经皮经肝穿刺溶拴在治疗急性门静脉栓塞中的应用

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经皮经肝穿刺溶拴在治疗急性门静脉栓塞中的应用
Percutaneous transhepatic thrombolysis in the treatment of acute portal venous thrombosis经皮经肝穿刺溶拴在治疗急性门静脉栓塞中的应用Keywords: portal vein, thrombosis, thrombolytic therapy, splenectomy关键词;门静脉，血栓形成，溶栓疗法，脾切除术SummaryAcute portal vein thrombosis (PVT) is a rare clinical condition that can cause portal hypertension and bowel infarction. Early diagnosis and treatment of PVT is crucial for the restoration of portal venous flow and reduction of morbidity and mortality. We report a successful treatment of acute PVT which was seen following splenectomy, utilizing catheter directed transhepatic thrombolysis. No complication was encountered related to the procedure. Thrombolytic therapy via transhepatic route proved to be a safe and effective method in the treatment of PVT.摘要急性门静脉血栓形成（PVT）是一种罕见的能引起门静脉高压和肠道梗死的临床疾病。PVT的早期诊断和治疗在门脉血流恢复及降低发病率和死亡率方面起着至关重要的作用。我们现在报道一种成熟的急性门静脉血栓的治疗方案，即脾切除术后，利用穿刺导管直接进行经肝门静脉溶栓。此操作未发生任何并发症。我们证明经肝门静脉溶栓术在治疗PVT上是一种安全有效的方法。IntroductionPortal venous thrombosis (PVT) is a rare clinical entity and necessitates early diagnosis and treatment for the prevention of mesenteric ischemia. Myeloproliferative diseases are the most common underlying conditions that result in PVT. Septicemia, abdominal surgery, intraabdominal infections, cirrhosis and primary or secondary liver tumors are other conditions which can cause PVT. Treatment options for PVT range from conservative anticoagulant therapy to surgical thrombectomy.简介PVT是一种少见的临床实例，对于预防肠系膜的缺血坏死，早期诊断和治疗是必要的。导致PVT的最常见原因是骨髓增生性疾病，其次为败血症、腹部外科手术、腹内感染、肝硬化以及原发或继发性肝癌，对于PVT的治疗，即可选择保守的抗凝治疗，亦可行外科血栓切除术Endovascular thrombolytic therapy is a new alternative technique for the treatment of PVT [1-4]. Presented here is a case of PVT which occurred after splenectomy and successfully treated with catheter directed transhepatic thrombolysis.在血管内进行的血栓溶解疗法是治疗PVT的一种新的可选技术。下面是一个PVT的病例，其继发于脾切除术后，并由穿刺导管直接进行经肝门静脉溶栓成功治愈。Case Report70 year-old female patient with a history of visceral leishmaniasis underwent to splenectomy 20 days ago and admitted to our emergency department with abdominal distention and pain. Thrombus formation was demonstrated in superior mesenteric vein (SMV), main and intrahepatic portal vein (PV) branches with color Doppler ultrasonography (CDUS) and computed tomography (CT). Since the patient was symptomatic and the thrombosis was extensive and there was no sign of peritoneal irritation which necessitates early surgical intervention, percutaneous endovascular intervention appeared to be best alternative for the treatment. According to patient`s history, there was no contraindication for thrombolytic therapy. Prior to the procedure, her platelet count was 157000/mm?/sup>. Prothrombin time and hemoglobine level were 12 seconds and 11 mg/dl respectively. Patient did not have a coagulation disorder so that percutaneous transhepatic access was preferred.病例报告70岁女性患者， 曾患内脏利什曼病而行脾切除术20年，因腹胀、腹痛收于急诊科。经彩色多普勒超声及CT检查发现在肠系膜上静脉、门静脉主干及肝内段分支有血栓形成。患者症状明显并且血栓形成范围广，而未出现腹膜**症状是进行外科手术的关键，经皮血管内介入治疗成为首先治疗方案。据患者病史，未有溶栓治疗禁忌症。术前，患者血小板是157000/mm3。凝血酶原时间和血红蛋白E水平分别是12s和11mg/dl。患者没有血凝障碍，经皮经肝穿刺成为首选。Under ultrasonographic guidance 6F vascular sheet was placed into the right PV with using Accustic Intervention System (Boston Scientific, Watertown, MA, USA). Diagnostic angiography catheter was then placed into SMV and venograms were obtained. Extensive filling defects in SMV, main PV, right and left PV due to thrombus formation were present (Figure 1). The distal portion of SMV was patent but proximal portions of SMV and PV were occluded. The first 15 cm portion of the infusion catheter that has side holes (Mewissen, Boston Scientific, Watertown, MA, USA) was placed into confluence of the main PV and proximal part of SMV. Pharmacomechanical thrombolysis was performed within the first 3 hours utilizing “pulse spray” method. Since there was no available pump for pharmacomechanical thrombolysis, manual technique was used. After the procedure, the patient was transferred to another room and monitorized. Five milligrams of recombinant tissue plasminogen activator (rd-PA, Actilyse, Boehringer Ingelheim, Germany) diluted with 25 ml saline solution was injected through the infusion catheter with a rate of 0.5 ml /min. Since the thrombus formation was extensive, pharmacomechanical thrombolysis was performed for 3 hours and a total of 15 mg rd-PA was infused. After 3 hours, control venograms showed partial and insufficient lysis of thrombus. Percutaneous transluminal angioplasty (PTA) was then performed with a size of 10x40 mm balloon (Smash, Boston Scientific, Watertown, MA, USA) to PV and SMV. After PTA, same infusion catheter placed into SMV and PV was used to perform rd-PA infusion for 12 hours with a rate of 1 mg/hour. 在超声引导下，利用Accustic介入体系将6F脉管穿刺针植入到右侧肝门静脉(Boston Scientific, Watertown, MA, USA)。诊断性动脉造影导管植入肠系膜上静脉并获得静脉描记图。由于血栓形成，在肠系膜上静脉、肝门静脉主干及左右支可发现广泛的充盈缺损区(Figure 1)。肠系膜上静脉的远侧部是开放的，但是其近侧部及肝门静脉是闭塞的。带有侧孔的注入导管(Mewissen, Boston Scientific, Watertown, MA, USA)的头15cm部分被植入主门静脉与肠系膜上静脉近心端的汇合处。在开始的三个小时利用“间歇喷射”的方法执行药物融栓。由于进行药物融栓没有合适的泵，便用手动操作。完成后，患者被转入另一房间并密切检测。5mg的rd-PA（重组组织型纤维蛋白酶原激活剂）被25 ml生理盐水稀释，并通过导管以0.5 ml /min速率注入。由于形成血栓的机制是多方面的，进行了3小时的药物融栓并且总共注入了15 mg rd-PA。3小时后，对照静脉描记图显示血栓局部不完全溶解。利用经皮腔内血管成形术（PTA）将一个大小10×40mm送到PV与SMV。PTA术后，相同的注入导管植入PV与SMV，用于将rd-PA以1mg/hour的速率注入12小时。Figure 1: Transhepatic venogram shows filling defects due to thrombus in SMV, main PV, right and left PV branches (SMV: superior mesenteric vein, PV: portal vein).图1：经肝静脉描记图显示由于在肠系膜上静脉、门静脉主干及其左右分支的血栓而形成的充盈缺损。A day after the procedure, although luminal patency was achieved in PV and SMV, since there were still filling defects in SMV, main PV and left PV branches, rd-PA was injected for an other 1 hour period a with a rate of 5 mg/hour to PV and SMV. After a total of 30 mg rd-PA infused, 90% lysis of thrombus in portal and mesenteric vein was achieved (Figure 2). Procedure was ended after restoring normal flow in PV. Vascular sheet was taken out from the liver parenchyma and to prevent possible bleeding, gelatin sponge (Spongostan, Johnson&Johnson, Skipton, England) was placed into the entry site of the catheter. 术后一天，尽管在门静脉及肠系膜上静脉官腔已经开通，但是在肠系膜上静脉、门静脉主干及其左支仍然存在充盈缺损现象，于是接着向门静脉及肠系膜上静脉以5 mg/hour的注射rd-PA大约一小时。总共注入了30 mg rd-PA后，门静脉及肠系膜上静脉90%血栓被溶解(Figure 2)。门静脉恢复正常流速后操作终止。从肝实质中去掉血管支架以防可能的出血，并将明胶海绵放置在导管进入的部位。Click to EnlargeFigure 2: Control venography following balloon angioplasty and rd-PA infusion shows 90% reduction of thrombosis in SMV and main PV, though there is still prominent thrombosis left in left PV branch (SMV: superior mesenteric vein, PV: portal vein).对照静脉描记图，由于气囊血管成形术及静注rd-PA，尽管在门静脉左支仍有明显的血栓剩余，但是在肠系膜上静脉脉及门静脉的血栓已减少了大约90％。The patient was heparinized during and until 3 days after the intervention. Oral warfarine-Na was given due to maintain optimal INR (international normalized ratio) value of 2-3. No complication was encountered during or after the procedure. After the end of the procedure abdominal pain has disappeared and abdominal distention was significantly decreased. On followup CDUS performed 3 months after the procedure, SMV and portal venous system were patent (Figure 3). 介入后三天内患者要行肝素化治疗。并口服华发林钠以维持最佳的国际标准。在治疗期间及治疗后没有并发症发生。术后腹痛已经消失，腹胀明显减轻。治疗后随访期间，服用了3个月的巴豆*二脲，肠系膜上静脉及门静脉系统完全开放(Figure 3)。Click to EnlargeFigure 3: Three months after the thrombolytic therapy, control CDUS image shows the restored patency in main PV and SMV (PV: portal vein, SMV: superior mesenteric vein).血栓溶解疗法术后三个月，服用巴豆*二脲后的影像显示门静脉主干及肠系膜上静脉已恢复开通。DiscussionAcute PVT is a rare clinical condition that may cause mesenteric ischemia and bowel infarct so that early diagnosis and treatment is crucial. Myeloproliferative diseases, intraabdominal infections or inflammations, septicemia, cirrhosis, intraabdominal surgery, trauma, hypercoagulable states (antithrombin III, protein C, protein S insufficiency and etc.), oral contraceptives, primary or secondary liver tumors are the most common reasons for PVT. 讨论急性门静脉血栓形成是一种少见的能引起肠系膜局部缺血和肠坏死的临床疾病。早期诊断与治疗是至关重要的。急性门静脉血栓形成的最常见的病因是骨髓增生性疾病、腹内感染及炎症、败血症、肝硬化、腹内手术、外伤、血液易凝状态（抗凝血酶Ⅲ、蛋白c、S蛋白缺乏等原因的引起）、口服避孕药、原发或继发的肝癌。PVT is usually seen after splenectomy. Thrombosis ratio after splenectomy especially for myeloproliferative disease and cirrhosis, is about 13-18% [5,6]. Hypercoagulation and blood stasis in the splenic remnant are the two major factors resulting in development of PVT after splenectomy [7]. 急性门静脉血栓形成常继发于脾切除术后。特别是继发于骨髓组织增生性疾病和肝硬化的脾切除其血栓形成的机率大约13-18% [5,6]。脾切除术后残余脾组织的高凝物质及淤血是导致急性门静脉血栓形成的两个重要的因素[7]。Surgical thrombectomy is not preferred as treatment method for PVT since it is invasive, technically difficult and can cause hepatic encephalopathy. Surgical treatment is not considered as an alternative treatment in patients with poor general condition [2]. If peritoneal irritation is present which is suggestive for bowel infarction, surgical thrombectomy with bowel resection should be performed. 对于PVT的治疗外科血栓切除术不是首选治疗方法，因为它具有侵入性，技术上存在困难并且易引起肝性脑病。身体一般情况比较弱的患者不考虑进行外科治疗[2]。若出现腹膜**征说明已出现肠梗死，此时应考虑进行外科血栓切除术，顺便将已坏死的肠腔一块切除。Endovascular treatment for PVT has been started to be used in last few years and its effectiveness has been demonstrated only in small series [1-4]. There is no place for endovascular thrombolysis in treatment of chronic PVT. Depending on patient's status, there are different ways for endovascular therapy of acute PVT. Thrombolysis can be achieved using pharmacological and/or mechanical methods. Thrombolytic agents might be given either directly into the PV or indirectly into the superior me senteric artery (SMA). Authors supporting thrombolytic therapy via SMA claim that thrombi in small veins can be disintegrated using this method [8,9]. But other authors reported that resolving thrombus formation in the small veins is not easy because of collateral vascular circulation and can lead to prolongation of total infusion time via SMA [10]. Increased infusion time of thrombolytic agents results in increased risk of bleeding. Antoch et al. reported two cases of PVT that they have restored the portal flow within 8 days using indirect SMA infusion technique. In another case, without restoring complete rec**ization, procedure was ended on fifth day because of the femoral hematoma at access site [11-14]. In our case, thrombolysis with pharmacomechanical (pulse spray) method was performed directly through the PV and after 3 hours partial flow restoration was achieved. Tissue plasminogen activator was utilized to enhance thrombolytic effect of pharmacomechanical thrombolysis. A day after the procedure, although significant amount of thrombus reduction was achieved, pharmacomechanical method again was performed for the residual thrombus and nearly normal flow was maintained in the PV within 24 hours. No complication was encountered during or after the procedure. 对于PVT的血管内介入治疗在最近几年已开始应用，其治疗效果只在小范围内被证实[1-4]。但是在治疗慢性PVT上血管内融栓未报道。根据患者的体质，对于急性PVT的血管内治疗有几种不同的治疗方法。血栓溶解可以通过药理作用或机械方法来达到。血栓溶解剂可以直接注入PV也可以间接注入SMA。作者建议通过SMA进行血栓溶解疗法，因为通过这种方法在小静脉的血栓也被溶解掉[8,9]。但是有人报道在小静脉的血栓溶解方式不容易达到，因为由于侧枝循环的存在使通过SMA注入的总时间延长[10]。增加血栓溶解剂的注入时间将会使出血等并发症的危险性增加。曾报道过两个PVT病例，他们通过间接的SMA注入技术8天内恢复了门静脉的血流。还有一个病例，没有完全恢复再通，因为在导管入口的股部出现血肿，操作被迫终止[11-14]。在我们的病例中，通过直接PV注入并利用药物机械偶联（间歇喷射）方法进行血栓溶解，3小时后达到部分血流再通。同时注入组织纤维蛋白溶酶原激活剂以增强药物机械偶联血栓溶解疗法的效果。术后一天，大部分血栓已溶解，再次利用药物机械偶联方法对残余血栓进行融解，在24小时内门静脉几乎恢复了正常血流。并且在术中及术后未出现任何并发症。Direct intervention of PV thrombus has advantages compared to indirect method. Due to direct injection of thrombolytic agents, procedure time is shorter. It is known that pharmacomechanic method is more effective and less time consuming than normal thrombolytic infusion [14]. 直接的门静脉介入血栓溶解疗法相对于间接方法有很多优点。由于血栓溶解剂的直接注入，缩短了操作时间。众所周知，药物机械偶联血栓溶解疗法较标准的血栓溶解剂注入疗法有效且所用时间短。Another advantage of direct intervention of PVT is having the opportunity to perform thromboaspiration, mechanic thrombectomy, baloon angioplasty and stenting [3,10,12]. Direct administration of thrombolytic agent in the occluded vessel decreases the systemic dose and related complications. In our case in addition to pharmacomechanical and pharmacological thrombolysis, baloon angioplasty was performed to disintegrate thrombus and to enhance the effect of rd-PA. PVT直接的介入治疗的另一个优点便是在操作过程中有机会进行血栓量的测定，血栓切除术，血管成形术及支架植入等操作[3,10,12]。直接在闭塞的血管中进行融栓治疗降低了全身药物的剂量及相关并发症的发生。在我们的病例中，除了利用药物机械偶联及药理融栓外，并进行血管成形术以分解血栓同时增强rd-PA的疗效。Another access for portal venous system is performing transjuguler intrahepatic portosystemic shunt. This procedure is generally preferred in patients of PVT with cirrhosis or portal hypertension. Transhepatic procedure is easier but the risk of hemorrhage is increased in patients with ascite and receiving anticoagulant therapy. Ultrasound guided approach with fine needles (21-22 G) and occlusion of access with gelatin sponge can decrease the risk of bleeding complication [13]. 在门静脉系统操作中的另一种方法是经颈静脉的肝内门体分流术。这种方法普遍应用在那些合并肝硬化及门脉高压的PVT患者。经肝操作是容易的，但是对于存在腹水及接受抗凝治疗的患者有增加出血的危险。超声引导下用细针穿刺并用明胶海绵将入路闭塞将会降低出血等并发症的危险。As a result, percutaneous transhepatic thrombolysis is a safe and effective method for the treatment of acute symptomatic PVT. Percutaneous transhepatic approach gives opportunity to pharmacomechanical thrombolysis and percutaneous transluminal angioplasty for rec**ization and increases the effectiveness of treatment.最后，经皮经肝穿刺溶栓对于急性PVT患者的治疗是一种安全有效的方法。经皮经肝操作使我们有机会进行药物机械偶联的溶栓治疗和经皮的血管成形术，以使血管再通并增加治疗的效果。