Youngchun Park; Jimyung Kim; Jinok Jung; Kyechul Kwon; Sunhoe Koo

doi:10.3343/lmo.2015.5.3.137

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Park, Kim, Jung, Kwon, and Koo: Platelet Activation Markers (β-thromboglobulin and platelet factor 4) and Clopidogrel Drug Response in Patients with Myocardiac Infarction

Original Article

Diagnostic Hematology

Laboratory Medicine Online 2015; 5(3): 137-142.

Published online: 1 July 2015

DOI: https://doi.org/10.3343/lmo.2015.5.3.137

Platelet Activation Markers (β-thromboglobulin and platelet factor 4) and Clopidogrel Drug Response in Patients with Myocardiac Infarction

Youngchun Park, M.D.¹, Jimyung Kim, M.D.¹, Jinok Jung, M.D.², Kyechul Kwon, M.D.¹, Sunhoe Koo, M.D.¹

¹Department of Laboratory Medicine, Chungnam National University, Daejeon, Korea.

²Department of Cardiology, Chungnam National University, Daejeon, Korea.

Corresponding author: Jimyung Kim. Department of Laboratory Medicine, Chungnam National University Hospital, 282 Moonhwa-ro, Joong-gu, Daejeon 301-721, Korea. Tel: +82-42-280-7998, Fax: +82-42-257-5365, jmkim@cnuh.co.kr

Received 30 August 2014 Revised 30 September 2014 Accepted 30 September 2014

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Dual antiplatelet therapy (aspirin and clopidogrel) is used to prevent adverse cardiac events in patients undergoing percutaneous coronary intervention (PCI). Some patients do not respond adequately to clopidogrel. Beta-thromboglobulin (β-TG) and platelet factor 4 (PF-4) can act as markers to detect platelet activation. We investigated the relationship between clopidogrel response and the dynamics of β-TG and PF4 concentrations.

Methods

This study included 36 myocardial infarction (MI) patients, who underwent PCI and was indicated for dual antiplatelet therapy. Platelet reactivity, using the VerifyNow P2Y12 assay, was measured on the 3rd day of PCI. At the time of admission, and on the 3rd and 10th day of PCI, the plasma β-TG and PF4 concentrations were quantified.

Results

Ten patients (27.8%) were clopidogrel non-responders displaying >208 P2Y12 reaction units. At the time of admission, levels of β-TG in patients were elevated than that in the healthy controls (P<0.001). A similar trend was observed on the 3rd and 10th day of PCI (P<0.001). The β-TG levels on the 10th day were reduced than those at the time of admission and on the 3rd day of PCI. PF4 levels were not different between patients and controls, and were not significantly reduced after PCI. Higher β-TG levels were observed in clopidogrel non-responders on the 10th day, but not significant.

Conclusions

Clopidogrel therapy in MI reduce β-TG concentration, but the β-TG and PF4 levels before and after therapy are not associated with the response to clopidogrel. Platelet-derived markers may not be suitable for distinguishing clopidogrel non-responders.

Keywords: Beta-thromboglobulin, Clopidogrel, Myocardial infarction, Platelet factor 4

Figures and Tables

Fig. 1

Comparison of β-thromboglobulin and platelet factor 4 at each time point of measurement in 36 patients with myocardial infarction. The central box and middle line represent 25 to 75 percentile and the median. A line extends from the minimum to the maximum value.

Table 1

Baseline characteristics of the patients in the study group at the time of hospital admission

Variables	No HOPR (N = 26)	HOPR (N = 10)	P value
Age (yr)	61.2 ± 10.3	66.6 ± 10.9	0.178
Male	21 (80.7%)	6 (60.0%)	0.390
BMI (kg/m²)	24.3 ± 3.1	22.6 ± 3.7	0.161
Hypertension	9 (34.6%)	3 (30.0%)	0.895
Diabetes mellitus	9 (34.6%)	5 (50.0%)	0.641
Dyslipidemia	7 (26.9%)	1 (10.0%)	0.518
Hemoglobin (g/dL)	14.9 ± 1.2	12.2 ± 2.1	<0.001
Platelet (×10³/µL)	216 ± 65	232 ± 58	0.505
Total cholesterol (mg/dL)	197 ± 41	207 ± 85	0.648
Triglyceride (mg/dL)	131 ± 66	94 ± 49	0.119
CRP (mg/dL)	0.5 ± 1.3	0.1 ± 0.1	0.361
LVEF (%)	51.2 ± 9.9	45.9 ± 13.7	0.209
Number of involved coronary arteries	1.8 ± 0.9	1.7 ± 0.8	0.829
ST segment elevation	15 (57.7%)	5 (50.0%)	0.967

Values are presented as mean±SD or number(%).

Abbreviations: HOPR, high on-clopidogrel platelet reactivity; BMI, body mass index; CRP, C-reactive protein; LVEF, left ventricular ejection fraction.

Table 2

Markers of platelet activation measured in the study group

Variables	No HOPR (N = 26)	HOPR (N = 10)	P value
Platelet factor 4 (ng/mL)
Admission	16.0 (9.0-23.0)	16.1 (12.0-31.5)	0.224
Day 3	14.9 (6.3-30.6)	13.4 (12.0-17.8)	0.908
Day 10	15.1 (11.1-27.4)	13.0 (5.9-21.5)	0.284
β-thromboglobulin (ng/mL)
Admission	47.5 (21.9-70.0)	45.3 (30.2-69.9)	0.608
Day 3	43.5 (27.1-102.7)	50.2 (22.7-88.7)	0.266
Day 10	34.3 (21.5-70.9)	44.7 (26.3-62.1)	0.104
MPV (fL)
Admission	9.5 ± 1.1	9.5 ± 1.2	0.899
Day 3	9.0 ± 1.1	9.3 ± 1.2	0.514
Day 10	8.9 ± 1.0	9.4 ± 0.9	0.192

Values are presented as mean±SD or median (range).

Abbreviations: HOPR, high on-clopidogrel platelet reactivity; MPV, mean platelet volume.

Notes

This article is available from http://www.labmedonline.org

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