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Thromb Haemost 2014; 111(06): 1150-1159
DOI: 10.1160/TH13-10-0856
Platelets and Blood Cells
Schattauer GmbH

Does the VerifyNow P2Y12 assay overestimate “therapeutic response” to clopidogrel?

Insights using short thrombelastography
Vikram Khanna
1   University Hospital Southampton NHS Foundation Trust, Southampton, UK
2   Faculty of Medicine, University of Southampton, Southampton, UK
,
Alex Hobson
3   Queen Alexandra Hospital, Portsmouth, UK
,
Rand Mikael
2   Faculty of Medicine, University of Southampton, Southampton, UK
,
Nalyaka Sambu
1   University Hospital Southampton NHS Foundation Trust, Southampton, UK
2   Faculty of Medicine, University of Southampton, Southampton, UK
,
Nicola Englyst
2   Faculty of Medicine, University of Southampton, Southampton, UK
,
Nick Curzen
1   University Hospital Southampton NHS Foundation Trust, Southampton, UK
2   Faculty of Medicine, University of Southampton, Southampton, UK
› Author Affiliations Financial support: This work was supported by an unrestricted research grant from Haemonetics Corporation.
Further Information

Publication History

Received: 17 October 2013

Accepted after major revision: 16 January 2014

Publication Date:
21 November 2017 (online)

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Summary

In contrast to short thrombelastography (s-TEG) which utilises adenosine diphosphate (ADP) alone, the VerifyNow P2Y12 assay (VN-P2Y12) additionally uses prostaglandin E1 (PGE1) as agonist to assess response to P2Y12 inhibitors. Based upon previous observations, we hypothesised that VN-P2Y12 overestimates the therapeutic effects of clopidogrel. Simultaneous assay with s-TEG and VN-P2Y12 was performed in 43 healthy volunteers and 170 patients either on or off clopidogrel. Furthermore, in 27 patients on clopidogrel 75 mg we compared the effects of adding 22 nM PGE1 to ADP on platelet aggregation in s-TEG to ADP alone. A higher proportion of individuals had a result indicating high platelet reactivity (HPR) with s-TEG than VN-P2Y12 in (i) 43 clopidogrel naïve volunteers (95.3% vs 81.4%, p = NS); (ii) 28 volunteers loaded with clopidogrel 600 mg (39.3% vs 10.7 %, p = < 0.01); (iii) 123 clopidogrel naïve patients (93.5% vs 78%, p = < 0.0001); (iv) 47 patients on clopidogrel 75 mg (42.6% vs 4.3%, p = < 0.0001). In 59 patients loaded with clopidogrel 600 mg/900 mg, a greater proportion had a “therapeutic response” with VN-P2Y12 compared to s-TEG, regardless of the threshold for defining HPR with VN-PY12 (P2Y12 reaction units ≥ 230 or 208). Furthermore, adding PGE1 to ADP in s-TEG potentiated the anti-aggregatory effects of clopidogrel compared with ADP alone. In conclusion, VN-P2Y12 overestimates the functional effects of clopidogrel in some individuals, possibly because it utilises PGE1 in addition to ADP. This could have implications for the ability of VN-P2Y12 to stratify patients as “responders” or “non-responders” to clopidogrel.

Keywords

Clopidogrel - high platelet reactivity - thrombelastography - VerifyNow P2Y12 assay - prostaglandin E1
 

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