Zusammenfassung
Seit Beginn der therapeutischen Anwendung von Heparin werden Thrombozytopenien unter der Heparingabe beobachtet. Aufgrund der weiten Verbreitung des Heparins zur Prophylaxe und Therapie thromboembolischer Komplikationen gilt die Heparin-induzierte Thrombozytopenie (HIT) zur Zeit als häufigste medikamenteninduzierte Thrombozytopenie.
Die biochemischen und gerinnungsphysiologischen Eigenschaften von Heparin, niedermolekularen (LMW-)Heparinen, Heparanen, Glykosami-noglykanen und Heparinoiden werden an anderer Stelle dieses Buches dargestellt.
Die HIT unterscheidet sich von allen anderen medikamenteninduzierten Thrombozytopenien durch ihren klinischen Verlauf, da sie mit schwerwiegenden arteriellen und venösen throm-boembolischen Gefäßverschlüssen einhergehen kann. Bei der HIT werden 2 Formen unterschieden und als Typ I und Typ II bezeichnet. Der Typ I hat nichtimmunologische, der Typ II immunologische Ursachen. Im folgenden werden im Abschnitt HIT Typ I die nichtimmunologischen Wechselwirkungen zwischen Heparin und Thrombozyten zusammengefaßt. Zur HIT Typ II werden neben den klinischen Kriterien und dem bisherigen Wissen zur Pathophysiologie der HIT die verschiedenen Möglichkeiten der Diagnosesicherung dargestellt und daraus Möglichkeiten der Therapie und Prophylaxe der HIT entwickelt.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
Literatur
AbuRahma AF, Boland JP, Witsberger T (1991) Diagnostic und therapeutic strategies of white clot syndrome. Am J Surg 162:175–179
Adelman B, Sobel M, Fujimura T et al. (1989) Heparin-asso-ciated thrombocytopenia: observations on the mechanism of platelet aggregation. J Lab Clin Med 113:204–210
Amiral J, Bridey F, Dreyfus M et al. (1992) Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia (letter). Thromb Haemost 68:95–96
Arthur CK, Grant SJB, Murray WK et al. (1985) Heparin-as-sociated acute adrenal insufficiency. Aust N Z J Med 15:454–455
Blockmans D, Bounameaux H, Vermylen J, Verstraete M (1986) Heparin-induced thrombocytopenia. Platelet aggregation studies in the presence of heparin fractions or semi-synthetic analogues of various molecular weights and anticoagulant activities. Thromb Haemost 55:90–93
Bouvier JL, Lefebre P, Villain P et al. (1988) Treatment of serious heparin-induced thrombocytopenia by plasma exchange: report on 4 cases. Thromb Res 51:335–336
Chong BH, Castaldi PA (1988 a) Heparin-induced thrombocytopenia: further studies of the effects of heparin-de-pendent antibodies on platelets. Br J Haematol 64:347–354
Chong BH, Castaldi PA (1986 b) Platelet proaggregating effect of heparin: possible mechanism for non-immune heparin-associated thrombocytopenia. Aust N Z J Med 16:715–716
Chong BH, Ismail F (1986) The mechanism of heparin-induced platelet aggregation. Eur J Haematol 43:245–251
Chong BH, Berndt MC (1989) Heparin-induced thrombocytopenia. Blut 58:53–57
Chong BH, Pitney WR, Castaldi PA (1982) Heparin-induced thrombocytopenia: association of thrombotic complications with heparin-dependent IgG antibody that induces thromboxane synthesis and platelet aggregation. Lancet 11:1246–1249
Chong BH, Fawaz I, Chesterman CN, Berndt MC (1989 a) Heparin-induced thrombocytopenia: mechanism of interaction of the heparin-dependent antibody with platelets. Br J Haematol 73:235–240
Chong BH, Ismail F, Cade J et al. (1989 b) Heparin-induced thrombocytopenia: Studies with a new low molecular weight heparinoid, Org 10172. Blood 73:1592–1596
Chong BH, Burgess J, Ismail F (1993) The clinical usefulness of the platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia. Thromb Haemost 64:344
Cines DB, Kaywin P, Bine M et al. (1980) Heparin-associated thrombocytopenia. N Engl J Med 303:788–795
Cines DB, Tomaski A, Tannenbaum S (1987) Immune en-dothelial-cell injury in heparin-associated thrombocytopenia. N Engl J Med 316:581–589
Demers C, Ginsberg JS, Brill-Edwards P et al. (1991) Rapid anticoagulation using ancrod for heparin-induced thrombocytopenia. Blood 78:2194–2197
Eichinger S, Kyrie PA, Brenner B et al. (1991) Thrombocytopenia associated with low-molecular-weight heparin (letter). Lancet 337:1425–1426
Ernest D, Fisher MM (1991) Heparin-induced thrombocytopenia complicated by bilateral adrenal haemorrhage. Intensive Care Med 17:238–240
Favaloro EJ, Bernal-Hoyos E, Exner T, Koutts J (1992) Heparin-induced thrombocytopenia: laboratory investigation and confirmation of diagnosis. Pathology 24:177–183
Follea G, Hamandjian I, Trzeciak MC et al. (1986) Pentosane polysulfate associated thrombocytopenia. Thromb Res 42:413–418
Frame JN, Mulvey KP, Phares JC, Anderson MJ (1989) Correction of severe heparin-associated thrombocytopenia with intravenous immunoglobulin. Ann Intern Med 111:946–947
Greinacher A (1995) Antigen generation in heparin-associated thrombocytopenia: the nonimmunologic type and the immunologic type are closely linked in their pathogenesis. Semin Thromb Hemost 21:106–116
Greinacher A, Mueller-Eckhardt C (1991a) Diagnostik der Heparin-assoziierten Thrombocytopenic. Dtsch Med Wo-chenschr 116:1479–1482
Greinacher A, Mueller-Eckhardt C (1991b) Therapie der Heparin-assoziierten Thrombozytopenie. Dtsch Med Wochenschr 116:1483–1484
Greinacher A, Michels I, Kiefel V, Mueller-Eckhardt C (1991) A rapid and sensitive test for diagnosing heparin-associated thrombocytopenia. Thromb Haemost 66:734–736
Greinacher A, Michels I, Mueller-Eckhardt C (1992 a) Heparin-associated thrombocytopenia: the antibody is not heparin specific. Thromb Haemost 67:545–549
Greinacher A, Michels I, Schäfer M et al. (1992 b) Heparin-associated thrombocytopenia in a patient treated with polysulphated chondroitin sulphate: evidence for immunological crossreactivity between heparin and polysulphated glycosaminoglycan. Br J Haematol 81:252–254
Greinacher A, Amiral J, Dummel V et al. (1994a) 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 34:381–385
Greinacher A, Liebenhoff U, Kiefel V et al. (1994b) 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 71:641–645
Greinacher A, Pötzsch B, Amirall J et al. (1994 c) Heparin-associated thrombocytopenia: isolation of the antibody and characterization of a multimolecular PF4-heparin complex as the major antigen. Thromb Haemost 71:247–251
Greinacher A, Alban S, Dummel V et al. (1995a) 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 74:886–892
Greinacher A, Volpel H, Pötzsch B (1995b) Recombinant hirudin (HBW 023) in the treatment of patients with heparin-associated thrombocytopenia (HAT) — a prospective study. Thromb Haemost 73(Abstract): 1456
Hach-Wunderle V, Kainer K, Krug B et al. (1994) Heparin-associated thrombosis despite normal platelet counts (letter). Lancet 344:469–470
Harenberg J, Zimmermann R, Schwarz F, Kubier W (1983) Treatment of heparin-induced thrombocytopenia with thrombosis by new heparinoid. Lancet 1:986–987
Hartman AR, Hood RM, Anagnostopoulos CE (1988) Phenomenon of heparin-induced thrombocytopenia associated with skin necrosis. J Vase Surg 7:781–784
Home MK, Chao ES (1989) Heparin binding to resting and activated platelets. Blood 74:238–343
Kelton IG, Sheridan D, Barin H et al. (1984) Clinical usefulness of testing for a heparin-dependent platelet-aggregating factor in patients with suspected heparin-associated thrombocytopenia. J Lab Clin Med 103:606–612
Kelton IG, Smith JW, Warkentin TE et al. (1994) Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4. Blood 83:3232–3239
Laster JL, Nichols K, Silver D (1989) Thrombocytopenia associated with heparin-coated catheters in patients with heparin-associated antiplatelet antibodies. Arch Intern Med 149:2285–2287
Leroy I, Leclerc MH, Delahousse B et al. (1985) Treatment of heparin-associated thrombocytopenia and thrombosis with low molecular weight heparin. Semin Thromb Hemost 11:326–329
Magnani HN (1993) Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with Orgaran (Org 10172). Thromb Haemost 70:554–561
Matsuo T, Yamada T, Chikahira Y, Kadowaki S (1989) Effect of aspirin on heparin-induced thrombocytopenia (HIT) in a patient requiring hemodialyis. Blut 59:393–395
Salzman EW, Rosenberg RD, Smith MH et al. (1980) Effect of heparin and heparin fractions on platelet aggregation. J Clin Invest 65:64–73
Schiele F, Vuillemenot A, Kramarz P et al. (1995) Use of recombinant hirudin as antithrombotic treatment in patients with heparin-induced thrombocytopenia. Am J Haematol 50:20–25
Sobel M, Adelman B (1988) Characterization of platelet binding of heparins and other glycosaminoglycans. Thromb Res 50:815–826
Tardy-Poncet B, Tardy B, Grelac F et al. (1994) Pentosan polysulfate-induced thrombocytopenia and thrombosis. Am J Hematol 45:252–257
Visentin GP, Ford SE, Scott JP, Aster RH (1994) 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 93:81–88
Warkentin TE, Kelton JG (1994) Interaction of heparin with platelets, including heparin-induced thrombocytopenia. In: Bounameaux H (ed) Low-molecular-weight heparins in prophylaxis and therapy of thromboembolic diseases. Dekker, New York, pp 75–127
Warkentin TE, Kelton JG (1991) Heparin-induced thrombocytopenia. In: Coller BS (ed) Progress in Hemostasis and Thrombosis, 10th edn. Saunders, Philadelphia London, Toronto Montreal Tokyo Sydney, pp 1–34
Warkentin TE, Hayward CPM, Smith CA et al. (1992) Determinants of donor platelet variability when testing for heparin-induced thrombocytopenia. J Lab Clin Med 120:371–379
Warkentin TE, Hayward CPM, Boshkov LK et al. (1994) Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagu-lant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia. Blood 84:3691–3699
Warkentin TE, Levine MN, Hirsh J et al. (1995) Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 332: 1330–1335
Weisman RE, Tobin RW (1958) Arterial embolism occuring during systemic heparin therapy. Arch Surg 76:219–226
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Greinacher, A. (1999). Heparin-induzierte Thrombozytopenie. In: Müller-Berghaus, G., Pötzsch, B. (eds) Hämostaseologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-07673-6_11
Download citation
DOI: https://doi.org/10.1007/978-3-662-07673-6_11
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-07674-3
Online ISBN: 978-3-662-07673-6
eBook Packages: Springer Book Archive