Labormedizinische Aspekte des Thrombophilie-Screenings

Zusammenfassung

Ein Thrombophilie-Screening ist indiziert, wenn erstmalig ein thromboembolisches Ereignis im Alter unter 45 Jahren aufgetreten ist, bei positiver Familienanamnese oder wenn eine besondere klinische Konstellation vorliegt. Um valide Untersuchungsergebnisse zu erhalten, müssen gerinnungsphysiologische und laboratoriumsmedizinische Besonderheiten beachtet werden. Hier wird eine Übersicht zu Fallstricken und Möglichkeiten während der präanalytischen Phase der Thrombophiliediagnostik gegeben und die laborchemische Methodik zur Abklärung einer Thrombophilie beleuchtet.

Summary

For thrombophilia should be screened, if a first thrombo - embolic event has occurred at the age of less than 45 years, if family history indicates thrombophilia, or in the case of a special clinical condition. To get valid diagnostic results a few pecularities concerning the physiology of coagulation and laboratory medicine have to be considered. This review gives an overview of pitfalls and options during the preanalytical phase of thrombophilia diagnostics. Furthermore , the laboratory assays to perform a screening are highlighted.

Schlüsselwörter

Thrombophilie - Gerinnungsdiagnostik - Präanalytik

Keywords

Thrombophilia - coagulation diagnostics - preanalytics

• Literatur

• 1 Adcock D, Kressin D, Marlar RA. The effect of time and temperature variables on routine coagulation tests. Blood Coagul Fibrinolysis 1998; 9: 463-470.
• 2 Alhenc-Gelas M, Reny J-L, Aubry M-L. et al. The FXIII Val 34 Leu mutation and the risk of venous thrombosis. Thromb Haemost 2000; 84: 1117-1118.
• 3 Bathum L, Münster A-M, Nybo M. et al. Denaturing High-Performance Liquid Chromatography mutation analysis in patients with reduced protein S levels. Clin Chim Acta 2008; 390: 76-81.
• 4 Bruhn HD, Schambeck CM, Hach-Wunderle V. Hämostaseologie für die Praxis. Stuttgart: Schattauer; 2007: 67-69.
• 5 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol (Basel) 1957; 17: 237-241.
• 6 Cooper PC, Hampton KK, Makris M. et al. Further evidence that activated protein C resistance can be misdiagnosed as inherited functional protein S deficiency. Br J Haematol 1994; 88: 201-203.
• 7 Cooper PC, Rezende SM. An overview of methods for detection of factor V Leiden and the prothrombin G20210A mutations. Int J Lab Hem 2007; 29: 153-162.
• 8 De Laat B, Derksen RH, De Groot PG. High-avidity anti-beta glycoprotein I antibodies highly correlate with thrombosis in contrast to low avidity anti-beta-glycoprotein I antibodies. J Thromb Haemost 2006; 4: 1619-1621.
• 9 Devreese KM. Evaluation of a new silica clotting time in the diagnosis of lupus anticoagulants. Thromb Res 2007; 120: 427-438.
• 10 Eichinger S. Globaltest versus Profil: Wird das endogene Thrombinpotential das etablierte Thrombophiliescreening ablösen?. J Lab Med. 2008 in Druck.
• 11 Galli M, Luciani D, Bertolini G. et al. Anti-beta 2-glycoprotein I, antiprothrombin antibodies and the risk of thrombosis int the antiphospholipid syndrome. Blood 2003; 102: 2717-2723.
• 12 Gessoni G, Valverde S. Clinical evaluation of a functional prothrombin time-based assay for identification of factor V Leiden carriers in a group of italian patiens with venous thrombosis. Blood Coag and Fibrinolysis 2007; 18: 603-610.
• 13 Goodwin AJ, Rosendaal FR, Kottke-Marchant K. et al. A review of the technical, diagnostic and epidemiologic considerations for protein S-Assays. Arch Pathol Lab Med 2002; 126: 1349-1366.
• 14 Gosselin RC, King JH, Janatpur KA. et al. Effects of pentasaccharide (Fondaparinux) and direct thrombin inhibtors on coagulation testing. Arch Pathol Lab Med 2004; 128: 1142-1145.
• 15 Heil W, Grunewald R, Amend M. et al. Influence of time and temperature on coagulation analytes in stored plasma. Clin Chem Lab Med 1998; 36: 459-462.
• 16 Jennings I, Kitchen S, Cooper P. et al. Sensitivity of functional protein S assays to protein S deficiency: a comparative study of three commercial kits. J Thromb Haemost 2003; 1: 1112-1117.
• 17 Johnson JV, Lowell JL, Badger GJ. et al. Effects of oral and transdermal hormonal contraception on vascular risk markers. Obstetr Gyn 2008; 111: 278-284.
• 18 Koenen RR, Tans G, van Oerle R. et al. The APCindependent anticoagulant activity of protein S in plasma is decreased by elevated prothrombin levels due to the prothrombin G20210A mutation. Blood 2003; 102: 1686-1692.
• 19 Kwok S, Higuchi R. Avoiding false posititves with PCR. Nature 1984; 339: 237-238.
• 20 Lim W, Crowther M. Antiphospholipid antibodies: a critical review of the literature. Curr Opin Hematol 2007; 14: 494-499.
• 21 Mackie I, Cooper P, Kitchen S. Quality assurance issues and interpretation of assays. Semin Hematol 2007; 44: 114-125.
• 22 Meijer P, Verbruggen W, de Weerd B. et al. Identification of determinants of the between-operator variation of the total protein S antigen assay: a collaborative study of the Dutch Working Group on Haemostasis Laboratory Diagnosis. Scand J Clin Lab Invest 2002; 62: 441-450.
• 23 Miyakis S, Lockshin MD, Atsumi T. et al. International consensus statement on an update of the classification criteria for definite antiphospho - lipid syndrome. J Thromb Haemost 2006; 4: 295-306.
• 24 Moore GW, Smith MP, Patel Y. et al. The Activated Seven Lupus Anticoagulant (ASLA) assay: a new test for lupus anticoagulants. Evidence that some LAs are detectable only in extrinsic pathway assays. Blood Coagul Fibrinolysis 2002; 13: 261-269.
• 25 Moore GW, Rangarajan S, Savidge F. The Activated Seven Lupus Anticoagulant Assay detects clinically significant antibodies. Clin Appl Thromb Hemost 2007; Sep 25 (epub) 1-6.
• 26 Moore GW, Savidge GF. Heterogeneity of Russel’s viper venom affects the sensitivity of the dilute Russel’s viper venom time to lupus anticoagulants. Blood Coagul Fibrinolysis 2004; 15: 279-282.
• 27 Moore GW. Combining Taipan snake venom Time/ Ecarin time screening with the mixing studies of conventional assays increases detection rates of lupus anticoagulants in orally anticoagulated patients. Thromb J 2007; 5: 12.
• 28 NCCLS Document H21-A3.. Collection, transport and processing of blood specimens for coagulation testing and general performance of coagulation assays. Wayne PA: 2000 3rd ed.
• 29 Pellegrino NM, Caccavo D. Variability in anticardioloipin antibody detection: Role of non-specific IgG binding and different microtiter plates. Clin Appl Thromb Haemost 2007; 13: 404-409.
• 30 Quehenberger P, Handler S, Mannhalter C. Evaluation of a highly specific functional test for the detection of factor V Leiden. Int J Clin Lab Res 2000; 30: 113-117.
• 31 Schöni R, Quenhenberger P, Wu JR. et al. Clinical evaluation of a new functional test for detection of activated protein C resistance (Pefakit® APC-R Factor V Leiden) at two centers in Europe and the USA. Thromb Res 2007; 119: 17-26.
• 32 Siegert G, Schellong S, Knoepfler R. et al. Low molecular weight heparin: a possible cause for higher protein S activity than free protein S concentration. Blood Coagul Fibrinolysis 2000; 11: 747-754.
• 33 Tomer A, Bar-Lev S, Fleisher S. et al. Antiphospholipid antibody syndrome: the flow cytometric annexin A5 competition assay as a diagnostic tool. Br J Haematol 2007; 139: 113-120.
• 34 Töpfer G, Funke U, Schulze M. et al. Determination of coagulation parameters in venous citrated blood, catheter blood and capillary blood: preanalytical problems. J Lab Med 2000; 24: 514-520.
• 35 Thomas L. Labor und Diagnose 6. Aufl. Frankfurt/Main: TH-Books; 2005: 596-600.
• 36 Tsuda T, Tsuda H, Yoshimura H. et al. Dynamic equilibrium between protein S and C4b binding protein ist important for accurate determination of free protein s antigen. Clin Chem Lab Med 2002; 40: 563-567.
• 37 Urbanus RT, Derksen RHMW, de Groot PG. Current insight into diagnostics and pathophysiology of the antiphospholipid syndrome. Blood Reviews 2008; 22: 93-105.
• 38 Van Cott EM, Ledford-Kraemer M, Meijer P. et al. An analysis of North American specialized coagulation laboratory association proficiency testing. Am J Clin Pathol 2005; 123: 778-785.
• 39 Vester B, Rassmussen K. High performance liquid chromatography method for rapid and accurate determination of homocysteine in plasma and serum. Eur J Clin Chem Clin Biochem 1991; 29: 549-554.
• 40 Wilson WA, Gharavi AE, Koike T. et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome report of an international workshop. Arthritis Rheum 1999; 42: 1309-1311.