Recombinant tissue plasminogen activators (rtPA): A review

Gurman, Pablo; Miranda, OR; Nathan, Aparna; Washington, Chad W.; Rosen, Yitzhak; Elman, N M

doi:10.1002/cpt.33

Cited by 43 publications

(45 citation statements)

References 59 publications

(64 reference statements)

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“…While surgeons typically employ a variety of tools to physically disrupt or remove a clot, only one pharmacological option exists, recombinant tissue plasminogen activator (tPA) (Mozaffarian et al, 2015; Rouchaud et al, 2011). Although proven effective, the therapeutic window of tPA administration is exceptionally short, due to the unacceptable increased risk of cerebral hemorrhage when given after that time point (Gurman et al, 2015). …”

Section: Estrogen Neuroprotection In Brain Injurymentioning

confidence: 99%

Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

Engler-Chiurazzi

Brown

Povroznik

et al. 2017

Progress in Neurobiology

165

121

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There is ample empirical evidence to support the notion that the biological impacts of estrogen extend beyond the gonads to other bodily systems, including the brain and behavior. Converging preclinical findings have indicated a neuroprotective role for estrogen in a variety of experimental models of cognitive function and brain insult. However, the surprising null or even detrimental findings of several large clinical trials evaluating the ability of estrogen-containing hormone treatments to protect against age-related brain changes and insults, including cognitive aging and brain injury, led to hesitation by both clinicians and patients in the use of exogenous estrogenic treatments for nervous system outcomes. That estrogen-containing therapies are used by tens of millions of women for a variety of health-related applications across the lifespan has made identifying conditions under which benefits with estrogen treatment will be realized an important public health issue. Here we provide a summary of the biological actions of estrogen and estrogen-containing formulations in the context of aging, cognition, stroke, and traumatic brain injury. We have devoted special attention to highlighting the notion that estrogen appears to be a conditional neuroprotectant whose efficacy is modulated by several interacting factors. By developing criteria standards for desired beneficial peripheral and neuroprotective outcomes among unique patient populations, we can optimize estrogen treatments for attenuating the consequences of, and perhaps even preventing, cognitive aging and brain injury.

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Section: Estrogen Neuroprotection In Brain Injurymentioning

confidence: 99%

Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

Engler-Chiurazzi

Brown

Povroznik

et al. 2017

Progress in Neurobiology

165

121

View full text Add to dashboard Cite

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“…Fibrinolytic therapy using plasminogen-activating agents remains a clinical mainstay in therapeutic intervention of occlusive vascular pathologies [26]. A persistent issue with the direct intravascular administration of plasminogen-activating drugs is their off-target action to cause systemic fibrinogenolysis and thereby severely affect body’s natural hemostatic capabilities to put patients at hemorrhagic risks.…”

Section: Discussionmentioning

confidence: 99%

Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis

et al. 2017

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Intravascular administration of plasminogen activators is a clinically important thrombolytic strategy to treat occlusive vascular conditions. A major issue with this strategy is the systemic off-target drug action, which affects hemostatic capabilities and causes substantial hemorrhagic risks. This issue can be potentially resolved by designing technologies that allow thrombus-targeted delivery and site-specific action of thrombolytic drugs. To this end, leveraging a liposomal platform, we have developed platelet microparticle (PMP)-inspired nanovesicles (PMINs), that can protect encapsulated thrombolytic drugs in circulation to prevent off-target uptake and action, anchor actively onto thrombus via PMP-relevant molecular mechanisms and allow drug release via thrombus-relevant enzymatic trigger. Specifically, the PMINs can anchor onto thrombus via heteromultivalent ligand-mediated binding to active platelet integrin GPIIb-IIIa and P-selectin, and release the thrombolytic payload due to vesicle destabilization triggered by clot-relevant enzyme phospholipase-A. Here we report on the evaluation of clot-targeting efficacy, lipase-triggered drug release and resultant thrombolytic capability of the PMINs in vitro, and subsequently demonstrate that intravenous delivery of thrombolytic-loaded PMINs can render targeted fibrinolysis without affecting systemic hemostasis, in vivo, in a carotid artery thrombosis model in mice. Our studies establish significant promise of the PMIN technology for safe and site-targeted nanomedicine therapies in the vascular compartment.

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“…Typical prevention regimes involve antiplatelet treatment using the thromboxane inhibitor Asprin 18) or Clopidogrel (ADP P2Y12 Receptor antagonist 18) ) and anticoagulant treatment using Warfarin (target Vit K-dependent coagulation factor 19) ). Treatment regimes involve thrombolytic actions (e.g., r-tPA that activates the fibrinolytic cascade 20) ). One easy point-of-care technique is the VerifyNow® System (http://www.itcmed.com/products/verifynow-system-platelet-reactivity-test) that assesses platelet reactivity to antiplatelet medications such as aspirin, clopidogrel, and GP IIb/IIIa inhibitors [21][22][23] .…”

Section: Pathogenesis Of Thrombo-embolic Ischaemic Strokementioning

confidence: 99%

Novel Diagnostic and Monitoring Tools in Stroke: an Individualized Patient-Centered Precision Medicine Approach

Villiers

Swanepoel

Bester

et al. 2016

JAT

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Central to the pathogenesis of ischaemic stroke are the normally protective processes of platelet adhesion and activation. Experimental evidence has shown that the ligand-receptor interactions in ischaemic stroke represent a thrombo-inflammatory cascade, which presents research opportunities into new treatment. However, as anti-platelet drugs have the potential to cause severe side effects in ischaemic stroke patients (as well as other vascular disease patients), it is important to carefully monitor the risk of bleeding and risk of thrombus in patients receiving treatment. Because thrombo-embolic ischaemic stroke is a major health issue, we suggest that the answer to adequate treatment is based on an individualized patient-centered approach, inline with the latest NIH precision medicine approach. A combination of viscoelastic methodologies may be used in a personalized patient-centered regime, including thromboelastography (TEG®) and the lesser used scanning electron microscopy approach (SEM). Thromboelastography provides a dynamic measure of clot formation, strength, and lysis, whereas SEM is a visual structural tool to study patient fibrin structure in great detail. Therefore, we consider the evidence for TEG® and SEM as unique means to confirm stroke diagnosis, screen at-risk patients, and monitor treatment efficacy. Here we argue that the current approach to stroke treatment needs to be restructured and new innovative thought patterns need to be applied, as even approved therapies require close patient monitoring to determine efficacy, match treatment regimens to each patient's individual needs, and assess the risk of dangerous adverse effects. TEG® and SEM have the potential to be a useful tool and could potentially alter the clinical approach to managing ischaemic stroke. As envisaged in the NIH precision medicine approach, this will involve a number of role players and innovative new research ideas, with benefits that will ultimately only be realized in a few years. Therefore, with this ultimate goal in mind, we suggest that an individualized patient-orientated approach is now available and therefore already within our ability to use. J Atheroscler Thromb, 2016; 23: 493-504.

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Recombinant tissue plasminogen activators (rtPA): A review

Cited by 43 publications

References 59 publications

Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis

Novel Diagnostic and Monitoring Tools in Stroke: an Individualized Patient-Centered Precision Medicine Approach

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