The uncalibrated prothrombinase-induced clotting time test

Summary

The activated partial thromboplastin time test (aPTT) represents one of the most commonly used diagnostic tools in order to monitor patients undergoing heparin therapy. Expression of aPTT coagulation time in seconds represents common practice in order to evaluate the integrity of the coagulation cascade. The prolongation of the aPTT thus can indicate whether or not the heparin level is likely to be within therapeutic range. Unfortunately aPTT results are highly variable depending on patient properties, manufacturer, different reagents and instruments among others but most importantly aPTT’s dose response curve to heparin often lacks linearity. Furthermore, aPTT assays are insensitive to drugs such as, for example, low molecular weight heparin (LMWH) and direct factor Xa (FXa) inhibitors among others. On the other hand, the protrombinase-induced clotting time assay (PiCT^®) has been show to be a reliable functional assay sensitive to all heparinoids as well as direct thrombin inhibitors (DTIs). So far, the commercially available PiCT assay (Pefakit^®-PiCT^®, DSM Nutritional Products Ltd. Branch Pentapharm, Basel, Switzerland) is designed to express results in terms of units with the help of specific calibrators, while aPTT results are most commonly expressed as coagulation time in seconds. In this report, we describe the results of a pilot study indicating that the Pefakit PiCT UC assay is superior to the aPTT for the efficient monitoring of patients undergoing UFH therapy; it is also suitable to determine and quantitate the effect of LMWH therapy. This indicates a distinct benefit when using this new approach over the use of aPPT for heparin monitoring.

Zusammenfassung

Die aPTT ist eine der meist verwendeten Überwachungsmöglichkeiten bei Patienten mit He-parin-Therapie. Die Beurteilung der Gerin-nungszeit mittels aPTT ist ein viel genutztes Instrument, um die Integrität der Gerinnungskaskade zu untersuchen. Die aPTT-Verlängerung unter Heparin kann daher als Marker dafür verwendet werden, ob der Heparinspiegel im gewünschten therapeutischen Bereich ist. Unglücklicherweise sind die aPTT-Resultate stark abhängig von Patienteneigenschaften, unterschiedlichen Herstellern, verschiedenen Reagenzien und Instrumenten, so dass die Dosisantwort der aPTT auf Heparin oft nicht linear ist. Außerdem ist die aPTT nicht sensitiv genug, um niedermolekulare Heparine bzw. direkte Faktor-Xa-Inhibitoren zu monitieren. An-dererseits ist die PiCT (prothrombinase induced clotting time) ein zuverlässiger funktioneller Assay, um alle Heparin- und Heparinoide sowie direkte Thrombininhibitoren zu monitieren. Bis jetzt wurde der kommerziell erhältliche PiCT-Assay verwendet, um mit Hilfe spezifischer Ka-libratoren die Konzentration der genannten In-hibitoren direkt anzugeben; aPTT-Resultate werden jedoch in Sekunden angegeben. Wir beschreiben die Resultate einer Pilot-Studie, die ergibt, dass die “PiCT-UC” der aPTT zum Monitoring bei Patienten mit unfraktionierter Heparintherapie überlegen ist. PiCT-UC ist auch geeignet den Einfluss von niedrig-molekularem Heparin quantitativ adäquat wi-derzuspiegeln. Diese Resultate zeigen, dass der Gebrauch der PiCT-UC gegenüber dem Gebrauch der aPTT eine deutliche Verbes-serung des Heparin-Monitorings darstellt.

Keywords

Anticoagulation monitoring - aPTT - PiCT - universal functional assay

Schlüsselwörter

Heparin - aPTT - Monitoring - PiCT

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