Serum Thromboxane B2 Compared to Five Other Platelet Function Tests for the Evaluation of Aspirin Effect in Stable Cardiovascular Disease

Kidson-Gerber, Giselle; Weaver, James; Gemmell, Rosalie; Prasan, Ananth M.; Chong, Beng Hock

doi:10.1016/j.hlc.2009.11.002

« Previous Next »Heart, Lung and Circulation
Volume 19, Issue 4 , Pages 234-242, April 2010

Serum Thromboxane B₂ Compared to Five Other Platelet Function Tests for the Evaluation of Aspirin Effect in Stable Cardiovascular Disease

Giselle Kidson-Gerber, FRACP, FRCPA
- South Eastern Area Laboratory Services (SEALS), Department of Haematology, Prince of Wales Hospital, Sydney, Australia
- University of New South Wales, Faculty of Medicine, Sydney, Australia
- Corresponding author at: Department of Haematology, SEALS, Level 4, Campus Centre, Prince of Wales Hospital, Barker St, Randwick, NSW 2031, Australia. Tel.: +61 2 9382 9047; fax: +61 2 9382 9247.
James Weaver, FRACP
- University of New South Wales, Faculty of Medicine, Sydney, Australia
- Department of Cardiology, St George Hospital, Sydney, Australia
Rosalie Gemmell, BApSci
- SEALS, Department of Haematology, St George Hospital, Sydney, Australia
Ananth M. Prasan, FRACP, PhD
- University of New South Wales, Faculty of Medicine, Sydney, Australia
- Department of Cardiology, St George Hospital, Sydney, Australia
Beng Hock Chong, FRACP, FRCPA, PhD, FRCP
- University of New South Wales, Faculty of Medicine, Sydney, Australia
- SEALS, Department of Haematology, St George Hospital, Sydney, Australia

Received 24 August 2009; received in revised form 9 November 2009; accepted 11 November 2009.

Background

To assess the role of serum thromboxane B₂ (TXB₂) 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 TXB₂, whole blood aggregometry (WBA) after stimulation with (i) arachidonic acid (0.5mM), (ii) ADP (5μM), (iii) collagen (1 and 5μg/ml), PFA-100^®, and Cone and Plate Analyzer. Clopidogrel patients were additionally assessed by the VerifyNow^® System.

Results

TXB₂ values ranged between 0.2 and 56.2ng/ml, with significant separation between those taking aspirin, clopidogrel and controls (0.45ng/ml vs 6.85ng/ml vs 12.97ng/ml, p<0.001). There was moderate correlation between WBA-AA and TXB₂ (r=0.487, p<0.001), PFA-100^® (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 TXB₂ and PFA-100^® (r=0.509, p<0.001). The prevalence of aspirin non-responders for WBA-AA, TXB₂, PFA-100^®, 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 ≥3 tests had higher TXB₂ 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 TXB₂ (p=0.02), WBA-AA (p<0.001), WBA-Col1 (p=0.012) and WBA-ADP (p<0.001) compared to controls. TXB₂ in patients ingesting fish oil tablets was lower compared to those without (0.4ng/ml vs 0.52ng/ml, p=0.004). Obesity was associated with higher TXB₂ values (0.61 vs 0.41, p=0.01).

Conclusion

Serum TXB₂ measurements are a direct measure of the pharmacological effect of aspirin, are easily performed and correlate with other measures of platelet function. Serum TXB₂ 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.

Keywords: Thromboxane B₂, Aspirin, Platelet function tests, Clopidogrel, Drug resistance, Fish oils