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1 Original ORIGINAL Article ARTICLE Korean Circulation J 2005;35: ISSN c 2005, The Korean Society of Circulation 급성관동맥증후군환자에서평균혈소판성분농도감소의임상적유용성 건양대학교의과대학심장병원심장내과학교실 김기영 배장호 The Clinical Usefulness of Decreased Mean Platelet Component Concentration in Patients with Acute Coronary Syndrome Ki-Young Kim, M.D. and Jang-Ho Bae, M.D. Division of Cardiology, Heart Center, College of Medicine, Konyang University, Daejeon, Korea ABSTRACT Background and Objectives:The reduction in the mean platelet component (MPC) concentration may be used to detect platelet activation. We performed this study to find the clinical usefulness of the MPC concentration in the differentiation of patients with stable angina from those with acute coronary syndrome (ACS). Subjects and Method:We evaluated 175 consecutive patients (57.9±10.4 years, 107 male) undergoing coronary angiography. The study patients were divided into two groups; patients with ACS (n=55, 57.5±11.8 years, 37 male) and those with stable angina (n=120, 58.1±9.7 years, 70 male). Venous blood samples were take into EDTA tube and immediately sent to laboratory room for measurement of the MPC concentration using the ADVIA 120 hematology system. Results:The MPC concentration was significantly decreased in those with ACS (27.3±1.2 g/dl vs. 28.6±0.9 g/dl, p=0.013) compared to those with stable angina, and also decreased in patients with unstable compared to stable angina (27.4±1.2 g/dl vs. 28.6±0.9 g/dl, p<0.001), but there was no difference in the MPC concentration between acute myocardial infarction and unstable angina (27.2±1.2 g/dl vs. 27.4± 1.2 g/dl, p=0.939). An MPC concentration (28.05 g/dl demonstrated 74.5% sensitivity and 75.0% specificity in the differentiation of patients with ACS from the others in the Receiver Operating Curve analysis. The positive and negative predictive values were 51.6 and 86.5%, respectively, at that level. Conclusion:Measurement of the MPC concentration may be useful in the detection of ACS. Also, a decreased MPC concentration may be a very useful marker for the differentiation of unstable and stable angina. (Korean Circulation J 2005;35: ) KEY WORDS:Acute coronary syndrome;platelet activation;mean platelet component;unstable angina. 서 급성관동맥증후군의기전은기존의관동맥죽상경화증의병변이여러가지요인에의하여죽상반의파열 ( 섬유막의 논문접수일 :2004 년 11 월 26 일수정논문접수일 :2005 년 1 월 13 일심사완료일 :2005 년 1 월 28 일교신저자 : 배장호, 대전광역시서구가수원동 685 건양대학교의과대학심장병원심장내과학교실전화 :(042) 전송 :(042) jhbae@kyuh.co.kr 론 파열또는내막의표재성미란 ) 과이로인한혈소판의활성화와혈전의생성으로관동맥폐쇄를유발하여일어난다고알려져있다. 1) 혈소판의활성화가급성관동맥증후군의중요한세포병리학적기전으로, 손상된혈관벽에혈소판의부착 (adhesion) 이가장먼저일어나고, 혈소판의모양변화및과립방출 (degranulation) 과 fibrinogen 을통한혈소판과혈소판의응집 (aggregation) 을일으켜서혈전생성을야기한다. 혈소판의활성도는혈소판모양의변화와혈소판의응집력, 혈액및소변의대사산물을측정함으로써정량화가가능해졌다. 혈소판표면분자발현의변화는면역형광법과 flow 240

2 Ki-Young Kim, et al:decreased MPC in Acute Coronary Syndrome 241 cytometry 로측정할수있다고알려져있다. 2-4) 예를들면, 혈장 P-selectin(CD62P) 농도를측정함으로써혈소판의활성화 5)6) 와급성심근경색증환자에서염증반응의병리생리기전을평가 7) 하는데도움이된다고보고되었다. Bayer AD- VIA 120 혈액측정기계를이용한평균혈소판성분 (mean platelet component, MPC) 농도의감소가혈소판의활성도를나타낸다고보고되어있다. 8) 급성관동맥증후군중급성심근경색증은심근괴사에의한 CK-MB 상승이나 troponin-i 또는 troponin-t 상승으로진단이가능하나어느정도시간이지난후파악할수있다는점과불안정형협심증은혈액검사로진단하는데한계가있다. 이에저자등은평균혈소판성분농도를측정하여혈소판의활성도를파악하면급성관동맥증후군을조기에진단하는데도움이있을것으로생각되고특히, 불안정형협심증과안정형협심증의감별에도움이되는지를알아보고자하였다. 대상및방법 대상흉통을주소로입원하여관상동맥조영술을실시한 175 명 ( 남자 107 명, 평균나이 57.9±10.4 세 ) 의환자를대상으로하였다. 내원시흉통의양상, 심근효소 (CK-MB, troponin-i) 의증가유무, 심전도상 ST절의변화유무에따라급성심근경색증, 불안정형협심증, 안정형협심증으로진단하였다. 급성심근경색증은 ESC/ACC(European Society of Cardiology/American College of Cardiology) 진단기준 9) 에따라 CK-MB 나 troponin 의상승과허혈성흉통의동반이나심전도에서병적인 Q파나허혈을시사하는소견이있는경우로하였다. 그리고불안정형협심증은심근효소는정상이나새롭게생겼거나안정시에발생또는심하거나악화되는흉통양상을보일때또는심전도에서 ST-T 절변화를보일때기준으로하였다. 10) 표준화된방법으로요골동맥또는대퇴동맥을통한관상동맥조영술을실시하여병변혈관의 50% 이상의협착이있을때에의미있는관상동맥질환으로진단하였고, 50% 미만의병변이나정상소견을보일때에는정상으로진단하였다. 진단에따라급성심근경색증과불안정형협심증을급성관동맥증후군으로, 안정형협심증과정상환자를대조군으로나누어각각비교하였다. 방법평균혈소판성분 (mean platelet component, MPC) 농도측정은응급실내원또는입원즉시아스피린, clopidogrel, 헤파린같은약물투여전에정맥혈을 EDTA 튜브에채취후 즉시또는늦어도 1시간이내에 Bayer ADVIA 120 혈액측정기계로분석하였다. 본연구에이용한 Bayer ADVIA 120 혈액측정기계는레이저빛산란에의해각각의혈소판의크기 ( 용적 ) 와굴절률 (refractive index, RI) 을측정하는데, 혈소판활성화로인한혈소판의팽창에따른용적변화와과립구방출후의혈소판밀도 (density) 를측정함으로평균혈소판성분농도를측정하게된다. 평균혈소판성분농도는혈소판밀도와직선의상관관계가있고, 다음과같은식으로계산된다 (RI: 혈소판굴절률, 1.333: 물굴절률, dl/g: 평균굴절률증가 ). 평균혈소판성분 (MPC)(g/dL)=[(RI-1.333)/ dl/g] 혈소판밀도 (density)=100 혈소판질량 (mass)(pg)/ 혈소판용적 (volume) 그리고심근효소 (CK-MB, troponin-i), 호모시스테인, high sensitivity C-reactive protein(hs-crp), 혈소판수치, 공복혈당, 총콜레스테롤, 중성지방, 고밀도지단백및저밀도지단백콜레스테롤농도를측정하였다. 좌심실수축기능평가로심초음파를이용한좌심실구출율 (ejection fraction) 을측정하였다. 급성관동맥증후군 ( 급성심근경색증과불안정형협심증 ) 과대조군 ( 안정형협심증과정상 ) 두군간및진단에따라평균혈소판성분농도와임상및검사실결과를비교하고, 관상동맥조영술에서병변혈관수에따라 0, 1, 2, 3-혈관질환으로나누어비교도하였다. 그리고평균혈소판성분농도와여러가지임상및혈액검사와의상관관계유무도파악하였다. 통계학적분석모든자료는평균 ± 표준편차로표시하였으며통계분석에는윈도우용 SPSS 11.0(Statistical Package for Social Science, SPSS Co., USA) 을이용하였다. 두군간의비교는 independent samples T-test 를이용하였고, 진단에따른비교와관상동맥조영술에서혈관병변수에따른비교는 oneway ANOVA 와 post hoc test의 Scheffe-type multiple comparison 을이용하였다. 급성관동맥증후군의진단에필요한평균혈소판성분농도의경계치 (cut-off value) 는민감도와특이도및예측도로써 ROC curve 를이용하여구하였다. 또한, 불안정형협심증과안정형협심증의감별진단에필요한평균혈소판성분농도의경계치도파악하였다. 급성관동맥증후군에영향을미치는독립적인자를평가하기위해다변량분석으로로지스틱회귀분석법 (logistic regression analysis) 을사용하였다. P값이 0.05 미만일때통계적유의성이있는것으로판정하였다.

3 242 Korean Circulation J 2005;35: 결 흉통으로내원하여관상동맥조영술을실시한전체환자 175 명중급성관동맥증후군은 55명 ( 남자 37명, 평균나이 57.5±11.8 세 ) 으로급성심근경색증이 33 명 ( 남자 24 명, 55.0± 13.2 세 ), 불안정형협심증이 22 명 ( 남자 13 명, 평균나이 61.1± 8.4 세 ) 이었고, 대조군은 120 명 ( 남자 70명, 평균나이 58.1± 9.7 세 ) 으로안정형협심증 66명 ( 남자 42명, 평균나이 60.1± 9.1 세 ), 정상이 54명 ( 남자 28 명, 평균나이 54.8±9.3세 ) 으로두군간의성별과나이의차이는없었다. 고혈압, 당뇨병, 고콜레스테롤혈증, 흡연력의차이는없었으나, 이전심근경색증의병력은급성관동맥증후군에서 7명 (12.7%) 으로대조군에서 3명 (2.5%) 과비교하여유의한차이가있었다 (p=0.012). 좌심실수축기능의평가로심초음파에서좌심실구출율은 Table 1. Clinical characteristics of acute coronary syndrome and control groups 과 ACS (n=55) Control (n=120) p Sex (M/F) 37/18 70/50 NS Age (years) 57.5± ±9.7 NS Hypertension 22 (40.0%) 40 (33.3%) NS Diabetes mellitus 10 (21.8%) 22 (18.3%) NS Hypercholesterolemia 29 (52.7%) 50 (41.7%) NS Smokers 21 (38.2%) 30 (25.0%) NS Prior MI 07 (12.7%) 03 (02.5%) LVEF (%) 57.1± ± Angiographic diagnosis 0 vessel disease 00 (00.0%) 54 (45.0%) 1 vessel disease 27 (49.1%) 43 (35.8%) 2 vessel disease 13 (23.6%) 16 (13.3%) 3 vessel disease 15 (27.3%) 07 (05.8%) ACS: acute coronary syndrome, MI: myocardial infarction, LVEF: left ventricular ejection fraction, NS: non-significant 57.1±12.1% vs. 65.5±9.7% 로급성관동맥증후군에서대조군에비해유의하게낮았다 (p=0.002)(table 1). 혈액학적검사에서두군간에평균혈소판성분농도는급성관동맥증후군에서대조군과비교하여유의하게낮았고 (27.3±1.2 g/dl vs. 28.6±0.9 g/dl, p=0.013), 심근효소수치는급성관동맥증후군과대조군에서 CK-MB 는 33.0± 66.8 U/L, 1.69±1.21 U/L 로 troponin-i 는 16.3±20.4 μg/l, 0.4±0.5 μg/l 로급성관동맥증후군에서대조군보다증가되었다 (p<0.001). 그러나혈장호모시스테인수치, Hs-CRP, 공복혈당, 지질수치및혈소판수치는두군간에유의한차이는없었다 (Table 2). 전체환자에서평균혈소판성분농도는좌심실구출율과양의상관관계 (r=0.163, p=0.032) 를보였고, CK-MB(r=-0.197, p=0.009) 와 troponin-i(r= , p<0.001) 는음의상관관계를보였다. Table 2. Laboratory findings of acute coronary syndrome and control groups ACS (n=55) Control (n=120) PLT count ( 10 3 /mm 3 ) 267.7± ±59.50 NS MPC (g/dl) 027.3± ± CK-MB (μg/l) 033.0± ±1.210 <0.001 Troponin I (μg/l) 016.3± ±0.500 <0.001 Homocysteine (μmol/l) 012.3± ±4.100 NS Hs-CRP (mg/l) 00.52± ±1.110 NS Total cholesterol (mg/dl) 194.2± ±39.60 NS Triglycerides (mg/dl) 193.8± ±147.2 NS HDL-cholesterol (mg/dl) 037.9± ±9.800 NS LDL-cholesterol (mg/dl) 119.2± ±38.00 NS Fasting glucose (mg/dl) 158.6± ±59.40 NS ACS: acute coronary syndrome, PLT: platelet, MPC: mean platelet component, CK-MB: creatine kinase, Hs-CRP: high sensitivity C-reactive protein, HDL: high density lipoprotein, LDL: low density lipoprotein, NS: non-significant p Table 3. Laboratory findings according to diagnosis ACS (n=55) Control (n=120) AMI (n=33) UA (n=22) AP (n=66) Nl (n=54) PLT count ( 10 3 /mm 3 ) 278.3±71.5* 251.7±59.4* 263.0± ±57.90 MPC (g/dl) 027.2±1.2* ±1.2* ± ±1.000 CK-MB (μg/l) 053.8±80.1* 001.8±0.90* 001.7± ±1.400 Troponin I (μg/l) 026.8±20.4* 000.5±0.90* 000.3± ±0.600 Homocysteine (μmol/l) 011.9±4.40* 012.8±3.50* 011.7± ±3.200 Hs-CRP (mg/l) 00.53±0.77* 00.50±0.72* 00.47± ±0.990 Total cholesterol (mg/dl) 189.5±39.0* 201.2±37.7* 194.3± ±39.10 Triglycerides (mg/dl) 183.6±81.8* 208.9±95.5* 191.7± ±168.8 HDL-cholesterol (mg/dl) 037.4±7.50* 038.4±10.3* 039.6± ±9.400 LDL-cholesterol (mg/dl) 117.6±33.6* 121.0±32.2* 117.3± ±35.00 Fasting glucose (mg/dl) 164.5±92.9* 149.9±82.4* 150.8± ±35.40 ACS: acute coronary syndrome, AMI: acute myocardial infarction, UA: unstable angina, AP: angina pectoris, Nl: normal, PLT: platelet, MPC: mean platelet component, CK-MB: creatine kinase, Hs-CRP: high sensitivity C-reactive protein, HDL: high density lipoprotein, LDL: low density lipoprotein. *: p<0.05 compare with angina pectoris, : p<0.05 compare with normal, : p<0.05 compare with unstable angina

4 Ki-Young Kim, et al:decreased MPC in Acute Coronary Syndrome 243 MPC concentration (g/dl) ±1.2 (n=33) p=ns AMI UA SA Normal ACS 27.4±1.2 (n=22) p= ±0.9 (n=66) p=ns Control 28.7±1.0 (n=54) Fig. 1. Mean platelet component (MPC) concentration according to the diagnosis. MPC concentration was significantly more decreased in ACS than control group. Additionally, MPC concentration was more decreased in patients with unstable angina than stable angina. But, there was no difference in MPC concentration between AMI and unstable angina. AMI: acute myocardial infarction, UA: unstable angina, SA: stable angina, ACS: acute coronary syndrome, NS: non-significant. Table 4. Logistic regression analysis evaluating the independent factors of acute coronary syndrome Variables B S.E p Exp (B) 95% C.I Prior MI < LVEF < CK-MB < Troponin-I < MPC < All the models included age, sex, diabetes mellitus, hypertension, prior myocardial infarction (MI), left ventricle ejection fraction (LVEF), high sensitivity C-reactive protein, homocysteine, CK-MB, troponin-i, mean platelet component (MPC), total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, fasting glucose as independent variables. HDL: high density lipoprotein, LDL: low density lipoprotein, CK-MB: creatine kinase, C.I: confident interval, B: coefficient, S.E: standard error 각각의진단에따른심근효소인 CK-MB 와 troponin-i 는심근경색증에서는증가되었으나, 불안정형협심증과안정형협심증에서는유의한차이를보이지않았다. 특징적으로평균혈소판성분농도는불안정형협심증에서안정형협심증에비해유의하게감소되었다 (27.4±1.2 g/dl vs. 28.6±0.9 g/dl, p<0.001). 그러나급성관동맥증후군 ( 불안정형협심증과급성심근경색증, 27.4±1.2 g/dl vs. 27.2±1.2 g/dl) 내에서와대조군 ( 안정형협심증과정상, 28.6±0.9 g/dl vs. 28.7±1.0 g/dl) 내에서평균혈소판성분농도의차이는없었다 (p>0.05)(table 3)(Fig. 1). ROC(receiver operation characteristic) curve 를이용한급성관동맥증후군의진단으로평균혈소판성분농도가 g/dl 이하일때민감도 74.5%, 특이도 75.0%, 양성 예측도 57.7%, 음성예측도 86.5% 이었고, 불안정형협심증과안정형협심증감별진단시평균혈소판성분농도가 g/dl 이하일때민감도 72.7%, 특이도 72.3%, 양성예측도 51.6%, 음성예측도 89.5% 였다. 로지스틱회귀분석을이용한다변량분석시급성관동맥증후군진단의독립적인자로는평균혈소판성분농도와 troponin-i 이었다. 그러나, 좌심실구출율, CK-MB, 이전심근경색증의병력은대조군과유의한차이가있었으나독립적인자는아니었다 (Table 4). 관상동맥조영술에서 50% 이상의협착이있는혈관수에따른분류를보면, 50% 미만이나정상소견을보인경우는 54명 ( 남자 28명, 평균나이 54.8±9.3 세 ), 단일혈관질환은 70명 ( 남자 50명, 평균나이 56.2±10.9 세 ), 두혈관질환은 29명 ( 남자 16명, 평균나이 62.9±9.1 세 ), 세혈관질환은 22명 ( 남자 13명, 평균나이 64.6±7.2 세 ) 이었다. 병변혈관수에따른평균혈소판성분농도는정상소견 28.7±0.9 g/ dl, 단일혈관질환 28.1±1.3 g/dl, 두혈관질환 27.8±1.3 g/dl, 세혈관질환 28.0±1.1 g/dl 으로정상소견과비교하여두혈관질환에서차이를보였다 (p=0.015). 고찰 혈소판은혈전형성에가장중심적인역할뿐아니라죽상동맥경화증의생성과진행에도관여하는것으로잘알려져있다. 11) 혈소판의활성화에는혈소판모양의변화, 혈소판의응집, 혈소판과립의방출등이관여하고 12) 이런혈소판의모양, 혈소판의응집정도, 혈소판활성화물질의정량적인측정으로혈소판의활성화정도를파악할수있다. 예를들면혈액에서 α- 과립성분, β-thromboglobulin, platelet factor 4, CD62P 의측정과소변에서 thromboxane B 2 를측정함으로써혈소판의활성도를평가하였다 ) Cin 등 17) 은급성흉통을가진환자에서 monocyte-platelet aggregates(mpa) 검출은 troponin-t 보다유용하다는것을보고하였다. Martin 등 18) 은증가된혈소판용적은혈소판재활성화와연관성이있어심근경색증뒤의결과에영향을끼친다고보고하였다. 그러나 Halbmayer 등 19) 은혈소판용적이나혈소판크기는관상동맥질환과밀접한연관성이없다고보고하여아직까지논란의소지가있다. 본연구에서는혈소판모양의변화와과립방출에따른밀도감소와평균혈소판성분농도측정이유용하다는것이보고되어있는 Bayer ADVIA 120 혈액측정기계를이용하여측정한평균혈소판성분농도의감소가혈소판활성화와연관성이있고, 또한 flow cytometry 로측정한 CD62P

5 244 Korean Circulation J 2005;35: 증가가평균혈소판성분농도의감소와밀접한연관성을보여주고있음을관찰할수있었다. 8) 정맥혈채취후에상온에서항응고제 EDTA 에의한혈소판의자가활성화가일어나서시간에따른용적변화를보이고, 이에따른평균혈소판성분농도도시간에따라차이가나타나는데, 첫 1 시간이내에는큰변화가없으나 1~2 시간내에큰변화로감소하기시작하여 2시간후에는안정기를이루는것으로보고되어, 20) 본연구에서는평균혈소판성분농도의시간에따른변화를최소화하기위해채혈후항응고제로 EDTA 를사용한튜브에보관즉시또는 1시간이내에측정을하였다. 그리고여러약제들도혈소판의활성화에영향을미치는것으로알려져있는데, 아스피린과고용량의헤파린은혈소판의 cyclo-oxygenase 를차단하고혈소판의과립방출을방해하여비특이적으로혈소판의활성화를감소시키고, clopidogrel 또는 ticlopidine 은혈소판의 ADP 수용체를차단하여혈소판의활성화를억제하고, abciximab 은혈소판의 GP Ⅱb/Ⅲa 수용체를차단하여혈소판응집의최종과정을방해하는작용이알려져있다. 21) 따라서이러한약제에의한영향을줄이기위해서어떠한약제도투여하기전에정맥혈을채취하여평균혈소판성분농도를측정하였다. 혈소판활성화는뇌혈관질환, 22) 말초혈관질환, 심방세동, 23) 알츠하이머질환, 24) 심부정맥혈전증 16)25) 등과연관되어있고, 당뇨병, 26) 흡연, 고혈압, 경구피임약의복용 27) 에의해영향을받는다고알려져있다. 본연구에서는급성관동맥증후군과대조군에서당뇨병, 흡연, 고혈압의유무에차이가없어이런요인에의한평균혈소판성분농도의영향을배제할수있었다. 이전심근경색증병력의빈도는급성관동맥증후군에서대조군에비해서높았고 (12.7% vs. 2.5%, p= 0.012), 이전심근경색증의병력이있었던환자의평균혈소판성분농도는급성관동맥증후군환자에서대조군에비해유의하게낮았다 (26.7±1.0 g/dl vs. 28.7±0.5 g/dl, p= 0.01). 최근아스피린저항성이있는환자에서심근경색증과뇌경색의위험성이높고, 28) 급성심근경색증으로일차적관동맥중재술을실시한환자중에서 clopidogrel 저항성이있는환자에서죽상혈전증재발의위험이높다고알려져있다. 29) 위의환자에서아스피린, clopidogrel 등의약물복용에차이가없음에도불구하고평균혈소판성분농도가차이가있었는데, 이것이급성관동맥증후군에의한것인지아니면항혈소판제재의저항성과관련이있는것인지파악하지는못하였다. 급성관동맥증후군에서염증반응의지표로 Hs-CRP 의증가가입원시와짧은기간예후에나쁜 결과와연관성이있고, 급성심근경색증환자의 50% 미만에서증가되어있다고보고되어있는데 30) 본결과에서는급성심근경색증환자에서증가된경향이나유의한차이는없었다. 이연구에서는대조군에비해급성관동맥증후군에서평균혈소판성분농도가유의하게감소하였고, 평균혈소판성분농도가급성관동맥증후군진단의독립적인자로밝혀졌다. 흥미로운것은급성심근경색증과불안정형협심증에서평균혈소판성분농도의차이는없었으나, 불안정형협심증에서안정형협심증에비해평균혈소판성분농도가감소하였다. 그러나불안정형협심증과급성심근경색증에서차이를보이지않은것은심근효소와는달리혈소판의활성화는이두질환에서비슷하다는것을나타냄으로써급성관동맥증후군으로언급되는것을뒷받침할수있다고생각된다. 본연구의제한점으로는급성관동맥증후군이발생시시간의경과에따른평균혈소판성분농도의변화는아직밝혀지지않았으나, 흉통발생후일정한시간내의환자를대상으로실시하여야하였으나내원당시의시간경과가다양하기때문에평균혈소판성분농도에영향을미치는시간요소를완전히배제하지못하였다는점이다. 결론적으로혈소판활성도를평가하는데한가지검사법이나정확한방법은아직까지논란의여지가있고, 대규모환자를대상으로연구가필요하겠으나평균혈소판성분농도의감소는급성관동맥증후군진단에도움이되는혈액학적인자의하나로서뿐아니라, 안정형협심증과불안정형협심증을감별진단하는데도움이될수있을것으로생각된다. 임상양상으로불안정형협심증과안정형협심증을감별하기어려울때평균혈소판성분농도가감소되었을때는불안정형협심증에준한더욱더적극적인치료가필요할것으로생각된다. 그리고향후급성관동맥증후군에서시간에따른평균혈소판성분농도의변화뿐아니라혈전용해제사용또는중재시술후의변화와약물사용에따른변화에대해서는좀더깊은연구가필요하겠다. 요약 배경및목적 : 급성관동맥증후군은죽상동맥경화증에서죽상반의파열, 혈소판의활성화와이로인한혈전형성에의해서발생한다. 평균혈소판성분농도의감소가혈소판의활성화를평가하는데도움이된다고알려져있다. 본연구의목적은

6 Ki-Young Kim, et al:decreased MPC in Acute Coronary Syndrome 245 급성관동맥증후군에서평균혈소판성분농도의유용성과안정형협심증의감별에도움이되는지를보고자하였다. 방법 : 관상동맥조영술을실시한 175 명 ( 평균나이 57.9±10.4 세, 남자 107 명 ) 의환자들을대상으로하였다. 급성관동맥증후군 ( 급성심근경색증과불안정형협심증 ) 과대조군 ( 안정형협심증과정상 ) 의두군으로나누어비교하였다. EDTA 튜브에채혈한후 1시간이내에 Bayer ADVIA 120 혈액측정기계로평균혈소판성분농도를측정하여평가하였다. 결과 : 급성관동맥증후군과대조군사이에성별, 나이, 흡연, 당뇨병, 고혈압, 고지혈증, 혈소판수치는차이가없었다 (p>0.05). 평균혈소판성분농도는급성관동맥증후군에서대조군에비해유의하게감소하였다 (27.3±1.2 g/dl vs. 28.6±0.9 g/ dl, p=0.013). 그리고불안정형협심증환자에서안정형협심증에비해평균혈소판성분농도는감소하였으나 (27.4± 1.2 g/dl vs. 28.6±0.9 g/dl, p<0.001), 불안정형협심증과급성심근경색증환자에서는차이가없었다 (27.4±1.2 g/ dl vs. 27.2±1.2 g/dl, p>0.05). 평균혈소판성분농도가 g/dl 이하일때급성관동맥증후군을진단하기위한민감도는 74.5%, 특이도는 75%, 양성예측도는 51.6%, 음성예측도는 86.5% 였다. 결론 : 평균혈소판성분농도의측정은급성관동맥증후군의진단뿐아니라, 임상상황에서불안정형협심증과안정형협심증의감별진단에도움이되는유용한검사법으로이용할수있겠다. 중심단어 : 급성관동맥증후군 ; 혈소판활성화 ; 평균혈소판성분 ; 불안정형협심증. REFERENCES 1) Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362: ) Goodall AH, Macey MG. Platelet Associated Molecules and Immunoglobulins: flow cytometry clinical application. London: Blackwell; p ) Singh N, Gemmell CH, Daly PA, Yeo EL. Elevated platelet-derived microparticle levels during unstable angina. Can J Cardiol 1995; 11: ) Blann AD, Lip GY. Hypothesis: is soluble P-selectin a new marker of platelet activation? Atherosclerosis 1997;128: ) Knight CH, Panesar M, Wright C, et al. Altered platelet function detected by flow cytometry: effects of coronary artery disease and age. Arterioscler Thromb Vasc Biol 1997;17: ) Hamamoto K, Ohga S, Nomura S, Yasunaga K. Cellular distribution of CD63 antigen in platelets and in three megakaryocytic cell lines. Histochem J 1994;26: ) Ikeda H, Nakayama H, Oda T, et al. Soluble form of P-selectin in patients with acute myocardial infarction. Coron Artery Dis 1994; 5: ) Macey MG, Carty E, Webb L, et al. Use of mean platelet component to measure platelet activation on the ADVIA 120 hematology system. Cytometry 1999;38: ) The Joint European Society of Cardiology/American College of Cardiology Committee. Myocardial infarction redefined. Eur Heart J 2000;21: ) Braunwald E. Unstable angina: a classification. Circulation 1989; 80: ) Bombeli T, Schwartz BR, Harlan JM. Adhesion of activated platelets to endothelial cells: evidence for a GPIIbIIIa-dependent bridging mechanism and novel roles for endothelial intercellular adhesion molecule 1 (ICAM-1), alphavbeta3 integrin, and GPIbalpha. J Exp Med 1998;187: ) Kamath S. Blann AD, Lip GY. Platelet activation: assessment and quantification. Eur Heart J 2001;22: ) Blann AD, Lip GY. Hypothesis: is soluble P-selectin a new marker of platelet activation? Atherosclerosis 1997;128: ) Schmitz G, Rothe G, Ruf A, et al. European Working Group on Clinical Cell Analysis: consensus protocol for the flow cytometric characterization of platelet function. Thromb Haemost 1998;79: ) Hollander JE, Muttreja MR, Dalesandro MR, Shofer FS. Risk stratification of emergency department patients with acute coronary syndromes using P-selectin. J Am Coll Cardiol 1999;34: ) Klotz TA, Cohn LS, Zipser RD. Urinary excretion of thromboxane B 2 in patients with venous thromboembolic disease. Chest 1984; 85: ) Cin VG, Pekdemir H, Avci ME, Yalciner A, Akkus N, Doven O. Monocyte-platelet aggregates (MPA) are better predictors than troponin T in patients with unstable angina. Int J Cardiol. In Press. 18) Martin JF, Bath PM, Burr ML. Influence of platelet size on outcome after myocardial infarction. Lancet 1991;338: ) Halbmayer WM, Haushofer A, Radek J, Schon R, Deutsch M, Fischer M. Platelet size, fibrinogen and lipoprotein (a) in coronary heart disease. Coron Artery Dis 1995;6: ) Macey M, Azam U, McCarthy D, et al. Evaluation of the anticoagulants EDTA and citrate, theophylline, adenosine, and dipyridamole (CTAD) for assessing platelet activation on the ADVIA 120 hematology system. Clin Chem 2002;48: ) Rosove MH. Platelet glycoprotein IIb/IIIa inhibitors. Best Pract Res Clin Haematol 2004;17: ) Grau AJ, Ruf A, Vogt A, et al. Increased fraction of circulating activated platelets in acute and previous cerebrovascular ischemia. Thromb Haemost 1998;80: ) Minamino T, Kitakaze M, Asanuma H, et al. Plasma adenosine levels and platelet activation in patients with atrial fibrillation. Am J Cardiol 1999;83: ) Sevush S, Jy W, Horstman LL, Mao WW, Kolodny L, Ahn YS. Platelet activation in Alzheimer disease. Arch Neurol 1998;55: ) de Boer AC, Han P, Turpie AG, Butt R, Zielinsky A, Genton E. Plasma and urine beta thromboglobulin concentrations in patients with deep vein thrombosis. Blood 1981;58: ) Tschoepe D, Driesch E, Schwippert B, Lampeter EF. Activated platelets in subjects at increased risk of IDDM. Diabetologia 1997; 40: ) Bonnar J. Coagulation effects of oral contraception. Am J Obstet Gynecol 1987;157:

7 246 Korean Circulation J 2005;35: ) Eikelboom JW, Hirsh J, Weitz JI, Johnston M, Yi Q, Yusuf S. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002;105: ) Matetzky S, Shenkman B, Guetta V, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infaction. Circulation 2004;109: ) Biasucci LM, Liuzzo G, Grillo RL, et al. Elevated levels of C- reactive protein at discharge in patients with unstable angina predict recurrent instability. Circulation 1999;99:

저작자표시 - 비영리 - 변경금지 2.0 대한민국 이용자는아래의조건을따르는경우에한하여자유롭게 이저작물을복제, 배포, 전송, 전시, 공연및방송할수있습니다. 다음과같은조건을따라야합니다 : 저작자표시. 귀하는원저작자를표시하여야합니다. 비영리. 귀하는이저작물을영리목적으로이용할

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