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Thromb Haemost 1999; 82(02): 457-467
DOI: 10.1055/s-0037-1615866
Research Article
Schattauer GmbH

Treatment of Heparin-Induced Thrombocytopenia

Andreas Greinacher
1   Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, GERMANY
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Publication History

Publication Date:
09 December 2017 (online)

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Introduction

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are the most widely used anticoagulants when parenteral anticoagulation with a short half-life is required. Both can be administered subcutaneously and intravenously, and both have been shown to be effective in a variety of clinical settings.1 UFH has several limitations. One is its poor bioavailability after subcutaneous injection and the marked variability in its anticoagulant response in patients with an acute thromboembolic complication.2,3 Another major issue associated with UFH is the induction of heparin-induced thrombocytopenia (HIT). Both limitations are closely linked,4 as the underlying cause is the high density of negative charges on the heparin molecule and its molecular weight. Both are responsible for the binding of heparin to plasma proteins other than antithrombin (AT), such as platelet factor 4 (PF4) and to several cell types. This leads to heparin-platelet interaction, the formation of HIT antigen (i.e., PF4/heparin complexes), and inhibition of the anticoagulant effect of heparin (aPTT-nonresponder).

 

  • References

  • 1 Hirsh J, Warkentin TE, Raschke R, Granger C, Ohman EM, Dalen J. Heparin and low molecular weight heparin. Mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy and safety. Chest 1998; 114: 489S-510S.
    CrossrefPubMedGoogle Scholar
  • 2 Hirsh J. Heparin. N Engl J Med 1991; 324: 1565-1574.
    CrossrefPubMedGoogle Scholar
  • 3 Young E, Prins MH, Levine MN, Hirsh J. Heparin binding to plasma proteins, an important mechanism for heparin resistance. Thromb Haemost 1992; 67: 639-643.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Greinacher A. Antigen generation in heparin-associated thrombocytopenia: The non-immunologic type and the immunologic type are closely linked in their pathogenesis. Semin Thromb Hemost 1995; 21: 106-116.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Kelton JG, Sheridan D, Santos A, Smith J, Steeves K, Smith C, Brown C, Murphy WG. Heparin-induced thrombocytopenia: Laboratory Studies. Blood 1988; 72: 925-930.
    PubMedGoogle Scholar
  • 6 Chong BH, Fawaz I, Chestermann CN, Berndt MC. Heparin-induced thrombocytopenia: Mechanism of interaction of the heparin-dependent antibody with platelets. Br J Haematol 1989; 73: 235-240.
    CrossrefPubMedGoogle Scholar
  • 7 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: 1535-1541.
    PubMedGoogle Scholar
  • 8 Cines DB, Tomaski A, Tannenbaum S. Immune endothelial-cell injury in heparin-associated thrombocytopenia. N Engl J Med 1987; 316: 581-589.
    CrossrefPubMedGoogle Scholar
  • 9 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: 81-88.
    CrossrefPubMedGoogle Scholar
  • 10 Greinacher A, Pötzsch B, Amiral J, Dummel V, Eichner A. Mueller-Eckhardt Heparin-associated thrombocytopenia: Isolation of the antibody and characterization of a multimolecular PF4-heparin complex as the major antigen. Thromb Haemost 1994; c; 71: 247-251.
    PubMedGoogle Scholar
  • 11 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: 3691-3699.
    PubMedGoogle Scholar
  • 12 Warkentin TE, Chong BH, Greinacher A. Heparin-induced thrombocytopenia: Towards consensus. Thromb Haemost 1998; 79: 1-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med 1996; 101: 502-507.
    CrossrefPubMedGoogle Scholar
  • 14 Greinacher A, Völpel H, Janssens U, Hach-Wunderle V, Kemkes-Matthes B, Eichler P, Mueller-Velten HG, Pötzsch B. Recombinant hirudin (lepirudin) provides safe and effective anticoagulation in patients with the immunologic type of heparin-induced thrombocytopenia: A prospective study. Circulation 1999; 99: 73-80.
    CrossrefPubMedGoogle Scholar
  • 15 Greinacher A. Lepirudin for the treatment of heparin-induced thrombocytopenia: A prospective study. Blood 1998; 92: #1490 [abstract].
    PubMedGoogle Scholar
  • 16 Warkentin TE. Greinacher, eds. Heparin-Induced Thrombocytopenia. New York: Marcel Dekker, Inc.; In press.
    Google Scholar
  • 17 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: 1330-1335.
    CrossrefPubMedGoogle Scholar
  • 18 Markwardt F. Hirudin: The promising antithrombotic. Cardiovasc Drug Rev 1992; 10: 211-232.
    CrossrefPubMedGoogle Scholar
  • 19 Hoog PJ, Jackson CM. Fibrin monomer protects thrombin from inactivation by heparin-antithrombin III: Implications for heparin efficacy. Proc Natl Acad Sci USA 1989; 86: 3619-3623.
    CrossrefPubMedGoogle Scholar
  • 20 Weitz JI, Hudoba M, Massel D, Marganore J, Hirsh J. 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: 385-391.
    CrossrefPubMedGoogle Scholar
  • 21 Weitz JI, Leslie B, Hudoba M. Thrombin binds to soluble fibrin degradation products where it is protected from inhibition by heparin-antithrombin but susceptible to inactivation by antithrombin-independent inhibitors. Circulation 1998; 97: 544-552.
    CrossrefPubMedGoogle Scholar
  • 22 Meyer BJ, Badimon JJ, Chesebro JH, Fallon JT, Fuster V, Badimon L. Dissolution of mural thrombus by specific thrombin inhibition with r-hirudin: Comparison with heparin and aspirin. Circulation 1998; 97: 681-685.
    CrossrefPubMedGoogle Scholar
  • 23 Glusa E, Markwardt F. Platelet functions in recombinant hirudin-anticoagulated blood. Hemostasis 1990; 20: 112-118.
    PubMedGoogle Scholar
  • 24 Nowak G, Bucha E, Göck T, Thieler H, Markwardt F. Pharmacology of r-hirudin in renal impairment. Thromb Res 1992; 66: 707-715.
    CrossrefPubMedGoogle Scholar
  • 25 Nurmohamed MT, Berckmans RJ, Morrien-Salomons WM, Berends F, Hammes WD, Rijnierse JJMM, Sturk A. Monitoring anticoagulant therapy by activated partial thromboplastin time: Hirudin assessment. Thromb Haemost 1994; 72: 685-692.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Pötzsch B, Madlener K, Seelig C, Riess CF, Greinacher A, Muller-Berghaus G. The whole blood ecarin clotting time assay allows rapid and accurate monitoring of the anticoagulant response of r-hirudin during cardiopulmonary bypass. Thromb Haemost 1997; 77: 920-925.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Nowak G, Bucha E. A new method for the therapeutical monitoring of hirudin. Thromb Haemost 1993; 69: 1306.
    PubMedGoogle Scholar
  • 28 Riess FC, Pötzsch B, Jäger K, Bleese N, Schaper W, Müller-Berghaus G. Elimination von rekombinantem Hirudin aus der Blutzirkulation mittels Hämofiltration. Hämostaseologie 1997; 17: 200-204.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Butler KD, Dolan SL, Talbot MD, Wallis RB. Factor VII and DDAVP reverse the effect of recombinant desulphatohirudin (CGB 39393) on bleeding in the rat. Blood Coagul Fibrinolysis 1993; 4: 459-464.
    CrossrefPubMedGoogle Scholar
  • 30 Bove CM, Casey B, Marder VJ. DDAVP reduces bleeding during continued hirudin administration in the rabbit. Thromb Haemost 1996; 75: 471-475.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Ibbotson SH, Grant PJ, Kerry R, Findlay VS, Prentice CRM. The influence of infusions of 1-Desamino-8-D-arginine vasopressin (DDAVP) in vivo on the anticoagulant effect of r-hirudin. Thromb Haemost 1991; 65: 64-66.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Dickneite G, Friesen HJ, Kumpe G, Reers M. Reduction of rh induced bleeding in pigs by the administration of von Willebrand Factor. Platelets 1996; 7: 283-290.
    CrossrefPubMedGoogle Scholar
  • 33 Dickneite G, Nicolay U, Friesen HJ, Reers M. Development of an anti-bleeding agent for recombinant hirudin induced skin bleeding in the pig. Thromb Haemost 1998; 80: 192-198.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Irami MS, Harvey JW, Sexon RG. Reversal of hirudin-induced bleeding diathesis by prothrombin complex concentrate. Am J Cardiol 1995; 75: 422-423.
    CrossrefPubMedGoogle Scholar
  • 35 Diehl KH, Römisch J, Hein B, Jessel A, Ronneberger H, Paques EP. Investigation of activated prothrombincomplex concentrate as potential hirudin antidote in animal models. Haemostasis 1995; 25: 182-192.
    PubMedGoogle Scholar
  • 36 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: 20-25.
    CrossrefPubMedGoogle Scholar
  • 37 Olbrich K, Wiersbitzky M, Wacke W, Eichler P, Zinke H, Schwock M, Möx B, Kraatz G, Motz W, Greinacher A. Atypical heparin-induced thrombocytopenia complicated by intracardiac thrombus, effectively treated with ultra-low-dose rt-PA lysis and recombinant hirudin (Lepirudin). Blood Coagul Fibrinolysis 1998; 9: 273-277.
    CrossrefPubMedGoogle Scholar
  • 38 Schmidt OH, Lang W. Heparin-induced thrombocytopenia with thromboembolic arterial occlusion treated with recombinant hirudin. N Engl J Med 1997; 337: 1389.
    PubMedGoogle Scholar
  • 39 Eichler P, Olbrich K, Pötzsch B, Greinacher A. Anti-hirudin anti bodies in patients treated with recombinant hirudin for more than five days, a prospective study. Thromb Haemost 1997; (Supplement):PS 2014.
    PubMedGoogle Scholar
  • 40 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: 1592-1596.
    PubMedGoogle Scholar
  • 41 Magnani HN. Heparin-induced thrombocytopenia (HIT): An overview of 230 patients treated with Orgaran (Org10172). Thromb Haemost 1993; 70: 554-561.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Wilde MI, Markham A. Danaparoid. A review of its pharmacology and clinical use in the management of heparin-induced thrombocytopenia. Drugs 1997; 54: 903-924.
    CrossrefPubMedGoogle Scholar
  • 43 Meuleman DG. Orgaran (Org 10172): Its pharmacological profile in experimental models. Haemostasis 1992; 22: 58-65.
    PubMedGoogle Scholar
  • 44 Danhof M, deBoer A, Magnani HM, Stiekema JCJ. Pharmacokinetic considerations on Orgaran (Org10172). Hemostasis 1992; 22: 73-84.
    PubMedGoogle Scholar
  • 45 Ortel TL, Chong BH. New treatment options for heparin-induced thrombocytopenia. Semin Hematol 1998; 35: 26-34.
    PubMedGoogle Scholar
  • 46 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: 74-81.
    PubMedGoogle Scholar
  • 47 Carlsson LE, Santoso S, Baurichter G, Kroll H, Papenberg S, Eichler P, Westerdaal NAC, Kiefel V, van de Winkel JGJ, Greinacher A. Heparin-induced thrombocytopenia: New insights into the impact of the FcγRIIa-R-H131 polymorphism. Blood 1998; 92: 1526-1531.
    PubMedGoogle Scholar
  • 48 Greinacher A, Amiral J, Dummel V, Vissac AM, Kiefel V, Mueller-Eckhardt C. Laboratory diagnosis of heparin-associated thrombocytopenia, comparison of platelet aggregation test, heparin-induced platelet activation (HIPA) test, and PF4/heparin ELISA. Transfusion 1994; 34: 381-385.
    CrossrefPubMedGoogle Scholar
  • 49 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 (abstract). Blood 1996; 88 (Suppl. 01) 626a.
    PubMedGoogle Scholar
  • 50 Newman PM, Swanson RL, Chong BH. Heparin-induced thrombocytopenia: IgG binding to PF4-heparin complexes in the fluid phase and cross-reactivity with low molecular weight heparin and heparinoid. Thromb Haemost 1998; 80: 292-297.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 51 Vun CM, Evans S, Chong BH. Cross-reactivity study of low-molecular weight heparins and heparinod in heparin-induced thrombocytopenia. Thromb Res 1996; 81: 525-532.
    CrossrefPubMedGoogle Scholar
  • 52 Warkentin TE. Limitations of conventional treatment options for heparin-induced thrombocytopenia. Semin Hematol 1998; 35 (Suppl. 04) 17-25.
    PubMedGoogle Scholar
  • 53 Tardy B, Tardy-Poncet B, Viallon A, Piot M, Mazet E. Fatal danaparoid-sodium induced thrombocytopenia and arterial thromboses. Thromb Haemost 1998; 80: 530.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 54 Bell Jr WR. Defibrinogenating enzymes. Drugs 1997; 54 (Suppl. 03) 18-31.
    CrossrefPubMedGoogle Scholar
  • 55 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: 2194-2197.
    PubMedGoogle Scholar
  • 56 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: 804-812.
    CrossrefPubMedGoogle Scholar
  • 57 Gupta AK, Kovacs MJ, Sauder DN. Heparin-induced thrombocytopenia. Ann Pharmacother 1998; 32: 55-59.
    CrossrefPubMedGoogle Scholar
  • 58 Greinacher A, Michels I, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: The antibody is not heparin specific. Thromb Haemost 1992; 67: 545-549.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 59 Copplestone A, Oscier DG. Heparin-induced thrombocytopenia in pregnancy. Brit J Haematol 1987; 65: 248.
    PubMedGoogle Scholar
  • 60 Meytes D, Ayalon H, Virag I, Weisbort Y, Zakut H. Heparin-induced thrombocytopenia and recurrent thrombosis in pregnancy. A case report. J Reprod Med 1986; 31: 993-996.
    PubMedGoogle Scholar
  • 61 Calhoun BC, Hesser JW. Heparin-associated thrombocytopenia with pregnancy: Discussion of two cases. Am J Obst Gynecol 1987; 156: 964-966.
    CrossrefPubMedGoogle Scholar
  • 62 Henny CHP, ten Cate H, ten Cate JW, Prummel MF, Peters M, Büller HR. Thrombosis prophylaxis in an ATIII deficient pregnant women: application of a low molecular weight heparinoid. Thromb Haemost 1986; 55: 301.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 63 Van Besien K, Hoffman R, Golichowski A. Pregnancy associated with lupus anticoagulant and heparin-induced thrombocytopenia: Management with a low molecular weight heparinoid. Thromb Res 1991; 62: 23-29.
    CrossrefPubMedGoogle Scholar
  • 64 Greinacher A, Eckhardt T, Mußmann J, Mueller-Eckhardt C. Pregnancy complicated by heparin-associated thrombocytopenia: Management by a prospectively in vitro selected heparinoid (Org 10172). Thromb Res 1993; 71: 123-126.
    CrossrefPubMedGoogle Scholar
  • 65 Potter C, Gill JC, Scott P, McFarland JG. Heparin-induced thrombocytopenia in a child. J Pediatr 1992; 121: 135-138.
    CrossrefPubMedGoogle Scholar
  • 66 Klement D, Rammos S, Kries R von, Kirschke W, Kniemeyer HW, Greinacher A. 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: 11-14.
    PubMedGoogle Scholar
  • 67 Murdoch IA, Beattie RM, Siver DM. Heparin-induced thrombocytopenia in children. Acta Paediatr 1993; 82: 495-497.
    CrossrefPubMedGoogle Scholar
  • 68 Oriot D, Wolf M, Wood C, Brun P, Sidi D, Devictor D, Tchernia G, Huault G. Severe thrombocytopenia induced by heparin in an infant with acute myocarditis. Arch Fr Pediatr 1990; 47: 357-359.
    PubMedGoogle Scholar
  • 69 Schiffmann H, Unterhalt M, Harms K, Figulla HR, Völpel H, Greinacher A. Erfolgreiche Behandlung einer Heparin-induzierten Thrombozytopenie Typ II im Kindesalter mit rekombinantem Hirudin. Monatsschr Kinderheilkunde 1997; 145: 606-612.
    PubMedGoogle Scholar
  • 70 Olinger GN, Hussey CV, Olive JA, Malik MI. Cardiopulmonary bypass in patients with previously documented heparin-induced platelet aggregation. J Thorac Cardiovasc Surg 1984; 87: 673-677.
    PubMedGoogle Scholar
  • 71 Smith JP, Walls JT, Muscato MS, McCord ES, Worth ER, Curtis JJ, Silver D. Extracorporeal circulation in a patient with heparin-induced thrombocytopenia. Anaesthesiology 1985; 62: 363-365.
    CrossrefPubMedGoogle Scholar
  • 72 Makhoul RG, Greenberg CS, McCann RL. Heparin associated thrombocytopenia and thrombosis: A serious clinical problem and potential solution. J Vasc Surg 1986; 4: 522-528.
    CrossrefPubMedGoogle Scholar
  • 73 Warkentin TE, Kelton JG. Timing of heparin-induced thrombocytopenia (HIT) in relation to previous heparin use: absence of an anamnestic immune response, and implications for repeat heparin use in patients with a history of HIT (abstract). Blood 1998; 92 (Suppl. 01) 182a.
    PubMedGoogle Scholar
  • 74 Magnani HN, Beijering RJR, Ten Cate JW, Chong BH. Orgaran anticoagulation for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. In: Pifarre R. ed. New Anticoagulants for the Cardiovascular Patient. Philadelphia: Hanley & Belfus Inc.; 1997: 487-500.
    Google Scholar
  • 75 Riess FC, Löwer C, Seelig C, Bleese N, Kormann J, Müller-Berghaus G, Pötzsch B. Recombinant hirudin as a new anticoag ulant during cardiac operations instead of heparin: Successful for aortic valve replacement in man. Thorac Cardiovasc Surg 1995; 110: 265-267.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 76 Riess FC, Pötzsch B, Bader K, Bleese N, Greinacher A, Löwer C, Madlener K, Müller-Berghaus G. A case report on the use of recombinant hirudin as an anticoagulant for cardiopulmonary bypass in open heart surgery. Eur J Cardiothorac Surg 1996; 10: 386-388.
    CrossrefPubMedGoogle Scholar
  • 77 Koster A, Kuppe H, Hetzer R, Sodian R, Crystal GJ, Mertzlufft F. Emergent cardiopulmonary bypass in five patients with heparin-induced thrombocytopenia type II employing recombinant hirudin. Anaesthesiology 1998; 89: 777-780.
    CrossrefPubMedGoogle Scholar
  • 78 Chong BH, Magnani HN. Orgaran in heparin-induced thrombocytopenia. Haemostasis 1992; 22: 85-91.
    PubMedGoogle Scholar
  • 79 Greinacher A, Drost W, Michels I, Leitl J, Gottsmann M, Kohl HJ, Glaser M, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: successful therapy with the heparinoid Org 10172 in a patient showing cross-reaction to LMW heparins. Ann Hematol 1992; a; 64: 40-42.
    CrossrefPubMedGoogle Scholar
  • 80 Greinacher A, Philippen KH, Kemkes-Matthes B, Möckl M, Mueller-Eckhardt C, Schaefer K. Heparin-associated thrombocytopenia type II in a patient with end-stage renal disease: Successful anticoagulation with the low-molecular-weight heparinoid Org 10172 during haemodialysis. Nephrol Dial Transplant 1993; 8: 1176-1177.
    PubMedGoogle Scholar
  • 81 Von Bonsdorff M, Stiekema J, Harjanne A, Alapiesse U. A new low molecular weight heparinoid Org 10172 as anticoagulant in hemodialysis. Int J Artif Organs 1990; 13: 103-108
    CrossrefPubMedGoogle Scholar
  • 82 Tholl U, Greinacher A, Overdick K, Anlauf M. Life-threatening anaphylactic reaction following parathyroidectomy in a dialysis patient with heparin-induced thrombocytopenia. Nephrol Dial Transplant 1997; 12: 2750-2755.
    CrossrefPubMedGoogle Scholar
  • 83 Vanholder RC, Camez A, Veys N, Soria J, Mirshahi MC, Soria C, Ringoir S. Recombinant hirudin. A specific thrombin-inhibiting anticoagulant for hemodialysis. Kidney Int 1994; 45: 1754-1759.
    CrossrefPubMedGoogle Scholar
  • 84 Van Wyk V, Badenhorst PN, Luus HG, Kotzé HF. A comparison between the use of recombinant hirudin and heparin during hemodialysis. Kidney Int 1995; 48: 1338-1343.
    CrossrefPubMedGoogle Scholar
  • 85 Nowak G, Bucha E, Brauns I, Czerwinski R. Anticoagulation with r-hirudin in regular haemodialysis with heparin-induced thrombocytopenia (HIT II). The first long term application of rhirudin in a haemodialysis patient. Wien Klin Wochenschr 1997; 109: 354-358.
    PubMedGoogle Scholar
  • 86 Hempel S, Lubenow N, Greinacher A. Nierenersatztherapie unter r-hirudin (Refludan) bei Heparin-induzierter Thrombozytopenie Typ II. Infusionsther Transfusionsmed 1998; 25: 5-7 p.
    PubMedGoogle Scholar
  • 87 Vanholder RC, Camez A, Veys N, Van Loo A, Dhondt AM, Ringoir S. Pharmacokinetics of recombinant hirudin in hemodialyzed end-stage renal failure patients. Thromb Haemost 1997; 77: 650-655.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 88 Mehta DP, Yoder EL, Appel J, Bergsman KL. Heparin-induced thrombocytopenia and thrombosis reversal with streptokinase. A case report and review of the literature. Am J Hematol 1991; 36: 275-279.
    CrossrefPubMedGoogle Scholar
  • 89 Krueger SK, Andreas E, Weinand E. Thrombolysis in heparin-induced thrombocytopenia with thrombosis. Ann Intern Med 1985; 103: 159.
    PubMedGoogle Scholar
  • 90 Clifton GD, Smith MD. Thrombolytic therapy in heparin-associated thrombocytopenia with thrombosis. Clin Pharm 1986; 5: 597-601.
    PubMedGoogle Scholar
  • 91 Dieck JA, Rizo-Patron C, Unisa A, Mathur V, Massumi GA. A new manifestation and treatment alternative for heparin-induced thrombosis. Chest 1998; 98: 1524-1526.
    PubMedGoogle Scholar
  • 92 Sobel M, Adelman B, Szentpeterey S, Hofmann M, Posner MP, Jenvey W. Surgical management of heparin-associated thrombocytopenia. Strategies in the treatment of venous and arterial thromboembolism. J Vasc Surg 1988; 8: 395-401.
    CrossrefPubMedGoogle Scholar
  • 93 Frame JN, Mulvey KP, Phares JC, Anderson MJ. Correction of severe heparin-associated thrombocytopenia with intravenous immunoglobulin. Ann Intern Med 1989; 111: 946-947.
    CrossrefPubMedGoogle Scholar
  • 94 Vender JS, Matthew EB, Silverman IM, Konoitz H, Dau PC. Heparin-associated thrombocytopenia: Alternative managements. Anesth Analg 1986; 65: 520-522.
    PubMedGoogle Scholar
  • 95 Nurden AT, Laroche-Traineau J, Jallu V, Broult J, Durrien C, Besse P. et al. Heparin-induced thrombocytopenia: Observation of the nature of the antibody activities and on the use of gammaglobulin concentrates in a patient with thrombotic complications. Thromb Haemost 1991; 65: 796a.
    PubMedGoogle Scholar
  • 96 Grau E, Linares M, Olaso MA, Ruvira J, Sanchis J. Heparin-induced thrombocytopenia response to intravenous immunoglobulin in vivo and in vitro. Am J Hematol 1992; 39: 312-313.
    CrossrefPubMedGoogle Scholar
  • 97 Warkentin TE, Kelton JG. Interaction of heparin with platelets, including heparin-induced thrombocytopenia. In: Bounameaux H. ed. Low-Molecular-Weight Heparins in Prophylaxis and Therapy of Thromboembolic Diseases. New York: Marcel Dekker, Inc.; 1994: 75-127.
    Google Scholar
  • 98 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: 641-645.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 99 Bouvier JL, Lefebre P, Villain P, Elias A, Durand JM, Juhan I, Serradigmigni A. Treatment of serious heparin-induced thrombocytopenia by plasma exchange: Report on 4 cases. Thromb Res 1988; 51: 335-336.
    CrossrefPubMedGoogle Scholar
  • 100 Brady J, Riccio JA, Yumen OH, Makary AZ, Greenwood SM. Plasmapheresis: A therapeutical option in the management of heparin-associated thrombocytopenia with thrombosis. Am J Clin Pathol 1991; 96: 394-397.
    CrossrefPubMedGoogle Scholar
  • 101 Nand S, Robinson JA. Plasmapheresis in the management of heparin-associated thrombocytopenia with thrombosis. Am J Hematol 1988; 28: 204-206.
    CrossrefPubMedGoogle Scholar
  • 102 Thorp D, Canty A, Whiting J, Dart G, Lloyd JV, Duncan E, Gallus A. Plasma exchange and heparin-induced thrombocytopenia. Prog Clin Biol Res 1990; 337: 521-522.
    PubMedGoogle Scholar
  • 103 Manzano L, Yebra M, Vargas JA, Barbolla L, Alvarez-Mon M. Plasmapheresis in heparin-induced thrombocytopenia and thrombosis. Stroke 1990; 21: 1236.
    PubMedGoogle Scholar
  • 104 Poullin P, Pietri P, Lefevre P. Heparin-induced thrombocytopenia with thrombosis: Successful treatment with plasma exchange. Brit J Haematol 1998; 102: 630-631.
    CrossrefPubMedGoogle Scholar
  • 105 Laster JL, Nichols WK, Silver D. Thrombocytopenia associated with heparin-coated catheters in patients with heparin-associated anti-platelet antibodies. Arch Intern Med 1989; 149: 2285-2287.
    CrossrefPubMedGoogle Scholar
  • 106 Gruel Y, Lermusiaux P, Lang M, Darnige L, Rupin A, Delahousse B, Guilmot JL, Leroy J. Usefulness of antiplatelet drugs in the manegement of heparin-associated thrombocytopenia and thrombosis. Ann Vasc Surg 1991; 5: 552-555.
    CrossrefPubMedGoogle Scholar
  • 107 Warkentin TE. Heparin-induced thrombocytopenia. Pathogenesis, frequency, avoidance and management. Drug Saf 1997; 17: 325-341.
    CrossrefPubMedGoogle Scholar
  • 108 Pedicord DL, Thomas BE, Mousa SA, Dicker IB. Glycoprotein IIb/IIIa receptor antagonists inhibit the development of platelet procoagulant activity. Thromb Res 1998; 90: 247-258.
    CrossrefPubMedGoogle Scholar
  • 109 Keularts IMLW, Béguin S, de Zwaan C, Hemker HC. Treatment with a GP IIb/IIIa antagonist inhibits thrombin generation in platelet rich plasma from patients. Thromb Haemost 1998; 80: 370-371.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 110 Hérault JP, Peyrou V, Savi P, Bernat A, Herbert JM. Effect of SR 121566A, a potent GP IIb-IIIa antagonist on platelet-mediated thrombin generation in vitro and in vivo. Thromb Haemost 1998; 79: 383-388.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 111 Hérault JP, Lalé A, Savi P, Pflieger AM, Herbert JM. In vitro inhibition of heparin-induced platelet aggregation in plasma from patients with HIT by SR121566, a newly developed GP IIb/IIIa antagonist. Blood Coagul Fibrinolysis 1997; 8: 206-207.
    CrossrefPubMedGoogle Scholar
  • 112 Mak KH, Kottke-Marchant K, Brooks LM, Topol EJ. In vitro efficacy of platelet glycoprotein IIb/IIIa antagonist in blocking platelet function in plasma of patients with heparin-induced thrombocytopenia. Thromb Haemost 1998; 80: 989-993.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 113 Herbert JM, Savi P, Jeske WP, Walenga JM. Effect of SR 121566A, a potent GP IIb-IIIa antagonist, on the HIT serum/heparin-induced platelet mediated activation of human endothelial cells. Thromb Haemost 1998; 80: 326-331.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 114 Polgar J, Eichler P, Greinacher A, Clemetson KJ. Adenosine diphosphate (ADP) and ADP receptor play a major role in platelet activation/aggregation induced by sera from heparin-induced thrombocytopenia patients. Blood 1998; 91: 549-554.
    PubMedGoogle Scholar
  • 115 Tsao PW, Forsythe MS, Mousa SA. Dissociation between the anti-aggregatory & anti-secretory effects of platelet integrin aIIbb2 (GPIIb/IIIa) antagonists, c7E3 and DMP728. Thromb Res 1997; 89 (02) 137-146.
    PubMedGoogle Scholar
  • 116 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: 90-95.
    CrossrefPubMedGoogle Scholar
  • 117 Hourellou MH, Conard J, Lecrubier C, Samama M, Roque D’Orbeostel O, de Fenoyl O. et al. Persistent heparin-induced thrombocytopenia despite therapy with low molecular weight heparin. Thromb Haemost 1984; 51: 134.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 118 Gouault-Heilmann M, Huet Y, Adnot S, Contant G, Bonnet F, Intrator L, Payen D, Levent M. Low molecular weight heparin fractions as an alternative therapy in heparin-induced thrombocytopenia. Haemostasis 1987; 17: 134-140.
    PubMedGoogle Scholar
  • 119 Leroy J, Leclerc MH, Delahousse B, Guerois C, Foloppe P, Gruel Y, Toulemonde F. Treatment of heparin-associated thrombocytopenia and thrombosis with low-molecular weight heparin (CY216). Semin Thromb Hemost 1985; 11: 326-329.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 120 Kleinschmidt S, Ziegenfuß T, Seyfert UT, Greinacher A. Septisch-toxisches Herz-Kreislauf-Versagen als Folge einer Heparin-induzierten Thrombozytopenie mit ”White-Clot-Syndrom.”. Anästhesiol Intensivmed Notfallmed Schmerzther 1993; 28: 58-60.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 121 Babcock RB, Dumper CW, Scharfman WB. Heparin-induced thrombocytopenia. N Engl J Med 1976; 295: 237-241.
    CrossrefPubMedGoogle Scholar
  • 122 Cimo PL, Moake JL, Weinger RS, Ben-Menachem Y, Khalil KG. Heparin-induced thrombocytopenia: Association with a platelet aggregating factor and arterial thromboses. Am J Hematol 1979; 6: 125-233.
    CrossrefPubMedGoogle Scholar
  • 123 Contreras M. The appropriate use of platelets: an update from the Edinburgh Consensus Conference. Br J Haematol 1998; 101 (Suppl. 01) 10-12.
    CrossrefPubMedGoogle Scholar