Thrombus Size Research Articles

TLR3 promotes venous thrombosis through neutrophil recruitment

Venous thromboembolism (VTE) remains the third most common cause of mortality among all cardiovascular diseases. Innate inflammatory mechanisms contribute to the pathogenesis of VTE. Toll-like receptors (TLRs) play pivotal roles in the innate immune system by detecting “danger signals”. Endogenous RNA has been identified as a potent procoagulant factor in thrombosis and may possibly act through TLR3. To investigate how eRNA mediate procoagulant effects through endothelial TLR3 in venous thrombosis. The FeCl 3 model was used to induce venous thrombosis in WT or TLR3 deficient (-/-) mice. A specific fluorescent probe for RNA (Syto RNA Select), RNase1, poly(I:C) or RNA extracted from murine endothelial cells (eRNA) were injected to mice. HUVECs were treated with poly(I:C) or eRNA extracted from HEK 293 cells in the presence of a TLR3 antagonist. Gene expression and signaling pathways activated were analyzed using western blot and real-time quantitative PCR. Turbidimetric measurement of plasma clot formation was performed by incubating HUVECs treated with poly(I:C) or eRNA with human plasma. We found that FeCl 3 promoted RNA release in vivo and increased the RNA content within the thrombus. RNase1 treatment reduced thrombus size compared to control mice. In contrast, eRNA and poly(I:C) treatment increased thrombus size in WT mice whereas no modifications were observed in TLR3-/- mice. Hence, poly(I:C) and eRNA treatments bolstered neutrophil infiltration in WT but not in TLR3-/- mice. In vitro, eRNA stimulated the release of CXCL5 in WT but not in TLR3-/- endothelial cells. In addition, eRNA enhanced plasma clot formation by downregulating thrombomodulin mRNA expression. These effects are mediated through NFkB activation. These results suggest that eRNA through TLR3 enhances neutrophil recruitment and clot formation leading to venous thrombosis.

Prostacyclin Analogues Inhibit Platelet Reactivity, Extracellular Vesicle Release and Thrombus Formation in Patients with Pulmonary Arterial Hypertension.

(1) Background: Prostacyclin analogues (epoprostenol, treprostinil, and iloprost) induce vasodilation in pulmonary arterial hypertension (PAH) but also inhibit platelet function. (2) Objectives: We assessed platelet function in PAH patients treated with prostacyclin analogues and not receiving prostacyclin analogues. (3) Methods: Venous blood was collected from 42 patients treated with prostacyclin analogues (49.5 ± 15.9 years, 81% female) and 38 patients not receiving prostacyclin analogues (55.5 ± 15.6 years, 74% female). Platelet reactivity was analyzed by impedance aggregometry using arachidonic acid (AA; 0.5 mM), adenosine diphosphate (ADP; 6.5 µM), and thrombin receptor-activating peptide (TRAP; 32 µM) as agonists. In a subset of patients, concentrations of extracellular vesicles (EVs) from all platelets (CD61+), activated platelets (CD61+/CD62P+), leukocytes (CD45+), and endothelial cells (CD146+) were analyzed by flow cytometry. Platelet-rich thrombus formation was measured using a whole blood perfusion system. (4) Results: Compared to controls, PAH patients treated with prostacyclin analogues had lower platelet reactivity in response to AA and ADP (p = 0.01 for both), lower concentrations of platelet and leukocyte EVs (p ≤ 0.04), delayed thrombus formation (p ≤ 0.003), and decreased thrombus size (p = 0.008). Epoprostenol did not affect platelet reactivity but decreased the concentrations of platelet and leukocyte EVs (p ≤ 0.04). Treprostinil decreased platelet reactivity in response to AA and ADP (p ≤ 0.02) but had no effect on the concentrations of EVs. All prostacyclin analogues delayed thrombus formation and decreased thrombus size (p ≤ 0.04). (5) Conclusions: PAH patients treated with prostacyclin analogues had impaired platelet reactivity, EV release, and thrombus formation, compared to patients not receiving prostacyclin analogues.

Unilateral Corporal Cavernosum Partial Thrombosis: A Challenging Presentation and Management

A 29-year-old African American male presented to our emergency department with a 5-day history of perineal pain and tender swelling of the left perineal body with no evidence of trauma. Physical examination revealed a firm left proximal corpus cavernosum body. Laboratory tests were within normal limits. Pelvic MRI confirmed the presence of a large left-sided unilateral corporal cavernosum partial thrombosis filling the proximal third of the left corpus cavernosum. The patient was managed conservatively with anticoagulation, pain control, and pelvic rest. At 3-month follow-up, perineal imaging showed reduction of thrombus size and resolution of pain and swelling. At 6-month follow-up, a penile ultrasound demonstrated almost complete resolution of the thrombus.

Simulation Study on Blood Flow Mechanism of Vein in Existence of Different Thrombus Size

Blood velocity is expected to be as a parameter for detecting abnormality of blood such as the existence of thrombus. Proper blood flow in veins is important to ensure effective return of deoxygenated blood to the heart. However, it is much challenging to recognize the vessel condition due to the inability to visualize the thrombus presence in the vessel. The presence of noise in the image obtained from ultrasound scanning is one of the obstructions in recognizing it. Considering the difficulty, this study aims to assess the velocity and vorticity at the vein valve region using Computational Fluid Dynamics (CFD) method. The velocity of blood and the size of valve orifice are considered important parameters in designing the vein since the stenosis and irregularities of velocity in blood vessels are known as the risk factors for thrombus formation. From the simulation, the velocity contour plot of the blood flow can be visualized clearly. The blood distribution was presented using velocity profile while the fluid particles movement was shown by the velocity vector. The low blood velocity clearly shows the low velocity region which reside at the cusps area and at the beginning of the valve leaflets. Therefore, the present study is able to visualize and evaluate the probable location of thrombus development in the blood vessel.

Incidence of Catheter Related Thrombosis in Chronic Kidney Disease Patients Admitted in Intensive Care Unit and their Outcome: An Observational Study

Introduction: Central Venous Catheter (CVC) insertion is a commonly performed procedure in the Intensive Care Unit (ICU) to facilitate administration of intravenous fluids and drugs, Central Venous Pressure (CVP) measurement, and Haemodialysis (HD). It is associated with various complications including thrombus formation. Aim:To determine the incidence of thrombus, its extent, associated risk factors and outcomes, in the triple lumen HD catheter inserted in Internal Jugular Vein (IJV) in Chronic Kidney Disease (CKD) patients admitted in the ICU. Materials and Methods: This was a prospective observational study including a total of 100 patients (63 males and 37 females) of CKD, who required HD in the ICU at Pacific Institute of Medical Sciences (PIMS), Girwa, Udaipur, Rajasthan, India. The study was done from March 2017 to Mrach 2018. After admission in ICU, Arterial Blood Gas (ABG) was performed and Electrocardiography (ECG), Noninvasive Blood Pressure (NIBP), Oxygen Saturation (SpO2) monitoring was done. A triple lumen HD catheter was inserted in the IJV under all aseptic precautions. After two weeks of insertion, a colour doppler Ultrasonography (USG) neck was performed to see the presence, size and extent of thrombus in the CVC. All the pre and postprocedural demographic and clinical data of relevant investigations, past history, risk factors and complications were compiled together and compared in Microsoft excel sheet and Statistical Package for the Social Sciences (SPSS)softwares for relevant results. Results: The study found that 30% were having thrombus after two weeks of HD catheter in the IJV and most commonly detected in the diabetic patients with CKD 10 (33.33%), followed by hypertension two (6.66%), cerebro-vascular accidents one(3.33%), chronic liver diseases one (3.33%) and no thrombus was detected in patients suffering from ischemic heart diseases. The most common risk factor for thrombus formation was chronic smoking 12(40%), followed by bedridden patients two(6.66%), and chronic alcoholic patients 2(6.66%). Conclusion: This study found that early catheter-related thrombus was common in male patients with diagnosed diabetes mellitus and chronic smoking is the most common associated risk factor.

Identification of thrombomodulin as a dynamic monitoring biomarker for deep venous thrombosis evolution.

It has been demonstrated that thrombomodulin (TM) serves an important role in the formation of deep venous thrombosis (DVT) and is regarded to be a marker that can be used to measure vascular endothelial cell damage. However, how TM levels change during DVT evolution has not yet been well understood. The current study aimed to investigate the dynamic changes of TM during the evolution of DVT and explore the possible mechanisms behind these. A total of 48 patients newly diagnosed with DVT and 23 matched healthy controls were enrolled in the present study, and their plasma TM levels were examined and compared. In addition, a DVT model was established using Sprague-Dawley rats via the ‘stenosis’ method. The thrombi size, histopathologic changes and expression of TM and NF-κB in plasma and venous endothelium were measured at 9 different time points (1, 4, 6, 12 and 24 h, and at 3, 7, 14 and 21 days). Finally, the effect of inhibiting the activation of NF-κB on TM was investigated using pyrrolidine dithiocarbamate (PDTC), which is a potent inhibitor of the NF-κB pathway. The results of the current study indicated that the mean level of plasma TM in patients with DVT was significantly increased compared with healthy controls. In addition, thrombi size (clot length and weight), TM and NF-κB expression in the animal model plasma exhibited three distinct periods (1-12, 24 h-day 7 and 14-21) of markedly different results between periods. Immunofluorescence results confirmed the co-localization of TM and NF-κB in endothelial cells. In addition, it was indicated that the expression of TM in the endothelium of DVT models was upregulated compared with the control, while NF-κB was significantly downregulated. Following the administration of PDTC, the level of NF-κB and TM in the plasma were decreased significantly dose-dependently. The results of the current study suggested that TM was involved in the evolution of DVT and may be used as a dynamic biomarker to measure disease activity. Furthermore, the expression of TM during the evolution of DVT was indicated to be associated with the NF-κB signaling pathway.

A case series of ventricular cystic masses.

BackgroundVentricular cystic masses are uncommon. Elucidating the cause is essential for early directed therapy and prevention of complications. We present two cases of ventricular cystic masses, one in each ventricle, after myocardial infarction (MI) and ventricular septal rupture (VSR), respectively.Case summaryPatient 1 is a 58-year-old male with left brachio-facial stroke and evolved anterior MI. A left ventricular (LV) cystic thrombus was seen on transthoracic echocardiogram (TTE) and cardiac magnetic resonance (CMR) imaging. He was started on anticoagulation with reduction in thrombus size 11 days later. Patient 2 is a 67-year-old male with evolved anterior MI, severe LV systolic dysfunction, and normal right ventricular (RV) function. He was readmitted two weeks later with fever, heart failure, Streptococcus agalactiae bacteraemia, and septic pulmonary emboli. Transthoracic echocardiogram showed biventricular systolic dysfunction and a RV cystic mass associated with a partial VSR. He was treated with anticoagulation and antibiotics. Repeat TTE 5 weeks later revealed near resolution of the cystic mass and complete VSR. Cardiac magnetic resonance confirmed these findings and also showed a localized mid-septal transmural infarction at the VSR site. He underwent percutaneous coronary intervention to the left anterior descending and circumflex arteries, and percutaneous VSR closure with a muscular ventricular septal defect device later.DiscussionOur two cases demonstrate that ventricular thrombi can present as cystic masses after MI and VSRs. Infectious, vascular, or oncogenic causes should be considered in the appropriate clinical context. Early diagnosis and treatment is essential to prevent embolic complications, and secondary infection.

A pilot image interpretation teaching intervention to improve competence and confidence of radiographers to detect left ventricular thrombus in routine cardiac MRI scans

IntroductionPrompt diagnosis of left ventricular (LV) thrombus is clinically important, as it may require immediate anti-coagulation treatment. The aim of this study was to determine if a teaching intervention delivered by cardiovascular magnetic resonance (CMR) physicians would increase the CMR radiographers’ ability to detect LV thrombus on a routine CMR scan. MethodsA cohort of 25 patients (14 with and 11 without LV thrombus) were identified. A multi-parametric CMR protocol had been performed in all patients. Ten radiographers reviewed the 25 randomised anonymised studies on a workstation, documenting the presence/absence of LV thrombus and their confidence level on a 7-point Likert scale. Two senior CMR fellows then delivered a focused teaching programme to the radiographers and all 25 randomised scans were reassessed 1 month after the teaching intervention. ResultsFollowing dedicated training, there was a significant improvement in correct thrombus identification per radiographer (pre-training: 75 ± 6% vs post-training: 85 ± 6%, p = 0.009). The size of the thrombus was not associated with the likelihood of incorrectly identifying LV thrombus size prior to the training session (p = 0.2), but a trend was observed between smaller thrombus size and incorrect identifications post-training (p = 0.06). The radiographers’ overall confidence in assessing the cases prior to the teaching session was high (5.6 ± 0.8 out of 7). Following the teaching session, self-reported confidence did not vary significantly (5.9 ± 0.7 out of 7, p = 0.42).When evaluating the teaching session, radiographers provided very positive feedback, rating the usefulness of the teaching intervention as highly educative (8.8 ± 0.4 out of 10). ConclusionsThis is the first study that has explored the ability and confidence of CMR radiographers in detecting LV thrombus on routine CMR scans as a result of the teaching intervention delivered by CMR physicians. Implications for practiceA teaching intervention can improve CMR radiographers’ diagnostic skills and diagnostic confidence.

Tumor Thrombus- a Single Center Experience with Tumor Thrombus and Role of Anticoagulation

Background: Children with cancer diagnosis are overall at a higher risk of thrombosis. For a newly diagnosed blood clot or bland thrombus (fibrin clot without neoplastic cells), patients are commonly started on anticoagulants such as unfractionated heparin (UFH) or low molecular weight heparin (LMWH) to prevent further extension and embolization of the clot. In the rare instance that a pediatric patient has a tumor thrombus, defined as the extension of the tumor into a vessel, the role of anticoagulation is less clear. Objective: The aim of this study was to review the data of patients at Texas Children's Hospital (TCH) in the past ten years with a diagnosis of tumor thrombus, the management strategy and role of anticoagulation- its indication, response and complications noted. Methods: Patients under 21 years of age with a finding of tumor thrombus on imaging from 2010-2020 at TCH were identified and their medical records were reviewed. Demographics, location of tumor thrombus, imaging, treatment approach, use of anticoagulation, response to standard treatment (chemotherapy/surgery) and anticoagulation, and outcomes were assessed. This retrospective chart review was approved by the Institutional review board at Baylor College of Medicine. Results: We identified a total of 50 patients with a finding of tumor thrombus in the past ten years treated at our center. Most of them were incidental findings at diagnosis, however there were two patients who initially presented with pulmonary embolism (PE) and later on pathological exam of thrombectomy tissue were found to have relapse of their primary malignancy and tumor thrombus to be the etiology of the PE. Tumor thrombus was mostly identified in the systemic vessels draining the primary tumor. IVC extension was found in 36% of the patients and 24% had an intracardiac tumor thrombus (Table 1). Hepatoblastoma (26%) was most commonly associated with tumor thrombus, followed by Wilms tumor (12%) (Figure 1). Anticoagulation was initiated in 10 patients (20%) with or without standard chemotherapy (rationale for anticoagulation mentioned in Table 2), while remaining patients received the standard treatment for the primary tumor, including chemotherapy, surgery, and/or radiation. In 32.5% of the patients who did not receive anticoagulation, there was a documented decrease in size of tumor thrombus with chemotherapy. Among patients who received anticoagulation, only 2 of the 10 patients showed response to anticoagulation in terms of improvement of symptoms (Improved leg swelling in patient F, improved kidney function with resolution of Renal vein thrombus in patient H). The three patients with pulmonary embolism did not show any resolution of symptoms with initiation of anticoagulation. However, 40% (4/10) patients were noted to have bleeding complications from anticoagulation requiring brief interruption or complete stoppage of anticoagulation (Table 2). On statistical analysis, this association was found to be statistically significant with higher proportion of bleeding events occurring in patients who received anticoagulation (p= 0.01). Conclusion: Children with intravascular extension of solid tumors were not commonly started on anticoagulation at the time of diagnosis despite evidence of extensive tumor thrombus. Furthermore, we observed a significant trend toward higher incidence of bleeding complications after initiation of anticoagulation. We conclude that there is not enough evidence to support routine initiation of anticoagulation in pediatric patients with intravascular extension of solid tumors. Further studies are needed to identify high-risk groups for whom the benefits of anticoagulation may outweigh its risks. We would also emphasize that it is essential to consider a possibility of relapsed disease if patient with a history of malignancy presents with symptoms of thromboembolism and is not responding to anticoagulation as would normally expect. Disclosures No relevant conflicts of interest to declare.

Apixaban versus Warfarin in Patients with Left Ventricular (LV) Thrombus, a prospective randomized trial

Abstract Background Patients with acute myocardial infarction (MI) have an elevated risk of stroke, mostly due to left ventricular (LV) thrombus formation, which typically occur within the first 2 weeks following an anterior MI. Currently the recommended management of LV thrombus after acute MI is anticoagulation with vitamin K antagonist. To date, there are no prospective data on the use of direct oral anticoagulants (DOACS) for stroke prevention in the setting of LV thrombus. Aim To assess the efficacy of apixaban vs. warfarin in treating LV thrombus after MI. Methods The study is a prospective, randomized, multi-center open label trial comparing apixaban (at a dose of 5 mg twice daily) with s.c enoxaparin 1mg/kg BID followed by dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months in patients with LV thrombus detected by echocardiography 3 to 14 days after acute MI. The primary outcome was the presence and size of LV thrombus 3 months after initiation of anticoagulation as assessed by 2D echocardiogram. Secondary outcomes were stroke or systemic embolism, major bleeding and death from any cause. Results 25 patients have been enrolled to date in 3 medical centers, 13 were randomized to apixaban and 12 to warfarin. Mean age was 59.8±10.7 and 19 (76%) were males with no difference between the study groups. Mean LV thrombus size at enrollment was 24X15 mm in the apixaban group and 19X14 in the warfarin group (p=NS). After 3 months of treatment thrombus completely resolved in all patients in the warfarin group and in 12 of 13 in the apixaban group. In one patient in the apixaban group who had a very large thrombus of 40x20mm size upon enrollment the thrombus size was reduced significantly to 20x12 after 3 months. No death, stroke or systemic embolism was documented in either group. There were two patients with major bleeding in the warfarin group, one had sub-arachnoid hemorrhage after 2 months and anticoagulation was stopped, and another had GI bleeding after 1 month and was switched to enoxaparin. One patient in the warfarin group refused to continue the treatment after 3 weeks. No major bleeding events were recorded in the apixaban group and all patients completed 3 months of treatment. Conclusions Our preliminary results indicate that apixaban is a safe and effective treatment for patients with LV thrombus post anterior wall MI. Funding Acknowledgement Type of funding source: None

Pulmonary emphysema and atherosclerosis: association or syndrome?

BackgroundAtherosclerosis is an inflammatory reaction of the vessel wall. Emphysema may induce systemic inflammation, part of which may be the development or progression of atherosclerosis. So, the relationship between emphysema and atherosclerosis, whether both are due to the same causative agent and pathogenesis or emphysema led to atherosclerosis, is still not clearly understood. So, the aim of this work is to study the relationship between carotid atherosclerosis versus pulmonary emphysema extent and airflow obstruction.ResultsCigarette smoking index was higher in patients than controls. According to FEV1%, patients were classified into: GOLD 1 (mild): FEV1 ≥ 80% predicted, GOLD 2 (moderate): 50% ≤ FEV1 < 80% predicted, GOLD 3 (severe):30% ≤ FEV1 < 50% predicted, and GOLD 4 (very severe): FEV1 < 30% predicted. There was a significant difference between the studied groups as regard to ABG parameters. Emphysema score showed a positive correlation with thrombus size, plaque size, and stenosis percent. Approximately 2/3 of patients had atherosclerotic changes and the other 1/3 had increased IMT. GOLD staging, also, correlated with thrombus size and stenosis percent. So, there was a strong positive correlation between both emphysema score and GOLD staging and carotid atherosclerosis.ConclusionThe relationship between emphysema and atherosclerosis is suggested to be the chronic inflammatory reaction (against the same risk factor) based on the positive correlation between carotid atherosclerosis versus emphysema score and GOLD staging. The inherence of emphysema and atherosclerosis may be considered a syndrome. If so, targeting the same pathogenic mechanism will be valuable for their control.

Platelet Dysfunction and Thrombosis in JAK2V617F-Mutated Primary Myelofibrotic Mice.

The risk of thrombosis in myeloproliferative neoplasms, such as primary myelofibrosis varies depending on the type of key driving mutation (JAK2 [janus kinase 2], CALR [calreticulin], and MPL [myeloproliferative leukemia protein or thrombopoietin receptor]) and the accompanying mutations in other genes. In the current study, we sought to examine the propensity for thrombosis, as well as platelet activation properties in a mouse model of primary myelofibrosis induced by JAK2V617F (janus kinase 2 with valine to phenylalanine substitution on codon 617) mutation. Approach and Results: Vav1-hJAK2V617F transgenic mice show hallmarks of primary myelofibrosis, including significant megakaryocytosis and bone marrow fibrosis, with a moderate increase in red blood cells and platelet number. This mouse model was used to study responses to 2 models of vascular injury and to investigate platelet properties. Platelets derived from the mutated mice have reduced aggregation in response to collagen, reduced thrombus formation and thrombus size, as demonstrated using laser-induced or FeCl3-induced vascular injury models, and increased bleeding time. Strikingly, the mutated platelets had a significantly reduced number of dense granules, which could explain impaired ADP secretion upon platelet activation, and a diminished second wave of activation. Together, our study highlights for the first time the influence of a hyperactive JAK2 on platelet activation-induced ADP secretion and dense granule homeostasis, with consequent effects on platelet activation properties.

Application of thromboelastography combined with point-of-care ultrasound to prevent internal jugular vein catheterization related thrombosis

To investigate the effect of thromboelastography (TEG) combined with point-of-care ultrasound (POCUS) guidance on the prevention of internal jugular vein catheterization related thrombosis. The patients who required internal jugular vein catheterization admitted to the department of critical medicine of Beihai People's Hospital from December 2018 to April 2020 were enrolled. Patients were divided into two groups according to the random number table method. For the combined cathetherization group, ultrasound was used to examine bilateral internal jugular veins before catheterization. The larger diameter and better filled vein and site were selected for puncture. If both internal jugular veins were not fulfilled well, puncture were performed after fluid administration. At the same time, anticoagulant, antiplatelet or reducing blood viscosity drugs were used according to coagulation function and bleeding risk under the monitoring of TEG. The hemodynamic state of the internal jugular vein was monitored by ultrasound every day. If the vein collapsed or the blood flow was slow, the cause should be tried to be found and improved. Once thrombosis was found, the catheter should be removed. For the routine cathetherization group, the right side internal jugular vein was prior to be punctured according to body surface symbols. The other treatment of the two groups were the same as routine treatment. The conditions of thrombosis and bleeding were recorded. Ninety-seven patients were selected, 51 cases in the combined cathetherization group and 46 cases in the routine cathetherization group. There was no significant differences in gender, age, acute physiology and chronic health evaluation II (APACHE II), risk of deep vein thrombosis score (Caprini), CRUSADE bleeding risk score, the proportion of high bleeding risk, disease types, the proportion of coagulation disorder and catheterization time between the two groups, but the anticoagulation treatment proportion in the combined cathetherization group was higher than that in the routine cathetherization group (66.7% vs. 30.4%, P < 0.01). The incidence of thrombosis in the combined cathetherization group was lower than that of the routine cathetherization group (39.2% vs. 78.3%, P < 0.01), and the thrombus of the combined cathetherization group was smaller than that of the routine cathetherization group [cm3: 0.077 (0.047, 0.089) vs. 0.341 (0.070, 0.378), P < 0.01]. There were no major bleeding events in the two groups. Based on TEG and POCUS, the antithrombotic bundles can reduce the incidence of thrombosis after internal jugular vein catheterization and the thrombus size, and does not increase the risk of bleeding, which is worthy of clinical application.

In vitro real-time magnetic resonance imaging for quantification of thrombosis.

Thrombosis is a leading cause of failure for cardiovascular devices. While computational simulations are a powerful tool to predict thrombosis and evaluate the risk for medical devices, limited experimental data are available to validate the simulations. The aim of the current study is to provide experimental data of a growing thrombus for device-induced thrombosis. Thrombosis within a backward-facing step (BFS), or sudden expansion was investigated, using bovine and human blood circulated through the BFS model for 30min, with a constant inflow rate of 0.76 L/min. Real-time three-dimensional flow-compensated magnetic resonance imaging (MRI), supported with Magnevist, a contrast agent improving thrombus delineation, was applied to quantify thrombus deposition and growth within the model. The study showed that the BFS model induced a flow recirculation region, which facilitated thrombosis. By 30min, in comparison to bovine blood, human blood resulted in smaller thrombus formation, in terms of the length (13.3 ± 0.6 vs. 18.1 ± 1.3mm), height (2.3 ± 0.1 vs. 2.6 ± 0.04mm), surface area exposed to blood (0.67 ± 0.03 vs 1.05 ± 0.08cm2), and volume (0.069 ± 0.004 vs. 0.093 ± 0.007cm3), with p < 0.01. Normalization of the thrombus measurements, which excluded the flow recirculation effects, suggested that the thrombus sizes increased during the first 15min and stabilized after 20min. Blood properties, including viscosity, hematocrit, and platelet count affected thrombosis. For the first time, contrast agent-supported real-time MRI was performed to investigate thrombus deposition and growth within a sudden expansion. This study provides experimental data for device-induced thrombosis, which is valuable for validation of computational thrombosis simulations.

Small thrombus size, thrombus composition, and poor collaterals predict pre-interventional thrombus migration

BackgroundDifferent imaging characteristics such as clot burden score, collaterals, and pre-interventional thrombus migration are associated with functional outcome in patients with acute ischemic stroke. Moreover, histological thrombus composition is associated...

AKT2 regulates endothelial-mediated coagulation homeostasis and promotes intrathrombotic recanalization and thrombus resolution in a mouse model of venous thrombosis.

Venous thromboembolism (VTE) carries a high risk of morbidity and mortality. Understanding the mechanisms of venous thrombus formation and resolution is critical for improving VTE management. AKT2 kinase is essential for platelet activation and arterial thrombosis. In this study, we examined the role of AKT2 in venous thrombosis in a mouse model of venous thrombosis induced by inferior vena cava (IVC) ligation. We observed an induction of AKT2 expression in the ligated IVC of wild-type (WT) mice. Interestingly, although the initial thrombus size of the ligated IVC was similar between Akt2-/- mice and WT mice, thrombus resolution was delayed in the ligated IVC of Akt2-/- mice. Compared with the ligated IVC of WT mice, the ligated IVC of Akt2-/- mice displayed decreased levels of thrombomodulin (TM) and increased levels of tissue factor (TF), apoptosis, and necroptosis. In addition, intrathrombotic endothelial cells in the ligated IVC of Akt2-/- mice failed to form small vessels, resulting in impaired recanalization and thrombus resolution. TGF-β signaling activation and fibrotic remodeling were increased in the thrombus and vein wall of the ligated IVC of Akt2-/-mice. We further investigated the AKT2-mediated regulation of coagulation factors in endothelial cells and found that forkhead box protein O1 (FOXO1), a target of AKT, enhanced TF and inhibited TM expression. By inhibiting FOXO1, AKT2 suppressed TF expression while increasing TM expression. Our findings indicate that AKT2 may protect endothelial cells against cell death, regulate endothelial-mediated coagulation homeostasis, and promote intrathrombotic recanalization and thrombus resolution in venous thrombosis. These observations suggest dynamic roles of AKT2 in venous thrombus formation and resolution.

Clinical outcomes and thrombus resolution in patients with solid left atrial appendage thrombi: results of a single-center real-world registry.

Data on thrombus resolution and clinical outcome data after a therapy of LAA thrombus with novel oral anticoagulants (NOACs) are scarce. In this single-center study, we retrospectively analyzed 78 patients diagnosed with a solid LAA thrombus by transesophageal echocardiography (TEE). We assessed baseline clinical and echocardiographic characteristics, the anticoagulatory regimens and outcomes of patients with (responders) and without (non-responders) thrombus resolution. Mean age was 76.1 ± 8.3years, patients were male in 57.7% and presented with a high risk for thromboembolism (CHA2DS2-VASc: 4.3 ± 1.1). At thrombus diagnosis, 44.9% patients were treated with a NOAC, while 41.0% were under therapy with a VKA. Complete thrombus resolution was achieved after a mean of 116 ± 79days in a total of 51.3% of patients, 35.9% showed a reduction of thrombus size, whereas 12.8% showed no changes in thrombus dimensions. There was no statistically significant difference in the rate of LAA thrombus resolution between VKA and NOACs (41.2 vs. 57.1%, p = 0.18). However, in cases in which only the therapy with a NOAC led to complete thrombus resolution, the time needed was significantly shorter than with VKA (81 ± 38 vs. 129 ± 46days, p = 0.03). Regarding safety outcomes, no differences in bleeding or thromboembolism were observed between patients with and without thrombus resolution. In this registry, approximately 85% of LAA thrombi were diagnosed in patients with ongoing OAC. Thrombus resolution was observed in nearly 50% of cases. Although there was no difference in the rate of LAA thrombus resolution between VKA and NOACs, the resolution time was shorter in patients prescribed a NOAC.

MP14-12 STEREOTACTIC ABLATIVE RADIATION THERAPY (SABR) FOR TREATMENT OF RENAL CELL CARCINOMA (RCC) WITH INFERIOR VENA CAVA TUMOR THROMBUS (IVC-TT)

INTRODUCTION AND OBJECTIVE:The mainstay of treatment for patients with RCC IVC-TT is surgical resection; however, surgery is associated with high morbidity rates. Furthermore, many of these patient...

Observation of granulocyte function during ex vivo thrombus formation for patients with ANKRD26-associated thrombocytopenia

ANKRD26-associated thrombocytopenia is a non-syndromic hereditary thrombocytopenia for which there are currently no formal diagnostic criteria. It is known that the probability of myeloid leukemia in patients with pathogenetic variants in the ANKRD26 gene significantly increases, however, studies of the functioning of granulocytes in this pathology have not been conducted. Aims: Analysis of the functioning of granulocytes and platelets during ex vivo thrombosis in patients with ANKRD26-associated thrombocytopenia. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. Two patients and 10 healthy volunteers were included in the study. Intracellular signaling and platelet functional responses were observed by continuous flow cytometry. Ex vivo thrombus formation and granulocyte functioning were observed on a fluorescence microscope in parallel-plane flow chambers containing fibrillar collagen. Upon physiological activation (ADP, collagen) of patients’ platelets in vitro, there were no significant differences between the platelets of patients and healthy donors. However, the observed ex vivo size of platelet aggregates was significantly reduced in comparison with healthy donors and published data on patients with other thrombocytopenias. The observed number and activity (movement velocity) of granulocytes of patients was within normal values. However, significant morphological differences were observed for granulocytes of patients compared with granulocytes of healthy donors: there was an increased spreading of granulocytes, in particular, expressed in a large number of thin pseudopodia, as well as an increased curvature of the motion trajectories of granulocytes. Ex vivo observation of thrombus formation in patients with ANKRD26- associated thrombocytopenia, a significantly reduced thrombus size is observed with normal platelet activity and increased variability in the shape of granulocytes.

LncRNA GUSBP5-AS promotes EPC migration and angiogenesis and deep vein thrombosis resolution by regulating FGF2 and MMP2/9 through the miR-223-3p/FOXO1/Akt pathway.

Long non-coding RNAs (lncRNAs) play an essential role in multitudinous physiological and pathological processes, including vascular disease. We previously showed that lncRNA GUSBP5-AS (enst00000511042) is upregulated in endothelial progenitor cells (EPCs) of deep veni thrombosis (DVT) patients. Here, we investigate the role and mechanism of GUSBP5-AS in EPCs and DVT. Using the DVT model, we found that GUSBP5-AS significantly reduced the thrombus size and weight and enhanced the homing ability of EPC to DVT sites to promote resolution and recanalization of thrombus. GUSBP5-AS promoted cell cycle progression, proliferation, migration and invasion in EPCs, enhanced EPC angiogenesis in vitro and in vivo, and inhibited apoptosis. Strikingly, this study showed that GUSBP5-AS was unbalanced and modulated Forkhead Box Protein O1 (FOXO1) in EPCs in patients with DVT by interacting with miR-223-3p. Mechanistically, GUSBP5-AS functions as a sponge of miR-223-3p, which targets FOXO1. Both GUSBP5-AS knockdown and miR-223-3p overexpression remarkably inhibited angiogenesis, migration and invasion in EPCs. Additionally, our data suggested that GUSBP-AS activated the Akt pathway and enhanced fibroblast growth factor 2 (FGF2), matrix metalloproteinase-2/9 (MMP2/9) and F-actin expression. Taken together, this study indicates that GUSBP5-AS modulates angiogenesis, proliferation and homing ability of EPCs via regulating FGF2 and MMP2/9 expression through the miR-223-3p/FOXO1/Akt pathway, which may provide a new direction for the development of DVT therapeutics.