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DOI: 10.1055/s-0037-1614206
Heparin-induced Thrombocytopenia: Towards Consensus
Publikationsverlauf
Received
29. Juli 1997
Accepted
13. August 1997
Publikationsdatum:
08. Dezember 2017 (online)
Summary
Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin-mediated thrombocytopenic disorder that is important for at least three reasons. First, it is a relatively common drug-induced immunohematologic adverse reaction. Second, it is frequently complicated by life- and limb-threatening thrombotic complications. And third, there remains uncertainty about the optimal treatment approach for these patients. Recently, there has emerged increasing consensus on such important issues as the frequency, pathogenesis, and diagnostic testing, which we will summarize here. Further, a greater appreciation of the activation of the coagulation pathways in this syndrome indicate a rationale to treatment approaches that emphasize thrombin inhibition (eg. danaparoid sodium; hirudin and its analogues).
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References
- 1 Chong BH, Pitney WR, Castaldi PA. Heparin-induced thrombocytopenia: association of thrombotic complications with heparin-dependent IgG antibody that induces thromboxane synthesis and platelet aggregation.. Lancet 1982; 2: 1246-9.
- 2 Warkentin TE, Kelton JG. Heparin-induced thrombocytopenia.. Progr Hemost Thromb 1991; 10: 1-34.
- 3 Warkentin TE, Kelton JG. Interaction of heparin with platelets, including heparin-induced thrombocytopenia.. In: Low-Molecular-Weight Heparins in Prophylaxis and Therapy of Thromboembolic Diseases.. Bounameaux H. ed. Marcel Dekker; New York: 1994. pp. 75-127.
- 4 Greinacher A. Antigen generation in heparin-associated thrombocytopenia: the nonimmunologic type and the immunologic type are closely linked in their pathogenesis.. Semin Thromb Hemostas 1995; 21: 106-16.
- 5 Balduini CL, Noris P, Bertolino G, Previtali M. Heparin modifies platelet count and function in patients who have undergone thrombolytic therapy for acute myocardial infarction (letter).. Thromb Haemost 1993; 69: 522-3.
- 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: 1330-5.
- 7 Chong BH, Ismail F. The mechanism of heparin-induced platelet aggregation.. Eur J Haematol 1989; 43: 245-51.
- 8 Chong BH, Castaldi PA. Platelet proaggregating effect of heparin: possible mechanism for non-immune heparin-associated thrombocytopenia.. Austr N Z J Med 1986; 16: 715-6.
- 9 Babcock RB, Dumper CW, Scharfman WB. Heparin-induced immune thrombocytopenia.. N Engl J Med 1976; 295: 237-41.
- 10 Sheridan D, Carter C, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia.. Blood 1986; 67: 27-30.
- 11 Kelton JG, Sheridan D, Santos A, Smith J, Steeves K, Smith C, Brown C, Murphy WG. Heparin-induced thrombocytopenia: laboratory studies.. Blood 1988; 72: 925-30.
- 12 Warkentin TE, Hayward CPM, Smith CA, Kelly PM, Kelton JG. Determinants of donor platelet variability when testing for heparin-induced thrombocytopenia.. J Lab Clin Med 1992; 120: 371-9.
- 13 Greinacher A, Michels I, Kiefel V, Mueller-Eckhardt C. A rapid and sensitive test for diagnosing heparin-associated thrombocytopenia.. Thromb Haemost 1991; 66: 734-6.
- 14 Greinacher A, Michels I, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: the antibody is not heparin specific.. Thromb Haemost 1992; 67: 545-9.
- 15 Greinacher A, Michels I, Schäfer M, Kiefel V, Mueller-Eckhardt C. Hepa rin-associated thrombocytopenia in a patient treated with polysulphated chondroitin sulphate: evidence for immunological crossreactivity between heparin and polysulphated glycosaminoglycan.. Br J Haematol 1992; 81: 252-4.
- 16 Greinacher A, Michels I, Liebenhoff U, Presek P, Mueller-Eckhardt C. 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.
- 17 Chong BH, Fawaz I, Chesterman CN, Berndt MC. Heparin-induced thrombocytopenia: mechanism of interaction of the heparin-dependent antibody with platelets.. Br J Haematol 1989; 73: 235-40.
- 18 Anderson CL, Chako GW, Osborne JM, Brandt JT. The Fc receptor for immunoglobulin G (FcγIIA) on human platelets.. Semin Thromb Hemost 1995; 21: 1-9.
- 19 Amiral J, Bridey F, Dreyfus M, Vissac AM, Fressinaud E, Wolf M, Meyer D. Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia (letter).. Thromb Haemost 1992; 68: 95-6.
- 20 Visentin GP, Ford SE, Scott JP, Aster RH. 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.
- 21 Kelton JG, Smith JW, Warkentin TE, Hayward CPM, Denomme GA, Horsewood P. Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4.. Blood 1994; 83: 3232-9.
- 22 Greinacher A, Pötzsch B, Amiral J, Dummel V, Eichner A, Mueller-Eck hardt C. 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.
- 23 Amiral J, Bridey F, Wolf M, Boyer-Neumann C, Fressinaud E, Vissac AM, Peynaud-Debayle E, Dreyfus M, Meyer D. Antibodies to macromolecular platelet factor 4-heparin complexes in heparin-induced thrombocytopenia: a study of 44 cases.. Thromb Haemost 1995; 73: 21-8.
- 24 Amiral J, Wolf M, Fischer AM, Boyer-Neumann C, Vissac AM, Meyer D. Pathogenicity of IgA and/or IgM antibodies to heparin-PF4 complexes in patients with heparin-induced thrombocytopenia.. Br J Haematol 1996; 92: 954-9.
- 25 Amiral J, Marfaing-Koka A, Wolf M, Alessi MC, Tardy B, Boyer-Neumann C, Vissac AM, Fressinaud E, Poncz M, Meyer D. Presence of autoantibodies to interleukin-8 or neutrophil-activating peptide-2 in patients with heparin-associated thrombocytopenia.. Blood 1996; 88: 410-6.
- 26 Chong BH, Murray B, Berndt MC, Dunlop LC, Brighton T, Chesterman CN. Plasma P-selectin is increased in thrombotic consumptive platelet disorders.. Blood 1994; 83: 1535-41.
- 27 Warkentin TE, Hayward CPM, Boshkov LK, Santos AV, Sheppard JI, Bode AP, Kelton JG. Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia.. Blood 1994; 84: 3691-9.
- 28 Cines DB, Tomaski A, Tannenbaum S. Immune endothelial-cell injury in heparin-associated thrombocytopenia.. N Engl J Med 1987; 316: 581-9.
- 29 Eichinger S, Kyrle PA, Brenner B, Wagner B, Kapiotis S, Lechner K, Korninger HC. Thrombocytopenia associated with low-molecular-weight heparin (letter).. Lancet 1991; 337: 1425-6.
- 30 Tardy B, Tardy-Poncet B, Zeni F, Comtet C, Reynaud J, Bertrand JC. Thrombocytopenia associated with low-molecular-weight heparin (letter).. Lancet 1991; 338: 1217.
- 31 Follea G, Hamandjian I, Trzeciak MC, Nedey C, Streichenberger R, Dechavanne M. Pentosane polysulfate associated thrombocytopenia.. Thromb Res 1986; 42: 413-8.
- 32 Tardy-Poncet B, Tardy B, Grelac F, Reynaud J, Mismetti P, Bertrand JC, Guyotat D. Pentosan polysulfate-induced thrombocytopenia and thrombosis.. Am J Hematol 1994; 45: 252-7.
- 33 Greinacher A, Alban S, Dummel V, Franz G, Mueller-Eckhardt C. 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.
- 34 Hach-Wunderle V, Kainer K, Krug B, Müller-Berghaus G, Pötzsch B. Heparin-associated thrombosis despite normal platelet counts (letter).. Lancet 1994; 344: 469-70.
- 35 Warkentin TE. Heparin-induced skin lesions.. Br J Haematol 1996; 92: 494-7.
- 36 Warkentin TE, Levine MN, Hirsh J, Klama LN, Kelton JG. Formation of heparin-induced thrombocytopenia IgG without thrombocytopenia: analysis of a clinical trial (abstract).. Blood 1995; 86 (Suppl. 01) 537a.
- 37 Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia.. Am J Med 1996; 101: 502-7.
- 38 Makhoul RG, Greenberg CS, McCann RL. Heparin-associated thrombocytopenia and thrombosis: a serious clinical problem and potential solution.. J Vasc Surg 1986; 4: 522-8.
- 39 Arthur CK, Grant SJB, Murray WK, Isbister JP, Stiel JN, Lauer CS. Heparin-associated acute adrenal insufficiency.. Aust N Z J Med 1985; 15: 454-5.
- 40 Ernest D, Fisher MM. Heparin-induced thrombocytopaenia complicated by bilateral adrenal haemorrhage.. Intensive Care Med 1991; 17: 238-40.
- 41 Warkentin TE, Soutar RL, Panju A, Ginsberg JS. Acute systemic reactions to intravenous bolus heparin therapy: characterization and relationship to heparin-induced thrombocytopenia (abstract).. Blood 1992; 80 (Suppl. 01) 160a.
- 42 Warkentin TE, Hirte HW, Anderson DR, Wilson WEC, O’Connell GJ, Lo RC. Transient global amnesia associated with acute heparin-induced thrombocytopenia.. Am J Med 1994; 97: 489-91.
- 43 Platell CFE, Tan EGC. Hypersensitivity reactions to heparin: delayed onset thrombocytopenia and necrotizing skin lesions.. Aust N Z J Surg 1986; 56: 621-3.
- 44 Hartman AR, Hood RM, Anagnostopoulos CE. Phenomenon of heparin-induced thrombocytopenia associated with skin necrosis.. J Vasc Surg 1988; 7: 781-4.
- 45 Greinacher A, Amiral J, Dummel V, Vissac A, Kiefel V, Mueller-Eckhardt C. 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.
- 46 Kelton JG, Sheridan D, Brain H, Powers PJ, Turpie AG, Carter CJ. Clinical usefulness of testing for a heparin-dependent platelet-aggregating factor in patients with suspected heparin-associated thrombocytopenia.. J Lab Clin Med 1984; 103: 606-12.
- 47 Favaloro EJ, Bernal-Hoyos E, Exner T, Koutts J. Heparin-induced thrombocytopenia: laboratory investigation and confirmation of diagnosis.. Pathology 1992; 24: 177-83.
- 48 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.
- 49 Nguyên P, Droullé C, Potron G. Comparison between platelet factor 4/ heparin complexes ELISA and platelet aggregation test in heparin-induced thrombocytopenia (letter).. Thromb Haemost 1995; 74: 804-5.
- 50 Artepally G, Reynolds C, Tomaski A, Amiral J, Jawad A, Poncz M, Cines DB. Comparison of PF4/heparin ELISA assay with the 14C-serotonin release assay in the diagnosis of heparin-induced thrombocytopenia.. Am J Clin Pathol 1995; 104: 648-54.
- 51 Amiral J, Peynaud-Debayle E, Wolf M, Bridey F, Vissac AM, Meyer D. Generation of antibodies to heparin-PF4 complexes without thrombocytopenia in patients treated with unfractionated or low-molecular-weight heparin.. Am J Hematol 1996; 52: 90-5.
- 52 Chong BH, Pilgrim RL, Cooley MA, Chesterman CN. Increased expression of platelet IgG Fc receptors in immune heparin-induced thrombocytopenia.. Blood 1993; 81: 988-93.
- 53 Brandt JT, Isenhart CE, Osborne JM, Ahmed A, Anderson CL. On the role of platelet FcγRIIa phenotype in heparin-induced thrombocytopenia.. Thromb Haemost 1995; 74: 1564-72.
- 54 Burgess JK, Lindeman R, Chesterman CN, Chong BH. Single amino acid mutation of Fcγ receptor is associated with the development of heparin-induced thrombocytopenia.. Br J Haematol 1995; 91: 761-6.
- 55 Denomme GA, Warkentin TE, Horsewood P, Sheppard JI, Warner MN, Kelton JG. Activation of platelets by sera containing IgG1 heparin-dependent antibodies: an explanation for the predominance of the FcγRIIa “low responder” (His131) gene in patients with heparin-induced thrombocytopenia.. J Lab Clin Med 1997; 130: 278-84.
- 56 Warketing TE, Elavathil LJ, Hayward CPM, Johnston MA, Russett JI, Kelton JG. The pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia.. Ann Intern Med 1997; 127: 804-12.
- 57 Warkentin TE. Heparin-induced thrombocytopenia: IgG-mediated platelet activation, platelet microparticle generation, and altered procoagulant/anticoagulant balance in the pathogenesis of thrombosis and venous limb gangrene complicating heparin-induced thrombocytopenia.. Transf Med Rev 1996; 10: 249-58.
- 58 Pötzsch B, Unkrig C, Madlener K, Greinacher A, Müller-Berghaus G. APC resistance and early onset of oral anticoagulation are high thrombotic risk factors in patients with heparin-associated thrombocytopenia (HAT) (abstract).. Ann Hematol 1996; 72 (Suppl. I) A6.
- 59 Warkentin TE, Kelton JG. Heparin-induced thrombocytopenia.. Annu Rev Med 1989; 40: 31-44.
- 60 Magnani HN. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with Orgaran (Org 10172).. Thromb Haemost 1993; 70: 554-61.
- 61 Chong BH. Low molecular weight heparinoid and heparin-induced thrombocytopenia (abstract).. Aust NZ J Med 1996; 26: 331.
- 62 Warkentin TE. Danaparoid (Orgaran® ) for the treatment of heparin-induced thrombocytopenia (HIT) and thrombosis: effects on in vivo thrombin and cross-linked fibrin generation, and evaluation of the clinical significance of in vitro cross-reactivity (XR) of danaparoid for HIT-IgG.. Blood 1996; 88 (Suppl. 01) 626a.
- 63 Chong BH, Ismail F, Cade J, Gallus AS, Gordon S, Chesterman CN. Heparin-induced thrombocytopenia: Studies with a new low molecular weight heparinoid, Org 10172.. Blood 1989; 73: 1592-6.
- 64 Cook DJ, Guyatt GH, Laupacis A, Sackett DL, Goldberg RJ. Clinical recommendations using levels of evidence for antithrombotic agents.. Chest 1995; 108 Suppl 227S-30S.
- 65 Greinacher A, Völpel 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.
- 66 Greinacher A, Völpel H, Pötzsch B. Recombinant hirudin in the treatment of patients with heparin-induced thrombocytopenia (HIT) (abstract).. Blood 1996; 88 (Suppl. 01) 281a.
- 67 Schiele F, Vuillemenot A, Kramarz P, Kieffer Y, Anguenot T, Bernard Y, Bassand JP. Use of recombinant hirudin as antithrombotic treatment in patients with heparin-induced thrombocytopenia.. Am J Hematol 1995; 50: 20-5.
- 68 Demers C, Ginsberg JS, Brill-Edwards P, Panju A, Warkentin TE, Anderson DR, Turner C, Kelton JG. Rapid anticoagulation using ancrod for heparin-induced thrombocytopenia.. Blood 1991; 78: 2194-7.
- 69 Fiessinger JN, Aiach M, Roncato M, Debure C, Gaux JC. Critical ischemia during heparin-induced thrombocytopenia. Treatment by intra-arterial streptokinase.. Thromb Res 1984; 33: 235.
- 70 Cohen JI, Cooper MR, Greenberg CS. Streptokinase therapy of pulmonary emboli with heparin-associated thrombocytopenia.. Arch Intern Med 1985; 145: 1725-6.
- 71 Janson PA, Moake JL, Carpinito G. Aspirin prevents heparin-induced platelet aggregation in vivo.. Br J Haematol 1983; 53: 166-8 (letter).
- 72 Bouvier JL, Lefebre P, Villain P, Elias A, Durand JM, Juhan I, Serradimigni A. Treatment of serious heparin-induced thrombocytopenia by plasma exchange: report on 4 cases.. Thromb Res 1988; 51: 335-6.
- 73 Frame JN, Mulvey KP, Phares JC, Anderson MJ. Correction of severe heparin-associated thrombocytopenia with intravenous immunoglobulin.. Ann Intern Med 1989; 111: 946-7.
- 74 Nurden AT, Laroche-Traineau J, Jallu V, Broult J, Durrieu C, Besse P, Brossel C, Hourdillé P. Heparin-induced thrombocytopenia: observations on the nature of the antibody activities and on the use of gammaglobulin concentrates in a patient with thrombotic complications (abstract).. Thromb Haemost 1991; 65: 796.
- 75 Greinacher A, Liebenhoff U, Kiefel V, Presek P, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: the effects of various intravenous IgG preparations on antibody mediated platelet activation – a possible new indication for high dose i.v. IgG.. Thromb Haemost 1994; 71: 641-5.
- 76 Reininger CB, Reininger AJ, Steckmeier B, Greinacher A, Lasser R, Schweiberer L. Platelet response to vascular surgery – a preliminary study on the effect of aspirin and heparin.. Thromb Res 1994; 76: 79-87.
- 77 Singer RL, Mannion JD, Bauer TL, Armenti FR, Edie RN. Complications from heparin-induced thrombocytopenia in patients undergoing cardio-pulmonary bypass.. Chest 1993; 104: 1436-40.