Towards a definition of aspirin resistance: a typological approach.
'Aspirin resistance' is a poorly defined term to describe the inability of aspirin to protect individuals from thrombotic complications and there are conflicting reports on incidence rates and clinical relevance of this phenomenon. Using collagen (1 microg/ml)-induced platelet aggregation and thromboxane formation (measured as thromboxane B(2)) in citrated platelet-rich plasma, this study demonstrates that aspirin resistance can be classified into three distinct types. In aspirin responders, both, collagen-induced platelet aggregation and thromboxane formation was completely (>95%) inhibited by oral aspirin treatment (100 mg/day). In type I resistance (pharmacokinetic type), oral treatment with aspirin was ineffective but addition of aspirin (100 microM) in vitro resulted in a complete inhibition of collagen-induced platelet aggregation and thromboxane formation. In type II resistance (pharmacodynamic type), neither oral treatment with aspirin nor addition of aspirin in vitro inhibited collagen-induced platelet aggregation and thromboxane formation. In type III resistance (pseudo-resistance), platelet aggregation was induced by a low concentration of collagen (1 microg/ml) despite of a complete inhibition of thromboxane formation by oral aspirin treatment. This typology of aspirin resistance should help to clarify the mechanisms, the actual rate, and the possible clinical consequences of this phenomenon.
Weber
Artur-Aron
AA
Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Przytulski
Boris
B
Schanz
Andrea
A
Hohlfeld
Thomas
T
Schrör
Karsten
K
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002561:Cerebrovascular Disorders / Q000188:drug therapy; D004351:Drug Resistance / Q000502:physiology*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012016:Reference Values; D013931:Thromboxanes / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; D001241:Aspirin