Thrombus Volume Research Articles

Predictors of non-stenting strategy for acute coronary syndrome caused by plaque erosion: four-year outcomes of the EROSION study.

The EROSION study demonstrated that patients with an acute coronary syndrome (ACS) caused by plaque erosion could be treated with antithrombotic therapy without stenting. However, the long-term prognosis of this strategy is still unclear. The aim of this study was to test whether a non-stenting antithrombotic strategy was still effective at four-year follow-up and to explore potential predictors of long-term prognosis. This study was a long-term follow-up of the EROSION study. Follow-up was conducted by phone call or clinical visit. Patients were divided into two groups - those with target lesion revascularisation (the TLR group), and the non-TLR group. Out of 55 patients who completed one-month follow-up, 52 patients finished four-year follow-up. The median duration was 4.8 years (range, 4.2-5.8 years). The majority of patients remained free from events, and all patients were free from hard endpoints (death, myocardial infarction, stroke, bypass surgery, or heart failure). Only one patient had gastrointestinal bleeding, and 11 patients underwent TLR. Patients in the non-TLR group had more optical coherence tomography (OCT) thrombus reduction from baseline to one month; 95% of patients in the non-TLR group versus 45% in the TLR group (p=0.001) met the primary endpoint (thrombus volume reduction >50%). Angiographic results showed that the TLR group had less improvement in diameter stenosis (p=0.014) at one month compared with the non-TLR group. Four-year follow-up findings reconfirmed the safety of an antithrombotic therapy without stenting for ACS caused by erosion. Patients with better response to antithrombotic therapy in the first month were less likely to require stent implantation during the next four years.

Laser Vaporization of Intracoronary Thrombus and Identifying Plaque Morphology in ST-Segment Elevation Myocardial Infarction as Assessed by Optical Coherence Tomography.

Objectives We evaluated the thrombus-vaporizing effect of excimer laser coronary angioplasty (ELCA) in patients with ST-segment elevation myocardial infarction (STEMI) by optical coherence tomography (OCT). Background Larger intracoronary thrombus elevates the risk of interventional treatment and mortality in patients with STEMI. Methods A total of 92 patients with STEMI who presented within 24 hours from the onset and underwent ELCA following manual aspiration thrombectomy (MT) were analyzed. Results The mean baseline thrombolysis in myocardial infarction flow grade was 0.4 ± 0.6, which subsequently improved to 2.3 ± 0.7 after MT (p < 0.0001) and 2.7 ± 0.5 after ELCA (p=0.0001). The median residual thrombus volume after MT was 65.7 mm3, which significantly reduced to 47.5 mm3 after ELCA (p < 0.0001). Plaque rupture was identified by OCT in only 22 cases (23.9%) after MT, but was distinguishable in 36 additional cases after ELCA (total: 58 cases; 63.0%). Ruptured lesions contained a higher proportion of red thrombus than nonruptured lesions (75.9% vs. 43.3%, p=0.001). Significantly larger thrombus burden after MT (69.6 mm3 vs. 56.3 mm3, p < 0.05) and greater thrombus reduction by ELCA (21.2 mm3 vs. 11.8 mm3, p < 0.01) were observed in ruptured lesions than nonruptured lesions. Conclusions ELCA effectively vaporized intracoronary thrombus in patients with STEMI even after MT. Lesions with plaque rupture contained larger thrombus burden that was frequently characterized by red thrombus and more effectively reduced by ELCA.

Post-implantation syndrome after frozen elephant trunk is associated with the volume of new-onset aortic thrombus.

BackgroundPost-implantation syndrome (PIS) is defined as non-infectious continuous fever and a concomitant rise in inflammatory markers shortly after endovascular aortic repair. PIS occurrence after hybrid procedures, such as the frozen elephant trunk (FET) technique, has not been adequately investigated. The current study aims to define the incidence of PIS after the FET and to identify possible risk factors associated with its occurrence.MethodsThe clinical charts of 59 patients undergoing the FET between February 2015 and April 2020 were reviewed retrospectively. The occurrence of PIS was defined as the presence of fever (>38 °C lasting longer than one day during the hospitalisation) and leucocytosis (white blood cell count >12,000/µL). Patients with concomitant conditions possibly leading to fever and/or leucocytosis were excluded. Beside demographic and procedure-related data, serum/plasma inflammatory markers were evaluated before surgery and daily up to seven days postoperatively. Computed tomography scans (CT) were examined to calculate the volume of pre-existent and new-onset mural thrombus after the FET.ResultsThirty-eight patients met the inclusion criteria. The study cohort was divided into two groups based on the occurrence of PIS (17 cases; 44.7%). Patients with PIS were significantly younger than those without PIS (53.5±8.9 vs. 62.5±9.6 years; P=0.005). Female patients were less likely to develop PIS (5.2% vs. 26.3%, P=0.018). Patients with PIS had a higher volume of new-onset thrombus in the postoperative CT (P<0.001). Patients treated for post-dissection aneurysm had, postoperatively, significantly more thrombus material developed in a false lumen (P=0.02). Among the PIS markers, CRP (C-reactive protein) levels on the third postoperative day were independently associated with the volume of new-onset thrombus (P=0.011). After multivariate analysis, the volume of new-onset thrombus (P=0.028) and age (P=0.036) remained the variable associated with a statistically significant increased incidence of PIS.ConclusionsPIS can occur after the frozen elephant trunk procedure. The volume of new-onset thrombus seems to be associated with an increased incidence of PIS. These findings need to be confirmed in larger patient cohorts.

Visceral segment aortic thrombus is associated with proximal aortic degeneration after infrarenal abdominal aortic aneurysm repair.

To identify predictors of aortic aneurysm formation at or above an infrarenal abdominal aortic aneurysm repair. A total of 881 infrarenal abdominal aortic aneurysm repairs were identified at a single institution from 2004 to 2008; 187 of the repairs were identified that had pre-operative and post-operative computed tomography imaging at least one year or greater to evaluate for aortic degeneration following repair. Aortic diameters at the celiac, superior mesenteric, and renal arteries were measured on all available computed tomographic scans. Aortic thrombus and calcification volumes in the visceral and infrarenal abdominal aortic segments were calculated. Multivariable modeling was used with log transformed variables to determine potential predictors of future aortic aneurysm development after infrarenal abdominal aortic aneurysm repair. Of the 187 patients in the cohort, 100 had an open abdominal aortic aneurysm repair while 87 were treated with endovascular repair. Proximal aortic aneurysms developed in 26% (n = 49) of the cohort during an average of 72 ± 34.2 months of follow-up. After multivariable modeling, visceral segment aortic thrombus on pre-operative computed tomography imaging increased the risk of aortic aneurysm development above the infrarenal abdominal aortic aneurysm repair within both the open abdominal aortic aneurysm (hazard ratio 2.04, p = 0.033) and endovascular repair (hazard ratio 3.31, p = 0.004) cohorts. Endovascular repair was independently associated with a higher risk of future aortic aneurysm development after infrarenal abdominal aortic aneurysm repair when compared to open abdominal aortic aneurysm (hazard ratio 2.19, p = 0.025). Visceral aortic thrombus present prior to abdominal aortic aneurysm repair and endovascular repair are both associated with an increased risk of future proximal aortic degeneration after infrarenal abdominal aortic aneurysm repair. These factors may predict patients at higher risk of developing proximal aortic aneurysms that may require complex aortic repairs.

In vitro assessment and phase I randomized clinical trial\xa0of anfibatide a snake venom derived anti-thrombotic agent targeting human platelet GPIb\u03b1

The interaction of platelet GPIbα with von Willebrand factor (VWF) is essential to initiate platelet adhesion and thrombosis, particularly under high shear stress conditions. However, no drug targeting GPIbα has been developed for clinical practice. Here we characterized anfibatide, a GPIbα antagonist purified from snake (Deinagkistrodon acutus) venom, and evaluated its interaction with GPIbα by surface plasmon resonance and in silico modeling. We demonstrated that anfibatide interferds with both VWF and thrombin binding, inhibited ristocetin/botrocetin- and low-dose thrombin-induced human platelet aggregation, and decreased thrombus volume and stability in blood flowing over collagen. In a single-center, randomized, and open-label phase I clinical trial, anfibatide was administered intravenously to 94 healthy volunteers either as a single dose bolus, or a bolus followed by a constant rate infusion of anfibatide for 24 h. Anfibatide inhibited VWF-mediated platelet aggregation without significantly altering bleeding time or coagulation. The inhibitory effects disappeared within 8 h after drug withdrawal. No thrombocytopenia or anti-anfibatide antibodies were detected, and no serious adverse events or allergic reactions were observed during the studies. Therefore, anfibatide was well-tolerated among healthy subjects. Interestingly, anfibatide exhibited pharmacologic effects in vivo at concentrations thousand-fold lower than in vitro, a phenomenon which deserves further investigation.Trial registration: Clinicaltrials.gov NCT01588132.

Society for Vascular Surgery implementation of clinical practice guidelines for patients with an abdominal aortic aneurysm: Endoleak management

Society for Vascular Surgery implementation of clinical practice guidelines for patients with an abdominal aortic aneurysm: Endoleak management

Optical Coherence Tomography-Based Patient-Specific Residual Multi-Thrombus Coronary Plaque Models With Fluid-Structure Interaction for Better Treatment Decisions: A Biomechanical Modeling Case Study.

Intracoronary thrombus from plaque erosion could cause fatal acute coronary syndrome (ACS). A conservative antithrombotic therapy has been proposed to treat ACS patients in lieu of stenting. It is speculated that the residual thrombus after aspiration thrombectomy would influence the prognosis of this treatment. However, biomechanical mechanisms affecting intracoronary thrombus remodeling and clinical outcome remain largely unknown. in vivo optical coherence tomography (OCT) data of a coronary plaque with two residual thrombi after antithrombotic therapy were acquired from an ACS patient with consent obtained. Three OCT-based fluid-structure interaction (FSI) models with different thrombus volumes, fluid-only, and structure-only models were constructed to simulate and compare the biomechanical interplay among blood flow, residual thrombus, and vessel wall mimicking different clinical situations. Our results showed that residual thrombus would decrease coronary volumetric flow rate by 9.3%, but elevate wall shear stress (WSS) by 29.4% and 75.5% at thrombi 1 and 2, respectively. WSS variations in a cardiac cycle from structure-only model were 12.1% and 13.5% higher at the two thrombus surfaces than those from FSI model. Intracoronary thrombi were subjected to compressive forces indicated by negative thrombus stress. Tandem intracoronary thrombus might influence coronary hemodynamics and solid mechanics differently. Computational modeling could be used to quantify biomechanical conditions under which patients could receive patient-specific treatment plan with optimized outcome after antithrombotic therapy. More patient studies with follow-up data are needed to continue the investigation and better understand mechanisms governing thrombus remodeling process.

Micro-CT-Based Quantification of Extracted Thrombus Burden Characteristics and Association With Angiographic Outcomes in Patients With ST-Elevation Myocardial Infarction: The QUEST-STEMI Study

Background: Angiographic detection of thrombus in STEMI is associated with adverse outcomes. However, routine thrombus aspiration failed to demonstrate the anticipated benefit. Hence, management of high coronary thrombus burden remains challenging. We sought to assess for the first time extracted thrombotic material characteristics utilizing micro-computed tomography (micro-CT).Methods: One hundred thirteen STEMI patients undergoing thrombus aspiration were enrolled. Micro-CT was undertaken to quantify retrieved thrombus volume, surface, and density. Correlation of these indices with angiographic and electrocardiographic outcomes was performed.Results: Mean aspirated thrombus volume, surface, and density (±standard deviation) were 15.71 ± 20.10 mm3, 302.89 ± 692.54 mm2, and 3139.04 ± 901.88 Hounsfield units, respectively. Aspirated volume and surface were significantly higher (p < 0.001) in patients with higher angiographic thrombus burden. After multivariable analysis, independent predictors for thrombus volume were reference vessel diameter (RVD) (p = 0.011), right coronary artery (RCA) (p = 0.039), and smoking (p = 0.027), whereas RVD (p = 0.018) and RCA (p = 0.019) were predictive for thrombus surface. Thrombus volume and surface were independently associated with distal embolization (p = 0.007 and p = 0.028, respectively), no-reflow phenomenon (p = 0.002 and p = 0.006, respectively), and angiographically evident residual thrombus (p = 0.007 and p = 0.002, respectively). Higher thrombus density was correlated with worse pre-procedural TIMI flow (p < 0.001). Patients with higher aspirated volume and surface developed less ST resolution (p = 0.042 and p = 0.023, respectively).Conclusions: Angiographic outcomes linked with worse prognosis were more frequent among patients with larger extracted thrombus. Despite retrieving larger thrombus load in these patients, current thrombectomy devices fail to deal with thrombotic material adequately. Further studies of novel thrombus aspiration technologies are warranted to improve patient outcomes.Clinical Trial Registration: QUEST-STEMI trial ClinicalTrials.gov number: NCT03429608 Date of registration: February 12, 2018. The study was prospectively registered.

Thrombin-Fibrinogen In Vitro Flow Model of Thrombus Growth in Cerebral Aneurysms.

Cerebral aneurysms are balloon-like structures that develop on weakened areas of cerebral artery walls, with a significant risk of rupture. Thrombi formation is closely associated with cerebral aneurysms and has been observed both before and after intervention, leading to a wide variability of outcomes in patients with the condition. The attempt to manage the outcomes has led to the development of various computational models of cerebral aneurysm thrombosis. In the current study, we developed a simplified thrombin–fibrinogen flow system, based on commercially available purified human-derived plasma proteins, which enables thrombus growth and tracking in an idealized cerebral aneurysm geometry. A three-dimensional printed geometry of an idealized cerebral aneurysm and parent vessel configuration was developed. An unexpected outcome was that this phantom-based flow model allowed us to track clot growth over a period of time, by using optical imaging to record the progression of the growing clot into the flow field. Image processing techniques were subsequently used to extract important quantitative metrics from the imaging dataset, such as end point intracranial thrombus volume. The model clearly demonstrates that clot formation, in cerebral aneurysms, is a complex interplay between mechanics and biochemistry. This system is beneficial for verifying computational models of cerebral aneurysm thrombosis, particularly those focusing on initial angiographic occlusion outcomes, and will also assist manufacturers in optimizing interventional device designs.

Curcumin protects against inflammation and lung injury in rats with acute pulmonary embolism with the involvement of microRNA-21/PTEN/NF-κB axis.

This study was intended to investigate the effect of Curcumin on acute pulmonary embolism (APE) via microRNA-21 (miR-21)/PTEN/NF-κB axis. APE model was induced on rats and administrated with Curcumin. Western blot analysis and RT-qPCR manifested the downregulation of Sp1, miR-21 and NF-κB, but the upregulation of PTEN in Curcumin-treated APE rats. Blood gas analysis, ELISA, and weighing of wet weight/dry weight (W/D) ratio indicated that Curcumin diminished mPAP and RVSP levels, W/D ratio, thrombus volume, and inflammatory factors in the lungs of APE rats. Further mechanical analysis was conducted by dual-luciferase reporter assays and ChIP assay, which showed that Sp1 increased miR-21 expression by binding to the miR-21 promoter, and that PTEN was targeted by miR-21. The APE rats were injected with adenovirus to evaluate the effect of Sp1, miR-21, or PTEN on lung injury and inflammation. It was observed that downregulation of miR-21 or Sp1, or upregulation of PTEN diminished mPAP and RVSP levels, W/D ratio, thrombus volume, and inflammatory factors in the lungs of APE rats. In summary, Curcumin decreased miR-21 expression by downregulating Sp1 to upregulate PTEN and to impair the NF-κB signaling pathway, thus suppressing lung injury and inflammation in APE rats.

Shear and Integrin Outside-In Signaling Activate NADPH-Oxidase 2 to Promote Platelet Activation.

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Abstract P347: Thrombus Age and Volume as Predictors of Recanalization and Functional Outcome in Patients With Cerebral Venous Thrombosis

Background: Cerebral Venous Thrombosis (CVT) is an infrequent type of cerebrovascular disease with variable functional outcomes. Different studies have been carried out to identify such predicting factors. Few studies have focused on imaging findings as predictive factors for recanalization and functional outcome after CVT. We analyzed the association of clot burden with image and functional outcomes in CVT. Methods: This is a retrospective, cross-sectional study of patients with diagnosis of CVT conducted from November 2003 to august 2019. Imaging data was obtained from PACS system and processed with ITK-SNAP1 program for 3D volumetric measurement of the thrombus; through analysis of T1, T2 and SWI sequences the age of the thrombus was determined. Functional outcome was evaluated using the modified Rankin Scale (mRS) at discharge and 3 months after index event. In order to assess the reproducibility of the thrombus measurement method, a second investigator was assigned to perform similar measurements in 10 patients selected randomly. The age and volume of the thrombus to predict recanalization was evaluated through ROC analysis. Results: Twenty-nine patients were studied of which 79.3% were women (n = 23), mean age was 37.79 ± 13.8 years; the superior longitudinal sinus (SLS) was the main sinus affected 44.8% (n = 13) and 44.7% (n = 13) had direct signs on CT study. Mean thrombus volume was 5,463 mm3 ± 6,501 mm3. Regarding the age of the thrombus 72.4% (n = 21) was qualified as acute thrombus with a mean time of 7.21 ± 8.1 days. Age of thrombus demonstrated statistical association with venous sinus recanalization (p = 0.033). Age and volume of the thrombus did not reach statistical significance for functional outcome. The optimal cut-off for the age of the thrombus for complete sinus recanalization in patients with CVT was 4.5 days (Sensitivity of 60% and Specificity of 30%). Conclusion: This is a pilot study that evaluated CVT imaging factors for sinus recanalization and functional outcome. Although volume of the thrombus did not predict recanalization, parenchymal lesions or functional outcome in patients with CVT, acute thrombus age could serve as a predictive factor for venous sinus recanalization which is related to functional outcome in these patients.

The role of platelets in thrombus fibrosis and vessel wall remodeling after venous thrombosis

PurposePlatelets are known to play an important role in venous thrombogenesis, but their role in thrombus maturation, resolution, and postthrombotic vein wall remodeling is unclear. The purpose of this study was to determine the role that circulating platelets play in the later phases of venous thrombosis. MethodsWe used a murine inferior vena cava (IVC) stenosis model. Baseline studies in untreated mice were performed to determine an optimal postthrombotic time point for tissue harvest that would capture both thrombus maturation/resolution and postthrombotic vein wall remodeling. This time point was found to be postoperative day 10. After undergoing IVC ultrasound on day 2 to confirm venous thrombus formation, mice were treated with a daily injection of platelet‐depleting antibody (anti‐GP1bα) to maintain thrombocytopenia or with control IgG until postoperative day 10, at which time IVC and thrombi were harvested and thrombus length, volume, fibrosis, neovascularization, and smooth muscle cell invasion analyzed. Vein wall fibrosis and intimal thickening were also determined. ResultsMice that were made thrombocytopenic after venous thrombogenesis had thrombi that were less fibrotic, with fewer invading smooth muscle cells. Furthermore, thrombocytopenia in the setting of venous thrombosis resulted in less postthrombotic vein wall intimal thickening. Thrombus volume did not differ between thrombocytopenic mice and their control peers. ConclusionsThis work suggests that circulating platelets contribute to venous thrombus maturation, fibrosis, and adverse vein wall remodeling, and that that inhibition of platelet recruitment may decrease thrombus and vein wall fibrosis, thus helping thrombolysis and preventing postthrombotic syndrome.

Quantitative evaluation of computed tomography findings in patients with pulmonary embolism: the link between D-Dimer level and thrombus volume.

To investigate the correlation of D-dimer levels and computed tomography properties of pulmonary embolism. A total of 58 treated patients with diagnosis of properties of pulmonary embolism were retrospectively studied. All patients underwent a D-dimer blood test. In computed tomography images, septal angle, interventricular septal thickness, and the diameters of all cardiac chambers and pulmonary arteries were measured. The thrombus volume (load) and density at all pulmonary arteries (main, right, left pulmonary arteries, and segmental arteries) were calculated. A significant correlation was found between D-dimer and total thrombus volume (p=0.009, r=0.342). Total thrombus volume and total thrombus density were calculated with mean value of 23.40±60.63 ml and 66.16±38.48 hounsfield unit (HU), respectively. Right ventricle/left ventricle ratio showed positive correlation with the D-dimer level (p=0.02). Increased D-dimer levels with RV/LV ratio and their correlation with total thrombus volume suggest that it may be a prognostic factor.

Serum Ceramides as Prognostic Biomarkers of Large Thrombus Burden in Patients with STEMI: A Micro-Computed Tomography Study.

ST-elevation myocardial infarction (STEMI) remains one of the leading causes of mortality worldwide. The identification of novel metabolic and imaging biomarkers could unveil key pathophysiological mechanisms at the molecular level and promote personalized care in patients with acute coronary syndromes. We studied 38 patients with STEMI who underwent primary percutaneous coronary intervention and thrombus aspiration. We sought to correlate serum ceramide levels with micro-CT quantified aspirated thrombus volume and relevant angiographic outcomes, including modified TIMI thrombus grade and pre- or post-procedural TIMI flow. Higher ceramide C16:0 levels were significantly but weakly correlated with larger aspirated thrombus volume (Spearman r = 0.326, p = 0.046), larger intracoronary thrombus burden (TB; p = 0.030) and worse pre- and post-procedural TIMI flow (p = 0.049 and p = 0.039, respectively). Ceramides C24:0 and C24:1 were also significantly associated with larger intracoronary TB (p = 0.008 and p = 0.001, respectively). Receiver operating characteristic analysis demonstrated that ceramides C24:0 and C24:1 could significantly predict higher intracoronary TB (area under the curve: 0.788, 95% CI: 0.629–0.946 and 0.846, 95% CI: 0.706–0.985, respectively). In conclusion, serum ceramide levels were higher among patients with larger intracoronary and aspirated TB. This suggests that quantification of serum ceramides might improve risk-stratification of patients with STEMI and facilitate an individualized approach in clinical practice.

Radial artery thrombosis in optical coherence tomography guided transradial coronary angiography and percutaneous coronary intervention in acute coronary syndrome patients and its risk factors analysis

Objective: To observe the radial artery thrombosis (RAT) during transradial coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) by optical coherence tomography (OCT), and to investigate the risk factors of RAT during the CAG and/or PCI. Methods: In this retrospective study, we consecutively reviewed the radial artery OCT examination results of the patients who underwent OCT guided transradial CAG and/or PCI for acute coronary syndrome in heart center of Beijing Luhe hospital, Capital Medical University from October 2017 to July 2018. The incidence of RAT was observed. The patients were divided into the RAT group and non-RAT group, clinical data were collected and compared. Moreover, the types and distributions of thrombus in radial artery as well as the acute radial artery injuries under OCT were observed. Univariate analysis followed by multivariate analysis were performed to identify potential risk factors. The radial artery patency and ischemic symptoms of the involved limb were followed up at the 24-hour and the 1-month after procedure. Results: A total of 107 patients were included, the age was (58.1±12.5), and 78.5% were male (n=84). The incidence of RAT was 26.2% (n=28, 95%CI 17.9%-34.5%), and the main type of thrombus was white thrombus (n=15, 53.6%). The commonest position of RAT was the proximal portion of radial artery (n=17, 60.7%). The median thrombus volume was 0.05(0.03, 0.38) mm3, and the median thrombus score was 6.5 (3.3, 13.8). In univariate analysis, the frequency of acute radial artery injury and use of bivalirudin were significantly higher and the procedure time was significantly longer in RAT group than those in non-RAT group (all P<0.05). Multivariate regression analysis showed that the radial artery acute injury (OR=5.82, 95%CI: 2.09-16.20, P=0.001) and the procedure time (OR=1.04, 95%CI: 1.01-1.06, P=0.006) were independent risk factors of RAT. Rate of radial artery occlusion at 24 hours follow-up was similar between RAT and non-RAT group (7.14%(2/28), vs. 10.13%(8/79), P=1.000). None of the patients complicated severe ischemic symptom of the operative limb. Conclusions: RAT is a high frequency access complication during transradial coronary intervention. This phenomenon can be accurately observed by OCT. Acute radial artery injury and prolonged procedure time are risk factors of RAT during transradial coronary intervention.

Reproducibility of Thrombus Volume Quantification and Aortic Wall Stress in Abdominal Aortic Aneurysm

Previous studies have suggested that the intra-luminal thrombus volume and aortic wall stress (AWS) can predict abdominal aortic aneurysm (AAA) rupture, however the accuracy and repeatability of these measures are unclear. This study aimed to assess the reproducibility of intra-luminal thrombus volume and AWS in participants with ruptured and asymptomatic intact AAAs.

Short‐Term Cessation of Dabigatran Causes a Paradoxical Prothrombotic State

It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short-term (1-3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect. Ten-week-old C57Bl/6 mice (n = 338) received one of the following oral treatments: phosphate-buffered saline (PBS), dabigatran for 7 days with or without 1 to 4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1 to 3 days received single-dose aspirin. Thereafter, we induced FeCl3 -mediated carotid thrombosis in 130 mice, after which we performed micro computed tomography thrombus imaging. The other 208 mice underwent coagulation assays or platelet function tests. As an explorative pilot study, we reviewed the medical records of 18 consecutive patients with NOAC cessation-related cerebral infarction in a large acute stroke cohort. We observed a ~ 40% higher volume of carotid thrombus after dabigatran cessation at 1 to 3 days than after vehicle treatment and showed that this effect could be prevented by single-dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through thrombin or arachidonic acid, which effect was significantly attenuated by single-dose aspirin pretreatment. In patients, short-term (≤ 3 days) cessation of NOAC therapy, compared with longer-term (≥ 5 days) cessation, tended to be associated with relatively high stroke severity. We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. ANN NEUROL 2021;89:444-458.

The role of flow stasis in transcatheter aortic valve leaflet thrombosis

ObjectiveWith the recent expanded indication for transcatheter aortic valve replacement to low-risk surgical patients, thrombus formation in the neosinus is of particular interest due to concerns of reduced leaflet motion and long-term transcatheter heart valve durability. Although flow stasis likely plays a role, a direct connection between neosinus flow stasis and thrombus severity is yet to be established. MethodsPatients (n = 23) were selected to minimize potential confounding factors related to thrombus formation. Patient-specific 3-dimensional reconstructed in vitro models were created to replicate in vivo anatomy and valve deployment using the patient-specific cardiac output and idealized coronary flows. Dye was injected into each neosinus to quantify washout time as a measure of flow stasis. ResultsFlow stasis (washout time) showed a significant, positive correlation with thrombus volume in the neosinus (rho = 0.621, P < .0001). Neither thrombus volume nor washout time was significantly different in the left, right, and noncoronary neosinuses (P ≥ .54). ConclusionsThis is the first patient-specific study correlating flow stasis with thrombus volume in the neosinus post-transcatheter aortic valve replacement across multiple valve types and sizes. Neosinus-specific factors create hemodynamic and thrombotic variability within individual patients. Measurement of neosinus flow stasis may guide strategies to improve outcomes in transcatheter aortic valve replacement.

Abstract 14458: Repeated Social Defeat Exaggerates Fibrin-rich Clot Formation in Fecl3 Induced Arterial Thrombosis Mice Model by Enhancing Nets Formation

Background and Objective: Depression is an independent risk factor of cardiovascular disease (CVD). We have recently shown that repeated social defeat (RSD) exaggerates atherosclerosis development by enhancing neutrophil extracellular traps (NETs) formation. Here, we investigated the impact of RSD on arterial thrombosis. Methods and Results: Eight-week-old male WT mice were exposed to RSD by housing with a larger CD-1 mouse in a shared home cage. They were subjected to vigorous physical contact daily for 10 consecutive days. Control mice were housed in the same gage without physical contact. After social interaction test to confirm depressive-like behaviors, defeated mice (19 of 31) and control mice (12 of 14) were underwent arterial injury at 10 wks of age. A filter paper saturated with 10% FeCl3 was applied on the adventitial surface of left carotid artery for 3 min and analyzed 3 hrs later. The volume of thrombi was comparable between the two groups. However, fibrinogen/fibrin-positive areas in immunofluorescent images significantly increased in defeated mice (48.8% vs. 27.8%, p &lt; 0.01). The number of Ly-6G-positive cells in thrombi was markedly higher in defeated mice (878/mm2 vs. 144/mm2, p &lt; 0.05). Further, Ly-6G-positive cells were co-localized with neutrophil elastase, Cit-H3, and CD42b-positive staining. Percentage of CD42b-positive area in thrombi and in vitro platelets aggregations induced by ADP or collagen were comparable between the two groups. Treatment with DNase I completely diminished the exaggerated fibrin-rich clot formation in defeated mice to an extent similar to that in control mice (22.3% vs. 25.7%, p = ns), although the number of Ly-6G-positive cells in thrombi was not affected. We therefore examined the vulnerability to NETs formation induced by thrombin-activated platelets. Flow cytometric analysis showed that in vitro NETs formation assessed by Cit-H3/MPO double-positive cells was significantly higher in defeated mice (20.7% vs 12.5%, p &lt; 0.01). Conclusions: Our findings demonstrate that RSD enhances fibrin-rich clot formation after arterial injury by enhancing NETs formation via platelet-neutrophil interactions, suggesting that NETosis could be a new therapeutic target in depression-related CVD development.