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Comparison of VerifyNow-P2Y12 test and Flow Cytometry for monitoring individual platelet response to clopidogrel. What is the cut-off value for identifying patients who are low responders to clopidogrel therapy?

Godino C, Mendolicchio L, Figini F, Latib A, Sharp AS, Cosgrave J, Calori G, Cera M, Chieffo A, Castelli A, Maseri A, Ruggeri ZM, Colombo A - Thromb J (2009)

Bottom Line: Evaluation of the same patients with the VerifyNow-P2Y12 test revealed that the area under the receiver-operating-characteristic (ROC) curve was 0.94 (95% CI: 0.84-0.98, p < 0.0001) for % inhibition and 0.85 (0.72-0.93, p < 0.005) for PRU.Cut-off values of ≤ 15% inhibition or > 213 PRU gave the maximum accuracy for the detection of patients defined as having LR by FC.In conclusion our findings show that a cut-off value of ≤ 15% inhibition or > 213 PRU in the VerifyNow-P2Y12 test may provide the best accuracy for the identification of patients with LR.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cardio-Thoracic and Vascular Diseases, San Raffaele Scientific Institute, Milan, Italy. cosmogodino@gmail.com.

ABSTRACT

Background: Dual anti-platelet therapy with aspirin and a thienopyridine (DAT) is used to prevent stent thrombosis after percutaneous coronary intervention (PCI). Low response to clopidogrel therapy (LR) occurs, but laboratory tests have a controversial role in the identification of this condition.

Methods: We studied LR in patients with stable angina undergoing elective PCI, all on DAT for at least 7 days, by comparing: 1) Flow cytometry (FC) to measure platelet membrane expression of P-selectin (CD62P) and PAC-1 binding following double stimulation with ADP and collagen type I either in the presence of prostaglandin (PG) E1; 2) VerifyNow-P2Y12 test, in which results are reported as absolute P2Y12-Reaction-Units (PRU) or % of inhibition (% inhibition).

Results: Thirty controls and 52 patients were analyzed. The median percentage of platelets exhibiting CD62P expression and PAC-1 binding by FC evaluation after stimulation in the presence of PG E1 was 25.4% (IQR: 21.4-33.1%) and 3.5% (1.7-9.4%), respectively. Only 6 patients receiving DAT (11.5%) had both values above the 1st quartile of controls, and were defined as LR. Evaluation of the same patients with the VerifyNow-P2Y12 test revealed that the area under the receiver-operating-characteristic (ROC) curve was 0.94 (95% CI: 0.84-0.98, p < 0.0001) for % inhibition and 0.85 (0.72-0.93, p < 0.005) for PRU. Cut-off values of ≤ 15% inhibition or > 213 PRU gave the maximum accuracy for the detection of patients defined as having LR by FC.

Conclusion: In conclusion our findings show that a cut-off value of ≤ 15% inhibition or > 213 PRU in the VerifyNow-P2Y12 test may provide the best accuracy for the identification of patients with LR.

No MeSH data available.


Related in: MedlinePlus

Correlation between the results obtained by flow cytometric evaluation of platelet activation parameters and VerifyNow-P2Y12 test in patients receiving antiplatelet therapy. The percent of inhibition (% inhibition) was plotted against the percentage of platelets that expressed P-selectin (CD62P) after stimulation with 20 μM ADP and 5 μg/mL collagen type I for 110 min at room temperature in the presence of 1 μM PG E1. (§) First quartile of control values for CD62P expression. Patients receiving antiplatelet therapy with levels of CD62P expression and PAC-1 binding above this limit were defined as "Low-responder"; those with both values below this limit were defined as "High-Responder"; those with one value above and the other below the corresponding limit were defined as "Intermediate-responder". ($) Cut-off value for % of inhibition in the VerifyNow-P2Y12 test giving minimal false negative and positive results (see Figure 1).
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Figure 2: Correlation between the results obtained by flow cytometric evaluation of platelet activation parameters and VerifyNow-P2Y12 test in patients receiving antiplatelet therapy. The percent of inhibition (% inhibition) was plotted against the percentage of platelets that expressed P-selectin (CD62P) after stimulation with 20 μM ADP and 5 μg/mL collagen type I for 110 min at room temperature in the presence of 1 μM PG E1. (§) First quartile of control values for CD62P expression. Patients receiving antiplatelet therapy with levels of CD62P expression and PAC-1 binding above this limit were defined as "Low-responder"; those with both values below this limit were defined as "High-Responder"; those with one value above and the other below the corresponding limit were defined as "Intermediate-responder". ($) Cut-off value for % of inhibition in the VerifyNow-P2Y12 test giving minimal false negative and positive results (see Figure 1).

Mentions: All six patients (11.5%) defined as low-responders on the basis of CD62P expression and PAC-1 binding were lower or equal to 15% inhibition, and all 23 patients (44.2%) defined as high-responders were above 15% inhibition (Figure 2 and 3). Of the remaining 23 (44.2%) patients defined as intermediate responders, five were below 15% inhibition; in all these individuals, the percentage of platelets expressing CD62P was below or equal the 1st percentile of normal controls (Figure 2), but that of platelets binding PAC-1 was above (Figure 3). In total 11 patients (21%) were lower or equal to 15% inhibition and as a result low clopidogrel responders.


Comparison of VerifyNow-P2Y12 test and Flow Cytometry for monitoring individual platelet response to clopidogrel. What is the cut-off value for identifying patients who are low responders to clopidogrel therapy?

Godino C, Mendolicchio L, Figini F, Latib A, Sharp AS, Cosgrave J, Calori G, Cera M, Chieffo A, Castelli A, Maseri A, Ruggeri ZM, Colombo A - Thromb J (2009)

Correlation between the results obtained by flow cytometric evaluation of platelet activation parameters and VerifyNow-P2Y12 test in patients receiving antiplatelet therapy. The percent of inhibition (% inhibition) was plotted against the percentage of platelets that expressed P-selectin (CD62P) after stimulation with 20 μM ADP and 5 μg/mL collagen type I for 110 min at room temperature in the presence of 1 μM PG E1. (§) First quartile of control values for CD62P expression. Patients receiving antiplatelet therapy with levels of CD62P expression and PAC-1 binding above this limit were defined as "Low-responder"; those with both values below this limit were defined as "High-Responder"; those with one value above and the other below the corresponding limit were defined as "Intermediate-responder". ($) Cut-off value for % of inhibition in the VerifyNow-P2Y12 test giving minimal false negative and positive results (see Figure 1).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2683811&req=5

Figure 2: Correlation between the results obtained by flow cytometric evaluation of platelet activation parameters and VerifyNow-P2Y12 test in patients receiving antiplatelet therapy. The percent of inhibition (% inhibition) was plotted against the percentage of platelets that expressed P-selectin (CD62P) after stimulation with 20 μM ADP and 5 μg/mL collagen type I for 110 min at room temperature in the presence of 1 μM PG E1. (§) First quartile of control values for CD62P expression. Patients receiving antiplatelet therapy with levels of CD62P expression and PAC-1 binding above this limit were defined as "Low-responder"; those with both values below this limit were defined as "High-Responder"; those with one value above and the other below the corresponding limit were defined as "Intermediate-responder". ($) Cut-off value for % of inhibition in the VerifyNow-P2Y12 test giving minimal false negative and positive results (see Figure 1).
Mentions: All six patients (11.5%) defined as low-responders on the basis of CD62P expression and PAC-1 binding were lower or equal to 15% inhibition, and all 23 patients (44.2%) defined as high-responders were above 15% inhibition (Figure 2 and 3). Of the remaining 23 (44.2%) patients defined as intermediate responders, five were below 15% inhibition; in all these individuals, the percentage of platelets expressing CD62P was below or equal the 1st percentile of normal controls (Figure 2), but that of platelets binding PAC-1 was above (Figure 3). In total 11 patients (21%) were lower or equal to 15% inhibition and as a result low clopidogrel responders.

Bottom Line: Evaluation of the same patients with the VerifyNow-P2Y12 test revealed that the area under the receiver-operating-characteristic (ROC) curve was 0.94 (95% CI: 0.84-0.98, p < 0.0001) for % inhibition and 0.85 (0.72-0.93, p < 0.005) for PRU.Cut-off values of ≤ 15% inhibition or > 213 PRU gave the maximum accuracy for the detection of patients defined as having LR by FC.In conclusion our findings show that a cut-off value of ≤ 15% inhibition or > 213 PRU in the VerifyNow-P2Y12 test may provide the best accuracy for the identification of patients with LR.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cardio-Thoracic and Vascular Diseases, San Raffaele Scientific Institute, Milan, Italy. cosmogodino@gmail.com.

ABSTRACT

Background: Dual anti-platelet therapy with aspirin and a thienopyridine (DAT) is used to prevent stent thrombosis after percutaneous coronary intervention (PCI). Low response to clopidogrel therapy (LR) occurs, but laboratory tests have a controversial role in the identification of this condition.

Methods: We studied LR in patients with stable angina undergoing elective PCI, all on DAT for at least 7 days, by comparing: 1) Flow cytometry (FC) to measure platelet membrane expression of P-selectin (CD62P) and PAC-1 binding following double stimulation with ADP and collagen type I either in the presence of prostaglandin (PG) E1; 2) VerifyNow-P2Y12 test, in which results are reported as absolute P2Y12-Reaction-Units (PRU) or % of inhibition (% inhibition).

Results: Thirty controls and 52 patients were analyzed. The median percentage of platelets exhibiting CD62P expression and PAC-1 binding by FC evaluation after stimulation in the presence of PG E1 was 25.4% (IQR: 21.4-33.1%) and 3.5% (1.7-9.4%), respectively. Only 6 patients receiving DAT (11.5%) had both values above the 1st quartile of controls, and were defined as LR. Evaluation of the same patients with the VerifyNow-P2Y12 test revealed that the area under the receiver-operating-characteristic (ROC) curve was 0.94 (95% CI: 0.84-0.98, p < 0.0001) for % inhibition and 0.85 (0.72-0.93, p < 0.005) for PRU. Cut-off values of ≤ 15% inhibition or > 213 PRU gave the maximum accuracy for the detection of patients defined as having LR by FC.

Conclusion: In conclusion our findings show that a cut-off value of ≤ 15% inhibition or > 213 PRU in the VerifyNow-P2Y12 test may provide the best accuracy for the identification of patients with LR.

No MeSH data available.


Related in: MedlinePlus