Serum thromboxane B2 compared to five other platelet function tests for the evaluation of aspirin effect in stable cardiovascular disease.
BACKGROUND
To assess the role of serum thromboxane B(2) (TXB(2)) measurements and the correlation between platelet function studies, in patients with stable cardiovascular disease on aspirin or clopidogrel.


METHODS
76 patients (47 on aspirin, 16 clopidogrel, 13 both) underwent assessment of TXB(2), whole blood aggregometry (WBA) after stimulation with (i) arachidonic acid (0.5mM), (ii) ADP (5 microM), (iii) collagen (1 and 5 microg/ml), PFA-100, and Cone and Plate Analyzer. Clopidogrel patients were additionally assessed by the VerifyNow System.


RESULTS
TXB(2) values ranged between 0.2 and 56.2 ng/ml, with significant separation between those taking aspirin, clopidogrel and controls (0.45 ng/ml vs 6.85 ng/ml vs 12.97 ng/ml, p<0.001). There was moderate correlation between WBA-AA and TXB(2) (r=0.487, p<0.001), PFA-100((R)) (r=0.599, p<0.001), WBA-Col1 (r=0.424, p<0.001), WBA-Col1:5 (r=0.417, p<0.001), and between TXB(2) and PFA-100((R)) (r=0.509, p<0.001). The prevalence of aspirin non-responders for WBA-AA, TXB(2), PFA-100((R)), CPA and Coll1:5 was 13.1%, 8.2%, 14.8%, 9.7% and 16.4% respectively. Individual patients were not consistently classified as aspirin non-responders in all tests. Those with inadequate aspirin response on > or =3 tests had higher TXB(2) levels (mean 1.57+/-1.66, range 0.553-4.45 vs mean 0.45+/-0.18, range 0.23-1.50) (p=0.001). Clopidogrel suppressed TXB(2) (p=0.02), WBA-AA (p<0.001), WBA-Col1 (p=0.012) and WBA-ADP (p<0.001) compared to controls. TXB(2) in patients ingesting fish oil tablets was lower compared to those without (0.4 ng/ml vs 0.52 ng/ml, p=0.004). Obesity was associated with higher TXB(2) values (0.61 vs 0.41, p=0.01).


CONCLUSIONS
Serum TXB(2) measurements are a direct measure of the pharmacological effect of aspirin, are easily performed and correlate with other measures of platelet function. Serum TXB(2) measurements could be a useful sole measure of aspirin non-response, and may be even more predictive when performed in tandem with a global measure of platelet function. Aspirin and clopidogrel both suppressed several platelet pathways.
Kidson-Gerber
Giselle
G
South Eastern Area Laboratory Services, Department of Haematology, Prince of Wales Hospital, Sydney, Australia. Giselle.Kidson-Gerber@sesiahs.health.nsw.gov.au
Weaver
James
J
Gemmell
Rosalie
R
Prasan
Ananth M
AM
Chong
Beng Hock
BH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D016022:Case-Control Studies; D000077144:Clopidogrel; D005260:Female; D005395:Fish Oils; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors; D010979:Platelet Function Tests; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D013929:Thromboxane B2 / Q000097:blood*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
D005395:Fish Oils; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin