抗心磷脂抗体、蛋白C与肝硬化门静脉血栓的关系

目的 研究肝硬化门静脉血栓(PVT)患者抗心磷脂抗体(ACA)和蛋白C(PC)的变化.方法 收集2006年1月至2007年12月肝硬化PVT患者20例作为血栓组,肝硬化非血栓患者40例作为对照组,对两组凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fib)、ACA和PC进行检测,对比血栓组和对照组各项指标的差异.根据两组患者肝功能Child-Pugh分级,比较各级别上述各指标差异.结果 血栓组ACA阳性患者7例(35%),对照组4例(10%,P=0.045).血栓组ACA-IgG为(10.15±5.31)U/ml、PC为(2.47±0.62)mg/L,对照组分别为(6.70±3.75)U/ml和(2.93±0.88)mg/L,两组比较差异有统计学意义(P<0.05);而两组的PT、APTT、Fib和ACA-IgM结果相似(P>0.05).PT、APTT、Fib和PC在Child-Pugh各级间比较差异均有统计学意义(P值均<0.05);ACA-IgG和ACA-IgM随肝功能恶化而升高,但各级间比较差异均无统计学意义(P值均>0.05).血栓组ACA阳性率为35%(7/20),而对照组ACA阳性率为10%(4/40),两组比较差异有统计学意义(P=0.045).结论 肝硬化患者凝血和抗凝系统存在明显异常.肝硬化PVT患者与无PVT患者相比,ACA-IgG明显升高而PC则明显降低,ACA-IgG和PC在肝硬化PVT形成中可能起有重要作用.     

Functional protein C and anti-cardiolipin antibody in children with portal vein thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) is a common cause of portal hypertension in children from developing countries. Deficiencies of proteins C and S and elevated anticardiolipin antibody (aCL) levels have been shown to predispose to venous thrombosis. We studied these factors in children with idiopathic PVT. METHODS: 19 children with PVT (mean [SD] age 5.7 [2.1] y; 15 boys) were studied; all had had variceal bleeding, and had PVT on ultrasonography. Functional protein C activity was measured using a clotting assay; if it was normal, a clotting assay for functional protein S activity was performed. IgG aCL levels were measured in all sera using an in-house standardized solid-phase ELISA. RESULTS: Protein C functional activity ranged from 4% to 109%. Eight children had activity below 70%, the lower cut-off of the normal range. Protein S assay, done in 10 of the 11 children with normal protein C activity levels, was normal (above the cut-off level of 65% of the normal range). IgG aCL levels were abnormally elevated (>mean + 2SD of 16 healthy control children) in nine children; of these, three had associated protein C deficiency. Thus, of the 19 children with idiopathic PVT, 14 had abnormality in one or more tests. CONCLUSION: A majority of children with PVT of unknown etiology have functional protein C deficiency or abnormally elevated levels of aCL antibodies.     

门静脉血栓介入治疗研究进展

正门静脉血栓是指门静脉主干及其分支血栓形成,可导致门静脉部分或完全性梗阻,部分门静脉血栓可以延伸至脾静脉或肠系膜上静脉。门静脉血栓的形成原因有多种,主要包括肝硬化、肿瘤、免疫系统疾病、感染、凝血功能障碍和口服避孕药物等~([1])。在肝硬化进展期或合并肿瘤患者,门静脉血栓的发生率更高~([2,3])。据统计,肝硬化并发门静脉高压患者门静脉血栓发生率约为0.6%～15.8%~([4])。伴有门静脉血栓的肝硬化患者发生消化道出血的风险更高~([5])。门静脉血栓形成所导致的临床表现差异较大,轻症患者可无任何临床症状,常常在随访过程中被发现。     

乙肝肝硬化患者门静脉宽度与门静脉血栓形成的关系

背景门静脉血栓(portal vein thrombosis,PVT)的早期诊断仍是临床上一个难题,急需要发现可早期预测诊断的无创指标.目的探讨门静脉宽度与PVT形成之间的关系.方法收集418例乙肝肝硬化患者.根据是否发生PVT分为PVT组(n=66)和非PVT组(n=352)组.比较两组患者的一般资料差异,使用多因素Logistic回顾分析影响PVT发生的危险因素.通过受试者工作特征(receiver operating characteristic,ROC)曲线评估不同危险因素预测PVT的效能.结果与非PVT组患者相比,PVT组患者的Child-Pugh评分更高、Child-Pugh A级比例更低、血小板水平更高、D-二聚体水平更高、门静脉宽度更宽、门静脉血流更慢,上述差异均存在统计学意义(P<0.05).Logistic回归显示门静脉宽度(OR=3.941,P=0.001)、门静脉血流(OR=0.841,P=0.007)、血小板水平(OR=1.024,P=0.008)和D-二聚体水平(OR=2.383,P=0.000)是肝硬化患者发生PVT的独立危险因素.门静脉宽度诊断PVT的ROC曲线下面积最大为0.874,最佳诊断值为>12.5 mm,此时的预测敏感性和特异性分别为78%和82%.结论门静脉直径增加是肝硬化患者PVT发生的危险因素,对PVT诊断具有一定价值.     

肝硬化合并门静脉血栓形成的临床特点

目的分析肝硬化患者合并门静脉血栓形成(PVT)的临床特点及危险因素,了解该类患者药物性预防措施是否有效.方法 2008年1月至2011年3月各种原因的肝硬化住院患者共339例,将其分为两组,分别为肝硬化合并有门静脉血栓形成组及未合并有门静脉血栓组.记录患者年龄、性别、凝血酶原时间(PT)、总胆红素、白蛋白、肝硬化的病因...     

肝硬化并发门静脉血栓研究进展

肝硬化并发门静脉血栓（Portal vein thrombosis,PVT）将增加肝硬化并发症的发生率。由于PVT可与上消化道出血同时发生,增加了治疗的难度。PVT形成的主要原因是门静脉血流速度降低。目前,治疗PVT仍以药物为主,研究表明抗凝治疗并不增加消化道出血的风险,因此对于有适应症的患者,在食管胃静脉曲张经治疗消失后,应及时针对PVT进行治疗。部分脾动脉栓塞患者,在治疗后常规给予抗凝处理可减少门静脉血栓的发生。在治疗过程中,早期诊断、抗凝治疗的监测指标、肝素用量、预防复发方面仍有较多问题等待解决。     

Thrombophilic gene mutations in cirrhotic patients with portal vein thrombosis

OBJECTIVE: Thrombophilic gene mutations have been reported to be associated with the formation of portal vein thrombosis (PVT). This study aimed to investigate the role of thrombophilic gene mutations in cirrhotic patients with PVT. PATIENTS AND METHODS: A total of 74 cirrhotic patients (17 with PVT, 57 without PVT), and 19 non-cirrhotic patients with PVT and 80 healthy controls were included. Factor V Leiden G1691A, prothrombin G20210A and methylenetetrahydrofolate reductase C677T mutations were analysed by restriction fragment length polymorphism. RESULTS: Aetiologies and Child-Pugh distribution of cirrhotic patients with and without PVT were similar. Five of 17 (29%) of cirrhotic patients with PVT but only two of 57 (3.5%) of cirrhotics without PVT, five of 80 (6%) of controls and none of the 19 non-cirrhotic patients with PVT had factor V Leiden G1691A mutation (P<0.05). Prothrombin G20210A mutation was found in five (29%) cirrhotic patients with PVT while only two (3.5%) cirrhotic patients without PVT, one (5%) non-cirrhotic patient with PVT and two (2.5%) controls had this mutation (P<0.05). The frequency of the homozygote methylenetetrahydrofolate reductase 677C-T mutation was similar in all four groups. CONCLUSIONS: Inherited thrombophilic gene mutations appear to increase the risk of PVT formation in cirrhotic patients but not in patients without liver disease in a cohort of Turkish patients.     

Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis

The prevalence and pathogenesis of portal vein thrombosis (PVT) in patients with cirrhosis without hepatocellular carcinoma are not clearly defined. The role of thrombophilic genetic factors is well established in other venous thrombotic diseases, as well as in noncirrhotic portal thrombosis. Recently, new, inherited thrombophilic disorders (factor V Leiden [FVL], mutation G20210A of prothrombin [PTHR A(20210)], and mutation TT677 of methylenetetrahydrofolate reductase [MTHFR C677-->T]) have been identified and associated with increased risk of venous thrombosis. The aim of our study was to investigate the role of these thrombophilic disorders in the pathogenesis of PVT in cirrhotic patients. Twenty-three cirrhotic patients with PVT and 40 cirrhotics without PVT were included. A group of 184 patients with deep vein thrombosis (DVT) and 431 healthy persons served as controls. The FVL, PTHR A(20210), and MTHFR C(677)-->T genotypes were identified by a polymerase chain reaction and restriction analysis. The frequencies of FVL, PTHR A(20210) mutation, and homozygous MTHFR C(677)-->T were 13%, 34.8%, and 43.5% in cirrhotic patients with PVT and 7.5%, 2.5%, and 5% in cirrhotic patients without PVT, respectively. Five patients in the former group had associated defects. A thrombophilic genotype was detected in 69.5% of the patients with PVT. Identification of this high-risk group may have implications in patients who are candidates for major surgery or liver transplantation, and may influence the duration of oral anticoagulation.     

Study of portal vein thrombosis in patients with idiopathic portal hypertension in Japan.

BACKGROUND/AIMS: The aim of this study was to elucidate the incidence and clinical manifestations of portal vein thrombosis (PVT) in patients with idiopathic portal hypertension (IPH) in Japan during long-term follow-up. PATIENTS AND METHODS: Twenty-two patients with IPH were examined for PVT by sonography during a follow-up of 12+/-6 years. Clinical manifestations and patient outcome related to PVT were studied. Seventy patients with liver cirrhosis were examined by sonography as an incidence control of thrombosis. RESULTS: Nine IPH patients had portal thrombosis (9/22, 41%), a higher incidence than in liver cirrhosis patients (7/70, 10%). Those with thrombosis showed ascites, marked hypersplenism, and low serum albumin. Four patients with thrombosis died. Patients without thrombosis showed less clinical problems after long-term follow-up. Plasma antithrombin III and protein C activity decreased in almost half of the patients. However, there were no differences in these parameters between patients with and without thrombosis. CONCLUSIONS: In Japan, IPH patients had a high incidence of portal thrombosis, a significant factor for poor prognosis. Whether the management of PVT contributes to an improvement of a clinical course of IPH or not should be clarified in further study.     

Protein C and D-dimer are related to portal vein thrombosis in patients with liver cirrhosis

Background and Aim: To profile changes of coagulation, anticoagulation and fibrolytic factors associated with liver function failure and portal vein thrombosis (PVT) formation in chronic liver cirrhosis patients. Methods: A total of 116 cirrhotic patients admitted to our hospital from June 2006 to October 2008 were included in our study. All patients were classified into two groups: PVT group (31 patients), composed of patients with PVT and a control group (85 patients), including patients without PVT. Platelet, prothrombin time (PT), activated partial prothrombin time (APTT) and fibrinogen were measured. Also, plasma samples from the patients were analyzed for the levels of antithrombin III (AT‐III), protein C (PC), protein S (PS), D‐dimer, tissue‐type plasminogen activator as well as plasminogen activator inhibitor‐1. Statistical analyses were carried out to evaluate the correlation of specific variations with the disease status. Results: In general, the higher Child‐Pugh scores, indicating the aggravation of hepatic impairment of the patients, correlated well with the prolonged PT/APTT and increased D‐dimer, as well as decreased platelet, fibrinogen, PC and AT‐III levels in the serum. Furthermore, we found that the PC, PS and D‐dimer levels in PVT patients were 2.32 ± 0.72 mg/L, 17.14 ± 3.62 mg/L and 0.99 ± 0.36 mg/L, respectively, both representing a significant difference compared with those in the control group without PVT. Logistic regression model shows that the odds ratio value of one unit of increase of PC and D‐dimer were 0.48 and 15.57. Conclusions: Cirrhotic patients displayed dysfunctions in the coagulation, anti‐coagulation and fibrolytic systems. The development of PVT in these patients may be independently associated with the decrease of PC, PS and D‐dimer. Furthermore, decreasing PC and increasing D‐dimer may be risk factors inducing PVT in cirrhotic patients.     

肝硬化门脉高压症并发血栓形成机制和治疗研究进展*

肝硬化门脉高压症并发血栓是临床研究实践过程中面临的难题。本文通过对其形成机制和治疗相关研究进展进行总结,重点介绍了近年来国内外关于肝硬化门脉高压并发门脉血栓发生机制和治疗进展。目前认识的主要发生机制包括肝星状细胞的活性、内皮细胞的功能、机体促凝血和凝血抑制失衡等,治疗措施包括低分子肝素等抗凝治疗、β受体阻滞剂和其他药物,如辛伐他汀、利福昔明和益生菌等联合应用以降低门脉压力治疗、提高一氧化氮合成酶磷酸化水平和针对线粒体的抗氧化治疗等措施。     

脾切除联合贲门周围血管离断术治疗肝硬化门脉高压症患者预防门静脉血栓形成研究

目的 探讨脾切除联合贲门周围血管离断术治疗肝硬化门脉高压症患者门静脉血栓(PVT)的预测措施。方法 2017年1月～2019年3月我院肝胆外科诊治的肝硬化并发门脉高压症患者60例,均接受脾切除联合贲门周围血管离断术。术后将患者分成A组和B组。在B组,当出现抗凝指针时给予低分子肝素短期抗凝治疗。使用彩超检查门脉指标和诊断PVT形成。结果 术后,在B组30例患者中有20例(66.7%)接受了短期抗凝治疗;在术后3 w末,超声检查发现PVT患者15例(25.0%),其中A组11例(36.7%),显著高于B组的4例【(13.3%),P<0.05】;血栓形成组门静脉直径为(1.5±0.3)cm,与无血栓形成组比,无显著性差异【(1.4±0.2)cm,P>0.05】,门静脉血流流速为(12.3±1.4)cm/s,显著低于无血栓形成组【(14.5±1.7)cm/s,P＜0.05】;血栓形成组血清D-二聚体水平显著高于无血栓形成组(P＜0.05);血栓形成组外周血血小板计数为(142.6±58.9)×10⁹/L,显著高于无血栓形成组【(91.4±52.4)×10⁹/L,P＜0.05】。结论 在采取脾切除联合贲门周围血管离断术治疗肝硬化并发门脉高压症患者时,需警惕术后PVT的形成。对术后血小板计数急剧升高、血清D-二聚体显著升高和门脉血流减慢的患者应该及时给予抗凝治疗。     

肝硬化患者门静脉血栓形成的相关危险因素

目的:研究肝硬化患者门静脉血栓(portal veinthrombosis,PVT)形成的相关危险因素.方法:2006-2007年我院确诊的肝炎和酒精性肝硬化患者90例,其中23例肝硬化PVT患者作为血栓组,67例肝硬化非血栓患者作为对照组.采用凝固法检测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)和纤维蛋白原(Fib),发色底物法检测抗凝血酶-Ⅲ(AT-Ⅲ),酶联免疫吸附双抗体夹心法检测蛋白-C(PC)、蛋白-S(PS)、D-二聚体(d-dimer)、组织纤溶酶原激活物剂(t-PA)和组织纤溶酶原激活物抑制剂-I(PAI-1).将门静脉血栓形成的相关因素纳入研究,进行统计学分析.结果:d-dimer升高是肝硬化PVT形成的危险因素(OR=13.236,95%CI:2.345-74.721),PC和AT-Ⅲ升高是肝硬化PVT形成的保护因素(OR=0.242,95%CI:0.08-0.727;OR=0.917,95%CI:0.841-0.999).研究未能提示性别、肝功能Child-Pugh分级和APTT等止凝血指标是PVT形成的危险因素.结论:d-dimer升高是肝硬化PVT形成的危险因素,PC和AT-Ⅲ升高是肝硬化PVT形成的保护因素.     

肝硬化后门静脉血栓形成的临床特点研究

目的研究肝硬化(liver cirrhosis,LC)后门静脉血栓(portal vein thrombosis,PVT)形成的临床特点。方法对9678例LC患者进行回顾性分析,采用腹部B超/腹部增强CT及腹部增强MRI检查门脉主干或左右分支,筛选出LC伴PVT形成者(PVT组),同时将LC后无PVT患者纳为对照组,比较2组的Child-Pugh分级、门静脉及脾静脉宽度、脾脏面积及厚度、腹水、上消化道出血、肝性脑病和肝肾综合征等并发症。结果 LC患者中有396例(4.09%)PVT形成。PVT组中LC的病因主要有乙型肝炎、酒精性及丙型肝炎LC,PVT主要分布在门静脉主干、门静脉右支、肠系膜上静脉、门静脉左支和脾静脉。按Child-Pugh进行分级,PVT组与对照组比较,肝损伤较重(P<0.01)。PVT组合并腹水、上消化道出血、肝性脑病及肝肾综合征等并发症的发病率均较对照组高(P<0.01)。PVT组门静脉和脾静脉宽度分别为(1.50±0.23)cm和(1.25±0.34)cm,对照组为(1.38±0.23)cm和(1.06±0.29)cm。PVT组脾脏面积为(97.48±32.90)cm2,脾脏厚度为(6.09±1.21)cm;对照组分别为(81.19±29.10)cm2和(5.26±0.99)cm。PVT组门静脉及脾静脉宽度和脾脏厚度均大于对照组,差异有统计学意义(P<0.05)。PVT组有侧支循环开放的患者占96.21%,对照组为78.25%,2组比较差异有统计学意义(P<0.05)。结论 LC后PVT形成对LC患者的临床转归有重要影响。     

肝硬化门静脉血栓形成的临床分析

目的　探讨肝硬化 (LC)门静脉血栓 (PVT)形成对LC病程发展的影响。方法　检索我院自 1 995至 2 0 0 2年肝硬化PVT形成患者 ,血栓诊断依据彩色多普勒和 (或 )CT。 4 8例肝硬化PVT形成患者入选血栓组 ;同阶段LC门脉高压症的非血栓病例中选择 5 2例作为对照组。对两组患者的肝功能Child Pugh分级、凝血功能、门静脉、脾静脉宽度及脾脏面积、厚度进行比较。行t检验 ,χ2 检验 ,Logistic回归分析。结果　肝硬化PVT形成除继发于脾切除等手术后 ,75 .0 %隐匿发病 ,85 .4 %的血栓发生于门静脉主干 ,脾脏增大与门静脉增宽是PVT形成的危险因素 (P =0 .0 0 3、0 .0 1 0 )。血栓组门静脉及脾静脉宽度分别为 (1 .4 8± 0 .2 6 )cm ,(1 .2 3± 0 .38)cm ,与对照组比较差异有显著性 [(1 .37± 0 .2 2 )cm ,(1 .0 5± 0 .30 )cm ,P =0 .0 37,0 .0 31 ]。血栓组脾面积平均值为 (96 .6 4± 33.4 )cm2 ,脾厚径为 (6 .0 7± 1 .2 0 )cm ,分别大于对照组的 (80 .81± 2 8.9)cm2 ,(5 .2 3± 1 .0 8)cm(P =0 .0 36 ,0 .0 0 1 )。血栓组食管胃底静脉曲张程度重于非血栓组 ,大出血、大量腹水比例高 (P <0 .0 5 )。血栓形成后 1年内死亡率为1 6 .6 % ,较非血栓组增高 (P =0 .0 2 3)。两组肝功能Child Pugh分级、凝血功能、血小板计     

肝硬化门静脉高压脾切除术后门静脉血栓形成的研究进展

门静脉血栓形成(PVT)是指门静脉或其分支、脾静脉和肠系膜上静脉内形成的血栓。PVT是门静脉高压症脾切除术后的一种常见并发症,往往可能会导致肝损伤、上消化道出血、肝昏迷,甚至是缺血性肠坏死。因而,早期发现PVT并进行有效干预,对降低PVT患者的病死率有十分重要的意义。对肝硬化脾切除术后PVT危险因素和治疗进行了综述,指出PVT应及早进行有效干预。     

经皮经肝介入门静脉血栓溶栓治疗

目的评价经皮经肝门静脉穿刺置管介入溶栓术的安全性和疗效。方法3例患者中,男性2例,女性1例,年龄分别为56岁,62岁,70岁。肝炎肝硬化2例,1例腹痛原因待查(后经手术证实为肠间脓肿)。3例患者均经彩色多普勒和CT检查发现门静脉血栓。3例患者均在B超引导下进行经皮经肝门静脉穿刺,置入5F CobraⅠ型导丝及导管鞘,经导管输注20万单位尿激酶后,继以每日30万单位持续注入,连续3天~5天行溶栓治疗,术后抗凝治疗。结果3例患者经皮经肝门静脉穿刺均一次成功,在置管造影及溶栓过程中均无不良反应;拔管前复查造影显示2例患者门静脉100%再通,1例80%再通;3例患者治疗后临床症状好转,腹水消退,肝功能改善,其中2例肝硬化患者食管静脉曲张程度减轻。1例腹痛原因待查患者溶栓后腹痛减轻但未完全缓解,体温较前下降但未正常,于溶栓后2周行剖腹探查,术中证实右下腹肠间包裹性脓肿,行脓肿切开引流,脓液培养为大肠杆菌,继续抗炎治疗2周后,体温降至正常,腹痛完全缓解。结论经皮经肝门静脉穿刺置管介入溶栓术是治疗门静脉血栓的安全、有效方法。     

Extrahepatic portal vein thrombosis

Noncirrhotic, nontumoral portal vein thrombosis (PVT) is the second most-frequent cause of portal hypertension in the world. General thrombophilic factors can be identified in approximately 60% of patients. PVT may manifest as an acute process. However, the acute episode more frequently is asymptomatic or paucisymptomatic and portal vein thrombosis is misdiagnosed until the development of complications secondary to portal hypertension, such as variceal bleeding or portal biliopathy. Although no randomized controlled trials have been performed, after the diagnosis of acute PVT early initiation of anticoagulation (within 30 days of the onset of symptoms) is recommended to achieve recanalization. In patients with portal cavernoma, anticoagulation is aimed to prevent the progression and recurrence of thrombosis. Because of the lack of data in this specific population, variceal bleeding is managed as in cirrhotic patients. Ursodeoxycholic acid has been proposed empirically for the treatment of patients with symptomatic portal biliopathy. Choledocholithiasis might be present, complicating a bile duct stenosis. Accordingly, an endoscopic retrograde cholangiopancreatography with sphincterotomy, extraction with balloon catheter, and stent placement is indicated. Mortality among patients with PVT is low (5-year mortality rate of 5 to 10%) and is mainly related to associated diseases rather than to complications of portal hypertension.