CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Dirk Sibbing, MD*,
Nicolas von Beckerath, MD and
Adnan Kastrati, MD
* Deutsches Herzzentrum and 1. Medizinische Klinik rechts der Isar, Lazarettstrasse 36, 80636 München, Germany (Email: dirk{at}sibbing.net).
We appreciate the comments made by Dr. Perez de Prado and colleagues concerning our recent article (1).
The observation of normally distributed platelet aggregation (PA) values is only an in vitro phenomenon depending on the population studied and the method applied. Indeed, PA measurements were not normally distributed in our study population (1), and in a previous study (2) we undertook with multiple electrode platelet aggregometry (MEA) on the Multiplate analyzer (Dynabyte GmbH, Munich, Germany). This is in contrast to observations made with light transmission aggregometry (LTA) and the VerifyNow P2Y12 assay (Accumetrics, San Diego, California). In MEA, adhesion and PA leads to an increased impedance signal; the more platelets that adhere to the electrode, the higher the impedance. Hence, MEA measurements have no inherent upper limit, and this is likely to explain not normally distributed PA data with MEA.
In fact, the observation of a higher proportion of active smokers in the group of clopidogrel low responders (1) is in contrast to a recently published study using LTA and finding lower PA values in active smokers compared with nonsmokers (3). For LTA, it must be kept in mind that platelet-rich plasma is an artificial milieu lacking erythrocytes, leukocytes, and larger platelet subspecies, all of which influence the amount of PA (4). The link of smoking and leukocytosis is well known, and also the interaction of leukocytes and platelets in atherothrombotic processes has been established (5). Endothelial dysfunctions and platelet hyper-reactivity have been well described in smokers, as well as a negative effect of smoking on the pharmacokinetics of clopidogrel (6). In light of this conflicting data, the issue of smoking and clopidogrel response warrants further investigations, which we are currently undertaking in separate studies.
Concerning predictors of stent thrombosis (ST), we are aware that other variables apart from the ones included in our primary analysis may play a role in this setting. ST is a very rare event, and a comprehensive analysis on its predictors requires thousands of patients. This was beyond the scope of our study, which was designed to assess the relationship of MEA measurements and ST. As requested, however, by Dr. Perez de Prado and colleagues, we expanded the multivariable analysis by adding the suggested variables (ejection fraction [already included], vessel diameter, total stent length, and final pressure to implant the stent) into the Cox proportional hazards model. Even after inclusion of these variables, MEA measurements maintained their highly significant prediction value for the occurrence of ST (hazard ratio: 12.0, 95% confidence interval: 2.3 to 63.2; p = 0.003).
 |
References
|
|---|
1. Sibbing D, Braun S, Morath T, et al. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis J Am Coll Cardiol 2009;53:849-856.[Abstract/Free Full Text]2. Sibbing D, Braun S, Jawansky S, et al. Assessment of ADP-induced platelet aggregation with light transmission aggregometry and multiple electrode platelet aggregometry before and after clopidogrel treatment Thromb Haemost 2008;99:121-126.[Web of Science][Medline] 3. Bliden KP, Dichiara J, Lawal L, et al. The association of cigarette smoking with enhanced platelet inhibition by clopidogrel J Am Coll Cardiol 2008;52:531-533.[Abstract/Free Full Text] 4. Guthikonda S, Alviar CL, Vaduganathan M, et al. Role of reticulated platelets and platelet size heterogeneity on platelet activity after dual antiplatelet therapy with aspirin and clopidogrel in patients with stable coronary artery disease J Am Coll Cardiol 2008;52:743-749.[Abstract/Free Full Text] 5. Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis J Clin Invest 2005;115:3378-3384.[CrossRef][Web of Science][Medline] 6. Yousef AM, Arafat T, Bulatova NR, Al-Zumyli R. Smoking behaviour modulates pharmacokinetics of orally administered clopidogrel J Clin Pharm Ther 2008;33:439-449.[CrossRef][Web of Science][Medline]
Related Article
-
Platelet Reactivity and Stent Thrombosis: Still Some Issues to Solve
- Armando Perez de Prado, Carlos Cuellas, Alejandro Diego, Antonio de Miguel, and Felipe Fernandez-Vazquez
J. Am. Coll. Cardiol. 2009 54: 666-667.
[Full Text]
[PDF]
|
Top
References