Transport Processes in Fibrinolysis and Fibrinolytic Therapy

Blinc, Aleš; Francis, Charles W.

doi:10.1055/s-0038-1650608

Cited by 83 publications

(66 citation statements)

References 100 publications

(139 reference statements)

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“…Transport of plasminogen activator into a thrombus is rate-limiting, because flow is obstructed. 16 Drug access by diffusion is very slow, but previous studies in a static system have shown that US increases clot uptake of activator and results in greater depth of penetration. 17 US also increases pressure-mediated perfusion through a fibrin matrix, 18 and both of these effects would increase drug delivery and accelerate fibrinolysis.…”

Section: Discussionmentioning

confidence: 99%

Effect of 40-kHz Ultrasound on Acute Thrombotic Ischemia in a Rabbit Femoral Artery Thrombosis Model

2000

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Background —We have shown previously that 40-kHz ultrasound (US) at low intensity accelerates fibrinolysis in vitro with little heating and good tissue penetration. These studies have now been extended to examine the effects of 40-kHz US on thrombolysis and tissue perfusion in a rabbit model. Methods and Results —Treatment was administered with either US alone at 0.75 W/cm 2 , streptokinase alone, or the combination of US and streptokinase. US or streptokinase resulted in minimal thrombolysis, but reperfusion was nearly complete with the combination after 120 minutes. US also reversed the ischemia in nonperfused muscle in the absence of arterial flow. Tissue perfusion decreased after thrombosis from 13.7±0.2 to 6.6±0.8 U and then declined further to 4.5±0.4 U after 240 minutes. US improved perfusion to 10.6±0.5 and 12.1±0.5 U after 30 and 60 minutes, respectively. This effect was reversible and declined to pretreatment values after US was discontinued. Similarly, tissue pH declined from normal to 7.05±0.02 after thrombosis, but US improved pH to 7.34±0.03 after 60 minutes. US-induced improvement in tissue perfusion and pH also occurred after femoral artery ligation, indicating that thrombolysis did not cause these effects. Conclusions —40-kHz US at low intensity markedly accelerates fibrinolysis and also improves tissue perfusion and reverses acidosis, effects that would be beneficial in treatment of acute thrombosis.

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Section: Discussionmentioning

confidence: 99%

Effect of 40-kHz Ultrasound on Acute Thrombotic Ischemia in a Rabbit Femoral Artery Thrombosis Model

2000

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“…Clot permeability using multiphase CTA/value of CTA in evaluating the clot Thrombolysis in any vascular bed depends on the ability of blood and thrombolytic agents to permeate clot [34,35] Permeation of blood flow through the clot or part of it is defined as residual blood flow; this allows the IVT to reach beyond the proximal part of the clot, leading to higher chance of recanalization. Residual blood flow can be observed in CTA source images by clearly visibly increased contrast attenuation through the clot compared with surrounding brain parenchyma [26].…”

Section: Assessment Of Clotmentioning

confidence: 99%

Multimodality CT based imaging to determine clot characteristics and recanalization with intravenous tPA in patients with acute ischemic stroke

et al. 2017

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Acute ischemic stroke (AIS) is a common neurovascular emergency causing significant burden to society. Currently the main focus of AIS treatment is to restore blood flow to at risk brain tissue. For the last twenty years, intravenous tissue plasminogen activator (tPA) was the only proven therapy for patients with AIS. More recently, five randomized clinical trials established the efficacy of endovascular therapy with or without intravenous tPA in selected patient populations with AIS. Not all stroke patients benefit from intravenous tPA or endovascular treatment. Nonetheless, the concept of early recanalization of occluded arteries resulting in better clinical outcomes is well established. In this focused review, we will discuss how imaging modalities such as Non-Contrast CT, CT-Angiography, and CT-Perfusion can potentially help physicians determine which patients are likely to recanalize early with intravenous tPA and therefore benefit from this therapy.

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“…49,50 Experimental and clinical evidence suggests that systemic administration of thrombolytic agents, which is effective in small arteries such as the coronaries, is ineffective for treatment of DVT, likely because of inefficient diffusion of these agents into the matrix of large venous thrombi under conditions of low flow. [51][52][53] Furthermore, systemic thrombolysis for DVT is associated with a greater risk of bleeding compared with that observed with anticoagulation alone. 47,48,54 These observations prompted studies of catheter-directed, local infusion of thrombolytic agents to minimize bleeding and enhance clot dissolution.…”

Section: Pharmacological Thrombolysismentioning

confidence: 99%

Invasive Approaches to Treatment of Venous Thromboembolism

Augustinos

Ouriel

2004

Circulation

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Abstract-Deep vein thrombosis (DVT) occurs in one-quarter of a million individuals annually in the United States and results in significant disability from pulmonary embolism and chronic venous insufficiency, especially when the proximal iliofemoral is involved. Treatment has centered on early institution of adequate anticoagulation to prevent thrombus propagation and embolism, but anticoagulation alone does not always restore venous patency and many patients are left with venous outflow obstruction and valvular incompetence-the anatomic underpinnings of the postthrombotic syndrome. Various strategies have been used to restore patency of thrombosed veins, including open surgical thrombectomy, pharmacological thrombolysis, and percutaneous mechanical thrombectomy. Each modality has benefits and shortcomings. Surgical thrombectomy had previously been abandoned secondary to poor long-term results.More recently, with improved techniques and better patient selection, surgical thrombectomy has regained a therapeutic role in treating acute DVT in young patients with short segment occlusions. The advent of percutaneous techniques has allowed thrombolysis, percutaneous mechanical thrombectomy, and stenting to be used in conjunction with each other-allowing for better resolution of venous clot burden than when an individual modality is used alone. Practitioners who treat patients with DVT should be familiar with all the options available to restore venous patency, preserve valvular function, and thereby minimize the risk of late postthrombotic complications.

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Transport Processes in Fibrinolysis and Fibrinolytic Therapy

Cited by 83 publications

References 100 publications

Effect of 40-kHz Ultrasound on Acute Thrombotic Ischemia in a Rabbit Femoral Artery Thrombosis Model

Effect of 40-kHz Ultrasound on Acute Thrombotic Ischemia in a Rabbit Femoral Artery Thrombosis Model

Multimodality CT based imaging to determine clot characteristics and recanalization with intravenous tPA in patients with acute ischemic stroke

Invasive Approaches to Treatment of Venous Thromboembolism

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