Aspirin "resistance".
A variable responsiveness to antiplatelet drugs is a clinical phenomenon that does not principally differ from other drug treatments in other therapeutic fields. The pharmacological part is to clarify whether a "true" resistance exists in pharmacological terms, i.e., a reduced potency of the compound to work as suggested and to find out the underlying cellular mechanism(s). Two principally different methods of laboratory control for platelet sensitivity to aspirin (ASA) are available: measurement of platelet function (ex vivo) or measurement of inhibition of thromboxane formation. Both methods have limitations and did not yet result in a generally accepted definition of a pharmacological ASA "resistance". The new typological approach of Weber et al. [A.A. Weber, B. Przytulski, A. Schanz, et al., Towards a definition of aspirin resistance: a typological approach. Platelets 13 (2002) 37.] helps to identify different subtypes of ASA resistance in pharmacological terms by combining in vitro aggregometry with thromboxane measurement. Using this method, a "true" pharmacological resistance, associated with a reduced antiplatelet response to ASA and reduced inhibition of thromboxane formation, was found in patients undergoing coronary artery bypass surgery. Platelets of these patients expressed a hitherto unknown isoform of COX-2-COX-2a which might generate a different gene product. In this context, it is interesting that CABG patients express transiently an immunoreactive COX-2 protein with lower molecular weight. Studies on the significance of this finding for ASA resistance are in progress.
Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, Geb. 22.21, D-40225 Düsseldorf, Germany. kschroer@uni-duesseldorf.de
Karsten
K
Schrör
Artur-Aron
AA
Weber
Thomas
T
Hohlfeld
D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000502:physiology; D004351:Drug Resistance; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D001241:Aspirin