Anticoagulants in Coronary Artery Disease

Lee, L. Veronica

doi:10.1016/j.ccl.2008.07.002

Cited by 5 publications

(8 citation statements)

References 96 publications

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“…The acute onset of localized thrombosis in the coronary and carotid arteries is the proximate cause of a heart attack and stroke, which typically are treated with a cocktail of various anticoagulants and antiplatelet agents administered orally and intravenously (i.v.) to prevent further clot progression [1][2][3][4][5][6][7][8][9]. Yet even with aggressive regimens, thrombus formation still proceeds unpredictably [2][3][4]7].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, stuttering thrombosis and micro-embolization can affect the assessment of outcomes with current treatment strategies [4]. Thus the development of safer and more effective anticoagulants remains an active pharmaceutical pursuit pertinent to the control of thrombotic events in acute vascular syndromes [3,[5][6][7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Thrombin‐inhibiting perfluorocarbon nanoparticles provide a novel strategy for the treatment and magnetic resonance imaging of acute thrombosis

Myerson

Lanza

et al. 2011

Journal of Thrombosis and Haemostasis

102

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Background As a regulator of the penultimate step in the coagulation cascade, thrombin represents a principal target of direct and specific anticoagulants. Objective A potent thrombin inhibitor complexed with a colloidal nanoparticle was devised as a first-in-class anticoagulant with prolonged and highly localized therapeutic impact conferred by its multivalent thrombin-absorbing particle surface. Methods PPACK (Phe(D)-Pro-Arg-Chloromethylketone) was secured covalently to the surface of perfluorocarbon-core nanoparticle structures. PPACK and PPACK nanoparticle inhibition of thrombin were assessed in vitro via thrombin activity against a chromogenic substrate. In vivo antithrombotic activity of PPACK, heparin, non-functionalized nanoparticles, and PPACK nanoparticles was assessed through IV administration prior to acute photochemical injury of the common carotid artery. Perfluorocarbon particle retention in extracted carotid arteries from injured mice was assessed via 19F magnetic resonance spectroscopy (MRS) and imaging (MRI) at 11.7 T. APTT measurements determined the systemic effects of the PPACK nanoparticles at various times after injection. Results Optical assay verified that PPACK nanoparticles exceeded PPACK’s intrinsic activity against thrombin. Application of the an in vivo acute arterial thrombosis model demonstrated that PPACK nanoparticles outperformed both heparin (p=.001) and uncomplexed PPACK (p=.0006) in inhibiting thrombosis. 19F MRS confirmed that PPACK nanoparticles specifically bound to sites of acute thrombotic injury. APTT normalized within twenty minutes of PPACK nanoparticles injection. Conclusions PPACK nanoparticles present thrombin-inhibiting surfaces at sites of acutely forming thrombi that continue to manifest local clot inhibition even as systemic effects rapidly diminish and thus represent a new platform for localized control of acute thrombosis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thrombin‐inhibiting perfluorocarbon nanoparticles provide a novel strategy for the treatment and magnetic resonance imaging of acute thrombosis

Myerson

Lanza

et al. 2011

Journal of Thrombosis and Haemostasis

102

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“…A variety of classes of drugs are used to modify coagulability. Anticoagulants can be divided into unfractionated and low molecular weight heparin (enoxaparin, dalteparin, tinzaparin), direct thrombin inhibitors (argatroban, bivalirudin, desirudin, lepirudin), heparinoids or synthetic heparins (danaparoid, fondaparinux), antithrombin agents, and coumarin derivatives (the oral anticoagulant warfarin) [6,7]. Antiplatelets agents are divided according to their site of action into those that inhibit 1) adhesion, 2) activation, 3) aggregation, or 4) platelet-mediated links with inflammation.…”

Section: Introductionmentioning

confidence: 99%

Anticoagulation and Psychotropic Medications

Bachawati

2010

Curr Psychiatry Rep

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Anticoagulants and psychotropic medications are commonly prescribed together. Thus, the potential for interaction exists. Whereas thrombolytics and heparins are implicated in few pharmacokinetic interactions, warfarin and platelet inhibitors have been implicated in various interactions with psychotropic medications. In this article, I review the various psychotropic drug classes' relationships to anticoagulants. In a field devoid of randomized, placebo-controlled trials, clinical vigilance is advised when managing patients on concomitant therapy.

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“…1-3 The deployment of direct thrombin inhibitors such as dabigatran recognizes the central role that thrombin plays in clot formation by proteolytic cleavage of fibrinogen into fibrin, but also its role in activation of platelets and Factor XIIIa, among others. 4,5 Many of these treatment options display small therapeutic windows, with concerns for deleterious side effects such as bleeding that hamper their clinical adoption. 4-7 …”

Section: Introductionmentioning

confidence: 99%

“…4,5 Many of these treatment options display small therapeutic windows, with concerns for deleterious side effects such as bleeding that hamper their clinical adoption. 4-7 …”

Section: Introductionmentioning

confidence: 99%

Thrombin-Targeted Liposomes Establish a Sustained Localized Anticlotting Barrier against Acute Thrombosis

et al. 2013

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The goal of the present work was to design and test an acute-use nanoparticle-based antithrombotic agent that exhibits sustained local inhibition of thrombin without requiring a systemic anticoagulant effect to function against acute arterial thrombosis. To demonstrate proof of concept, we functionalized the surface of liposomes with multiple copies of the direct thrombin inhibitor, D-phenylalanyl-L-prolyl-L-arginyl-chloromethyl ketone (PPACK), which exhibits high affinity for thrombin as a free agent, but manifests too rapid clearance in vivo to be effective alone. The PPACK-Liposomes were formulated as single unilamellar vesicles, with a diameter of 170.78 ± 10.59 nm and a near neutral charge. In vitro models confirmed the inhibitory activity of PPACK-Liposomes, demonstrating a KI′ of 172.6 nM. In experimental clots in vitro, treatment of formed clots completely abrogated any further clotting upon exposure to human plasma. The liposomes were evaluated in vivo in a model of photochemical-induced carotid artery injury, resulting in significantly prolonged arterial occlusion time over that of controls (69.06 ± 5.65 min for saline treatment, N=6, 71.33 ± 9.46 min for free PPACK treated 85.75 ± 18.24 min for precursor liposomes; N=4, 139.75 ± 20.46 min for PPACK-Liposomes; P = 0.0049, N=6). Systemic anticoagulant profiles revealed a rapid return to control levels within 50 minutes, while still maintaining antithrombin activity at the injury site. The establishment of a potent and long-acting anticoagulant surface over a newly forming clot with the use of thrombin targeted nanoparticles that do not require systemic anticoagulation to be effective offers an alternative site-targeted approach to the management of acute thrombosis.

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Anticoagulants in Coronary Artery Disease

Cited by 5 publications

References 96 publications

Thrombin‐inhibiting perfluorocarbon nanoparticles provide a novel strategy for the treatment and magnetic resonance imaging of acute thrombosis

Thrombin‐inhibiting perfluorocarbon nanoparticles provide a novel strategy for the treatment and magnetic resonance imaging of acute thrombosis

Anticoagulation and Psychotropic Medications

Thrombin-Targeted Liposomes Establish a Sustained Localized Anticlotting Barrier against Acute Thrombosis

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