Immunoassays for diagnosis of coagulation disorders

Summary

Immunoassays play a pivotal role in the clinical laboratory. In the coagulation section of the laboratory, they are used as an aid for diagnosis of deep vein thrombosis or pulmonary embolism, thrombophilia screening, or detection of coagulation factor deficiencies, respectively. Enzyme-linked immunosorbent assay (ELISA) and latex agglutination immunoassay technologies are currently most widely used, while Luminescent Oxygen Channeling Immuno - assay (LOCI^®) and other chemiluminescencebased immunoassays are emerging technologies for the coagulation laboratory. However, not all immunoassay technologies employed are compatible with the workflow requirements of the coagulation laboratory, and, not all technologies are suitable for detection or quantification of every marker.

This review focuses on technical and performance aspects of those immunoassay technologies that are most widely used in the coagulation laboratory, and provides a description of markers that are typically tested by immunoassays.

Zusammenfassung

Immunoassays spielen im klinischen Labor eine herausragende Rolle. Im Gerinnungslabor werden sie unterstützend bei der Diagnose der tiefen Beinvenenthrombose und der Lungenembolie eingesetzt und beim Thrombophilie-Screening sowie der Ermittlung von Gerinnungsfaktorenmängeln verwendet. ELISA (enzyme-linked immunosorbent assay) und latexverstärkte Agglutinationstests werden gegenwärtig am häufigsten im Gerinnungslabor verwendet, während die Luminescent- Oxygen-Channeling-Immunoassay(LOCI^®)Technologie und andere Chemilumineszenzbasierte Immunoassays aufkommende Technologien darstellen.

In diesem Übersichtsartikel werden technische und Leistungsaspekte der verschiedenen im Gerinnungslabor verwendeten Immunoassay-Technologien sowie die typischerweise mittels Immunoassays getesteten Marker vorgestellt.

Keywords

ELISA - immunoassay - luminescent oxygen channeling - latex agglutination

Schlüsselwörter

ELISA - Immunoassay - LOCI - Agglutinationstest

• Literature

• 1 Bates SM, Weitz JI. Coagulation assays. Circulation 2005; 112: e53-e60.
• 2 Dempfle CE. Use of D-dimer assays in the diagnosis of venous thrombosis. Semin Thromb Hemost 2000; 26: 631-641.
• 3 Meijer P, Haverkate F, Kluft C. et al. A model for the harmonisation of test results of different quantitative D-dimer methods. Thromb Haemost 2006; 95: 567-572.
• 4 Dempfle CE. D-dimer: standardization versus harmonization. Thromb Haemost 2006; 95: 399-400.
• 5 Pelzer H, Schwarz A, Strüber W. Determination of human prothrombin activation fragment 1+2 in plasma with an antibody against a synthetic peptide. Thromb Haemost 1992; 65: 153-159.
• 6 Merz M, Eidam A, Braun S. et al. Multicenter evaluation of a new ELISA for the determination of prothrombin fragment F 1+2. J Thromb Haemost 2005; 03 (Suppl. 01) P0099.
• 7 Tripodi A, Cattaneo M, Moltene A. et al. Changes of prothombin fragment 1+2 (F 1+2) as a function of increasing intensity of oral anticoagulation. Thromb Haemost 1998; 79: 571-573.
• 8 De Raucourt E, Meyer G, Landais P. et al. Markers of the hemostatic system activation in pulmonary embolism. Changes during and after cessation of anticoagulant treatment. Blood Coag Fibrinol 2000; 11: 249-253.
• 9 Mammen EF. Disseminated intravascular coagulation (DIC). Clin Lab Sci 2000; 13: 239-245.
• 10 MacCallum PK, Thomson JM, Poller L. Effects of fixed minidose warfarin on coagulation and fibrinolysis following major gynaecological surgery. Thromb Haemost 1990; 64: 511-515.
• 11 Hollenstein UM, Pernerstorfer T, Homoncik M. et al. Effect of factor X inhibition on coagulation activation and cytokine induction on human systemic inflammation. J Infect Dis 2002; 86: 1270-1276.
• 12 Pelzer H, Schwarz A, Heimburger N. Determination of human thrombin-antithrombin III complex in plasma with an enzyme-linked immunosorbent assay. Thromb Haemost 1988; 59: 101-106.
• 13 Blanke H, Prätorius G, Leschke M. et al. Die Bedeutung des Thrombin-Antithrombin-III-Komplexes in der Diagnostik der Lungenembolie und der tiefen Venenthrombose – Vergleich mit Fibrinopeptid A, Plättchenfaktor 4 und b-Thromboglobulin. Klin Wochensch 1987; 65: 757-763.
• 14 Hoek JA, Sturk A, ten Cate JW. et al. Laboratory and clinical evaluation of an assay of thrombin-antithrombin III complexes in plasma. Clin Chem 1988; 34: 2058-2062.
• 15 Gulba DC, Barthels M, Reil GH, Lichtlen PR. Thrombin/antithrombin-III complex level as early predictor of reocclusion after successful thrombolysis. Lancet 1988; 332: 97.
• 16 Seitz R, Blanke H, Prätorius G. et al. Increased thrombin activity during thrombolysis. Thromb Haemost 1988; 59: 541-542.
• 17 Seitz R, Wolf M, Egbring R, Havemann K. The disturbance of hemostasis in septic shock: role of neutrophil elastase and thrombin, effects of antithrombin III and plasma substitution. Eur J Haematol 1989; 43: 22-28.
• 18 Kobayashi T, Terao T. Preeclampsia as chronic disseminated intravascular coagulation. Study of two parameters: thrombin-antithrombin III complex and D-dimers. Gynecol Obstet Invest 1987; 24: 170-178.
• 19 Dahlbäck B. Protein S and C4b-binding protein: Components involved in the regulation of the protein C anticoagulant system. Thromb Haemost 1991; 66: 49-61.
• 20 De Stefano V, Finazzi G, Mannucci PM. Inherited thrombophilia: Pathogenesis, Clinical Syndromes and management. Blood 1996; 87: 3531-3544.
• 21 Kemkes-Matthes B. Aquired protein S deficiency. Clin Invest 1992; 70: 529-534.
• 22 Patzke J, Merz M, Siegemund A. Characterization of a protein S assay measuring the APC cofactor activity. J Lab Med 2007; 31: 262-272.
• 23 Wolf M, Boyer-Neumann C, Peynaud-Debayle E. et al. Clinical applications of a direct assay of free protein S antigen using monoclonal antibodies. A study of 59 cases. Blood Coagul Fibrinolysis 1994; 05: 187-192.
• 24 Deffert C, Esteve F, Grimaux M, Gouault-Heilmann M. A direct, automated immuno-turbidimetric assay for free protein S antigen in plasma. Blood Coag Fibrinol 2001; 12: 137-141.
• 25 Serra J, Sales M, Chitolie A. et al. Multicentre evaluation of IL test free PS: A fully automated assay to quantify free protein S. Thromb Haemost 2002; 88: 975-983.
• 26 Zöller B, Garcia de Frutos P, Dahlbäck B. Evaluation of the relationship between protein S and C4b-binding protein isoforms in protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease. Blood 1995; 85: 3524-3531.
• 27 Muszbek L, Yee VC, Hevessy Z. Blood coagulation factor XIII: structure and function. Thromb Res 1999; 94: 271-305.
• 28 Bereczky Z, Katona E, Muszbek L. Fibrin stabilization factor (factor XIII), fibrin structure and thrombosis. Pathophysiol Haemost Thromb 2004; 33: 430-437.
• 29 Board PG, Losowsky MS, Miloszewski KJ. Factor XIII: inherited and acquired deficiency. Blood Rev 1993; 07: 229-242.
• 30 Tosetto A, Castaman G, Rodeghiero F. Acquired plasma factor XIII deficiencies. Haematologica 1993; 78: 5-10.
• 31 Karimi M, Bereczky Z, Cohan N, Muszbek L. Factor XIII deficiency. Semin Thromb Hemost 2009; 35: 426-438.
• 32 Bartels M, von Depka M. Das Gerinnungskompendium. Stuttgart: Thieme; 2003
• 33 Wilmer M, Schroder V, Kohler HP. Methods for the determination of factor XIII/XIIIa. Hämostaseologie 2002; 22: 32-42.
• 34 Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med 2002; 346: 752-763.
• 35 Giannakopoulos B, Passam F, Ioannou Y, Krilis SA. How we diagnose the antiphospholipid syndrome. Blood 2009; 113: 985-993.
• 36 Miyakis S, Lockshin MD, Atsumi T. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 04: 295-306.
• 37 Lackner KJ, Peetz D, von Landenberg P. Revision of the Sapporo criteria for the antiphospholipid syndrome – Coming to grips with evidence and Thomas Bayes?. Thromb Haemost 2006; 95: 917-919.
• 38 Galli M. The antiphospholipid triangle. J Thromb Haemost 2010; 08: 234-236.
• 39 Warkentin TE, Chong BH, Greinacher A. Heparininduced thrombocytopenia: towards consensus. Thromb Haemost 1998; 79: 1-7.
• 40 Baglin TP. Heparin induced thrombocytopenia thrombosis (HIT/T) syndrome: diagnosis and treatment. J Clin Pathol 2001; 54: 272-274.
• 41 Amiral J, Bridey F, Dreyfus M. et al. Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia. Thromb Haemost 1992; 68: 95-96.
• 42 Greinacher A, Pötzsch B, Amiral J. et al. Heparin-associated thrombocytopenia: isolation of the antibody and characterization of a multimolecular PF4-heparin complex as the major antigen. Thromb Haemost 1994; 71: 247-251.
• 43 Warkentin TE, Sheppard JA. Testing for heparin-induced thrombocytopenia antibodies. Transfus Med Rev 2006; 20: 259-272.
• 44 Yalow RS, Berson SA. Immunoassay of endogenous plasma insulin in man. J Clin Invest 1960; 39: 1157-1175.
• 45 Köhler G, Milstein C. Continuous culture of fused cells secreting specific antibody of predefined specificity. Nature 1975; 256: 495-497.
• 46 Wide L, Bennich H, Johannson SGO. Diagnosis of allergy by an in-vitro test for allergen antibodies. Lancet 1967; 02: 1105-1107.
• 47 Miles LEH, Hales CN. Labelled antibodies and immunological assay systems. Nature 1968; 219: 186-189.
• 48 Engvall E, Perlmann P. Enzyme linked immunosorbent assay (ELISA).Quantitative assay of immunoglobulin G. Immunochemistry 1971; 08: 871-874.
• 49 Bozic M, Blinc A, Stegnar M. D-dimer, other markers of haemostasis activation and soluble adhesion molecules in patients with different clinical probabilities of deep vein thrombosis. Thromb Res 2002; 108: 107-114.
• 50 Stephan S, Schwarz H, Borchert A. et al. Tests for the measurement of factor VII-activating protease (FSAP) activity and antigen levels in citrated plasma, their correlation to PCR testing, and utility for the detection of the Marburg I-polymorphism of FSAP. Clin Chem Lab Med 2008; 46: 1109-1116.
• 51 Amiral J, Grosley B, Boyer-Neumann C. et al. New assay for free protein S antigen using two distinct monoclonal antibodies specific for the free form. Blood Coag Fibrinol 1994; 05: 179-186.
• 52 Katona E, Haramura G, Karpati L. et al. A simple, quick one-step ELISA assay for the determination of complex plasma factor XIII (A2B2). Thromb Haemost 2000; 83: 268-273.
• 53 Warkentin TE, Linkins LA. Immunoassays are not created equal. J Thromb Hemost 2009; 07: 1256-1259.
• 54 Galli M. Clinical utility of laboratory tests used to identify antiphospholipid antibodies and to diagnose the antiphospholipid syndrome. Semin Thromb Hemost 2008; 34: 329-334.
• 55 Avrameas S, Ternyck T. Peroxidase labeled antibody and Fab conjugates with enhanced intracellular penetration. Immunochemistry 1971; 08: 1175-1179.
• 56 Kato K, Hamaguchi Y, Fukui H, Ishikawa E. Enzyme linked immunosorbent conjugation of rabbit antibody with β-D-galactosidase. Eur J Biochem 1976; 62: 285-287.
• 57 Litchfield WJ, Craig AR, Frey WA. et al. Novel shell/ core particles for automated immunoassays. Clin Chem 1984; 30: 1489-1493.
• 58 Galvin JP, Looney CE, Leflar CC. et al. Particle enhanced photometric immunoassay systems. In: Nakamura RM, Ditto WR, Tucker III ES. (eds). Clinical laboratory assays: new technology and future directions. New York: Masson Publishing; 1983: 73-95.
• 59 Prize CP, Trull AK, Berry D, Gorman EG. Development and validation of a particle-enhanced immunoassay for C-reactive protein. J Immunol Methods 1987; 99: 205-211.
• 60 Prize CP, Newman DJ. Light scattering immunoassay. In: Price CP, Newman DJ. Principles and practice of immunoassay. London: MacMillan Reference; 1997: 443-480.
• 61 Prize CP, Newman DJ. Precipitation and agglutination methods. 1. Turbidimetric and nephelometric immunoassay. In Masseyeff RF, Albert WH, Staines NA. (eds). Methods of immunological analysis. Weinheim: VCH; 1993: 134-158.
• 62 Coen DHerak, Milos M, Zadro R. Evaluation of the Innovance D-dimer analytical performance. Clin Chem Lab Med 2009; 47: 945-951.
• 63 Engelhardt W, Palareti G, Legnani C, Gringel E. Comparative evaluation of D-dimer assays for exclusion of deep venous thrombosis in symptomatic outpatients. Thromb Res 2003; 112: 25-32.
• 64 Veyradier A, Fressinaud E, Sigaud M. A new automated method for von Willebrand factor antigen measurement using latex particles. Thromb Haemost 1999; 81: 320-321.
• 65 Piñol M, Sales M, Costa M. et al. Evaluation of a new turbidimetric assay for von Willebrand factor activity useful in the general screening of von Willebrand disease. Haematologica 2007; 92: 712-713.
• 66 Patzke J, Althaus H, Schneppenheim R. Development of a new particle enhanced agglutination VWF activity assay with no need of ristocetin. Hämostaseologie 2010; 30: P07-P02.
• 67 Patzke J, Althaus H, Budde U. et al. Evaluation of a new VWF activity assay based on GPIbα ???????????binding in the absence of ristocetin. Hämostaseologie 2010; 30: P07-P03.
• 68 Sykulev YK, Sherman DA, Cohen RJ, Eisen HN. Quantitation of reversible binding by particle counting: hapten-antibody interaction as a model system. Proc Natl Acad Sci USA 1992; 89: 4703-4707.
• 69 Vitzthum F, Behrens F, Anderson NL, Shaw JH. Proteomics: from basic research to diagnostic application. A review of requirements & needs. J Proteome Res 2005; 04: 1086-1097.
• 70 Ullman EF, Kirakossian H, Switchenko AC. et al. Luminescent oxygen channeling assay (LOCI): sensitive, broadly applicable homogeneous immunoassay method. Clin Chem 1996; 42: 1518-1526.
• 71 Ullman EF, Kirakossian H, Singh S. et al. Luminescent oxygen channeling immunoassay: measurement of particle binding kinetics by chemiluminescence. Proc Natl Acad Sci USA 1994; 91: 5426-5430.
• 72 Kappel A, Althaus H, Ehm M. Quantitation of D-dimer by LOCI^™ technology. J Thromb Haemost. 2007 05. (Suppl 2):P-T-072.
• 73 Kricka LJ. Chemiluminescent and bioluminescent techniques. Clin Chem 1991; 37: 1472-1481.
• 74 de Moerloose P, Reber G, Arnout J. Evaluation of a new quantitative highly sensitive D-dimer assay for exclusion of venous thromboembolism. J Thromb Haemost 2009; 07: 1590-1591.
• 75 De Moerloose P, Reber G, Musial J, Arnout J. Analytical and clinical performance of a new, automated assay panel for the diagnosis of antiphos - pholipid syndrome. J Thromb Haemost 2010; 08: 1540-1546.
• 76 La’ulu SL, Dominguez CM, Roberts WL. Performance characteristics of the AxSYM D-dimer assay. Clin Chim Acta 2008; 390: 148-151.
• 77 Elf JL, Strandberg K, Svensson PJ. Performance of two relatively new quantitative D-dimer assays (Innovance D-dimer and AxSYM D-dimer) for the exclusion of deep vein thrombosis. Thromb Res 2009; 124: 1701-1705.
• 78 Reber G, Bounameaux H, Perrier A, de Moerloose P. A new rapid point-of-care D-dimer enzyme-linked immunosorbent assay (Stratus CS D-dimer) for the exclusion of venous thromboembolism. Blood Coagul Fibrinolysis 2004; 15: 435-438.
• 79 Villalta D, Alessio MG, Tampoia M. et al. Accuracy of the first fully automated method for anti-cardiolipin and anti-beta2 glycoprotein I antibody detection for the diagnosis of antiphospholipid syndrome. Ann NY Acad Sci 2009; 1173: 21-27.