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Heparin-Induced Thrombocytopenia

Minimising the Risks in the Elderly Patient

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Abstract

Heparin therapy may sometimes be seriously complicated by heparin-induced thrombocytopenia (HIT). Heparin use for treatment and prevention of thromboembolism is more common in the elderly and that may be the reason why HIT is reported more frequently in this group of patients. The first approach in the management of HIT is awareness of this disorder. The morbidity and mortality associated with HIT may be reduced by avoiding unnecessary heparin exposure, by reducing the duration of heparinisation and by using low molecular weight heparins rather than unfractionated heparin. A decrease from baseline values of at least 30% in the platelet count, any unexplained thrombotic event and the finding of a white clot at thrombectomy are clinical warning signs that should alert physicians to a possible diagnosis of HIT. Indeed, early clinical recognition of HIT may sometimes prevent the severe complications associated with this disorder. Objective confirmation of the diagnosis of HIT is difficult because none of the available biological tests possess 100% sensitivity or 100% specificity. It is, however, possible to optimise the performances of the functional assay, mainly the platelet aggregation test (PAT), by following the manoeuvres described by different investigators. The use of 2 classes of assay (functional and antigen assays) and repeat testing on another day can avoid misdiagnosis of HIT. An alternative parenteral anticoagulant treatment is most often mandatory after heparin withdrawal. Danaparoid sodium and lepirudin are 2 drugs that are currently available for the treatment of HIT, and the efficacy of argatroban needs to be confirmed in greater numbers of patients with HIT. The use of these drugs has contributed to the reduction in the mortality and morbidity associated with HIT.

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References

  1. Boon DMS, Kappers-Klunne MC, Michiels JJ, et al. Heparin-induced thrombocytopenia and thrombosis: a potential fatal complication in a routine treatment. Neth J Med 1995; 46: 146–52

    Article  PubMed  CAS  Google Scholar 

  2. Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med 1996; 101: 502–7

    Article  PubMed  CAS  Google Scholar 

  3. Nand S, Wong W, Yuen B, et al. Heparin-induced thrombocytopenia with thrombosis: incidence, analysis of risk factors, and clinical outcomes in 108 consecutive patients treated at a single institution. Am J Hematol 1997; 56: 12–6

    Article  PubMed  CAS  Google Scholar 

  4. Magnani HN. Orgaran (danaparoid sodium) use in the syndrome of heparin-induced thrombocytopenia: proceedings of a workshop held in London, 1996 Nov 1. Platelets 1997; 8(1): 74–81

    Google Scholar 

  5. Tardy-Poncet B, Tardy B, Reynaud J, et al. Efficacy and safety of Orgaran (ORG 10172) in critically ill patients with heparin associated thrombocytopenia. Chest 1999; 115: 1616–20

    Article  PubMed  CAS  Google Scholar 

  6. Kelton JG, Sheridan D, Santos A, et al. Heparin-induced thrombocytopenia: laboratory studies. Blood 1988; 72: 925–30

    PubMed  CAS  Google Scholar 

  7. Warkentin TE, Kelton JG. Heparin-induced thrombocytopenia. Annu Rev Med 1989; 40: 31–44

    Article  PubMed  CAS  Google Scholar 

  8. Visentin GP, Ford SE, Scott JP, et al. Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells. J Clin Invest 1994; 93: 81–8

    Article  PubMed  CAS  Google Scholar 

  9. Greinacher A, Potzsch B, Amiral J, et al. Heparin-associated thrombocytopenia: isolation of the antibody and characterization of a multimolecular PF4-heparin complex as the major antigen. Thromb Haemost 1994; 71: 247–51

    PubMed  CAS  Google Scholar 

  10. Amiral J, Wolf M, Fischer AM, et al. Pathogenicity of IgA and/or IgM antibodies to heparin-Pf4 complexes in patients with heparin-induced thrombocytopenia [letter]. Br J Haematol 1996; 92: 954

    Article  PubMed  CAS  Google Scholar 

  11. Greinacher A. Antigen generation in heparin-associated thrombocytopenia: the nonimmunologic type and the immunologic type are closely linked in their pathogenesis. Thromb Haemost 1995; 21: 106–16

    Article  CAS  Google Scholar 

  12. Warkentin TE, Hayward CPM, Bochkov LK. Sera from patients with heparin-induced thrombocytopenia generate platelet derived microparticles with pro-coagulant activity an explanation for the thrombotic complications of heparin-induced thrombocytopenia [abstract]. Blood 1994; 84: 3691

    PubMed  CAS  Google Scholar 

  13. Cines DB, Tomaski A, Tannenbaum S. Immune endothelial-cell injury in heparin-associated-thrombocytopenia. N Engl J Med 1987; 316: 581–9

    Article  PubMed  CAS  Google Scholar 

  14. Zalcberg JR, McGrath K, Dauer R, et al. Heparin-induced thrombocytopenia with associated disseminated intravascular coagulation. Br J Haematol 1983; 54: 955–60

    Article  Google Scholar 

  15. Warkentin TE, Kelton JG. Heparin-induced thrombocytopenia. Prog Hemost Thromb 1991; 10: 1–34

    PubMed  CAS  Google Scholar 

  16. Tardy-Poncet B, Tardy B, Grelac F, et al. Pentosan polysulph-ate-induced thrombocytopenia and thrombosis. Am J Hematol 1994; 45: 252–7

    Article  PubMed  CAS  Google Scholar 

  17. Tardy B, Tardy-Poncet B, Zeni F, et al. Thrombocytopenia associated with low molecular weight heparin [letter]. Lancet 1991; 338: 1217

    Google Scholar 

  18. Doty JR, Alving BM, Mc Donnell DE, et al. Heparin-associated thrombocytopenia in the neurosurgical patient. Neurosurgery 1986; 19: 69–72

    Article  PubMed  CAS  Google Scholar 

  19. Chong BH. Heparin-induced thrombocytopenia. Br J Haematol 1995; 89: 431–9

    Article  PubMed  CAS  Google Scholar 

  20. Hirsch J, Raschke R, Warkentin TE, et al. Heparin: mechanism of action, pharmacokinetic, dosing considerations, monitoring, efficacy and safety. Chest 1995; 108 Suppl.: 258–75S

    Article  Google Scholar 

  21. Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low molecular weight heparin or unfractionated heparin. N Engl J Med 1995; 332: 1330–5

    Article  PubMed  CAS  Google Scholar 

  22. Wallis DE, Workman DL, Lewis BE, et al. Failure of early heparin cessation as treatment for heparin-induced thrombocytopenia. Am J Med 1999; 106: 629–35

    Article  PubMed  CAS  Google Scholar 

  23. Boskhov LK, Warkentin TE, Hayward CPM, et al. Heparin-induced thrombocytopenia and thrombosis: clinical and laboratory studies. Br J Haematol 1993; 84: 322–8

    Article  Google Scholar 

  24. Belmain J, Trivalle C, Medjahed S, et al. Use of low molecular weight heparin in geriatric hospitals and institutions in France: a national one-day survey in 97 centers [abstract]. Haemostasis 1998; S2: 297

    Google Scholar 

  25. Gallus AS, Jackaman J, Tillett J, et al. Safety and efficiency of warfarin started early after submissive venous thrombosis or pulmonary embolism. Lancet 1986; II: 1293–6

    Article  Google Scholar 

  26. Chong BH. Heparin-induced thrombocytopenia. Aust N Z J Med 1992; 22: 145–52

    Article  PubMed  CAS  Google Scholar 

  27. Erni J, Frey HR, Locher G. The heparin-induced thrombosis-thrombocytopenia syndrome. Dtsch Med Wochenschr 1987; 112: 801–5

    Article  PubMed  CAS  Google Scholar 

  28. Ansell J, Deykin D. Heparin-induced thrombocytopenia and recurrent thromboembolism. Am J Hematol 1980; 8: 325–2

    Article  PubMed  CAS  Google Scholar 

  29. Hach-Wunderle V, Kainer K, Krug B. Heparin-associated thrombosis despite normal platelet counts. Lancet 1994; 344: 469–70

    PubMed  CAS  Google Scholar 

  30. Leroy J, Leclerc MH, Delahousse B. Treatment of heparin-associated thrombocytopenia and thrombosis with low molecular weight heparin (CY216). Semin Thromb Haemost 1985; 11: 326–9

    Article  CAS  Google Scholar 

  31. Buge A, Poisson M, Vidhaillet M, et al. Thrombopenia and disseminated intravascular coagulation during treatment with heparin: two cases with neurological complications. Rev Neu-rol 1988; 144: 289–94

    CAS  Google Scholar 

  32. Warkentin TE. Heparin-induced skin lesions. Br J Haematol 1996; 92: 494–7

    Article  PubMed  CAS  Google Scholar 

  33. Warkentin TE. Heparin-induced thrombocytopenia, heparin-induced skin lesions, and arterial thrombosis [abstract]. Thromb Haemost 1997; Suppl.: 562

    Google Scholar 

  34. Silver D, Kapsch D, Tsoi E. Heparin-induced thrombocytopenia, thrombosis and hemorrahge. Ann Surg 1983; 198: 301–6

    Article  PubMed  CAS  Google Scholar 

  35. Laster J, Cikrit D, Walker N, et al. The heparin-induced throm-bocytopenia syndome: an update. Surgery 1987; 102: 763–8

    PubMed  CAS  Google Scholar 

  36. Greinacher A, Amiral J, Dummel V. Laboratory diagnosis of heparin-associated thrombocytopenia and comparison of platelet aggregation test, heparin-induced platelet activation test and platelet factor 4/heparin enzyme linked immunosorbent assay. Transfusion 1994; 34: 381–5

    Article  PubMed  CAS  Google Scholar 

  37. Sheridan D, Carter C, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia. Blood 1986; 67: 27–30

    PubMed  CAS  Google Scholar 

  38. Chong BH, Burgess J, Ismail F. The clinical usefulness of the platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia. Thromb Haemost 1993; 69: 344–50

    PubMed  CAS  Google Scholar 

  39. Brandt J, Isenhart CE, Osborne JM. On the role of platelet FCγ IIA phenotype in heparin-induced thrombocytopenia. Thromb Haemost 1995; 74: 1564–72

    PubMed  CAS  Google Scholar 

  40. Lecompte T. Drug-dependent platelet activating IgG: heparin and streptokinase. In: Seghatchian MJ, Samama MM, Hecker SP, editors. Hypercoagulable states. New York (NY): CRC Press, 1996: 173–8

    Google Scholar 

  41. Isenhart CE, Brandt JT. Platelet aggregation studies for the diagnosis of heparin-induced thrombocytopenia. Am J Clin Pathol 1993; 99: 324–30

    PubMed  CAS  Google Scholar 

  42. Salem HH, van der Weyden MB. Heparin-induced thrombo-cytopenia: variable platelet rich plasma reactivity to heparin dependent aggregating factor. Pathology 1983; 15: 297–9

    Article  PubMed  CAS  Google Scholar 

  43. Greinacher A, Michels I, Liebenhoff U, et al. Heparin-associated thrombocytopenia: immune complexes are attached to the platelet membrane by the negative charge of highly sulphated oligosaccharides. Br J Haematol 1993; 84: 711–6

    Article  PubMed  CAS  Google Scholar 

  44. Salzman EW, Rosenberg RD, Smith MH, et al. Effect of heparin and heparin fractions on platelet aggregation. J Clin Invest 1980; 65: 64–73

    Article  PubMed  CAS  Google Scholar 

  45. Greinacher A, Michels I, Kiefel V. Arapid and sensitive test for diagnosing heparin-associated thrombocytopenia. Thromb Haemost 1991; 66: 734–6

    PubMed  CAS  Google Scholar 

  46. Amiral J, Bridey F, Dreyfus M. Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-in-duced thrombocytopenia. Thromb Haemost 1992; 68: 95–6

    PubMed  CAS  Google Scholar 

  47. Arepally G, Reynolds C, Tomaski A, et al. Comparison of PF4/heparin ELISA with the 14C serotonin release assay in the diagnosis of heparin-induced thrombocytopenia. Am J Clin Pathol 1995; 104: 648–54

    PubMed  CAS  Google Scholar 

  48. Amiral J, Marfaing-Koka A, Wolf M. Presence of auto-antibodies to interleukin 8 or neutrophil activating peptide-2 in patients with heparin-associated thrombocytopenia. Blood 1996; 88: 410–6

    PubMed  CAS  Google Scholar 

  49. Amiral J. Diagnostic tests in heparin-induced thombocyto-penia: proceedings of a workshop held in London on 1 November 1996. Heparin-induced thrombocytopenia: an under-diagnosed syndrome? Platelets 1997; 8: 65–82

    Article  Google Scholar 

  50. Hirsh J, Warkentin TE, Raschke R, et al. Heparin and low molecular weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998; 114: 489S–510S

    Article  PubMed  CAS  Google Scholar 

  51. Tardy B, Tardy-Poncet B, Fournel P, et al. Lower limb veins should be systematically explored in patients with isolated heparin-induced thrombocytopenia. Thromb Haemost 1999; 82: 1199–200

    PubMed  CAS  Google Scholar 

  52. Tardy-Poncet B, Mahul P, Beraud AM, et al. Failure of Orgaran therapy in a patient with a previous heparin-induced thrombocytopenia syndrome. Br J Haematol 1995; 90: 969–70

    Article  CAS  Google Scholar 

  53. Tardy B, Tardy-Poncet B, Viallon A. Fatal danaparoid sodium-induced thrombocytopenia and thromboses [letter]. Thromb Haemost 1998; 80: 530

    PubMed  CAS  Google Scholar 

  54. Meuleman DG. Orgaran (Org 10172): its pharmacological profile in experimental models. Haemostasis 1992; 22: 58–65

    PubMed  CAS  Google Scholar 

  55. ten Cate H, Henny CP, ten Cate JW, et al. Anticoagulant effects of a low molecular weight heparinoid (Org10172) inhuman volunteers and haemodialysis patients. Thromb Res 1985; 38: 211–22

    Article  Google Scholar 

  56. ten Cate H, Lamping RJ, Henny CP, et al. Automated amidolytic method for determining heparin, a heparinoid and a low-Mr heparin fragment, based on their anti-Xa activity. Clin Chem 1984; 30(6): 860–4

    PubMed  Google Scholar 

  57. Bradbrook ID, Magnani HN, Moelker HC, et al. Org 10172: a low molecular weight heparinoid anticoagulant with a long half-life in man. Br J Clin Pharmacol 1987; 23: 667–75

    Article  PubMed  CAS  Google Scholar 

  58. Henny CP, ten Cate H, ten Cate JW, et al. Thrombosis prophylaxis in an ATIII deficient pregnant woman: application of a low molecular weight heparinoid [letter]. Thromb Haemost 1986; 55: 301

    PubMed  CAS  Google Scholar 

  59. Magnani HN. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with Orgaran (Org 10172). Thromb Haemost 1993; 70: 554–61

    PubMed  CAS  Google Scholar 

  60. Greinacher A, Eckhardt T, Mussmann J. Pregnancy complicated by heparin-associated thrombocytopenia: management by prospectively in vitro selected heparinoid (Org 10172). Thromb Res 1993; 71: 123–6

    Article  PubMed  CAS  Google Scholar 

  61. Mikhailidis DP, Barradas MA, Mikhailidis AM, et al. Comparison of the effect of a conventional heparin and a low molecular weight heparinoid on platelet function. Br J Clin Pharmacol 1984; 17: 43–8

    Article  PubMed  CAS  Google Scholar 

  62. Mikhailidis DP, Fonseca VA, Barradas MA, et al. Platelet activation following intravenous injection of a conventional heparin: absence of effect with a low molecular weight heparinoid (Org 10172). Br J Clin Pharmacol 1987; 24: 415–24

    Article  PubMed  CAS  Google Scholar 

  63. Chong BH, Magnani HN. Orgaran in heparin-induced thrombocytopenia. Haemostas is 1992; 22: 85–91

    CAS  Google Scholar 

  64. Ramakrishna R, Manoharan A, Kwan YL. Heparin-induced thrombocytopenia: cross-reactivity between standard heparin, low molecular weight heparin, dalteparin (Fragmin), and heparinoid, danaparoid (Orgaran). Br J Haematol 1995; 91: 736–8

    Article  PubMed  CAS  Google Scholar 

  65. Wilde MI, Markham A. Danaparoid: a review of its pharmacology and clinical use in the management of heparin-induced thrombocytopenia. Drugs 1997; 6: 903–24

    Article  Google Scholar 

  66. Chong BH, Ismail F, Cade J. Heparin-induced thrombocytopenia: studies with a new low molecular weight heparinoid, Org 10172. Blood 1989; 73: 1592–6

    PubMed  CAS  Google Scholar 

  67. Rowlings PA, Mansberg R, Rozenberg MC, et al. The use of a low molecular weight heparinoid (Org 10172) for extracorporeal procedures in patients with heparin-dependent thrombocytopenia and thrombosis. Aust N Z J Med 1991; 21: 52–4

    Article  PubMed  CAS  Google Scholar 

  68. Tardy-Poncet B. French experience in the use of Orgaran as an alternative antithrombotic treatment for patients with hepa-rin-induced thrombocytopenia [abstract]. Thromb Haemost 1997; Suppl.: 1825

    Google Scholar 

  69. Greinacher A, Vôlpel H, Janssens U, et al. Recombinant hirudin (lepirudin) provides safe and effective anticoagulation in patients with heparin-induced thrombocytopenia: a prospective study. Circulation 1999; 99: 73–80

    Article  PubMed  CAS  Google Scholar 

  70. Greinacher A, Janssens U, Berg G, et al. Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Circulation 1999; 100: 587–93

    Article  PubMed  CAS  Google Scholar 

  71. Eichler P, Greinacher A. Anti-hirudin antibodies induced by recombinand hirudin in the treatment of patients with hepa-rin-induced thrombocytopenia [abstract]. Ann Hematol 1996; 72 Suppl.: A4

    Google Scholar 

  72. Schwarz RP. Update on the clinical development of Novastan (Argatroban): a small-molecule direct thrombin inhibitor. In: Zavoico G, editor. Advances in anticoagulant and antithrombotic drugs, IBC Biomedical Library Series. Southborough (MA): International Business Communication Inc., 1996

    Google Scholar 

  73. Lewis BE, Walenga JM, Wallis DW. Anticoagulation with Novastan (argatroban) in patients with heparin-induced throm-bocytopenia and heparin-induced thrombocytopenia and thrombosis syndrome. Semin Thromb Hemost 1997; 23: 197–202

    Article  PubMed  CAS  Google Scholar 

  74. Weitz JL, Hudoba M, Massel D, et al. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. J Clin Invest 1990; 86: 385–91

    Article  PubMed  CAS  Google Scholar 

  75. Willerson JT, Casscells W. Thrombin inhibitors in unstable angina: rebound or continuation of angina after argatroban withdrawal? J Am Coll Cardiol 1993; 21: 1048–51

    Article  PubMed  CAS  Google Scholar 

  76. Wallis DE, Lewis BE, Messmore H. Heparin-induced thrombocytopenia and thrombosis syndrome. Clin Appl Thromb Hemost 1998; 4: 160–3

    Article  Google Scholar 

  77. Warkentin TE, Elavathil LJ, Hayward CPM, et al. The pathogenis of venous limb gangrene associated with heparin-in-duced thrombocytopenia. Ann Intern Med 1997; 127: 804–12

    PubMed  CAS  Google Scholar 

  78. Cairns JA, Kennedy JW, Fuster V. Coronary thrombolysis. Chest 1998; 114: 634–57S

    Article  Google Scholar 

  79. Meneveau N, Bassand JP, Schiele F, et al. Safety of thrombolytic therapy in the elderly patients with massive embolism: a comparison with non-elderly patients. J Am Coll Cardiol 1993; 22: 1075–9

    Article  PubMed  CAS  Google Scholar 

  80. Kanter DS, Mikkola KM, Patel SR, et al. Thrombolytic therapy for pulmonary embolism: frequency of intracranial hemorrhage and associated factors. Chest 1997; 111: 1241–5

    Article  PubMed  CAS  Google Scholar 

  81. Decousus H, Leizorovicz A, Parent F, et al. A clinical trial of vena cava filters in the prevention of pulmonary embolism in patients with proximal deep vein thrombosis. N Engl J Med 1998; 338: 409–15

    Article  PubMed  CAS  Google Scholar 

  82. Sobel M, Adelman B, Szentpetery S, et al. Surgical management of heparin-associated thrombocytopenia: strategies in the treatment of venous and arterial thromboembolism. J Vasc Surg 1988; 8: 395–401

    PubMed  CAS  Google Scholar 

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  1. Department of Haematology, University Hospital of St Etienne, Etienne, France

    Brigitte Tardy-Poncet

  2. Intensive Care Unit, University Hospital of St Etienne, Etienne, France

    Bernard Tardy

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  1. Brigitte Tardy-Poncet
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Tardy-Poncet, B., Tardy, B. Heparin-Induced Thrombocytopenia. Drugs & Aging 16, 351–364 (2000). https://doi.org/10.2165/00002512-200016050-00005

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