Determination of aspirin responsiveness by use of whole blood platelet aggregometry.
BACKGROUND
Insufficient platelet inhibition is associated with an increased cardiovascular risk in up to 30% of patients taking regular doses of aspirin. We describe an assay to study aspirin responsiveness.


METHODS
We performed impedance aggregometry on diluted whole blood with 1 mg/L collagen and 0.5 mmol/L arachidonic acid (AA). We measured thromboxane B(2) (TXB(2)) by RIA. We examined 66 healthy control individuals, 144 aspirin users with stable coronary artery disease (CAD), and 245 CAD patients treated with aspirin and clopidogrel. Nonresponsive samples were incubated with excess DL-lysinmonoacetylsalicylic acid.


RESULTS
Assay imprecision (CV) was 9.8% and 8.2% at mean (SD) 6-min impedance of 13.7 (2.8) Omega and 13.6 (2.3) Omega for collagen and AA, respectively. Collagen induced stronger aggregation (P = 0.0199) in women [n = 28, 14.6 (2.4) Omega] than in men [n = 38, 13.1 (2.9) Omega], even after sample incubation with 0.1 mmol/L acetylsalicylic acid (ASA) or 1 micromol/L terbogrel, a combined inhibitor of thromboxane synthase and receptors. The sex association persisted in aspirin users, but not if clopidogrel was also taken. A 6-min impedance >8 Omega with collagen (mean - 2 SD of the controls) was taken as evidence of nonresponsiveness, particularly if incubation with ASA did not inhibit aggregation further (>2 Omega). Compared with AA, collagen identified more nonresponsive samples among aspirin users (15%) and CAD patients who also received clopidogrel (10%). Incubation with ASA improved inhibition of aggregation in 70% of samples and consistently reduced TXB(2) formation during aggregation.


CONCLUSIONS
Impedance aggregometry may prove useful to study aspirin responsiveness, and incubation with ASA may help to identify nonresponders and classify resistance.
Ivandic
Boris T
BT
Department of Medicine III, University of Heidelberg, Germany. Boris.Ivandic@med.uni-heidelberg.de
Giannitsis
Evangelos
E
Schlick
Philipp
P
Staritz
Peter
P
Katus
Hugo A
HA
Hohlfeld
Thomas
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology*; D001782:Blood Donors; D000077144:Clopidogrel; D003094:Collagen / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000097:blood / Q000517:prevention & control; D004351:Drug Resistance; D017097:Electric Impedance; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology; D012016:Reference Values; D012737:Sex Factors; D013929:Thromboxane B2 / Q000097:blood; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D013929:Thromboxane B2; C112331:terbogrel; D003094:Collagen; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin