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Hamostaseologie 1991; 11(01): 17-32
DOI: 10.1055/s-0038-1660276
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Schattauer GmbH

Anwendung und Bedeutung von enzymimmunologischen Methoden in der Gerinnungsdiagnostik

E. Spanuth
1   Boehringer Mannheim GmbH, Mannheim
,
K.-E. Stötzer
1   Boehringer Mannheim GmbH, Mannheim
› Author Affiliations
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Publication History

Publication Date:
26 June 2018 (online)

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Zusammenfassung

Das hämostaseologische Laboratorium hat sich schon seit langem immunologischer Analysentechniken bedient. Die am meisten eingesetzen Methoden sind die Immunelektrophorese nach Laurell und immunologische Latex-Agglutinationstests. Als beispielhaft ist in diesem Zusammenhang die Bestimmung des von-Willebrand-Faktors und der Fibrin(ogen)-Spaltprodukte zu erwähnen.

Durch die Entwicklung hochsensitiver Meßmethoden, zunächst auf radioimmunologischer, inzwischen jedoch enzymimmunologischer Basis, hat sich das Spektrum der Parameter erweitert. Insbesondere die Vorgänge der intravaskulären Aktivierung der Hämostase sowie die thrombophile Diathese und damit die Thromboseprophylaxe sind durch die neuen immunologischen Analysetechniken besser beherrschbar geworden.

Nach ausführlicher Darstellung der Grundlagen der enzymimmunologischen Meßverfahren werden die wichtigsten Anwendungsbereiche aufgezeigt und ein Überblick zu den bisher vorliegenden klinischen Erfahrungen gegeben. Im einzelnen wird auf die Thrombophiliediagnostik mit der Bestimmung von Protein C, Protein S und Antiphospholipid-Antikörpern sowie der Abklärung der Fibrinolysekapazität durch Bestimmung des t-PA und PAI eingegangen. Darüber hinaus werden die neuen diagnostischen Möglichkeiten umrissen, die sich durch die Bestimmung der »Thrombosemarker« Antithrombin-Ill-Neoantigene, Antithrombin-Ill-Thrombinkomplexe und der spezifischen Fibrinspaltprodukte D-Dimere ergeben.

 

  • LITERATUR

  • 1 Aillaud MF, Roul C, Elias A, Bouvier JL, Serradimign A, Juhan IVague. Clinical relevance of plasma fibrin degradation products determination in patients with deep vein thrombosis (DVT). Thromb Haemost 1987; 58: 332-41.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Amiral J, Adalbert B, Adam M. Application of enzym immunoassays to coagulation testing. Clin Chem 1984; 30: 1512-6.
    PubMedGoogle Scholar
  • 3 Amiral J, Walenga JM, Adam M. Development and performance characteristics of a competitive enzyme immunoassay for fibrinopeptid A. Semin Thromb Haemost 1984; 10: 228-42.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Amiral J, Adam M, Plassart V, Minard F, Vissac AM. Immunoassays for the measurement of protein S. In: Fibrinolysis: Current Prospects. PJ Caffney. et al. (eds) London: Libbey; 1988: 125-8.
    Google Scholar
  • 5 Amiral J, Minard F, Laroche P. Assay of anti-phospholipid antibodies (APA) and clinical significane. Xllth International Congress of the I.S.T.H. Tokyo 1989
    PubMedGoogle Scholar
  • 6 Amiral J, Vissac AM, Mimilla F, Grosley B. Assay of blood activation by measurement of AT III-serin esterasecomplexes (ATM) using a specific monoclonal antibody »4C9«. Oral Presentation at Xllth Congress of I. S.T.H. Tokyo 1989
    PubMedGoogle Scholar
  • 7 Bartlett A, Dormandy KM, Hawkey CM, Stableforth P, Voller A. Factor VIII related antigen; measurement by enzyme immunoassay. Br Med J 1976; 01: 994-6.
    CrossrefPubMedGoogle Scholar
  • 8 Bertina RM, Broekmanns AW, von der Linden IK, Mertens K. Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemost 1982; 48: 1-5.
    PubMedGoogle Scholar
  • 9 Bounameaux H, Slossmann D, Moerloos PE, Reber G. Diagnostic value of plasma D-Dimer in suspected pulmonary embolism. Lancet 1988; 09: 628-9.
    PubMedGoogle Scholar
  • 10 Boyer C, Wolf M, Rothschild C, Migaud M, Amiral J, Mannuci PM, Meyer D, Larrien MJ. An enzyme immunoassay (ELISA) for the quantitation of human factor VII. Thromb Haemost 1986; 56: 250-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Boyer C, Rothschild C, Wolf M, Amiral J, Meyer D, Larriue MJ. A new method for the estimation of protein C by ELISA. Thromb Res 1984; 36: 579-89.
    CrossrefPubMedGoogle Scholar
  • 12 Boyer-Neumann C, Wolf M, Amiral J, Gujader AM, Meyer D, Larriue MJ. Familial type I protein S deficiency associated with severe venous thrombosis. Thromb Haemost 1988; 60: 128-32.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Broekmann AW, Veitkamp JJ, Bertina RM. Cogenital protein C deficiency and venous thromboembolism. N Engl J Med 1983; 309: 340-4.
    CrossrefPubMedGoogle Scholar
  • 14 Comp PC, Esmon CT. Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 1984; 310: 1525-8.
    CrossrefPubMedGoogle Scholar
  • 15 Contant G, Gouault-Heilmann M, Martinoli JL. Heparin inactivation during blood storage: its prevention by blood collection in citric acid, theophylline, adenosin, dipyridamole CTAD mixture. Thromb Res 1983; 31: 365-74.
    CrossrefPubMedGoogle Scholar
  • 16 Dahlbäck B. Interaction between vitamin K dependent protein S and the complement protein C4b-binding protein-A. Link between coagulation and the complement system. Semin Thromb Haemostas 1984; 10: 139-48.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Dudczak R, Niessner H, Thaler E, Lechner K, Kletter K, Frischauf H, Domanig E, Aicher H. Plasma concentration of platelet specific proteins and fibrinopeptide A in patients with artificial heart valves. Haemostasis 1981; 10: 186-94.
    PubMedGoogle Scholar
  • 18 Fair DS, Plow EF, Edgington TS. Combined functional and immunochemical analysis of normal and abnormal human factor X. J Clin Invest 1979; 64: 884-94.
    CrossrefPubMedGoogle Scholar
  • 19 Gaffney PJ. Fibrin fragmentation by plasmin: molecular considerations and their relevance to DIC and thrombosis. In: FibrinogenRecent Biochemicals and Medical Aspects. Henschen A, Graeff H, Lottspeich F. (eds). Berlin, New York: de Grayter; 1982: 407-23.
    Google Scholar
  • 20 Gaffney PJ, Curtis AD. A collaborative study of a proposed international standard for tissue plasminogen activator (t-PA). Thromb Haemost 1985; 53: 134-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Hagenaars AM, Kuipers AH, Nagel J. Elimination of interference of rheumatoid factor in ELISA by peptic digestion of antibodies. Imm Enz Assay Tech 1980; 01: 209-15.
    PubMedGoogle Scholar
  • 22 Harenberg J, Zimmermann R, Schettler C. Protein C: Bestimmung und klinische Wertigkeit. Ärztl Lab 1985; 31: 116-20.
    PubMedGoogle Scholar
  • 23 Hoyer LW. The factor VIII-complex: structure and function. Blood 1981; 58: 1-13.
    PubMedGoogle Scholar
  • 24 Holvoet P, Cleemput H, Collen D. Assay of human tissue-type plasminogen activator (t-PA) with an enzyme linked immunosorbent assay (ELISA) based on three murine monoclonal antibodies to t-PA. Thromb Haemost 1985; 54: 684-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Hubbard AR. Standardization of protein C in plasma : establishment of an international standard. Thromb Haemost 1988; 59: 464-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Juhan-Vague I, Valadier J, Alessi MC, Aillaud MF, Ansaldi J, Philip-Joet C, HoeL Pvoet, Serradimigni A, Collens D. Deficient t-PA-release and elevated PA-inhibitor levels in patients with spontaneous or recurrent deep venous thrombosis. Thromb Haemost 1987; 57: 67-72.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Kerry PJ, Curtis AD. Standardisation of b-thromboglobulin (B-TG) and platelet factor 4 (PF4), a collaborative study to establish international standards for B-TG and PF4. Thromb Haemost 1985; 53: 51-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Korninger C, Lechner K, Niessner H, Gössinger H, Kundi M. Impaired fibrinolytic capacity predisposes for recurrence of venous thrombosis. Thromb Haemost 1984; 52: 127-30.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Lichey J, Reschowski I, Dissmann Th, Lode H, Priesnitz M, Hoffmann M, Huckauf H, Spanuth E. D-Dimer as highly specific and sensitive parameter in the diagnosis of lung embolism. In: Fibrinogen 4, Current Basic and Clinical Aspects. Matsuda M, Iwanaga S, Takada A, Henschen A. (eds). Amsterdam: Elsevier Science Publishers; 1990: 209-12.
    Google Scholar
  • 30 Marder VJ, Mannucci PM, Firkin BC, Hoyer LW, Meyer D. Standard nomenclature for FVIII and von Willebrand-factor: a recommendation by the international Committee on Thrombosis and Haemostasis. Thromb Haemost 1985; 54: 871-2.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Meyer D, Frommei D, Larriue MJ, Zimmermann TS. Selective absence of large forms of F VIII, von Willebrand Factor in acquired von Willebrand’s syndrom. Response to transfusion. Blood 1979; 54: 600-6.
    PubMedGoogle Scholar
  • 32 Nakane PK, Kamaci A. Peroxidase labeled antibody: a new method of conjugation. I. Histochem Cytochem 1974; 22: 1084-91.
    PubMedGoogle Scholar
  • 33 Neises M, Platz M, Strittmatter HJ, Melchert F, Spanuth E. D-Dimers indicates the progression of malignant disease in patients with breast cancer. In: Fibrinogen 4, Current Basic and Clinical Aspects. Matsuda M, Iwanga A, Takada A, Henschen A. (eds). Amsterdam: Elsevier Science Publishers; 1990: 201-7.
    Google Scholar
  • 34 Orstavik KH, Veitkamp JJ, Bertin RM, Hermanns J. Detection of carriers of haemophilia B. Br J Haemost 1979; 42: 293-301.
    PubMedGoogle Scholar
  • 35 Paramo JA, Jonker JJC, Collen D. Plasminogen activator inhibitor (PAQ-Inhibitor) activity in the blood of patients with deep vein thrombosis. Thromb Haemost 1985; 54: 725-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Parekh VR, Mannucci PM, Ruggeri ZM. Immunological heterogeneity of haemophilia B: a multicentre study of 98 kindreds. Br J Haemat 1978; 40: 643-55.
    CrossrefPubMedGoogle Scholar
  • 37 Parquet-Guernez A, Mazurier C, Amiral J, Martinoli JL. Assay of factor IX: Ag using an enzym immuno assay. Thromb Res 1984; 35: 703-12.
    CrossrefPubMedGoogle Scholar
  • 38 Parvez Z. Immunoassays in coagulation testing. New York. Berlin: Heidelberg, Tokyo: Springer, 1984
    Google Scholar
  • 39 Pechel L, Tiarks CY, Stevens J, Sudhindra RR, Lipworth L. Relationship of factor IXAntigen and coagulant in haemophilia B patient and carriers. Thromb Haemost 1978; 40: 465-77.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Röka L, Spanuth E. Neue Aspekte in der Gerinnungsdiagnostik. Stuttgart, New York: Schattauer; 1984
    Google Scholar
  • 41 Rowbotham BJ, Caroll P, Whitaker AN, Rylatt DB, Webber AJ. Measurement of crosslinked fibrin derivates use in the diagnosis of venous thrombosis. Thromb Haemost 1987; 57: 59-61.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Scharf RE, Schneider W. Zur klinischen Bedeutung der thrombozytenspezifischen Proteine. Therapiewoche 1981; 31: 8443-47.
    PubMedGoogle Scholar
  • 43 Scharrer J. The von Willebrand Syndrom. Blut 1983; 47: 123-30.
    CrossrefPubMedGoogle Scholar
  • 44 Schlegelberger B, Plendl H, Grotz W. Die Bestimmung von Faktor VIII R:Ag: Vergleich zwischen Enzymimmunoassay und Immunoelektrophorese. In: Neue Aspekte der Gerinnungsdiagnostik. Röka L, Spanuth E. (Hrsg). Stuttgart, New York: Schattauer; 1984: 121-8.
    Google Scholar
  • 45 Schröck R, Hafter R, Schmid L, Babic R, Ulm K, Gössner W, Graeff H. Tumorassoziierte Antigene und Fibrinderivate als Reaktionsprodukte des Ovarialkarzinoms. Geburtshilfe Frauenheilkd 1986; 46: 1-10.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 46 Schwarz HP, Lämmle B, Griffin JH. Protein S und venöse Thrombophilie. Hämostaseologie 1985; 05: 139-43.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Schwieder G, Vieregge P, Wiedemann G, Wagner T. Kongenitaler Protein-C-Mangel und thromboembolische Erkrankungen. Dtsch med Wschr 1987; 112: 425-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Simank HG, Simon M, Bode Ch, Zimmermann R, Kübler W, Weber E. Clinical usefullness of D-Dimer: elevation during fibrinolytic treatment of venous thrombosis or myocardial infarction. Thromb Res 1989; 56: 541-6.
    CrossrefPubMedGoogle Scholar
  • 49 Sprengers ED, Akkermann JWN, Jansen BG. Blood platelet plasminogen activator inhibitor: two different polls of endothelial cell type plasminogen activator inhibitor in blood. Thromb Haemost 1986; 55: 325-49.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 50 Stötzer KE, Spanuth E, Amiral J. Neue Methoden zur spezifischen Bestimmung von Fibrinspaltprodukten (D-Dimere). Lab med 1988; 12: 51-9.
    PubMedGoogle Scholar
  • 51 Tripplett DA. Clinical significance of antiphospholipid antibodies. Thromb Haemost 1988; 10: 2-10.
    PubMedGoogle Scholar
  • 52 Tsakiris DA, Marbet CA, Zbinden B, Dukkert F, Biland L. Thrombosen bei einem wahrscheinlich doppelt-heterozygoten jungen Mann aus einer asymptomatischen Familie mit Protein-C-Mangel und Protein-SDysfunktion. Schweiz med Wschr 1988; 188: 1583-5.
    PubMedGoogle Scholar
  • 53 Wagner T, Schwieder C. Wertigkeit verschiedener Protein-C-Bestimmungsmethoden bei kongenitalem Protein-C-Mangel und unter Phenprocoumontherapie. Ärztl Lab 1987; 33: 136-40.
    PubMedGoogle Scholar
  • 54 Wagner T, Schwieder C, Wiedemann C. Kumarinnekrose und Protein C. Hämostaseologie 1987; 07: 53-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 55 Weidmann CE, Wallace DJ, Peter JB, Knight PJ, Bear MB, Klingenberg JR. Studies of IgG, IgM, and IgA antiphospholipid antibody isotopes in systemic lupus erythematosus. J Rheumatol 1988; 15: 74-9.
    PubMedGoogle Scholar
  • 56 Weiss P, Soff GA, Halkin H, Seligsohn U. Decline of proteins C and S and factor II, VII, IX and X during initiation of warfarin therapy. Thromb Res 1987; 45: 783-90.
    CrossrefPubMedGoogle Scholar
  • 57 Werner W, Rey HC, Wielinger H. Über die Eigenschaften eines neuen Chromogens für die Blutzuckerbestimmung nach der COD/ POD-Methode. Z Anal Chem 1970; 225-8.
    PubMedGoogle Scholar
  • 58 Witt I. Testsysteme mit synthetischen Peptidsubstraten in der Hämostaseologie. Hämostaseologie 1988; 08: 47-61.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 59 Woodhams BJ. The simultaneous measurement of total and free Protein S by ELISA. Thromb Res 1988; 50: 213-20.
    CrossrefPubMedGoogle Scholar