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Hamostaseologie 2003; 23(04): 181-185
DOI: 10.1055/s-0037-1619595
Original Article
Schattauer GmbH

Thrombozytenaggregationshemmer

Inhibitors of platelet aggregation
H. Patscheke
1   Zentrum für Labormedizin, Mikrobiologie und Transfusionsmedizin, Städtisches Klinikum Karlsruhe
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Publication History

Publication Date:
20 January 2018 (online)

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Zusammenfassung

Unabhängig von ihrem Wirkungsmechanismus greifen Antikoagulanzien stets unmittelbar in die Bildung und Wirkung von Thrombin und damit die Endstrecke der Gerinnung ein. Von den Aggregationshemmern hemmen nur die GPIIb/IIIa-Antagonisten die gemeinsame Endstrecke der Plättchenaggregation, indem sie die Bildung von Fibrinogen/von-Willebrand-Faktor-vermittelten Plättchen-Plättchen-Brücken hemmen.

Azetylsalizylsäure (ASS), NSARs, Clopidogrel oder Ticlopidin begrenzen die Plättchenaktivierung dagegen, indem sie die Bildung bzw. Wirkung der sekundären Plättchenagonisten Thromboxan A2 bzw. ADP ausschalten, aber z. B. die durch Thrombin direkt induzierbare Plättchenaggregation nicht. Deshalb rufen ASS, Clopidogrel oder Ticlopidin allein kein wesentliches Blutungsrisiko hevor, wenn nicht weitere, die Hämostase beeinträchtigende Faktoren (z.B. ausgeprägte Thrombozytopenie, Antikoagulation) vorliegen. Deshalb entfällt für diese Hemmstoffe auch die Notwendigkeit der Therapiekontrolle. Beim therapeutischen Einsatz von ASS als Aggregationshemmer ist vielmehr die Dosierung darauf abzustellen, eine vollständige Blockade (mind. 90%) der Thromboxanbiosynthese in den Plättchen zu erreichen, um überhaupt einen therapeutischen bzw. prophylaktischen Effekt zu erzielen.

Von den GPIIb/IIIa-Antagonisten sind nur die parenteral eingesetzten (Abciximab, Eptifibatid, Tirofiban) zugelassen. Orale GPIIb/IIIa-Antagonisten zeigten bisher in klinischen Studien ein erhöhtes Blutungsrisiko bei nicht ausreichendem therapeutischen Nutzen. Die meisten GPIIb/IIIa-Antagonisten verursachen eine leichte Thrombozytopenie, als deren Auslöser die Inhibitor-Rezeptor-Wechselwirkung bzw. immunologische Mechanismen diskutiert werden. Für das spezifische Monitoring dieser potenten Aggregationshemmer ist ein »Point-of-Care«-Testsystem verfügbar. Für die Einschätzung des Blutungsrisikos müssen jedoch stets alle, die Hämostase beeinflussende Faktoren berücksichtigt werden. Das gilt insbesondere, wenn neben GPIIb/IIIa-Antagonisten Heparin u.a. Wirkstoffe eingesetzt werden.

Summary

Irrespective of their mechanism of action, anticoagulants reduce the formation and action of thrombin. Thus they interfere with a final step in coagulation. Among platelet inhibitors only the GPIIb/IIIa antagonists inhibit the common pathway of aggregation, namely the formation of platelet-to-platelet bridges which are mediated by fibrinogen or von Willebrand factor.

In contrast, acetylsalicylic acid (ASA), NSAIDs, clopidogrel (Plavix®) or ticlopidine (Tyklid®) inhibit platelet activation by abrogating the formation or action of a secondary platelet agonist, namely of thromboxane A2 or ADP. They do not block platelet aggregation which is directly induced by thrombin. Therefore, ASA, clopidogrel, or ticlopidine are not associated with a significant risk of bleeding as long as other factors such as an extensive thrombocytopenia or anticoagulation are not involved. Therefore, in contrast to anticoagulants, therapeutic drug monitoring is not necessary with ASA, clopidogrel, nor ticlopidine. On the other hand, ASA has even to be applied at a dosage that almost completely inhibits thromboxane synthesis in order to act on platelet aggregation at all.

Among the GPIIb/IIIa-antagonists only parenteral drugs have been approved for therapeutic use, e. g. abciximab (ReoPro®), eptifibatide (Integrilin®), and tirofiban (Aggrastat®). Clinical studies revealed an increased risk of bleeding without a sufficient therapeutic benefit of oral GPIIb/IIIa antagonists. GPIIb/IIIa antagonists may induce thrombocytopenia that is attributed to an outside-in signalling or immunological phenomena. A test system (Ultegra, Accumetrics) is available for a therapeutic drug monitoring of GPIIb/IIIa antagonists. However, estimation of the bleeding risk always requires an evaluation of all factors influencing the haemostatic system, especially when heparin or other inhibitors are applied additionally.

Schlüsselwörter

GPIIb/IIIa-Antagonisten - Azetylsalizylsäure - Clopidogrel - Ticlopidin - Thrombozytenaggregation

Keywords

GPIIb/IIIa antagonists - acetylsalicylic acid - clopidogrel - ticlopidine - platelet aggregation
 

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