Nontumoral Portal Vein Thrombosis: A Challenging Consequence of Liver Cirrhosis

Nontumoral portal vein thrombosis (PVT) is an increasingly recognized complication in patients with cirrhosis. Substantial evidence shows that portal flow stasis, complex thrombophilic disorders, and exogenous factors leading to endothelial dysfunction have emerged as key factors in the pathogenesis of PVT. The contribution of PVT to hepatic decompensation and mortality in cirrhosis is debatable; however, the presence of an advanced PVT increases operative complexity and decreases survival after transplantation. The therapeutic decision for PVT is often determined by the duration and extent of thrombosis, the presence of symptoms, and liver transplant eligibility. Evidence from several cohorts has demonstrated that anticoagulation treatment with vitamin K antagonist or low molecular weight heparin can achieve recanalization of the portal vein, which is associated with a reduction in portal hypertension-related events and improved survival in cirrhotic patients with PVT. Consequently, interest in direct oral anticoagulants for PVT is increasing, but clinical data in cirrhosis are limited. Although the most feared consequence of anticoagulation is bleeding, most studies indicate that anticoagulation therapy for PVT in cirrhosis appears relatively safe. Interestingly, the data showed that transjugular intrahepatic portosystemic shunt represents an effective adjunctive therapy for PVT in cirrhotic patients with symptomatic portal hypertension if anticoagulation is ineffective. Insufficient evidence regarding the optimal timing, modality, and duration of therapy makes nontumoral PVT a challenging consequence of cirrhosis. In this review, we summarize the current literature and provide a potential algorithm for the management of PVT in patients with cirrhosis.     

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。     

肝硬化患者门静脉血栓形成危险因素的Logistic回归分析

目的研究肝硬化患者门静脉血栓（PVT）形成的相关危险因素。方法回顾性分析我院消化内科2007—2008年确诊的肝硬化患者80例,其中19例肝硬化PVT患者作为血栓组,61例肝硬化非血栓患者作为对照组,收集相关临床资料,对可能影响PVT形成的因素进行单因素分析和Logistic回归模型分析。结果Logistic回归模型分析结果显示,血浆D-二聚体、门静脉宽度（MPV）、血小板（PLT）是肝硬化患者PVT形成的独立危险因素（P值分别为0.003、0.012、0.036）。结论肝硬化患者应注意监测血浆D-二聚体、门静脉宽度、血小板等指标,以便早期预防和发现PVT的形成。     

Role of anticoagulant therapy in liver disease

Anticoagulant therapy is a cornerstone in the treatment of different liver diseases. In Budd-Chiari syndrome (BCS), survival rates have increased considerably since the introduction of a treatment strategy in which anticoagulation is the treatment of first choice. In all patients diagnosed with acute portal vein thrombosis (PVT), anticoagulant therapy for at least 3 months is indicated. Anticoagulation should also be considered in patients with chronic PVT and a concurrent prothrombotic risk factor. Current evidence suggests that patients with PVT in cirrhosis will benefit from treatment with anticoagulation as well. In severe chronic liver disease the levels of both pro- and anticoagulant factors are decreased, resetting the coagulant balance in an individual patient and making it more prone to deviate to a hypo- or hypercoagulable state. An increased activity of the coagulation cascade is not solely a feature of chronic liver disease; it influences the development of liver fibrosis as well. Several studies in animals and humans have shown that anticoagulation could prevent or improve fibrogenesis and even disease progression in cirrhosis. Anticoagulation is therefore a promising antifibrotic treatment modality.     

肝硬化并发门静脉血栓患者临床特征及其危险因素分析

目的 总结肝硬化并发门静脉血栓(PVT)患者的临床特征并分析PVT形成的危险因素。方法 回顾性分析2015年2月～2019年2月我院肝胆包虫科治疗的160例肝硬化患者,分析比较PVT组与未发生PVT组患者临床资料的差异,采用多因素分析发生PVT的危险因素。结果 80例PVT患者腹痛、腹水和消化道出血发生率、血小板(PLT)和白细胞(WBC)计数显著高于80例未发生PVT组(P<0.05);经多因素分析,发现PLT计数、糖尿病史和脾切除史为肝硬化并发门静脉血栓形成的独立危险因素(P<0.05)。结论 肝硬化并发PVT患者以HGB、PLT、WBC为主要实验室表现,以腹水、下消化道出血、肝功异常为主要临床症状。PLT、糖尿病史和脾切除史为肝硬化并发门静脉血栓的独立危险因素。     

Efficacy and safety of anticoagulation in non-malignant portal vein thrombosis in patients with liver cirrhosis

Background and aim

Treatment for portal vein thrombosis (PVT) is not well established. Nevertheless, anticoagulation therapy can seemingly be used as first-line therapy. However, there are limited data on the role of this treatment in patients with PVT and cirrhosis. We sought to assess the safety and efficacy of anticoagulation therapy in a series of patients with non-malignant PVT and liver cirrhosis.

Portal vein thrombosis associates with high platelet-fibrin clot strength and platelet activation in decompensated cirrhosis: A retrospective study

Background and aimsAlteration of platelet status associates with decompensation and death in cirrhosis, while its effect on portal vein thrombosis (PVT) remains unclear. We aimed to retrospectively investigate whether PVT associates with platelet-fibrin clot strength and platelet activation in decompensated cirrhosis.MethodsPlatelet-fibrin clot strength (G) was measured by thromboelastography (TEG). Platelet activation was reflected by plasma concentrations of soluble p-selectin (sPs) and a platelet aggregation test adjusted for platelet counts.ResultsAmong 166 patients, 45 had PVT. The platelet count was significantly lower in PVT. While the G value was positively correlated with platelet count (ρ = 0.74, P < 0.01), increased G was associated with PVT after adjusting for platelet count in the logistic regression (P = 0.04). The normalized G value according to the linear relation with platelet count was calculated as follows: G_platelet = [(G - 2622)/platelet count]. This coefficient had no correlation with platelet count and was an independent risk factor of PVT (OR = 1.03, CI_95%: 1.01-1.05, P = 0.012). In two subanalyses, the collagen-induced platelet aggregation (n = 37, P = 0.029) and plasma concentration of sPs (n = 56, P = 0.001) adjusted for platelet count were significantly higher in PVT.ConclusionThis study showed a positive correlation of high platelet-fibrin clot strength detected via TEG and platelet activation with PVT in decompensated cirrhosis.     

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...     

Nonmalignant portal vein thrombosis in adults

Portal vein thrombosis (PVT) consists of two different entities: acute PVT and chronic PVT. Acute PVT usually presents as abdominal pain. When the thrombus extends to the mesenteric venous arches, intestinal infarction can occur. Chronic PVT is usually recognized after a fortuitous diagnosis of hypersplenism or portal hypertension, or when there are biliary symptoms related to portal cholangiopathy. Local risk factors for PVT, such as an abdominal inflammatory focus, can be identified in 30% of patients with acute PVT; 70% of patients with acute and chronic PVT have a general risk factor for PVT, most commonly myeloproliferative disease. Early initiation of anticoagulation therapy for acute PVT is associated with complete and partial success in 50% and 40% of patients, respectively. A minimum of 6 months' anticoagulation therapy is recommended for the treatment of acute PVT. For patients with either form of PVT, permanent anticoagulation therapy should be considered if they have a permanent risk factor. In patients with large varices, beta-adrenergic blockade or endoscopic therapy seems to prevent bleeding as a result of portal hypertension, even in patients on anticoagulation therapy. In patients with jaundice or recurrent biliary symptoms caused by cholangiopathy, insertion of a biliary endoprosthesis is the first treatment option. Overall, the long-term outcome for patients with PVT is good, but is jeopardized by cholangiopathy and transformation of underlying myeloproliferative disease into myelofibrosis or acute leukemia.     

肝硬化并发门静脉血栓防治研究进展

门静脉血栓（PVT）是肝硬化的常见并发症,也是患者预后不良的临床标志之一。肝硬化常并发食管胃底静脉曲张、凝血酶原时间延长和血小板降低,存在门脉高压所致出血的风险。临床上,对应用抗凝药物防治PVT存在较多的疑虑。目前,防治肝硬化并发PVT仍缺乏可以遵循的诊疗指南。然而,日益增加的证据显示,抗凝治疗不仅不会增加肝硬化患者出血的风险,而且可获得较高的血管再通率。预防性抗凝治疗可有效降低肝硬化患者PVT发病率,并可能改善肝硬化疾病进程。如抗凝治疗无效,经颈静脉肝内门体静脉支架分流术（TIPS）或溶栓治疗可作为肝硬化并发PVT的备选处理方案。TIPS可获较高的血管再通率,但技术难度较大,而溶栓治疗存在出血风险,需谨慎进行。     

Nonselective β-blockers may induce development of portal vein thrombosis in cirrhosis

Currently, nonselective β-blockers (NSBBs) are commonly used for the prevention of variceal bleeding in liver cirrhosis. The beneficial effects of NSBBs are primarily attributed to the reduction in cardiac output by blockade of β1 receptors and vasoconstriction of the splanchnic circulation by the blockade of β2 receptors. The prognostic value of occlusive portal vein thrombosis (PVT) in cirrhotic patients has been increasingly recognized. The most important risk factor for the development of PVT in liver cirrhosis is the decreased portal vein inflow velocity. Collectively, we propose that the use of NSBBs potentially increases the development of portal vein thrombosis by reducing portal vein inflow velocity. The hypothesis should be confirmed by prospective cohort studies, in which cirrhotic patients without prior PVT treated with and without NSBBs are enrolled, and the development of PVT during follow-up is compared between the two groups. Additionally, subgroup analyses should be performed according to the dosage of NSBBs and the reduction of portal inflow velocity after use of NSBBs.     

肝硬化门静脉血栓形成的危险因素

门静脉血栓(PVT)在肝硬化患者中较常见,合并PVT的静脉曲张更容易出血,止血失败率及再出血率更高,对于肝移植患者,其预后更差。目前PVT形成的相关危险因素较多,如肝功能严重程度、非选择性β受体阻滞剂的使用、门静脉血流速度等。重点对肝硬化PVT形成的危险因素进行综述,以进一步了解PVT形成的相关机制和PVT的危险程度。     

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.     

Portal vein thrombosis in liver cirrhosis

Portal vein thrombosis (PVT) is observed in 10-20% of patients with liver cirrhosis, which is responsible for 20% of all PVT cases. The main pathogenic factor of PVT in cirrhosis is the obstacle to portal flow, but acquired and inherited clotting abnormalities may play a role. The formation of collateral veins allows many patients to remain asymptomatic and prevents the onset of clinical complications also in patients with totally occlusive PVT. Gastrointestinal bleeding, thrombosis of superior mesenteric vein and refractory ascites are typical manifestations of PVT. Instrumental diagnosis can be obtained by colour-doppler ultrasonography. Future studies should verify whether asymptomatic PVT worsens liver failure, or if its life-threatening complications reduce survival in patients with cirrhosis. Moreover, randomized controlled trials should clarify the potential effectiveness of anticoagulant therapy in the treatment of PVT.     

Portal vein thrombosis: What is new?

Portal vein thrombosis (PVT) is one of the most common vascular disorders of the liver with significant morbidity and mortality. Large cohort studies have reported a global prevalence of 1%, but in some risk groups it can be up to 26%. Causes of PVT are cirrhosis, hepatobiliary malignancy, abdominal infectious or inflammatory diseases, and myeloproliferative disorders. Most patients with PVT have a general risk factor. The natural history of PVT results in portal hypertension leading to splenomegaly and the formation of portosystemic collateral blood vessels and esophageal, gastric, duodenal, and jejunal varices. Diagnosis of PVT is made by imaging, mainly Doppler ultrasonography. According to its time of development, localization, pathophysiology, and evolution, PVT should be classified in every patient. Some clinical features such as cirrhosis, hepatocellular carcinoma, and hepatic transplantation are areas of special interest and are discussed in this review. The goal of treatment of acute PVT is to reconstruct the blocked veins. Endoscopic variceal ligation is safe and highly effective in patients with variceal bleeding caused by chronic PVT. In conclusion, PVT is the most common cause of vascular disease of the liver and its prevalence has being increasing, especially among patients with an underlying liver disease. All patients should be investigated for thrombophilic conditions, and in those with cirrhosis, anticoagulation prophylaxis should be considered.     

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.     

Changing perspectives in portal vein thrombosis

The aetiology of portal vein thrombosis (PVT) is heterogeneous. Important primary risk factors for PVT are cirrhosis, hepatobiliary malignancies and pancreatitis. Newly discovered thrombotic risk factors, such as latent myeloproliferative disorders and prothrombotic genetic defects, have also been identified as major risk factors for PVT. At least one-third of PVT patients demonstrate a combination of thrombotic risk factors. PVT, which does not have a detrimental effect on liver function, usually becomes manifest as a variceal haemorrhage in the oesophagus months to years after the development of thrombosis. Owing to intact coagulation variceal bleeding has a better prognosis among patients with PVT than cirrhotics. Endoscopic sclerotherapy or band ligation is the primary therapeutic option for variceal bleeding in patients with PVT. It is questionable whether anticoagulant therapy should be started, since it has not proven beneficial for most PVT patients. Therapy with anticoagulants is only recommended for those with acute PVT (especially in association with mesenteric vein thrombosis), those who recently underwent a portosystemic shunt procedure, and those with other thrombotic manifestations, particularly in case of proven hypercoagulability. Mortality of patients with PVT may be associated with concomitant medical conditions which lead to the PVT or with manifestations of portal hypertension, such as variceal haemorrhage. Multivariate analysis of a large Dutch PVT population has shown that age, malignancy, ascites and the presence of mesenteric vein thrombosis are independently related to survival. Death due to a variceal haemorrhage is rare. Poor outcome of PVT thus appears to be associated primarily with concomitant diseases which lead to PVT, and not the complications of portal hypertension. It is therefore uncertain whether surgical portosystemic shunting affects survival favourably.     

Diagnóstico y tratamiento de la trombosis portal en la cirrosis hepática

Improved imaging techniques and the routine use of color Doppler ultrasound in the follow-up of patients with liver cirrhosis has increased diagnosis of portal vein thrombosis (PVT) in these patients. The extension of PVT should be evaluated with computed tomography angiography or magnetic resonance angiography. The natural history of PVT in cirrhosis and its impact on liver disease is unknown but it seems clear that PVT could increase the morbidity and mortality associated with liver transplantation and can even be a contraindication to this procedure when the thrombus extends to the superior mesenteric vein. Anticoagulation is a relatively safe and effective treatment in achieving recanalization of the splenoportal axis or in preventing progression of thrombosis and is therefore frequently used. The use of transjugular intrahepatic portosystemic shunts (TIPS) is reserved for patients unresponsive to anticoagulation or in those with severe complications of portal hypertension.     

Portal Vein Thrombosis in Patients with End Stage Liver Disease Awaiting Liver Transplantation: Outcome of Anticoagulation

Background

The prevalence of portal vein thrombosis (PVT) increases with the severity of liver disease. Development of PVT is often accompanied by increased rate of morbidity and mortality and may affect patient candidacy for liver transplant. There is limited data regarding the role of anticoagulation therapy in patients with PVT and liver cirrhosis.

Objectives

The aims of this study were to describe the prevalence of hypercoagulable disorders in patients with liver cirrhosis and PVT, and to describe the outcome of anticoagulation in patients with liver cirrhosis and PVT.

Methods

A retrospective chart review was conducted of patients with liver cirrhosis awaiting liver transplant who were diagnosed with PVT between January 2005 and November 2011.

Results

During the study period, 537 patients were evaluated for liver transplant. Sixty-nine (13 %) patients were diagnosed with portal vein thrombosis. Chronic hepatitis C was the cause of liver disease in 24/69 (35 %) patients, and hepatocellular carcinoma was present in 39 % of patients. In 22 patients screened for hypercoagulable disorders, hypercoagulable disorder was diagnosed in one patient (5 %). Twenty-eight (28/69) patients were treated during the study period with warfarin: PVT resolved in 11/28 (39 %), no change in 5/28 (18 %), and 12/28 (43 %) patients showed partial resolution of thrombus. Eight patients received liver transplant while on anticoagulation, and operative notes confirmed patency of PV in all eight patients.

Conclusions

PVT is frequently seen in patients with end stage liver disease with prevalence of 13 %. Hypercoagulable disorder was detected in 5 % of the patients screened. Careful use of anticoagulation is safe and effective in patients with PVT.     

Preoperative predictors of portal vein thrombosis after splenectomy with periesophagogastric devascularization

AIM: To evaluate the predictive value of preoperative predictors for portal vein thrombosis (PVT) after splenectomy with periesophagogastric devascularization.METHODS: In this prospective study, 69 continuous patients with portal hypertension caused by hepatitis B cirrhosis underwent splenectomy with periesophagogastric devascularization in West China Hospital of Sichuan University from January 2007 to August 2010. The portal vein flow velocity and the diameter of portal vein were measured by Doppler sonography. The hepatic congestion index and the ratio of velocity and diameter were calculated before operation. The prothrombin time (PT) and platelet (PLT) levels were measured before and after operation. The patients’ spleens were weighed postoperatively.RESULTS: The diameter of portal vein was negatively correlated with the portal vein flow velocity (P < 0.05). Thirty-three cases (47.83%) suffered from postoperative PVT. There was no statistically significant difference in the Child-Pugh score, the spleen weights, the PT, or PLT levels between patients with PVT and without PVT. Receiver operating characteristic curves showed four variables (portal vein flow velocity, the ratio of velocity and diameter, hepatic congestion index and diameter of portal vein) could be used as preoperative predictors of postoperative portal vein thrombosis. The respective values of the area under the curve were 0.865, 0.893, 0.884 and 0.742, and the respective cut-off values (24.45 cm/s, 19.4333/s, 0.1138 cm/s^-1 and 13.5 mm) were of diagnostically efficient, generating sensitivity values of 87.9%, 93.9%, 87.9% and 81.8%, respectively, specificities of 75%, 77.8%, 86.1% and 63.9%, respectively.CONCLUSION: The ratio of velocity and diameter was the most accurate preoperative predictor of portal vein thrombosis after splenectomy with periesophagogastric devascularization in hepatitis B cirrhosis-related portal hypertension.