Elsevier

American Heart Journal

Volume 168, Issue 4, October 2014, Pages 545-551
American Heart Journal

Clinical Investigation
Interventional Cardiology
Does baseline hematocrit influence the assays of on-treatment platelet reactivity to clopidogrel?

https://doi.org/10.1016/j.ahj.2014.06.029Get rights and content

Background

High on-treatment platelet reactivity (HTPR) has been shown to be associated with adverse cardiac events in patients undergoing percutaneous coronary intervention, but the effect of baseline hematologic parameters upon platelet reactivity remains controversial.

Objective

The present study aims to evaluate the impact of hematocrit on 2 different assay methods used to assess on-treatment platelet reactivity to clopidogrel.

Methods

We tested clopidogrel on-treatment platelet reactivity in 466 consecutive patients using VerifyNow P2Y12 (VN) and light transmission aggregometry (LTA) with adenosine diphosphate (ADP) 5 and 20 μM assays 6 to 24 hours after percutaneous coronary intervention. Patients were categorized into 4 groups according to baseline hematocrit. One-year major adverse cardiac events, including death, nonfatal myocardial infarction, and definite stent thrombosis, were collected.

Results

Lower hematocrit was associated with higher P2Y12 reaction unit (PRU) and a higher rate of HTPR (P < .001) as measured by VN assay. No differences were seen among the 4 groups in platelet reactivity measured by LTA using ADP 5 μM (P = .23) and ADP 20 μM (P = .21). In a multivariable logistic regression model, baseline hematocrit was independently associated with PRU ≥208 (odds ratio [OR] 0.92, 95% CI 0.86-0.97, P = .005) but had no correlation with LTA ADP 5 μM ≥46% (OR 1.0, 95% CI 0.95-1.06, P = .88) or LTA ADP 20 μM ≥59% (OR 1.03, 95% CI 0.97-1.09, P = .39). In a logistic regression model, the addition of VN assay results, hematocrit, and interaction between the hematocrit and assay results had shown a significant influence on the area under curve for prediction of 1-year major adverse cardiac events compared with baseline clinical variables only for PRU (0.63 vs 0.76, P = .006) but not with LTA (0.64 vs 0.74, P = .13).

Conclusion

Baseline hematocrit has a differential influence on results of the ex vivo platelet functional assays. Lower baseline hematocrit was independently associated with HTPR by VN but not LTA. This may affect the interpretation of platelet function testing in patients with significant anemia.

Section snippets

Study population and data collection

The study cohort included patients ≥18 years of age presenting for elective and urgent PCI who were consecutively enrolled in a prospective observational registry from October 2009 to March 2012. Patients who received the glycoprotein IIb/IIIa inhibitor eptifibatide up to 24 hours before platelet reactivity testing were excluded (no patients received abciximab or tirofiban). Similarly, patients on warfarin, nonsteroidal anti-inflammatory drugs, or with a contraindication for aspirin or

Results

Platelet reactivity was tested in 466 consecutive patients with VN and LTA ADP 5 and 20 μM. Baseline characteristics stratified by hematocrit ≥39% are presented in Table I. To evaluate the influence of hematocrit upon platelet function assays, further analysis was done by dividing the patients into quartiles (Q1: 25-35.9, Q2: 36-38.9, Q3: 39-41.9, Q4: 42-51) based upon baseline hematocrit (percentages). The patients in Q1 and Q2 were considered anemic, and Q3 and Q4 were considered nonanemic.

Discussion

The main findings of the present study are (1) there was clear influence of the hematocrit on PRU and BASE results by VN assay, whereas no such influence was seen with LTA assay; (2) lower hematocrit was independently correlated with HTPR by the VN assay but not by LTA; and (3) the interaction between the hematocrit and the platelet function assay results was shown to impact the predictive power of long-term adverse outcomes for the VN assay but not for the LTA assay.

Currently, several

Conclusions

In the present study, baseline hematocrit is noted to have differential influence on the results of ex vivo platelet functional assays. The PRU measured by the VN P2Y12 assay is clearly influenced by a patient's baseline hematocrit, whereas the platelet reactivity measured by LTA does not seem to be influenced by hematocrit.

References (22)

Cited by (11)

  • <sup>1</sup>H NMR based pharmacometabolomics analysis of urine identifies metabolic phenotype of clopidogrel high on treatment platelets reactivity in coronary artery disease patients

    2017, Journal of Pharmaceutical and Biomedical Analysis
    Citation Excerpt :

    The negative correlations between Hct and Hb, and both PRU and BASE but not with the %Inh which were indicated in our study are in line with previous results [36,37]. However, similar correlations were absent in LTA ADP 5 μM and the multiple electrode platelet aggregometry (MEA) ADP when compared to VN-P2Y12 [36,37]. Although VN-P2Y12 and LTA have similar PFT mechanism, VN-P2Y12 uses whole blood specimen rather than platelets rich plasma (PRP); the specimen of LTA.

  • A laboratory association between hemoglobin and VerifyNow P2Y12 reaction unit: A systematic review and meta-analysis

    2017, American Heart Journal
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    Among 51 studies with full-text review, 41 studies did not report the correlation coefficient between PRU and hemoglobin (or hematocrit). Finally, 10 studies1,8,9,12-15,17,19,23 were included in the present meta-analysis. The results of NOS of each study are presented in Supplementary Table S3.

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