Artículos relacionadosArtículos relacionadosArtículos relacionados
Artículos afines de siicsalud publicados en los últimos 4 meses
CARDIOPATÍAS Y EVENTOS ADVERSOS CARDIOVASCULARES, OBSTÉTRICOS Y PERINATALES
Revista Clínica Española 224(6):337-345
Difundido en siicsalud: 20 sep 2024
APIXABÁN EN ADULTOS CON CARDIOPATÍAS CONGÉNITAS Y ARRITMIAS AURICULARES
International Journal of Cardiology 406(131993):1-8
Difundido en siicsalud: 16 jul 2024

TRATAMIENTO DE LA TROMBOSIS CON WARFARINA

(especial para SIIC © Derechos reservados)
Ante el estrecho margen terapéutico que presenta el tratamiento anticoagulante con cumarínicos surgieron otras opciones. Se comparan en este artículo el clásico tratamiento con cumarínicos, la heparina endovenosa y el ximelagatran por vía oral.
pineo9.jpg Autor:
Pineo, graham f
Columnista Experto de SIIC

Institución:
Faculty of Medicine University of Calgary Alberta, Canada


Artículos publicados por Pineo, graham f
Coautor
Russell D. Hull, MBBS, MSc* 
Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada*
Recepción del artículo
22 de Junio, 2004
Primera edición
6 de Abril, 2005
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
La warfarina y sus derivados demostraron ser eficaces y seguros en una amplia variedad de trastornos clínicos trombóticos, como el tromboembolismo venoso, la prevención del accidente cerebrovascular (ACV) en la fibrilación auricular no valvular, la prevención del tromboembolismo sistémico en pacientes con infarto de miocardio o válvulas cardíacas protésicas. Al presentar estas drogas un estrecho margen terapéutico en lo que se refiere a la Razón Internacional Normalizada (RIN), el tratamiento insuficiente se asoció con aumento del riesgo trombótico, mientras que el exceso de anticoagulación se asoció con hemorragias. Por estas razones se hicieron varios intentos para hallar alternativas a la warfarina. La heparina de bajo peso molecular (HBPM) provee una alternativa para el tratamiento a largo plazo del tromboembolismo venoso, pero debe ser aplicada a través de una inyección. El ximelagatran, un inhibidor directo de la trombina de uso oral, demostró una eficacia equivalente y segura al compararse con la warfarina por tiempo prolongado en el tratamiento de varias enfermedades trombóticas. Cuando esta droga esté disponible simplificará el uso del tratamiento antitrombótico prolongado.

Palabras clave
Antagonistas de la vitamina K, warfarina, trombosis, hemorragia, ximelagatran


Artículo completo

(castellano)
Extensión:  +/-15.81 páginas impresas en papel A4
Exclusivo para suscriptores/assinantes

Abstract
Warfarin and related compounds have been shown to be efficacious and safe in a wide variety of clinical thrombotic disorders including venous thromboembolism, stroke prevention in nonvalvular atrial fibrillation, prevention of systemic emboli in patients with myocardial infarction or prosthetic heart valves. With these drugs having a narrow therapeutic window with respect to INR, inadequate therapy is associated with an increased thrombotic risk whereas over anticoagulation is associated with bleeding. For these reasons attempts have been made to develop alternatives to warfarin. Low-molecular-weight heparin provides an alternative for the long term treatment of venous thromboembolism but it must given by injection. ximelagatran an oral direct thrombin inhibitor has been shown to be of equal efficacy and safety when compared with long-term warfarin for the treatment of number of different thrombotic disorders. When this drug becomes available it should simplify the use of long-term antithrombotic therapy.

Key words
Vitamin K antagonists, warfarin, thrombosis, bleeding, ximelagatran


Full text
(english)
para suscriptores/ assinantes

Clasificación en siicsalud
Artículos originales > Expertos del Mundo >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Cardiología, Farmacología, Hematología
Relacionadas: Bioquímica, Cardiología, Cuidados Intensivos, Diagnóstico por Laboratorio, Farmacología, Hematología, Medicina Farmacéutica, Medicina Interna



Comprar este artículo
Extensión: 15.81 páginas impresas en papel A4

file05.gif (1491 bytes) Artículos seleccionados para su compra



Enviar correspondencia a:
Pineo, Graham F
Bibliografía del artículo
  1. Wallin R, Martin LF. Vitamin K-dependent carboxylation and vitamin K metabolism in liver: effects of warfarin. J Clin Invest 1985; 76: 1879-1884.
  2. Vermeer C. Gamma-carboxylglutamate-containing proteins and the vitamin K-dependent carboxylase. Biochem J 1990; 266: 625-636.
  3. Furie B, Furie BC. Molecular basis of vitamin K-dependent gamma-carboxylation. Blood 1990; 75: 1753-1762.
  4. Furie B, Bouchard BA, Furie BC. Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid. Blood 1999; 93; 1798-1808.
  5. Choonara IA, Malia RG, Haynes BP, et al. The relationship between inhibition of vitamin K1 2,3-epoxide reductase and reduction of clotting factor activity with warfarin. Br J Clin Pharmacol 1988; 25: 1-7
  6. Malhotra OP. Dicoumarol-induced 9-gamma-carboxyglutamic acid pro-thrombin: isolation and comparison with the 6-, 7-, 8-, and 10-gamma-carboxyglutamic acid isomers. Biochem Cell Biol 1990; 68: 705-715.
  7. Malhotra OP. Dicoumarol-induced prothrombins containing 6, 7, and 8 gamma-carboxyglutamic acid residues: isolation and characterization. Biochem Cell Biol 1989; 67: 411-421.
  8. Pineo GF, Gallus AS, Hirsh J. Unexpected vitamin K deficiency in hospitalized patients. Can Med Assoc J 1973; 109: 880-883.
  9. Lipsky JJ. Antibiotic-associated hypoprothrombinaemia. J Antimicrobrial Chemotherapy 1998; 21: 281-300.
  10. Chakraverty R, Davidson S, Peggs K, et al. The incidence and cause of coagulopathies in an intensive care population. Br J Haemotol 1996; 93: 460-463.
  11. Udall JA. Human sources and absorption of vitamin K in relation to anticoagulation stability. JAMA 1965; 194: 127-129.
  12. Frick PG, Riedler G, Brogli H. Dose response and minimal daily requirement for vitamin K in man. J Appl Physiol 1967; 23: 387-389.
  13. Exner DV, Brien WF, Murphy MJ. Superwarfarin ingestion. Can Med Assoc J 1992; 146: 34-35.
  14. Lipton RA, Klass EM. Human ingestion of a ‘superwarfarin’ rodenticide resulting in a prolonged anticoagulant effect. J Am Med Assoc 1984; 252: 3004-3005.
  15. O’Reilly RA, Pool JG, Aggeler PM. Hereditary resistance to coumarin anticoagulant drugs in man and rat. Ann N Y Acad Sci 1968; 151: 913-931.
  16. Alving BM, Strickler MP, Knight RD, et al. Hereditary warfarin resistance: investigation of a rare phenomen. Arch Intern Med 1985; 145: 499-501.
  17. Freedman MD. Oral anticoagulants: pharmacodynamics, clinical indication and adverse effects. J Clin Pharmacol 1992; 32: 196-209.
  18. Hirsh J, Dalen JE, Anderson D, et al. Oral anticoagulants; mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 2000 119: 8S-2S.
  19. Breckenridge A, Orme M, Wesseling H, et al. Pharmacokinetics and pharmacodynamics of the enantiomers of warfarin in man. Clin Pharmacol Ther 1974; 15: 424-430.
  20. Kelly JG, O’Malley K. Clinical pharmacokinetics of oral anticoagulants. Clin Pharmacokinet 1979; 4: 1-15.
  21. Sutcliffe FA, MacNicoll AD, Gibson GG. Aspects of anticoagulant action: a review of the pharmacology, metabolism and toxicology of warfarin and congeners. Rev Drug Metab Drug Interact 1987; 5: 225-272.
  22. Aithal GP, Day CP, Kesteven PJ, et al. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999; 353: 717-
  23. Miners JO, Birkett DJ. Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 1998; 45: 525-538.
  24. Shikata E, Leiri I, Ishiguro S, et al. Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and -glutamyl carboxylase) gene variants with warfarin sensitivity. Blood 2004; 103: 2630-2635.
  25. Oldenburg J, Quenzel EM, Harbrecht U, et al. Missense mutations at ALA-10 in the factor IX propeptide: an insignificant variant in normal life but a decisive cause of bleeding during oral anticoagulant therapy. Br J Haematol 1997; 98: 240-244.
  26. Broze GJ. Protein Z-dependent regulation of coagulation. Thromb Haemost. 2001 86: 8-13.
  27. Clouse LH, Comp PC. The regulation of hemostasis: the protein C system. N Engl J Med 1986; 314: 1298-1304.
  28. Brandjes DP, Heijboer H, Buller HR, et al. Acenocoumarol and heparin compared with acenoucoumarol alone in the initial treatment of proximal-vein thrombosis. N Engl J Med 1992; 327: 1485-1489.
  29. Vigano S, Mannucci PM, Solinas S, et al. Decrease in protein C antigen and formation of an abnormal protein soon after starting oral anticoagulant therapy. Br J Haematol 1984; 57: 213-220.
  30. O’Reilly RA, Aggeler PM. Studies on coumarin anticoagulant drugs: initiation of warfarin therapy without a loading dose. Circulation 1968; 368: 169-177.
  31. Wessler S, Gitel SN. Warfarin: from bedside to bench. N Engl J Med 1984; 311: 645-652.
  32. Hellemans J, Vorlat M, Verstraete M. Survival time of prothrombin and factors VII, IX, X after complete synthesis blocking doses of coumarin derivatives. Br J Haematol 1963; 9: 506-512.
  33. Patel P, Weitz J, Brooker LA, et al. Decreased thrombin activity of fibrin clots prepared in cord plasma compared with adult plasma. Pediatr Res 1996; 39: 826-830.
  34. Zivelin A, Rao LV, Rapaport SI. Mechanism of the anticoagulant effect of warfarin as evaluated in rabbits by selective depression of individual procoagulant vitamin K-dependent clotting factors. J Clin Invest 1993; 92: 2131-2140.
  35. Khan T, Wynne H, Wood P, et al. Dietary vitamin K influences intra-individual variability in anticoagulant response to warfarin. Brit J of Haematology 2004; 124: 348-354.
  36. O’Reilly RA, Rytand DA. “Resistance” to warfarin due to unrecognized vitamin K supplementation. N Eng J Med 1980; 303: 160-161.
  37. Ansell J, Hirsh J, Dalen J, et al. Managing oral anticoagulant therapy. Chest 2001; 119: 22S-38S.
  38. Wells PS, Holbrook AM, Crowther R, Hirsh J. Warfarin and its drug/food interactions: a critical appraisal of the literature. Ann Intern Med 1994; 121: 676-683.
  39. Hylek EM, Heiman H, Skates SJ, et al. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA 1998; 279: 657-662.
  40. Turpie AG, Gent M, Laupacis A, et al. A comparison of aspirin with placebo in patients treated with warfarin after heart-valve replacement. N Eng J Med 1993; 329: 524-529.
  41. Poller L, Taberner DA. Dosage and control of oral anticoagulants: an international collaborative survey. Br J Haematol 1982; 51: 479-485.
  42. Hull R, Hirsh J, Jay R, et al. Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis. N Engl J Med 1982; 307: 1676-1681.
  43. Crowther MA, Ginsberg J, Kearon C, at al. A randomized trial comparing 5-mg and 10-mg warfarin loading doses. Arch Intern Med 1999; 159: 46-48.
  44. Kovacs MJ, Rodger M, Anderson DR, Morrow B, et al. Comparison of 10-mg and 5-mg warfarin initiation nomograms together with low-molecular-weight heparin for outpatient treatment of acute venous thromboembolism. A randomized, double-blind, controlled trial. Ann Intern Med 2003; 138: 714-719.
  45. O’Donnell M, Hirsh J. Establishing an Optiman Therapeutic Range for Coumarins. Filling in the Gaps. Arch Intern Med 2004; 164: 588-590.
  46. Landefeld CS, Rosenblatt MW, Goldman L. Bleeding in outpatients treated with warfarin: relation to the prothrombin time and important remediable lesions. Am J Med 1989; 87: 153-159.
  47. Hull R, Hirsh J, Jay R, et al. Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis. N Engl J Med 1982; 307: 1676-1681.
  48. Gitter MJ, Jaeger TM, Petterson TM, et al. Bleeding and thromboembolism during anticoagulant therapy: a population-based study in Rochester, Minnesota. Mayo Clin Proc 1995; 70: 725-733.
  49. Levine MN, Raskob G, Landefeld S, Kearon C. Hemorrhagic complications of anticoagulant treatment. Chest 2001; 119: 108S-121S.
  50. van der Meer FJM, Rosendaal FR, Vandenbroucke JP, et al. Bleeding complications in oral anticoagulant therapy: an analysis of risk factors. Arch Intern Med 1995; 153: 1557-1562.
  51. Launbjerg J, Egeblad H, Heaf J, et al. Bleeding complications to oral anticoagulant therapy: multivariate analysis of 1010 treatment of overanticoagulated patients. Chest 1995; 108: 987-990.
  52. Hylek EM, Regan S, Go AS. Clinical predictors of prolonged delay in return of the international normalized ratio to within the therapeutic range after excessive anticoagulation with warfarin. Ann Intern Med 2001; 135: 393-400.
  53. Henderson MC, White RH. Anticoagulation in the elderly. Current opinion in Pulmonary Medicine 2001; 7: 365-370.
  54. White RH, Beyth RJ, Zhou H, Romano PS. Major bleeding after hospitalization for deep-vein thrombosis. Am J Med 1999; 107: 414-424.
  55. Steward DJ, Haining RL, Henna KR, et al. Genetic association between sensitivity to warfarin and expression of CYP2C9*3. Pharmacogenetics 1997; 7: 361-367.
  56. Siguret V, Gouin I, Golmard JL, et al. Cytochrome P450 2C9 polymorphisms (CYP2C9) and warfarin maintenance dose in elderly patients. Rev Med Interne 2004; 25: 271-274.
  57. Beyth BJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting risk of major bleeding in outpatients treated with warfarin. Am J Med 1998; 105: 91-99.
  58. Kuijer PM, Hutten BA, Prins MH, et al. Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism. Arch Intern Med 1999; 159; 457-460.
  59. Fihn SD, McDonell M, Martin D, et al. Risk factors for complications of chronic anticoagulation: a multicentre study. Warfarin Optimized Outpatient Follow-up Study Group. Ann Intern Med 1993; 118: 511-520.
  60. Shetty HG, Backhouse G, Bentley DP, et al. Effective reversal of warfarin-induced excessive anticoagulation with low dose vitamin K1. Thromb Haemost 1992; 67: 13-15.
  61. Pengo V, Banzato A, Garelli E, et al. Reversal of excessive effect of regular anticoagulation: low oral dose of phytonadione (vitamin K1) compared with warfarin discontinuation. Blood Coagul Fibrinolysis 1993; 4: 739-741.
  62. Crowther MA, Julian J, Douketis JD, et al. Treatment of warfarin-associated coagulopathy with oral vitamin K: a randomized clinical trial. Lancet 2000; 3356: 1551-1553.
  63. Fiore LD, Scola MA, Cantillon CE, et al. Anaphylactoid reactions to vitamin K. Journal of Thrombosis and Thrombolysis 2001; 11: 175-183.
  64. de la Rubia J, Grau E, Montserrat I, et al. Anaphylactic shock and vitamin K1. Ann Intern Med 1989; 110:943.
  65. Lemlich G, Green M, Phelps R, et al. Cutaneous reactions to vitamin K1 injections. J Am Acad Dermatol 1993; 28: 345-347.
  66. Sanders MN, Winkelmann RK. Cutaneous reactions to vitamin K. J Am Acad Dermatol 1988; 19: 699-704.
  67. Johnsen, SP, Sorensen, HT, Mellemkjoer L, et al. Hospitalisation for upper gastrointestinal bleeding associated with use of oral anticoagulants. Thromb Haemost 2001; 86: 563-8.
  68. Grimaudo V, Gueissaz F, Hauert J, et al. Necrosis of skin induced by coumarin in a patient deficient in protein S. Br Med J 1989; 298: 233.
  69. Becker CG. Oral anticoagulant therapy of skin necrosis: Speculation on pathogenesis. Adv Exp Med Biol 1987; 214: 217.
  70. Verhagen HJ. Local hemorrhage and necrosis of the skin and underlying tissues, during anticoagulant therapy with dicumarol or dicumacyl. Acta Med Scand 1954; 148: 453.
  71. Broekmans AW, Bertina RM, Loeliger EA, et al. Protein C and the development of skin necrosis during anticoagulant therapy. Thromb Haemost 1983; 49: 251.
  72. Samama M, Horellou MH, Soria J, et al. Successful progressive anticoagulation in a severe protein C deficiency and previous skin necrosis at the initiation of oral anticoagulant treatment. Thromb Haemost 1984; 51: 132-133.
  73. Hall JG, Pauli RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med 1980; 68: 122.
  74. Ginsberg JS, Greer I, Hirsh J. Use of antithrombotic agents during pregnancy. Chest 2001; 119: 122S-131S.
  75. Iturbe-Alessio I, del Carmen Fonseca M, Mutchinik O, et al. Risks of anticoagulant therapy in pregnant women with artificial heart valves. N Engl J Med 1986; 315: 1390.
  76. Sbarouni E, Oakley CM. Outcome of pregnancy in women with valve prostheses. Br Heart J 1994; 71: 196-201.
  77. Bauersachs R, Lindhoff-Last E. Anticoagulation of pregnant women with mechanical heart valves using low-molecular-weight heparin. Arch Intern Med 2003;1 63: 2788-2789.
  78. McLintock C, North RA, White HD. Prosthetic heart valves and pregnancy. Circulation 2003; 108: e159-160.
  79. Ageno W, Crotti S, Turpie AG. The safety of antithrombotic therapy during pregnancy. Expert Opin Drug Saf 2004; 3: 113-118.
  80. Kearon C, Hirsh J. Management of anticoagulation before and after elective surgery. N Engl J Med 1997; 336 (21): 1506-1511.
  81. Stein PD, Alpert JS, Bussey HI, Dalen JE Turpie G.G. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. Chest 2001; 119: 220S-227S.
  82. Johnson J, Turpie AGG. Temporary discontinuation of oral anticoagulants: role of low-molecular-weight heparin. Thromb Haemost 2001 Suppl (July): 2323 (Abst.).
  83. Tinmouth A, Kovacs MJ, Cruikshank M, et al. Out-patient peri-operative and peri-procedure treatment with dalteparin for chronically anticoagulated patients at high risk for thromboembolic complications. Thromb Haemost 1999; Suppl (Aug): 662.
  84. Spandorfer JM, Lynch S, Weitz HH, et al. Use of enoxaparin for the chronically anticoagulated patient before and after procedures. Am J Cardiol 1999; 84: 478-480.
  85. Ansell JE, Hughes R. Evolving models of warfarin management: anticoagulation clinics, patient self-monitoring and patient self-management. Am Heart J 1996; 132: 1095-1100.
  86. Ansell JE, Buttaro ML, Voltis-Thomas O & KNowlton C. Consensus guidelines for coordinated outpatient oral anticoagulation therapy management. Annals of Pharmoctherapy 1997; 31: 604-615.
  87. Poller L, Shiach CR, MacCallum PK, et al. Multicentre randomized study of computerized anticoagulant dosage. European concerted action on Anticoagulation. Lancet 1998: 352 (9139): 1505-9.
  88. Leaning KE, Ansell JE. Advances in the monitoring of oral anticoagulation. J Thrombosis and Thrombolysis 1996; 3: 377-383.
  89. White RH, McCurdy SA, von Marensdorff H, et al. Home prothrombin time monitoring after initiation of warfarin therapy. Ann Intern Med 1989; 111: 730-37.
  90. Bernardo A. Experience with patient self-management of oral anticoagulation. J Thrombosis and Thrombolysis 1996; 2: 321-325.
  91. Gadisseur APA, Kaptein AA, Breukink-Engbers WGM, et al. Patients self-management of oral anticoagulant care vs. management by specialized anticoagulation clinics: positive effects on quality of life. J of Thrombosis and Haemostasis 2003; 2: 584-591.
  92. Hylek EM Skates SJ, Sheehan MA, et al. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med 1995; 335: 540-546.
  93. Perret-Guillaume C, Wahl DG. Low-dose warfarin in atrial fibrillation leads to more thromboembolic events without reducing major bleeding when compared to adjusted-dose. A meta-analysis. Thromb Haemost 2004; 91: 394-402.
  94. Hart RG, Sherman DG, Easton JD, et al. Prevention of stroke in patients with nonvalvular atrial fibrillation. Neurology 1998; 51: 674-681.
  95. Ridker PM, Goldhaber SZ, Danielson E, et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003; 348: 1425-34.
  96. Kearon C, Ginsberg JS, Kovacs MJ, et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349: 631-639.
  97. Bern MM, Lokich JJ, Wallach SR, et al. Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial. Ann Intern Med 1990; 112: 423-428.
  98. Couban S, Goodyear M, Burnell M, et al. A randomized double-blind placebo-controlled study of low dose warfarin for the prevention of symptomatic central venous catheter-associated thrombosis in patients with cancer. Blood 2002; 100: 703a (abst).
  99. Heaton DC, Han DY, Inder A. Minidose (1 mg) warfarin as prophylaxis for central vein catheter thrombosis. Intern Med J 2002; 32: 84-88.
  100. Masci G, Magagnoli M, Zucali PA, et al. Minidose warfarin prophylaxis for catheter-associated thrombosis in cancer patients: can it be safely associated with fluorouracil-based chemotherapy J Clin Oncol 2003; 21: 736-739.
  101. Hyers T, Agnelli G, Hull R, et al. Antithrombotic therapy for venous thromboembolic disease. Chest 2001; 119: 176S-193S.
  102. Khamashta MA, Cuadrado MJ, Mujic F, et al. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med 1995; 332: 993-997.
  103. Rosove MH, Brewer PM. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med 1992; 117: 303-308.
  104. Ruiz-Irastorza G, Khamashta MA, Hunt BJ, et al. Bleeding and recurrent thrombosis in definite antiphospholipid syndrome: analysis of a series of 66 patients treated with oral anticoagulation to a target international normalized ratio of 3.5. Arch Intern Med 2002; 162: 1164-1169.
  105. Crowther MA, Ginsberg JS, Julian J, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients wit the antiphospholipid antibody syndrome. N Engl J Med 349: 12: 1133-1138.
  106. Kakkar VV, Gebska M, Kadziola Z, et al. Low-molecular-weight heparin in the acute and long-term treatment of deep vein thrombosis. Thromb Haemost 2003; 89: 674.
  107. van der Heijden JF, Hutten BA, Buller HR, et al. Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism. Cochrane Database of Systematic Reviews 2000; 1:1-28.
  108. Lee A, Levine M, Baker R, et al for the CLOT Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349: 146-53.
  109. Hull RD, Pineo GF, Mah AF, et al. A randomized trial evaluating long-term low-molecular-weight heparin therapy for three months vs. intravenous heparin followed by warfarin sodium in patients with current cancer. Thromb Haemost 2003; 1 (supplement July), abstract P137a.
  110. Meyer G, Marjanovic Z, Valcke J, et al. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med. 2002; 162: 1729-35.
  111. Eriksson UG, Bredberg U, Gislen K, et al. Pharmacokinetics and pharmacodynamics of ximelagatran, a novel oral direct thrombin inhibitor, in young healthy male subjects. Eur J Clin Pharmacol 2003; 59: 35-43
  112. Eriksson UG, Mandema J, Karlsson MO, et al. Pharmacokinetics of melagatran and the effect on ex vivo coagulation time in orthopaedic surgery patients receiving subcutaneous melagatran and oral ximelagatran: a population model analysis. Clin Pharmacokinet 2003; 42: 687-701.
  113. Wåhlander K, Lapidus L, Olsson CG, et al. Pharmacokinetics, pharmacodynamics and clinical effects of the oral direct thrombin inhibitor ximelagatran in acute treatment of patients with pulmonary embolism and deep vein thrombosis. Thromb Res 2002; 107: 93-99.
  114. Johansson LC, Frison L, Logren U, et al. Influence of age on the pharmacokinetics and pharmacodynamics of ximelagatran, an oral direct thrombin inhibitor. Clin Pharmacokinet 2003; 42: 381-392.
  115. Bredberg E, Andersson TB, Frison L, et al. ximelagatran, an oral direct thrombin inhibitor, has a low potential for cytochrome P450-mediated drug-drug interactions. Clin Pharmacokinet. 2003; 42: 765-777.
  116. Eriksson UG, Johansson S, Attman P-O, et al. Influence of severe renal impairment on the pharmacokinetics and pharmacodynamics of oral ximelagatran and subcutaneous melagatran. Clin Pharmacokinet 2003; 42: 743-753.
  117. Boström SL, Hansson G, Sarich TC, Wolzt M. The inhibitory effect of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, compared with enoxaparin and r-hirudin on ex vivo thrombin generation in human plasma. Thromb Res 2004; 113: 85-91.
  118. Klement P, Carlsson S, Rak J, et al. The benefit-to-risk profile of melagatran is superior to that of hirudin in a rabbit arterial thrombosis prevention and bleeding model. J Thromb Haemost 2003; 1: 587-594.
  119. Sarich TC, Osende JI, Eriksson UG, et al. Acute antithrombotic effects of ximelagatran, an oral direct thrombin inhibitor, and r-hirudin in a human ex vivo model of arterial thrombosis. J Thromb Haemost 2003; 1: 999-1004.
  120. Sarich TC, Wolzt M, Eriksson UG, et al. Effects of ximelagatran, an oral direct thrombin inhibitor, r-hirudin and enoxaparin on thrombin generation and platelet activation in healthy male subjects. J Am Coll Cardiol 2003; 41: 557-564.
  121. Heit JA, Colwell CW, Francis CW, et al. AstraZeneca Arthroplasty Study Group: Comparison of the oral direct thrombin inhibitor ximelagatran with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement: a phase 2 dose-finding study. Arch Intern Med 2001; 161: 2215-2221.
  122. Eriksson BI, Bergqvist D, Kalebo P, et al. Melagatran for Thrombin inhibition in Orthopaedic surgery. ximelagatran and melagatran compared with dalteparin for prevention of venous thromboembolism after total hip or knee replacement: the METHRO II randomised trial. Lancet 2002; 360: 1441-1417.
  123. Francis CW, Davidson BL, Berkowitz SD, et al. ximelagatran versus warfarin for the prevention of venous thromboembolism after total knee arthroplasty. A randomized, double-blind trial. Ann Intern Med 2002; 137: 648-655.
  124. Eriksson H, Wahlander K, Gustafsson D, et al. THRIVE Investigators: A randomized, controlled, dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute deep vein thrombosis: THRIVE I. J Thromb Haemost 2003; 1: 41-47.
  125. Huisman MV on behalf of the THRIVE Treatment Study Investigators. Efficacy and safety of the oral direct thrombin inhibitor ximelagatran compared with current standard therapy for acute symptomatic deep vein thrombosis, with or without pulmonary embolism: a randomized, double-blind, multinational study. J. Thromb. Haemost. 1(Suppl): OC003, 2003.
  126. Schulman S, Wahlander K, Lundstrom T, et al. Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran. N Engl J Med 349; 18: 1713-1721.
  127. Petersen P, Grind M, Adler J; SPORTIF II Investigators: ximelagatran versus warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. SPORTIF II: a dose-guiding, tolerability, and safety study. J Am Coll Cardiol 2003; 41: 1445-1451.
  128. Executive Steering Committee on behalf 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): randomized controlled trial. The Lancet 2003; 362: 1691-1698.
  129. Wallentin L, Wilcox RG, Weaver WG, et al. Oral ximelagatran for secondary prophylaxis after myocardial infarction: the ESTEEM randomised controlled trial. Lancet 2003; 362: 789-97.

 
 
 
 
 
 
 
 
 
 
 
 
Está expresamente prohibida la redistribución y la redifusión de todo o parte de los contenidos de la Sociedad Iberoamericana de Información Científica (SIIC) S.A. sin previo y expreso consentimiento de SIIC.
Artículos relacionadosMás relacionadosAtículos relacionados
APIXABÁN Y ANTAGONISTAS DE LA VITAMINA K EN PACIENTES CON DIÁLISIS
Renal Failure 46(1):1-10
Difundido en siicsalud: 30 may 2024
ua31618
Home

Copyright siicsalud © 1997-2024 ISSN siicsalud: 1667-9008