Non-cirrhotic Portal Vein Thrombosis Research Articles

New targets for the prevention and treatment of cirrhotic portal vein thrombosis

Portal vein thrombosis (PVT) is divided into cirrhotic and non-cirrhotic PVTs. The incidence rate of PVT varies greatly among different clinical stages of cirrhosis, with an overall incidence rate of about 13.92%, and the prevalence of cirrhotic PVT following splenectomy is as high as 60%. The pathogenesis of cirrhotic PVT is still unclear. However, the activation of Janus kinase/signal transduction and activator transcription signaling pathways, the rise in the expression of von Willebrand factor, and the gut microbiota along with its metabolite trimethylamine-N-oxide play an important role in the injury of vascular endothelial cells and the formation of PVT in cirrhosis. Therefore, these could be a new target for cirrhotic PVT prevention and treatment.

Current concepts in the management of non-cirrhotic non-malignant portal vein thrombosis.

Non-cirrhotic non-malignant portal vein thrombosis (NCPVT) is an uncommon condition characterised by thrombosis of the portal vein, with or without extension into other mesenteric veins, in the absence of cirrhosis or intra-abdominal malignancy. Complications can include intestinal infarction, variceal bleeding and portal biliopathy. In this article, we address current concepts in the management of NCPVT including identification of risk factors, classification and treatment, and review the latest evidence on medical and interventional management options.

Recurrent splanchnic and extrasplanchnic thrombotic events in patients with non-cirrhotic portal vein thrombosis associated with local factors

One third of recent non-cirrhotic portal vein thrombosis are associated with local factors. The risk of rethrombosis after anticoagulation withdrawal is unknown. We aimed to determine factors associated with splanchnic or extrasplanchnic new thrombotic events in that setting. MethodsRetrospective study including recent non-cirrhotic portal vein thrombosis associated with local factors. High and low prothrombotic risk factors, prespecified according to Riport study criteria, were assessed. Quantitative and qualitative variables are presented as median (inter-quartile range), and absolute and relative frequencies respectively. Univariate and multivariate Cox models assessed the influence of different variables on the occurrence of a new thrombotic event. ResultsAt baseline, 83/154 (53.9%) had at least one prothrombotic factor including 50 (32.5%) high-risk and 33 (21.4%) low-risk prothrombotic factors. Oestrogen containing contraception was discontinued in all patients. During follow up, 63/140 (45%) patients had at least one prothrombotic factor, including 47 (33.6%) with a high risk, and 16 (11.4%) a low risk prothrombotic factor. Seventeen new thrombotic events occurred after a median follow-up of 52 (IQR 14-62) (min–max 3.0-69.0) months. New thrombosis were associated with high risk factors (HR 3.817, 95% CI [1.303-11.180], p= 0.015), but inversely related to recanalization (HR 0.222, 95% CI [0.078-0.635], p=0.005) and anticoagulation (HR 0.976, 95% CI [0.956-0.995], p=0.016). When a high-risk factor was present a new thrombotic event occurred in 7.4%, 14.6%, 14.6% and 28.8% of patients at 1, 3, 5 and 7 years under anticoagulants compared to 21.2%, 21.2%, 58% and 58% without anticoagulants. ConclusionsIn recent non-cirrhotic portal vein thrombosis associated with local factors, high risk factors for thrombosis are associated with new thrombotic events. Permanent anticoagulation appears beneficial in this high-risk situation. Impact and implicationsIn noncirrhotic portal vein thrombosis (NCPVT) associated with local factors, systematic screening for prothrombotic factors is recommended, but prevalence of the latter is not clearly established, and the risk of recurrent intra or extra splanchnic thromboembolism is poorly described. Thus, interest in permanent anticoagulation therapy is still pending.NCPVT associated with local factors, is a matter of concern for hepatologists, gastroenterologists and digestive surgeons. Due to a lack of knowledge, practices are heterogeneous.Our findings highlight that systematic screening for prothrombotic factors in NCPVT is strongly needed even when associated with local factors, as it may justify long-term anticoagulation therapy for the prevention of new intra or extra-splanchnic thrombotic events in at least one-third of cases.The interest in long-term anticoagulation should be investigated prospectively in the absence of prothrombotic factors with high risk of thrombosis. Clinical trial numberNCT0536064

Transjugular Intrahepatic Portosystemic Shunt in Nonmalignant Noncirrhotic Portal Vein Thrombosis and Portosinusoidal Vascular Disorder.

Transjugular intrahepatic portosystemic shunt (TIPS) emerges as a key treatment for portal hypertension (PH) complications. While international guidelines provide clear indications for its use in cirrhosis, empirical knowledge is notably scarcer in non-cirrhotic PH, particularly in nonmalignant noncirrhotic portal vein thrombosis (NNPVT) and in patients with portosinusoidal vascular disorder (PSVD). Patients afflicted by these rare diseases exhibit distinct clinical profiles compared to their cirrhotic counterparts, often characterized by a younger age, predominantly preserved hepatic functionality even in cases of severe PH, and a higher propensity for extensive splanchnic thrombosis, which intricately complicates TIPS placement, posing unique challenges for its creation. The objective of this review is to synthesize existing literature on the effectiveness, safety, specific indications, and clinical outcomes of TIPS in adult patients with NNPVT or PSVD, focusing also on the technical challenges of TIPS insertion in the presence of portal cavernoma.

Prothrombotic states in portal vein thrombosis and Budd-Chiari syndrome in India: A systematic review and meta-analysis.

Both Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT) have been linked to various prothrombotic (PT) conditions. The PT profile in Asians is different from the west and there are no nationwide epidemiological surveys from India. Hence, the present meta-analysis was aimed at analyzing the prevalence of acquired and hereditary thrombophilia among Indian patients with non-cirrhotic PVT and BCS. A comprehensive literature search of Embase, Medline and Scopus was conducted from January 2000 to February 2022 for studies evaluating the prevalence of various PT conditions in Indian patients with PVT and BCS. Pooled prevalence rates across studies were expressed with summative statistics. Thirty-five studies with 1005 PVT patients and 1391 BCS patients were included in the meta-analysis. At least one PT condition was seen in 46.2% (28.7-63.7) of the PVT patients and 44.9% (37.3-60.7) of the BCS patients. Multiple PT conditions were seen in 13.0% (4.2-21.8) of the PVT patients and 7.9% (3.5-12.4) of the BCS patients. Among PVT patients, hyperhomocysteinemia was the commonest prothrombotic condition (21.6%) followed by protein C (PC) deficiency (10.7%), Janus kinase 2(JAK-2) mutation (8.5%) and antiphospholipid antibodies (APLA) (7.5%). Among patients with BCS, PC deficiency was the commonest prothrombotic condition (10.6%) followed by methylenetetrahydrofolate reductase (MTHFR) mutation (9.8%), APLA (9.7%) and JAK-2 mutation (9.1%). The PT profile in Indian patients with abdominal vein thrombosis is different from that of the western data with a lower prevalence of PT conditions in patients with BCS.

Transjugular Intrahepatic Portosystemic Shunt and Thrombectomy (TIPS-Thrombectomy) for Symptomatic Acute Noncirrhotic Portal Vein Thrombosis

PurposeTo report the safety and effectiveness of transjugular intrahepatic portosystemic shunt and mechanical thrombectomy (TIPS-thrombectomy) for symptomatic acute noncirrhotic portal vein thrombosis (NC-PVT). Materials and MethodsPatients with acute NC-PVT who underwent TIPS-thrombectomy between 2014 and 2021 at a single academic medical center were retrospectively reviewed. Thirty-two patients were included (men, 56%; median age, 51 years [range, 39–62 years]). The causes for PVT included idiopathic (n = 12), prothrombotic disorders (n = 11), postsurgical sequelae (n = 6), pancreatitis (n = 2), and Budd-Chiari syndrome (n = 1). The indications for TIPS-thrombectomy included refractory abdominal pain (n = 14), intestinal venous ischemia (n = 9), ascites (n = 4), high-risk varices (n = 3), and variceal bleeding (n = 2). Variables studied included patient, disease, and procedure characteristics. Patients were monitored over the course of 1-year follow-up. ResultsSuccessful recanalization of occluded portal venous vessels occurred in all 32 patients (100%). Compared with pretreatment patency, recanalization with TIPS-thrombectomy resulted in an increase in patent veins (main portal vein [28% vs 97%, P < .001], superior mesenteric vein [13% vs 94%, P < .001], and splenic vein [66% vs 91%, P < .001]). Three procedure-related adverse events occurred (Society of Interventional Radiology grade 2 moderate). Hepatic encephalopathy developed in 1 (3%) of 32 patients after TIPS placement. At 1-year follow-up, return of symptoms occurred in 3 (9%) of 32 patients: (a) ascites (n = 1), (b) variceal bleeding (n = 1), and (c) intestinal venous ischemia (n = 1). The intention-to-treat 1-year portal vein and TIPS primary and secondary patency rates were 78% (25/32) and 100% (32/32), respectively. Seven patients required additional procedures, and the 1-year mortality rate was 3% (1/32). ConclusionsTIPS-thrombectomy is a safe and effective method for treating patients with symptomatic acute NC-PVT.

Successful therapy of non-cirrhotic non-malignant portal vein thrombosis (NCNMPT) by interventional therapy using transjugular lysis catheter

NCNMPT is a rare condition with a prevalence of 0.3%. THERAPY: Patient (69 y) with NCNMPT and small bowel ileus received interventional therapy using transjugular local lysis into the superior mesenteric vein. OUTCOME/DISCUSSION: Successful lysis with complete remission. Improved therapeutic efficacy of interventional versus drug therapy alone.

Conservative short-term treatment of non-cirrhotic non-malignant portal vein thrombosis

Introduction. Portal vein (PV) thrombosis (PVT) is a partial or complete obstruction of blood f low as a result of a thrombus mass in the lumen of PV. In the acute phase, the symptoms such as right upper quadrant pain, nausea, and fever are unspecific. A diversity of subacute and chronic symptoms is associated with complications related to PVT and portal hypertension. Case report. A 50-year-old female was admitted to the hospital due to acute abdominal cramping pain. The pain lasted for 15 to 20 min and was followed by defecation of normal stool and hematochezia on three occasions. The abdominal pain recurred after several hours, again followed by hematochezia and tenesmus every 10 min. After admission, a colonoscopy was performed, and it revealed vulnerable, erythematous mucosa of the colon with contact bleeding from the lienal flexure to the rectosigmoid junction. During the colonoscopy, a biopsy was performed. A computed tomography (CT) scan revealed partial PVT of intrahepatic branches of PV, and thrombosis of the inferior mesenteric vein. After conservative treatment with low molecular weight heparin (LMWH) and other supportive measures, the digestive bleeding ceased, and defecation became normal. During the one-month follow-up, the patient had no complications, and the control CT scan revealed normal PV flow without thrombosis. Conclusion. Although rare, a non-malignant and non-cirrhotic PVT should not be neglected in the differential diagnosis because timely and vigilant therapy with LMWH can lead to complete resolution without serious complications.

From the Editor’s Desk…

From the Editor’s Desk…

Rivaroxaban Prophylaxis in Noncirrhotic Portal Vein Thrombosis

BackgroundIn patients with noncirrhotic chronic portal vein thrombosis (PVT), the benefit of long-term anticoagulation is unknown. We assessed the effects of rivaroxaban on the risk of venous thromboembolism and portal hypertension-related bleeding in such patients.MethodsIn this multicenter, controlled trial, we randomly assigned patients with noncirrhotic chronic PVT without major risk factors for thrombosis to receive either rivaroxaban 15 mg/day or no anticoagulation. The primary end point was 2-year thrombosis-free survival. Secondary end points included the occurrence of site-specific thromboses and major bleeding events.ResultsA total of 111 participants were enrolled in the trial, with a mean age of 50.4±13.2 years; 58% of participants were men. An unplanned interim analysis was requested by the independent data safety monitoring board (DSMB) after 10 thrombotic events occurred. The thrombosis incidence rate was 0 per 100 person-years in the rivaroxaban group and 19.71 per 100 person-years (95% confidence interval, 7.49 to 31.92) in the no anticoagulation group (log-rank P=0.0008) after a median follow-up of 11.8 months. Based on the interim analysis, the DSMB recommended switching patients from the no anticoagulation group to anticoagulation. After a median follow-up of 30.3 months (intraquartile range, 24.3 to 47.8), major bleeding occurred in two patients receiving rivaroxaban and in one patient not receiving anticoagulation. No deaths occurred.ConclusionsAfter a median follow-up of 11.8 months, among patients with noncirrhotic chronic PVT without major risk factors for thrombosis, daily rivaroxaban reduced the incidence of venous thromboembolism and did not increase major bleeding events. (Funded by grants from the French Ministry of Health and the Association de Malades des Vaisseaux du foie; ClinicalTrials.gov number, NCT02555111.)

Incidence and factors predictive of recurrent thrombosis in people with non-cirrhotic portal vein thrombosis

Clinical guidelines do not recommend long-term anticoagulation in non-cirrhotic splanchnic vein thrombosis (NC-SVT) without underlying thrombophilia because it is assumed that there is a very low risk of recurrent thrombosis (RT). Our first aim was to describe the incidence of RT in people with NC-SVT without an indication for long-term anticoagulation. The second aim was to identify RT risk factors and afterwards verify them in a validation cohort. This is a multicentre, retrospective observational study evaluating risk factors for RT in 64 people with NC-SVT of idiopathic/local factor aetiology. In a subgroup of 48 individuals, the potential value of additional thrombophilic parameters to predict RT was analysed. Findings were validated in 70 individuals with idiopathic/local factor NC-SVT. Of the 64 participants in the training cohort, 17 (26%) presented splanchnic and/or extrasplanchnic RT (overall-RT) during follow-up (cumulative incidence: 2, 10, 19, and 34% at 1, 2, 5, and 10 years, respectively). In addition, 53% of people with splanchnic RT were asymptomatic. No clinical or biochemical parameters predicted overall-RT. However, in the 48 people with an additional comprehensive thrombophilic study, factor VIII ≥150% was the only independent factor predicting overall-RT (hazard ratio 7.10, 95% CI 2.17-23.17, p <0.01). In the validation cohort, 19 individuals (27%) presented overall-RT, and it was also independently predicted by factor VIII >150% (hazard ratio 3.71, 95% CI 1.31-10.5, p <0.01). The predictive value of factor VIII was confirmed in both people with idiopathic/local factor aetiology associated NC-SVT. People with idiopathic/local factor NC-SVT are at risk of overall-RT. Splanchnic RT can be asymptomatic and requires screening for its detection. Values of factor VIII ≥150% may help identify individuals at high risk of overall-RT who could benefit from long-term anticoagulation. People with idiopathic/isolated local factor non-cirrhotic portal vein thrombosis were previously thought to be at minimal risk of re-thrombosis and therefore did not receive scheduled follow-up. The results of this study are of special interest for hepatologists treating people with non-cirrhotic splanchnic thrombosis, as they show a 25% incidence of re-thrombosis and support the close follow-up of people with factor VIII >150% to ensure the early identification of new thrombotic events.

OS076 - High-risk Thrombophilia predict early thrombosis recurrence in acute non-cirrhotic portal vein thrombosis related to local factors: LOCAPORT

OS076 - High-risk Thrombophilia predict early thrombosis recurrence in acute non-cirrhotic portal vein thrombosis related to local factors: LOCAPORT

Usage of Direct Acting Oral Anticoagulants in Cirrhotic and Non-Cirrhotic Portal Vein Thrombosis: A Systematic Review.

Thrombosis of the portal vein (PVT) is generally seen in the setting of liver cirrhosis and to a lesser extent in the absence of cirrhosis. There is no clear guidance in relation to approaching treatment with anticoagulation in this condition. The professional societies and guidelines recommend treatment with traditional anticoagulation like low-molecular-weight heparin and vitamin-K antagonists in patients presenting with acute portal vein thrombosis. There is no clarity in relation to treatment in the setting of chronic PVT and in patients with cirrhosis. Also, the role of direct-acting oral anticoagulants (DOACs) that are becoming a preferred choice for anticoagulation for various other indications is not clear in the case of PVT. There are a very few studies in the medical literature that have investigated the role of DOACs in patients with PVT in different settings. Thus, we performed a systematic review of the literature to study the use of DOACs in PVT in patients with and without cirrhosis. The results of the available studies show that DOACS appears to be a promising choice for the treatment of patients with PVT. The availability of more data in the future along with better availability of the approved reversal agents for various DOACs is expected to make DOACS a preferred choice for the clinicians to treat patients with PVT.

Portal Vein Thrombosis in Adult Omani Patients-a Retrospective Study

Objective:To study the occurrence of portal vein thrombosis (PVT) in Omani patients.Methods:This is a Retrospective analysis performed on patients diagnosed with PVT which was confirmed by radiological imaging from two tertiary hospitals over a 10 year period.Results:A total of 39 PVT patients were enrolled in this study, with 15(38.5%) showing cirrhosis of liver whereas, 24(61.5%) were classified as non-cirrhotic. Non cirrhotic PVT patients were further subdivided as acute or chronic; 15 (62.5%) had an acute non-cirrhotic PVT whereas the remaining 9 (37.5%) had chronic PVT. PVT were more common in males i.e. 25(64.1%) in contrast to 14(35.9%) females (p=0.02, Chi Square test). Abdominal pain in 64%, nausea in 31.1%, and fever in 20%, gastrointestinal bleeding (hematemesis or melena) 14%, and weight loss in 10%. Demonstrable ascites and splenomegaly were seen in 28% and 38% respectively. Amongst the 18 patients who were tested (majority of non-cirrhotic PVT patients) for an underlying thrombophilia, 4/10(40%) had protein C deficiency, 5/10(50%) had protein S deficiency, and 2/6(33.3%) had antithrombin deficiency. Antiphopholipid antibodies (anti-cardiolipin, lupus anticoagulant and anti-beta2 glycoprotein antibodies) were found in 4/16 (25%) patients, V617F JAK mutation was positive in 3/15 (20%) of patients. Factor V Leiden mutation, prothrombin G20210A mutation, hyperhomocystinemia, and paroxysmal nocturnal hemoglobinuria PNH (tested 7, 4, 2 and 1 patients, respectively) were all negative. Local factors were seen 8 (20.5%) patients of PVT; six had cholangitis and one patient had cholecystitis with and liver abscess. Cirrhosis of liver was the only risk factor in 15(38.5%) patients. However, 8 (53%) cirrhosis patients had hepatocellular carcinoma which is considered as risk for PVT. 13 (33.3%) patients in this study had an underlying malignancy. 8 cases were HCC all noted in cirrhosis patients. Three patients had Cholangiocarcinoma, and one patient had recto-sigmoid carcinoma, and one patient had carcinoma of head pancreas. 18(46.2%) PVT patients received immediate anticoagulation with heparin followed by warfarin, 16 patients (66.7%) were non-cirrhotic PVT. Thrombectomy was done for one patient. 7 (17.9%) patients with acute non-cirrhotic PVT had full recovery and 6(15.4%) of total PVT patients died. 26 (66.7%) patients had no detail follow up as they were lost or their care had been transferred to local hospital but we concluded their condition was stableConclusions:This is the first study reflects the real life practice of portal vein thrombosis which occur due to inherited and acquired prothrombotic conditions and happen as a complications of local and malignant causes. We have studied the prevalence, clinical presentation, treatment given and outcomes. Causative factors were found in 36 patients (92.3%) of the present cohort, etiological screening seems worthwhile in every case with PVT. Significant number of PVT found to have underlying malignancies. Thrombophilia screening may not be cost-effective. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Splanchnic Vein Thrombosis in Overt Myeloproliferative Neoplasms: The Mayo Clinic Experience with 107 Unselected Consecutive Cases

Background:Splanchnic vein thrombosis (SVT) is a characteristic feature of JAK2 mutation-enriched myeloproliferative neoplasms (MPN). MPN constitutes the most frequent cause of Budd-Chiari syndrome (BCS) and non-malignant, non-cirrhotic portal vein thrombosis (Blood. 2012;120:4921). Reported risk factors for recurrent SVT included BCS, thrombosis history, splenomegaly, leukocytosis and absence of warfarin therapy (Blood Cancer J. 2016;6:e493). The main objective of the current study was to share the experience from a single tertiary center.Methods:Study patients were selected from institutional databases, with additional cases identified through Advanced Cohort Explorer Tool. Conventional diagnostic criteria were utilized (Blood 2016;127:2391) Diagnosis of SVT in all cases was confirmed by imaging studies. Cases with latent MPN (MPN-U) or evidence of other cancer were excluded. All analyses considered clinical and laboratory parameters obtained at time of SVT.Results:i) Presenting features107 patients (median age 56 years; range 22-84; 62% females) were considered; specific MPN diagnosis was primary myelofibrosis (PMF) 36%, polycythemia vera (PV) 29%, essential thrombocythemia (ET) 29%, post-PV 6% and post-ET myelofibrosis (MF) 1%. Among evaluable cases, JAK2 mutation was detected in 85% and abnormal karyotype in 33%. At the time of SVT, 80% were not receiving aspirin (ASA) therapy and 4% had history of OCP use. Thrombosis history was recorded in 51% and included history of SVT in 38%. 39 (36%) patients had pre-SVT history of splenectomy, including 16 (15%) in the month before. Presentation included abdominal pain 62%, ascites 31% and GI bleed 15%.ii) Type of SVT and clinical correlatesSVT types included BCS ± other vessels (n=9; 6 PV, 2 ET and 1MF), portal ± splenic (n=73; 38 MF, 20 PV, 15 ET), portal + mesenteric ± splenic (n=23; 14 ET, 5 MF and 4 PV). Comparison of these three SVT categories disclosed significant associations with MPN sub-category (p<0.01; BCS with PV and “portal + mesenteric” with ET), abdominal pain (p=0.02; with BCS and “portal + mesenteric”) and ascites (p=0.007; with BCS).iii) Initial management of SVTInitial treatment included systemic anticoagulation (SA) only in 39% of the patients, SA + ASA 4%, SA + cytoreductive drug 21%, SA + ASA + cytoreductive drug 4%, and no SA 33%. In addition, trans-jugular intrahepatic portosystemic (TIPS) or other surgical shunting was undertaken in 13% and variceal banding in 14%.iv) Post-SVT survival, causes of death and prevalence of liver failureAt median post-SVT follow up of 2.6 years (range .02-17.5), 35 (33%) deaths and 5 (5%) leukemic transformations were noted; the corresponding percentages for PV/ET vs MF were 18% vs 53% and 1.6% vs 9%. Causes of death were unrelated to SVT in 17 instances, unknown in 6, liver failure in 5 (all MF), upper gastrointestinal bleed in 4 (3 MF 1 PV), AML in 2 MF cases and thrombosis in one ET patient.v) Risk factors for post-SVT survival and recurrent SVTAs expected, post-SVT survival was significantly shorter in patients with MF vs PV/ET (HR 4.6, 95% CI 2.2-9.6). In multivariable analysis, older age (p<0.01), MF diagnosis (vs PV/ET) (HR 4.0; 95% CI 1.9-8.4) and presentation with ascites (HR 2.7, 95% CI 1.3-5.8) were independently associated with shorter survival; the latter was also associated with post-SVT complications (p=0.01). When analysis was restricted to the 62 patients with PV/ET, median post-SVT survival was not reached and advanced age was the only predictor of shortened survival (p<0.01), while associations of BCS with PV and “portal + mesenteric” with ET were confirmed (p<0.01). Seven of 8 BCS cases occurred in patients younger than age 60 (p=0.07) and 7 of 8 BCS presented with ascites (p<0.01). The only predictor of SVT relapse was male sex (p<0.01). In general, post-SVT survival and recurrence rate were not affected by type of SVT or initial treatment strategy.Conclusions:Outcome in MPN-associated SVT mostly depends on the underlying MPN type, with limited influence from SVT-directed treatment strategies; importantly, there was no overt evidence of adverse effect, from SVT, on overall or leukemia-free survival in PV or ET; liver failure and GI bleed were relatively frequent causes of death in MF-associated SVT. Other noteworthy observations from the current study included association of BCS with PV, ascites and younger age; and recurrent SVT with male sex. DisclosuresNo relevant conflicts of interest to declare.

Divergences in Macrophage Activation Markers Soluble CD163 and Mannose Receptor in Patients With Non-cirrhotic and Cirrhotic Portal Hypertension.

IntroductionMacrophages are involved in development and progression of chronic liver disease and portal hypertension. The macrophage activation markers soluble (s)CD163 and soluble mannose receptor (sMR), are associated with portal hypertension in patient with liver cirrhosis but never investigated in patients with non-cirrhotic portal hypertension. We hypothesized higher levels in cirrhotic patients with portal hypertension than patients with non-cirrhotic portal hypertension. We investigated sCD163 and sMR levels in patients with portal hypertension due to idiopathic portal hypertension (IPH) and portal vein thrombosis (PVT) in patients with and without cirrhosis.MethodsWe studied plasma sCD163 and sMR levels in patients with IPH (n = 26), non-cirrhotic PVT (n = 20), patients with cirrhosis without PVT (n = 31) and with PVT (n = 17), and healthy controls (n = 15).ResultsMedian sCD163 concentration was 1.51 (95% CI: 1.24–1.83) mg/L in healthy controls, 1.96 (95% CI: 1.49–2.56) in patients with non-cirrhotic PVT and 2.16 (95% CI: 1.75–2.66) in patients with IPH. There was no difference between non-cirrhotic PVT patients and healthy controls, whereas IPH patients had significantly higher levels than controls (P < 0.05). The median sCD163 was significantly higher in the cirrhotic groups compared to the other groups, with a median sCD163 of 6.31 (95% CI: 5.16–7.73) in cirrhotics without PVT and 5.19 (95% CI: 4.18–6.46) with PVT (P < 0.01, all). Similar differences were observed for sMR.ConclusionSoluble CD163 and sMR levels are elevated in patients with IPH and patients with cirrhosis, but normal in patients with non-cirrhotic PVT. This suggests that hepatic macrophage activation is more driven by the underlying liver disease with cirrhosis than portal hypertension.

Treatment of portal vein thrombosis: an updated narrative review.

Portal vein thrombosis (PVT) is the most frequent among the splanchnic vein thrombosis, accounting for 90% of cases. More than half of PVT are provoked by liver cirrhosis, solid cancer or myeloproliferative neoplasms. The remaining cases are non-malignant non-cirrhotic PVT and include either unprovoked events or thrombosis secondary to other less common risk factors (e.g. abdominal surgery, intrabdominal inflammations/infections, or hormonal stimuli). Anticoagulant therapy in patients with acute symptomatic PVT should be started early after diagnosis, if no active bleeding, to obtain greater vessel recanalization and reduce the occurrence of portal-hypertension related complications. Gastroesophageal varices do not represent a contraindication to anticoagulant treatment, as long as adequate measures have been undertaken for the prophylaxis of gastroesophageal bleeding. Different treatment options (unfractionated or low molecular weight heparin, vitamin K antagonists and direct oral anticoagulants [DOACs]) can be considered. In this narrative review we will discuss the treatment of PVT in the three most common scenarios (cirrhosis-associated, cancer-associated and non-malignant non-cirrhotic PVT). We will also discuss the role of the DOACs and summarize recent guidelines on this topic.

Increased Morbidity and Mortality of Patients with Non-cirrhotic Portal Vein Thrombosis After Abdominal and Pelvic Surgeries: a Study of the National Inpatient Sample 2002 to 2015

BackgroundA higher rate of postoperative morbidity and mortality in patients with portal hypertension from cirrhosis is well recognized; however, the rate of postoperative morbidity and mortality among patients with portal hypertension from non-cirrhotic portal vein thrombosis (NCPVT) is largely unknown. MethodAll adults undergoing abdominal and pelvic surgery were identified from the National Inpatient Sample database from 2002 to 2015. Patients were then categorized into three groups: non-cirrhotic non-portal vein thrombosis (NCNPVT), NCPVT, and cirrhotic portal vein thrombosis (CPVT). Inpatient mortality, type of disposition, transfusions, length of stay, postoperative complications, and total charges were compared. Logistic regression and ordinary least squares regression analyses were performed for factors associated with inpatient mortality, transfusions, surgery-related complications, and log length of stay. ResultsPatients with NCPVT had significantly higher inpatient mortality rates, surgery-related complications, and longer length of stays compared with patients with NCNPVT (2.64% vs. 0.34%, 10.26% vs. 3.26%, 8 vs. 2 days) but less than patients with CPVT (2.64% vs. 6.31%, 10.26% vs. 17.48%, 8 vs. 11 days). In multiple logistic regression analyses, NCPVT groups remained associated with increased inpatient mortality rate, transfusions, and postoperative complications with odds ratios of 3.71 (1.88, 7.32), 3.43 (2.54, 4.62), and 3.08 (2.16, 4.39), respectively. NCPVT was also associated with 2.4 times increased length of stay. DiscussionPatients with NCPVT had significantly higher risks of postoperative morbidity and mortality than patients with NCNPVT but less than patients with CPVT. Future studies with detail regarding the characteristics of PVTs are needed to confirm the findings in this study.

Next-generation sequencing in the diagnosis of non-cirrhotic splanchnic vein thrombosis

Myeloproliferative neoplasms (MPNs) are the most frequent cause of non-tumoural non-cirrhotic splanchnic vein thrombosis (NC-SVT). Diagnosis of MPN is based on blood cell count alterations, bone marrow histology, anddetection of specific gene mutations. Next-generation sequencing (NGS) allows the simultaneous evaluation of multiple genes implicated in myeloid clonal pathology. The aim of this study was to evaluate the potential role of NGS in elucidating the aetiology of NC-SVT. DNA samples from 80 patients (75 with idiopathic or exclusively local factor [Idiop/loc-NC-SVT] and 5 with MPN and NC-SVT [SVT-MPN] negative for Janus kinase 2 gene [JAK2] [V617F and exon 12], calreticulin gene [CALR], and thrombopoietin gene [MPL] mutations by classic techniques) were analysed by NGS. Mutations involved in myeloid disorders different from JAK2, CALR, and MPL genes were categorised as high-molecular-risk (HMR) variants or variants of unknown significance. In 2/5 triple-negative SVT-MPN cases (40%), a mutation in exon 12 of JAK2 was identified. JAK2-exon 12 mutation was also identified in 1/75 patients with Idiop/loc-NC-SVT. Moreover, 28/74 (37.8%) of the remaining Idiop/loc-NC-SVT had at least 1 HMR variant. Sixty-two patients with Idiop/loc-NC-SVT were not receiving long-term anticoagulation and 5 of them (8.1%) had recurrent NC-SVT. This cumulative incidence was significantly higher in patients with HMR variants than in those without. NGS identified JAK2-exon12 mutations not previously detected by conventional techniques. In addition, NGS detected HMR variants in approximately one-third of patients with Idiop/loc-NC-SVT. These patients seem to have a higher risk of splanchnic rethrombosis. NGS might be a useful diagnostic tool in NC-SVT. Next-generation sequencing (NGS) performs massive sequencing of DNA allowing the simultaneous evaluation of multiple genes even at very low mutational levels. Application of this technique in a cohort of patients with non-cirrhotic non-tumoral portal vein thrombosis (NC-SVT) and a negative study for thrombophilic disorders was able to identify patients with a mutation in exon 12 not previously detected by conventional techniques. Moreover, NGS detected High Molecular Risk (HMR)-variants (Mutations involved in myeloid disorders different from JAK2, CALR and MPL genes) in approximately one third of patients. These patients appear to be at increased risk of rethrombosis. All these findings supports NGS as a potential useful tool in the management of NC-SVT.

PORTAL CAVERNOMA AS A CAUSE OF HEMATEMESIS IN A YOUNG UNMARRIED FEMALE: A CASE REPORT

Thrombotic incidents are usually uncommon in unusual sites like portal vein and further in the adolescent age group which presents a potential diagnostic dilemma. Chronic non-cirrhotic non-malignant portal vein thrombosis (PVT) can present at any age group, usually as acute upper gastrointestinal (UGI) bleed. Diagnosis depends on imaging modalities involving Doppler, computed tomography (CT), magnetic resonance imaging, and portography. We report the case of a 20-year-old unmarried girl presented with multiple episodes of hematemesis. Ultrasonography abdomen and CT abdomen revealed PVT with portal cavernous transformation of the portal vein. Her prothrombin time and activated partial thromboplastin time were normal. Her connective tissue workup was normal. A diagnosis of PVT secondary to umbilical vein sepsis during infancy was made. Adolescent patients presented with acute hematemesis should not be neglected for some local cause of UGI bleed but should be evaluated for other rare causes like PVT, for early diagnosis and management to reduce feared complications.