Treatment Of Vascular Thrombosis Research Articles

In Silico docking studies on thrombolytic properties ofHomoeopathic Medicine Cactus grandiflorus by activationof tissue-Plasminogen Activator in the treatment of Vascular Thrombosis

In Silico docking studies on thrombolytic properties ofHomoeopathic Medicine Cactus grandiflorus by activationof tissue-Plasminogen Activator in the treatment of Vascular Thrombosis

In Silico docking studies on thrombolytic properties ofHomoeopathic Medicine Cactus grandiflorus by activationof tissue-Plasminogen Activator in the treatment of Vascular Thrombosis

In Silico docking studies on thrombolytic properties ofHomoeopathic Medicine Cactus grandiflorus by activationof tissue-Plasminogen Activator in the treatment of Vascular Thrombosis

Treatment of Vascular Thrombosis in Antiphospholipid Syndrome: An Update.

The antiphospholipid syndrome (APS) is an acquired autoimmune disorder associated with arterial, venous, or microvascular thrombosis and/or pregnancy complications mainly in young age. The diagnosis is made by the persistent detection of anticardiolipin antibodies, β2-glycoprotein I antibodies (β2GPIA), and/or lupus anticoagulants (LAs) for at least 12 weeks. Patients should present with at least one clinical and one laboratory criterion. Patients presenting with all three types of antibodies and vascular events are high-risk patients and should receive vitamin K antagonists (VKAs) as long as the antibodies persist. In patients with prior arterial thrombosis, VKA with or without low-dose aspirin is the current treatment of choice. The international normalized ratio (INR) should be between 2 and 3 although in some cases keeping the target INR above 3 may be necessary. Patients with venous thrombosis and negative LA may alternatively be treated with direct oral anticoagulants although more data are needed. Minimizing vascular risk factors is always necessary in APS patients. Aspirin can be given as primary prevention in asymptomatic patients with positive antiphospholipid antibodies without thrombosis or pregnancy complications especially when additional vascular risk factors are present. Catastrophic APS occurs in less than 1% of APS patients and presents as a thrombotic storm. Early use of a combined triple therapy such as anticoagulation, plasma exchange, and steroids with either or not addition of immunoglobulins is important to reduce mortality.

Comparison of recombinant and plasma-derived antithrombin biodistribution in a rabbit model

Antithrombin (AT) is a native plasma protein that acts as the main inhibitor of enzymes generated by the coagulation cascade. In extreme thrombotic conditions, consumption of plasma AT can make treatment with AT-associated heparin therapies less effective. Supplementation with recombinant human AT (rhAT) has shown promise but altered pharmacokinetics were observed when comparing stable heparin complexes of the plasma-derived AT (pAT) and rhAT proteins. To understand the differential clearance mechanisms, biodistribution of rhAT and pAT was determined. (125)I-labelled ATryn (rhAT) or Kybernin P (pAT) was intravenously injected into rabbits. At various time points, animals were sacrificed and organs analysed for bound radioactivity. (131)I-albumin, injected shortly before termination, was used as a marker for trapped blood. Levels of circulating protein + metabolites were significantly less for rhAT than pAT (p < 0.001) and removal of acid soluble fragments confirmed that differences were due to more rapid rhAT clearance. More rhAT (28% dose) than pAT (3% dose) was liver-associated by the earliest time points, corresponding to elevated rhAT degradation products in urine/feces. However, at intermediate times (4 hours), rhAT showed significantly increased arterial and venous uptake over pAT (p </= 0.001). These vessel wall interactions accounted for the primary differences between clearance of rhAT and pAT during these time periods. Overall, circulating rhAT is more rapidly lost to the liver and vessels than pAT. Increased vessel wall binding may facilitate rhAT treatment of vascular thrombosis.

Augmentation of in-stent clot dissolution by low frequency ultrasound combined with aspirin and heparin. An ex-vivo canine shunt study

Introduction: Ultrasound can accelerate clot dissolution in vitro and in vivo. We used an ex vivo canine shunt to investigate low frequency ultrasound effects on platelet-rich stent thrombosis. Methods and results: Nitinol stents were expanded to 2 mm in diameter in two perfusion chambers in a parallel shunt and exposed to flowing arterial blood at 2100 s −1 to generate stent thrombi ( n=224 perfusion runs). Dethrombotic effects were assessed during treatment with saline and combined treatment with aspirin and heparin. One stent was exposed to ultrasound (27 kHz, 1.4 W/cm 2), while the other was not. Stent thrombi were weighed before and after treatment. There was no significant effect of ultrasound during saline infusion. Treatment with aspirin+heparin alone reduced thrombus weight by 37±25% (18.9±6.1 to 11.8±7.7 mg, p<0.0001). Combined treatment with aspirin+heparin+ultrasound produced a 49±23% reduction in thrombus weight (19.0±6.3 to 9.6±7.8 mg, p<0.0001). The reduction in thrombus weight was significantly greater in aspirin+heparin+ultrasound compared with aspirin+heparin alone ( p=0.04). Conclusions: Transcutaneous ultrasound significantly enhances dethrombotic effect of aspirin plus heparin on preformed stent thrombi. These findings suggest the potential of ultrasound as an adjunct to antithrombotic therapy to improve effectiveness without increasing the risk of bleeding complications during treatment of vascular thrombosis.

Treatment of vascular thrombosis with enoxaparin in orthotopic heart transplant patients during the early postoperative period

Management of anti-coagulation in the early period after orthotopic heart transplantation, when the frequency of invasive procedures to assess for graft rejection is high, presents a difficult clinical problem in which the need for effective therapy must be weighed against the desire for outpatient treatment. In this report, we summarize the clinical course and long-term outcome of 6 patients from our center in whom vascular thrombosis was treated on an outpatient basis with enoxaparin. We conclude that the use of enoxaparin may provide a safe and reasonable alternative to conventional anti-coagulation therapy during this period.

Percutaneous mechanical thrombolysis and thrombectomy

Devices and methods for mechanically dissolving (thrombolysis) and removing (thrombectomy) thrombus using a percutaneous approach have been developed to address the deficiencies of the previously available methods of treating thrombus, namely Fogarty balloon thromboembolectomy and pharmacologic thrombolysis. Goals of percutaneous mechanical thrombectomy (PMT) include faster, safer, and less expensive treatment of vascular thrombosis, either alone or in conjunction with prior methods. PMT devices have rapidly assumed a role in declotting thrombosed hemodialysis access synthetic grafts, and may eventually play an integral part in many other thrombotic conditions. However, significant device refinement and modification, as well as properly conducted clinical trials, will be necessary before routine use in many applications can be advocated. In this article, each of the PMT devices currently (or soon to be) available in the United States are presented and compared. Each is approved by the Food and Drug Administration for use only in hemodialysis access at the present time.

Polycations increase the efficiency of adenovirus-mediated gene transfer to epithelial and endothelial cells in vitro

Recombinant adenoviruses are being developed for gene therapy for cystic fibrosis and other lung diseases, and for prevention and treatment of vascular thrombosis. A major limitation to the clinical utility of adenoviruses is the low efficiency of gene transfer achieved in vivo. In addition, little is known about the initial interactions between adenoviruses and the target cell. To address the hypothesis that the negative charge presented by membrane glycoproteins reduces the efficiency of adenovirus-mediated gene transfer, primary cultures of human airway, Madin–Darby canine kidney cells, an immortalized cystic fibrosis airway epithelial cell line, and primary cultures of sheep pulmonary artery endothelium were infected with recombinant adeno- virus containing the E. coli lacZ reporter gene (Ad2βgal2) in the presence of various polyions. For each cell type, adsorption of Ad2βgal2 in the presence of the polycations polybrene, protamine, DEAE-dextran, and poly-L-lysine significantly increased the percentage of cells that express lacZ. The polyanion heparin did not significantly alter gene transfer efficiency, but completely abrogated the effects of polycations. These data provide evidence that negatively charged moieties on the cell surface reduce the efficiency of adenovirus-mediated gene transfer, and that alteration of the charge interaction between adenoviruses and the cell surface may improve the potential clinical application of these vectors.

Intravascular fibrinolysis of small vessel thrombosis

The effect of intraarterial fibrinolysin infusion on the prevention and treatment of vascular thrombosis in arterial and venous systems of large and small dogs was studied by use of a free groin flap model. Vessel patency and clot lysis after microvascular repair of the superficial caudal epigastric artery and vein were compared in 14 dogs that received prophylactic infusion of fibrinolysin and in 10 control dogs that did not. In 22 additional dogs, after the formation of a standard fibrin clot, arterial infusion of fibrinolysin was performed to determine its therapeutic effect on fibrin clot lysis. The results demonstrate that, after blunt trauma to peripheral vessels in the dog, prophylactic infusion of fibrinolysin has no significant effect on either vessel patency or percentage of local thrombus formation at the anastomatic site. From a therapeutic standpoint, fibrinolysin was effective in fibrin clot lysis in the large vessels (internal diameter 1.8 to 3.0 mm) of 7 of 10 dogs infused within 48 hours after thrombus formation, but was not effective in the small vessels (internal diameter 0.8 to 1.5 mm) of 11 of 12 small dogs with infusion as early as 1 hour after thrombus formation. The therapeutic effectiveness of the fibrinolytic agents to lyse preformed thromboses in small vessels appears doubtful.

Intravascular fibrinolysis of small-vessel thrombosis

The effect of intraarterial fibrinolysin infusion on the prevention and treatment of vascular thrombosis in arterial and venous systems of large and small dogs was studied by use of a free groin flap model. Vessel patency and clot lysis after microvascular repair of the superficial caudal epigastric artery and vein were compared in 14 dogs that received prophylactic infusion of fibrinolysin and in 10 control dogs that did not. In 22 additional dogs, after the formation of a standard fibrin clot, arterial infusion of fibrinolysin was performed to determine its therapeutic effect on fibrin clot lysis. The results demonstrate that, after blunt trauma to peripheral vessels in the dog, prophylactic infusion of fibrinolysin has no significant effect on either vessel patency or percentage of local thrombus formation at the anastomatic site. From a therapeutic standpoint, fibrinolysin was effective in fibrin clot lysis in the large vessels (internal diameter 1.8 to 3.0 mm) of 7 of 10 dogs infused within 48 hours after thrombus formation, but was not effective in the small vessels (internal diameter 0.8 to 1.5 mm) of 11 of 12 small dogs with infusion as early as 1 hour after thrombus formation. The therapeutic effectiveness of the fibrinolytic agents to lyse preformed thromboses in small vessels appears doubtful.

Fibrinolysin as an agent for treatment of thromboembolic accidents.

THE DEVELOPMENT of effective fibrinolytic (thrombolytic) agents has offered new hope for the treatment of vascular thrombosis and emboli. Many investigations have reported significant improvement over the results obtained by other means of therapy in large numbers of patients with venous thrombosis, pulmonary embolus, and peripheral arterial thrombosis or embolus. Other conditions which have been treated satisfactorily include central retinal vein and artery thrombosis. Cerebral and coronary thrombosis remain, in the opinion of almost all investigators, a subject which requires prolonged investigation before an opinion concerning usefulness of these agents can be offered. 1 As with many such developments, there has been difference of opinion among investigators concerning specific types of materials to be used to produce the activity desired. This has been compounded in the case of fibrinolysin (Thrombolysin) because of the inability to develop truly objective methods of testing for activity and response. As a result strong opinions