NIR Light-Fuse Drug-Free Photothermal Armor-Piercing Microcapsule for Femoral Vein Thrombosis Therapy.

Acute thrombosis and its complications are leading global causes of disability and death. Existing thrombolytic drugs, such as alteplase and urokinase (UK), carry a significant bleeding risk during clinical treatments. Thus, the development of a novel thrombolysis strategy is of utmost urgency. Based on the previous work, the hollow structure of microcapsules (MC) is fabricated. Subsequently, armor-piercing MC, known as Fucoidan/S-Nitrosoglutathione/Melanin@MC (FGM@MC) is obtained, using a layer-by-layer (LBL) self-assembly method. Utilizing near-infrared (NIR) light as a trigger, the FGM@MC demonstrated photothermal thrombolysis at the site of thrombus due to its stable and outstanding photothermal properties. Simultaneously, photothermal stimulation leads to the release of a significant amount of nitric oxide from the FGM@MC, resulting in cavitation effects for mechanical thrombolysis. In vivo experiments confirmed the stable release of nitric oxide under NIR light irradiation. Treatment of femoral vein thrombosis in rats revealed that the thrombolytic effectiveness of FGM@MC+NIR (53.71%) is comparable to that of UK (59.70%). Notably, FGM@MC does not interfere with the coagulation function of rats and exhibits a favorable safety profile. In conclusion, this study demonstrates that the drug-free armor-piercing microcapsule has significant potential in the treatment of thrombosis, offering a safe and effective alternative to traditional thrombolytic therapies.

A Biomimicking and Multiarm Self-Indicating Nanoassembly for Site-Specific Photothermal-Potentiated Thrombolysis Assessed in Microfluidic and In Vivo Models.

Thrombolytic and antithrombotic therapies are limited by short circulation time and the risk of off-target hemorrhage. Integrating a thrombus-homing strategy with photothermal therapy are proposed to address these limitations. Using glycol chitosan, polypyrrole, iron oxide and heparin, biomimicking GCPIH nanoparticles are developed for targeted thrombus delivery and thrombolysis. The nanoassembly achieves precise delivery of polypyrrole, exhibiting biocompatibility, selective accumulation at multiple thrombus sites, and enhanced thrombolysis through photothermal activation. To simulate targeted thrombolysis, a microfluidic model predicting thrombolysis dynamics in realistic pathological scenarios is designed. Human blood assessments validate the precise homing of GCPIH nanoparticles to activated thrombus microenvironments. Efficient near-infrared phototherapeutic effects are demonstrated at thrombus lesions under physiological flow conditions ex vivo. The combined investigations provide compelling evidence supporting the potential of GCPIH nanoparticles for effective thrombus therapy. The microfluidic model also offers a platform for advanced thrombolytic nanomedicine development.

Role of Fibrinolytic Enzymes in Anti-Thrombosis Therapy.

Thrombosis, a major cause of deaths in this modern era responsible for 31% of all global deaths reported by WHO in 2017, is due to the aggregation of fibrin in blood vessels which leads to myocardial infarction or other cardiovascular diseases (CVDs). Classical agents such as anti-platelet, anti-coagulant drugs or other enzymes used for thrombosis treatment at present could leads to unwanted side effects including bleeding complication, hemorrhage and allergy. Furthermore, their high cost is a burden for patients, especially for those from low and middle-income countries. Hence, there is an urgent need to develop novel and low-cost drugs for thrombosis treatment. Fibrinolytic enzymes, including plasmin like proteins such as proteases, nattokinase, and lumbrokinase, as well as plasminogen activators such as urokinase plasminogen activator, and tissue-type plasminogen activator, could eliminate thrombi with high efficacy rate and do not have significant drawbacks by directly degrading the fibrin. Furthermore, they could be produced with high-yield and in a cost-effective manner from microorganisms as well as other sources. Hence, they have been considered as potential compounds for thrombosis therapy. Herein, we will discuss about natural mechanism of fibrinolysis and thrombus formation, the production of fibrinolytic enzymes from different sources and their application as drugs for thrombosis therapy.

Predicting Recurrent Venous Thromboembolism in Patients With Deep-Vein Thrombosis: Development and Internal Validation of a Potential New Prediction Model (Continu-8).

Background: Previous prediction models for recurrent thromboembolism (VTE) are often complicated to apply and have not been implemented widely. Aim: To develop and internally validate a potential new prediction model for recurrent VTE that can be used without stopping anticoagulant treatment for D-dimer measurements in patients with provoked and unprovoked DVT. Methods: Cohort data of 479 patients treated in a clinical care pathway at Maastricht University Medical Center were used. Predictors for the Cox proportional hazards model (unprovoked DVT, male gender, factor VIII levels) were derived from literature and using forward selection procedure. The scoring rule was internally validated using bootstrapping techniques and the predictive ability was compared to existing prediction models. Results: Patients were followed for a median of 3.12 years after stopping anticoagulation treatment (IQR 0.78, 3.90). Sixty-four of 479 patients developed recurrent VTE (13%). The scoring rule consisted of unprovoked DVT (yes: 2 points), male sex (yes: 1 point), and factor VIII > 213 % (yes: 2 points) and was categorized into three groups [i.e., low risk (score 0), medium risk (scores 1, 2, or 3) and high risk (scores 4 and 5)]. The concordance statistic was 0.68 (95% CI: 0.61, 0.75). Conclusion: The discriminative ability of the new Continu-8 score was adequate. Future studies shall verify this score in an independent setting without stopping anticoagulation treatment.

Virus-Inspired Gold Nanorod-Mesoporous Silica Core-Shell Nanoparticles Integrated with tTF-EG3287 for Synergetic Tumor Photothermal Therapy and Selective Therapy for Vascular Thrombosis.

Synergetic therapy includes the combination of two or more conventional therapeutic approaches and can be used for tumor treatment by combining the advantages and avoiding the drawbacks of each type of treatment. In the present study, truncated tissue factor (tTF)-EG3287 fusion protein-encapsulated gold nanorod (GNR)-virus-inspired mesoporous silica core-shell nanoparticles (vinyl hybrid silica nanoparticles; VSNP) (GNR@VSNP-tTF-EG3287) were synthesized to achieve synergetic therapy by utilizing selective vascular thrombosis therapy (SVTT) and photothermal therapy (PTT). By integrating the targeted coagulation activity of tTF-EG3287 and the high tumor ablation effect of GNR@VSNP, local hyperthermia could induce a high percentage of apoptosis of vascular endothelial cells by using near-infrared light. This provided additional phospholipid sites for tTF-EG3287 and enhanced its procoagulant activity in vitro. In addition, the nanoparticles, which had unique topological viral structures, exhibited superior cellular uptake properties leading to significant antitumor efficacy. The in vivo antitumor results further demonstrated an interaction between SVTT and PTT, whereas the synergetic therapy (SVTT and PTT) achieved an enhanced effect, which was superior to the respective treatment efficacy of each modality or the additive effect of their individual efficacies. In summary, the synthesized GNR@VSNP-tTF-EG3287 exerted synergetic effects and enhanced the antitumor efficiency by avoiding multiple injections and suboptimal administration. These effects simultaneously affected both tumor blood supply and cancer cell proliferation. The data suggested that the integration of SVTT induced by tTF-EG3287 and PTT could provide potential strategies for synergetic tumor therapy.

Septic coronary artery embolism treated with aspiration thrombectomy: case report and review of literature.

Coronary embolization is a potentially fatal sequela of endocarditis. We report a case of Candida endocarditis with septic embolism to the left anterior descending coronary artery. This embolism was successfully treated with aspiration thrombectomy followed by balloon angioplasty. The treatment of acute coronary syndrome in the presence of septic embolism is controversial. Aspiration thrombectomy has been performed in this situation before, and it appears to be safer and more feasible than is thrombolysis or percutaneous transluminal angioplasty.

Use of heparin alone in treating pulmonary emboli found in association with in-transit right-heart thrombi in a nonagenarian.

In patients who present with pulmonary embolism, right-heart thrombus is a rare condition that is associated with increased mortality rates, compared with pulmonary embolism alone. Thrombolytic therapy has been associated with a survival benefit in previous studies of pulmonary embolism arising from right-heart thrombus. However, older patients have been excluded from such studies because thrombolysis places them at excessively high risk of bleeding. We present a case, in a 92-year-old woman, of pulmonary embolism arising from right-heart thrombi that we successfully treated with heparin.

May-Thurner syndrome in a 68-year-old woman after remote abdominal surgery.

May-Thurner syndrome, also called iliac vein compression syndrome, is a rare cause of left iliac deep vein thrombosis, which arises from pulsatile compression of the left common iliac vein by the right common iliac artery. The resultant endothelial damage and intraluminal spur formation can lead to iliac deep vein thrombosis and sudden-onset left-lower-extremity edema and pain. Patients typically present with May-Thurner syndrome in their 2nd to 4th decades of life. In chronic form, the syndrome can be debilitating because of venous claudication and stasis ulcers. Surgical approaches and endovascular interventions have been effective in the acute phase of the disease, and intravenous stents can resolve the manifestations of chronic venous compression. Anticoagulation alone is ineffective, and a consensus regarding the usage and duration of antiplatelet and antithrombotic therapy has not been established. We present the case of a 68-year-old woman with a remote history of abdominal surgery who presented with left-lower-extremity edema and pain. Magnetic resonance venography of the pelvic veins yielded a definitive diagnosis of May-Thurner syndrome. Catheter-directed thrombolysis and intravenous stent placement resolved her symptoms, and she was discharged from the hospital on anticoagulative therapy. A year later, she had no residual pain or edema, and the affected veins were patent with normal phasic flow and normal responses to compression and augmentation.

Management of the thrombosed filter-bearing inferior vena cava.

Inferior vena cava (IVC) filter thrombosis is a complex problem. Thrombus within an IVC filter may range from an asymptomatic small thrombus to critical IVC occlusion that affects both lower extremities. The published experience of IVC thrombosis management in relation to filters is either anecdotal or limited to a small group of patients; however, endovascular treatment methods appear to be safe and effective in patients with IVC thrombosis. This review focuses on filter-related IVC thrombosis and its endovascular management.