顱內(nèi)動(dòng)脈瘤支架輔助栓塞術(shù)中急性血栓形成的治療

劉偉 王卓然 郭慶東* 張?chǎng)蝹?張磊 付洛安 費(fèi)舟

(1空軍軍醫(yī)大學(xué)西京醫(yī)院神經(jīng)外科，陜西 西安 710032; 2空軍軍醫(yī)大學(xué)學(xué)員一旅一營(yíng)二連，陜西 西安 710032)

隨著支架材料的廣泛應(yīng)用，支架輔助栓塞動(dòng)脈瘤栓塞技術(shù)應(yīng)用越來越多，尤其應(yīng)用于寬頸動(dòng)脈瘤及夾層動(dòng)脈瘤中[1]。支架提供機(jī)械保護(hù)，防止彈簧圈脫出到載瘤動(dòng)脈中，同時(shí)支架網(wǎng)眼為血管內(nèi)皮提供附著點(diǎn)，促進(jìn)動(dòng)脈瘤頸重塑，支架可以改變動(dòng)脈瘤頸處血流方向，促進(jìn)瘤腔內(nèi)血流減慢形成血栓[2]。隨著臨床病例積累，相應(yīng)并發(fā)癥也逐漸顯現(xiàn)，支架內(nèi)血栓形成導(dǎo)致缺血發(fā)作是支架輔助栓塞技術(shù)中較常見的并發(fā)癥之一。如何預(yù)防和處理支架內(nèi)血栓事件發(fā)生，仍有許多爭(zhēng)論之處。我們對(duì)西京醫(yī)院2012年1月至2015年1月行支架輔助彈簧圈栓塞動(dòng)脈瘤術(shù)中急性血栓形成患者進(jìn)行總結(jié)，現(xiàn)報(bào)告如下。

對(duì)象與方法

一、一般資料

2012年1月至2015年1月共276例支架輔助栓塞動(dòng)脈瘤患者，支架包括Solitaire、Enterprise，其中支架內(nèi)急性血栓形成16例，其中男12例，女4例；年齡31～65歲，平均年齡50.3歲；囊性動(dòng)脈瘤14例，夾層動(dòng)脈瘤2例；破裂動(dòng)脈瘤9例，未破裂動(dòng)脈瘤7例；其中前交通動(dòng)脈瘤5例，基底動(dòng)脈動(dòng)脈瘤5例，頸內(nèi)動(dòng)脈后交通段動(dòng)脈瘤4例，大腦中動(dòng)脈動(dòng)脈瘤2例。

二、介入手術(shù)治療方案及方法

破裂動(dòng)脈瘤手術(shù)患者全身靜脈復(fù)合麻醉，股動(dòng)脈穿刺前阿司匹林腸溶300 mg，硫酸氫氯吡格雷片300 mg，經(jīng)肛門納入。未破裂動(dòng)脈瘤患者術(shù)前3～5 d阿司匹林腸溶100 mg，硫酸氫氯吡格雷片75 mg口服。股動(dòng)脈穿刺成功后按公斤體重給予全身肝素化治療，術(shù)中每1 h候按半量維持。術(shù)中尼莫地平注射液4～8 mL/h 持續(xù)泵入。術(shù)后低分子肝素鈣0.4 mL皮下注射2次/d連續(xù)3 d，第一天開始均給予阿司匹林腸溶100 mg，硫酸氫氯吡格雷片75 mg口服1次/d。所有手術(shù)均采用支架平行釋放技術(shù)，栓塞導(dǎo)管為Echelon-10，支架導(dǎo)管為Rebar-18，Prowler。其中14例囊性動(dòng)脈瘤均采用單支架與微導(dǎo)管平行釋放技術(shù)輔助彈簧圈栓塞，1例夾層動(dòng)脈瘤采用雙支架后釋放輔助彈簧圈栓塞。在支架釋放后發(fā)現(xiàn)有支架內(nèi)血栓形成8例，支架載瘤動(dòng)脈遠(yuǎn)端小血管閉塞8例。未破裂動(dòng)脈瘤采用替羅非班聯(lián)合動(dòng)脈接觸性溶栓和靜脈溶栓5例；已破裂動(dòng)脈瘤使用替羅非班聯(lián)合動(dòng)脈接觸性溶栓和靜脈溶栓2例，采用Solitaire AB取栓2例，采用微導(dǎo)管微導(dǎo)絲通過血栓部位3例，未做處理4例。

結(jié) 果

一、血栓發(fā)現(xiàn)時(shí)間和治療方案選擇

16例患者共16枚動(dòng)脈瘤均達(dá)到致密栓塞，支架均一次釋放及調(diào)整完畢。14例患者在動(dòng)脈瘤治療術(shù)中發(fā)現(xiàn)支架內(nèi)血栓形成，其中9例在支架釋放結(jié)束填塞最后一枚彈簧圈時(shí)發(fā)現(xiàn)支架內(nèi)血栓形成。2例患者在手術(shù)結(jié)束麻醉蘇醒后3～6 h出現(xiàn)意識(shí)不清等情況，急診復(fù)查頭顱CT除外再出血，立即進(jìn)造影手術(shù)室復(fù)查造影，如病例1、10(圖1、2)。前交通動(dòng)脈瘤治療術(shù)中，已在術(shù)前評(píng)估對(duì)側(cè)頸內(nèi)動(dòng)脈代償情況，若代償情況良好則不予術(shù)中特殊處理，如病例3、4。若對(duì)稱頸內(nèi)動(dòng)脈不經(jīng)過前交通動(dòng)脈代償供血，則給予溶栓或微導(dǎo)管微導(dǎo)絲通過治療。椎基底動(dòng)脈動(dòng)脈瘤術(shù)中發(fā)生血栓形成，若位于椎基底動(dòng)脈匯合處則，行對(duì)側(cè)椎動(dòng)脈和同側(cè)頸內(nèi)動(dòng)脈后交通動(dòng)脈造影代償良好，可不予特殊處理，如病例6、7、8。代償不良好則給予溶栓或微導(dǎo)管微導(dǎo)絲通過治療，如病例9、10。頸內(nèi)動(dòng)脈動(dòng)脈瘤若支架內(nèi)血栓形成，頸動(dòng)脈主干血流受影響，則給予溶栓或微導(dǎo)管微導(dǎo)絲通過治療，如病例12、13、14。若后交通動(dòng)脈受到影響，而同側(cè)椎動(dòng)脈造影大腦后動(dòng)脈供血良好，則不予處理，如病例11。大腦中動(dòng)脈動(dòng)脈瘤支架內(nèi)血栓形成，未破裂動(dòng)脈瘤則給予積極溶栓或微導(dǎo)管微導(dǎo)絲通過治療，如病例15；已破裂動(dòng)脈瘤單純給予微導(dǎo)管微導(dǎo)絲通過血栓部位疏通血管，如病例16(表1)。

圖1 一例64歲女性顱內(nèi)動(dòng)脈瘤破裂蛛網(wǎng)膜下腔出血患者(病例1)

Fig 1 One 64-year old female patient with ruptured intracranial aneurysm (Case No.1)

A: The left internal carotid artery angiography showed no development of bilateral anterior cerebral artery; B: AcoAn was seen on the right internal carotid artery; C: A Solitaire 4 mm×20 mm stent was placed on the right side of the A1/2 to assist the embolization of aneurysms, and the embolization effect was satisfactory; D: After anesthesia recovery for 3 h, the consciousness became worse gradually, and then the stent thrombosis was seen in angiography, the right A1 was accumulated, and the right middle cerebral artery; E: The Rebar-18 micro catheter was inserted into the site of thrombosis and a Solitaire 4 mm × 20 mm thrombectomy was performed; F: Left side internal carotid angiography without compensation; G: Recovery of blood flow after thrombectomy and thrombolysis.

表1 動(dòng)脈瘤術(shù)中支架內(nèi)血栓形成患者一般情況

Tab 1 Stent thrombosis in patients with aneurysms

CaseSexAgeAneurysmsiteTreatmentmethodsDisposalresult 1F64AcoAn(ruptured)Tirofibanthrombolysis；stentthrombectomyRebleeding；Death 2M47AcoAn(ruptured)UsemicrowirethroughRecanalization；withoutneurologicdeficits 3M45AcoAn(ruptured)UntreatedGoodbloodsupply；withoutneurologicdeficits 4M42AcoAn(ruptured)UntreatedGoodbloodsupply；withoutneurologicdeficits 5M57AcoAn(ruptured)UsemicrowirethroughRecanalization；recheckblock 6M54BaAn(ruptured)UntreatedBilateralposteriorcerebralarteryocclusion；PcoAwaswellcompensated；withoutneurologicaldeficits 7M31VB?An(un?ruptured)UntreatedArterialocclusion；wellcompensated；withoutneurologicaldeficits 8M45VB?An(un?ruptured)UntreatedArterialocclusion；wellcompensated；withoutneurologicaldeficits 9M42BaAn(un?ruptured)TirofibanthrombolysisRecanalization；withoutneurologicdeficits 10F52BaAn(un?ruptured)TirofibanthrombolysisRecanalization；posteriorcranialnervedisorder；leftlimbmusclestrength4；drinkingwatercough；hoarsevoice；wellcompensated；withoutneurologicaldeficits 11F65PcoAn(ruptured)UntreatedWellcompensated；withoutneurologicaldeficits 12M50PcoAn(ruptured)Tirofibanthrombolysis，stentthrombectomyRecanalization；withoutneurologicdeficits 13M51OaAn(un?ruptured)Tirofibanthrombolysis，usemicrowirethroughRecanalization；withoutneurologicdeficits 14F51PcoAn(un?ruptured)TirofibanthrombolysisRecanalization；recheckblock 15M64MCAn(un?ruptured)TirofibanthrombolysisOcclusion；leftupperextremity；musclestrengthGrade3 16M42MCAn(ruptured)UsemicrowirethroughRecanalization；recheckblock；aphasia；rightupperandlowerlimbmusclestrength3?4

圖2 一例52歲女性未破裂動(dòng)脈瘤患者(病例10)

Fig 2 One 52-year old female patient with un-ruptured BaAn (Case No. 10)

A: The right common carotid artery angiography showed that the right internal carotid artery was occluded, the anterior cerebral artery was not developed, and the right middle cerebral artery was poorly developed; B: The right vertebral artery angiography showed an aneurysm at the top of the basilar artery. The right posterior cerebral artery was compensated by the posterior communicating artery to the right middle cerebral artery; C: An Enterprise 4.5 mm×22.0 mm stent was placed in the basilar artery and the right posterior cerebral artery aneurysm was embolized. The effect is good, and the basilar artery and bilateral posterior cerebral artery patency was observed; D: Six hours after operation, the patient was agitated with the left limb weakness, and then the angiography revealed stent thrombosis, the right posterior cerebral artery developed poorly, and the right middle cerebral artery was not developed; E: Using a Rebar-18 micro catheter through the right posterior cerebral artery thrombosis site to find the posterior communicating artery angiography can be seen in the right middle cerebral artery development, along with thrombosis in the site of arterial contact thrombolysis; F: After 20 min, the right posterior cerebral artery was re-opened and the right middle cerebral artery was developed.

二、療效評(píng)估

全部患者術(shù)中溶栓后均復(fù)查DSA，動(dòng)脈瘤均致密填塞。血栓形成的部位經(jīng)治療后血流通暢。替羅非班使用量為0.4 g/kg 5 min由到達(dá)血栓形成部位的微導(dǎo)管內(nèi)進(jìn)行動(dòng)脈接觸性溶栓，5 min后改為0.1 g/kg·min，本組病例均在10～70 min獲得再通，再通后顯影不佳再行支架取栓2例。血管再通后，撤出微導(dǎo)管，改為靜脈持續(xù)10 mL/h，持續(xù)給予3 d泵入，監(jiān)測(cè)凝血酶原時(shí)間和纖維蛋白原含量。

三、術(shù)后及隨訪情況

該組病例中病例1，前交通動(dòng)脈瘤由左側(cè)頸內(nèi)動(dòng)脈優(yōu)勢(shì)供血，右側(cè)頸內(nèi)動(dòng)脈造影雙側(cè)大腦前動(dòng)脈均不顯影，手術(shù)順利，動(dòng)脈瘤栓塞致密，術(shù)后雙側(cè)大腦前動(dòng)脈顯影良好。麻醉復(fù)蘇后3 h患者出現(xiàn)煩躁不安，復(fù)查CT未見顱內(nèi)再出血。立即給予再次行全腦血管造影，左側(cè)頸內(nèi)動(dòng)脈造影發(fā)現(xiàn)支架內(nèi)血栓形成，雙側(cè)大腦前動(dòng)脈均不顯影，血栓波及到左側(cè)大腦中動(dòng)脈，雖經(jīng)積極動(dòng)靜脈聯(lián)合溶栓并支架取栓，患者于術(shù)后36 h死亡。該組病例中病例12，頸內(nèi)動(dòng)脈后交通段動(dòng)脈瘤，動(dòng)脈瘤栓塞術(shù)中支架內(nèi)血栓形成，頸內(nèi)動(dòng)脈血流緩慢，后交通動(dòng)脈動(dòng)脈不顯影，經(jīng)動(dòng)靜脈聯(lián)合溶栓并支架取栓，約30 min后血管再通良好。未處理組患者因術(shù)前術(shù)中評(píng)估完善，本組經(jīng)隨訪均有小血管閉塞，但無神經(jīng)功能障礙遺留。微導(dǎo)管微導(dǎo)絲通過4例，即刻再通4例，復(fù)查閉塞2例，閉塞2例均有神經(jīng)功能障礙表現(xiàn)(病例5、16)。

討 論

血栓形成導(dǎo)致缺血發(fā)作是彈簧圈栓塞動(dòng)脈瘤中較常見并發(fā)癥之一[3]。支架輔助彈簧圈栓塞顱內(nèi)動(dòng)脈瘤技術(shù)越來越多應(yīng)用于臨床，并取得良好療效[4-5]。支架輔助動(dòng)脈瘤栓塞能夠提高動(dòng)脈瘤內(nèi)致密栓塞率，防止彈簧圈脫出或游走，并由于支架網(wǎng)絲覆蓋瘤口而改變局部血流，為血管內(nèi)膜再生提供支架，有利于動(dòng)脈瘤頸再塑形和內(nèi)皮化達(dá)到解剖治愈。金屬支架本身為異物，手術(shù)中推送釋放調(diào)整支架均對(duì)血管壁形成刺激，在血管內(nèi)引起血小板聚集形成血栓。顱內(nèi)動(dòng)脈瘤手術(shù)患者術(shù)前大部分患者未經(jīng)過規(guī)范化抗血小板治療等術(shù)前準(zhǔn)備，支架內(nèi)急性血栓形成發(fā)生率更高[6-7]。Derdeyn[8]統(tǒng)計(jì)約11%栓塞術(shù)中出現(xiàn)血栓，形成從動(dòng)脈瘤腔可擴(kuò)展至載瘤動(dòng)脈，缺血事件可發(fā)生在術(shù)中、術(shù)后幾小時(shí)或幾天內(nèi)。Qureshi等[9]報(bào)道1547例栓塞動(dòng)脈瘤患者，127例出現(xiàn)缺血發(fā)作，其中80例發(fā)生在手術(shù)當(dāng)中。因此重視支架內(nèi)血栓形成，強(qiáng)調(diào)超早期復(fù)查造影，及早處理，可以降低血栓形成帶來的嚴(yán)重后果。

替羅非班對(duì)血小板Ⅱb/Ⅲa受體具有高度的選擇性和特異性，它能阻止血小板Ⅱb/Ⅲa受體與纖維蛋白原的結(jié)合，從而抑制血小板聚集，究其原因是因?yàn)樘媪_非班是一種非肽類血小板表面糖蛋白Ⅱb/Ⅲa受體拮抗劑。替羅非班給藥5 min中就可起效，30 min后對(duì)血小板的抑制作用可以達(dá)到90%，而且停藥后約3 h血小板功能基本恢復(fù)[10-11]。有文獻(xiàn)報(bào)道在蛛網(wǎng)膜下腔出血急性期支架輔助顱內(nèi)動(dòng)脈瘤栓塞術(shù)前給予靜脈注射替羅非班預(yù)防血栓形成，18例患者中有1例因再出血死亡[12]。Chalouhi N[13]報(bào)道16例蛛網(wǎng)膜下腔出血患者支架輔助栓塞術(shù)前給予替羅非班靜脈注射0.4 g/kg·min持續(xù)30 min，然后0.1 g/kg·min維持。其中3例發(fā)生顱內(nèi)再出血，與對(duì)照組比較得出30 min較大起始量的替羅非班似乎有高的腦出血風(fēng)險(xiǎn)，而較低維持量的替羅非班在動(dòng)脈瘤破裂情況下也是非常安全和有效的。Liang[14]報(bào)道221例顱內(nèi)動(dòng)脈瘤破裂出血患者，在支架釋放前給予8.0 g/kg超過3 min靜脈注射，然后0.1 g/kg·min維持。6例發(fā)生顱內(nèi)再出血，其中2例為致死性腦出血。他們認(rèn)為替羅非班靜脈注射在支架輔助動(dòng)脈瘤栓塞術(shù)中預(yù)防血栓性事件是一種安全，有效的治療方案。本組病例在破裂動(dòng)脈瘤術(shù)中發(fā)生血栓性事件后使用替羅非班靜脈注射0.4 g /kg·min動(dòng)脈接觸性溶栓持續(xù)30 min，然后0.1 g/kg·min靜脈注射維持2例，其中一例發(fā)生再出血導(dǎo)致死亡，一例獲得良好效果。未破裂動(dòng)脈瘤使用替羅非班溶栓5例，均取得良好效果，無再出血事件發(fā)生。破裂動(dòng)脈瘤術(shù)中血栓形成使用替羅非班動(dòng)脈接觸性溶栓所帶來更大的再出血風(fēng)險(xiǎn)。故本組病例治療中破裂動(dòng)脈瘤若術(shù)中發(fā)生血栓形成，我們先評(píng)估其他血管代償情況，再評(píng)估血栓形成帶來的危害性。若代償良好，我們不予特殊處理也能得到良好結(jié)果(病例3、4、6、11)。若血栓形成危害性較大涉及大血管(病例1)，或基底動(dòng)脈栓塞(病例12)，可能導(dǎo)致嚴(yán)重后果，那么使用替羅非班動(dòng)脈接觸性溶栓是值得的。那么對(duì)于破裂動(dòng)脈瘤，術(shù)中支架內(nèi)血栓發(fā)生導(dǎo)致小血管栓塞，可能帶來神經(jīng)功能損傷等后果，不建議冒險(xiǎn)使用替羅非班。本組2、5、16病例采用微導(dǎo)管微導(dǎo)絲通過血栓形成部位，即刻再通血管，經(jīng)復(fù)查有2例發(fā)生閉塞，并出現(xiàn)神經(jīng)功能障礙。未發(fā)生如死亡或嚴(yán)重神經(jīng)功能損傷，亦獲得較滿意效果。

故未破裂動(dòng)脈瘤術(shù)中血栓形成使用替羅非班動(dòng)脈接觸性溶栓聯(lián)合靜脈給藥是安全有效的。已破裂動(dòng)脈瘤術(shù)中血栓形成后使用替羅非班動(dòng)脈接觸性溶栓聯(lián)合靜脈給藥溶栓治療方法的安全有效性仍需進(jìn)一步觀察，可使用微導(dǎo)管微導(dǎo)絲通過的辦法達(dá)到血管再通。

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