Thrombus Resolution Research Articles

Discovery and Preclinical Characterization of Fulacimstat (BAY 1142524), a Potent and Selective Chymase Inhibitor As a New Profibrinolytic Approach for Safe Thrombus Resolution.

Chymase is a serine-protease produced by mast cells. In the past few decades, its role in fibrotic diseases triggered the search for orally available chymase inhibitors. Aiming at reducing adverse cardiac remodeling after myocardial infarction, our research efforts resulted in the discovery of fulacimstat (BAY 1142524). While clinical trials did not demonstrate efficacy in this indication, the recent discovery of a new unexpected biological role of chymase spurred a revival of interest in chymase inhibition: chymase was shown to inactivate plasmin within fibrin-rich clots. Chymase inhibitors are now considered as potential profibrinolytic drugs with low bleeding risk and therefore exceptional safety for the treatment of acute thrombosis settings such as stroke, pulmonary embolism, or venous thrombosis. This article describes the chemical optimization journey from a screening hit to the discovery of fulacimstat (BAY 1142524), a selective chymase inhibitor with a good safety profile, as well as its preclinical in vitro and in vivo characterization.

Abstract 4125528: Interleukin-6-Modulated Inflammation Augments Deep Vein Thrombosis Organization in Mice

Background: A disorganized thrombus jeopardizes its stability, leading to an augmented risk of fatal acute complications following deep vein thrombosis (DVT). One of its plausible causes is impaired immune cell responses. While the importance of the cytokine interleukin-6 (IL-6) in immune responses is well established, its action towards DVT organization is poorly elucidated. Accordingly, we aimed to investigate the role of IL-6 in the acute immunoinflammatory orchestration of DVT organization in vivo. Methods and Results: We performed total ligation of the infrarenal inferior vena cava (IVC) in 8–12-week-old male C57BL/6J mice a day after starting continuous, subcutaneous mini-osmotic pump infusion of recombinant IL-6 (rIL-6; 1.2 µg/day, n = 21) or vehicle (n = 21), after which DVT pathology was examined. Exogenous IL-6 administration significantly decreased DVT mass at day 2 (16.6±1.9 vs. 23.0±0.9 mg/cm; p<0.01) and day 4 (16.2±1.6 vs. 21.4±0.8 mg/cm; p<0.05) compared to vehicle-treated mice. Intriguingly, rIL-6-treated mice’s DVT exhibited distal tropism of a macroscopically white lesion with abundant neutrophils and platelet accumulation, indicating enhanced DVT organization (Figures A–B). Quantitative polymerase chain reaction (qPCR) analysis revealed the distal edge upregulation of leukocyte chemoattractants, leukocyte-platelet interaction markers, and extracellular matrix regulator genes, confirming that the IL-6-driven inflammatory response was linked to augmented DVT organization. Spatiotemporally, real-time intravital imaging on stasis- and irradiation-induced saphenous vein thrombosis among intraperitoneal rIL-6 (0.3 µg/mouse)-treated mice demonstrated marked acute leukocyte and platelet recruitment with subsequent aggregation to the distal edge of the thrombus (Figures C–D), which consequently yielded an enhanced thrombus resolution at the distal edge. Conclusions: Our findings suggest that IL-6-driven inflammation results in distal tropism of leukocyte-platelet infiltration, which is important for modulating thrombus organization and subsequent DVT amelioration. This study presents a novel insight into the immunothrombosis process, with potential clinical implications for DVT.

Efficacy of direct oral anticoagulants vs. warfarin in left ventricular thrombus in myocardial infarction: systematic review and meta-analysis.

Current recommendations for antithrombotic strategies in left ventricular (LV) thrombus following myocardial infarction (MI) remain uncertain. This study aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to warfarin in LV thrombus following MI. A systematic search using four databases, including PubMed, Embase, Web of Science, and Cochrane CENTRAL, was conducted from inception to 8 July 2024, without language restrictions. The inclusion criteria were studies that included patients with LV thrombus following MI and compared the efficacy or safety of DOACs and warfarin. There were 11 studies (3 randomized and 8 nonrandomized) included in this meta-analysis, involving 14 927 participants. We used a random-effects model for this meta-analysis. DOACs were associated with higher thrombus resolution than warfarin, with a risk ratio (RR) of 1.07 [95% confidence interval (CI) 1.00-1.15], P = 0.04. Similarly, DOACs were associated with a lower rate of stroke and systemic embolism, with an RR of 0.84 (95% CI 0.78-0.90), P < 0.01. DOACs also marginally reduced the rate of major bleeding compared with warfarin, with an RR of 0.87 (95% CI 0.75-1.00), P = 0.05. DOACs were associated with higher rates of LV thrombus resolution, lower rates of stroke/systemic embolism, and marginally reduced major and bleeding events compared with warfarin in patients with LV thrombus following acute MI. Therefore, DOACs may be a reasonable alternative to warfarin in this setting.

Circulating Angiopoietin-2 (Angpt2) levels predict diagnosis of Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Abstract Background Vascular remodeling following incomplete thrombus resolution is considered to be a key factor in the progression to chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE). Recent data demonstrated that Angpt2, which controls signaling via the Tie2 receptor, could interfere with the normal process of thrombus resolution. Our prior findings have shown that patients presenting with acute PE and having plasma levels of Angt-2 ≥5.5 ng/ml at admission are at a significantly increased risk (93 times higher) of being diagnosed with CTEPH in subsequent assessments. Purpose To externally validate the prognostic performance of Angpt2 for the development of CTEPH. Methods In a prospective cohort study of unselected consecutive all-comers with PE, survivors of the index acute event underwent 3-, 12- and 24-month follow-up with venous blood sampling for subsequent biomarker measurements. Angpt2 was measured on admission using specific enzyme linked immunosorbent assays (ELISA) detecting both the endogenous and the recombinant protein, according to the manufacturer (R&amp;D Systems). Results Overall, 319 patients with acute PE (median age: 62 [IQR, 50-73]; females: 55.2%) were included in the analysis with a median Angpt2 plasma level of 2.6 ng/ml (IQR, 1.8-3.7) (Figure 1). Patients with PE and Angpt-2 plasma levels above the median had more often comorbidities, such as chronic heart failure (24.2% and 11.0.%; p=0.045), chronic kidney disease (33.3% vs 14.0%; p=0.010), or diabetes (27.3% vs. 12.9%; p=0.032). Angpt2 plasma levels correlated with haemodynamic status and parameters indicating severe PE (right ventricle dysfunction, r=0.129 [p=0.021) and troponin, r=0.246 [p&amp;lt;0.001]). In total, post-PE impairment (PPEI) was diagnosed in 33 (10.3%) and CTEPH in four (1.3%) patients during follow-up. Angpt2 plasma levels were higher on admission in patients developing PPEI or CTEPH during follow-up compared to patients without PPEI or CTEPH (PPEI vs non-PPEI: median, 3.2 [2.3-4.1] ng/ml vs. 2.5 [1-3.4] ng/ml, p=0.035; CTEPH vs. non-CTEPH: median, 5.1 [2.9-10.5] ng/ml vs. 2.5 [1.7-3.6] ng/ml, p=0.055). Regarding the diagnosis of CTEPH during follow-up, ROC analysis illustrated an AUC for Angpt2 (0.779 [95% CI 0.56–0.99]; p=0.055]) (Figure 2). By using univariate logistic regression analysis, the calculated predefined Angpt2 cut-off value of ≥5.5 ng/ml was associated with a 9.2-fold increased risk (1.3–67.4, p=0.030) for a diagnosis of CTEPH during follow-up. Conclusion We were able to validate in a different patient cohort the usefulness of Angpt2 as a novel biomarker to identify patients at risk for CTEPH.

Direct oral anticoagulants or warfarin in patients with left ventricular thrombus: a meta-analysis of randomized clinical trials

Abstract Background/Introduction There are limited randomized controlled trials (RCTs) data on the use of direct oral anticoagulants (DOAC) versus warfarin in patients with left ventricular (LV) thrombus. Current AHA and ESC guidelines recommend oral anti-coagulants (either DOAC or warfarin) for 3 to 6 months without any preference. Purpose We aimed to compare outcomes with DOACs versus warfarin in patients with LV thrombus. Methods A comprehensive literature search was performed from inception to 02/01/2024 of the PubMed database. RCTs of adult patients comparing DOAC to warfarin were evaluated for mortality, major bleeding, stroke, and LV thrombus resolution. Meta-analytic Odds ratio (OR) with 95% confidence intervals (CI) were calculated using DerSimonian-Laird method. Results From 100 studies, four RCTs with 188 subjects (95 DOAC and 93 warfarin) were included with mean age of 53.4 years, 69.5% males, and mean follow up 5.03 months. There was no difference in mortality (OR= 0.67 [95% CI 0.15-3.06]; p=0.60; I2=0%; 3 trials), stroke (OR= 0.46 [95% CI 0.09-2.44]; p=0.37; I2=0%; 4 trials), major bleeding (OR= 0.43 [95% CI 0.12-1.55]; p=0.20; I2=0%; 4 trials), and LV thrombus resolution (OR= 1.33 [95% CI 0.45-3.95]; p=0.61; I2=0%; 2 trials) with use of DOAC compared to warfarin (Figure Panel A to D). Overall, there was no evidence of publication bias using either funnel plot or eggers test (p &amp;gt; 0.05). Conclusions In this meta-analysis of 4 RCTs, there was similar efficacy and safety of DOAC and warfarin in patients with LV thrombus. However, the evidence is limited by small sample size with lesser precision in the estimates. Future large-scale trials are needed to confirm these findings.

Direct Oral Anticoagulants versus Vitamin K Antagonists for the management of left ventricular thrombus after myocardial infarction: A meta-analysis

Abstract Background/Introduction Left ventricular (LV) thrombus formation is not an uncommon complication after acute myocardial infarction (AMI) in the modern era of early reperfusion. The optimal anticoagulation regimen in this clinical scenario remains poorly-defined. Purpose The present meta-analysis sought to investigate the efficacy and safety profile of direct oral anticoagulants (DOACs) compared with Vitamin K antagonists (VKAs) for the management of LV thrombus following AMI. Methods A systematic literature review was conducted in electronic databases to identify studies reporting efficacy and safety outcome data regarding the use of DOACs versus VKAs for patients with LV thrombus after MI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and random-effects meta-analyses were conducted to synthesize pooled ORs. Results Eight studies comprising a total of 605 patients were included (Table). DOACs were associated with an almost 2-fold higher likelihood for achieving thrombus resolution compared to VKAs (pooled OR 1.95 [1.25-3.04]; p =0.003, I2 =0 %), while they achieved a 70% lower risk for systemic embolism (pooled OR 0.30 [0.12-0.75]; p =0.01, I2 =0%). The use of DOACs was associated with a 54% lower risk for bleeding compared to VKAs (pooled OR 0.46 [0.26-0.84]; p =0.01, I2 =0 %). Overall, patients receiving DOACs had a 63% lower risk to reach the composite outcome of any bleeding, systemic embolism, cardiovascular hospitalization, or all-cause death, compared with patients using VKAs (pooled OR 0.37 [0.23-0.60]; p &amp;lt;0.0001, I2 =0%) (Figure). Conclusion DOACs appear to have a more favorable efficacy and safety profile compared to VKAs for the management of LV thrombus following AMI.Graphical abstractTable

Evolution of Left Ventricular Thrombus on Serial Cardiovascular Magnetic Resonance Imaging.

Current management of left ventricular (LV) thrombus relies on limited, non-contemporary, echocardiography-based studies. Data on LV thrombus evolution and the associated embolic risk are scarce. We aimed to describe the evolution of LV thrombus on serial cardiovascular magnetic resonance imaging (CMR) - the current reference standard for the detection of LV thrombus, and identify correlates of no resolution and the embolic risk associated with resolution status. We conducted a retrospective cohort study of 107 consecutive patients with LV thrombus who had 213 serial CMRs at a median of 255 days after the index CMR. Of these, 97.2% were anticoagulated. At 3 months after detection by CMR, 75% (47/63) had no resolution of LV thrombus; at 6 months, 53% (35/66) had no resolution; and at 12 months, 37% (23/63) had no resolution. Correlates of no resolution at 6 months included a history of myocardial infarction, LV aneurysm, ischemic etiology of cardiomyopathy, and larger thrombus volume. Recurrence of LV thrombus was rare at 5.3%. On survival analysis using the landmark analysis method, embolic events often occurred beyond 6 months, more frequently in patients with unresolved LV thrombus. Our findings challenge previous literature by demonstrating a lower rate of resolution of LV thrombus and substantial embolic risk beyond 6 months associated with unresolved LV thrombus on serial CMR. Our findings advocate for extended anticoagulation, particularly in patients with markers associated with no resolution. These findings have important implications for clinical practice and research into managing patients with LV thrombus.

Intravenous Direct Thrombin Inhibitors for Acute Venous Thromboembolism or Heparin-Induced Thrombocytopenia with Thrombosis in Children: A Systematic Review of the Literature.

Intravenous direct thrombin inhibitors (DTIs) are used for thromboembolic disorders. This systematic review aims to characterize intravenous DTI agents, dosing, monitoring strategies (or use), bleeding, and mortality, in pediatric patients with acute venous thromboembolism (VTE) or heparin-induced thrombocytopenia with thrombosis (HITT). MEDLINE, Embase, and Cochrane's CENTRAL were searched from inception through July 2023. Case series, retrospective studies, and prospective studies providing per-patient or summary data for patients < 18 years of age with VTE or HITT treated with an intravenous DTI were included. Selection and data extraction were conducted independently by two reviewers. Sixteen studies (7 case reports, 1 case series, 5 retrospective studies, 3 prospective studies) with 85 patients were included. Target conditions included acute VTE in 54 (64%) and HITT in 31 (36%) patients. Bivalirudin, argatroban, and lepirudin were used in 52 (61%), 27 (32%), and 6 (7%) patients, respectively. Fifty-two (61%) patients received a bolus dose, and weighted mean infusion rates for bivalirudin, argatroban, and lepirudin were 0.2 mg/kg/hr, 1.2 mcg/kg/min, and 0.15 mg/kg/hr, respectively. The activated partial thromboplastin time was utilized for monitoring in 82 (96%) patients. Complete or partial thrombus resolution was reported in 53 (62%) patients, mortality in 6 (7%) patients, and bleeding complications in 14 (16%) patients. In this systematic review involving 85 pediatric patients treated with an intravenous DTI for acute VTE or HITT, bivalirudin was the most commonly utilized agent, with a rate of resolution over 60% despite a high acuity in the population studied. Prospective collaborative studies are warranted to establish optimal dosing and further characterize VTE and bleeding outcomes.

Incidence and risk factors for postthrombotic syndrome in neonates and children in a single-center cohort study

Postthrombotic syndrome (PTS) is a chronic condition following deep vein thrombosis (DVT) and is associated with pain, swelling, and restricted use of the affected limb. In pediatric age groups, its incidence and risk factors are not well-known. This observational cohort study of all consecutive children (≤18 years) with DVT treated at the Emma Children’s Hospital Amsterdam between January 2001 and January 2021 was conducted to identify incidence and risk factors for PTS in neonates aged ≤2 months and children aged >2 months. PTS was diagnosed using the modified Villalta scale. In total, 315 patients were included. The 20-year incidence of PTS was 20.0% in neonates and 40.0% in children. In neonates, involvement of ≥3 vessels (odds ratio [OR], 6.6; 95% CI, 1.6-26.4) and incomplete thrombus resolution (OR, 3.0; 95% CI, 1.1-8.0) were risk factors for PTS. In children, involvement of ≥3 vessels (OR, 6.2; 95% CI, 2.2-17.8), recurrent DVT (OR, 3.7; 95% CI, 1.3-10.3), and incomplete thrombus resolution (OR, 5.2; 95% CI, 1.6-17.0) were associated with PTS. Exercise ≥3 times/wk (OR, 0.4; 95% CI, 0.2-0.9), central venous catheter-related DVT (OR, 0.2; 95% CI, 0.1-0.5), and provoked DVT (OR, 0.4; 95% CI, 0.1-0.97) were protective factors for PTS. This study demonstrated a high incidence of pediatric PTS. Additionally, risk factors for PTS differed between neonates and children. These findings provide a basis for better prevention and management of PTS that may differ between neonates and children.

Clinical characteristics, treatment, and outcomes of provoked acute cerebral sinovenous thrombosis in patients

BackgroundProspective multicenter data on the treatment and outcomes of children with cerebral sinovenous thrombosis (CSVT) are limited. We aimed to describe the clinical characteristics, treatment strategies, and outcomes of patients with a first-episode of provoked acute CSVT enrolled in the Kids-DOTT trial and compare these features with those of participants with non-CSVT venous thromboembolism (VTE). MethodsThis was a subgroup analysis from the Kids-DOTT trial, a multinational randomized clinical trial on duration of anticoagulation for provoked acute VTE in patients younger than 21 years. Patient and thrombus characteristics, treatments, and outcomes of patients diagnosed with CSVT were compared with those of patients with non-CSVT VTE. ResultsCSVT was diagnosed in 75 of the 532 (14%), 25 of whom received 6 weeks of anticoagulant treatment and 50 received 3 or more months. When compared with non-CSVT VTE, CSVT was more likely to occur in neonates and young children, associated with infection in general and acute head/neck infection in particular, and less likely to be related to central venous catheter. No patient in either group developed symptomatic recurrent VTE or clinically relevant bleeding, and there was no significant difference in rates of complete thrombus resolution between the 2 treatment durations. ConclusionCSVT is most common in neonates and young children and those with acute head and neck infections. A 6-week anticoagulation treatment course appears to be safe (no clinically relevant bleeding) and effective (no difference in symptomatic recurrent VTE) for provoked acute pediatric CSVT. Nevertheless, given the nature of a subpopulation analysis, these findings should be interpreted with caution.

The Aortic Prosthesis and Aortic Valve Bioprosthesis Trombosis as a Late Complication in Patients after the Bentall Procedure Followed by a Valve-in-Valve Transcatheter Aortic Valve Implantation.

Background: Valve-in-Valve (ViV) transcatheter aortic valve implantation (TAVI) has emerged as a viable therapeutic option for structural valve degeneration following surgical aortic valve replacement (SAVR) or prior TAVI. However, the understanding of long-term complications and their management remains limited. Case presentation: We present the case of a 69-year-old male with a history of ViV-TAVI, who presented with symptoms of non-ST elevation myocardial infarction (NSTEMI) and transient ischemic attack (TIA). Computed tomography (CT) revealed thrombosis of the ascending aortic graft and aortic valve prosthesis. Transthoracic echocardiography (TTE) further confirmed new valve dysfunction, indicated by an increase in the aortic valve mean gradient. Treatment with low-molecular-weight heparin (LMWH) resulted in partial thrombus resolution. The multidisciplinary Heart Team opted against coronary angiography and recommended the long-term administration of vitamin K antagonists (VKAs). Follow-up CT showed the complete resolution of the thrombus. Conclusions: Thrombosis of the aortic graft and aortic valve following ViV-TAVI may be attributed to alterations in blood flow or mechanical manipulations during the TAVI procedure, yet it can be effectively managed with VKA therapy. CT is a valuable tool in coronary assessment in patients with NSTEMI and aortic valve and/or aortic graft thrombosis.

Evaluating the Effectiveness of Enoxaparin in Treating Pediatric Arterial Thrombosis in Saudi Arabia.

Thrombosis is the abnormal formation of blood clots within blood vessels; it results from an imbalance between fibrinolytic, pro-coagulant, and anticoagulant systems. Pediatric arterial thrombosis, especially related to catheter usage, is an emerging issue with limited evidence. This study evaluates the efficacy of enoxaparin in treating arterial thrombosis in pediatric patients at a single center. A retrospective single-center study included children under 14 years old diagnosed with catheter-related arterial thrombosis (CAT) and treated with low-molecular-weight heparin (LMWH) at King Abdulaziz Medical City between 2016 and 2021. Patients without follow-up at our institution or those using other anticoagulants were excluded. Data collected included age, sex, weight, catheter type, location and degree of thrombosis, ultrasonographic results, treatment duration, hemoglobin and platelet levels, and missed refills. Radiologic confirmation of CAT was required for inclusion. This study included 111 children treated with enoxaparin for non-cerebral arterial thrombosis. The median age at diagnosis was 3 months, with 58% being male patients. Most cases (87%) involved cardiac catheterization, and all were confirmed using ultrasonography. Complete thrombus resolution was achieved in 90% of patients, partial resolution in 8.1%, and 1.8% had no resolution. The median duration of enoxaparin therapy was 20 days. Multivariate analysis indicated that higher age and lower body weight were associated with a higher risk of non-resolution. Indwelling catheters also posed a greater risk of non-resolution compared to cardiac catheters. Enoxaparin proved effective in treating catheter-related arterial thrombosis in children, with high resolution rates and few side effects. This study helps inform treatment strategies in pediatric thrombosis management and highlights the need for further research to refine treatment durations and address patient risk factors.

Regulation of macrophage fibrinolysis during venous thrombus resolution

BackgroundVenous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), is a serious cardiovascular disease with significant mortality and morbidity. Clinically, patients with faster resolution of a venous thrombi have improved prognosis. Urokinase-plasminogen activator (uPA), produced by macrophages, is a key mediator of fibrinolysis required for resolving venous thrombi and restoring vascular integrity. The major macrophage protein, plasminogen activator inhibitor type-2 (PAI-2), was originally identified as an inhibitor of uPA and is implicated in the modulation of pathways affecting fibrinolytic uPA activity, however its direct role in blocking uPA-mediated clot lysis is not known. ObjectiveTo determine the contribution of macrophage PAI-2 in inhibiting uPA-mediated fibrinolysis during resolution of DVT. MethodsUsing a murine model of venous thrombosis and resolution, we determined histological changes and molecular features of fibrin degradation in venous thrombi from WT mice and mice genetically deficient in PAI-2 and PAI-1, and determined the fibrinolytic activities of macrophages from these genotypes ex vivo. ResultsAcceleration of venous thrombus resolution by PAI-2−/− mice increases fibrin degradation in venous thrombi showing a pattern similar to genetic deficiency of PAI-1, the major attenuator of fibrinolysis. PAI-2 deficiency was not associated with increased macrophage infiltration into thrombi or changes in macrophage PAI-1 expression. uPA-initiated fibrinolysis by macrophages in vitro could be accelerated by PAI-1 deficiency, but not PAI-2 deficiency. ConclusionPAI-2 has an alternate anti-fibrinolytic activity that is macrophage uPA independent, where PAI-1 is the dominant uPA inhibitor during DVT resolution.

Direct Oral Anticoagulants Versus Vitamin K Antagonists for the Management of Left Ventricular Thrombus After Myocardial Infarction: A Meta-Analysis

Left ventricular (LV) thrombus formation remains a post-acute myocardial infarction (AMI) complication even in the modern era of early reperfusion. The optimal anticoagulation regimen in this clinical scenario is poorly defined. The present meta-analysis sought to investigate the efficacy and safety profile of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for the management of LV thrombus after AMI. A systematic literature review was conducted in electronic databases to identify studies reporting efficacy and safety outcome data regarding the use of DOACs versus VKAs for patients with LV thrombus after AMI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and random-effects meta-analyses were conducted to synthesize pooled ORs. Eight studies comprising a total of 605 patients were included. DOACs were associated with an almost twofold higher likelihood of thrombus resolution compared with VKAs (pooled OR 1.95 [1.25 to 3.04], p = 0.003, I2 = 0%), and decreased the risk of systemic embolism by 70% (pooled OR 0.30 [0.12 to 0.75]; p = 0.01, I2 = 0%). The use of DOACs was associated with a 54% lower risk of bleeding compared with VKAs (pooled OR 0.46 [0.26 to 0.84], p = 0.01, I2 = 0%). Overall, patients receiving DOACs had a 63% lower risk of reaching the composite outcome of safety and efficacy compared with patients using VKAs (pooled OR 0.37 [0.23 to 0.60], p <0.0001, I2 = 0%). In conclusion, DOACs appear to have a more favorable efficacy and safety profile compared with VKAs for the management of LV thrombus related to AMI.

Anticoagulation for Septic Cerebral Venous Thrombosis in Childhood.

Anticoagulation is recommended for most children with cerebral venous thrombosis (CVT) to prevent venous infarction and promote recanalization. An exception is CVT associated with head and neck infection (septic CVT), for which treatment of infection without concomitant use of anticoagulation is recommended. Despite this, the use of anticoagulation in septic CVT is controversial, and children with septic CVT are often anticoagulated due to concerns about thrombus progression and persistence despite infection treatment. A retrospective study of children with septic CVT cared for at Seattle Children's Hospital between 2009 and 2023 was conducted to assess the safety and outcome of anticoagulation. Among 40 children with septic CVT, 25 (63%) received anticoagulation. None had bleeding complications. Performance of follow-up venous imaging was inconsistent and more commonly pursued in patients treated with anticoagulation. A total of 23/40 (58%) patients were evaluable at 1 month, among whom 26% (6/23) had resolution of thrombus and 74% (17/23) had persistence. A total of 22/40 (55%) patients were evaluable at 3 months, among whom 77% (17/22) had resolution of thrombus and 23% (5/22) had persistence. This supports the safety of anticoagulation, but further studies are needed to determine whether anticoagulation improves outcomes after septic CVT.

Resolution of oval thrombus in a case of external jugular venous aneurysm.

Resolution of oval thrombus in a case of external jugular venous aneurysm.

Novel Challenges and Therapeutic Options for Pulmonary Embolism and Deep Vein Thrombosis.

Acute pulmonary embolism (PE), often resulting from deep vein thrombosis (DVT), is the third most frequent cause of cardiovascular death and is associated with increasing incidence, causing considerable morbidity and mortality. This review aims to evaluate the efficacy, safety, and outcomes of treatment options in the management of acute PE and DVT, encompassing both established and emerging technologies, such as catheter-directed thrombolysis, aspiration thrombectomy, and other endovascular techniques. A comprehensive literature review was conducted, assessing clinical studies, trials, and case reports that detail the use of percutaneous interventions for PE and DVT and analyzing the advantages and disadvantages of each percutaneous system. Several percutaneous treatments have shown promising results, especially in cases where rapid thrombus resolution is critical, such as in high- and intermediate-high-risk patients. The incidence of major complications, such as bleeding, remains a consideration, though it is generally manageable with proper patient selection and technique. It is fundamentally important to tailor the specific treatment strategy to the clinical and anatomical characteristics of each patient. Percutaneous treatments for acute PE and DVT represent valuable options in the therapeutic arsenal, offering enhanced outcomes in appropriately selected patients. Ongoing advancements in technology and technique, along with comprehensive clinical trials, are essential to further define the role and optimize the use of these interventions.

The Efficacy of Medical Interventions for Free-Floating Thrombus in Cerebrovascular Events: A Systematic Review.

Although free-floating thrombus (FFT) poses a significant risk of stroke or transient ischemic attack (TIA), optimal management strategies are uncertain. To determine the state-of-the-art of medical interventions for FFT, we conducted a systematic review of the efficacy of various medical interventions and factors influencing FFT resolution and recurrence. A comprehensive search of Embase, PubMed, and ScienceDirect identified 61 studies encompassing 179 patients with FFT-related stroke or TIA treated with anticoagulants, antiplatelets, or their combinations. Primary outcomes assessed were stroke recurrence and thrombus resolution. Statistical analyses (Fisher's exact test, chi-square test, Mann-Whitney test, and Kruskal-Wallis test) utilized significance set at p < 0.05. Over a median follow-up of 7 months, thrombus resolution occurred in 65% of patients, while 11.2% experienced recurrence, primarily as TIAs. Cardioembolism was significantly less common in resolved cases (p = 0.025). Combination therapy (antiplatelets, anticoagulants, and statins) significantly enhanced clot resolution (OR 11.4; 95% CI 1.436-91.91; p = 0.021) compared to monotherapies. Ulcerated plaque was a significant predictor of recurrence (OR 8.2; 95% CI 1.02-66.07; p = 0.048). These findings underscore the superiority of combination therapy in FFT management and highlight the need for targeted interventions in patients with ulcerated plaques to mitigate recurrence risk.

To Compare the Efficacy of Rivaroxaban with Nicoumolone in the Management of Patients with Intraventricular Thrombus

Objectives: Left ventricular thrombus (LVT) poses serious risks, including stroke and systemic embolism. Anticoagulant therapy is crucial, yet uncertainty persists in optimal management. This study aims to compare nicoumalone and rivaroxaban for LVT, assessing efficacy, safety, and monitoring considerations to inform clinical decision-making. Materials and Methods: This prospective and open-label trial compared rivaroxaban and nicoumalone efficacy in managing LVT over a 1-year period (September 2021–September 2022). Thirty-one patients from Government General Hospital, Guntur, meeting inclusion criteria were enrolled. Data were collected through interviews and echocardiography. Primary outcomes included thrombus resolution and recurrence; secondary outcomes encompassed adverse effects such as bleeding and stroke. Standard dosing and monitoring protocols were followed for each intervention. Results: In this study, both nicoumalone and rivaroxaban groups exhibited a reduction in LVT size over time, although not statistically significant (P &gt; 0.05). Complete resolution was achieved in 70.0% of nicoumalone patients and 81.8% of rivaroxaban patients, with no significant difference (P = 0.472). However, rivaroxaban group patients achieved complete resolution significantly faster (176.67 ± 43.589 days) compared to nicoumalone group patients (271.67 ± 115.24 days) (P = 0.028). Notably, one nicoumalone patient experienced LVT recurrence post-anticoagulation cessation. Conclusion: Rivaroxaban was discovered to be non-inferior to nicoumolone in terms of efficacy and safety in patients with LVT.

Evaluation of the efficacy and safety of rivaroxaban compared to warfarin in patients with left ventricular apical thrombus: a randomized clinical trial

IntroductionThis research is one of the pioneering randomized clinical trials (RCTs) aimed at assessing the effectiveness and safety of rivaroxaban in treating left ventricular thrombus (LVT) in patients who have experienced acute coronary syndrome (ACS).Materials and methodsThis is a randomized, controlled, interventional, open-label study. The patients were randomly divided into warfarin and rivaroxaban groups. We performed transthoracic echocardiography at the start of the study and again after three months to measure the thrombus area in square millimeters. The morphology of the thrombus was categorized into mural and round, and the mobility was classified into immobile, semi-mobile and hypermobile. We also monitored for adverse events including bleeding, systemic embolic occurrences, rehospitalization, and major adverse cardiac events (MACE).ResultsThe study included fifty-two patients in the intention-to-treat analysis, with an equal split between the rivaroxaban and warfarin groups (26 patients each). The average follow-up duration was three months. The thrombus resolution rates in the rivaroxaban (76.9%) and warfarin (69.2%) groups, as well as the thrombus size reduction, did not show statistical significance between groups. All semi-mobile or hypermobile thrombi transformed into immobile and all of the round LVTs changed into a mural in both rivaroxaban and warfarin groups. No significant difference was observed in bleeding complications and rehospitalization between the two groups.ConclusionThe trial demonstrated that rivaroxaban is as effective as warfarin in terms of thrombus resolution rate, reduction in thrombus size, bleeding risk, and rehospitalization rate. Our findings suggest that rivaroxaban is a viable alternative to warfarin for managing left ventricular thrombus.Graphical