[Platelet aggregation disorders]

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 A(2) 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 out-side-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.