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1 대한내과학회지 : 제 84 권제 4 호 다른관상동맥에서반복적으로발생한스텐트내혈전 단국대학교의과대학내과학교실 조선영 신경황 신현성 이수진 이지은 정경연 강태수 Recurrent Stent Thrombosis in Different Coronary rteries Sun Young Cho, Kyoung Hwang Shin, Hyun Sung Shin, Su Jin Lee, Ji Eun Lee, Kyong Yeun Jung, and Tae Soo Kang Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea Drug-eluting stents (DES) dramatically reduce the rate of restenosis and the need for repeat revascularization. Despite these promising results, stent thrombosis seems to occur more frequently with DES and often seems to be associated with premature discontinuation of antiplatelet agents. We experienced a case of recurrent stent thrombosis with separate lesions. Recurrent stent thrombosis is a very rare event, and simultaneous stent thrombosis is also rare. Here, we report a case of recurrently developing stent thrombosis involving separate lesions. (Korean J Med 2013;84: ) Keywords: Drug-eluting stents; Coronary thrombosis; ntiplatelet agents 서론약물방출스텐트 (drug-eluting stents, DES) 의등장으로관상동맥중재술후재협착률및재시술비율이현저하게감소하였다. 그러나일반스텐트에비해혈전생성경향성이높고, 이에다양한요인이관련되어있다고알려졌다 [1,2]. 혈전생성경향성에는약물방출스텐트자체에의한요인, 환자의특성이나관상동맥병소와관련된요인및항혈소판약제사용의적정성이관련되어있다. 이러한요인들이단독으로또는복합적으로작용하여혈전경향성을높인다고알려져있지만, 국소적인문제가아닌아직완전하게이해하지못한전신적인문제때문에발생할수있다는몇몇증거가 있고명확하게그원인을파악하지못하는경우도있다 [3]. 반복적으로스텐트내혈전이발생하는것은드문것으로알려져있고, 게다가혈전이다른부위에서반복적으로발생하는것은더욱드물다. 우리는두배용량의 clopidogrel을포함한항혈소판삼제요법으로치료받던환자에서다른두혈관내의스텐트에서반복적으로혈전이발생했던증례를경험하여보고하는바이다. 증례 72세남자가 2일전부터발생한안정시흉통및호흡곤란을주소로입원하였다. 심전도여러유도에서 T 파의역위가 Received: Revised: ccepted: Correspondence to Tae Soo Kang, M.D., Ph.D. Department of Internal Medicine, Dankook University College of Medicine, 359 Manghyang-ro, Dongnam-gu, Cheonan , Korea Tel: , Fax: , neosoo70@dankook.ac.kr Copyright c 2013 The Korean ssociation of Internal Medicine This is an Open ccess article distributed under the terms of the Creative Commons ttribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

- The Korean Journal of Medicine: Vol. 84, No. 4, 2013 - 관찰되었고, 초기심장효소검사에서 CK-M 와 Troponin-I 가상승되어환자는즉시관상동맥조영술을시행받았다.

0 24 mm 의 Endeavor Resolute Stents (Medtronic, Minneapolis, MN, US), 좌측회선관상동맥의근위부에는 2.75 24 mm Endeavor Resolute stent를성공적으로삽입하였다 (Fig. 1).

응급으로시행한관상동맥조영술에서우측 관상동맥의근위부가혈전으로완전폐색되어 (Fig. 2), 2.5 mm 풍선카테터를이용한풍선혈관성형술 (balloon angioplasty) 을시행하였고, TIMI 3 혈류가회복된것 (Fig.

5일후다시환자는흉통을호소하였고, 심전도상에서는여러유도에서 ST 분절의하강이보이면서수축기혈압은 90 mmhg 이하로측정되었다. 응급으로다시검사한관상동맥조영술에서이전에스텐트를삽입하였던, 좌측회선관상동맥의근위부와우측관상동맥의완전폐색이동시에발견 C D Figure 1.

2 - The Korean Journal of Medicine: Vol. 84, No. 4, 관찰되었고, 초기심장효소검사에서 CK-M 와 Troponin-I 가상승되어환자는즉시관상동맥조영술을시행받았다. 좌측회선관상동맥 (left circumflex coronary artery, LCX) 의근위부및우측관상동맥 (right coronary artery, RC) 의협착을확인한뒤우측관상동맥에는 mm와 mm 의 Endeavor Resolute Stents (Medtronic, Minneapolis, MN, US), 좌측회선관상동맥의근위부에는 mm Endeavor Resolute stent를성공적으로삽입하였다 (Fig. 1). 이후환자는항혈소판약제 aspirin 100 mg과 clopidogrel 75 mg으로치료받던중, 관상동맥성형술시행 6일후갑자기설하 nitroglycerin에도호전되지않는심한흉통을호소하였고, 심전도에서는 II, III, avf 유도에서 ST 분절의상승이관찰되었다. 응급으로시행한관상동맥조영술에서우측 관상동맥의근위부가혈전으로완전폐색되어 (Fig. 2), 2.5 mm 풍선카테터를이용한풍선혈관성형술 (balloon angioplasty) 을시행하였고, TIMI 3 혈류가회복된것 (Fig. 2) 을확인한뒤정맥으로 glycoprotein IIb/IIIa 억제제 (abciximab) 를주입하면서검사를종료했다. cilostazol 200 mg을포함하여항혈소판삼제요법을시작하면서, clopidogrel 저항에대한가능성을고려하여 clopidogrel을 150 mg으로증량하여치료하였다. 5일후다시환자는흉통을호소하였고, 심전도상에서는여러유도에서 ST 분절의하강이보이면서수축기혈압은 90 mmhg 이하로측정되었다. 응급으로다시검사한관상동맥조영술에서이전에스텐트를삽입하였던, 좌측회선관상동맥의근위부와우측관상동맥의완전폐색이동시에발견 C D Figure 1. (, ) Coronary angiography revealed critical stenosis in the proximal LCX and RC. Coronary intervention with a drug-eluting stent for the proximal LCX and two drug-eluting stents for the RC were performed successfully. (C, D) Final angiography showed no residual lesions with good distal flow. LCX, left circumflex artery; RC, right coronary artery

() Emergent coronary angiography shows total

() Final angiography after balloon angioplasty shows

occlusion of both stents in the proximal LCX and

(C) Final angiography after angioplasty showed good

3 Sun Young Cho, et al. Recurrent stent thrombosis Figure 2. () Emergent coronary angiography shows total occlusion of stents in the proximal RC. () Final angiography after balloon angioplasty shows good distal flow. RC, right coronary artery. C D Figure 3. (, ) Emergent coronary angiography reveals total occlusion of both stents in the proximal LCX and proximal RC without distal flow. (C) Final angiography after angioplasty showed good distal flow with some intraluminal haziness of the proximal LCX lesion. (D) Final RC angiography after angioplasty shows good distal flow. LCX, left circumflex artery; RC, right coronary artery

4 - 대한내과학회지 : 제 84 권제 4 호통권제 632 호 되었다 (Fig. 3). 대동맥내풍선펌프 (intra-aortic balloon counterpulsation) 삽입후 2.75 mm 풍선카테터를이용하여풍선혈관성형술을시행한뒤, 좌측회선관상동맥의원위부혈류가 TIMI 3 정로로회복되었지만우측관상동맥의혈류는호전되지않았고, 우측관상동맥스텐트근위부의가장자리에서관상동맥박리가보였다. 그래서 mm Xience V 스텐트 (bbott, Santa Clara, C, US) 를우측관상동맥근위부에시술한뒤혈류가호전된것을확인후검사를종료하였다. 2일후다시시행한관상동맥조영술에서도관상동맥내음영결손없이좌측회선관상동맥과우측관상동맥스텐트의혈류가호전된상태로유지된것을확인할수있었다. 비록환자는다른두스텐트내반복적으로발생한혈전에대해관상동맥성형술을성공적으로시행받았으나, 이후급성신부전, 폐부종그리고소뇌경색이발생하였고, 결국에는다기관부전을동반한심장성쇽으로사망하였다. 고찰반복적으로발생하는스텐트내혈전에관한몇몇의증례가보고되어왔으나, 반복적으로다른병소에서스텐트내혈전이발생한증례는보고되지않았다. 우리가알고있는한이증례는반복적으로다른병소에서발생한스텐트내혈전에관한첫보고이다. 증례에서환자는급성심근경색과상대적으로긴병소의길이등스텐트내혈전생성에관한여러위험요소를가지고있었다. 초기에환자는급성심근경색으로승압제를유지해야하는상황이었고, 첫심전도확인후병변을좌측전하행관상동맥 (left anterior descending coronary artery, LD) 으로추측하고검사를시작했지만우측관상동맥과좌측회선관상동맥의협착이발견되어관상동맥성형술을시행하였다. 당시병변의적절한평가를할여유가되지않아혈관내초음파 (intravascular ultrasound, IVUS) 검사없이관상동맥성형술을시행하였으나, 먼저병변에대한평가가적절하게이루어졌다면긴병변에대한스텐트사용을피함으로써환자의예후가달라졌을수도있었을것이다. 게다가전통적으로아급성스텐트내혈전생성의경우시술관련인자가많이연관되어있는것으로알려져있다. 여러스텐트사용에도불구하고, 육안적으로는스텐트가장자리의박리, 불충분한팽창및부적절한위치는없었기때문 에우리는이러한혈전생성이시술에관련된문제가아니라고판단하였으나, 혈관내초음파검사를통해서만확인될수있는시술관련문제에관해서는완전히배제할수없다는제한점이있다. 스텐트혈전증발생에대한다른원인을파악하기위해혈소판기능및과응고성 / 과혈전증을일으킬만한소인에대한검사를시행하였다. 비록 VerifyNow system analyser상 480 PRU로중등도의저항성을확인하였지만, VerifyNow 검사시점이 glycoprotein IIb/IIIa 억제제 (abciximab) 투여후 24 시간내의시점이었고, cilostazol 역시병행투여중이었으므로검사결과의신뢰성에문제가있을것으로판단하였다. 과응고성을알아보기위한검사에서 nticardiolipin b IgM, IgG 항목은정상치를보였다. 이증례에서흥미로운점은두번째로발생한스텐트내혈전은 clopidogrel을두배용량으로증량하면서항혈소판삼제요법을사용하는중에발생하였다는것이다. 이전의보고에따르면 [4], 항혈소판삼제요법은관상동맥스텐트시술후이제요법보다혈전생성을예방하는데더효과적이다. spirin 은 thromboxane 의합성을저해하고, clopidogrel은 DP 로인한혈소판응집을저해하지만, cilostazol은기존약물과다르게 phosphodiesterase (PDE) III 억제제로서 cmp 증가를통해항혈소판효과를나타내어혈소판응집을방해하는데추가적인역할을하기때문이다 [5]. spirin 을포함하여두배용량의 clopidogrel에 cilostazol 까지추가로사용하였으나스텐트내혈전을예방하지못한주요원인에대해저자들은급성관상동맥증후군 (acute coronary syndrome) 환자에게투여된항혈소판약제들의불충분한효과때문일것이라고결론내렸다. 이전의연구에따르면 [6], clopidogrel 저항성의경우 ST 상승심근경색 (STEMI) 환자의 25% 에서보고됐고, 심혈관계질환의재발위험이증가되는것과연관성이있었다. 이는일부환자들에게있어서현재의표준항혈소판치료요법으로는혈전을안전하게예방할수없다는것을의미한다. 비록이증례보고에서반복적으로발생하는스텐트내혈전의정확한병리생리학적기전에대해설명하지는못했지만, 혈전생성발생의위험성은스텐트가덜펴지는것과같은간단한문제가아니라이중또는삼중항혈소판약제에의해서도억제되지않는혈소판재활성화를전신적으로높이는혈전유발의잠재성 (thrombogenic potentials) 으로부터기인

5 - 조선영외 6 인. 반복적으로발생한스텐트내혈전 - 한것이라생각한다. 이전연구에서명확한스텐트내혈전의재발비율또는그에따른사망은약 18% 로, 예후가매우나쁘다고보고되어있어 [7,8], 스탠트내혈전이발생했던환자들에대한관리와주의깊은추적관찰은매우중요하다. 또한항혈소판제에대한반응저하 (hypo-responsiveness) 또는혈전유발의잠재성 (thrombogenic potentials) 의증가와같은문제를적절하게파악하고, 이러한고위험군환자들에게적합한항혈소판치료요법에대해연구하는것또한필요하다. 요약하면이증례는스텐트내혈전이국소적인문제가아니라아직충분히밝혀지지않은전신적인문제에서기인한것이라는것을언급하고, 약물방출스텐트를시술받은급성심근경색환자에있어서관상동맥성형술이후스텐트내혈전의발생위험을줄일수있는효과적인항혈소판제치료법에대한추가적인연구가필요함을강조하고있다. 요약약물방출스텐트 (drug-eluting stents, DES) 의등장으로관상동맥중재술후재협착율및재시술비율이현저하게감소하였다. 그러나이런결과에도불구하고, 일반스텐트에비해높은혈전생성경향성때문에약물방출스텐트삽입후에발생하는스텐트내혈전예방에관하여광범위하게논의되어왔다. 항혈소판약물요법에도불구하고, 반복적으로스텐트내혈전이발생하는것은드문것으로알려져있고, 게다가혈전이다른부위에서반복적으로발생하는것은더욱드물다. 저자들은두배용량의 clopidogrel 을포함한항혈소판삼제요법으로치료받던 72세남자에게서다른두스텐트내반복적으로혈전이발생했던증례를경험하였기 에문헌고찰과함께보고하는바이다. 중심단어 : 약물방출스텐트 ; 관상동맥혈전 ; 항혈소판약제 REFERENCES 1. iroldi F, Colombo, Morici N, et al. Incidence and predictors of drug-eluting stent thrombosis during and after discontinuation of thienopyridine treatment. Circulation 2007;116: Win HK, Caldera E, Maresh K, et al. Clinical outcomes and stent thrombosis following off-label use of drug-eluting stents. JM 2007;297: Park SH, Hong GR, Seo HS, Tahk SJ. Stent thrombosis after successful drug-eluting stent implantation. Korean Circ J 2005;35: Lee SW, Park SW, Hong MK, et al. Triple versus dual antiplatelet therapy after coronary stenting: impact on stent thrombosis. J m Coll Cardiol 2005;46: Kim JS, Lee KS, Kim YI, Tamai Y, Nakahata R, Takami H. randomized crossover comparative study of aspirin, cilostazol and clopidogrel in normal controls: analysis with quantitative bleeding time and platelet aggregation test. J Clin Neurosci 2004;11: Matetzky S, Shenkman, Guetta V, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004;109: van Werkum JW, Heestermans, de Korte FI, et al. Long-term clinical outcome after a first angiographically confirmed coronary stent thrombosis: an analysis of 431 cases. Circulation 2009;119: Moon JY, Jeong MH, Kim IS, et al. Long-term clinical outcome and prognosis after treatment of the first generation drug-eluting stent thrombosis. Int J Cardiol 2010;145:

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Microsoft Word doc ORIGINAL ARTICLE Korean Circ J 2007;37:641-646 Print ISSN 1738-5520 / On-line ISSN 1738-5555 Copyright c 2007 The Korean Society of Cardiology TAXUS TM 스텐트시술후스텐트혈전증발생률과임상경과 전남대학교병원심장센터, 1 전남대학교심혈관계특성화연구사업단,