不同溶栓途径在急性下肢深静脉血栓形成中的应用评价


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[摘要] 目的 探討不同溶栓途径治疗急性下肢深静脉血栓形成(DVT)的临床效果。方法 选取承德医学院附属医院血管外科2013年1月~2016年1月收治的60例急性下肢DVT患者,按照随机数字表法分为三组,每组20例。经健侧股静脉置管逆行溶栓为A组,经患侧腘静脉置管顺行溶栓为B组,经患侧足部静脉溶栓为C组,比较各组近期和远期疗效。 结果 各组治疗后健、患肢周径差均较治疗前减小,差异有高度统计学意义(P < 0.01);A、B组治疗后健、患肢周径差均小于C组,差异有高度统计学意义(P < 0.01)。各组治疗后血栓评分均低于治疗前,差异有统计学意义(P < 0.05);A、B组治疗后血栓评分均低于C组,差异有统计学意义(P < 0.05);A、B组患肢静脉再通率均高于C组,差异有统计学意义(P < 0.05)。随访1年,各组间深静脉瓣膜保存率比较差异有统计学意义(P < 0.05)。A、B组Villalta评分及PTS发生率均明显低于C组(P < 0.01),A、B组组间比较差异无统计学意义(P > 0.05)。 结论 置管溶栓可有效治疗急性DVT,在采用不同的溶栓途径中,经患侧腘静脉顺行置管的途径更为安全有效。

[关键词] 急性下肢深静脉血栓;导管接触溶栓;途径;疗效

[中图分类号] R654 [文献标识码] A [文章编号] 1673-7210(2017)10(b)-0111-04

Application evaluation of different approaches for catheter-directed thrombolysis in acute lower-extremity deep venous thrombosis

ZHANG Qingyun1 DING Meng2 CHEN Lei1 GAO Jianguo1 ZHANG Hong1 YANG Zhi1

1.Department of Vascular Surgery, Affiliated Hospital of Chengde Medical College, Hebei Province, Chengde 067000, China; 2.Department of Laboratory, Affiliated Hospital of Chengde Medical College, Hebei Province, Chengde 067000, China

[Abstract] Objective To investigate the effect of different approaches for catheter-directed thrombolysis (CDT) in the treatment of acute lower-extremity deep venous thrombosis (DVT). Methods Sixty patients with acute lower-extremity DVT admitted to the Vascular Surgery Department of Affiliated Hospital of Chengde Medical College from January 2013 to January 2016 were selected. All patients were divided into three groups according to the random number table method, each group of 20 cases. The retrograde thrombolysis of the contralateral femoral vein was group A, arranged thrombolysis by ipsilateral popliteal vein was group B, stomach thrombolysis by ipsilateral foot vein was group C. Recent and long-term efficacy of each group was compared. Results After treatment, circumference differences between uninjured limb and injured limb in two groups were less than before treatment, the differences were statistically significant (P < 0.01). After treatment, circumference differences between uninjured limb and injured limb in group A and B were less than those in group C, the differences were statistically significant (P < 0.01). After treatment, thrombosis score of each group was lower than before treatment, the difference was statistically significant (P < 0.05). After treatment, thrombosis scores in group A and B were lower than those in group C, the differences were statistically significant (P < 0.05). The recanalization rates of injured limb in group A and B were higher than those in group C, the differences were statistically significant (P < 0.05). Follow up for 1 year, there were significant differences in preservation rate of deep venous valve in each group (P < 0.05). The incidence of Villalta and PTS in group A and B were significantly lower than those in group C (P < 0.01), there was no significant difference between group A and group B (P > 0.05). Conclusion CDT is an effective method to manage acute DVT. In the three routes tested, lateral popliteal vein route is more safe and effective.

[Key words] Acute lower-extremity deep vein thrombosis; Catheter-directed thrombolysis; Pathway; Efficacy

下肢深静脉血栓形成(deep venous thrombosis,DVT)患者早期如得不到及时正确处理,肢体肿胀的同时易并发致命性肺栓塞,后期易出现下肢DVT后综合征(post-thrombotic syndrome,PTS),严重影响患者的生活质量[1]。近年来,随着微创血管治疗技术的发展,对急性DVT患者采用不同途径的导管接触性溶栓技术(catheter-directed thrombolysis,CDT),得到了日益广泛应用并取得了一定的疗效。本研究主要探讨不同溶栓途径治疗急性下肢DVT的临床效果。

1 资料与方法

1.1 一般资料

选取承德医学院附属医院血管外科2013年1月~2016年1月收治的60例患者,男32例,女28例,平均年龄(41.23±1.61)岁,所有患者入院前均经下肢静脉多普勒或静脉造影检查确诊为单侧DVT(中央型或混合型)。发病时间≤7 d且无抗凝、溶栓禁忌。其中左下肢38例,右下肢22例。中央型44例,混合型16例。主要臨床表现:肢体肿胀疼痛、皮温及肌肉张力高,无呼吸困难。所有患者入院后采用随机数字表法分为三组,每组20例。A组为逆行溶栓组;B组为顺行溶栓组;C组为外周溶栓组,各组间一般资料比较,差异无统计学意义(P > 0.05),具有可比性。见表1。

1.2 方法

1.2.1 下腔静脉滤器置入(inferior vena cava filter,IVCF)与取出 所有置管溶栓组患者均于置管前,经健侧肢体行IVCF;外周静脉溶栓组中,根据患者意愿行可回收型IVCF。术中造影定位右肾静脉开口水平位置释放滤器,顶端距离右肾静脉开口下方0.5~1.0 cm。当患者溶栓结束,造影显示血栓稳定或完全消失,根据患者意愿行可回收滤器取出术。

1.2.2 溶栓抗凝处理 逆行置管溶栓组在滤器置入后,导管“翻山”进入患侧髂总静脉内,溶栓导管逆行至远端正常静脉管腔;顺行置管溶栓组术前患侧腘静脉超声定位,滤器置入后,更改为俯卧位,经腘静脉将溶栓导管顺行通过患侧静脉血栓形成处至近心端下腔静脉内;外周静脉溶栓组中,经患肢足背静脉穿刺留着套管针,踝部扎止血带。三组均于术中经导管或套管针造影评估血栓范围,术后继续抗凝并经溶栓导管持续溶栓处理,注意监测凝血时间及造影复查,当血栓溶解无进展或纤维蛋白原<1 g/L时终止溶栓。所有患者出院后继续口服华法林规律正规抗凝3~6个月。下腔静脉滤器未取出者或髂静脉支架置入者,终身抗凝处理。

1.2.3 近期疗效观察 所有患者溶栓结束后测量健、患肢周径差,经导管或外周静脉留置针造影观察静脉通畅情况,肺栓塞发生情况等评估近期疗效。静脉血栓评估标准[2]:患肢深静脉分为6段并设不同分值,每段血管分数相加即为总的血栓评分。患肢静脉再通率=(溶栓前血栓评分-溶栓后血栓评分)/溶栓前血栓评分×100%。

1.2.4 远期疗效随访 术后所有患者患肢穿弹力袜,随访12个月。彩色多普勒超声检查瓣膜的保存及功能情况,根据患肢症状、体征等情况进行Villalta评分,对远期PTS的发生情况进行评估。Villalta评分[3]是通过对患者5个症状和6个重要临床体征进行的总和及评分,当总评分≥5分或出现溃疡者,可诊断为PTS;当病程<3个月或上述评分总和<5分时均不诊断PTS。

1.3 统计学方法

采用SPSS 20.0统计软件对数据进行分析和处理,计量资料以均数±标准差(x±s)表示,采用t检验,计数资料采用χ2检验,等级资料采用符号秩和Wilcoxon检验,以P < 0.05为差异有统计学意义。

2 结果

2.1 三组患者治疗前后健、患肢周径差比较

各组治疗后健、患肢周径差均较治疗前减小,差异有高度统计学意义(P < 0.01);A、B组治疗后健、患肢周径差均小于C组,差异有高度统计学意义(P < 0.01)。见表2。

2.2 三组患者治疗前后血栓评分及患肢静脉再通率比较

各组治疗后血栓评分均低于治疗前,差异有统计学意义(P < 0.05);A、B组治疗后血栓评分均低于C组,差异有统计学意义(P < 0.05);A、B组患肢静脉再通率均高于C组,差异有统计学意义(P < 0.05)。见表3。治疗过程中,A组1例患者出现置管溶栓处血肿,局部适当加压包扎后好转。B组1例患者溶栓后造影发现左侧髂静脉狭窄,术中置入支架。C组1例患者出现肉眼血尿,停止溶栓药物后好转,另外1例患者出现肺栓塞,行IVCF并继续抗凝溶栓处理后逐渐好转。

2.3 滤器的置入与回收

A、B两组40例患者均成功行IVCF,C组根据患者意愿及后期出现肺栓塞再次行IVCF患者,共有15例患者成功行IVCF,术中无并发症出现,治疗后所有置入滤器除并发肺栓塞1例患者未行取出外,其余54例滤器置入患者当病情稳定后均成功取出,2例患者滤器取出时发现滤器局部血栓附着,给予继续溶栓处理,血栓消失后取出。1例患者滤器尾端倾斜贴壁,经置入导管辅助成功回收。

2.4 深静脉瓣膜保存率及功能

患者经彩色多普勒超声检查瓣膜的保存情况及功能,各组深静脉瓣膜保存率分别为A组(66.31±9.91)%,B组(75.42±10.83)%,C组(89.42±8.21)%,各组之间比较差异有高度统计学意义(P < 0.01)。其中A、B组瓣膜功能较好,轻度反流,C组深静脉瓣膜功能不全较重,反流较为明显。

2.5 Villalta总评分及PTS发生率

全部患者出院后继续抗凝3~6个月并完成随访1年。无PE及DVT复发。各组Villalta总评分及PTS的发生率分别为A组(3.61±3.23)分,15.44%;B组(3.52±2.92)分,14.39%;C组(5.12±2.24)分,38.53%。A、B组Villalta总评分及PTS的发生率明显低于C组(P < 0.01),A、B组组间比较差异无统计学意义(P > 0.05)。

3 讨论

急性下肢DVT治疗的及时性、合理性与患者的预后密切相关[4]。国内外多数学者认为,对于急性期中央型或混合型DVT患者,在抗凝治疗的同时,如能得到积极的溶栓处理,可有效降低PTS的发生率,与单纯抗凝治疗相比优势明显[5]。目前,主要溶栓方法有CDT和外周静脉系统溶栓两种。国际指南提示,相对于外周静脉溶栓治疗血栓完全溶解率较低的缺陷,CDT将溶栓导管置于血栓闭塞段静脉,通过血栓内部溶栓导管的持续泵入药物,显著减少药物剂量和缩短溶栓治疗时间,出血风险较外周静脉系统溶栓明显降低了1/3,减少PTS的发生[6-9]。经典的经静脉CDT途径中存在多种入路方法,但对于急性中央型或混合型DVT患者,究竟采用那种途径CDT的临床疗效更具有优势,迄今尚未有确切统计数字和定论[10-12]。

本研究通过对逆行置管溶栓及顺行置管溶栓的分组前瞻性研究分析显示,与外周静脉溶栓相比,近期患者的肢体肿胀消退程度明显,临床起效时间明显缩短,不同置管方式间比较无明显差异。溶栓后造影可见,置管溶栓组中,血栓消融迅速,静脉再通率较高[13],不同置管方式之间比较无明显差异,由于置管溶栓的高效性和靶向性,大大缩短了尿激酶溶栓的起效时间和减少了应用剂量,结合溶栓过程中对于凝血常规指标、血小板等指标的严密监测,从而降低了溶栓出血的风险[14-15],本研究中,逆行置管组出现穿刺处血肿1例考虑为滤器置入后,更换“翻山”导鞘较粗所致。外周溶栓组中1例患者出现肉眼血尿,经停止溶栓药物后好转。

对于急性DVT患者溶栓过程中的IVCF与否仍然是国际上争论的焦点[16]。本研究中,考虑介入操作或溶栓过程中,机械触碰及血栓消融物理力学因素可能导致血栓脱落风险,均向患者建议放置可回收滤器并于血栓稳定或消融后取出,明显减少了医源性因素导致的肺栓塞发生,同时也要注意,滤器的置入及再次取出明显增加了患者的治疗费用及手术风险。在治疗过程中,1例外周溶栓组患者出现胸闷憋气感,经肺动脉造影考虑存在肺栓塞,给予IVCF并继续抗凝溶栓处理后逐渐好转。1例患者靜脉滤器取出时出现贴壁造成取出困难。

研究中外周静脉溶栓的静脉瓣膜保存率明显高于置管溶栓组,但因血栓溶解缓慢,血栓机化导致下肢静脉瓣膜功能不全明显,反流程度较重,发生PTS的概率较高[17]。而置管溶栓组可迅速消融血栓,避免静脉血栓机化导致的瓣膜功能不全。其中,逆行置管溶栓组中,因与滤器置入采用共同通路,故仅需一个穿刺点,但由于导丝导管的逆血流机械操作导致静脉瓣膜破坏较重,同时对于混合型DVT患者,溶栓导管常难以达到血栓远心端,从而遗留腘静脉及以下静脉血栓,与顺行置管溶栓组相比,静脉瓣膜保存率低,差异有显著性。而经腘静脉途径的顺行CDT,因腘静脉血管变异较少,并且顺血流方向,介入操作的应力好,术中能够较为顺利地将溶栓导管通过血栓闭塞段进入近心端下腔静脉内,快速消融血栓。同时顺血流方向的操作最大限度地保存静脉瓣膜[18-20],虽然近期随访PTS的发生率与逆行溶栓组相比无明显差异,但相信随着时间的延长,功能保存良好的瓣膜将成为后期降低患者发生PTS发生率、提高患者生活质量的重要保障。

总之,对于急性中央型及混合型DVT患者,经患侧腘静脉顺行插管溶栓,能够迅速消融血栓,改善症状并保护静脉瓣膜,降低PTS发生率,安全有效,值得推荐。

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(收稿日期:2017-07-24 本文编辑:李亚聪)