Morales PMR, López-Velarde BP, Gómez ME, Murillo MEE

Idioma: Español
Referencias bibliográficas: 34
Paginas: 192-197
Archivo PDF: 120.12 Kb.

RESUMEN

El síndrome de trombocitopenia provocada por heparina se caracteriza por trombocitopenia, trombosis o ambos, entre otras manifestaciones; se relaciona con heparina estándar o de bajo peso molecular. Es más frecuente con la primera (promedio, 6.5%) que con heparina de bajo peso molecular (‹1%) y se asocia con el origen de la heparina, tiempo de exposición a ésta, población estudiada y sexo del paciente. Sus manifestaciones clínicas son variadas y las más graves son las trombosis venosas o arteriales que pueden ser incapacitantes e inclusive mortales. La fisiopatogenia del síndrome se relaciona con la aparición de anticuerpos anti heparina- factor 4 plaquetario que activan plaquetas y células endoteliales, entre otras, y mediadores de la inflamación, todos responsables de eventos que culminan con la formación paradójica de trombos. El tratamiento requiere un diagnóstico clínico temprano e incluye suspensión de la heparina, su cambio a inhibidores directos de trombina como lepidurina y argatrobán o del factor Xa como danaparoid o fondaparinux. La posible aparición del síndrome se debe tener presente siempre que se utilice heparina y por sus repercusiones tan graves es importante evitar su empleo indiscriminado y conocer sus manifestaciones indeseables, en particular el síndrome motivo de la presente revisión.

REFERENCIAS (EN ESTE ARTÍCULO)

1. Hirsch DR, Ingenito EP, Goldhaber SZ. Prevalence of deep venous thrombosis among patients in medical intensive care. JAMA 1995; 274: 335-337.

2. Warketin TE, Kelton GJ. A 14 year study of heparin-induced thrombocytopenia. Am J Med 1996; 101: 502-507.

3. Nand S, Wong W, Yuen B, Yetter A, Schmulbach E, Gross Fisher S. Heparin-induced thrombocytopenia with thrombosis: Incidence, analysis of risks factors, and clinical outcomes in 108 consecutive patients treated at a single institution. Am J Hematol 1997; 56: 12-16.

4. Randolph AG, Cook DJ, Gonzales CA, Andrew M. Benefit of heparin in central venous and pulmonary artery catheters: a meta-analysis of randomized controlled trials. Chest 1998; 113: 161-171.

5. Heeger PS, Backstrom JR. Heparin flushes and thrombocytopenia [letter]. Ann Intern Med 1986; 105: 143.

6. Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995; 332: 1330-1335.

7. Creager MA, Beckman JA. Assesment of arterial and venous thrombosis. In: Loscalzo J, Schafer A (eds). Thrombosis and Hemorrhage. Baltimore: Williams and Wilkins, 1998. p. 491.

8. Hirsh J, Warkentin TE, Saughnessy SG, Anand SS, Halperin JL, Raschke R, Granger Ch, Ohman EM, Dalen JE. Heparin and low-molecular-weight heparin: Mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy and safety. Chest 2001; 119: 64S-94S.

9. Rice L, Attisha WK, Drexler A, Francis JL. Delayed-onset heparin-induced thrombocytopenia. Ann Intern Med 2002; 136: 210-215.

10. Ahmad S, Igbal O, Tobu M, Demir M. Immunobiology and pathophysiology of heparin-induced thrombocytopenia/trombosis syndrome-An update. Turk J Haematol 2002; 19: 127-131.

11. Fabris F, Ahmad S, Cella G, Jeske WP, Walenga JM, Fareed J. Pathophysiology of heparin-induced thrombocytopenia. Clinical and diagnostic implications-a review. Arch Pathol Lab Med 2000; 124: 1657-1666.

12. Schmugge M, Risch L, Huber AR, Benn A, Fischer J. Heparin-induced thrombocytopenia-associated thrombosis in pediatric intensive care patients. Pediatrics 109; 10: 1-4.

13. Warkentin TE, Kelton JG. Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med 2001; 344: 1286-1292.

14. Warketin TE, Chong BH, Greinacher A. Heparin-induced thrombocytopenia. Towards consensus. Thromb Haemost 1998; 79: 1-7.

15. Brandt E, Flad HD. Structure and function of platelet-derived cytokines of the Beta-thromboglobulin/interleukin 8 family. Platelets 1992; 3: 295-298.

16. Amiral, Marfaing-Koka A, Poncz M, Meyer D. The biological basis of immune heparin-induced thrombocytopenia. Platelets 1998; 9: 77-82.

17. Bock PE, Luscombe M, Marshall SE,Pepper DS, Holbrook JJ. The multiple complexes formed by the interaction of platelet factor IV with heparin. Biochem J 1980; 191: 769-76.

18. Ahmad S, Walenga JM, Jeske WP, Cella G, Fareed J. Functional heterogeneity of antiheparin-platelet factor IV antibodies: Implications in the pathogenesis of HIT syndrome. Clin Appl Thromb Hemost 1999; 5 (suppl I): 32 A.

19. Amiral J, Bridey F, Dreyfus M, Vissoc AM, Fressinaud E, Wolf M, Meyer D. Platelet factor IV complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia. Thromb Haemost 1992; 68: 95-96.

20. Warketin TE, Soutar RI, Panju A, Ginsberg JS. Acute systemic reactions to IV bolus heparin therapy: Characterization and relationship to heparin-induced thrombocytopenia (Abstract). Blood 1992; 80 (suppl 1): 160a.

21. Rosenzweig A. Endothelial progenitor cells. N Engl J Med 2003; 348: 581-582.

22. Hughes M, Hayward CPM, Warketin TE, Horsewood P, Cherneyko KA, Kelton JG. Morphological analysis of microparticle generation in heparin-induced thrombocytopenia. Blood 2000; 96: 188-194.

23. Walenga JM, Lewis BE, Hoppensteadt DA, Wood JJ, Ahmad S, Bakhos M. Management of heparin-induced thrombocytopenia and heparin-induced thrombocytopenia with thrombosis syndrome. Clin Appl Thromb Haemat 1997; 3 (suppl 1): 53A.

24. Girolami B, Girolami A. Heparin Induced Thrombocytopenia: A review. Semin Thromb Hemost 2006; 32: 803-809.

25. Fareed J, Walenga JM, Hoppensteadt DA, Jeske WP, Lietz H, Ahmad S, Callas D, Messmore HL, Haas S. Selectins in the HIT syndrome: Pathophysiologic role and therapeutic modulation. Semin Thromb Hemost 1999; 25 (suppl 1): 37.

26. Pötszch B, Klövekorn WP, Madlener K. Use of heparin during cardiopulmonary bypass in patients with a history of heparin-induced thrombocytopenia. N Engl J Med 2000; 343: 515.

27. Breddin HKL, Hach-Wunderle V, Nakov R, Kakkar VV, for the CORTES Investigators. Effects of a low-molecular-weight heparin on thrombus regression and recurrent thromboembolism in patients with deep-vein thrombosis. N Engl J Med 2001; 344: 626-631.

28. Ahmad S, Lietz H, Daud AN. Upregulation of tissue factor pathway inhibitor by a low-molecular-weight heparin, clivarin, is associated with decreased prevalence of antiheparin-PF 4 antibodies: Diagnostic and therapeutic implications. Int Angiol 2001; 20 (suppl 1): 42A.

29. Untch B, Ahmad S, Jeske WP, Messmore Hl, Hopenssteadt DA, Walenga JM, Lietz H, Fareed J. Prevalence, isotype and functionality of anti-heparin-platelet factor IV antibodies in patients treated with heparin and clinically suspected for heparin-induced thrombocytopenia: The pathogenic role of IgG. Thromb Res 2002; 105: 17.

30. Lindhoff-Last E, Gerdsen F, Acherman H, Bauersacks R. Determination of heparin-platelet factor 4-IgG antibodies improves diagnosis of heparin-induced thrombocytopenia. Br J Haematol 2001; 113: 886-889.

31. Amiral J, Wolf M, Fischer AM, Beyer-Neumann C, Vissar A, Meyer D. Pathogenicity of IgA and/or IgM antibodies to heparin-PF 4 complexes with heparin-induced thrombocytopenia. Br J Haematol 1996; 92: 954-959.

32. Warkentin TE, Kelton JG. A 14-year study of heparin induced thrombocytopenia. Am J Med 1996; 101: 502–507.

33. Arthur CK, Grant SJB, Murray WK, Isbister JP, Stiel JN, Lauer CS. Heparin associated acute adrenal insufficiency. Aust NZ J Med 1985; 15: 454–455.

34. Warkentin TE, Hirte HW, Anderson DR,Wilson WE, O’Conell GJ, Lo RC. Transient global amnesia associated with acute heparin-induced thrombocytopenia. Am J Med 1994; 97: 489–491.