Portal vein thrombosis with protein C-S deficiency in a non-cirrhotic patient.
ABSTRACT: There are several conditions that can lead to portal vein thrombosis (PVT), including including infection, malignancies, and coagulation disorders. Anew condition of interest is protein C and S deficiencies, associated with hypercoagulation and recurrent venous thromboembolism. We report the case of a non-cirrhotic 63-year-old male diagnosed with acute superior mesenteric vein thrombosis and PVT and combined deficiencies in proteins C and S, recanalized by short-term low molecular heparin plus oral warfarin therapy.
Project description:Portal vein thrombosis is an important cause of portal hypertension. PVT occurs in association with cirrhosis or as a result of malignant invasion by hepatocellular carcinoma or even in the absence of associated liver disease. With the current research into its genesis, majority now have an underlying prothrombotic state detectable. Endothelial activation and stagnant portal blood flow also contribute to formation of the thrombus. Acute non-cirrhotic PVT, chronic PVT (EHPVO), and portal vein thrombosis in cirrhosis are the three main variants of portal vein thrombosis with varying etiological factors and variability in presentation and management. Procoagulant state should be actively investigated. Anticoagulation is the mainstay of therapy for acute non-cirrhotic PVT, with supporting evidence for its use in cirrhotic population as well. Chronic PVT (EHPVO) on the other hand requires the management of portal hypertension as such and with role for anticoagulation in the setting of underlying prothrombotic state, however data is awaited in those with no underlying prothrombotic states. TIPS and liver transplant may be feasible even in the setting of PVT however proper selection of candidates and type of surgery is warranted. Thrombolysis and thrombectomy have some role. TARE is a new modality for management of HCC with portal vein invasion.
Project description:The presence of occlusive portal vein thrombosis (PVT) greatly changes the natural history of liver cirrhosis, because it not only significantly increases the incidence of variceal rebleeding but also negatively influences the survival. However, due to the absence of strong evidence, no standard treatment algorithm for the secondary prophylaxis of variceal bleeding in cirrhotic patients with non-tumoral PVT has been established. Previous randomized controlled trials have demonstrated that transjugular intrahepatic portosystemic shunt (TIPS) can significantly decrease the incidence of variceal rebleeding in cirrhotic patients without PVT, compared with conservative therapy (i.e., endoscopic plus pharmacological therapy). Further, several large cohort studies have confirmed that TIPS can effectively prevent variceal rebleeding in cirrhotic patients with non-tumoral PVT. On the other hand, TIPS can facilitate recanalizing the thrombosed portal vein by endovascular manipulations, even in the presence of cavernous transformation of the portal vein (CTPV). More importantly, successful TIPS insertions can maintain the persistent portal vein patency, and avoid thrombus extension into the portal venous system. By comparison, anticoagulation therapy can achieve portal vein recanalization only in patients with partial PVT, but not in those with occlusive PVT or CTPV, and the use of anticoagulants may aggravate the risk of variceal bleeding in cirrhotic patients with a history of variceal bleeding. Collectively, we hypothesize that TIPS may be superior to conservative therapy for the prevention of variceal rebleeding in cirrhotic patients with non-tumoral PVT. Randomized controlled trials should be conducted to evaluate the survival benefit of TIPS in these patients.
Project description:Portal vein thrombosis (PVT) increases the risk of variceal rebleeding in liver cirrhosis. However, the strategy for preventing variceal rebleeding in cirrhotic patients with PVT has not been explored. This study aims to evaluate whether the transjugular intrahepatic portosystemic shunt (TIPS) or conventional therapy is preferable for the prevention of variceal rebleeding in liver cirrhosis patients with PVT.This is a randomised controlled trial comparing the safety and efficacy of TIPS versus conventional therapy (ie, endoscopic therapy combined with non-selective ?-blockers and anticoagulants) for the prevention of variceal rebleeding in cirrhotic patients with non-tumoral PVT. A total of 50 cirrhotic patients with PVT (thrombus >50% of portal vein lumen occupancy) and a history of variceal bleeding will be stratified according to the Child-Pugh class and degree of PVT, and randomised into the TIPS and conventional therapy groups. The primary objective was to compare the incidence of variceal rebleeding between the two groups. The secondary objectives were to compare the overall mortality, variceal rebleeding-related mortality, portal vein recanalisation and complications between the two groups, and to observe the progression of PVT in patients without portal vein recanalisation.This study was approved by the ethics committee of Xijing hospital (No. 20110224-5), and was registered at ClinicalTrials.gov (NCT01326949). All participants give written informed consent. The first patient was recruited into our study on 4 June 2011. A total of 29 patients were recruited through 5 March 2013 (14 and 15 patients assigned to the TIPS and conventional therapy groups, respectively). If TIPS is superior to conventional therapy for the prevention of variceal rebleeding in cirrhotic patients with PVT, TIPS might be recommended as the first-line therapy in such patients. But a small sample size potentially limits the generalisation of our conclusions.This study was registered at ClinicalTrials.gov on 29 March 2011. The trial registration number is NCT01326949.The first patient was recruited into our study on 4 June 2011. A total of 29 patients were recruited through 5 March 2013 (14 and 15 patients assigned to the TIPS and conventional therapy groups, respectively).
Project description:INTRODUCTION:Anticoagulation therapy in portal vein thrombosis (PVT) in patients with cirrhosis is still a matter of debate. Therefore, the aim of this work was to evaluate the efficacy and safety of nadroparin calcium-warfarin sequential (NWS) anticoagulation therapy in cirrhotic patients and to find an optimal anticoagulation strategy. METHODS:Consecutive cirrhotic patients with PVT who have not received anticoagulation therapy were randomly divided into the NWS therapy group (1-month nadroparin calcium by subcutaneous injection followed by 5-month warfarin by oral administration) and control group (no anticoagulation therapy). Overall recanalization rate of PVT and risks of bleeding were evaluated at the sixth month. RESULTS:Among 64 patients, complete or partial recanalization of PVT was observed in 20/32 NSW therapy group patients vs 11/32 control group patients (62.5% vs 34.4%, P = 0.024), with no statistically significant difference in bleeding rate. Child-Pugh score (P = 0.023), D-dimer < 2.00 ?g/mL (P = 0.020), and NWS anticoagulation therapy (P = 0.004) were predictors associated with the recanalization. NWS anticoagulation therapy (P = 0.008) was an independent predicting factor of recanalization. In the NWS therapy group, the Child-Pugh score (P = 0.007) and albumin level (P = 0.004) were improved in the sixth month. DISCUSSION:NWS anticoagulation therapy was effective and safe in PVT patients with cirrhosis and could increase the level of albumin. NWS therapy is safe and easily accepted.
Project description: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.
Project description:The clinical management of portal vein thrombosis (PVT) remains ambiguous due to its heterogeneous presentations and its associations with liver disease, malignancy, and hypercoagulable states. The natural history and clinical outcome of PVT are highly variable, dependent upon size, extent and degree of the thrombotic occlusion, as well as the physiological impact of patient comorbidities. While existing clinical guidelines consistently recommend low molecular weight heparin or vitamin K antagonist anticoagulation in cirrhotic patients with symptomatic acute PVT, management of asymptomatic and chronic PVT may need to be determined on a case-by-case basis, factoring in the state of underlying liver disease. In general, patients with PVT and underlying malignancy should be anticoagulated to alleviate symptoms and prevent recurrences that could disrupt the cancer management. However, existing clinical data does not support routine anticoagulation of cirrhotic patients with asymptomatic PVT in the absence of underlying cancer. While low molecular weight heparin and vitamin K antagonist remain the most commonly used agents in PVT, an emerging body of clinical evidence now suggests that direct-acting oral anticoagulants may be used safely and effectively in PVT. As such, direct-acting oral anticoagulants may offer a more convenient anticoagulation alternative for PVT management in future practice.
Project description:Liver cirrhosis but also portal vein obstruction cause portal hypertension (PHT) and angiogenesis. This study investigated the differences of angiogenesis in cirrhotic and non-cirrhotic PHT with special emphasis on the canonical (Shh/Gli) and non-canonical (Shh/RhoA) hedgehog pathway. Cirrhotic (bile duct ligation/BDL; CCl4 intoxication) and non-cirrhotic (partial portal vein ligation/PPVL) rats received either atorvastatin (15 mg/kg; 7d) or control chow before sacrifice. Invasive hemodynamic measurement and Matrigel implantation assessed angiogenesis in vivo. Angiogenesis in vitro was analysed using migration and tube formation assay. In liver and vessel samples from animals and humans, transcript expression was analyzed using RT-PCR and protein expression using Western blot. Atorvastatin decreased portal pressure, shunt flow and angiogenesis in cirrhosis, whereas atorvastatin increased these parameters in PPVL rats. Non-canonical Hh was upregulated in experimental and human liver cirrhosis and was blunted by atorvastatin. Moreover, atorvastatin blocked the non-canonical Hh-pathway RhoA dependently in activated hepatic steallate cells (HSCs). Interestingly, hepatic and extrahepatic Hh-pathway was enhanced in PPVL rats, which resulted in increased angiogenesis. In summary, statins caused contrary effects in cirrhotic and non-cirrhotic portal hypertension. Atorvastatin inhibited the non-canonical Hh-pathway and angiogenesis in cirrhosis. In portal vein obstruction, statins enhanced the canonical Hh-pathway and aggravated PHT and angiogenesis.
Project description:Introduction ?Timely diagnosis and treatment of portal vein thrombosis (PVT) is crucial to prevent morbidity and mortality. However, current imaging tests cannot always accurately differentiate acute from chronic (nonocclusive) PVT. Magnetic resonance noncontrast thrombus imaging (MR-NCTI) has been shown to accurately differentiate acute from chronic venous thrombosis at other locations and may also be of value in the diagnostic management of PVT. This study describes the first phase of the Rhea study (NTR 7061). Our aim was to select and optimize MR-NCTI sequences that would be accurate for differentiation of acute from chronic PVT. Study Design ?The literature was searched for different MRI sequences for portal vein and acute thrombosis imaging. The most promising sequences were tested in a healthy volunteer followed by one patient with acute PVT and two patients with chronic PVT, all diagnosed on (repetitive) contrast-enhanced computed tomography (CT) venography to optimize the MR-NCTI sequences. All images were evaluated by an expert panel. Results ?Several MR-NCTI sequences were identified and tested. Differentiation of acute from chronic PVT was achieved with 3D T1 TFE (three-dimensional T1 turbo field echo) and 3D T1 Dixon FFE (three-dimensional T1 fast field echo) sequences with best image quality. The expert panel was able to confirm the diagnosis of acute PVT on the combined two MR-NCTI sequences and to exclude acute PVT in the two patients with chronic PVT. Conclusion ?Using 3D T1 TFE and 3D T1 Dixon FFE sequences, we were able to distinguish acute from chronic PVT. This clinical relevant finding will be elucidated in clinical studies to establish their test performance.
Project description:In patients with liver cirrhosis the contribution of inherited and acquired prothrombotic disorders in the development of non-malignant portal vein thrombosis (PVT) is inconclusive. The purpose of this retrospective study was to examine the prevalence of thrombophilia in this setting at our center from January 2012 to November 2019. Tests included gene mutational analysis for Factor V Leiden, prothrombin G20210A, JAK2 (V617F), Calreticulin (CARL), in addition to activated protein C resistance, antithrombin III, protein C and S levels, and antiphospholipid antibodies. We included 77 patients, six of whom (7.8%) had a thrombophilic disorder: antiphospholipid syndrome in four patients, prothrombin gene mutation in one and factor V Leiden mutation in one. This latter patient had also been diagnosed with polycythemia vera years before PVT development. Complete thrombosis of the main portal vein and re-thrombosis after stopping anticoagulation were more frequent in patients with thrombophilia, but the rates of recanalization under anticoagulant therapy were similar among groups. No other difference was accounted between groups. The low prevalence of acquired and inherited thrombophilia found in patients with cirrhosis and PVT support testing for these disorders on an individual basis and avoiding universal screening to reduce costs and unwarranted testing.
Project description:Background:Well-defined guidelines for the treatment of portal vein thrombosis (PVT) in patients with cirrhosis are lacking, given the paucity of robust data. Among the available treatment options the best choice is unknown. Methods:We conducted a comprehensive search of multiple electronic databases and conference proceedings (through December 2019) to identify studies that reported on the use of anticoagulants in the treatment of PVT in patients with cirrhosis. Our goals were to evaluate the pooled odds ratio (OR) and pooled rate of treatment responders and bleeding events. Results:A total of 17 studies were included: 648 patients were treated with anticoagulation and 96 were controls. Pooled OR for treatment responders was 5.1 (95% confidence interval [CI] 2.5-10.2, P = 0.001) and pooled OR for bleeding was 0.4 (95%CI 0.1-1.5, P = 0.2) for anticoagulation treatment versus control. Pooled rate of treatment responders with anticoagulation was 66.7% (95%CI 58.3-74.1) compared to 26% (95%CI 14.2-42.7) for the control group. Pooled rate of bleeding seemed comparable (7.8%, 95%CI 4.5-13.3, and 15.4%, 95%CI 4.3-42.7). On subgroup analysis, pooled rates of treatment responders and bleeding events seemed similar between low molecular weight heparin, vitamin K antagonists, and direct oral anticoagulants. Conclusions:Our study demonstrated that anticoagulation is effective and safe in the treatment of PVT in patients with cirrhosis. Owing to the comparable outcomes, direct oral anticoagulants may be considered as first-line treatment, depending on patient preferences.