Hamostaseologie 1999; 19(01): 13-18
DOI: 10.1055/s-0038-1660373
Übersichtsarbeiten/Review Articles
Schattauer GmbH

Messung von Heparin-induzierten IgG-Antikörpern mittels »Fluorescence-Linked Immunofiltration Assay« (FLIFA) bei Heparin-induzierter Thrombozytopenie Typ II

Ursula Hoffmann
1   I. Medizinische Klinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg
,
G. Huhle
1   I. Medizinische Klinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg
,
L. C. Wang
1   I. Medizinische Klinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg
,
X. H. Song
1   I. Medizinische Klinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg
,
J. Harenberg
1   I. Medizinische Klinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg
› Author Affiliations
Further Information

Publication History

Publication Date:
27 June 2018 (online)

Zusammenfassung

Die Heparin-induzierte Thrombozytopenie ist eine seltenere, jedoch schwere Nebenwirkung der Heparintherapie. Heparin-induzierter IgG-Antikörper wurde als Haupt-Isotyp und hauptsächlicher pathogener Antikörper bei der Pathophysiolgie abgeklärt. Da die Patienten ein hohes Risiko für die Entwicklung thrombotischer Ereignisse aufweisen, ist es wichtig und wünschenswert, die klinische Diagnose zu bestätigen und eine Heparin-Reexposition zu vermeiden. Zur Bestimmung von Heparin-induziertem IgG bei Patienten mit Heparin-induzierter Thrombozytopenie (HIT) Typ II wurde ein »Fluorescence-Iinked immunofiltration assay« (FLIFA) entwickelt. Anhand dieses Neoantigen-Assays läßt sich eine hohe Frequenz von Heparin-induziertem IgG bei HIT Typ II nachweisen. Die sofortige Bestimmung von pathogenem, Heparin-induziertem IgG kann ein nützliches Verfahren zur raschen Diagnose einer HIT Typ II sein, das die weitere Behandlung der Patienten erleichtern könnte.

 
  • Literatur

  • 1 Amiral J, Bridey F, Dreyfus M. et al. Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia (letter). Thromb Hae-most 1992; 68: 95-6.
  • 2 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.
  • 3 Amiral J, Marfaing-Koka Wolf M. et al. Presence of autoantibodies to interleukin-8 or neutrophil-activating peptide-2 in patients with heparin-associated thrombocytopenia. Blood 1996; 88: 410-6.
  • 4 Arepally G, Reynolds C, Tomaski A. et al. Comparison of PF4/Heparin ELISA assay with the 14-C-serotonin release assay in the diagnosis of heparin-induced thrombocytopenia. Am J Clin Pathol 1995; 104: 648-54.
  • 5 Aster RH. Heparin-induced thrombocytopenia and thrombosis. N Engl J Med 1995; 332: 1374-6.
  • 6 Benhamou AG, Gruel Y, Barsotti J, Castellani L, Marchand M, Guerois C, Leclere MH, Delahousse B, Leroy J. The white clot syndrome of heparin associated thrombocytopenia and thrombosis (WCS or HATT): (26 cases). Int Angiol 1985; 4: 303-10.
  • 7 Chong BH. Heparin-induced thrombocytopenia. Aus N Z J Med 1992; 22: 145-52.
  • 8 Chong BH. Heparin-induced thrombocytopenia. Br J Haematol 1995; 89: 431-9.
  • 9 Eichinger S, Kyrie PA, Brenner B. et al. Thrombocytopenia associated with low-molecular weight heparin. Lancet 1991; 377: 1425-6.
  • 10 Eichler P, Barthels K, Budde U. et al. Workshop on the validation of the heparin-induced-platelet activation (HIPA). Ann Hematol 1997; 74 Suppl. II 229 (Abstr).
  • 11 Franantoni JC, Pollet R, Gralnick HR. Heparin-induced thrombocytopenia: confirmation of diagnosis with in vitro methods. Blood 1995; 45: 395-401.
  • 12 Gouault-Heilmann M, Huet Y, Adnot S, Contant G, Intrator L, Payen D, Lèvent M. Low-molecular weight heparins as an alternative therapy in heparin-induced thrombocytopenia. Haemostasis 1967; 17: 134-40.
  • 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, Pötzsch Amiral J, Dummel V, Eichner A, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: isolation of the antibody and characterization of a multi-molecular PF4-heparin complex as the major antigen. Thromb Haemost 1994; 71: 247-51.
  • 16 Gruel Y, Rupin A, Darnige L, Moalic RP, Poumier GP, Binet C. Specific quantification of heparin-dependent antibodies for the diagnosis of heparin-associated thrombocytopenia using an enzyme-linked immunosorbent assay. Thromb Res 1991; 62: 377-87.
  • 17 Hach-Wunderle V, Kainer K, Krug B, Müller-Berghaus G, Pötzsch B. Heparin-associated thrombosis despite normal platelet count (letter). Lancet 1994; 344: 469-70.
  • 18 Harenberg J, Huhle G, Piazolo L, Wang LC, Heene DL. Anticoagulation in patients with heparin-induced thrombocytopenia type II. Semin Thromb Hemost 1997; 23: 189-96.
  • 19 Harenberg J, Huhle G, Wang L, Hoffmann U, Bayeri C, Kerowgan M. Association of heparin-induced skin lesions, intracutaneous tests and heparin-induced IgG. Allergy. 1999 im Druck.
  • 20 Hawkes R, Niday E, Gordon J. A dot Immu-noblotting assay for monoclonal and other antibodies. Anal Biochem 1982; 119: 142-7.
  • 21 Horellou MH, Conard J, Lecrubier C. et al. Persistent heparin-induced thrombocytopenia despite therapy with low molecular weight heparin. Th rombos Haemostas 1984; 5: 134.
  • 22 Kapsch DD, Adelstein EH, Rhodes GR, Silver D. Heparin-induced thrombocytopenia, thrombosis, and hemorrhage. Surgery 1979; 86: 148-55.
  • 23 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.
  • 24 Kelton JK, Warketin TE. Diagnosis of heparin-induced thrombocytopenia. Still a journey, not yet a destination. Am J Clin Pathol 1995; 104: 611-3.
  • 25 Lee DH, Warkentin TE, Denmme 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.
  • 26 Magnani HN. Heparin-induced thrombocytopenia: an overviews of 230 patients treated with Orgaran (Org 10172). Thromb Haemost 1993; 70: 554-61.
  • 27 Newmann PM, Swanson RL, Chong BH. Heparin induced thrombocytopenia: IgG binding to PF4-heparin complexes in the fluid phase and cross-reacitivity with low molecular weight heparin and heparinoid. Thromb Haemost 1998; 80: 292-7.
  • 28 Ngai PK, Ackermann F, Wendt H. et al. Protein A Antibody-capture ELISA (Pace): an ELISA format to avoid denaturation of surface-adsorbed antigens. J Immunol Methods 1993; 158: 267-76.
  • 29 Paffard SM, Miles RJ, Clark CR, Price RG. A rapid and sensitive enzyme linked immu-nofilter assay (ELIFA) for whole bacterial cells. J Immunol Methods 1996; 192: 133-6.
  • 30 Pinon JM, Foudrinier F, Mouget G. et al. Evaluation of risk and Diagnostic value of quantitative assays for anti-Toxoplasma gondii Immunoglobulin A (IgA), IgE and IgM and analytical study of specific IgG in immunodeficient patients. J Clin Microbio 1995; 33: 878-84.
  • 31 Ramakrishna R, Manoharan A, Kwan YL, Kyle PW. Heparin-induced thrombocytopenia: cross-reactivity between standard heparin, low molecular weight heparin, daltepa-rin (Fragmin) and heparinoid, danaparoid (Orgaran). Br J Haematol 1995; 91: 736-8.
  • 32 Richman DD, Cleveland PH, Oxman MN, Johson KM. The binding of staphylococcal protein A by the sera of different animal species. J Immunol 1982; 128: 2300-5.
  • 33 Sheridan D, Carter C, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia. Blood 1986; 67: 27-30.
  • 34 Stewart M, Etches WS, Boshkow LK, Gordon PA. Heparin-induced thrombocytopenia: an improved mehtod of detection based on lumiaggregometry. Br J Haematol 1995; 91: 173-7.
  • 35 Visetin 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.
  • 36 Vun CM, Evans S, Chong BH. Cross-reactivity study of low molecular weight heparins and heparinoid in heparin-induced thrombocytopenia. Thromb Res 1995; 81: 525-32.
  • 37 Wang LC, Huhle G, Hoffman U, Song XH, Harenberg J. Heparin-induced thrombocytopenia: New methods for determination, diagnosis and pathophysiology. Clin Lab 1998; 44: 771-80.
  • 38 Wang LC, Huhle G, Malsch R, Hoffmann U, Song XH, Harenberg J. Determination of heparin-induced IgG antibody by fluorescence-linked immunofiltration assay (FLIFA). J Immunol Meth 1998; 222: 93-9.
  • 39 Wang LC, Huhle G, Malsch R, Hoffmann U, Song XH, Harenberg J. Determination of heparin-induced IgG antibody in heparin-induced thrombocytopenia type II. Eur J Clin Invest. 1999 im Druck.
  • 40 Walenga JM. Sensitivity and specificity of various laboratory methods for heparin-induced thrombocytopenia syndrome. Acad Clin Appli Thromb Haemost 1996; (2nd annual meeting). Frankfurt. Nov 14th-17th (Abstract).
  • 41 Warkentin TE, Kelton JG. Heparin-induced thrombocytopenia. Ann Rev Med 1989; 40: 31-44.
  • 42 Warkentin TE, Chong BH, Greinacher A. Heparin-induced thrombocytopenia: towards consensus. Thromb Haemost 1998; 79: 1-7.
  • 43 Chong BH, Ismail F, Cade J, Gallus AS, Gordon S, Chestermann CN. Heparin-induced thrombocytopenia: Studies with a low molecular weight heparinoid Org 10172. Blood 1989; 73: 1592-6.
  • 44 Tomer A. A sensitive and specific functional flow cytometric assay for the diagnosis of heparin-induced thrombocytopenia. Br J Haematol 1997; 98: 648-56.
  • 45 Worley J, Lee S, Ma MS, Eisenberg A, Chen HY, Mansfield E. Fluorescence imaging in human identity testing. Biotechniques 1997; 23: 148-53.