심근경색 환자에서 클로피도그렐 반응성에 따른 혈소판활성표지자(β-thromboglobulin과 platelet factor 4)의 분석 = Platelet Activation Markers (β-thromboglobulin and platelet factor 4) and Clopidogrel Drug Response in Patients with Myocardiac Infarction

다국어 초록 (Multilingual 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.

국문 초록 (Abstract)

배경: 아스피린과 클로피도그렐을 병합하는 이원적 항혈소판 요법은 경피적관상동맥중재술을 시행받은 환자에서 심혈관질환의 재발을 예방하기 위해 사용되는데 일부 환자들은 클로피도그렐에 의한 적절한 치료 효과를 나타내지 않기도 한다. 많은 연구들은 platelet factor 4 (PF4)와 beta-thromboglobulin (β-TG)을 혈소판 활성의 증가를 반영하는 표지자로 제안해왔다. 저자들은 클로피도그렐에 대한 혈소판 반응도가 beta-TG 및 PF4 농도와 관련되는지 평가하고자 하였다.
방법: 심근경색으로 경피적관상동맥중재술을 시행하고 이원적 항혈소판 요법을 받은 36명의 환자를 대상으로 하였다. 클로피도그렐에 대한 혈소판 반응도는 중재술 시행 3일째 VerifyNow P2Y12 검사법으로 측정하였으며 혈장 β-TG와 PF4 농도는 내원 시, 중재술 시행 3일째 및 10일째에 검사하였다.
결과: 36명의 환자 중 10명(27.8%)이 클로피도그렐 무반응군(P2Y12 반응도>208)이었다. 내원 시 환자군의 β-TG 농도는 정상 대조군에 비해 유의하게 상승되었으며(P<0.001) 중재술 시행 3일째 및 10일째에도 β-TG 농도는 높았다(P<0.001). 또한 중재술 시행 10일째에 β-TG 농도는 내원 시 및 시행 3일째에 비해 유의하게 감소하였다. 반면 PF4 농도는 정상 대조군과 유의한 차이를 나타내지 않았으며 중재술 후 유의한 감소를 보이지 않았다. 중재술 시행 10일째의 β-TG 농도는 클로피도그렐 무반응군에서 반응군에 비해 높았으나 차이가 유의하지 않았다.
결론: 비록 심근경색에서 클로피도그렐 투여가 β-TG 농도를 감소시키나 치료 전후의 β-TG 및 PF4 농도가 클로피도그렐에 대한 혈소판 반응도와 관련되지는 않았다. 혈소판 유래 표지자는 클로피도그렐 무반응군을 예측하는 데 유용하지 않은 것으로 사료된다.

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