Individual variations of platelet inhibition after loading doses of clopidogrel

Abstract

Objective: To investigate individual variations of platelet inhibition after clopidogrel-loading doses.

Setting: Department of Cardiology, Linköping University Hospital, Linköping, Sweden.

Subjects: Individuals with stable angina pectoris (n = 18) subject to percutaneous coronary interventions (PCI) and subsequent stenting were investigated. METHODS AND EXPERIMENTAL PROTOCOL: A 300-mg clopidogrel loading dose was administrated immediately after stenting (day 1) followed by an additional 75 mg clopidogrel after 24 h (day 2). The ADP-evoked platelet fibrinogen binding was analysed to estimate platelet reactivity immediately before angiography and on day 2. A flow cytometry technique was used with two ADP solutions (final concentrations 0.6 and 1.7 micromol L-1) employed as platelet activating agents. Soluble P-selectin was used as a marker of platelet activity.

Results: When using 1.7 micromol L-1 ADP to activate platelets four individuals had a strong inhibition (i.e. platelet reactivity <10% of the day 1-value day 2). In contrast, five patients demonstrated a weak inhibition (i.e. platelet reactivity >60% of the day 1-value day 2). Similar results were obtained when using 0.6 micromol L-1 ADP as a platelet-activating agent. Clopidogrel, however, fails to suppress platelet activity as estimated from soluble P-selectin.

Conclusions: Clopidogrel evoked platelet inhibition exhibits a considerable individual heterogeneity. Some individuals only had weak responses whereas others displayed strong platelet inhibition. The present flow cytometry technique appears suitable for identifying patients with abnormal reactions after clopidogrel exposure.