Khanna Vikram, Hobson Alex, Mikael Rand, Sambu Nalyaka, Englyst Nicola, Curzen Nick
Prof. N. Curzen, Wessex Cardiothoracic Unit, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, United Kingdom, Tel.: +44 2380794972, Fax: +44 2380795174, E-mail:
Thromb Haemost. 2014 Jun;111(6):1150-9. doi: 10.1160/TH13-10-0856. Epub 2014 Mar 27.
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.
与仅使用二磷酸腺苷（ADP）的短血栓弹力图（s-TEG）不同，VerifyNow P2Y12检测（VN-P2Y12）额外使用前列腺素E1（PGE1）作为激动剂来评估对P2Y12抑制剂的反应。基于先前的观察结果，我们推测VN-P2Y12高估了氯吡格雷的治疗效果。对43名健康志愿者和170名服用或未服用氯吡格雷的患者同时进行了s-TEG和VN-P2Y12检测。此外，在27名服用75 mg氯吡格雷的患者中，我们比较了在s-TEG中向ADP添加22 nM PGE1与仅使用ADP对血小板聚集的影响。在以下人群中，与VN-P2Y12相比，s-TEG检测显示高血小板反应性（HPR）结果的个体比例更高：（i）43名未服用氯吡格雷的志愿者（95.3%对81.4%，p=无显著差异）；（ii）28名服用600 mg氯吡格雷的志愿者（39.3%对10.7%，p=<0.01）；（iii）123名未服用氯吡格雷的患者（93.5%对78%，p=<0.0001）；（iv）47名服用75 mg氯吡格雷的患者（42.6%对4.3%，p=<0.0001）。在59名服用600 mg/900 mg氯吡格雷的患者中，与s-TEG相比，无论用VN-P2Y12定义HPR的阈值如何（P2Y12反应单位≥230或208），VN-P2Y12检测显示“治疗反应”的患者比例更高。此外，在s-TEG中向ADP添加PGE1与仅使用ADP相比，增强了氯吡格雷的抗聚集作用。总之，VN-P2Y12在某些个体中高估了氯吡格雷的功能效果，可能是因为它除了使用ADP外还使用了PGE1。这可能会影响VN-P2Y12将患者分层为氯吡格雷“反应者”或“无反应者”的能力。
