Search Results (54)

Defibrotide, which is approved for treating hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), exhibits pleiotropic anti-inflammatory, anti-thrombotic, and fibrinolytic properties, conferring broad endothelial protective effects. Given these mechanisms, defibrotide has potential utility in various conditions involving endothelial injury or activation. In this review we outline the endothelial-protective mechanisms of defibrotide and comprehensively summarize current evidence supporting its applications in hematologic malignancies, including the prevention and treatment of hepatic VOD/SOS, graft-versus-host disease, and transplant-associated thrombotic microangiopathy. Additionally, we discuss its role in mitigating key toxicities linked to chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We also explore emerging evidence on defibrotide’s potential in SARS-CoV-2 infection-associated endotheliopathies, including acute COVID-19 and post-acute sequelae of SARS-CoV-2 infection (“long-COVID”), and the endothelial protective activity of defibrotide in these settings. Finally, we highlight potential future applications of defibrotide in hematologic malignancies and viral infections, emphasizing its multimodal mechanism of action. Full article

Background: Deep vein thrombosis (DVT) is an important component of venous thromboembolism and can lead to pulmonary embolism with high morbidity and mortality. Anticoagulant therapy alone (AC) and catheter-directed thrombolysis (CDT) are commonly used strategies for the management of DVT. Although CDT has been reported to be effective in reducing the risk of post-thrombotic syndrome (PTS), it remains unclear in which patient groups it should be preferred due to the risk of bleeding. Methods: This retrospective study included 175 patients diagnosed with DVT between 2015 and 2024 (98 AC, 77 CDT). Patients with a diagnosis of proximal DVT, aged ≥18 years, and with at least 30 days of follow-up data were included. The primary endpoint was 30-day mortality and secondary endpoints were the length of hospitalization, pulmonary embolism, and bleeding complications. Results: The CDT group was superior to AC in thrombus clearance rates, especially in iliac vein thrombosis (97.7% vs. 78%, p = 0.003). Clinical symptoms improved faster in the CDT group, but total hospitalization was longer. There were no significant differences in bleeding complications and mortality rates between the two groups. Conclusions: The optimal approach to DVT treatment should be based on the patient’s individual risk factors. Although CDT provides a higher thrombus clearance rate, especially in iliac vein thrombosis, it may not be suitable for all patients. Future large-scale studies will contribute to a better understanding of the long-term outcomes of interventional therapies. Full article

Background: GATA2-related myelodysplastic syndrome (GATA2-MDS) is a unique predisposition syndrome with a high risk of leukemic transformation. This systematic review synthesizes current literature and presents two illustrative pediatric GATA2-MDS cases. Methods: Data retrieval from eight cohort and case–control studies provides comprehensive analysis on disease features, diagnostic complexities, management, and outcomes related to hematopoietic stem cell transplantation (HSCT) in GATA2-related myeloid malignancies. Additionally, two pediatric cases are included to exemplify clinical and therapeutic challenges in real-world setting. Results: The literature data demonstrates high incidence of monosomy 7, and recurrent infections as the most common clinical feature, followed by immunodeficiency and lymphedema. Prognosis clearly worsens with age and HSCT remains the only curative treatment. GATA2 patients undergoing HSCT experience high rates of graft versus host disease (GvHD) as well as unique neurological, thrombotic, and infectious complications. Transplant-related mortality (TRM) is linked to GvHD and infections. Post-transplant cyclophosphamide (PT/Cy) strategies seem to improve survival by reducing GvHD incidence. Overall survival (OS) remains variable across groups. The first case presents rapid disease progression to pulmonary alveolar proteinosis (PAP) and leukemic transformation, further developing severe HSCT complications. The second case addresses novel GATA2 mutation and raises concerns regarding alternative prophylactic and therapeutic strategies in transplant setting. Conclusions: Collaborative efforts aim to enhance understandings of GATA2-related myeloid malignancies and guide towards more effective management approaches. Full article

Deep vein thrombosis (DVT) of the lower extremities, as part of venous thromboembolism disorder, is the third leading cause of acute cardiovascular syndrome after heart attack and stroke. It can result in disability due to pulmonary embolism (PE) and post-thrombotic syndrome (PTS), particularly in cases where the thrombosis extends to the iliofemoral veins. Anticoagulation therapy is effective in preventing thrombus propagation and embolism but may not be sufficient for thrombus degradation and venous patency restoration. Up to 50% of patients with iliofemoral DVT develop PTS, mainly due to venous outflow obstruction or valvular incompetence. To date, the advent of new devices that enables rapid thrombus elimination and the restoration of deep venous patency, known as the “OPEN VEIN hypothesis”, may prevent valvular damage and reflux, cutting down the rate of PTS. Similarly, chronic venous disease could be related to a stenosis or occlusion of a major vein that can restrict blood flow. In this setting, intravascular ultrasound (IVUS) is an essential tool for correct diagnostic and therapeutic planning in acute and chronic vein disease. Only angiography in vein disease can limit the procedure’s efficacy, with a high rate of stenosis misdiagnosed; IVUS provides further imaging that complements traditional angiographic study, and its role is now established by different international guidelines. If compared to angiography, IVUS allows for the evaluation of major axial veins in a 360-degree ultrasound image of the lumen and of the vessel wall structure. At the same time, the precise location and size of the major lower extremity veins allow for the placement of the stent to be more straightforward with a precise dimension of the vein in all of its diameters; moreover, other abnormalities should be visualized as acute or chronic thrombus, fibrosis, or trabeculations. This review aims to provide an in-depth analysis of IVUS findings in acute and chronic lower extremity DVT, emphasizing its diagnostic and therapeutic implications. 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

Pulmonary embolism (PE) is a life-threatening medical condition caused by the thrombotic occlusion of one or more branches of the lung vasculature, which represents the third most common cause of cardiovascular mortality after myocardial infarction and stroke. PE treatment requires a tailored approach based on accurate risk stratification and personalized treatment decision-making. Anticoagulation is the cornerstone of PE management, yet patients at higher clinical risk may require more rapid reperfusion therapies. In recent years, transcatheter treatment has emerged as a valuable option for patients with intermediate–high or high-risk PE who have contraindications to systemic thrombolysis. Recent advancements in catheter-directed therapies, such as catheter-directed thrombolysis (CDT) and catheter-directed mechanical thrombectomy (CDMT), provide minimally invasive options for swift symptom relief and hemodynamic stabilization. This review aims to provide a practical approach for optimal patient selection and management for PE percutaneous therapies, supported by a thorough evaluation of the current evidence base supporting these procedures. A focus on post-procedural management, the prevention of recurrence, and monitoring for long-term complications such as chronic pulmonary hypertension and post-PE syndrome is also specifically tackled. Full article

Background: Complement-mediated hemolytic uremic syndrome (CM-HUS), formerly known as atypical HUS, is a rare but potentially fatal thrombotic microangiopathy (TMA) characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and acute kidney injury. It is primarily caused by complement dysregulation. The condition can progress to end-stage renal disease (ESRD), often necessitating kidney transplant. In rare instances, it can develop in post-renal-transplant patients. Methods: Here, we present the cases of two patients with ESRD status post kidney transplant who presented with thrombocytopenia, anemia, and acute kidney injury. In both cases, work-up was suggestive of CM-HUS, and stabilization was achieved with eculizumab. Discussion: The pathogenesis of CM-HUS involves dysregulation of the complement system, and complement inhibitors such as eculizumab can be used for initial management and relapse. The relapse rate following eculizumab treatment can range from 20 to 67%. Patients with a history of kidney transplant are more prone to relapse than those with native kidneys. Re-treatment with complement inhibitors has proven effective in managing relapses, and long-term continuation of complement inhibitor medications is recommended to prevent recurrence. Conclusions: CM-HUS is rare, especially in post-transplant patients, and can be potentially fatal. It is crucial for clinicians to recognize and treat this condition promptly. Management often involves complement inhibitors. The risk of relapse is particularly high in patients with a history of kidney transplant, but long-term continuation of these medications can prevent relapse. Full article

Pulmonary Embolism (PE) is a life-threatening condition initiated by the presence of blood clots in the pulmonary arteries, leading to severe morbidity and mortality. Underlying mechanisms involve endothelial dysfunction, including impaired blood flow regulation, a pro-thrombotic state, inflammation, heightened oxidative stress, and altered vascular remodeling. These mechanisms contribute to vascular diseases stemming from PE, such as recurrent thromboembolism, chronic thromboembolic pulmonary hypertension, post-thrombotic syndrome, right heart failure, and cardiogenic shock. Detailing key risk factors and utilizing hemodynamic stability-based categorization, the review aims for precise risk stratification by applying established diagnostic tools and scoring systems. This article explores both conventional and emerging biomarkers as potential diagnostic tools. Additionally, by synthesizing existing knowledge, it provides a comprehensive outlook of the current enhanced PE management and preventive strategies. The conclusion underscores the need for future research to improve diagnostic accuracy and therapeutic effectiveness in PE. Full article

A better understanding of the long-term safety, efficacy, and immunogenicity of COVID-19 vaccines is needed. This phase 3, randomized, placebo-controlled study for AZD1222 (ChAdOx1 nCoV-19) primary-series vaccination enrolled 32,450 participants in the USA, Chile, and Peru between August 2020 and January 2021 (NCT04516746). Endpoints included the 2-year follow-up assessment of safety, efficacy, and immunogenicity. After 2 years, no emergent safety signals were observed for AZD1222, and no cases of thrombotic thrombocytopenia syndrome were reported. The assessment of anti-SARS-CoV-2 nucleocapsid antibody titers confirmed the durability of AZD1222 efficacy for up to 6 months, after which infection rates in the AZD1222 group increased over time. Despite this, all-cause and COVID-19-related mortality remained low through the study end, potentially reflecting the post-Omicron decoupling of SARS-CoV-2 infection rates and severe COVID-19 outcomes. Geometric mean titers were elevated for anti-SARS-CoV-2 neutralizing antibodies at the 1-year study visit and the anti-spike antibodies were elevated at year 2, providing further evidence of increasing SARS-CoV-2 infections over long-term follow-up. Overall, this 2-year follow-up of the AZD1222 phase 3 study confirms that the long-term safety profile remains consistent with previous findings and supports the continued need for COVID-19 booster vaccinations due to waning efficacy and humoral immunity. Full article

Evans Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger’s Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal–tibioperoneal artery bypass surgery and the subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach to managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD. Full article

Background: This study aims to evaluate and compare the outcomes and clinical efficacy of pharmacomechanical thrombectomy (PMCT) plus catheter-directed thrombolysis (CDT) and PMCT combined with CDT and venous stenting in managing acute iliofemoral deep vein thrombosis (DVT), while also assessing the long-term safety and efficacy of these interventions. Methods: A retrospective case–control study spanning 3 years involved 112 patients presenting with acute symptomatic iliofemoral deep vein thrombosis (DVT), each with a symptom duration of less than 14 days. Patients were consecutively categorized into two groups based on individual clinical indications: PMCT + CDT vs. PMCT + CDT + venous stent. Statistical analyses were conducted to compare clinical features and outcomes between the two groups. Additionally, patients were followed up for 24 months post-treatment, during which quality of life (QoL) and severity of post-thrombotic syndrome (PTS) were analyzed. Results: In this retrospective study, we analyzed a total of 112 consecutive patients, with 63 patients undergoing PMCT + CDT and 49 patients undergoing PMCT + CDT + venous stent. Between the two groups, regarding primary outcomes at 6 months, there was no difference in the observed cumulative patency rates, standing at 82.5% for PMCT + CDT and 81.6% for PMCT + CDT + stent. Survival analyses for primary, primary-assisted, and secondary patency yielded comparable results for PMCT + CDT, with p-values of 0.74, 0.58, and 0.72, respectively. The two-year patency rate was high in both groups (85.7% for PMCT + CDT vs. 83.7% for PMCT + CDT + stent). Additionally, during the follow-up period, there were no statistically significant differences observed in the incidence of PTS or the average Villalta score between the two groups. At 24 months post-intervention, the incidence of post-thrombotic syndrome (PTS) was 11.1% in the PMCT + CDT group and 22% in the PMCT + CDT + stent group (p = 0.381). Both treatment arms of the study groups experienced bleeding complications during the thrombolysis therapy; in the PMCT + CDT group, there were three cases of gastrointestinal bleeding, compared to two cases in the PMCT + CDT + stent group (p = 0.900). Additionally, there was one intracranial hemorrhage in the PMCT + CDT group and two in the PMCT + CDT + stent group. Conclusions: Pharmacomechanical thrombectomy (PMCT) combined with catheter-directed thrombolysis (CDT) therapy has shown significant efficacy in alleviating leg symptoms and reducing the occurrence of post-thrombotic syndrome (PTS), including the incidence of moderate-to-severe PTS. On the other hand, the utilization of PMCT + CDT + stent therapy, tailored to individual patients’ clinical and venous conditions, may enhance long-term venous patency and lead to superior outcomes, including improved quality of life parameters. Full article

Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of its pathogenesis, highlighting the fact that there is a specific pulmonary vascular disorder. Indeed, COVID-19 may predispose patients to thrombotic disease in both venous and arterial circulation, and many cases of severe acute pulmonary embolism have been reported. The demonstrated presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the endothelial cells suggests that direct viral effects, in addition to indirect effects of perivascular inflammation and coagulopathy, may contribute to pulmonary vasculopathy in COVID-19. In this review, we discuss the pathological mechanisms leading to pulmonary vascular damage during acute infection, which appear to be mainly related to thromboembolic events, an impaired coagulation cascade, micro- and macrovascular thrombosis, endotheliitis and hypoxic pulmonary vasoconstriction. As many patients develop post-COVID symptoms, including dyspnea, we also discuss the hypothesis of pulmonary vascular damage and pulmonary hypertension as a sequela of the infection, which may be involved in the pathophysiology of long COVID. Full article

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50–70% are hospitalised. It has also been shown that 10–12% of those vaccinated against COVID-19 were affected by PASC and its complications. The severity and the later development of PASC symptoms are positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. The cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as conditions that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with the respiratory system in long-COVID causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. The renal system also was impacted, which resulted in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite, and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints linked to PASC. Conclusions: Long-COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy, and more study to address its underlying causes and long-term effects is needed. Full article

The therapeutic management and short-term consequences of the coronavirus disease 2019 (COVID-19) are well known. However, COVID-19 post-acute sequelae are less known and represent a public health problem worldwide. Patients with COVID-19 who present post-acute sequelae may display immune dysregulation, a procoagulant state, and persistent microvascular endotheliopathy that could trigger microvascular thrombosis. These elements have also been implicated in the physiopathology of postural orthostatic tachycardia syndrome, a frequent sequela in post-COVID-19 patients. These mechanisms, directly associated with post-acute sequelae, might determine the thrombotic consequences of COVID-19 and the need for early anticoagulation therapy. In this context, heparin has several potential benefits, including immunomodulatory, anticoagulant, antiviral, pro-endothelial, and vascular effects, that could be helpful in the treatment of COVID-19 post-acute sequelae. In this article, we review the evidence surrounding the post-acute sequelae of COVID-19 and the potential benefits of the use of heparin, with a special focus on the treatment of postural orthostatic tachycardia syndrome. Full article

Background: Anticoagulation for venous thromboembolism (VTE) is required for at least three to six months; however, it is advisable to extend the duration in certain cases, in which case a reduced dose of Direct Oral Anticoagulants (DOACs) may be an option. Our objective was to investigate the efficacy and safety of reduced-dose DOACs in extended anticoagulation treatment compared to full doses. Methods and Results: This retrospective single-centre study included 185 patients treated with DOACs for at least 6 months who were divided into two groups: (1) the Full Dose (FD) group (n = 113) and (2) the Reduced Dose (RD) group (n = 72), which included patients treated with Apixaban at 2.5 mg bis in die (BID) and Rivaroxaban at 10 mg once daily (OD). Post-thrombotic syndrome (PTS) and its progression were evaluated. During an overall follow-up of 48.32 ± 29.49 months, no VTE occurred, and no patients experienced major bleeding; clinically relevant non-major bleeding occurred in three patients in each group (2.7% vs. 4.2% in FD vs. RD, respectively, p = 0.57). From baseline to follow-up, the prevalence of PTS was not significantly decreased in either group (FD: 54.9% vs. 51.3%, p = 0.29; RD 51.4% vs. 44.4%, p = 0.12); conversely, the Villalta score values were significantly decreased at the last follow-up (FD: 5.51 ± 4.18 vs. 5.12 ± 4.36, p < 0.001; RD 5.49 ± 4.06 vs. 5.11 ± 3.73, p = 0.006). Conclusion: In this real-world retrospective registry, very long-term extended anticoagulant therapy with DOACs at full or reduced doses showed comparable efficacy, safety, and impact on PTS progression. Larger studies are needed. Full article