Search Results (17)

Direct oral anticoagulants (DOACs) have emerged as the preferred oral anticoagulant therapy for patients with deep vein thrombosis of the lower extremities and pulmonary embolism. DOACs offer several advantages over vitamin K antagonists, including fixed dosage, fewer drug interactions, faster onset of action, and a lower risk of major bleeding, especially intracranial. Although evidence on the use of DOACs in unusual-site venous thrombosis (USVT) is limited, their use in such cases is becoming increasingly common. This narrative review examines the evidence derived from randomized controlled trials, and large observational studies focused on the use of the DOACs in USVT, including cerebral, splanchnic, upper extremity, ovarian, renal, and retinal vein thrombosis. In addition, it also provides practical advice for their use in these clinical settings according to the updated scientific literature. Full article

Background: Portal vein thrombosis (PVT) leads to portal hypertension (PH) with its sequelae. Computed tomography spleno-mesenterico-portography (CT-SMPG) combines sequential CT spleno-portography and CT mesenterico-portography. CT-SMPG comprehensively illustrates the venous hemodynamic changes due to PH. Objective: To assess the effects of PV confluence thrombosis (PVCT) and liver cirrhosis on venous blood flow characteristics of patients with PVT. Method: CT-SMPG was performed in 21 patients with chronic PVT. CT-SMPG was compared to standard contrast-enhanced CT (CECT) and gastroscopy concerning the patency of splanchnic veins, varices and venous congestion. Results: PVCT had a significant effect on perfusion patterns: in patients without PVCT, esophageal varices (EV) and gastric varices were supplied by either the splenic vein (SV), the superior mesenteric vein (SMV), or both. In patients with PVCT, EV and gastric varices were mostly supplied by the SV (p = 0.021, p = 0.016). In patients without PVCT, small bowel varices were fed by both systems or the SMV, while in patients with PVCT they were fed by the SMV (p = 0.031). No statistically significant changes were detected regarding gastropathy, colorectal varices and small bowel congestion. Liver cirrhosis had no statistically relevant effect on hemodynamics. Conclusions: In CT-SMPG, patients with PVCT showed different venous hemodynamics to patients without PVCT, and this can serve as a basis for selecting therapy options. Full article

Deep venous thrombosis (DVT) is a pathological condition that develops when a thrombus forms within the deep venous system. Typically, it involves the lower limbs and, less frequently, the upper extremities or other unusual districts such as cerebral or splanchnic veins. While leg DVT itself is rarely fatal and occasionally can lead to limb-threatening implications, its most fearsome complication, namely pulmonary embolism, is potentially fatal and significantly contributes to increased healthcare costs and impaired quality of life in affected patients and caregivers. Thanks to its high accuracy, ease of use, and safety profile, duplex ultrasound (DUS), particularly compression ultrasound (CUS), has emerged as the first-line imaging modality for DVT diagnosis. The evaluation of suspected DVT needs a multifaceted approach, and in this context, CUS rapidly became a key diagnostic tool owing to its many unique advantages. Its central role in the diagnostic algorithm of suspected DVT is clearly established in the latest clinical practice guidelines from the European Society for Vascular Surgery and the American Society of Haematology. Indeed, DUS effectively visualizes blood flow and identifies abnormalities like clot formation with high sensitivity (typically exceeding 90% for proximal DVT) and specificity (often approaching 100% for proximal DVT). Additionally, CUS is non-invasive, readily available at the bedside, and avoids radiation exposure, resulting in an ideal method for various clinical settings. CUS has been shown to have a substantial role not only in the diagnosis of an acute DVT but also in the follow-up of its management. Moreover, this method can provide a prognostic assessment, mostly in terms of risk stratification for recurrent thrombosis and/or for potential complications, such as post-thrombotic syndrome. In summary, given its established benefits, CUS is a technique that many physicians should be familiar with, especially those working in emergency departments, intensive care units, or general wards. When needed, healthcare operators with more advanced US skills (such as radiologists, angiologists, or vascular surgeons) may be called upon to provide a second look in case of uncertainty and/or need for additional information. Full article

Introduction. Cancer-associated thrombosis is a significant prognostic marker in pancreatic neoplasia, with a venous thromboembolism incidence of 17–34%. This study focuses on cancer-associated thrombosis risk factors, screening scores, and treatment options. Materials and Methods. Comprehensive database searches were conducted across Web of Science, PubMed, Reaxys, ScienceDirect, and Scopus. Results. Of the 37 articles reviewed, findings include splanchnic vein thrombosis correlating with pancreatic complications and survival rates. Gender differences in cancer-associated thrombosis risk were inconclusive, while African Americans showed a higher incidence of pulmonary embolism. Various cancer-associated thrombosis staging scores were evaluated, with ONKOTEV score outperforming Khorana. Direct oral anticoagulants were suggested as viable alternatives to low molecular weight heparins. Non-anticoagulant sulfated low molecular weight heparin emerged as a future option, offering reduced bleeding risks with similar efficacy. Conclusions. Managing cancer-associated thrombosis in pancreatic cancer is challenging, highlighting the need for improved understanding, better screening methods, and more effective treatments. Full article

Cancer is associated with an increased risk of developing venous thromboembolism, due to its direct influence on the three pillars of Virchow’s triad (e.g., compression on the blood vessels by the tumour, blood vessels invasion, and cytokine release), together with the effect of exogenous factors (such as chemotherapy, radiotherapy, surgery). In cancer patients, the risk of thrombosis at unusual sites, such as splanchnic, ovarian and renal vein thrombosis, is also increased. Abdominal vein thromboses are frequently incidental findings on abdominal imaging performed as part of the diagnostic/staging workup or the follow-up care of malignancies. There is little evidence on the management of unusual site venous thromboembolism in cancer patients since there are only a few specific recommendations; thus, the management follows the general principles of the treatment of cancer-associated deep vein thrombosis and pulmonary embolism. This narrative review summarises the latest evidence on cancer-associated abdominal vein thrombosis, i.e., thrombosis of the splanchnic, ovarian and renal veins. Full article

Splanchnic vein thrombosis (SVT) encompasses thrombosis in the vessels of the splanchnic basin and has a relatively rare occurrence with a reported frequency in the general population of 1–2%. An episode of seemingly unprovoked SVT almost always triggers a diagnostic work-up for a Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), since atypical site thrombosis is a hallmark of MPN-associated thrombophilia. Primary myelofibrosis (PMF) is a rare MPN with an estimated incidence between 0.1 and 1/100,000 per year. Although prothrombotic tendency in PMF is not envisioned as a subject of specific therapeutic management, unlike other MPNs, such as polycythemia vera (PV) and essential thrombocythemia (ET), thrombotic risk and SVT prevalence in PMF may be comparably high. Additionally, unlike PV and ET, SVT development in PMF may depend more on procoagulant mechanisms involving endothelium than on blood cell activation. Emerging results from registry data also suggest that PMF patients with SVT may exhibit lower risk and better prognosis, thus highlighting the need for better thrombotic risk stratification and identifying a subset of patients with potential benefit from antithrombotic prophylaxis. This review highlights specific epidemiological, pathogenetic, and clinical features pertinent to SVT in myelofibrosis. Full article

An effective worldwide vaccination campaign started and is still being carried out in the face of the coronavirus disease 2019 (COVID-19) pandemic. While vaccines are great tools to confront the pandemic, predominantly adenoviral vector-based vaccines can cause a rare severe adverse effect, termed vaccine-induced immune thrombocytopenia and thrombosis (VITT), in about 1 in 100,000 vaccinated individuals. VITT is diagnosed 5–30 days post-vaccination and clinically characterized by thrombocytopenia, strongly elevated D-dimer levels, platelet-activating anti-platelet factor 4 (PF4) antibodies and thrombosis, especially at atypical sites such as the cerebral venous sinus and/or splanchnic veins. There are striking similarities between heparin-induced thrombocytopenia (HIT) and VITT. Both are caused by anti-PF4 antibodies, causing platelet and leukocyte activation which results in massive thrombo-inflammation. However, it is still to be determined why PF4 becomes immunogenic in VITT and which constituent of the vaccine triggers the immune response. As VITT-like syndromes are increasingly reported in patients shortly after viral infections, direct virus-PF4 interactions might be most relevant. Here we summarize the current information and hypotheses on the pathogenesis of VITT and address in vivo models, especially murine models for further studies on VITT. Full article

Splanchnic vein thrombosis is a rare but potentially life-threatening manifestation of venous thromboembolism, with challenging implications both at the pathological and therapeutic level. It is frequently associated with liver cirrhosis, but it could also be provoked by myeloproliferative disorders, cancer of various gastroenterological origin, abdominal infections and thrombophilia. A portion of splanchnic vein thrombosis is still classified as idiopathic. Here, we review the mechanisms of splanchnic vein thrombosis, including new insights on the role of clonal hematopoiesis in idiopathic SVT pathogenesis, with important implications from the therapeutic standpoint. Full article

Circulating endothelial cells (CECs) are viable, apoptotic or necrotic cells, identified by CD 146 surface antigen expression, considered a biomarker of thrombotic risk, given their active role in inflammatory, procoagulant and immune processes of the vascular compartment. Growing evidence establishes that CECs are also involved in the pathogenesis of several hematological and solid malignancies. The primary aim of this study was to verify if CEC levels could predict both the course and treatment responses of splanchnic vein thrombosis (SVT), either in patients affected by myeloproliferative neoplasms (MPNs) or liver disease. Thus, a retrospective multicenter study was performed; fifteen patients receiving anticoagulant oral treatment with vitamin k antagonists (VKA) for SVT were evaluated. Nine patients were affected by MPN, and all of them received cytoreduction in addition to anticoagulant therapy; four of these patients had primary myelofibrosis (PMF) and were treated with ruxolitinib (RUX), and one patient with primary myelofibrosis, two patients with essential thrombocythemia (ET), and two patients with polycythemia vera (PV) were treated with hydroxyurea (HU). Six patients affected by liver diseases (three with liver cirrhosis and three with hepatocellular carcinoma) were included as the control group. CECs were assayed by flow cytometry on peripheral blood at specific time points, for up to six months after enrollment. The CEC levels were related to C-reactive protein (CRP) levels, splenic volume reduction, and thrombus recanalization, mainly in MPN patients. In patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC), for which the mechanism of SVT development is quite different, the relationship between CEC and SV reduction was absent. In conclusion, the CEC levels showed a significant correlation with the extent of venous thrombosis and endothelial cell damage in myeloproliferative neoplasm patients with splanchnic vein thrombosis. Although preliminary, these results show how monitoring CEC levels during cytoreductive and anticoagulant treatments may be useful to improve SVT outcome in MPN patients. Full article

The coronavirus disease 2019 (COVID-19), a deadly pandemic that has affected millions of people worldwide, is associated with cardiovascular complications, including venous and arterial thromboembolic events. Viral spike proteins, in fact, may promote the release of prothrombotic and inflammatory mediators. Vaccines, coding for the spike protein, are the primary means for preventing COVID-19. However, some unexpected thrombotic events at unusual sites, most frequently located in the cerebral venous sinus but also splanchnic, with associated thrombocytopenia, have emerged in subjects who received adenovirus-based vaccines, especially in fertile women. This clinical entity was soon recognized as a new syndrome, named vaccine-induced immune thrombotic thrombocytopenia, probably caused by cross-reacting anti-platelet factor-4 antibodies activating platelets. For this reason, the regulatory agencies of various countries restricted the use of adenovirus-based vaccines to some age groups. The prevailing opinion of most experts, however, is that the risk of developing COVID-19, including thrombotic complications, clearly outweighs this potential risk. This point-of-view aims at providing a narrative review of epidemiological issues, clinical data, and pathogenetic hypotheses of thrombosis linked to both COVID-19 and its vaccines, helping medical practitioners to offer up-to-date and evidence-based counseling to their often-alarmed patients with acute or chronic cardiovascular thrombotic events. Full article

Philadelphia chromosome negative myeloproliferative neoplasms (MPN) are clonal haematopoietic stem cell disorders. Of the MPNs, polycythaemia vera (PV) and essential thrombocythaemia (ET) confer a high thrombotic risk which may be the presenting feature of the disease. Thrombotic complications consist of both arterial and venous events and the presence of the JAK2 V617F mutation is associated with higher risk. Patients presenting with an unprovoked thrombus, particularly at an unusual site, e.g., splanchnic circulation, should be screened for the presence of this mutation. Historically, warfarin has been the only option for oral anticoagulation; however, there is now increasing evidence and practise to use direct oral anticoagulants (DOACs) in cancer. The seminal randomised control trials have demonstrated non-inferiority compared to low molecular weight heparin (LMWH) with a preferable bleeding profile. DOACs are now the first line treatment for atrial fibrillation and venous thromboembolic disease, as recommended by NICE, and therefore there is increasing familiarity with these agents. Furthermore, there are now targeted antidotes available. This paper reviews evidence for efficacy and safety of DOACs in MPN. Whilst no randomised control trials have been performed, several retrospective studies and reviews of registry data have reproducibly demonstrated that, alongside cytoreduction, DOACs represent an effective modality of anticoagulation for treatment of venous thromboembolism in MPN. Furthermore, dosing regimens provide the option for longer term secondary prophylaxis. Use of DOACs in arterial thrombosis is an area for future development and there is already some evidence for utility in peripheral vascular disease. Full article

Introduction: Chronic pancreatitis (CP) is a long-standing progressive inflammation of the pancreas, which can lead to a variety of vascular complications, such as splanchnic venous thrombosis (VT) and arterial pseudoaneurysm (PA). There is a lack of studies on vascular complications in Scandinavian countries. Methods: We performed a retrospective analysis of medical records of patients with CP identified from the Karolinska University Hospital database between 2003 and 2018. A total of 394 patients with definite CP were included in the study. Results: There were 33 patients with vascular complications, with a median age of 62 (IQR 55–72) years. The cumulative incidence of vascular events was 3.2% at 5 years. Thirty patients had isolated VT, whereas three patients had PA (7.6% and 0.8%, respectively). Isolated splenic vein thrombosis was most common (53.3%), followed by a combination with other splanchnic veins. PA was found in the splenic artery in two patients and in the left gastric artery in one patient. Varices were present in three (10%) patients; variceal bleeding was not recorded. All patients had asymptomatic splanchnic VT, most with chronic VT with developed collaterals (83.3% had abdominal collateral vessels). Nearly two-thirds of patients with VT (63.3%) received no treatment, whereas 11 (36.6%) were treated with anticoagulants. Pseudocysts and alcoholic etiology of CP are risk factors for vascular complications. Conclusions: The cumulative incidence of vascular complications was 3.2% at 5 years. Splanchnic VT is more common than PA. Patients were asymptomatic with no variceal bleeding, explained by well-developed collateral vessels and strong study inclusion criteria. Full article

Acute pancreatitis (AP) is an acute inflammatory process of the pancreas with variable clinical presentations. Splanchnic venous thrombosis is a well-known vascular complication of AP and commonly present as thrombosis of the splanchnic venous system: splenic vein (SplV), portal vein (PV) and superior mesenteric vein (SMV), either separately or in combinations. Involvement of extra-splanchnic vessels is rare and associated with morbidity and mortality. Vascular complications are late phenomena and usually associated with local complications of AP, namely acute fluid collections, necrotizing pancreatitis and walled-off pancreatic necrosis. Pathogenesis of venous thrombosis is multifactorial in which pancreatic inflammation and systemic inflammatory response play a key role. At present, there are no consensus guidelines on treatment and use of anticoagulation for venous thrombosis in the setting of AP. Limited literature suggests the use of anticoagulation in presence of PV with or without SMV thrombosis and extrasplanchnic vessel involvement. Literature on extra-splanchnic vessels involvement in acute pancreatitis is sparse. Here we present two cases with multiple extra-splanchnic vessels involvement and their management. Full article

Upon activation, neutrophils release their content through different mechanisms like degranulation and NETosis, thus prompting thrombosis. The natural anticoagulant activated protein C (APC) inhibits neutrophil NETosis and, consequently, this may lower the levels of neutrophil activation markers in plasma, further diminishing the thrombotic risk exerted by this anticoagulant. We aimed to describe the status of markers of neutrophil activation in plasma of patients with venous thrombosis, their association with the thrombotic risk and the potential contribution of APC. We quantified three markers of neutrophil activation (cell-free DNA, calprotectin, and myeloperoxidase) in 253 patients with venous thromboembolism (VTE) in a stable phase (192 lower extremity VTE and 61 splanchnic vein thrombosis) and in 249 healthy controls. In them, we also quantified plasma APC, soluble endothelial protein C receptor (EPCR), and soluble thrombomodulin (TM), and we genotyped two genetic regulators of APC: the EPCR gene (PROCR) haplotypes (H) and the TM gene (THBD) c.1418C>T polymorphism. We found a significant increase in plasma cell-free DNA (p < 0.0001), calprotectin (p = 0.0001) and myeloperoxidase (p = 0.005) in VTE patients compared to controls. Furthermore, all three neutrophil activation markers were associated with an increase in the thrombotic risk. Cell-free DNA and calprotectin plasma levels were significantly correlated (Spearman r = 0.28; p < 0.0001). As expected, the natural anticoagulant APC was significantly decreased in VTE patients (p < 0.0001) compared to controls, what was mediated by its genetic regulators PROCR-H1, PROCR-H3, and THBD-c.1418T, and inversely correlated with cell-free DNA levels. This is the largest case-control study that demonstrates the increase in markers of neutrophil activation in vivo in VTE patients and their association with an increased thrombotic risk. This increase could be mediated by low APC levels and its genetic regulators, which could also increase NETosis, further enhancing thrombosis and inflammation. Full article

Cerebral vein thrombosis (CVT) and splanchnic vein thrombosis (SVT) are two manifestations of venous thromboembolism (VTE) at unusual sites. They have an incidence at least 25–50 times lower than usual site VTE, but represent true clinical challenges. Recent evidence on the epidemiology, risk factors, prognosis, and treatment of CVT and SVT has been published in the last two decades, thus contributing to a better understanding of these diseases. The improvement in imaging techniques and a higher degree of clinical suspicion may have led to the observed increased frequency, whereas a better knowledge of provoking mechanisms could have contributed to reducing the proportion of events classified as unprovoked or idiopathic (13–21% of CVT, 15–27% of SVT). Few small randomized clinical trials and a number of observational studies, although hampered by heterogeneous therapeutic approaches, shed light on the safety and effectiveness of anticoagulant therapy in these populations. However, there are still some grey areas that warrant future research. In this narrative review, we discuss recent advances and therapeutic challenges in CVT and SVT. Full article