First Workshop for Detection of Heparin-induced Antibodies: Validation of the Heparin-induced Platelet-activation Test (HIPA) in Comparison with a PF4/Heparin ELISA

P. Eichler; U. Budde; S. Haas; H. Kroll; R. M. Loreth; O. Meyer; U. Pachmann; B. Pötzsch; A. Schabel; D. Albrecht; A. Greinacher

doi:10.1055/s-0037-1614536

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1999; 81(04): 625-629
DOI: 10.1055/s-0037-1614536

Rapid Communication

Schattauer GmbH

First Workshop for Detection of Heparin-induced Antibodies: Validation of the Heparin-induced Platelet-activation Test (HIPA) in Comparison with a PF4/Heparin ELISA

P. Eichler

¹From the Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany

,

U. Budde

²Transfusion Medicine, Hospital Hamburg-Harburg, Hamburg

,

S. Haas

³Institute for Experimental Surgery, Technical University, München

,

H. Kroll

⁴Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University, Gießen, Germany

,

R. M. Loreth

⁵Westpfalz Hospital, Kaiserslautern, Germany

,

O. Meyer

⁶Hospital Rudolf Virchow, Humboldt-University, Berlin

,

U. Pachmann

⁷Red Cross, Bayreuth, Germany

,

B. Pötzsch

⁸Institute for Hemostasis Research and Transfusion Medicine, Kerckhoff-Klinik, Bad Nauheim, Germany

,

A. Schabel

⁹Katharinen Hospital, Stuttgart, Germany

,

D. Albrecht

¹From the Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany

,

A. Greinacher

¹From the Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany

› Institutsangaben

Abstract

Summary

Background. No data exist regarding the inter-laboratory reproducibility of the heparin-induced-platelet-activation (HIPA) test, the most widely used functional assay in Germany for the detection of heparin-induced thrombocytopenia (HIT) antibodies. Methods. Nine laboratories used an identical protocol to test eight different sera with the HIPA test. Five laboratories also tested the sera with a platelet factor 4 (PF4)/heparin-complex ELISA. Cross-reactivity with danaparoid-sodium was assessed using 0.2 aFXa units instead of heparin in the HIPA test. Results. Two of nine laboratories had no discrepant HIPA test results. Four laboratories differed in one sample, one reported two discrepant results, and two laboratories reported more than two discrepant results. Cross-reactivity with danaparoid-sodium test results differed among laboratories. PF4/heparin ELISA results were identical in all five laboratories. Conclusion. The HIPA test requires strict quality control measures. Using both a sensitive functional assay (HIPA test) and a PF4/heparin ELISA will allow detection of antibodies directed to antigens other than PF4/heparin complexes as well as detection of IgM and IgA antibodies with PF4/heparin specificity.

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Referenzen

References
1 Warkentin TE, Kelton JG. Heparin-induced thrombocytopenia. Prog Hemost 1991; 10: 1-34.
2 Warkentin TE, Kelton JG. Interaction of heparin with platelets, including HIT In: Low-molecular weight heparins in prophylaxis and therapy of thromboembolic diseases. Bounameaux ed New York: Marcel Dekker; 1994: 75-127.
3 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.
4 Greinacher A, Poetzsch B, Amiral J, Dummel V, Eichner A, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: isolation of the antibodyand characterization of a multimolecular PF4-heparin complex as the major antigen. Thromb Haemost 1994; 71: 247-51.
5 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.
6 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.
7 Chong BH. HIT: Mechanism of interaction of the heparin-dependent antibody with platelets. Br J Haematol 1989; 73: 235-40.
8 Kelton JG, Sheridan D, Santos A, Smith J, Steeves K, Smith C, Brown C, Murphy DJ. Heparin-induced thrombocytopenia: Laboratory studies. Blood 1988; 72: 925-30.
9 Cines DB. Disorders associated with antibodies to endothelial cells. Rev Infect Dis 1989; 11: 705-11.
10 Cines DB, Tomaski A, Tannenbaum S. Immune endothelial-cell injury in heparin-associated thrombocytopenia. N Engl J Med 1987; 316: 581-9.
11 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.
12 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.
13 Visentin GP, Malik M, Cyganiak KA, Aster RH. Patients treated with unfractionated heparin during open heart surgery are at high risk to form antibodies reactive with heparin-platelet factor 4 complexes. J Lab Clin Med 1996; 128: 376-83.
14 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 HIT: a study of 44 cases. Thromb Haemost 1995; 73: 21-8.
15 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.
16 Sheridan D, Carter C, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia. Blood 1986; 67: 27-30.
17 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.
18 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.
19 Burgess JK, Lindemann R, Chesterman CN, Chong BH. Single amino acid mutation of Fc gamma receptor is associated with the development of heparin-induced thrombocytopenia. Br J Haematol 1995; 91: 761-6.
20 Denomme GA, Warkentin TE, Horsewood P, Sheppard JA, Warner MN, Kelton JG. Activation of platelets by sera containing IgG1 heparin-dependent antibodies: an explanation for the predominance of the Fc gamma “low responder” (His131) gene in patients with heparin-induced thrombocytopenia. J Lab Clin Med 1997; 130: 278-84.
21 Carlsson LE, Santoso S, Baurichter G, Kroll H, Papenberg S, Eichler P, Westerdaal NA, Kiefel V, van de Winkel JG, Greinacher A. Heparin-induced thrombocytopenia: new insights into the impact of the Fc gamma RIIa-R-H131 polymorphism. Blood 1998; 92: 1526-31.
22 Bachelot-Loza C, Saffroy R, Lasne D, Chatellier G, Aiach M, Rendu F. Importance of the Fc gamma RIIa-Arg/His-131 polymorphism in heparin-induced thrombocytopenia diagnosis. Thromb Haemost 1998; 79: 523-8.
23 Arepally G, McKenzie SE, Jiang XM, Poncz M, Cines DB. Fc gamma RIIA H/R 131 polymorphism, subclass-specific IgG anti-heparin/platelet factor 4 antibodies and clinical course in patients with heparin-induced thrombocytopenia and thrombosis. Blood 1997; 89: 370-5.
24 Griffiths E, Dzik WH. Assays for heparin-induced thrombocytopenia. Transf Med 1997; 7: 1-11.
25 Chong BH, Eisbacher M. Pathophysiology and laboratory testing of heparin-induced thrombocytopenia. Sem Hematol 1998; 35: 3-8.
26 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: 344-50.
27 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.
28 Lee DH, Warkentin TE, Denomme A, Hayward CPM, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia: detection of platelet microparticles using flow cytometry. Brit J Haemat 1996; 95: 724-31.
29 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; 2: 410-6.
30 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. Brit J Haemat 1996; 92: 954-9.
31 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 rtPA lysis and recombinant hirudin (Lepirudin). Blood Coagulat Fibrinol 1998; 9: 273-7.
32 Warkentin TE, Chong BH, Greinacher A. Heparin-induced thrombocytopenia: Towards consensus. Thromb Haemost 1998; 79: 1-7.