Inconsistency of different methods for assessing ex vivo platelet function: relevance for the detection of aspirin resistance.
BACKGROUND
Assays to evaluate platelet function are often interchangeably used to assess "resistance" to aspirin. We compared different platelet function assays in patients treated or untreated with aspirin.


METHODS
Platelet function was evaluated in 162 subjects, 85 of whom were not being treated with any antiplatelet drug and 77 of whom were receiving chronic therapy with low-dose aspirin. Platelet Function Analyzer collagen/ADP- and collagen/epinephrine closure times, as well as light transmittance aggregometry in response to ADP, collagen and arachidonic acid (this last in 47 aspirin-treated patients) were determined. In 43 aspirin-treated patients, serum thromboxane B(2) levels were also measured.


RESULTS
In untreated patients, collagen/ADP- and collagen/epinephrine-closure times were correlated with each other (r=0.5, P=0.0001), but did not correlate with ADP- or collagen-induced aggregation. In patients treated with aspirin, collagen/ADP-closure time values were not different from those in untreated patients, while the collagen/epinephrine-closure time was prolonged. ADP-induced aggregation was unaffected by aspirin, while collagen-induced aggregation was reduced. Arachidonic acid-induced aggregation was almost completely suppressed (% maximum light transmittance aggregometry =5 ± 13%). There was, however, no correlation between the various platelet function tests. Serum thromboxane B(2), an index of platelet cyclooxygenase-1 activity, was almost completely suppressed (down to 8 ± 17 ng/mL) in treated patients, and was not correlated with arachidonic acid-, ADP- and collagen-induced aggregation or with collagen/ADP-closure time, but was inversely correlated with collagen/epinephrine-closure time.


CONCLUSIONS
There is a high heterogeneity of results of tests evaluating inhibition of platelet function by aspirin, and the results of functional tests do not match biochemical measurement of cyclooxygenase-1 activity. Extreme caution should, therefore, be used in defining "resistance" to aspirin on the basis of the results of these tests.
The Institute of Cardiology and Center of Excellence on Aging at G. d'Annunzio University, Chieti, Italy.
Giulia
G
Renda
Maria
M
Zurro
Gelsomina
G
Malatesta
Benedetta
B
Ruggieri
Raffaele
R
De Caterina
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D003094:Collagen / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010979:Platelet Function Tests / Q000379:methods*; D013929:Thromboxane B2 / Q000097:blood; D055815:Young Adult
D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D001241:Aspirin