Heparin-induced thrombocytopenia. Pathogenesis, frequency, avoidance and management

Drug Safety

Volumn 17, Issue 5, 1997, Pages 325-341

  Warkwntin, Theodore E ^a,b  

^a MCMASTER UNIVERSITY   (Canada)

^b HAMILTON HEALTH SCIENCES   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANTITHROMBIN; ARGATROBAN; FC RECEPTOR; HEPARIN; IMMUNOGLOBULIN G; LEPIRUDIN; THROMBIN; THROMBOCYTE FACTOR 4; THROMBOCYTE RECEPTOR; WARFARIN;

DEEP VEIN THROMBOSIS; NECROSIS; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN C DEFICIENCY; REVIEW; THROMBOCYTE ACTIVATION; THROMBOCYTOPENIA;

EID: 0030722915     PISSN: 01145916     EISSN: None     Source Type: Journal    
DOI: 10.2165/00002018-199717050-00005     Document Type: Review

References (111)

1. Rhodes GR, Dixon RH, Silver D. Heparin induced thrombocytopenia with thrombotic and haemorrhagic manifestations. Surg Gynecol Obstet 1973; 136: 409-16
2. Fratantoni JC, Pollet R, Gralnick HR. Heparin-induccd thromhocytopcnia: confirmation of diagnosis with in vitro methods. Blood 1975; 45: 395-401
3. Babcock RB, Dumper CW, Scharfman WB. Heparin-induced immune thromhocytopenia. N Engl J Med 1976; 295: 237-41
4. Chong BH, Grace CS, Rozenherg MC. Heparin-induccd thrombocytopenia: effect of heparin platelet antibody on platelets. Br J Haematol 1981; 49: 531-40
5. Kelton JG, Sheridan D, Santos A, et al. Heparin-induced thromhocytopenia: laboratory studies. Blood 1988; 72: 925-30
6. Aster RH. Heparin-induced thromhocytopenia and thrombosis [editorial]. N Engl J Med 1995; 332: 1374-6
7. Warkentin TE, Kelton JG. Heparin-induccd thrombocytopenia. Prog Hemost Thromb 1991; 10: 1-34
8. Greinacher A. Antigen generation in heparin-associated thrombocytopenia: the nonimmunologic type and the immunologic type are closely linked in their pathogenesis. Semin Thromb Hemost 1995; 21: 106-16
9. Amiral J, Bridey F, Dreyfus M, et al. Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thromhocytopenia [letter]. Thromb Haemost 1992; 68: 95-6
10. Visentin GP, Ford SE, Scott JP, et al. Antibodies from patients with heparin-induccd thromhocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells. J Clin Invest 1994; 93: 81-8
11. Greinacher A, Potzsch B, Amiral J, et al. Heparin-associated thrombocytopenia: isolation of the antibody and characterization of a multimoleculur PF4-heparin complex as the major antigen. Thromb Haemost 1994; 71: 247-51
12. Kelton JG, Smith JW, Warkentin TE, et al. Immumiglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4. Blood 1994; 83: 3232-9
13. Greinacher A, Michels I, Kiefel V, et al. A rapid and sensitive test for diagnosing heparin-associated thrombocytopenia. Thromb Haemost 1991; 66: 734-6
14. Chong BH, Murray B, Berndt MC, et al. Plasma P-selectin is increased in thrombotic consumptive platelet disorders. Blood 1994; 83: 1535-41
15. Sheridan D, Carter C, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia. Blood 1986; 67: 27-30
16. Warkentin TE, Hayward CPM, Smith CA, et al. Determinants of donor platelet variability when testing for heparin-induced thromhocytopenia. J Lab Clin Med 1992; 120: 371-9
17. Warkenlin TE, Hayward CPM, Boshkov LK, et al. Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparininduced thrombocytopenia. Blood 1994; 84: 3691-9
18. Lee DH, Warkentin TE, Denomme GA, et al. A diagnostic test for heparin-induced thrombocytopenia: detection of platelet microparticles using flow cytometry. Br J Huematol 1996; 95: 724-31
19. Warkentin TE. Heparin-induccd thrombocytopenia: IgG-mediated platelet activation, platelet microparticle generation, and altered procoagulant/anticoagulant balance in the pathogenesis of thrombosis and venous limb gangrene complicating heparin-induccd thrombocytopenia. Transfus Med Rev 1996; 10: 249-58
20. Warkentin TE, Elavathil LJ, Hayward CPM, et al. The pathogenesis of vennus limb gangrene associated with heparin-induccd thrombocylopenia. Ann Intern Med 1997; 127: 804-12
21. Warkentin TE. Danaparoid (Orgaran®) for the treatment of heparin-induccd thrombocytopenia (HIT) and thrombosis: effects on in vivo thrombin and cross-linked fibrin generation, and evaluation (if the clinical significance of in vitro cross-reactivity (XR) of danaparoid for HIT-lgG. Blood 1996; 88 Suppl. 1:626a
22. Leroy J, Leclerc MH, Delahousse B, et al. Treatment of heparin-associated thrombocytopenia and thrombosis with low molecular weight heparin (CY 216). Semin Thromb Hemost 1985; 11: 326-9
23. Zuleherg JR, McGrath K, Dauer R, et al. Heparin-induced thrombocylopenia with associated disseminated intravascular coagulation. Br J Haematol 1983; 54: 655-60
24. Warkentin TE, Levine MN, Hirsh J, et al. Hepurin-induced thromhocytonenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995; 132: 1330-5
25. Warkentin TE, Kelton JG, A 14-year study of heparin-induced thrombocylupenia. Am J Med 1996; 101: 502-7
26. Warkentin TE, Sheppard JI, Santos AV, Generation of plateletderived microparticles and procoagulant activity by IgG platelet agonists: comparison with standard platelet agonists [abstracl]. Blood 1994; 84 Suppl. 1: 528a
27. Cines DB, Tomaski A, Tannenbaum S. Immune endothelial-cell injury in heparin-associated thrombocytopenia. N Engl J Med 1987; 316: 581-9
28. Weitz JI, Hudoba M, Massel D, et al. Clot-bound thromhin is protected from inhibition by heparin-antithroinbin III hut is susceptible to inactivation by untithrombin III-independent inhibitors. J Clin Invest 1990; 86: 385-91
29. Cassel DL, Keller MA, Surrey S, et al. Differential expression of FeγRIIA, FeγRIIB, FeγRIIC in hematopoictic cells: analysis of transcripts. Mol Immunol 1993; 30: 451-60
30. Burgess JK, Lindeman R, Chesterman CM, et al. Single amino acid mutation of Fey receptor is associated with the development of heparin-induced thrombocytopenia. Br J Haemalol 1995; 91: 761-6
31. Brandt JT, Isenhart CE, Oshorne JM, et al. On the role of platelet FeγRIIa phenotype in heparin-induced thrombocytopenia. Thromb Haemost 1995; 74: 1564-72
32. 131) gene in patients with heparin-induced thrombocytopenia. J Lab Clin Med 1997; 130: 278-84
33. 131 polymorphism, subclass-specific IgG anti-heparin/platelet factor 4 antibodies and clinical course in patients with heparin-induccd thrombocytopenia and thrombosis. Blood 1997; 89: 370-5
34. Anderson CL, Ryan DH, Lunney RJ, et al. Structural polymorphism of the human monocyle 40 kilodalton Fe receptor for IgG. J Immunol 1987; 138: 2254-6
35. Horsewood P, Hayward CPM, Warkentin TE, et al. The investigation of the mechanisms of monoclonal antibody-induced platelet activation. Blood 1991; 78: 1019-26
36. Tomiyama Y, Kunicki TJ, Zipf TF, et al. Response of human platelets to activating monoclonal antibodies: importance of FCγRIl (CD32) phenotype and level of expression. Blood 1992; 80: 2261-8
37. Bachelot C, Saffroy R, Gandrille S, et al. Role of FcγRII A gene polymorphism in human platelet activation by monoclonal antibodies. Thromb Haemost 1995; 74: 1557-63
38. Warmerdam PAM. van de Winkel JGJ, Vlug A. et al. A single amino acid in the second Ig-like domain of the human Fc̀ receptor II is critical for human lgC2 binding. J Immunol 1991; 147: 1338-43
39. Suh JS, Malik MI, Aster RH, et al. Characterization of the humoral immune response in heparin-induced thrombocytopenia. Am J Hematol 1997; 54: 196-201
40. Greinacher A, Mueller-Eckhardt C, Heparin-associated thrombocytopenia: no association of immune response with HLA. Vox Sang 1993; 65: 151-3
41. Bertina RM, Koeleman BPC, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7
42. Lee DH, Warkentin TE, Denomme GA, et al. Factor V Leiden and thrombotic complications in heparin-induced thrombocytopenia. Thromb Haemost. In press
43. Phelan BK, Heparin-associated thrombosis without thrombocytopenia. Ann Intern Med 1983; 99: 637-8
44. Warkentin TE, Levine MN, Hirsh J, et al. Formation of heparin-induced thrombocytopenia IgG without thromhocytopenia: analysis of a clinical trial (abstract). Blood 1995; 86 Suppl. 1: 537a
45. Warkentin TE, Kellon JG. Interaction of heparin with platelets, including heparin-induced thrombocylopenia. In: Bounameaux H, editor. Low-molecular-weight heparins in prophylaxis and therapy of thromboembolic diseases. New York: Marcel Dekker, 1994: 75-127
46. Boshkov LK, Warkentin TE, Hayward CPM, et al. Heparin-induced thrombocylopenia and thrombosis: clinical and laboratory studies. Br J Haematol 1993; 84: 322-8
47. Arthur CK, Grant SJB, Murray WK, et al. Heparin-associated acute adrenal insufficiency. Aust N Z J Med 1985; 15: 454-5
48. Delhumcau A, Houel JF, Bourrier P, et al. Thrombopénies à l'héparine compliquées d'hématome des surrénales et d'insuffisance surrénalienne aiguë. Ann Fr Anesth Reanim 1989; 8: 656-8
49. Warkentin TE, Soutar RL, Panju A. et al. Acute systemic reactions to intravenous bolus heparin therapy: characterization and relationship to heparin-induced thrombocytopenia [abstract]. Blood 1992; 80 Suppl. 1: 160a
50. Warkentin TE, Hirte HW. Anderson DR. et al. Transient global amnesia associated with acute heparin-induced thrombocytopenia. Am J Med 1994; 97: 489-91
51. Warkentin TE. Heparin-induced skin lesions. Br J Haematol 1996; 92: 494-7
52. Warkentin TE. Heparin-induced thrombocytopenia, heparin-induced skin lesions, and arterial thrombosis [abstract]. Thromb Haemost 1997; Suppl: 562
53. Greinacher A, Amiral J, Dummel V, et al. 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
54. Favaloro EJ, Bernal-Hoyos E, Exner T, et al. Heparin-induced thrombocytopenia: laboratory investigation and confirmation of diagnosis. Pathology 1992; 24: 177-83
55. 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
56. 14C-serotonin release assay in the diagnosis of heparin-induced thrombocytopenia. Am J Clin Pathol 1995; 104: 648-54
57. Amiral J, Marfaing-Koka A, Wolf M, et al. Presence of autoantibodies to interleukin-8 or neutrophil-activaling peptide-2 in patients with heparin-associated thrombocytopenia. Blood 1996; 88: 410-6
58. 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. Br J Haematol 1996; 92: 954-9
59. 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
60. Singer RL, Mannion JD, Bauer TL, et al. Complications from heparin-induced thrombocytopenia in patients undergoing cardiopulmonary bypass. Chest 1993; 104: 1436-40
61. Reininger CB, Greinacher A, Graf J, et al. Platelets of patients with peripheral arterial disease are hypersensitive to heparin. Thromb Res 1996; 81: 641-9
62. Yamamoto S, Koide M, Matsuo M, et al. Heparin-induced thrombocytopenia in hemodialysis patients. Am J Kidney Dis 1996; 28: 82-5
63. Visentin GP, Malik M, Cyganiak KA, et al. Patients treated with unfractionated heparin during open heart surgery are at high risk from antibodies reactive with heparin: platelet factor 4 complexes. J Lab Clin Med 1996; 128: 376-83
64. Horsewood P, Warkentin TE, Hayward CPM, et al. The epitope specificity of heparin-induced thrombocytopenia. Br J Haematol 1996; 95: 161-7
65. Greinacher A, Alban S, Dummel V, et al. Characterization of the structural requirements for a carbohydrate based anticoagulant with a reduced risk of inducing the immunological type of heparin-associated thrombocytopenia. Thromb Haemost 1995; 74: 886-92
66. Elalamy I, Lecrubier C, Potevin F, et al. Absence of in vitro cross-reaction of pentasaccharide with the plasma heparindependent factor of twenty-five patients with heparin-associated thrombocytopenia [letter]. Thromb Haemost 1995; 74: 1384-5
67. Amiral J, Bridey F, Wolf M, et al. Antibodies to macromolecular platelet factor 4-heparin complexes in heparin-induced thrombocytopenia: a study of 44 cases. Thromb Haemost 1995; 73: 21-8
68. Balduini CL, Noris P, Bertolino G, et al. Heparin modifies platelet count and function in patients who have undergone thrombolytic therapy for acute myocardial infarction [letter]. Thromb Haemost 1993; 69: 522-3
69. Hach-Wunderle V, Kainer K, Krug B, et al. Heparin-associated thrombosis despite normal platelet counts [letter]. Lancet 1994; 344: 469-70
70. Klement D, Rammos S, van Kries R, et al. Heparin as a cause of thrombus progression. Heparin-associated thrombocytopenia is an important differential diagnosis in paediatric patients even with normal platelet counts. Eur J Pediatr 1996; 155: 11-4
71. Elalamy I, Potevin F, Lecrubier C, et al. A fatal low-molecular-weight heparin-associated thromhocytopenia after hip surgery: possible usefulness of PF4-heparin ELISA test. Blond Coagul Fibrinolysis 1996; 7: 665-71
72. Eichinger S, Kyrle PA, Brenner B, et al. Thromhocytopenia associated with low-molecular-weight heparin [lelter]. Lancet 1991; 337: 1425-6
73. Peters FPJ, Doevendans PAFM, Erdkamp FLG, et al. Low molecular weight heparin-induced thromhocytopenia and thrombosis [letter]. Eur J Haematol 1996; 56: 329-30
74. Ramakrishna R, Manoharan A, Kwan YL, et al. Heparin-induced thromhocytopenia: cross-reactivity between standard heparin, low molecular weight heparin. dalteparin (Fragmin) and heparinoid, danaparoid (Orgaran). Br J Haematol 1995; 91: 736-8
75. Slocum MM, Adams Jr JG, Teel R, et al. Use of enoxaparin in patients with heparin-induced thromhocytopenia syndrome. J Vasc Surg 1996; 23: 839-43
76. Vun CM, Evans S, Chong BH. Cross-reactivity study of low molecular weight heparins and hcparinoid in heparin-induced thrombocytopenia. Thromh Res 1996; 81: 525-32
77. Greinacher A, Michels I, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: the antibody is not heparin specific. Thromb Haemost 1992; 67: 545-9
78. Vitoux JF, Roncato M, Hourdebaigi P, et al. Heparin-induced thrombocytopenia and penlosan polysulfate: treatment with a low molecular weight heparin despite in vitro platelet aggregation. Thromb Haemost 1985; 55: 294-5
79. Pernod G, Duret J, Pouzol P, et al. Thromhopénie induite par l'héparine: discordance entre l'efficacité clinique de l'énoxaparine et les test d'aggrégation plaquetlaire in vitro [letter]. Presse Méd 1993; 22: 737
80. Luzzatto G, Cordiano I, Patrassi G, et al. Heparin-induced thrombocytopenia: discrepancy between the presence of IgG cross-reacting in vitro with fraxiparine and its successful clinical use [letter]. Thromb Haemost 1995; 74: 1607-8
81. Maurin N, Binick R, Heintz B, et al. Heparin-induced thrombocytopenia and thrombosis with spinal ischaemia - recovery of platelet count following a change to a low molecular weight heparin [letter]. Intensive Care Med 1991; 17: 185-6
82. Patrassi GM, Luzzallo G. Heparin-induced thrombocytopenia with thrombosis of the aorta, iliac arteries and right axillary vein successfully treated by low-molecular-weight heparin [letter]. Acta Haematol 1994; 91: 55-6
83. Huisse MG, Huet Y, Zygelman M, et al. Thrombopenie induite par l'héparine standard. Tentative thérapeutique à l'aide d'une héparine de bas poids moléculaire. Presse Méd 1983; 12: 643
84. Horellou MH, Conard J, Lecrubier C, et al. Persistent heparin induced thrombocytopenia despite therapy with low molecular weight heparin [letter]. Thromb Haemost 1984; 51: 134
85. Reuter HD. Niedermolekulares Heparin in der Therapie der heparininduzierten Thromrxwytopenic. Med Klin 1987; 82: 115-8
86. Chong BH, Ismail F, Cade J, et al. Heparin-induced thrombocytopenia: studies with a new low molecular weight heparinoid, Org 10172. Blood 1989; 73: 1592-6
87. Deniers C, Ginsberg JS, Brill-Edwards P, et al. Rapid anticoagulation using ancrod for heparin-induced thromhocytopenia. Blood 1991; 78: 2194-7
88. Cole CW, Bormanis J. Ancrod: a practical alternative to heparin. J Vasc Surg 1988; 8: 59-63
89. Meuleman DG. Orgaran (Org 10172): its pharmacological profile in experimental models. Haemostasis 1992; 22: 58-65
90. Makboul RG, Greenberg CS, McCann RL. Heparin-associated thromhocytopenia and thrombosis: a serious clinical problem and potential solution. J Vasc Surg 1986; 4: 522-8
91. Mikbailidis 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
92. Magnani HN. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with Orgaran (Org 10172) Thromb Haemost 1993; 70: 554-61
93. Ortel TL, Gockerman JP, Califf RM, et al. Parenteral anticoagulation with the heparinoid Lomoparan (Org 10172) in patients with heparin induced thromhocytopenia and thrombosis. Thromh Haemost 1992; 67: 292-6
94. Chong BH. Low molecular weight heparinoid and heparin-induced thrombocylopenia (abstract). Aust N Z J Med 1996; 26: 331
95. Markwardt F. Hirudin: the promising antithrombotic. Cardiovasc Drug Rev 1992; 10: 211-32
96. Schiele F, Vuillemenot A, Kramarz P, et al. Use of recombinant hirudin as antithrombotic treatment in patients with heparin-induced thromhocytopenia. Am J Hematol 1995; 50: 20-5
97. Greinacher A, Volpel H, Poetzsch B. Recombinant hirudin (HBW 023) in the treatment of patients with heparin-associated thrombocytopenia (HAT) - a prospective study [abstract]. Thromb Haemost 1995; 73: 1456
98. Greinacher A, Völpel H, Pötzsch B. Recombinant hirudin in the treatment of patients with heparin-induced thrombocytopenia (HIT) [abslract]. Blood 1996; 88 Suppl. 1: 281a
99. Eichler P, Greinacher A. Anti-hirudin antibodies induced by recombinant hirudin in the treatment of patients with heparin-induced thrombocytopenia (HIT) (abstract). Ann Hematol 1996; 72 Suppl.: A4
100. Matsuo T, Nakao K, Yamada T, et al. Effect of a new anticoagulant (MD 805) on platelet activation in the hemodialysis circuit. Thromb Res 1986; 41: 33-41
101. Matsuo T, Kario K, Chikahira Y, et al. Treatment of heparin-induced thrombocytopenia by use of argatroban, a synthetic thrombin inhibitor. Br J Haematol 1992; 82: 627-9
102. Lewis BE, Iaffaldano R, McKieman TL, et al. Report of successful use of argatroban as an alternative anticoagulant during coronary stem implantation in a patient with heparin-induced thromnocytopenia and thrombosis syndrome. Cathet Cardiovasc Diagn 1996; 38: 206-9
103. Hunting MJ, Joffrion JL, Brooks RL, et al. Effect of renal function on the pharmacokinetics and pharmacodynamics of argatrohun (a direct thrombin inhibitor) (abstract). Blood 1996; 88 Suppl. 1: 167a
104. Fiessinger JN, Aiach M, Roncato M, et al. Critical ischemia during heparin-induced thrombocytopenia: treatment by intra-arterial streptokinase. Thromb Res 1984; 33: 235
105. Calligaro KD, Kansagra A, Dougherty MJ, et al. Thrombolysis to treat arterial thrombotic complications of heparin-induced thrombocytopenia. Ann Vase Surg 1995; 9: 397-400
106. Weinmann EE, Carpenter JP. Intraoperative urokinase as an alternative to heparin for patients with suspected heparin-induced thrombocytopenia requiring arterial reconstruction: report of a case and review of the literature. J Cardiovasc Surg (Torino) 1996; 37: 463-5
107. Bouvier JL, Lefebre P, Villain P, et al. Treatment of serious heparin-induced thrombocytopenia by plasma exchange: report on 4 cases. Thromb Res 1988; 51: 335-6
108. Brady J, Riccio JA, Yumen OH, et al. Plasmapheresis: a therapeutic option in the management of heparin-associated thrombocytopenia with thrombosis. Am J Clin Pathol 1991; 96: 394-7
109. Janson PA, Moake JL, Carpinilo G. Aspirin prevents heparin-induced platelet aggregation in vivo (letter]. Br J Haematol 1983; 53: 166-8
110. Jouanny P, Jeandel C, Laurain MC, et al. Thrombopénie a l'héparine et filtre cave. Difficultés du traitement. J Mal Vas 1993; 18: 320-2
111. 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