一、支架內(nèi)血栓的病理（見(jiàn)圖1至圖3）

歐洲PRISTIGE組織者進(jìn)行了一項(xiàng)支架內(nèi)血栓的組織病理研究，共分析了253個(gè)支架內(nèi)血栓樣本，79例（31.2%）來(lái)自于早期ST，174例（68.8%）來(lái)自于晚發(fā)ST，79例（31.2%）為金屬裸支架，166例（65.6%）為藥物洗脫支架，8例支架類型不明（3.2%）。血栓形態(tài)多樣，富含血小板和纖維蛋白碎片。平均血小板覆蓋比例占血栓區(qū)域的57%，白細(xì)胞浸潤(rùn)在早期和晚期ST均很明顯。其中，主要是中性粒細(xì)胞，ST患者栓子中白細(xì)胞計(jì)數(shù)明顯高于自發(fā)性心肌梗死患者的栓子。23%的樣本中觀察到了中性粒細(xì)胞胞外陷阱現(xiàn)象。幾乎所有支架類型都觀察到了嗜酸性粒細(xì)胞，在使用雷帕霉素和依維莫司藥物洗脫支架的晚發(fā)ST患者中嗜酸性粒細(xì)胞數(shù)量更高。

二、支架血栓的危險(xiǎn)因素

通常將危險(xiǎn)因素分為患者、手術(shù)及設(shè)備相關(guān)（見(jiàn)圖4）。

1.早期支架內(nèi)血栓

在早期ST中，手術(shù)相關(guān)危險(xiǎn)因素是最主要的，支架過(guò)小、殘余狹窄、術(shù)后TIMI血流分級(jí)降低、支架近端或遠(yuǎn)端殘余病變是ST的最主要預(yù)測(cè)因素^[7]。一項(xiàng)法國(guó)研究顯示，病變復(fù)雜性和PCI指數(shù)強(qiáng)烈預(yù)測(cè)術(shù)后ST^[8]。此外，患者左心室功能減低、對(duì)ADP拮抗劑反應(yīng)差同樣增加術(shù)后ST風(fēng)險(xiǎn)，術(shù)后30天內(nèi)早期停用抗血小板治療是ST的最重要預(yù)測(cè)因素^[9]。此外，相當(dāng)多研究關(guān)注ADP拮抗劑治療反應(yīng)性對(duì)ST的預(yù)測(cè)。首先，基于氯吡格雷代謝相關(guān)酶的基因多態(tài)性的藥代動(dòng)力學(xué)檢測(cè)似乎能夠確定患者風(fēng)險(xiǎn)^[10-12]。其次，許多研究已經(jīng)展示了血小板功能檢測(cè)中血小板高反應(yīng)性與隨后ST的相關(guān)性^[6,13]。例如，在Sibbing等所在中心的一項(xiàng)研究顯示，血小板高反應(yīng)性患者ST風(fēng)險(xiǎn)為其他患者的9倍^[13]。

最后，雖然支架相關(guān)危險(xiǎn)因素相對(duì)于其他稍顯不重要，大數(shù)據(jù)庫(kù)研究顯示相對(duì)于藥物洗脫支架，金屬裸支架可能增加早期ST風(fēng)險(xiǎn)^[14]。的確，研究顯示聚合物包被能通過(guò)改善支架-血流接觸減少ST^[15]，一項(xiàng)關(guān)于急性心肌梗死介入治療的隨機(jī)試驗(yàn)也進(jìn)一步證實(shí)了此類觀點(diǎn)^[16]。

2.晚發(fā)支架內(nèi)血栓

雖然明顯的術(shù)中技術(shù)缺點(diǎn)主要造成早期支架失敗，但也是晚發(fā)支架內(nèi)血栓的重要原因，如支架過(guò)小或擴(kuò)張不足^[7]，支架移位也不少見(jiàn)^[17]。此外，患者相關(guān)危險(xiǎn)因素如糖尿病、左心射血分?jǐn)?shù)降低也與晚發(fā)ST相關(guān)^[7]。另外，ADP拮抗劑治療反應(yīng)性的降低也是晚發(fā)ST的危險(xiǎn)因素^[12]。

支架類型是遲發(fā)型ST重要影響因素。2006年歐洲心血管年會(huì)提出初代藥物洗脫支架可能增加ST進(jìn)而導(dǎo)致心源性死亡^[18]，后來(lái)的一些meta分析也顯示雷帕霉素和紫杉醇藥物洗脫支架有此類風(fēng)險(xiǎn)^[14,19-20]。此外，注冊(cè)研究顯示4~5年內(nèi)ST風(fēng)險(xiǎn)逐漸增加，沒(méi)有隨著時(shí)間減輕的證據(jù)^[21]。尸檢顯示原因可能與推遲動(dòng)脈愈合有關(guān)，主要表現(xiàn)為內(nèi)膜覆蓋受損、持續(xù)的纖維蛋白沉積和動(dòng)脈壁炎癥浸潤(rùn)。新一代支架似乎解決了動(dòng)脈延遲愈合問(wèn)題，更薄的支架支柱，更生物兼容的聚合物包被，更低劑量的雷帕霉素類藥物。

三、雙抗持續(xù)時(shí)間和支架內(nèi)血栓的預(yù)防

防止ST的關(guān)鍵是適當(dāng)?shù)碾p抗。1990年的隨機(jī)臨床試驗(yàn)已經(jīng)證明了在阻止金屬裸支架并發(fā)癥方面，雙抗優(yōu)于抗凝。早期的使用藥物支架的臨床研究推薦術(shù)后雙抗3~6個(gè)月，雖然此后發(fā)現(xiàn)可能增加術(shù)后晚發(fā)ST風(fēng)險(xiǎn)。此后，人們開(kāi)始增加雙抗時(shí)間至12個(gè)月，并且探索更精確和最佳的雙抗時(shí)間。

早期研究顯示延長(zhǎng)雙抗時(shí)間不能減少缺血事件，而且，此類早期研究均不能顯示ST的減少。新近發(fā)表的一個(gè)雙抗試驗(yàn)，9921位DES治療患者，隨機(jī)分為雙抗30個(gè)月和12個(gè)月組，結(jié)果顯示延長(zhǎng)雙抗明顯降低ST（0.4%vs.1.4%；HR，0.29；P<>

目前，口服抗凝的最佳方案尚不清楚，僅有2個(gè)隨機(jī)對(duì)照試驗(yàn)（RCT），且效力較低。因此，口服抗凝劑目前僅推薦用于支架術(shù)后急性冠狀動(dòng)脈綜合征患者，此外，新型的靜脈用ADP受體拮抗劑可能能夠進(jìn)一步減少支架后急性期ST的發(fā)生率。

翻譯：張晶晶 赤峰市醫(yī)院神經(jīng)內(nèi)科

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編輯  黃越