Subscribe to RSS
DOI: 10.1055/s-0037-1619662
Überwachung der Antikoagulanzientherapie mit Fondaparinux
Bestimmung der Anti-Faktor-Xa-SpiegelMonitoring anticoagulation by fondaparinuxdetermination of anti factor Xa-levelsPublication History
Publication Date:
27 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00034925/200503/lookinside/thumbnails/10-1055-s-0037-1619662_de-1.jpg)
Zusammenfassung
Im Gegensatz zu niedermolekularem und unfraktioniertem Heparin besitzt Fondaparinux, ein synthetisch hergestelltes Pentasaccharid, einen selektiv hemmenden Effekt auf den Gerinnungsfaktor X. Die Substanz ist seit drei Jahren zur Hochrisikothromboseprophylaxe nach großen orthopädischen Operationen zugelassen. Auf Grund der ausgezeichneten Bioverfügbarkeit nach subkutaner Gabe, die einmal pro Tag in körpergewichtsunabhängiger Dosierung (bei einem Körpergewicht von 50-100 kg) erfolgen kann, ist normalerweise ein Monitoring nicht erforderlich. Insbesondere seit der europaweiten Zulassung zur Therapie venöser Thrombosen ist jedoch im Ausnahmefall (z. B. Verdacht auf Fehldosierung, bei Niereninsuffizienz oder Blutungen) ein Monitoring im Routinelabor sinnvoll.
Inzwischen wurden chromogene Substratmethoden, basierend auf zur Verfügung stehenden Monitoring-Methoden zur Messung des Faktor Xa inhibierenden Effektes der niedermolekularen Heparine, publiziert. Unter Berücksichtigung dieser Publikationen sollte Fondaparinux als Kalibrator verwendet und die Einheiten in μg/ml angegeben werden. Wegen der synthetischen Herstellung der Substanz findet sich eine lineare Dosis/Wirkungsbeziehung in einem weiten Konzentrationsbereich, so dass eine sehr gute Präzision der Methodik an Vollautomaten erreicht werden kann.
Summary
In contrast to low molecular weight heparin and unfractionated heparin fondaparinux is a selective synthetic factor Xa inhibitor. It was approved for thromboprophylaxis after major orthopaedic surgery three years ago. Because of its excellent bioavailability after subcutaneous application once daily independent of body weight (within the range of 50-100 kg) monitoring of the substance is usually not necessary. Since its recent approval for therapeutic use in acute venous thrombosis monitoring might be useful in special clinical situations (e. g. suspected over- or underdosing, renal insufficiency or severe bleeding complications).
Based on standard laboratory methods for the chromogenic determination of the anti-factor Xa activity of low molecular weight heparin several chromogenic substrate assays were published for monitoring. Only fondaparinux should be used for calibration and measured fondaparinux levels should be expressed in μg/ml of the fondaparinux calibrator. Because of its single synthetic chemical entity, a linear dose/response relationship over a wide concentration range is observed and measurements are of high precision.
-
Literatur
- 1 Amiral J, Lormeau JC, Marfing-Koka A. et al. Absence of cross-reactivity of SR 90107A/ORG 31540 pentasaccharid with antibodies to heparin PF 4 complexes developed in heparin-induced thrombozytopenia. Blood Coag Fibrinol 1997; 8: 114-7.
- 2 Bauer KA, Erikkson BI, Lassen MR. et al. Fondaparinux compared with Enoxaparin for the prevention of venous thrombembolism after elective major knee surgery. N Engl J Med 2001; 345: 1305-10.
- 3 Boneu B, Necciari J, Cariou R. et al. Pharmacokinetics and tolerance of the natural pentasaccharide (SR 90107/ORG-31540) with high affinity to antithrombin III in man. Thromb Haemost 1995; 74: 1468-73.
- 4 Depasse F, Gerotziafas GT, Busson J. et al. Assessment of three chromogenic and one clotting assays for the measurment of synthetic pentasaccharide fondaparinux (Arixtra) anti-Xa activity. J Thromb Haemost 2004; 2: 346-8.
- 5 Donat F, Duret JP, Santoni A. et al. The pharmacokinetics of fondaparinux sodium in healthy volunteers. Clin Pharmacokinet 2002; 41 (Suppl. 02) 1-9.
- 6 Eriksson BI, Bauer KA, Lassen MR. et al. Fondaparinux compared with Enoxaparin for the prevention of venous thromboembolism after hipfracture surgery. N Engl J Med 2001; 345: 1298-304.
- 7 Harenberg J, Jörg I, Fenyvesi T. Treatment of heparin-induced thrombocytopenia with fondaparinux. Haematologica 2004; 89: 1017-8.
- 8 Heinzelmann M, Bosshart H. Fondaparinux sodium lacks immunmodulatory effects of heparin. Am J Surg 2004; 187: 111-3.
- 9 Herbert JM, Petitou M, Lormeau JC. et al. SR 90107 A/Org 31540, a novel anti factor Xa antithrombotic agent. Cardiovasc Drug Rev 1997; 15: 1-26.
- 10 Kirchmayr K, Piechottka G, Kläffling C. et al. Development of two chromogenic substrate methods for monitoring of Fondaparinux sodium, a new selective inhibitor of factor Xa. Hämostaseologie 2004; 24: A8 (V9).
- 11 Lassen MR. The EHPHESUS study: Comparison of the first synthetic factor Xa inhibitor with low molecular weight heparin in the prevention of venous thromboembolism after elective hip replacement surgery. Thromb Haemost 2001; (Suppl): OC45.
- 12 Lormeau JC, Herault JP. The effect of the synthetic pentasaccharide SR 90107/ORG 31540 on thrombin generation ex vivo is uniquely due to AT. mediated neutralization of Factor Xa. Thromb Haemost 1995; 74: 1474-7.
- 13 Matisse Investigators. Subcutaneous Fondaparinux versus Intravenous Unfractionated Heparin in the Initial Treatment of Pulmonary Embolism. N Eng J Med 2003; 349: 1695-702.
- 14 Matziolis G, Perka C, Disch A. et al. Effects of fondaparinux compared with dalteparin, enoxaparin and unfractionated heparin on human osteoblasts. Calcif Tissue Int 2003; 73: 370-9.
- 15 Paolucci F, Frasa H, van Aarle F. et al. Two sensitive and rapid chromogenic assays of fondaparinux Sodium (Arixtra) in human plasma and other biological matrices. Clin Lab 2003; 49: 451-60.
- 16 Petitou M, Duchaussoy P, Ledermann I. et al. Synthesis of heparin fragments. A chemical synthesis of the pentasachcharide O-(2-deoxy-2-sulfamido-6-O-sulfo-alpha-D-glucopyranosyl)-1à4)-O-(beta-D-glucopyranosyluronic acid)-(1à4)-0-(2-deoxy-2-sulfamido-3, 6-di-O-sulfo-alpha-D-glucopyranosyl)-1à4)-O-(2-O-sulpho-alpha-Lidopyrano-syluronic acid)-(1à4)-2-deoxy-2sulfamido-6-O-sulfo-D-glucopyranose decasodium salt, a heparin fragment having high affinity for antithrombin III. Carbohydr Res 1986; 147: 221-36.
- 17 The Rembrandt Investigators. Treatment of proximal deep vein thrombosis with a novel synthetic compound (SR90107A/ORG31540) with pure anti-factor Xa activity. Circulation 2000; 102: 2726-31.
- 18 Turpie AGG, Bauer KA, Eriksson BI. et al. Superiority of fondaparinux over enoxaparin in preventing venous thrombembolism in major orthopedic surgery using different efficacy end points. Chest 2004; 126: 501-8.
- 19 Walenga J.M, Fareed J, Jeske WP. et al. Development of a synthetic heparin pentasaccharide: Fondaparinux. Turk. J Haematol 2002; 19: 137-50.
- 20 Walenga JM, Hoppensteadt D, Mayuga M. et al. Functionality of pentasaccharide depends on endogenous antithrombin levels. Blood 2000; 96: 817.