Individualised Assessment of Response to Clopidogrel in Patients Presenting with Acute Coronary Syndromes: A Role for Short Thrombelastography?

Abstract

SUMMARYIntroduction: There is considerable interindividual variation in response to the antiplatelet agent clopidogrel. Hyporesponse predicts negative outcomes in patients presenting with a variety of ischemic cardiac conditions and following intracoronary stent placement. Many tests of clopidogrel activity are time consuming and complex. Short thromboelastography (s-TEG) allows rapid measurement of platelet clopidogrel response. Aims: We initiated this study to investigate the utility of s-TEG in assessing the response to clopidogrel in patients presenting with acute coronary syndromes (ACS) and to compare these results with established clopidogrel monitoring techniques. Methods: Patients admitted with unstable angina (UA) or Non ST elevation myocardial infarction (NSTEMI) undergoing coronary angiography were recruited. After routine loading with clopidogrel, all patients were tested with s-TEG and Accumetrics Verify-Now rapid platelet function analyzer (VN-RPFA). We used the modified TEG technique of measuring area under the curve at 15 min (AUC15), which allows a rapid estimation of antiplatelet response. Vasodilator-stimulated phosphoprotein phosphorylation (VASP) was also tested in a subgroup of patients. Clinical follow-up was obtained at 1 year. s-TEG results were correlated with VN-RPFA and VASP findings. Results: A total of 49 patients (33 male, mean age 63) were recruited and tested with s-TEG and VN-RPFA and a total of 39 patients were also assessed with VASP. s-TEG readings correlated well with VN-RPFA (r 2 = 0.54, P < 0.0001) and VASP (r 2 = 0.26, P = 0.001). Conclusion: s-TEG provides timely results which compare to current tests of clopidogrel activity. This technique can also be used to measure a variety of other clotting parameters and as such could develop into a valuable near patient test for the interventional cardiologist.

A Randomized Crossover Study Comparing the Antiplatelet Effect of Plavix Versus Generic Clopidogrel

“…13 The AUC15 TEG method, known as short TEG, has been well validated by this group and is described in detail elsewhere. [12][13][14][15][16]18,19 Recent data from this group 12,14 has shown that the novel parameter AUC15 is not only easily reproducible with minimal intraindividual and interindividual variability but also correlates well with VerifyNow in the assessment of responses to antiplatelet therapy (AUC15 AA Channel and VerifyNow aspirin response units, correlation coefficient r = 0.701; P , 0.001; and AUC15 ADP channel and VerifyNow P2Y12 reactivity units, correlation coefficient r = 0.609, P , 0.001). 12 In this study, platelet reactivity and response to clopidogrel was determined from AUC15 of the ADP channel.…”

“…Platelet reactivity was measured using a well-validated point-of-care platelet function test known as short thrombelastography (TEG), which has been described in detail elsewhere. [12][13][14][15][16] …”

High on-treatment platelet reactivity – definition and measurement

“…It is influenced by platelet function, coagulation factors, natural inhibitors of coagulation and fibrinolysis. Some studies showed that TEG is potentially useful for studying patients on antiplatelet treatment (59)(60)(61)(62)(63)(64)(65)(66).…”

Expression of miRNA-26a in platelets is associated with clopidogrel resistance following coronary stenting

“…Vasodilator-stimulated phosphoprotein (VASP) is a type of intracellular actin regulatory protein, which is a reaction VASP phosphorylation levels can be determined using flow cytometry to determine the treatment efficacy of clopidogrel in patients (11,12). Previous studies have demonstrated that platelets exhibit high levels of microRNA (miRNA) expression (13,14), which has an important role in the pathology of diseases associated with platelets (15,16).…”

“…Following transformation by cytochrome P450, the active metabolites of clopidogrel irreversibly bind to the P2Y 12 ADP receptor on the surface of platelets and block the inhibition of cyclic adenosine monophosphate (cAMP) by inhibiting the binding sites of ADP, which promotes cAMP-dependent phosphorylation of proteins. Inhibition of the binding between fibrinogen and platelet glycoprotein GPIIb/IIIa receptor, and the subsequent deactivation of glycoprotein GPIIb/IIIa complexes inhibits the aggregation of platelets (10).…”