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Phlebologie 1998; 27(04): 111-116
DOI: 10.1055/s-0037-1616965
Übersichtsarbeit
Schattauer GmbH

Die Heparin-induzierte Thrombozytopenie

R. Pihusch
1   Aus der Medizinischen Klinik III der Ludwig-Maximilians-Universität, Klinikum Großhadern (Direktor: Prof. Dr. med. Dr. h. c. Wolfgang Wilmanns)
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
29. Dezember 2017 (online)

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Zusammenfassung

Die Heparin-induzierte Thrombozytopenie (HIT) ist eine häufige Komplikation nach Heparingabe. Während die HIT Typ 1 eine harmlose pharmakologische Begleiterscheinung ist, bedroht die HIT Typ 2 den Patienten vital durch eine paradoxe Thromboembolieneigung und arterielle Gefäßverschlüsse. Der Typ 2 beruht auf einer immunologischen Reaktion gegen einen Komplex aus Heparin und Plättchenfaktor-4 (PF4)-Aggregaten. Die dabei entstehenden IgG-Antikörper aktivieren per Fc-Rezeptor die Thrombozyten, schädigen Endothelzellen und lassen hochthrombogene Mikropartikel entstehen. Patienten mit HIT Typ 2 haben daher ein massiv erhöhtes Thromboembolierisiko und neigen zudem zu arteriellen Gefäßverschlüssen mit entsprechend deletäten Folgen. Die Therapie besteht in einer sofortigen Heparinkarenz und Fortsetzung der Antikoagulation mit Hirudin oder Heparinoiden.

Summary

Heparin-induced thrombocytopenia (HIT) is a relatively common disorder induced by therapeutic or prophylactic administration of heparin. HIT type 1 is an insignificant pharmacologic epiphenomenon of heparin therapy. However, HIT type 2 leads to live-threatening thromboembolic complications and arterial occlusions. It is caused by an immunologic reaction to a complex of platelet factor 4 (PF4) and heparin. The induced IgG-antibodies activate platelets via the Fc-receptor, affect the endothelium and produce highly thrombogenic microparticles. Patients with HIT type 2 have a massive increased thromboembolic risk and tend toward arterial occlusions with deletary consequences. Therapy includes stopping heparin and further anticoagulation with hirudin or heparinoids.

Résumé

La thrombopénie induite par l’héparine (TIH) est une complication suite à l’administration d’héparine. Alors que la TIH de type 1 est une manifestation pharmacologique associée bénigne, la TIH de type 2 menace le pronostic vital du patient par une tendance paradoxale à faire une thromboembolle et par des occlusion artérielles. Le type 2 response sur une réaction immunologique à un complexe d’héparine et d’héparine et d’agrégats du facteur plaquettaire 4 (FP4). Les anticorps IgG en résultant activent les thrombocytes par le récepteur Fc, endommagent les cellules endothéliales et produisent des microparticules hautement thrombogènes. Les patients atteints d’une TIH de type 2 présentent par conséquent un risque extrémement élevé de faire une thromboembolie et ont an outre tendance à étre atteints d’occlusions artérielles et leurs conséquences délétères. La thérapie consiste en l’arrêt de l’administration d’héparine et en poursuivant le traitement anticoagulant par de l’hirudine ou des héparinoides.

Schlüsselwörter

Heparin-induzierte Thrombozytopenie - Pathogenese - Therapie

Keywords

Heparin-induced thrombocytopenia - pathogenesis - therapy

Mots clés

Thrombopénie indulte par l’héparine - pathogenése - thérapie
 

  • Literatur

  • 1 Warkentin TE, Chong BH, Greinacher A. Heparin-induced thrombocytopenia: towards consensus. Thromb haemostas 1988; 79: 1-7.
    Google Scholar
  • 2 Chong BH, Ismail F. The mechanism of heparin-induced platelet aggregation. Eur J Haematol 1989; 43: 245-51.
    PubMedGoogle Scholar
  • 3 Chong BH, Castaldi PA. Platelet proaggre-gating effects of heparin: possible mechanism for non-immune heparin-associated thrombocytopenia. Austr N Z J Med 1986; 16: 715-6.
    Google Scholar
  • 4 Chong BH, Berndt MC. Heparin-induced thrombocytopenia. Blut 1989; 58: 53-7.
    CrossrefPubMedGoogle Scholar
  • 5 Ansell J, Deykin D. Heparin-induced thrombocytopenia and recurrent thromboembolism. Am J Hematol 1980; 8: 325-32.
    CrossrefPubMedGoogle Scholar
  • 6 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.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 7 Greinacher A, Mueller-Eckhardt C. Diagnostik der Heparin-assoziierten Thrombozytopenie. Dtsch Med Wochenschr 1991; 116: 1479-82.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 8 Bell WR, Tomasula PA, Alving BM, Duffy TP. Thrombocytopenia occuring during the administration of heparin. A prospective study in 52 patients. Ann Intern Med 1976; 85: 155-60.
    CrossrefPubMedGoogle Scholar
  • 9 Malcohn JD, Wigmore UP, Steinbracher UP. Heparin associated thrombocytopenia. Low frequency in 104 patients treated with heparin of intestinal mucosal origin. Canad Med Ass J 1979; 120: 1086-8.
    PubMedGoogle Scholar
  • 10 King DJ, Kelton JG. Heparin-associated thrombocytopenia. Ann Intern Med 1984; x100: 536-40.
    Google Scholar
  • 11 Greinacher A, Michels I, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: the antibody is not heparin-specific. Thromb Haemost 1992; 67: 545-9.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 12 Warkentin TE, Levine MN, Hirsh J, Horse-wood 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.
    CrossrefPubMedGoogle Scholar
  • 13 Greinacher A, Potzsch 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.
    PubMedGoogle Scholar
  • 14 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.
    CrossrefPubMedGoogle Scholar
  • 15 Kelton JG, Sheridan D, Santos A, Smith J. Heparin-induced thrombocytopenia. Laboratory studies. Blood 1988; 72: 925-30.
    PubMedGoogle Scholar
  • 16 Lee DH, Warkentin TE, Denomme GA, Hayward CPM, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia: detection of platelet microparticles using flow cytometry. Br J Haematol 1996; 95: 724-31.
    CrossrefPubMedGoogle Scholar
  • 17 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. Transfusion Med Rev 1996; 10: 249-58.
    CrossrefPubMedGoogle Scholar
  • 18 Warkentin TE, Hayward CP, Boshkov LK, Santos AV, Sheppard JA, 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.
    PubMedGoogle Scholar
  • 19 Warkentin TE, Hayward CP, 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.
    PubMedGoogle Scholar
  • 20 Bekanntmachung der Bundesärztekammer. Deutsches Ärzteblatt 1992; 89: B2119-20.
    Google Scholar
  • 21 Scharf RE, Riess H, Greinacher A, Breddin HK. Leserbrief. Deutsches Ärzteblatt 1994; 51: B1293-4.
    Google Scholar
  • 22 Kelton JG, Sheridan D, Brain H, Powers PJ, Turpie AG, Carter CJ. Clinical usefulness of testing for a hepa-rin-dependent platelet-aggregating factor in patients with suspected heparin-associated thrombocytopenia. J Lab Clin Med 1984; 103: 606-12.
    PubMedGoogle Scholar
  • 23 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.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 24 Sheridan D, Carter C, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia. Blood 1986; 67: 27-30.
    PubMedGoogle Scholar
  • 25 Reuter HD. Niedermolekulares Heparin in der Therapie der heparininduzierten Thrombopenie. Med Klinik 1987; 82: 115-8.
    Google Scholar
  • 26 Nand S. Hirudin therapy for heparin-associated thrombocytopenia and deep venous thrombosis. Am J Haematol 1993; 43: 310-1.
    CrossrefPubMedGoogle Scholar
  • 27 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. Ann J Hematol 1995; 50: 20-5.
    Google Scholar
  • 28 Chong BH, Magnani HN. Orgaran in heparin-induced thrombocytopenia. Haemostasis 1992; 22: 85-91.
    PubMedGoogle Scholar
  • 29 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.
    PubMedGoogle Scholar
  • 30 Magnani HN. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with orgaran (ORG 10172). Thromb Haemost 1993; 70: 554-61.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 31 Warkentin 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.
    CrossrefPubMedGoogle Scholar
  • 32 Raskob GE, George JN. Thrombotic complications of antithrombotic therapy: a paradox with implications for clinical practice. Ann Intern Med 1997; 127: 839-41.
    CrossrefPubMedGoogle Scholar
  • 33 Lewis BE, Iaffaldano R, McKiernan TL, Rao L, Donkin J, Wallenga JM. Report of successful use of argatroban as an alternative anticoagulant during coronary stent implantation in a patient with heparin-induced thrombocytopenia and thrombosis syndrome. Cathet Cardiovasc Diagn 1996; 38: 206-9.
    CrossrefPubMedGoogle Scholar
  • 34 Lewis BE, Walenga JM, Wallis DE. Anticoagulation with novastan (argatroban) in patients with heparin-induced thrombocytopenia and thrombosis syndrome. Semin Thromb Hemost 1997; 23: 197-202.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 35 Greinacher A, Mueller-Eckhardt C. Therapie der Heparin-assoziierten Thrombozytopenie. Dtsch Med Wochenschr 1991; 116: 1483-4.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 36 Addonizio VP, Fisher CA, Kappa JR, Ellison N. Prevention of heparin-induced thrombocytopenia during open heart surgery with iloprost. Surgery 1987; 102: 796-807.
    PubMedGoogle Scholar
  • 37 Kappa JR, Cotrell ED, Berkowitz HD, Fisher CA, Sobel M, Ellison N, Addonizio VP. Carotid endarterectomy in patients with heparin-induced platelet activation. Comparative efficacy of aspirin and iloprost. J Vasc Surg 1987; 5: 693-701.
    CrossrefPubMedGoogle Scholar
  • 38 Cole CW, Boramis J. Ancrod: A practical alternative to heparin. J Vasc Surg 1988; 8: 59-63.
    CrossrefPubMedGoogle Scholar
  • 39 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.
    PubMedGoogle Scholar
  • 40 Cole CW, Fournier LM, Bormannis J. Heparin-associated thrombocytopenia and thrombosis: optimal therapy with ancrod. Can J Surg 1990; 33: 207-10.
    PubMedGoogle Scholar
  • 41 Greinacher A, Liebenhoff U, Kiefel V, Presek P, Mueller-Eckhardt C. Heparin-induced thrombocytopenia: the effect 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.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 42 Aster RH. Heparin-induced thrombocytopenia and thrombosis. N Engl J Med 1995; 332: 1374-6.
    CrossrefPubMedGoogle Scholar