凝血因子ⅡG20210A突变在布加综合征和门静脉血栓形成中的意义

大量研究发现凝血因子ⅡG20210A突变与布加综合征和门静脉血栓形成有关。介绍了凝血因子Ⅱ及凝血因子ⅡG20210A突变,回顾了有关凝血因子ⅡG20210A突变对血栓形成的影响,并对凝血因子ⅡG20210A突变的患病率进行了分析,着重总结了凝血因子ⅡG20210A突变与门静脉血栓和布加综合征的关系。认为凝血因子ⅡG20210A突变在一定程度上增加了门静脉血栓和布加综合征的风险。但凝血因子ⅡG20210A突变在中国患者中的患病率极低,其也许并不足以作为中国门静脉血栓和布加综合征的病因。     

布加综合征诊治研究进展

<正>肝血管病是罕见的累及肝脏循环系统的异质性疾病,可累及肝动脉、门静脉、肝窦和肝静脉系统,主要包括布加综合征(Budd-Chiari syndrome, BCS)、门静脉血栓(portal vein thrombosis, PVT)、特发性非肝硬化性门静脉高压(idiopathic non-cirrhotic portal hypertension, INCPH)、     

布加综合征与妊娠

布加综合征是一种少见的肝脏疾病,其与妊娠之间相互影响。系统论述了布加综合征与妊娠的关系,并指出了在疾病诊断和治疗中的注意事项。其一,妊娠是布加综合征的危险因素。对于妊娠期间出现门静脉高压和(或)下腔静脉高压表现的患者,应高度怀疑合并布加综合征。其二,布加综合征患者妊娠具有一定的风险。经治疗病情稳定的患者可以妊娠,但孕期和产后须严密监查,以防止血栓复发。其三,布加综合征可导致女性不孕。原因不明的不孕患者应行腹部超声及CT检查,以排除布加综合征的可能。     

肝硬化门静脉高压诊治Baveno Ⅶ共识解读——介入科视角

2021年10月召开的BavenoⅦ专家共识会，总结了门静脉高压的主要进展及待解决的问题，介入诊疗是其重要内容，如：肝静脉压力梯度对门静脉高压的评估作用、危险分层指导治疗，经颈静脉肝内门体分流术在急性静脉曲张出血、静脉曲张出血二级预防、复发性腹水以及布加综合征、门静脉血栓等方面的应用。为了更好地规范和推动介入诊疗在门静脉高压诊治的临床及科研领域的应用，该文对其相关重点内容进行解读。     

食管胃静脉曲张出血合并门静脉血栓的临床监测与处理

门静脉血栓是肝硬化常见的并发症，也出现在非肝硬化性门静脉高压疾病中，门静脉血栓进一步加重门静脉高压，增加食管胃静脉曲张出血风险。对于合并食管胃静脉曲张的门静脉血栓患者，抗凝治疗与出血风险存在矛盾。明确门静脉血栓的病因与危险因素，对门静脉血栓进行诊断分类，对食管胃静脉曲张出血高危的血栓患者进行动态监测和个体化分层诊疗，是改善食管胃静脉曲张出血合并门静脉血栓患者预后的关键。     

骨髓增殖性肿瘤患者内脏静脉血栓复发的危险因素分析

<正>【据《Blood Cancer J》2016年11月报道】题:骨髓增殖性肿瘤患者内脏静脉血栓复发的危险因素:一项181例患者的队列研究(作者De Stefano V等)来自意大利天主教大学血液学研究所的De Stefano等回顾性分析了181例骨髓增殖性肿瘤患者,包括真性红细胞增多症67例、原发性血小板增多症67例、原发性骨髓纤维化47例,均以内脏静脉血栓为首发表现。其中,诊断为布加综合征和门静脉血栓的患者分别为31例(17.1%)和109例(60.3%);孤立性肠系膜血栓或脾     

肝硬化门静脉血栓的中西医诊治进展

<正>门静脉血栓(PVT)是肝硬化的常见并发症，主要与血流缓慢、局部血管损伤和血液高凝状态有关。本文就肝硬化PVT的危险因素、中医证候特点及中西医治疗手段等方面进行综述。1 流行病学门静脉血栓(PVT)是指门静脉主干和(或)门静脉左、右分支发生血栓，伴或不伴肠系膜静脉和脾静脉血栓形成^[1]。正常人群中发病率仅为0.7/10万～1/10万^[2],而PVT在肝硬化患者中却非罕见，由于起病隐匿，且认识不足，曾经一度未得到重视，     

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。     

低分子肝素钙联合右旋糖酐在肝硬化门静脉高压症术后静脉血栓形成预防中的应用

目的分析低分子肝素钙联合右旋糖酐在肝硬化门静脉高压症术后静脉血栓形成预防中的应用。方法选择2013年3月至2018年3月我院收治的肝硬化门静脉高压症患者83例为研究对象,根据入院顺序经随机数字表法分为研究组41例和对照组42例,对照组于术后12 h开始皮下注射低分子肝素钙进行治疗,研究组在对照组基础上,于术后12 h开始静脉滴注右旋糖酐进行治疗,对比两组患者的门静脉指标情况、门静脉血栓发生率和不良反应发生率。结果治疗后,两组患者的门静脉最大血流速度、平均血流速度和门静脉直径等指标均增大,且研究组更为显著(P0.05);住院期间,研究组患者的门静脉血栓发生率4.9%(2/41)显著低于对照组23.8%(10/42)(P0.05);治疗3个月后,研究组患者的门静脉血栓发生率7.3%(3/41)显著低于对照组33.3%(14/42)(P0.05);经对比,两组患者的上消化道出血、切口感染、腹腔出血和肝功能异常等不良反应发生率与对照组无差异(P0.05)。结论低分子肝素钙联合右旋糖酐可有效预防肝硬化门静脉高压症患者术后静脉血栓的形成,并改善其门静脉指标,且安全性较好,值得临床推荐使用。     

抗炎治疗促进肝硬化出血患者门静脉血栓再通的队列研究

目的 肝硬化肠道炎症参与门脉血栓的形成与进展,探索抗炎治疗是否促进肝硬化食管胃静脉曲张破裂出血合并门静脉血栓患者短期内血栓再通,为肝硬化门脉高压抗炎治疗提供更多证据。方法 采用队列研究方法,在肝硬化门脉高压静脉曲张数据库中选取2018年1月1日至2021年3月1日因急诊出血就诊复旦大学附属中山医院的肝硬化患者,采用增强CT确认其存在门静脉血栓,按照是否应用抗生素分组,在患者后续短期连续观察的病程中,增强CT随访门静脉血栓再通情况,权衡其他因素,用生存曲线评估两组的血栓再通差异。结果 共124例肝硬化食管胃静脉曲张破裂出血合并门静脉血栓的患者纳入本研究,其中70例应用抗生素治疗,54例未应用抗生素治疗。中位随访时间182.00(126.00～245.75)d,抗生素组门静脉血栓再通率显著高于无抗生素组（30.00%比14.81%,P=0.048）。结论抗生素治疗可促进肝硬化食管胃静脉曲张破裂出血合并门静脉血栓的患者短期内门静脉血栓的再通。     

Successful liver transplantation in a patient with splanchnic vein thrombosis and pulmonary embolism due to polycythemia vera with Jak2v617f mutation and heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin treatment resulting in a severe acquired thrombophilic condition with an associated mortality of about 10 %. We report the first case of successful urgent liver transplantation (LT) in a patient with end-stage liver disease due to a Budd–Chiari syndrome, portal vein thrombosis and pulmonary embolism due to acquired thrombophilia associated to polycythemia vera carrying JAK2V617F gene mutation and HIT in the acute phase. Lepirudin was used to provide anticoagulation in the LT perioperative period that was performed without haemorrhagic and thrombotic complications despite the donor received heparin during liver explantation.     

Prevalence of the factor V Leiden mutation in hepatic and portal vein thrombosis.

BACKGROUND: The factor V Leiden (FVL) mutation has been shown to be the most frequent cause of hereditary thrombophilia. The prevalence of the mutation in patients with Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT) has not been fully elucidated. AIMS: To investigate the association between the FVL mutation and BCS and PVT. PATIENTS: Thirty patients with BCS, 32 patients with PVT, and a control group of 54 patients with liver disorders and no history of thrombosis. METHODS: The factor V gene was analysed for the presence of the FVL mutation by a polymerase chain reaction (PCR) technique. The presence of the mutation was confirmed by DNA sequencing. RESULTS: Seven (23%) patients with BCS, one (3%) patient with PVT, and three (6%) patients in the control group were identified as having the FVL mutation. There of the BCS patients had coexisting hypercoagulable states. The prevalence of the FVL mutation was significantly higher in patients with BCS compared with patients with PVT and controls (p < 0.04). The FVL mutation was the second most common aetiology associated with BCS. CONCLUSION: The FVL mutation is an important factor in the pathogenesis of BCS and screening for the disorder must be included in the investigation of patients presenting with this condition. In contrast, the FVL mutation is not a major predisposing factor in the pathogenesis of PVT.     

Multiple thrombophilic factors in a patient with Budd–Chiari syndrome

Myeloproliferative disorders are the main cause of Budd–Chiari syndrome in western countries. Inherited or acquired thrombophilic factors have also been implicated. A novel mutation of the prothrombin gene (G→A20210) has only been described in a few cases of Budd–Chiari syndrome so far. Venous thrombosis is often the result of multiple concomitant thrombophilic factors. We report the case of a patient with essential thrombocythemia and Budd–Chiari syndrome in which heterozygosity for both factor V Leiden and the mutation G20210A of the prothrombin gene were identified.     

Liver in haematological disorders

Prothrombotic haematological disorders, in particular myeloproliferative disorders, are identified in a significant proportion of patients with Budd–Chiari syndrome and portal vein thrombosis (PVT). Multiple prothrombotic disorders may coexist. PVT is diagnosed in one fourth of patients with cirrhosis and is more common with advanced liver disease and hepatocellular carcinoma. PVT in cirrhosis can precipitate decompensation. Intrahepatic microthrombosis may play a role in the pathogenesis of hepatic fibrosis. Sinusoidal obstruction syndrome is usually a complication of myeloablative treatment before haematopoietic stem cell transplantation. Post-transplant lymphoproliferative disorders can complicate liver transplantation and are related to Epstein–Barr virus infection. Hepatitis B reactivation in patients receiving chemotherapy for haematological malignancies is very common without pre-emptive treatment, and can lead to liver failure. Liver involvement is common in primary haematological diseases, such as haemolytic anaemias, lymphomas and leukaemia.     

Budd‐Chiari and inferior caval vein syndromes due to membranous obstruction of the liver veins: successful treatment with angioplasty and transcaval transjugular intrahepatic porto‐systemic shunt

The case is presented of a 25‐year‐old Caucasian patient with Budd‐Chiari syndrome due to membranous obstruction of the liver veins and inferior caval vein syndrome as a result of secondary hyperplasia of the caudate lobe of the liver, obstructing the caval vein. Diagnosis was established by intravascular pressure measurements, ultrasound examinations and caval and liver vein angiograms. Treatment consisting of stent placement in the outlet of a hepatic vein and subsequent transjugular intrahepatic porto‐systemic shunt (TIPS) insertion via the caval vein was successful. After 34 months of follow‐up the stents remain open and the patient is symptom free. This successful combination of stent placement and TIPS has not been described before. The case report is followed by a review of the literature on the use of angioplasty in short hepatic vein stenosis and TIPS in Budd‐Chiari syndrome. It is concluded that angioplasty and TIPS are safe and efficient procedures to reduce liver engorgement and complications of portal hypertension in selected patients with Budd‐Chiari syndrome.     

Transjugular intrahepatic portosystemic shunt in the management of Budd Chiari syndrome

Budd Chiari syndrome presents with a wide range of severity and duration of symptoms. Transjugular intrahepatic portosystemic shunt has been used to treat selected Budd Chiari syndrome patients for several years. The technique of transjugular intrahepatic portosystemic shunt may be more challenging than in cirrhosis because of hepatic vein occlusion. Covered transjugular intrahepatic portosystemic shunt stents have reduced the requirement for follow-up interventions. Transjugular intrahepatic portosystemic shunt has been a successful bridge to liver transplant for Budd Chiari syndrome but is the definitive treatment in many cases. Patient selection is important to determine who will benefit from transjugular intrahepatic portosystemic shunt or other treatments such as hepatic vein recanalization or liver transplant.     

Japanese case of Budd-Chiari syndrome due to hepatic vein thrombosis successfully treated with liver transplantation

A 22‐year‐old Japanese woman was found to have severe esophageal varices and then suffered from hepatic encephalopathy. She was diagnosed with Budd‐Chiari syndrome (BCS) due to hepatic vein (HV) thrombosis accompanied by portal vein thrombosis without inferior vena cava (IVC) obstruction. Latent myeloproliferative neoplasm (MPN) lacking the JAK2‐V617F mutation was considered to be the underlying disease. Liver transplantation was strikingly effective for treating the clinical symptoms attributable to portal hypertension. Although thrombosis of the internal jugular vein occurred due to thrombocythemia, which manifested after transplantation despite anticoagulation therapy with warfarin, the thrombus immediately disappeared with the addition of aspirin. Neither thrombosis nor BCS has recurred in more than 4 years since the amelioration of the last thrombotic event, and post‐transplant immunosuppression with tacrolimus has not accelerated the progression of MPN. In Japan, IVC obstruction, which was a predominant type of BCS, is suggested to have decreased in incidence with recent improvements in hygiene. The precise diagnosis of BCS and causative underlying diseases should be made with attention to the current trend of the disease spectrum, which fluctuates with environmental sanitation levels. Because the stepwise strategy, including liver transplantation, has been proven effective for patients with pure HV obstruction in Western countries, this strategy should also be validated for utilization in Japan and in developing countries where HV obstruction potentially predominates.     

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.     

A case of the Budd Chiari syndrome attributed to a deficit in protein C

We report a case of Budd Chiari syndrome associated with a deficit in protein C, in a young women admitted to hospital for investigation of thromboembolic disease and ascites. This coagulation defect was thought to be an aetiological factor in the suprahepatic vein thrombosis. The diagnosis and treatment of this rare form of the syndrome are discussed.     

Budd‐Chiari syndrome in Sweden: epidemiology,clinical characteristics and survival – an 18‐year experience

Background: The exact incidence and prevalence of Budd‐Chiari syndrome (BCS) is unknown in the general population. Published reports differ in terms of the clinical characteristics, effects of therapy and survival. Aims: To investigate the epidemiology, clinical presentation and survival in patients with BCS. Methods: Retrospective multicentre study in Sweden reviewing the medical records of all patients with BCS 1986–2003, identified from the computerised diagnosis database of 11 hospitals, including all university hospitals and liver transplantation centres. Results: Forty‐three patients with BCS were identified, of whom nine (21%) had concomitant portal vein thrombosis. The mean age‐standardised incidence and prevalence rates in 1990–2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. Myeloproliferative disorders (38%), thrombophilic factors (31%) and oral contraceptives (30%) were common aetiological factors. Two or more risk factors were present in 44%. In 23%, no risk factor was evident. The median follow‐up time was 2.7 years. Seventy‐two percent were on anticoagulant therapy during follow‐up. Transjugular intrahepatic portosystemic shunting, surgical shunting procedures and liver transplantation were performed in 4, 6 and 18 patients respectively. Nineteen patients died. The overall transplantation‐free survival at 1, 5 and 10 years was 47, 28 and 17% respectively. Conclusions: Budd‐Chiari syndrome is a rare disorder; the mean age‐standardised incidence and prevalence rates in Sweden in 1990–2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. The presence of a myeloproliferative disorder was a common aetiological factor in our cohort and about half of the patients had a multifactorial aetiology. The transplantation‐free survival was poor.