Überwachung der Antikoagulanzientherapie mit Fondaparinux

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.

Schlüsselwörter

Fondaparinux - Anti-Faktor-Xa-Spiegel - chromogene Testmethoden

Keywords

Fondaparinux - anti-factor Xa-level - chromogenic substrate assay

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