Monitoring of antiplatelet therapy

Summary

Screening of platelet function can be performed by point-of-care testing followed by platelet aggregometry in response to agonists such as collagen, adenosine diphosphate, epinephrine, and arachidonic acid. Despite in use for decades, this technique is not well standardized. Monitoring of antiplatelet therapy is increasingly applied in patients at high risk for re-thrombosis or bleeding. To assess pharmacological inhibition of platelet function, agonist-induced platelet aggregation, thromboxane B2 (TxB2) and vasodilator-stimulated protein phosphorylation (VASP) are being measured. While serum TxB2 levels of < 2 ng/ml reflect aspirin-induced inhibition of cyclo-oxygenase-1 activity with high sensitivity, VASP exhibits a wide variability upon treatment with clopidogrel or prasugrel. Multiple studies reveal an association between high residual platelet reactivity and adverse cardiovascular events in patients on antiplatelet therapy. However, despite the plethora of platelet function assays currently under investigation, their use in daily practice cannot be recommended. This is due to several reasons: (i) there is no consensus on the method and a respective cut-off value associated with clinical adverse outcome, and (ii) data demonstrating any benefit of tailored antiplatelet therapy and its monitoring (based on assessment of platelet functions) are still limited. Thus, appropriate identification of ‘resistant’ or ‘poor responders’ to antiplatelet agents remains challenging in clinical practice.

Zusammenfassung

Zum Screening der Plättchenfunktion werden Point-of-Care-Techniken, anschließend die Aggregometrie nach Stimulation mit Agonisten wie Kollagen, Adenosindiphosphat, Adrenalin und Arachidonsäure eingesetzt. Zunehmend erfolgt ein Monitoring der antithrombozytären Therapie bei Patienten mit hohem Rethrombose- oder Blutungsrisiko. Als Nachweis der pharmakologischen Plättchenfunktionshemmung dienen neben Aggregometrie, die trotz ihres jahrzehntelangen Einsatzes nur unzureichend standardisiert ist, Messung der Thromboxan-B2 (TxB2)-Spiegel und Bestimmung der Vasodilator-stimulierten Proteinphosphorylierung (VASP). Serum-TxB2-Konzentrationen < 2 ng/ml spiegeln die Aspirin-induzierte Hemmung der Zyklooxygenase-1-Aktivität mit hoher Empfindlichkeit wider. Hingegen zeigen VASP-Spiegel eine große Streubreite unter Behandlung mit Clopidogrel bzw. Prasugrel. Zahlreiche Studien belegen eine Assoziation zwischen erhöhter residueller Plättchenreaktivität und kardiovaskulären Ereignissen bei Patien-ten unter antithrombozytärer Therapie. Trotz der Fülle an Messmethoden, die derzeit untersucht werden, kann ihr Routine-Einsatz gegenwärtig nicht empfohlen werden. Gründe hierfür sind: (i) Es besteht bislang kein Konsens über Methode und jeweils anzulegende Grenzwerte, die mit unerwünschten Ereignissen assoziiert sind und (ii) ist die Datenlage über den Nutzen einer maßgeschneiderten antithrom-bozytären Therapie und ihrem Monitoring (basierend auf Plättchenfunktionsuntersuchungen) noch begrenzt. Somit bleibt die Identifizierung individueller Patienten mit ‚Resistenz’ bzw. „unzureichender Antwort’ auf Behandlung mit plättchenfunktionshemmenden Substanzen eine Herausforderung im klinischen Alltag.

Keywords

Assessment of platelet function(s) - point-of-care testing - drug resistance - clinical resistance - high on-treatment residual platelet reactivity

Schlüsselwörter

Plättchenfunktionsprüfungen - patientennahe Testung - Arzneimittel-Resistenz - klinische Resistenz - hohe residuelle Plättchenreaktivität unter Behandlung

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