Update on Management of Portal Vein Thrombosis and the Role of Novel Anticoagulants.
ABSTRACT: 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: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: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: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.
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:Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.
Project description:BACKGROUND:Clinicians confront numerous practical issues in optimizing the use of anticoagulants to treat venous thromboembolism (VTE). OBJECTIVE:These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians and other health care professionals in their decisions about the use of anticoagulants in the management of VTE. These guidelines assume the choice of anticoagulant has already been made. METHODS:ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. RESULTS:The panel agreed on 25 recommendations and 2 good practice statements to optimize management of patients receiving anticoagulants. CONCLUSIONS:Strong recommendations included using patient self-management of international normalized ratio (INR) with home point-of-care INR monitoring for vitamin K antagonist therapy and against using periprocedural low-molecular-weight heparin (LMWH) bridging therapy. Conditional recommendations included basing treatment dosing of LMWH on actual body weight, not using anti-factor Xa monitoring to guide LMWH dosing, using specialized anticoagulation management services, and resuming anticoagulation after episodes of life-threatening bleeding.
Project description:Prosthetic valve thrombosis (PVT) can be a life-threatening complication that requires immediate treatment. We present a case of 57-year-old woman with tricuspid PVT who was definitely diagnosed by multi-detector-row computed tomography limited with echocardiography. The patient was treated successfully with an alternative approach using low molecular weight heparin bridging therapy followed by intensifying anticoagulation alone.
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: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.