Nadroparina cálcica: una revisión de su farmacología básica y clínica
Publicado
may 10, 2011
Almetrics
Dimensions
Google Scholar
##plugins.themes.bootstrap3.article.details##
Resumen
Objetivo. Evaluar críticamente la información sobre la farmacología básica y clínica de la nadroparina cálcica.
Fuente de datos. Se hizo una búsqueda en la literatura científica de octubre de 1985 a septiembre de 2010, en las bases de datos electrónicas: Pubmed, Cochrane, MDConsult, Scielo y Medscape, y en el Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA).
Selección de estudios. Se incluyeron los estudios publicados en inglés, español o francés, realizados en humanos y animales de experimentación, en los que se revisara la farmacología básica y clínica de la nadroparina cálcica. Extracción y síntesis de datos. Se revisaron 792 resúmenes y se seleccionaron 60 artículos que cumplieron los criterios de inclusión, de acuerdo con un método se resolvieron todas las discrepancias por discusión y consenso.
Conclusión. En algunos estudios la nadroparina cálcica ha mostrado una eficacia igual o superior a la de la heparina no fraccionada y la de un placebo. Sin embargo, la información evaluada no es lo suficientemente sólida para considerar superior la nadroparina frente a las otras heparinas de bajo peso molecular. La literatura científica muestra que, en general, el tratamiento con estas últimas es más seguro y costo-efectivo que con heparina no fraccionada. No existen pruebas suficientes, fuertes y concluyentes para calificar la nadroparina cálcica como superior a otras heparinas de bajo peso molecular en el tratamiento antitrombótico. Las de bajo peso molecular han demostrado una reducción significativa en la angiogénesis tumoral y un aumento en la supervivencia de pacientes con enfermedades oncológicas. Sin embargo, se requieren más investigaciones para caracterizar y comprender mejor este nuevo hallazgo.
Keywords
nadroparin calcium, anticoagulants, low molecular weight heparins, blood coagulation disorders, venous thromboembolism and pharmacoeconomicsnadroparina cálcica, anticoagulantes, heparinas de bajo peso molecular, trastornos de la coagulación sanguínea, tromboembolia venosa, farmacoeconomía,
References
1. Davis R, Faulds D. Nadroparin calcium. A review of its pharmacology and clinical use in the prevention and treatment of
thromboembolic disorders. Drugs Aging. 1997;10:299-322.
2. Barradell LB, Buckley MM. Nadroparin calcium. A review of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disorders. Drugs. 1992;44:858-88.
3. GlaxoSmithKline Company. Product´s monograph Nadroparin Calcium. Fecha de consulta: 16 de septiembre de 2009. Disponible en: http://www.gsk.ca/english/html/our-products/fraxiparine.html.
4. Frydman A. Low-molecular-weight heparins: An overview of their pharmacody namics, pharmacokinetics and metabolism in humans. Haemostasis. 1996;26(Suppl. 2):24-38.
5. Collignon F, Frydman A, Caplain H, Ozoux ML, Le Roux Y, Bouthier J, et al. Comparison of the pharmacokinetic profiles of three low molecular mass heparins-deltaparin, enoxaparin and nadroparin- administred subcutaneously in healthy volunteers (doses for prevention of thromboembolism). Thromb Haemost. 1995;73:630-40.
6. Samama MM, Gerotziafas GT. Comparative pharmacokinetics of LMWHs. Semin Thromb Hemost. 2000;26(Suppl.1):31-8.
7. Lourdes R. Heparina no fraccionada y heparinas de bajo peso molecular. Principales diferencias. Fecha de consulta: 18 de noviembre de 2009. Disponible en: http://fcmfajardo.sld.cu/cev2002/conferencias/farmacologia_lourdes_ramos.htm.
8. Hardman JG, Limbird LE, Gilman AG. Goodman & Gilman’s the pharmacological basis of therapeutics. 10th edition. New York: McGraw-Hill; 2001;1519-38.
9. Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ; American College of Chest Physicians. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition).
Chest. 2008;133(Suppl.):454S-5S.
10. Schmid P, Fischer AG, Wuillemin WA. Low-molecular-weight heparin in patients with renal insufficiency. Swiss Med Wkly. 2009;139:438-52.
11. Hirsh J, Raschke R. Heparin and lowmolecular-weight heparin: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:188S-203S.
12. Turpie AGG, Gallus AS, Hoek JA, for the Pentasaccharide Investigators. A synthetic pentasaccharide for the prevention of
deep-vein thrombosis after total hip replacement. N Engl J Med. 2001;344:619-25.
13. Instituto Nacional de Vigilancia de Medicamentos y Alimentos. Información de nadroparina cálcica. Fecha de consulta: el 12 de diciembre de 2009. Disponible en: http://web.invima.gov.co/Invima//consultas/informacion_registros_sanitarios.jsp?codigo=341.
14. Ministerio de la Protección Social, Plan Obligatorio de Salud (POS). [Sitio en Internet] Fecha de consulta: 5 de diciembre de 2009. Disponible en: http://www.pos.gov.co/Paginas/default.aspx.
15. Instituto Nacional de Vigilancia de Medicamentos y Alimentos, Actas de medicamentos-nadroparina cálcica. Fecha de consulta: 3 de diciembre del 2009. Disponible en: http://www.invima.gov.co/Invima/consultas/docs_actas/medicamentos/2007/CerActa282007.htm, http://www.invima.gov.co/Invima/consultas/docs_actas/medicamentos/2005/ceracta362005.htm.
16. Secretaría de Salud de Bogotá. Manual tarifario de medicamentos 2009. Fecha de consulta: 20 de noviembre de 2009. Disponible en: http://www.saludcapital.gov.co/Publicaciones/Manual tarifario de medicamentos/Manual 2009.xls.
17. Oliveros H, Lobelo R, Martínez F. Análisis costo-efectividad de las heparinas de bajo peso molecular en tromboprofilaxis temprana
en pacientes médicos y quirúrgicos. Acta Med Colomb. 2006;31:71-82.
18. Hauch O, Khattar SC, Jørgensen LN. Cost- benefit of prophylaxis against deep vein thrombosis in surgery. Semin Thromb Hemost. 1991;17(Suppl.3):280S-3S.
19. Oster G, Tuden RL, Colditz GA. A cost effectiveness analysis of prophylaxis against deep-vein thrombosis in major orthopedic surgery. JAMA. 1987;257:203-8.
20. Bergqvist D, Matzsch T. Cost/benefit aspects on thromboprophylaxis, Haemostasis. 1993;23(Suppl.1):15S-9S.
21. Bergqvist D, Mätzsch T, Jendteg S, Lindgren B, Persson U, et al. The cost-effectiveness of prevention of post-operative thromboembolism. Acta Chir Scand. 1990;556(Suppl.):36-41.
22. Bergqvist D, Lindgren B, Matzsch T. Comparison of the cost of preventing postoperative deep vein thrombosis with either unfractionated or low molecular weight heparin. Br J Surg. 1996;83:1548-52.
23. Heaton D, Pearce M. Low molecular weight Vs. unfractionated heparin: A clinical and economic appraisal. Pharmacoeconomics. 1995;8;91-9.
24. Lévesque H, Cailleux N, Vasse D, Legallicier B, Moore N, Borg JY, et al. Evaluation of hospital cost of six days of treatment of deep venous thrombosis. Comparison of subcutaneous nadroparin and intravenous heparin in 40 patients. Therapie. 1994;49:101-5.
25. Koopman MM, Prandoni P, Piovella F, Ockelford PA, Brandjes DP, van der Meer J, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecularweight heparin administered at home. The Tasman Study Group. N Engl J Med.
1996;334:682-7.
26. McGarry LJ, Thompson D, Weinstein MC, Goldhaber SZ. Cost effectiveness of thromboprophylaxis with a low-molecular- weight heparin versus unfractionated heparin in acutely ill medical inpatients. Am J Manag Care. 2004;10:632-42.
27. Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133(Suppl.):381S-453S.
28. Hirsh J, Dalen J, Guyatt G. American College of Chest Physicians. The sixth (2000) ACCP guidelines for antithrombotic therapy for prevention and treatment of thrombosis. American College of Chest
Physicians. Chest. 2001;119:1S-47S.
29. Forette B, Wolmark Y. Calcium nadroparin in the prevention of thromboembolic disease in elderly subjects. Study of tolerance. Presse Med. 1995;24:567-71.
30. Kadusevicius E, Kildonaviciute G, Varanaviciene B, Jankauskiene D. Low-molecular- weight heparins: Pharmacoeconomic decision modeling based on meta-analysis data. Int J Technol Assess Health
Care. 2010;26:272-9.
31. Shorr AF, Jackson WL, Weiss BM, Moores LK. Low-molecular weight heparin for deep vein thrombosis prophylaxis in hospitalized
medical patients: Results from a cost-effectiveness analysis. Blood Coagul Fibrinolysis. 2007;18:309-16.
32. Rodger M, Bredeson C, Wells PS, Beck J, Kearns B, Huebsch LB. Cost-effectiveness of low-molecular-weight heparin and unfractionated heparin in treatment of deep vein thrombosis. CMAJ. 1998;159:931-8.
33. Wilke T, Tesch S, Scholz A, Kohlmann T, Greinacher A. The costs of heparininduced thrombocytopenia: A patientbased cost of illness analysis. J Thromb Haemost. 2009;7:766-73.
34. Zawilska K, Jaeschke R, Tomkowski W, Mayzner-Zawadzka E, Nizankowski R, Olejek A, et al. Polish guidelines for the prevention and treatment of venous thromboembolism: 2009 update. Pol Arch Med Wewn. 2009;119(Suppl.1):1-69.
35. Magee KD, Sevcik W, Moher D, Rowe BH. Low molecular weight heparins versus unfractionated heparin for acute coronary syndromes. Cochrane Database Syst Rev. 2003;(1):CD002132.
36. van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation. G Ital Cardiol (Rome). 2009;10:450-89.
37. Tapson VF. Acute pulmonary embolism. N Engl J Med. 2008;358:1037-52.
38. Alonso JL, Abínzano ML, Urbieta MA, Annichérico FJ, Fernández V, García JL. Tratamiento de la trombosis venosa profunda con heparinas de bajo peso molecular: estudio comparativo con anticoagulación oral. An Med Interna (Madrid). 2008;25:4-8.
39. Shafiq N, Malhotra S, Pandhi P, Sharma N, Bhalla A, Grover A. A randomized controlled clinical trial to evaluate the efficacy, safety, cost-effectiveness and effect on PAI-1 levels of the three low-molecularweight heparins –enoxaparin, nadroparin and dalteparin. The ESCAPe-END study. Pharmacology. 2006;78:136-43.
40. Bergqvist D. Low-molecular-weight heparin for the prevention of postoperative venous thromboembolism after abdominal surgery: A review. Curr Opin Pulm Med. 2005;11:392-7.
41. Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, et al. Randomized comparison of low-molecular-weight heparin versus oral anticoagulant therapy for the prevention of recurrent venous thromboembolism in patients with cancer (CLOT) investigators. N Engl J Med. 2003;349:146-53.
42. Kanaan AO, Silva MA, Donovan JL, Roy T, Al-Homsi AS. Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients. 2007;29:2395-405.
43. Bermúdez AF, Bermúdez PV, Cano PC, Medina RM, Núñez PM, Restrepo H, et al. Heparinas de bajo peso molecular en la cardiopatía isquémica metabólica. Bases moleculares: experiencia clínica y resultados. AVFT. 2000;19: 82-97.
44. García JR, López F, Asis C. Tratamiento a largo plazo de coagulación intravascular diseminada crónica con heparina de bajo peso molecular. An Med Interna (Madrid). 2003;20:35-8.
45. Bounameaux H, Huber O, Khabiri E, Schneider PA, Didier D, Rohner A, Unexpectedly high rate of phlebographic deep venous thrombosis following elective general abdominal surgery among patients given prophylaxis with lowmolecular-weight heparin. Arch Surg. 1993;128(3):326-8.
46. Eurin B. Efficacy and tolerance of fraxiparine in the prevention of deep vein thrombosis in general surgery performed with medullar conduction anesthesia. Ann Fr Anesth Reanim. 1994;13:311-7.
47. European Fraxiparin Study. Comparison of a low molecular weight heparin and unfractionated heparin for the prevention of deep vein thrombosis in patients undergoing abdominal surgery. Br J Surg. 1988;75:1058-63.
48. Kakkar VV, Murray WJ. Efficacy and safety of low-molecular-weight heparin (CY216) in preventing postoperative venous thrombo-embolism: A co-operative study. Br J Surg. 1985;72:786-91.
49. Pezzuoli G, Neri GG, Settembrini P, Coggi G, Olivari N, Buzzetti G, et al. Prophylaxis of fatal pulmonary embolism in general surgery using low-molecular weight heparin Cy 216: A multicentre, double-blind, randomized, controlled, clinical trial versus placebo (STEP). Int
Surg. 1989;74:205-10.
50. Hamulyák K, Lensing AW, van der Meer J, Smid WM, van Ooy A, Hoek JA. Subcutaneous low-molecular weight heparin or oral anticoagulants for the prevention of deep-vein thrombosis in elective hip and knee replacement? Fraxiparine Oral Anticoagulant Study Group. Thromb Haemost. 1995;74:1428-31.
51. Leyvraz PF, Bachmann F, Hoek J, Büller HR, Postel M, Samama M, et al. Prevention of deep vein thrombosis after hip replacement: Randomized comparison between unfractionated heparin and low molecular weight heparin. BMJ. 1991;303:543-8.
52. German Hip Arthroplasty Trial (GHAT). Prevention of deep vein thrombosis with low molecular-weight heparin in patients undergoing total hip replacement. A randomized trial. Arch Orthop Trauma Surg. 1992;111:110-20.
53. Simonneau G, Laporte S, Mismetti P, Derlon A, Samii K, Samama CM, et al. A randomized study comparing the efficacy and safety of nadroparin 2,850 IU (0.3 ml) vs. enoxaparin 4,000 IU (40 mg) in the prevention of venous thromboembolism after colorectal surgery for cancer. J Thromb Haemot. 2006;4:1693-700.
54. Gerkens S, Crott R, Closon MC, Horsmans Y, Beguin C. Comparing the quality of care across Belgian hospitals from medical
basic datasets: The case of thromboembolism prophylaxis after major orthopaedic surgery. J Eval Clin Pract. 2010;16:685-92.
55. Harenberg J, Roebruck P, Heene DL. Subcutaneous low-molecular-weight heparin versus standard heparin and the prevention of thromboembolism in medical inpatients. The Heparin Study in Internal Medicine Group. Haemostasis. 1996;26:127-39.
56. van Dongen CJ, MacGillavry MR, Prins MH. Once versus twice daily LMWH for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev. 2005;3:CD003074.
57. van Dongen CJ, van den Belt AG, Prins MH, Lensing AW. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev. 2004;4:CD001100.
58. García RM, Antuña MT, Lapuerta JA, Gutiérrez M J. Hematoma abdominal secundario al empleo de nadroparina. An Med Interna (Madrid). 2004;21: 612.
59. Sanofi Pharma. Fraxiparine technical brochure. France Sanofi Pharma; 1995.
60. Schindewolf M, Schwaner S, Wolter M, Kroll H, Recke A, Kaufmann R, et al. Incidence and causes of heparin-induced skin
lesions. CMAJ. 2009;181:477-81.
61. Aster RH. Heparin-induced thrombocytopenia and thrombosis (letter). N Engl J Med. 1995;332:1374-6.
62. Greinacher A. Heparin-induced thrombocytopenia. J Thromb Haemost. 2009;7(Suppl.1):9-12.
63. Battistelli S, Genovese A, Gori T. Heparininduced thrombocytopenia in surgical patients. Am J Surg. 2010;199:43-51.
64. Maraveyas A, Johnson MJ, Xiao YP, Noble S. Malignant melanoma as a target malignancy for the study of the anti-metastatic properties of the heparins. Cancer Metastasis Rev. 2010;29(4):777-84.
65. Borsig L. Heparin as an inhibitor of cancer progression. Prog Mol Biol Transl Sci. 2010;93:335-49.
66. Nagy Z, Turcsik V, Blaskó G.The effect of LMWH (nadroparin) on tumor progression. Pathol Oncol Res. 2009;15:689-92.
67. Klerk CP, Smorenburg SM, Otten HM, Lensing AW, Prins MH, Piovella F, et al. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol. 2005;23:2130-5.
68. Debergh I, van Damme N, Pattyn P, Peeters M, Ceelen WP. The low-molecular- weight heparin, nadroparin, inhibits tumour angiogenesis in a rodent dorsal skinfold chamber model. Br J Cancer.
2010;102:837-43.
69. Mousa SA, Linhardt R, Francis JL, Amirkhosravi A. Anti-metastatic effect of a non-anticoagulant low-molecular-weight heparin versus the standard low-molecular-weight heparin, enoxaparin. Thromb Haemost. 2006;96(6):816-21.
70. van Sluis GL, Nieuwdorp M, Kamphuisen PW, van der Vlag J, van Noorden CJ, Spek CA. A low molecular weight heparin inhibits experimental metastasis in mice independently of the endothelial glycocalyx. PLoS One. 2010;5:e11200.
thromboembolic disorders. Drugs Aging. 1997;10:299-322.
2. Barradell LB, Buckley MM. Nadroparin calcium. A review of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disorders. Drugs. 1992;44:858-88.
3. GlaxoSmithKline Company. Product´s monograph Nadroparin Calcium. Fecha de consulta: 16 de septiembre de 2009. Disponible en: http://www.gsk.ca/english/html/our-products/fraxiparine.html.
4. Frydman A. Low-molecular-weight heparins: An overview of their pharmacody namics, pharmacokinetics and metabolism in humans. Haemostasis. 1996;26(Suppl. 2):24-38.
5. Collignon F, Frydman A, Caplain H, Ozoux ML, Le Roux Y, Bouthier J, et al. Comparison of the pharmacokinetic profiles of three low molecular mass heparins-deltaparin, enoxaparin and nadroparin- administred subcutaneously in healthy volunteers (doses for prevention of thromboembolism). Thromb Haemost. 1995;73:630-40.
6. Samama MM, Gerotziafas GT. Comparative pharmacokinetics of LMWHs. Semin Thromb Hemost. 2000;26(Suppl.1):31-8.
7. Lourdes R. Heparina no fraccionada y heparinas de bajo peso molecular. Principales diferencias. Fecha de consulta: 18 de noviembre de 2009. Disponible en: http://fcmfajardo.sld.cu/cev2002/conferencias/farmacologia_lourdes_ramos.htm.
8. Hardman JG, Limbird LE, Gilman AG. Goodman & Gilman’s the pharmacological basis of therapeutics. 10th edition. New York: McGraw-Hill; 2001;1519-38.
9. Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ; American College of Chest Physicians. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition).
Chest. 2008;133(Suppl.):454S-5S.
10. Schmid P, Fischer AG, Wuillemin WA. Low-molecular-weight heparin in patients with renal insufficiency. Swiss Med Wkly. 2009;139:438-52.
11. Hirsh J, Raschke R. Heparin and lowmolecular-weight heparin: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:188S-203S.
12. Turpie AGG, Gallus AS, Hoek JA, for the Pentasaccharide Investigators. A synthetic pentasaccharide for the prevention of
deep-vein thrombosis after total hip replacement. N Engl J Med. 2001;344:619-25.
13. Instituto Nacional de Vigilancia de Medicamentos y Alimentos. Información de nadroparina cálcica. Fecha de consulta: el 12 de diciembre de 2009. Disponible en: http://web.invima.gov.co/Invima//consultas/informacion_registros_sanitarios.jsp?codigo=341.
14. Ministerio de la Protección Social, Plan Obligatorio de Salud (POS). [Sitio en Internet] Fecha de consulta: 5 de diciembre de 2009. Disponible en: http://www.pos.gov.co/Paginas/default.aspx.
15. Instituto Nacional de Vigilancia de Medicamentos y Alimentos, Actas de medicamentos-nadroparina cálcica. Fecha de consulta: 3 de diciembre del 2009. Disponible en: http://www.invima.gov.co/Invima/consultas/docs_actas/medicamentos/2007/CerActa282007.htm, http://www.invima.gov.co/Invima/consultas/docs_actas/medicamentos/2005/ceracta362005.htm.
16. Secretaría de Salud de Bogotá. Manual tarifario de medicamentos 2009. Fecha de consulta: 20 de noviembre de 2009. Disponible en: http://www.saludcapital.gov.co/Publicaciones/Manual tarifario de medicamentos/Manual 2009.xls.
17. Oliveros H, Lobelo R, Martínez F. Análisis costo-efectividad de las heparinas de bajo peso molecular en tromboprofilaxis temprana
en pacientes médicos y quirúrgicos. Acta Med Colomb. 2006;31:71-82.
18. Hauch O, Khattar SC, Jørgensen LN. Cost- benefit of prophylaxis against deep vein thrombosis in surgery. Semin Thromb Hemost. 1991;17(Suppl.3):280S-3S.
19. Oster G, Tuden RL, Colditz GA. A cost effectiveness analysis of prophylaxis against deep-vein thrombosis in major orthopedic surgery. JAMA. 1987;257:203-8.
20. Bergqvist D, Matzsch T. Cost/benefit aspects on thromboprophylaxis, Haemostasis. 1993;23(Suppl.1):15S-9S.
21. Bergqvist D, Mätzsch T, Jendteg S, Lindgren B, Persson U, et al. The cost-effectiveness of prevention of post-operative thromboembolism. Acta Chir Scand. 1990;556(Suppl.):36-41.
22. Bergqvist D, Lindgren B, Matzsch T. Comparison of the cost of preventing postoperative deep vein thrombosis with either unfractionated or low molecular weight heparin. Br J Surg. 1996;83:1548-52.
23. Heaton D, Pearce M. Low molecular weight Vs. unfractionated heparin: A clinical and economic appraisal. Pharmacoeconomics. 1995;8;91-9.
24. Lévesque H, Cailleux N, Vasse D, Legallicier B, Moore N, Borg JY, et al. Evaluation of hospital cost of six days of treatment of deep venous thrombosis. Comparison of subcutaneous nadroparin and intravenous heparin in 40 patients. Therapie. 1994;49:101-5.
25. Koopman MM, Prandoni P, Piovella F, Ockelford PA, Brandjes DP, van der Meer J, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecularweight heparin administered at home. The Tasman Study Group. N Engl J Med.
1996;334:682-7.
26. McGarry LJ, Thompson D, Weinstein MC, Goldhaber SZ. Cost effectiveness of thromboprophylaxis with a low-molecular- weight heparin versus unfractionated heparin in acutely ill medical inpatients. Am J Manag Care. 2004;10:632-42.
27. Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133(Suppl.):381S-453S.
28. Hirsh J, Dalen J, Guyatt G. American College of Chest Physicians. The sixth (2000) ACCP guidelines for antithrombotic therapy for prevention and treatment of thrombosis. American College of Chest
Physicians. Chest. 2001;119:1S-47S.
29. Forette B, Wolmark Y. Calcium nadroparin in the prevention of thromboembolic disease in elderly subjects. Study of tolerance. Presse Med. 1995;24:567-71.
30. Kadusevicius E, Kildonaviciute G, Varanaviciene B, Jankauskiene D. Low-molecular- weight heparins: Pharmacoeconomic decision modeling based on meta-analysis data. Int J Technol Assess Health
Care. 2010;26:272-9.
31. Shorr AF, Jackson WL, Weiss BM, Moores LK. Low-molecular weight heparin for deep vein thrombosis prophylaxis in hospitalized
medical patients: Results from a cost-effectiveness analysis. Blood Coagul Fibrinolysis. 2007;18:309-16.
32. Rodger M, Bredeson C, Wells PS, Beck J, Kearns B, Huebsch LB. Cost-effectiveness of low-molecular-weight heparin and unfractionated heparin in treatment of deep vein thrombosis. CMAJ. 1998;159:931-8.
33. Wilke T, Tesch S, Scholz A, Kohlmann T, Greinacher A. The costs of heparininduced thrombocytopenia: A patientbased cost of illness analysis. J Thromb Haemost. 2009;7:766-73.
34. Zawilska K, Jaeschke R, Tomkowski W, Mayzner-Zawadzka E, Nizankowski R, Olejek A, et al. Polish guidelines for the prevention and treatment of venous thromboembolism: 2009 update. Pol Arch Med Wewn. 2009;119(Suppl.1):1-69.
35. Magee KD, Sevcik W, Moher D, Rowe BH. Low molecular weight heparins versus unfractionated heparin for acute coronary syndromes. Cochrane Database Syst Rev. 2003;(1):CD002132.
36. van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation. G Ital Cardiol (Rome). 2009;10:450-89.
37. Tapson VF. Acute pulmonary embolism. N Engl J Med. 2008;358:1037-52.
38. Alonso JL, Abínzano ML, Urbieta MA, Annichérico FJ, Fernández V, García JL. Tratamiento de la trombosis venosa profunda con heparinas de bajo peso molecular: estudio comparativo con anticoagulación oral. An Med Interna (Madrid). 2008;25:4-8.
39. Shafiq N, Malhotra S, Pandhi P, Sharma N, Bhalla A, Grover A. A randomized controlled clinical trial to evaluate the efficacy, safety, cost-effectiveness and effect on PAI-1 levels of the three low-molecularweight heparins –enoxaparin, nadroparin and dalteparin. The ESCAPe-END study. Pharmacology. 2006;78:136-43.
40. Bergqvist D. Low-molecular-weight heparin for the prevention of postoperative venous thromboembolism after abdominal surgery: A review. Curr Opin Pulm Med. 2005;11:392-7.
41. Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, et al. Randomized comparison of low-molecular-weight heparin versus oral anticoagulant therapy for the prevention of recurrent venous thromboembolism in patients with cancer (CLOT) investigators. N Engl J Med. 2003;349:146-53.
42. Kanaan AO, Silva MA, Donovan JL, Roy T, Al-Homsi AS. Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients. 2007;29:2395-405.
43. Bermúdez AF, Bermúdez PV, Cano PC, Medina RM, Núñez PM, Restrepo H, et al. Heparinas de bajo peso molecular en la cardiopatía isquémica metabólica. Bases moleculares: experiencia clínica y resultados. AVFT. 2000;19: 82-97.
44. García JR, López F, Asis C. Tratamiento a largo plazo de coagulación intravascular diseminada crónica con heparina de bajo peso molecular. An Med Interna (Madrid). 2003;20:35-8.
45. Bounameaux H, Huber O, Khabiri E, Schneider PA, Didier D, Rohner A, Unexpectedly high rate of phlebographic deep venous thrombosis following elective general abdominal surgery among patients given prophylaxis with lowmolecular-weight heparin. Arch Surg. 1993;128(3):326-8.
46. Eurin B. Efficacy and tolerance of fraxiparine in the prevention of deep vein thrombosis in general surgery performed with medullar conduction anesthesia. Ann Fr Anesth Reanim. 1994;13:311-7.
47. European Fraxiparin Study. Comparison of a low molecular weight heparin and unfractionated heparin for the prevention of deep vein thrombosis in patients undergoing abdominal surgery. Br J Surg. 1988;75:1058-63.
48. Kakkar VV, Murray WJ. Efficacy and safety of low-molecular-weight heparin (CY216) in preventing postoperative venous thrombo-embolism: A co-operative study. Br J Surg. 1985;72:786-91.
49. Pezzuoli G, Neri GG, Settembrini P, Coggi G, Olivari N, Buzzetti G, et al. Prophylaxis of fatal pulmonary embolism in general surgery using low-molecular weight heparin Cy 216: A multicentre, double-blind, randomized, controlled, clinical trial versus placebo (STEP). Int
Surg. 1989;74:205-10.
50. Hamulyák K, Lensing AW, van der Meer J, Smid WM, van Ooy A, Hoek JA. Subcutaneous low-molecular weight heparin or oral anticoagulants for the prevention of deep-vein thrombosis in elective hip and knee replacement? Fraxiparine Oral Anticoagulant Study Group. Thromb Haemost. 1995;74:1428-31.
51. Leyvraz PF, Bachmann F, Hoek J, Büller HR, Postel M, Samama M, et al. Prevention of deep vein thrombosis after hip replacement: Randomized comparison between unfractionated heparin and low molecular weight heparin. BMJ. 1991;303:543-8.
52. German Hip Arthroplasty Trial (GHAT). Prevention of deep vein thrombosis with low molecular-weight heparin in patients undergoing total hip replacement. A randomized trial. Arch Orthop Trauma Surg. 1992;111:110-20.
53. Simonneau G, Laporte S, Mismetti P, Derlon A, Samii K, Samama CM, et al. A randomized study comparing the efficacy and safety of nadroparin 2,850 IU (0.3 ml) vs. enoxaparin 4,000 IU (40 mg) in the prevention of venous thromboembolism after colorectal surgery for cancer. J Thromb Haemot. 2006;4:1693-700.
54. Gerkens S, Crott R, Closon MC, Horsmans Y, Beguin C. Comparing the quality of care across Belgian hospitals from medical
basic datasets: The case of thromboembolism prophylaxis after major orthopaedic surgery. J Eval Clin Pract. 2010;16:685-92.
55. Harenberg J, Roebruck P, Heene DL. Subcutaneous low-molecular-weight heparin versus standard heparin and the prevention of thromboembolism in medical inpatients. The Heparin Study in Internal Medicine Group. Haemostasis. 1996;26:127-39.
56. van Dongen CJ, MacGillavry MR, Prins MH. Once versus twice daily LMWH for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev. 2005;3:CD003074.
57. van Dongen CJ, van den Belt AG, Prins MH, Lensing AW. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev. 2004;4:CD001100.
58. García RM, Antuña MT, Lapuerta JA, Gutiérrez M J. Hematoma abdominal secundario al empleo de nadroparina. An Med Interna (Madrid). 2004;21: 612.
59. Sanofi Pharma. Fraxiparine technical brochure. France Sanofi Pharma; 1995.
60. Schindewolf M, Schwaner S, Wolter M, Kroll H, Recke A, Kaufmann R, et al. Incidence and causes of heparin-induced skin
lesions. CMAJ. 2009;181:477-81.
61. Aster RH. Heparin-induced thrombocytopenia and thrombosis (letter). N Engl J Med. 1995;332:1374-6.
62. Greinacher A. Heparin-induced thrombocytopenia. J Thromb Haemost. 2009;7(Suppl.1):9-12.
63. Battistelli S, Genovese A, Gori T. Heparininduced thrombocytopenia in surgical patients. Am J Surg. 2010;199:43-51.
64. Maraveyas A, Johnson MJ, Xiao YP, Noble S. Malignant melanoma as a target malignancy for the study of the anti-metastatic properties of the heparins. Cancer Metastasis Rev. 2010;29(4):777-84.
65. Borsig L. Heparin as an inhibitor of cancer progression. Prog Mol Biol Transl Sci. 2010;93:335-49.
66. Nagy Z, Turcsik V, Blaskó G.The effect of LMWH (nadroparin) on tumor progression. Pathol Oncol Res. 2009;15:689-92.
67. Klerk CP, Smorenburg SM, Otten HM, Lensing AW, Prins MH, Piovella F, et al. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol. 2005;23:2130-5.
68. Debergh I, van Damme N, Pattyn P, Peeters M, Ceelen WP. The low-molecular- weight heparin, nadroparin, inhibits tumour angiogenesis in a rodent dorsal skinfold chamber model. Br J Cancer.
2010;102:837-43.
69. Mousa SA, Linhardt R, Francis JL, Amirkhosravi A. Anti-metastatic effect of a non-anticoagulant low-molecular-weight heparin versus the standard low-molecular-weight heparin, enoxaparin. Thromb Haemost. 2006;96(6):816-21.
70. van Sluis GL, Nieuwdorp M, Kamphuisen PW, van der Vlag J, van Noorden CJ, Spek CA. A low molecular weight heparin inhibits experimental metastasis in mice independently of the endothelial glycocalyx. PLoS One. 2010;5:e11200.
Cómo citar
Ospina-González, D. A., Martínez, J. A., & Cifuentes, L. F. (2011). Nadroparina cálcica: una revisión de su farmacología básica y clínica. Universitas Medica, 52(4), 371–398. https://doi.org/10.11144/Javeriana.umed52-4.ncrf
Número
Sección
Artículos originales