Resolution Of Thrombosis Research Articles

Efficacy and safety of the ultraslow low-dose thrombolytic regimen for mechanical prosthetic valve thrombosis: a prospective cohort study

Abstract Background Mechanical prosthetic valve thrombosis (MPVT) remains a significant and life-threatening complication. While surgery is here considered the gold standard therapy, it has a high perioperative risk in the acute setting. Preliminary evidence suggests that an ultraslow low-dose thrombolytic regimen may offer a safer and equally effective alternative compared to both conventional fast-infusion thrombolytic approaches or surgical options. Purpose We aimed at evaluating efficacy and safety of a previously described ultraslow low-dose thrombolytic regimen for treating acute MPVT in hospitalized adult patients. Methods This prospective single-center cohort study included all consecutive adult patients with acute MPVT treated with our ultraslow low-dose thrombolytic regimen. Patients with contraindication to thrombolytic therapy or left-sided MPVT with a minimum thrombus size of 0.8 cm2 or severe dyspnea with NYHA FC IV were excluded, and considered candidate to surgery. The regimen here used consisted of 25 mg rtPA infused over 25 hours. If initially failed, a repeat 6-hour infusion of 25 mg rtPA was administered up to a maximum total cumulative dose of 150 mg or until an adverse event occurred. The primary objective was the rate of complete MPVT resolution, defined as >75% reduction in the obstructive gradient by transthoracic echocardiography, less than 10 degrees residual constraint in opening and closing valve motion angles as quantified by fluoroscopy, and alleviation of patients’ thrombosis-associated symptoms or signs. Results From April 2018 to November 2023, 135 infusions of thrombolytic therapy were administered in 118 patients (median age: 35 years (IQR, 25-49); 59 [50%] women) (Table 1). 12 patients had more than one episode of MPVT during the study period. Obstructive prosthetic valve thrombosis occurred in 89.6% (121/135) of cases. Pulmonary valves were most frequently affected (n = 84, 62.2%), followed by tricuspid (n = 34, 25.2%), mitral (n = 10, 7.4%), and aortic (n = 7, 5.2%) valves. A complete thrombolysis success was achieved in 119/135 episodes of thrombolytic therapy (88.1%); of these, 47/119 patients (39.5%) responded after the first thrombolytic dose. The median total dose administered was 50 mg (IQR, 25-75) over a median infusion duration of 30 hours (IQR, 25-36). Four patients responded partially to the regimen, six patients were candidates for bailout surgery, and only one fatal intracranial bleeding occurred. No other thromboembolic or bleeding adverse events were observed. Conclusion This is the largest prospective evaluation on the safety and efficacy of the ultraslow low-dose thrombolytic regimen, which proved highly effective - in this prospective cohort - in achieving prosthetic valve thrombosis resolution with minimal complications. Further larger clinical trials are warranted.Table 1- baseline CharacteristicsStudy Outcomes

Spontaneous Resolution of Dural Sinus Thrombosis.

Spontaneous Resolution of Dural Sinus Thrombosis.

Cerebral Sinus Venous Thrombosis in Pediatric Acute Lymphoblastic Leukemia: Incidence, Clinical Characteristics, and Long-term Neurologic Outcomes.

To describe the incidence, clinical characteristics, and long-term outcomes of cerebral sinus venous thrombosis in children with acute lymphoblastic leukemia. This was a retrospective cohort study comprising pediatric patients with newly diagnosed or first-relapse acute lymphoblastic leukemia who developed cerebral sinus venous thrombosis at Texas Children's Hospital from 2002 to 2019. Nineteen cases (1.7%) with cerebral sinus venous thrombosis were identified in all pediatric patients with acute lymphoblastic leukemia (n = 1129). Increased risk of cerebral sinus venous thrombosis was observed with age >10 years (P = .006). Twelve cases (63%) occurred during the induction, 4 (21%) during maintenance, and 3 (16%) during the consolidation phases of leukemia therapy. Seizures (10/19) and headaches (9/19) were the most common presenting symptoms. After treatment with anticoagulation therapy, we observed full resolution of thrombosis in 10 (53%) and partial resolution in 8 patients (42%). Long-term neurologic outcomes at follow-up in the 14 patients who survived included normal neurologic examinations (n = 10), epilepsy (n = 3), and focal neurologic deficits (n = 2). The death occurred in 5 individuals. Cerebral sinus venous thrombosis is a notable complication of pediatric acute lymphoblastic leukemia therapy. Older age (>10 years) was a risk factor for developing cerebral sinus venous thrombosis. Despite variable patient presentations and treatment durations, favorable clinical outcomes were observed in most patients after the treatment with anticoagulation for a minimum of 3 months.

Sciatica secondary to deep venous thrombosis of the persistent sciatic vein: the first case in the literature. Illustrative case.

Sciatica usually results from lumbar nerve compression due to factors like disc herniations or lumbar canal stenosis. Despite its common causes, sciatic pain in a 52-year-old man following a coronavirus disease 2019 infection highlighted the importance of considering less common factors. Initially, minor disc protrusions were suspected as the cause of the symptoms, leading to the offer of surgery at another facility. The patient sought a second opinion, and our evaluation revealed a unique finding. Pelvic magnetic resonance imaging uncovered varicose structures displacing the left sciatic nerve. Subsequent pelvic computed tomography angiography identified a remarkable finding-the lack of opacification in a left persistent sciatic vein ascending toward a left internal iliac vein, originating from a common internal iliac venous trunk-confirming a suspicion for deep venous thrombosis. These findings represented not 1, but 2, extremely rare and distinct variants in the venous anatomy. The authors promptly initiated anticoagulant therapy and tailored pain management strategies, observing progressive thrombosis resolution on follow-up imaging. This report highlights the need for comprehensive diagnostics when symptoms and imaging differ. Misdiagnosis could lead to unnecessary surgeries and potential risks for the patient. https://thejns.org/doi/10.3171/CASE23652.

Rising total leukocyte counts correspond with rising platelet counts in thrombotic thrombocytopenic purpura

AbstractThrombotic thrombocytopenic purpura (TTP) is a rare disorder involving pathological platelet–von Willebrand factor interaction, resulting in microvascular thrombosis. The consumption of platelets in TTP microthrombi results in severe thrombocytopenia which resolves with resolution of the microvascular thrombosis. Over the course of treatment, patient platelet counts often rise and fall multiple times before stable remission is achieved. On casual inspection, we noted that total leukocyte counts follow a pattern that appears to correspond to platelet counts. To explore whether changing leukocyte counts track significantly with changing platelet counts, we examined paired daily platelet counts and total leukocyte counts in 27 episodes of TTP in 13 patients across 2 institutions comprising 423 days of data. We modeled the nonlinear behavior in the data using a threshold mixed-effects regression model, in which we found a significant temporal relationship between total leukocyte counts and platelet counts. The model proved that, on a day when platelet counts were rising in previous days, the total leukocyte count is predictive of the rise in platelet count. The higher the total leukocyte count, the greater the rise in platelet count. Our results support the hypothesis that leukocytes play a role in the resolution of TTP microvascular thrombosis.

Abstract 148: Loss Of Tlr4 Signaling Inhibits Thrombus Resolution In A Non-monocyte Dependent Manner

Background: Loss of TLR4 signaling reduces Venous Thrombosis (VT) resolution. Leukocyte expression of TLR4 is elevated in humans undergoing acute to chronic DVT transformation. We hypothesized that TLR4 signaling in monocytes directs thrombus clearance. Methods: Wild type, Tlr4 -/- , LysM cre+/- Tlr4 fl/fl mice underwent VT via IVC stasis at 4/7/14d timepoints. Thrombi subtypes were identified by flow cytometry. Thrombus size was assessed, and fibrinolytic mediators were assayed in splenic/bone marrow Mφs. Whole blood from mice was stimulated with TLR2/4 and assayed for thrombolytic potential via HALO assay. Immunohistochemistry was performed for cellular infiltrate. Results: We observed elevated TLR4 cell surface expression on CD11b+/Ly6C- Mo/Mφ from wild type thrombi. Thrombus weight in Tlr4 -/ mice was elevated at 4d stasis, confirming impaired thrombus clearance. In basal conditions, circulating Mo/Mφ saw decreased Urokinase & MMP9 mRNA levels in LysM cre+/- mice. In post thrombotic conditions, we saw decreased protein levels of Urokinase and MMP9 in Cre+ bone marrow-derived Mφs. Whole blood thrombolysis efficiency increased with TLR4 agonism in Cre- mice compared to Cre+. Efficiency was restored with LPS-mediated dual TLR2/4 agonism. Total thrombus weight was unchanged. No difference was identified in monocyte infiltrate into the thrombus (Fig. 1) Conclusions: Genetic deficiency of Mo/Mφ TLR4 signaling alters induction of fibrinolytic/matrix remodeling gene expression. Ex vivo TLR4 agonism increased whole blood thrombolysis in Cre- but not Cre+ mice. Additional TLR2 agonism of Cre+ mice restored thrombolytic activity, suggesting TLR2 as a compensatory pathway that may account for the unchanged in vivo phenotype in LysMcreTlr4fl/fl mice. Further clarifying these cellular pathways may provide an alternate pathway to target VT resolution.

A Retrospective Study Comparing Pharmacomechanical Thrombectomy with Catheter-Directed Thrombolysis for Acute Deep Venous Thrombosis

PurposeThis study aims to conduct a comparative analysis of the clinical efficacy and safety between pharmacomechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) in the context of acute lower-extremity deep venous thrombosis (LEDVT). Materials and MethodsA retrospective review of our institution's patient database spanning from February 2011 to December 2019 was performed to identify cases of acute LEDVT. The patients were categorized into two distinct groups based on the thrombolytic interventions administered: the PMT group, specifically denoting PMT with AngioJet in our investigation, and the CDT group. Comprehensive data sets encompassing patient demographics, risk factors, procedural specifics, thrombolysis grading, and complications were collected. Subsequent follow-up evaluations at the two-year mark post-treatment included assessments of post-thrombotic syndrome (PTS) and the quality of life (QOL). ResultsAmong the 348 patients identified (mean age: 50.12 ± 15.87 years; 194 females), 200 underwent catheter-directed thrombolysis (CDT) during the early stage (2011 to 2017), while 148 received pharmacomechanical thrombectomy (PMT) between 2017 and 2019. Baseline data between the two groups exhibited no statistically significant differences. Thrombus scores significantly decreased in both cohorts post-therapy (each p < 0.001).Patients subjected to PMT demonstrated higher thrombolysis rates (77.35±9.44% vs 50.85±6.72%), reduced administration of the thrombolytic agent urokinase [20(20-20) vs 350(263-416), p < 0.001], larger limb circumference differences (above the knee: 6.03±1.76cm vs 4.51±1.82cm, p < 0.001; below the knee: 2.90±1.16cm vs 2.51±0.90cm, p < 0.001), and shorter lengths of stay (7.19±3.11 days vs 12.33±4.77 days, p < 0.001). However, the PMT group exhibited a higher decline in hemoglobin levels (13.41±10.59 g/L vs 10.88±11.41 g/L, p = 0.038) and an increase in creatinine levels [9.58(2.32-15.82) umol/L vs 4.53(2.87-6.08) umol/L, p < 0.001] compared to the CDT group. No statistically significant differences were observed in the numbers of balloon angioplasty, stent implantation (each p > 0.050), and minor and major complications between the two groups. At the 1-year follow-up, post-thrombotic syndrome (PTS) occurred in 13.51% of the PMT group compared to 26% of the CDT group (p = 0.025), with a higher incidence of moderate-severe PTS in the CDT group (8% vs 2.7%, p = 0.036). At the 2-year follow-up, PTS was observed in 16.2% of the PMT group and 31.5% in the CDT group, p = 0.004. Preoperative and postoperative D-values of SF-36 PCS and SF-36 MCS showed no statistically significant between-group differences. ConclusionIn our institutional experience, both pharmacomechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) have proven to be effective and safe therapeutic approaches for managing acute lower-extremity deep venous thrombosis (LEDVT). PMT, in particular, demonstrated superior efficacy in achieving thrombosis resolution and mitigating the risk of post-thrombotic syndrome, affirming its role as a favorable intervention in this clinical context.

A case report of extranodal diffuse large B-cell lymphoma involving upper limb soft tissue in a patient with rheumatoid arthritis on immunosuppressive therapy

An 80-year-old woman affected by rheumatoid arthritis on immunosuppressive therapy was evaluated for an 11-month history of swelling of her left upper limb. The patient did not report systemic symptoms. Ultrasonographic examination showed hypoechoic masses in the upper limb soft tissue, brachial vein thrombosis, and suspected malignant axillary lymphadenopathy. The patient underwent an excisional biopsy of the lymphadenopathy for histologic examination; a diagnosis of diffuse large B-cell lymphoma was made. The patient started anticoagulation therapy and chemotherapy, with a follow-up at a hematology clinic. At a 3-month follow-up visit in our clinic, the swelling of her left upper limb decreased, and an ultrasonographic control demonstrated a reduction in the size and number of the soft tissue masses and resolution of vein thrombosis.

Reduced Monocyte and Neutrophil Infiltration and Activation by P-Selectin/CD62P Inhibition Enhances Thrombus Resolution in Mice.

Venous thromboembolism is a major health problem. After thrombus formation, its resolution is essential to re-establish blood flow, which is crucially mediated by infiltrating neutrophils and monocytes in concert with activated platelets and endothelial cells. Thus, we aimed to modulate leukocyte function during thrombus resolution post-thrombus formation by blocking P-selectin/CD62P-mediated cell interactions. Thrombosis was induced by inferior vena cava stenosis through ligation in mice. After 1 day, a P-selectin-blocking antibody or isotype control was administered and thrombus composition and resolution were analyzed. Localizing neutrophils and macrophages in thrombotic lesions of wild-type mice revealed that these cells enter the thrombus and vessel wall from the caudal end. Neutrophils were predominantly present 1 day and monocytes/macrophages 3 days after vessel ligation. Blocking P-selectin reduced circulating platelet-neutrophil and platelet-Ly6Chigh monocyte aggregates near the thrombus, and diminished neutrophils and Ly6Chigh macrophages in the cranial thrombus part compared with isotype-treated controls. Depletion of neutrophils 1 day after thrombus initiation did not phenocopy P-selectin inhibition but led to larger thrombi compared with untreated controls. In vitro, P-selectin enhanced human leukocyte function as P-selectin-coated beads increased reactive oxygen species production by neutrophils and tissue factor expression of classical monocytes. Accordingly, P-selectin inhibition reduced oxidative burst in the thrombus and tissue factor expression in the adjacent vessel wall. Moreover, blocking P-selectin reduced thrombus density determined by scanning electron microscopy and increased urokinase-type plasminogen activator levels in the thrombus, which accelerated caudal fibrin degradation from day 3 to day 14. This accelerated thrombus resolution as thrombus volume declined more rapidly after blocking P-selectin. Inhibition of P-selectin-dependent activation of monocytes and neutrophils accelerates venous thrombosis resolution due to reduced infiltration and activation of innate immune cells at the site of thrombus formation, which prevents early thrombus stabilization and facilitates fibrinolysis.

Extensive Cerebral Venous Sinus Thrombosis during COVID-19 Infection in a Patient with Autoimmune Hyperthyroidism: A Case Report

Abstract Cerebral venous sinus thrombosis (CVST) in the setting of coronavirus disease 2019 (COVID-19) is an uncommon phenomenon with increasing incidence. CVST is an uncommon subtype of stroke caused by thrombotic occlusion of the cerebral veins. We report the case of an adult women with headache, fever, nausea, vomiting, and no known autoimmune diseases. Diagnostics revealed elevated infammatory and hypercoagulability markers, free T4, low TSHs, and positive SARS-CoV-2 PCR. Neuroimaging demonstrated a thrombosis of the superior sagittal sinus, both right and left transverse sinus extending into the right jugular vein. A diagnosis of CVST with associated COVID-19 and hyperthyroidism was established. In patients with suspected COVID-19, especially in the presence of causes of hypercoagulability and presence of atypical features, venous sinus thrombosis needs to be kept in mind in making the differential diagnosis. Follow-up examination revealed complete symptomatic resolution and regression of thrombosis.

Short versus long-term anticoagulation for left ventricular thrombosis resolution during vitamin k antagonist therapy

Abstract Background The optimal duration of anticoagulant therapy to achieve thrombus resolution and prevent cardioembolic events in left ventricular thrombosis (LVT) has not yet been established. Purpose The purpose of our study is to evaluate the incidence of LVT resolution at 3 versus 12 months of vitamin K antagonists (VKAs) therapy. Methods Consecutive patients diagnosed with LVT and treated with VKAs for at least 12 months at 5 anticoagulant outpatient clinics in Italy were retrospectively included. The primary effectiveness outcome was on-treatment thrombus resolution while the secondary was objectively documented on-treatment acute ischemic stroke, peripheral embolism, and myocardial infarction at 12-months follow-up. Safety outcomes were on-treatment major and clinically relevant non-major bleedings at 12-months follow-up as defined by the ISTH criteria. Cumulative incidences of thrombus resolution with 95% confidence intervals (CIs) were calculated while other outcomes were descriptively reported. Multivariable Cox hazards models were calculated using age, sex, reduced left ventricular ejection fraction (EF &amp;lt; 35%), VKAs monotherapy, and time in therapeutic range (TTR) below 60% as covariates for thrombus persistence at 12-months of follow-up. Results Out of 95 patients, 87 were finally included (Table) and 8 excluded due to the lack of relevant data. Median age was 67 years and 75.9% were men. A total of 64.4% of patients had acute myocardial infarction as risk factor for LVT development while 21.8% and 5.7% of patients had dilated and primary hypertrophic cardiomyopathy, respectively. A reduced EF and atrial fibrillation were present in 77.0% and 19.5% of patients, respectively. All but one patient received warfarin with a median TTR of 54%, and 35.5% of patients did not receive concomitant antiplatelet therapy. All included patients received VKAs for at least 12-months. The 3 and 12 month cumulative incidences (Figure) of thrombus resolution were 34.5% (95% CI, 24.7%-44.5%) and 68.3% (95% CI, 57.2%-77.1%), respectively. At multivariable Cox regression analysis, the presence of a reduced EF appeared to be associated with a higher risk of thrombus persistence at 12-months follow-up (Hazard Ratio 3.09; 95% CI 1.27-7.55; p=0.013). During 12-months follow-up, two patients (2.3%) had acute ischemic stroke at 4 and 7 months from the start of VKAs therapy. Three patients (3.4%) had a major and 5 (5.7%) a clinically relevant non-major bleeding that occurred within the first three months of VKAs. Conclusions A 12-month course of anticoagulant therapy with VKA appeared to be effective and safe in patients with LVT and appeared to be associated with a higher cumulative incidence of LVT resolution than a 3-month course. A reduced left ventricular EF was associated with a higher risk of LVT persistence. Whether anticoagulant agents with improved ease-of-use and safety profile are effective in this setting remains undefined.Baseline patients' characteristicsCumulative incidences of LVT resolution

Un extraño caso de trombosis venosa

Ovarian vein thrombosis is a rare condition that is usually due to prothrombotic states. The clinical presentation is nonspecific, commonly with abdominal pain. Anticoagulation is fundamental to prevent complications and reduce morbidity and mortality. Enoxaparin and warfarin have traditionally been the anticoagulants of choice. Direct-acting anticoagulants are an alternative under study. This publication presents a case of a 60-year-old patient without predisposing factors for ovarian thrombosis, with low back pain, where the diagnosis was only achieved with Computed Tomography. Anticoagulation with rivaroxaban was started for a period of 3 months, obtaining resolution of symptoms and thrombosis.

External Jugular Veinous Thrombosis: A Rare Presentation of Hansen’s Disease

Veinous thrombosis is a rare manifestation of leprosy (Hansen’s disease). In this case report, we bring to notice this extremely rare presentation and challenges faced during management. A 26-year-old young healthy individual presented with painless cord-like swellings on both sides of the neck for 1 month. This was evaluated to be external jugular vein (EJV) thrombosis on ultrasonography Doppler. Trying to evaluate the cause of the thrombosis, there was no specific etiology found. On further detailed evaluation, it was found that he had hypopigmented skin patches. This led to the diagnosis of borderline tuberculoid leprosy downgrading to borderline lepromatous in type 1 lepra reaction. He responded to rifampicin, clofazimine, and dapsone with progressive resolution of skin lesions. Simultaneous treatment with apixaban caused complete resolution of EJV thrombosis. Further evaluation revealed heterozygous methylenetetrahydrofolate reductase mutation and beta-2-glycoprotein immunoglobulin M positivity. An extensive literature review suggested that intimal damage caused by lepra bacilli can lead to veinous thrombosis in Hansen’s disease. However, the interplay of genetic procoagulant predispositions in phenotypic presentation is yet to be determined.

P393 EDOXABAN: NEW PERSPECTIVE IN A PATIENT WITH CANCER–ASSOCIATED THROMBOSIS COMPLICATED BY BRAIN METASTASES. A RARE CLINICAL CASE

Abstract Herein, we present the case of a 58 y–o Caucasian man with unremarkable cardiovascular history and a strong family history for cancer. He was diagnosed with lung adenocarcinoma IVb (pleura, pleural effusion, lymph nodes), PDL1: 2% TPS and absence of actionable driver mutations on DNA and RNA NGS (only ERBB2 mutation). Started first–line chemotherapy with cisplatin–pemetrexed regimen and immunotherapy with pembrolizumab. He developed common/superficial femoral and popliteal deep vein thrombosis (DVT) and pulmonary embolism (PE). The patient started low–molecular–weight heparin (LMWH) namely enoxaparin 1 mg/kg x 2/d (weight: 65 Kg). After 1 mo, CT showed PE resolution. Due to DVT persistence and patient’s preference for oral administration, LMWH was replaced with direct oral anticoagulant (DOAC) namely edoxaban 60 mg 1 cp/d. After 2 mo, resolution of common femoral and popliteal vein thrombosis with partial recanalization of superficial femoral DVT were detected. However, he developed brain metastases treated with WB radiotherapy. We decided for edoxaban full dose long–term anticoagulant treatment with monthly cardioncological surveillance. After 6 mo since cancer diagnosis, the patient was still adherent to DOAC therapy, although in a maintenance combined regimen pemetrexed–pembrolizumab based, without both drug–drug interactions and brain bleeding. Conclusions Thromboembolism is the second leading cause of death in malignancy. In this clinical case, a man with advanced lung cancer developed extended cancer–associated thrombosis (CAT). However, the appearance of brain metastases has posed a clinical dilemma: to continue or to withdraw the anticoagulant therapy and, also, which drug to choose between LMWH and DOAC. Literature is limited on the use of DOACs in cancer patients with brain metastases. Besides, current guidelines neither advocate contraindication to DOAC, nor suggest caution as requested for gastrointestinal and genitourinary sites of cancer. We decided to proceed with edoxaban therapy, despite chemotherapy combined to immunotherapy were still ongoing and the concurrent appearance of brain metastases, with good results in efficacy, patient’s adherence and, mostly, safety. In conclusion, in regard to our clinical experience, we point out DOAC as a reliable and manageable therapeutical choice in CAT, also in active cancer patients with brain metastases receiving chemo–immunotherapy.

P209 HUGE AND OCCLUDING LAA THROMBUS DISSOLUTION IN A CASE OF SEVERE TACHI–CARDIOMYOPATHY

Abstract A 62–year–old man was admitted to our emergency department for worsening nocturnal dyspnea and orthopnea for 15 days. Finding of Acute Pulmonary Edema in a setting of non datable high ventricular response atrial fibrillation (AF) associated with severe LV dysfunction. NT–proBNP 8.252 pg/ml. ECG: atrial fibrillation with high ventricular response (120/bpm). TTE: Severe left ventricular systolic disfunction (EF 20%). TOE/3D TOE: evidence of voluminous oval–shaped thrombotic formation (10 x 17 mm) protruding in LA and completely occluding the left atrial appendage (LAA). LA thrombosis in patients with AF is relatively rare and represents a contraindication to rhythm control strategies. Once an LAA thrombus is identified, effective anticoagulation is recommended for at least three weeks or until LAA thrombus resolution is detected. Available evidence on left atrial thrombus dissolution largely refers to the use of vitamin K antagonist oral anticoagulant (VKAs), but their effectiveness may be influenced by variability in the level of anticoagulant activity obtained, wich may be suboptimal. In a recent prospective observational study has been evaluated the effectiveness of Edoxaban for the resolution of LA thrombosis in 25 patients with AF: it has been demonstrated a complete thrombus resolution in 56% of patients at 4 weeks, similar to studies using VKAs and the other NOACs. Use of NOACs in this setting represents a great field of interest for the near future. In our experience, indeed, after confirmed diagnosis of LAA thrombus, we started anticoagulant therapy with warfarin (currently the first choice), however due to poor INR control, we switched to continuous infusion of unfractionated heparin (UFH), wich represents, in a hospital setting, a safe and effective method for thrombus dissolution, allowing continuous monitoring of efficacy and a rapid cessation of effect in case of major bleeding. In this way we obtained complete thrombus dissolution in about 3 weeks. At the meantime we initiate a rate control therapy, an optimized treatment for HFrEF and intravenous diuretics. Our experience highlights the need of great ductility in the choice of anticoagulant therapy in patients with evidence of voluminous LAA thrombus, monitoring treatment’s efficacy parameters and being ready to change strategy if necessary and it reminds that auricular thrombosis is often inserted in a wider picture of heart disease wich requires multiple other specifics treatments.

P299 WATCHMAN DEVICE THROMBOSIS FOLLOWING THE PERCUTANEOUS CLOSURE OF THE LEFT ATRIUM APPENDAGE: A "CUL–DE–SAC" IN THE ANTITHROMBOTIC STRATEGY

Abstract Background The percutaneous closure of the left atrium appendage (LAA) is a valuable therapeutic tool in patients with atrial fibrillation (AF) who have contraindications to anticoagulant drugs. However, the procedure can lead to complications and the device positioning determines a risk of thrombosis that can‘t be underestimated, especially during the first period from the intervention. Clinical Case In this report we propose the case of a 72 years old man in chronic therapy with NOAC (non–vitamin K antagonist oral anticoagulants) for a paroxysmal AF (CHA2DS2–VASC = 3), that presented intracranial hemorrhage after 3 years due to a cerebral arteriovenous malformation. This condition represents an absolute contraindication to anticoagulant therapy, because of the high hemorrhagic risk, and led to the percutaneous device positioning (WATCHMAN 24 mm) for LAA closure. After the implantation procedure we started a single antiplatelet therapy (SAPT) with clopidogrel 75 mg for 6 months. At one month follow–up a trans–esophageal echocardiogram (TEE) showed the presence of a swinging samll trombotic formation (4x2,5 mm) attached to the device. At that time antithrombotic therapy with enoxaparin 6000 IU was started, in addition to SAPT. Ten days later, another TEE showed the thrombus resolution and we decided to continue with clopidogrel alone. No relevant clinical events were observed to the subsequent follow–up. Discussion Current recommendations suggest double antiplatelet therapy (DAPT) for 1–6 months followed by SAPT, in patients who have absolute contraindication to anticoagulant drugs, or SAPT for at least 1 month in those who have an extreme hemorrhagic risk. LAA closure device thrombosis affects 3% of patients and represents an independent predictor of cerebral ischemic events, according to various registers and meta–analyses. This event determines an indication to anticoagulant therapy in patients who would have an absolute contraindication, creating a difficult management that assume clinical relevance. In our experience a 10 days therapy with heparin added to SAPT led to thrombosis resolution. However the therapeutic management of these complications is currently not standardized and more studies are needed.

Toll-like receptor 4 deficiency in mice impairs venous thrombus resolution.

Objective: Toll-like receptor 4 (TLR4) is crucial to the development of sterile inflammatory responses. The deep venous thrombosis resolution (DVT) is similar to sterile inflammation, so we hypothesize that TLR4 is involved. Methods and Results: We evaluated the effects of TLR4 deficiency on thrombus lysis in vivo, and explored the mechanisms in vitro. DVT mouse model was established by inferior vena cava (IVC) ligation. After the IVC ligation (1, 3, and 7d), the mice were euthanized to collect the venous thrombus. The Tlr4-/- mice had significantly elevated weight/length ratios of thrombi at 3 and 7d and increased collagen content at 3d after IVC ligation, in addition to significantly lesser intrathrombus infiltration of neutrophils and macrophages, lower monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) expression in thrombus tissue sections and homogenates, and lower pro-MMP-9 activity at 3d after IVC ligation than wild-type mice. After 7days of IVC ligation, VEGF, IFNβ, and MCP-5 protein expression were decreased in venous thrombus from Tlr4-/- mice. 2ml of 3% thioglycolate was injected intraperitoneally and peritoneal exudate was collected 3days later from Tlr4-/- and wild type mice respectively. The intraperitoneal macrophages were isolated from adherent culture after centrifugation. Lipopolysaccharide (LPS) can activate TLR4/NF-κB signalling pathway in a concentration-dependent manner, initiated p65 nuclear translocation, IκBα phosphorylation and degradation, MMP-9 and MCP-1 transcription in WT intraperitoneal macrophages but not in Tlr4-/- intraperitoneal macrophages. Conclusion: TLR4 is involved in venous thrombosis resolution through NF-κB pathway. Loss of TLR4 in mice impairs the process.

Abstract Number ‐ 48: Cerebral Sinus Venous Thrombosis Secondary to Chronic Inflammatory Disorders in Children

Introduction Cerebral Sinus Venous Thrombosis (CSVT) is a rare form of venous thromboembolism that can lead to significant morbidity and mortality predominantly in young people. While previous literature has identified prothrombotic and infectious pathologies as significant risk factors for CSVT, chronic systemic conditions such as connective tissue diseases (CTD) are less studied. The purpose of the current study is to describe the clinical features, neuroimaging characteristics, treatment, and long‐term neurological outcomes in children with CSVT secondary to CTD. Methods We reviewed electronic medical records of patients under 18 years of age diagnosed with CSVT secondary to CTD between 2002–2018 in a single center. We analyzed data regarding demographics, comorbidities, neuroimaging and neurological examination findings during the initial encounter. Subsequent long‐term follow‐up neurological examinations, lab and imaging workup, and medical management was also analyzed. Results Eight patients (Male:Female: 6:2) met the criteria and were included in the analysis. The patient’s age ranged from 6 weeks to 17 years. CTDs include Behcet’s (n = 2), Kawasaki (n = 1), systemic lupus erythematosus (n = 1), Wegener granulomatosis (n = 1), sarcoidosis (n = 1), and inflammatory bowel disease (n = 1). Five patients had a normal neurological examination on initial presentation, two had papilledema, and one had hypotonia and poor suck reflex. On initial neuroimaging, the most common thrombosis locations were transverse sinuses (n = 7). All patients received anti‐thrombolytic therapy (heparin, warfarin, or Lovenox) between 2.5 to 6 months. Three patients had complete resolution and one had partial resolution of thrombosis on follow‐up neuroimaging (average = 4.3 months, range 3–8 months). On long‐term clinical follow‐up (average: 41.3 months, SD: 62.1), all patients had normal neurological examinations. Conclusions Our case series demonstrated that 50% of patients with CSVT secondary to CTD showed full/partial resolution of thrombosis on follow‐up neuroimaging. In addition, they also had good clinical outcomes on long‐term clinical follow‐up with anticoagulation or antithrombotic treatment. This study uncovers the favorable outcomes of CSVT associated with CTD in children, but more cohort studies are required in order to make accurate conclusions.

Salutary Effects of Locally Delivered Dexamethasone on Murine Acute Deep Venous Thrombosis Resolution

Salutary Effects of Locally Delivered Dexamethasone on Murine Acute Deep Venous Thrombosis Resolution

Development and external validation of prognostic scoring models for portal vein thrombosis: a multicenter retrospective study

BackgroundPortal vein thrombosis is a common complication of liver cirrhosis and hepatocellular carcinoma; however, few studies have reported its long-term clinical prognosis. This study aimed to establish and validate easy-to-use nomograms for predicting gastrointestinal bleeding, portal vein thrombosis resolution, and mortality of patients with portal vein thrombosis.MethodsThis multicenter retrospective cohort study included 425 patients with portal vein thrombosis who were divided into training (n = 334) and validation (n = 91) sets. Prediction models were developed using multivariate Cox regression analysis and evaluated using the consistency index and calibration plots.ResultsPredictors of gastrointestinal bleeding included a history of gastrointestinal bleeding, superior mesenteric vein thrombosis, red color sign observed during endoscopy, and hepatic encephalopathy. Meanwhile, predictors of resolution of portal vein thrombosis included a history of abdominal infection, C-reactive protein and hemoglobin levels, and intake of thrombolytics. Predictors of death included abdominal infection, abdominal surgery, aspartate aminotransferase level, hepatic encephalopathy, and ascites. All models had good discriminatory power and consistency. Anticoagulation therapy significantly increased the probability of thrombotic resolution without increasing the risk of bleeding or death.ConclusionsWe successfully developed and validated three prediction models that can aid in the early evaluation and treatment of portal vein thrombosis.