Role of splanchnic circulation in the pathogenesis of heart failure: State-of-the-art review.

A hallmark of heart failure (HF), whether it presents itself during rest or periods of physical exertion, is the excessive elevation of intracardiac filling pressures at rest or with exercise. Many mechanisms contribute to the elevated intracardiac filling pressures, and notably, the concept of volume redistribution has gained attention as a cause of the elevated intracardiac filling pressures in patients with HF, particularly HF with preserved ejection fraction, who often present without symptoms at rest, with shortness of breath and fatigue appearing only during exertion. This phenomenon suggests cardiopulmonary system non-compliance and inappropriate volume distribution between the stressed and unstressed blood volume components. A substantial proportion of the intravascular blood volume is in the splanchnic vascular compartment in the abdomen. Preclinical and clinical investigations support the critical role of the sympathetic nervous system in modulating the capacitance and compliance of the splanchnic vascular bed via modulation of the greater splanchnic nerve (GSN). The GSN activation by stressors such as exercise causes excessive splanchnic vasoconstriction, which may contribute to the decompensation of chronic HF via volume redistribution from the splanchnic vascular bed to the central compartment. Accordingly, for example, GSN ablation for volume management has been proposed as a potential therapeutic intervention to increase unstressed blood volume. Here we provide a comprehensive review of the role of splanchnic circulation in the pathogenesis of HF and potential novel treatment options for redistributing blood volume to improve symptoms and prognosis in patients with HF.

Splanchnic vein thrombosis in necrotizing pancreatitis: a post-hoc analysis of a nationwide prospective cohort.

BACKGROUND: Treatment guidelines for splanchnic vein thrombosis in necrotizing pancreatitis are lacking due to insufficient data on the full clinical spectrum. METHODS: We performed a post-hoc analysis of a nationwide prospective necrotizing pancreatitis cohort. Multivariable analyses were used to identify risk factors and compare the clinical course of patients with and without SVT. RESULTS: SVT was detected in 97 of the 432 included patients (22%) (median onset: 4 days). Risk factors were left, central, or subtotal necrosis (OR 28.52; 95% CI 20.11-40.45), right or diffuse necrosis (OR 5.76; 95% CI 3.89-8.51), and younger age (OR 0.94; 95% CI 0.90-0.97). Patients with SVT had higher rates of bleeding (n = 10,11%) and bowel ischemia (n = 4,4%) compared to patients without SVT (n = 14,4% and n = 2,0.6%; OR 3.24; 95% CI 1.27-8.23 and OR 7.29; 95% CI 1.31-40.4, respectively), and were independently associated with ICU admission (adjusted OR 2.53; 95% CI 1.37-4.68). Spontaneous recanalization occurred in 62% of patients (n = 40/71). Radiological and clinical outcomes did not differ between patients treated with and without anticoagulants. DISCUSSION: SVT is a common and early complication of necrotizing pancreatitis, associated with parenchymal necrosis and younger age. SVT is associated with increased complications and a worse clinical course, whereas anticoagulant use does not appear to affect outcomes.

Natural history of cancer-associated splanchnic vein thrombosis.

BACKGROUND: There is uncertainty in the management of cancer-associated isolated splanchnic vein thrombosis (SpVT). OBJECTIVES: To describe the natural history of SpVT by cancer type and thrombus composition and to review anticoagulation (AC) practices and associated rates of usual-site venous thromboembolism (VTE), major and clinically relevant nonmajor bleeding (MB/CRNMB), recanalization/progression, and mortality. METHODS: We performed a retrospective cohort study in patients with SpVT at 2 cancer care centers in Houston, Texas. We estimated the incidence of usual-site VTE and MB/CRNMB at 6 months using competing risk methods and examined venous patency in a subset of patients with repeat imaging. We assessed associations with mortality using Cox regression. RESULTS: Among 15 342 patients with an incident cancer diagnosis from 2011 to 2020, we identified 298 with isolated SpVT. Patients with hepatocellular carcinoma (HCC) and SpVT (n = 146) had the highest disease prevalence (20%), lowest rate of AC treatment (2%), and similar rate of usual-site VTE (4.2%) vs those without SpVT (5.2%) at 6 months, though tumor thrombus vs bland was associated with worse overall survival. In patients with non-HCC bland SpVT (n = 114), AC (n = 37) was more common in those with non-upper gastrointestinal cancers and fewer comorbidities. AC was associated with more recanalization (44% vs 15%, P = .041) but no differences in usual-site VTE, MB/CRNMB, or mortality at 6 months. CONCLUSION: Cancer-associated isolated SpVT is a common but heterogeneous thrombotic disease that is treated differently from usual-site VTE. Tumor thrombus is a negative prognostic factor. Initiation of AC in bland thrombi requires judicious consideration of thrombotic and bleeding risk.

[Modern biochemical markers of acute mesenteric ischemia]. / Sovremennye biokhimicheskie markery ostroi mezenterial'noi ishemii.

OBJECTIVE: To analyze modern literature data on biochemical markers of critical mesenteric ischemia. MATERIAL AND METHODS: We analyzed the most promising, highly specific and sensitive biochemical markers of total and segmental intestinal damage following acute mesenteric ischemia. Analysis included domestic and foreign literature data between 2015 and 2023. RESULTS: We identified the most easy-to-use for any hospitals biochemical markers with at least 90% sensitivity and specificity for further practical research. CONCLUSION: Further prospective research will provide a new step in solving the problem of timely diagnosis of acute mesenteric circulatory disorders.

Cancer-associated splanchnic vein thrombosis: Clinical implications and management considerations.

Splanchnic vein thrombosis (SVT), a thrombosis which involves the portal, mesenteric, and splenic veins, and the Budd-Chiari syndrome, represents an uncommon type of venous thromboembolism (VTE). Like with deep vein thrombosis of the lower extremities and pulmonary embolism, ample evidence suggests a significant association between SVT and cancer, particularly intra-abdominal solid malignancies (e.g. hepatobiliary and pancreatic cancers) and myeloproliferative neoplasms (MPN). Clinical symptoms of SVT in cancer patients can be ambiguous, and frequently attributed to the primary cancer itself. Alternatively, SVT may be asymptomatic and detected incidentally during cancer staging or follow-up evaluations. SVT can also precede the diagnosis of cancer and has been associated with poorer outcomes in patients with liver or pancreatic cancers. Therefore, an unprovoked SVT warrants a thorough evaluation for an underlying malignancy or MPN. Cancer-associated SVT carries a high risk of VTE extension, recurrence and bleeding. Extended anticoagulant treatment is often required in the absence of a high bleeding risk. Guidelines suggest treatment with either low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs), although available data on the safety and effectiveness of DOACs in these patients is limited. This comprehensive review outlines the epidemiology, pathogenesis, risk factors, and diagnosis of cancer-associated SVT and underscores the importance of comprehensive patient evaluation and evidence-based management.

Metabolic Tissue Swelling and Local Microcirculation in Splanchnic Artery Occlusion Shock: Implications for Critical Illness.

Trauma is a leading cause of death in the United States. Advancements in shock resuscitation have been disappointing because the correct upstream mechanisms of injury are not being targeted. Recently, significant advancements have been shown using new cell-impermeant molecules that work by transferring metabolic water from swollen ischemic cells to the capillary, which restores tissue perfusion by microcirculatory decompression. The rapid normalization of oxygen transfer improves resuscitation outcomes. Since poor resuscitation and perfusion of trauma patients also causes critical illness and sepsis and can be mimicked by ischemia-reperfusion of splanchnic tissues, we hypothesized that inadequate oxygenation of the gut during trauma drives development of later shock and critical illness. We further hypothesized that this is caused by ischemia-induced water shifts causing compression no-reflow. To test this, the superior mesenteric artery of juvenile anesthetized swine was occluded for 30 minutes followed by 8 hours of reperfusion to induce mild splanchnic artery occlusion (SAO) shock. One group received the impermeant polyethylene glycol 20,000 Da (PEG-20k) that prevents metabolic cell swelling, and the other received a lactated Ringer's vehicle. Survival doubled in PEG-20k-treated swine along with improved macrohemodynamics and intestinal mucosal perfusion. Villus morphometry and plasma inflammatory cytokines normalized with impermeants. Plasma endotoxin rose over time after reperfusion, and impermeants abolished the rise. Inert osmotically active cell impermeants like PEG-20k improve intestinal reperfusion injury, SAO shock, and early signs of sepsis, which may be due to early restoration of mucosal perfusion and preservation of the septic barrier by reversal of ischemic compression no-reflow. SIGNIFICANCE STATEMENT: Significant advancements in treating shock and ischemia have been disappointing because the correct upstream causes have not been targeted. This study supports that poor tissue perfusion after intestinal ischemia from shock is caused by capillary compression no-reflow secondary to metabolic cell and tissue swelling since selectively targeting this issue with novel polyethylene glycol 20,000 Da-based cell-impermeant intravenous solutions reduces splanchnic artery occlusion shock, doubles survival time, restores tissue microperfusion, and preserves gut barrier function.

A narrative review of acute pancreatitis-induced splanchnic vein thrombosis: from pathogenesis to clinical management.

Acute pancreatitis-induced splanchnic vein thrombosis (APISVT) is an important sequela complication of acute pancreatitis, which may cause poor prognosis, such as severe gastrointestinal hemorrhage, bowel ischemic necrosis and liver failure. However, its mechanism remains uncertain, and there is not a general consensus on the management. In this study, we reviewed the latest academic publications in APISVT, and discussed its pathogenesis, clinical presentation, adverse outcome and treatment, especially focused on the role of anticoagulant therapy. It was indicated that anticoagulation therapy can significantly elevate thrombus recanalization and reduce the incidence of complications and mortality with no increase of bleeding. Actually, as most of these studies were retrospective analyses and prospective studies included small samples, the conclusion remains controversial. Thus, well-designed randomized controlled trials are urged to verify the effectiveness and safety of anticoagulation therapy for APISVT.

Efficacy and safety of direct oral anticoagulants in splanchnic vein thrombosis: a pooled analysis of literature studies.

BACKGROUND: Limited evidence is available on management of splanchnic vein thrombosis (SVT). OBJECTIVES: This study aimed to evaluate safety and efficacy of direct oral anticoagulants (DOACs) for SVT treatment. METHODS: Studies were systematically searched in the PubMed, Web of Science, and Scopus databases according to PRISMA guidelines. We assessed any recanalization, full recanalization, recurrence, mortality, and major bleeding as outcomes of interest. Results were reported as weighted mean prevalence (WMP) with 95% CI. Subgroup analyses and meta-regressions have been performed to address heterogeneity and adjust for potential confounders. RESULTS: We included a total of 16 studies (17 datasets) on 648 patients with SVT treated with DOACs. We found any recanalization in 60.3% (95% CI: 41.8%-76.3%; I2 = 84.9%; P < .001) and full recanalization in 51.7% (95% CI: 36.0%-67.0%; I2 = 87.4%; P < .001). Recurrent venous thromboembolism occurred in 2.8% (95% CI: 1.4%-5.9%; I2 = 0%; P = .787) and death in 3.4% (95% CI: 1.6%-7.3%; I2 = 13.2%; P = .318) of patients. Major bleeding was reported by 5.8% (95% CI: 3.7%-8.9%; I2 = 29.2%; P = .125) of patients. Results were consistent when separately analyzing prospective studies, retrospective studies, studies on cirrhotic patients, and studies enrolling patients with portal vein thrombosis. Meta-regression analyses showed that an increasing age and cancer impacted the rate of recanalization. Cirrhosis was associated with a higher rate of major bleeding and mortality. CONCLUSION: The results of the present study, mostly based on observational studies, suggest good safety and efficacy profiles of DOACs in patients with SVT. Randomized studies are needed to corroborate our findings.

How to manage splanchnic vein thrombosis in patients with liver disease.

Liver cirrhosis and splanchnic vein thrombosis (SVT) are strictly correlated. Portal vein thrombosis, the most common location of SVT, is frequently diagnosed in liver cirrhosis (pooled incidence 4.6 per 100 patient-years), and liver cirrhosis is a common risk factor for SVT (reported in 24%-28% of SVT patients). In cirrhosis-associated SVT, anticoagulant treatment reduces mortality rates, thrombosis extension, and major bleeding, and increases the rates of recanalization, compared to no treatment. Achieving vessel recanalization improves the prognosis of cirrhotic patients by reducing liver-related complications (such as variceal bleeding, ascites, hepatic encephalopathy). Anticoagulation should be therefore routinely prescribed to cirrhotic patients with acute SVT unless contraindicated by active bleeding associated with hemodynamic impairment or by excessively high bleeding risk. Of note, early treatment is associated with higher probability of achieving vessel recanalization. The standard treatment consists of low-molecular-weight heparin, followed by oral anticoagulants (eg, vitamin K antagonists or direct oral anticoagulants), if not contraindicated by severe liver dysfunction. Cirrhotic patients with SVT should be treated long-term (especially if candidate for liver transplantation) since liver cirrhosis is a persistent risk factor for recurrent thrombosis. In this review, we discuss the management of SVT in patients with liver cirrhosis, with a focus on the anticoagulant treatment in terms of indications, timing, drugs, duration, and particular scenarios, such as gastroesophageal varices and thrombocytopenia.

Cancer-associated splanchnic vein thrombosis: Clinical features upon diagnosis and short-term outcomes.

INTRODUCTION: The incidence of splanchnic vein thrombosis (SVT) in cancer patients has increased in recent years and its real clinical significance and management can be challenging. This study aimed to describe the clinical presentation and short-term outcomes of patients with cancer-associated SVT. MATERIAL AND METHODS: This was a retrospective observational study of consecutive patients with cancer-associated SVT diagnosed during the period 2015-2020. The primary objective was to describe the clinical presentation of SVT. Patients were clinically classified into two groups based on the presence of symptoms on SVT diagnosis. The main outcomes were overall and SVT-related mortality, major and non-major bleeding rates, and the thrombosis recurrence rate in the first 30 days of follow-up. RESULTS: This study enrolled 203 patients. Intra-abdominal tumors (76 %) and metastatic disease (68 %) predominated. A total of 79 (39 %) patients without symptoms were diagnosed with SVT during a scheduled radiological test and were classified as "asymptomatic", while 124 (61 %) patients presented some potential SVT symptoms and were considered as "symptomatic". Although the 30-day outcomes showed no significant differences between the two groups, mortality in the asymptomatic group was slightly lower compared to the symptomatic group (3 % vs. 10 %, p = 0.085). CONCLUSIONS: Almost 40 % of cases of cancer-associated SVT are asymptomatic. There were no significant differences in short-term outcomes between the symptomatic and asymptomatic patients. More studies are required to better define long-term management and outcomes in these patients.

Anticoagulation Therapy for Splanchnic Vein Thrombosis Associated With Acute Pancreatitis: A Systematic Review and Meta-Analysis.

Splanchnic vein thrombosis (SVT) is not rare in patients with acute pancreatitis. It remains unclear about whether anticoagulation should be given for acute pancreatitis-associated SVT. The PubMed, EMBASE, and Cochrane Library databases were searched. Rates of SVT recanalization, any bleeding, death, intestinal ischemia, portal cavernoma, and gastroesophageal varices were pooled and compared between patients with acute pancreatitis-associated SVT who received and did not receive therapeutic anticoagulation. Pooled rates and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Heterogeneity among studies was evaluated. Overall, 16 studies including 698 patients with acute pancreatitis-associated SVT were eligible. After therapeutic anticoagulation, the pooled rates of SVT recanalization, any bleeding, death, intestinal ischemia, portal cavernoma, and gastroesophageal varices were 44.3% (95%CI = 32.3%-56.6%), 10.7% (95%CI = 4.9%-18.5%), 13.3% (95%CI = 6.9%-21.4%), 16.8% (95%CI = 6.9%-29.9%), 21.2% (95%CI = 7.5%-39.5%), and 29.1% (95%CI = 16.1%-44.1%), respectively. Anticoagulation therapy significantly increased the rate of SVT recanalization (RR = 1.69; 95%CI = 1.29-2.19; P < .01), and marginally increased the risk of bleeding (RR = 1.98; 95%CI = 0.93-4.22; P = .07). The rates of death (RR = 1.42; 95%CI = 0.62-3.25; P = .40), intestinal ischemia (RR = 2.55; 95%CI = 0.23-28.16; P = .45), portal cavernoma (RR = 0.51; 95%CI = 0.21-1.22; P = .13), and gastroesophageal varices (RR = 0.71; 95%CI = 0.38-1.32; P = .28) were not significantly different between patients who received and did not receive anticoagulation therapy. Heterogeneity was statistically significant in the meta-analysis of intestinal ischemia, but not in those of SVT recanalization, any bleeding, death, portal cavernoma, or gastroesophageal varices. Anticoagulation may be effective for recanalization of acute pancreatitis-associated SVT, but cannot improve the survival. Randomized controlled trials are warranted to further investigate the clinical significance of anticoagulation therapy in such patients.

Therapeutic anticoagulation for splanchnic vein thrombosis in acute pancreatitis: A national survey and case-vignette study.

BACKGROUND: Splanchnic vein thrombosis (SVT) is a major complication of moderate and severe acute pancreatitis. There is no consensus on whether therapeutic anticoagulation should be started in patients with acute pancreatitis and SVT. AIM: To gain insight into current opinions and clinical decision making of pancreatologists regarding SVT in acute pancreatitis. METHODS: A total of 139 pancreatologists of the Dutch Pancreatitis Study Group and Dutch Pancreatic Cancer Group were approached to complete an online survey and case vignette survey. The threshold to assume group agreement was set at 75%. RESULTS: The response rate was 67% (n = 93). Seventy-one pancreatologists (77%) regularly prescribed therapeutic anticoagulation in case of SVT, and 12 pancreatologists (13%) for narrowing of splanchnic vein lumen. The most common reason to treat SVT was to avoid complications (87%). Acute thrombosis was the most important factor to prescribe therapeutic anticoagulation (90%). Portal vein thrombosis was chosen as the most preferred location to initiate therapeutic anticoagulation (76%) and splenic vein thrombosis as the least preferred location (86%). The preferred initial agent was low molecular weight heparin (LMWH; 87%). In the case vignettes, therapeutic anticoagulation was prescribed for acute portal vein thrombosis, with or without suspected infected necrosis (82% and 90%), and thrombus progression (88%). Agreement was lacking regarding the selection and duration of long-term anticoagulation, the indication for thrombophilia testing and upper endoscopy, and about whether risk of bleeding is a major barrier for therapeutic anticoagulation. CONCLUSION: In this national survey, the pancreatologists seemed to agree on the use of therapeutic anticoagulation, using LMWH in the acute phase, for acute portal thrombosis and in the case of thrombus progression, irrespective of the presence of infected necrosis.

Anticoagulant treatment for pediatric splanchnic vein thrombosis: a systematic review and meta-analysis.

BACKGROUND: The clinical characteristics of splanchnic vein thrombosis (SVT) in pediatric patients and its optimal treatment strategies are unknown. OBJECTIVES: This study aimed to assess the effectiveness and safety of anticoagulant therapy for pediatric SVT. METHODS: MEDLINE and EMBASE databases were searched up to December 2021. We included observational and interventional studies that enrolled pediatric patients with SVT and reported anticoagulant treatment and outcomes, including rates of vessel recanalization, SVT extension, venous thromboembolism (VTE) recurrence, major bleeding, and mortality. Pooled proportions of vessel recanalization were calculated with their 95% CI. RESULTS: A total of 506 pediatric patients (aged 0-18 years) across 17 observational studies were included. The majority of patients had portal vein thrombosis (n = 308, 60.8%) or Budd-Chiari syndrome (n = 175, 34.6%). Most events were triggered by transient provoking factors. Anticoagulation (heparins and vitamin K antagonists) was prescribed in 217 (42.9%) patients, and 148 (29.2%) patients underwent vascular interventions. The overall pooled proportions of vessel recanalization were 55.3% (95% CI, 34.1%-74.7%; I2 = 74.0%) among anticoagulated patients and 29.4% (95% CI, 2.6%-86.6%; I2 = 49.0%) among non-anticoagulated patients. SVT extension, major bleeding, VTE recurrence, and mortality rates were 8.9%, 3.8%, 3.5%, and 10.0%, respectively, in anticoagulated patients and 2.8%, 1.4%, 0%, and 50.3%, respectively, in non-anticoagulated patients. CONCLUSION: In pediatric SVT, anticoagulation appears to be associated with moderate recanalization rates and a low risk of major bleeding. VTE recurrence is low and comparable to that reported in pediatric patients with other types of provoked VTE.

Immediate Norepinephrine in Endotoxic Shock: Effects on Regional and Microcirculatory Flow.

OBJECTIVES: To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock. DESIGN: Animal experimental study. SETTING: University translational research laboratory. SUBJECTS: Fifteen Landrace pigs. INTERVENTIONS: Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance. MEASUREMENTS AND MAIN RESULTS: Hypotension was significantly shorter in i-NE group (7.5 min [5.5-22.0 min] vs 49.3 min [29.5-60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively). CONCLUSIONS: In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.

Myeloproliferative neoplasms and splanchnic vein thrombosis: Contemporary diagnostic and therapeutic strategies.

Myeloproliferative neoplasms (MPNs) are the most common etiologies of primary splanchnic vein thrombosis, present in almost forty percent of patients with Budd-Chiari syndrome or portal vein thrombosis. Diagnosis of MPNs can be difficult in these patients because key characteristics, such as elevated blood cell counts and splenomegaly, are confounded by portal hypertension or bleeding complications. In recent years, diagnostic tools have improved to provide more accurate diagnosis and classification of MPNs. Although bone marrow biopsy findings remain a major diagnostic criterion, molecular markers are playing an increasing role not only in diagnosis but also in better estimating prognosis. Therefore, though screening for JAK2V617F mutation should be the starting point of the diagnostic workup performed in all patients with splanchnic vein thrombosis, a multidisciplinary approach is needed to accurately diagnose the subtype of myeloproliferative neoplasm, recommend the useful additional tests (bone marrow biopsy, search for an additional mutation using targeted next-generation sequencing), and suggest the best treatment strategy. Indeed, providing a specific expert care pathway for patients with splanchnic vein thrombosis and underlying myeloproliferative neoplasm is crucial to determine the optimal management to reduce the risk of both hematological and hepatic complications.

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

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. IMPACT AND IMPLICATIONS: 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.