Serum thromboxane B2 compared to five other platelet function tests for the evaluation of aspirin effect in stable cardiovascular disease

Abstract

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).

Conclusion: 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.