesis of venous thrombosis. Blood Rev 2009; 23: 225-229. DOI:10.1016/j.blre.2009.07.002
  37. McNally MA, Mollan RA. Total hip replacement, lower limb blood flow and venous thrombogenesis. J Bone Joint Surg Br 1993; 75: 640-644.
  38. Dahl OE, Aspelin T, Arnesen H, et al. Increased activation of coagulation and formation of late deep venous thrombosis following discontinuation of thromboprophylaxis after hip replacement surgery. Thromb Res 1995; 80: 299-306. DOI:10.1016/0049-3848(95)00180-Y
  39. Lindahl TL, Lundahl TH, Nilsson L, et al. APC-resistance is a risk factor for postoperative thromboembolism in elective replacement of the hip or knee - a prospective study. Thromb Haemost 1999; 81: 18-21.
  40. Meltzer ME, Doggen CJ, de Groot PG, et al. The impact of the fibrinolytic system on the risk of venous and arterial thrombosis. Semin Thromb Hemost 2009; 35: 468-477. DOI:10.1055/s-0029-1234142
  41. Singer DE, Albers GW, Dalen JE, et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133: 546S-592S. DOI:10.1378/chest.08-0678
  42. Bassand JP, Hamm CW, Ardissino D, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J 2007; 28: 1598-1660. DOI:10.1093/eurheartj/ehm132
  43. Davies MJ. The pathophysiology of acute coronary syndromes. Heart 2000; 83: 361-366. DOI:10.1136/heart.83.3.361
  44. Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008; 451: 914-918. DOI:10.1038/nature06797
  45. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352: 1685-1695. DOI:10.1056/NEJMra043430
  46. Ballantyne CM, Hoogeveen RC, Bang H, et al. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Circulation 2004; 109: 837-842. DOI:10.1161/01.CIR.0000116763.91992.F1
  47. Crisby M, Nordin-Fredriksson G, Shah PK, et al. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation 2001; 103: 926-933.
  48. Lefer DJ. Statins as potent antiinflammatory drugs. Circulation 2002; 106: 2041-2042. DOI:10.1161/01.CIR.0000033635.42612.88
  49. Stewart RA. Predicting benefit from statins by C-reactive protein, LDL-cholesterol or absolute cardiovascular risk. Future Cardiol 2009; 5: 231-236. DOI:10.2217/fca.09.8
  50. Kinlay S. Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein: a meta-analysis. J Am Coll Cardiol 2007; 49: 2003-2009. DOI:10.1016/j.jacc.2007.01.083
  51. Wang K, Tarakji K, Zhou Z, et al. Celecoxib, a selective cyclooxygenase-2 inhibitor, decreases monocyte chemoattractant protein-1 expression and neointimal hyperplasia in the rabbit atherosclerotic balloon injury model. J Cardiovasc Pharmacol 2005; 45: 61-67. DOI:10.1097/00005344-200501000-00011
  52. Chen SS, Jenkins AJ, Majewski H. Elevated plasma prostaglandins and acetylated histone in monocytes in Type 1 diabetes patients. Diabet Med 2009; 26: 182-186. DOI:10.1111/j.1464-5491.2008.02658.x
  53. Goodman SG, Menon V, Cannon CP, et al. Acute ST-segment elevation myocardial infarction: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133: 708S-775S. DOI:10.1378/chest.08-0665
  54. Lip GYH, Boos CJ. Antithrombotic treatment in atrial fibrillation. Heart 2006; 92: 155-161. DOI:10.1136/hrt.2005.071555
  55. Fuster V, Rydén LE, Asinger RW, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22: 1852-1923. DOI:10.1053/euhj.2001.2983
  56. Watson T, Shantsila E, Lip GY. Mechanisms of thrombogenesis in atrial fibrillation: Virchow's triad revisited. Lancet 2009; 373: 155-166. DOI:10.1016/S0140-6736(09)60040-4
  57. Olsson SB, Rasmussen LH, Tveit A, et al. Safety and tolerability of an immediate-release formulation of the oral direct thrombin inhibitor AZD0837 in the prevention of stroke and systemic embolism in patients with atrial fibrillation. Thromb Haemost 2010; 103: 604-612. DOI:10.1160/TH09-07-0509
  58. Perzborn E. Factor Xa inhibitors - New anticoagulants for secondary haemostasis. Hamostaseologie 2009; 29: 260-267.
  59. Mann KG, Brummel K, Butenas S. What is all that thrombin for? J Thromb Haemost 2003; 1: 1504-1514. DOI:10.1046/j.1538-7836.2003.00298.x
  60. Ansell J. Factor Xa or thrombin: is factor Xa a better target? J Thromb Haemost 2007; 5 (Suppl. 1): 60-64. DOI:10.1111/j.1538-7836.2007.02473.x
  61. Perzborn E, Strassburger J, Wilmen A, et al. In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939 - an oral, direct Factor Xa inhibitor. J Thromb Haemost 2005; 3: 514-521. DOI:10.1111/j.1538-7836.2005.01166.x
  62. Leadley RJ, Jr. Coagulation factor Xa inhibition: biological background and rationale. Curr Top Med Chem 2001; 1: 151-159. DOI:10.2174/1568026013395380
  63. Orvim U, Barstad RM, Vlasuk GP, et al. Effect of selective factor Xa inhibition on arterial thrombus formation triggered by tissue factor/factor VIIa or collagen in an ex vivo model of shear-dependent human thrombogenesis. Arterioscler Thromb Vasc Biol 1995; 15: 2188-2194.
  64. Depasse F, Busson J, Mnich J, et al. Effect of BAY 59-7939 - a novel, oral, direct Factor Xa inhibitor - on clot-bound Factor Xa activity in vitro. J Thromb Haemost 2005; 3 (Suppl. 1): Abstract P1104.
  65. Jiang X, Crain EJ, Luettgen JM, et al. Apixaban, an oral direct factor Xa inhibitor, inhibits human clot-bound factor Xa activity in vitro. Thromb Haemost 2009; 101: 780-782.
  66. Eisenberg PR, Siegel JE, Abendschein DR, et al. Importance of factor Xa in determining the procoagulant activity of whole-blood clots. J Clin Invest 1993; 91: 1877-1883. DOI:10.1172/JCI116404
  67. Prager NA, Abendschein DR, McKenzie CR, et al. Role of thrombin compared with factor Xa in the procoagulant activity of whole blood clots. Circulation 1995; 92: 962-967.
  68. Varin R, Mirshahi S, Mirshahi P, et al. Effect of rivaroxaban, an oral direct Factor Xa inhibitor, on whole blood clot permeation and thrombolysis: critical role of red blood cells. Blood (ASH Annual Meeting Abstracts) 2009; 114: Abstract 1064.
  69. Bachli EB, Pech CM, Johnson KM, et al. Factor Xa and thrombin, but not factor VIIa, elicit specific cellular responses in dermal fibroblasts. J Thromb Haemost 2003; 1: 1935-1944. DOI:10.1046/j.1538-7836.2003.00363.x
  70. Shimizu T, Nishihira J, Watanabe H, et al. Macrophage migration inhibitory factor is induced by thrombin and factor Xa in endothelial cells. J Biol Chem 2004; 279: 13729-13737. DOI:10.1074/jbc.M400150200
  71. Busch G, Seitz I, Steppich B, et al. Coagulation factor Xa stimulates interleukin-8 release in endothelial cells and mononuclear leukocytes: implications in acute myocardial infarction. Arterioscler Thromb Vasc Biol 2005; 25: 461-466. DOI:10.1161/01.ATV.0000151279.35780.2d
  72. Borensztajn K, Stiekema J, Nijmeijer S, et al. Factor Xa stimulates proinflammatory and profibrotic responses in fibroblasts via protease-activated receptor-2 activation. Am J Pathol 2008; 172: 309-320. DOI:10.2353/ajpath.2008.070347
  73. Blanc-Brude OP, Chambers RC, Leoni P, et al. Factor Xa is a fibroblast mitogen via binding to effector-cell protease receptor-1 and autocrine release of PDGF. Am J Physiol Cell Physiol 2001; 281: C681-C689.
  74. Ko FN, Yang YC, Huang SC, et al. Coagulation factor Xa stimulates platelet-derived growth factor release and mitogenesis in cultured vascular smooth muscle cells of rat. J Clin Invest 1996; 98: 1493-1501. DOI:10.1172/JCI118938
  75. Joo SS, Won TJ, Kim JS, et al. Inhibition of coagulation activation and inflammation by a novel Factor Xa inhibitor synthesized from the earthworm Eisenia andrei. Biol Pharm Bull 2009; 32: 253-258. DOI:10.1248/bpb.32.253
  76. Walenga JM, Jeske WP, Hoppensteadt D, et al. Factor Xa inhibitors: today and beyond. Curr Opin Investig Drugs 2003; 4: 272-281.
  77. Ragosta M, Gimple LW, Gertz SD, et al. Specific factor Xa inhibition reduces restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits. Circulation 1994; 89: 1262-1271.
  78. Schwartz RS, Holder DJ, Holmes DR, et al. Neointimal thickening after severe coronary artery injury is limited by a short-term administration of a factor Xa inhibitor. Results in a porcine model. Circulation 1996; 93: 1542-1548.
  79. Laurent M, Varin R, Joimel U, et al. A novel mechanism of action of rivaroxaban: inhibition of monocyte and macrophage procoagulant activity and consequence on inflammatory process. Blood (ASH Annual Meeting Abstracts) 2009; 114:Abstract 3124.
  80. Mann KG, Butenas S, Brummel K. The dynamics of thrombin formation. Arterioscler Thromb Vasc Biol 2003; 23: 17-25. DOI:10.1161/01.ATV.0000046238.23903.FC
  81. Stangier J, Rathgen K, Stahle H, et al. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol 2007; 64: 292-303. DOI:10.1111/j.1365-2125.2007.02899.x
  82. Bar-Shavit R, Kahn A, Fenton JW, et al. Chemotactic response of monocytes to thrombin. J Cell Biol 1983; 96: 282-285. DOI:10.1083/jcb.96.1.282
  83. Scholz M, Vogel JU, Hover G, et al. Thrombin stimulates IL-6 and IL-8 expression in cytomegalovirus-infected human retinal pigment epithelial cells. Int J Mol Med 2004; 13: 327-331.
  84. Patrono C, Baigent C, Hirsh J, et al. Antiplatelet drugs: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133: 199S-233S. DOI:10.1378/chest.08-0672
  85. Glynn RJ, Danielson E, Fonseca FA, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med 2009; 360: 1851-1861. DOI:10.1056/NEJMoa0900241
  86. Ramcharan AS, Van Stralen KJ, Snoep JD, et al. HMG-CoA reductase inhibitors, other lipid-lowering medication, antiplatelet therapy, and the risk of venous thrombosis. J Thromb Haemost 2009; 7: 514-520. DOI:10.1111/j.1538-7836.2008.03235.x
  87. Sørensen HT, Horvath-Puho E, Søgaard KK, et al. Arterial cardiovascular events, statins, low-dose aspirin and subsequent risk of venous thromboembolism: a population-based case-control study. J Thromb Haemost 2009; 7: 521-528. DOI:10.1111/j.1538-7836.2009.03279.x
  88. Undas A, Celinska-Lowenhoff M, Brummel-Ziedins KE, et al. Simvastatin given for 3 days can inhibit thrombin generation and activation of factor V and enhance factor Va inactivation in hypercholesterolemic patients. Arterioscler Thromb Vasc Biol 2005; 25: 1524-1525. DOI:10.1161/01.ATV.0000168913.25278.38
  89. Sen-Banerjee S, Mir S, Lin Z, et al. Kruppel-like factor 2 as a novel mediator of statin effects in endothelial cells. Circulation 2005; 112: 720-726. DOI:10.1161/CIRCULATIONAHA.104.525774
  90. Masamura K, Oida K, Kanehara H, et al. Pitavastatin-induced thrombomodulin expression by endothelial cells acts via inhibition of small G proteins of the Rho family. Arterioscler Thromb Vasc Biol 2003; 23: 512-517. DOI:10.1161/01.ATV.0000060461.64771.F0
  91. Albert MA, Danielson E, Rifai N, et al. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. J Am Med Assoc 2001; 286: 64-70. DOI:10.1001/jama.286.1.64
  92. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151. DOI:10.1056/NEJMoa0905561
  93. Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008; 358: 2765-2775. DOI:10.1056/NEJMoa0800374
  94. Kakkar AK, Brenner B, Dahl OE, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 2008; 372: 31-39. DOI:10.1016/S0140-6736(08)60880-6
  95. Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008; 358: 2776-2786. DOI:10.1056/NEJMoa076016
  96. Lassen MR, Gallus AS, Pineo GF, et al. The ADVANCE-2 study: a randomized double-blind trial comparing apixaban with enoxaparin for thromboprophylaxis after total knee replacement. J Thromb Haemost 2009; 7 (Suppl 2): AbstractLB-MO-005.
  97. Turpie AGG, Lassen MR, Davidson BL, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009; 373: 1673-1680. DOI:10.1016/S0140-6736(09)60734-0
  98. Olsson SB, Executive Steering Committee of the SPORTIF III Investigators. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet 2003; 362: 1691-1698. DOI:10.1016/S0140-6736(03)14934-3
  99. Ludwig RJ. Therapeutic use of heparin beyond anticoagulation. Curr Drug Discov Technol 2009; 6: 281-289. DOI:10.2174/157016309789869001

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