Human platelet activation by thrombolytic agents: Effects of tissue-type plasminogen activator and urokinase on platelet surface P-selectin expression

Kawano, Koichi; Aoki, I; Aoki, Nobuo; Hòmori, Masashi; Maki, Akira; Hioki, Yoshiko; Hasumura, Yukihisa; Terano, Akiyo; Arai, Tomoko; Mizuno, Haruyoshi; Ishikawa, Kinya

doi:10.1016/s0002-8703(98)70092-4

Cited by 21 publications

(12 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, uPA (urokinase) administration reduces the serum levels of soluble E-selectin in patients with acute myocardial infarction (65,66). The presence of uPA increases platelet surface Pselectin expression in a concentration-dependent manner (67). It has also been suggested that intravascular fibrinolysis induced by uPA may induce P-selectin (68).…”

Section: Differentiation Of Etiologic Agent Class By Examination Of Hmentioning

confidence: 99%

Identification of Diagnostic Biomarkers for Infection in Premature Neonates

Kennedy

Halliday

Velkinburgh

et al. 2008

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P-and E-selectins, interleukin 2 soluble receptor ␣, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.

show abstract

Section: Differentiation Of Etiologic Agent Class By Examination Of Hmentioning

confidence: 99%

Identification of Diagnostic Biomarkers for Infection in Premature Neonates

Kennedy

Halliday

Velkinburgh

et al. 2008

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

show abstract

“…In addition, the dose depending hazard of cerebral hemorrhage resulting in a high risk of treatment-related mortality is another limitation of the fibrinolytic therapy. Furthermore, fibrinolytic substances induce a strong activation of platelets which counteracts the initial fibrinolytic effect leading to secondary thrombus formation and even large vessel reocclusion [10,11]. This has been documented by transcranial Doppler sonography and intraarterial angiography in up to some 60% of acute stroke patients subjected to systemic fibrinolysis and was related to severity of cerebral artery disease, severity of stroke, and poor clinical outcome [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Platelet GPIIb/IIIa Receptor Antagonists in Human Ischemic Brain Disease

Seitz¹,

Siebler

2008

CVP

View full text Add to dashboard Cite

The goal of acute stroke therapy is to salvage brain tissue by rapid cerebral artery recanalization to improve microcirculation. A major drawback of fibrinolysis is the activation of platelets leading to a high rate of re-occlusion. Antagonists of the platelet GPIIb/IIIa-receptor inhibit the binding of fibrinogen to platelets counteracting secondary thrombus formation. Also, they were shown to suppress thrombembolus formation and to limit lesion development in cerebral ischemia. We review the literature concerning the use of intravenously administered GPIIb/IIIa-receptor antagonists abciximab, eptifibatide and tirofiban for the treatment of patients with acute ischemic brain infarction. In multicenter, prospective, randomized and placebo-controlled trials abciximab had a higher cerebral bleeding risk, while tirofiban did not increase hemorrhage. When combined with fibrinolysis, abciximab and tirofiban were found to improve cerebral artery recanalization and tissue reperfusion resulting in reduced infarct volumes and improved neurological outcome. Thus, GPIIb/IIIa-receptor antagonists have a great potential for the treatment of acute stroke.

show abstract

“…77,78 Unfortunately, studies to guide thienopyridine administration in primary PCI have not been performed. However, in STEMI patients receiving fibrinolytic therapy (a situation similar to primary PCI in that ADPinduced platelet responsiveness is enhanced), 79 early treatment with clopidogrel increases TIMI flow, reduces IRA reocclusion, and improves survival. 80,81 In the Clopidogrel as Adjunctive Reperfusion Therapy: Percutaneous Coronary Intervention Subgroup Study (PCI-CLARITY), PCI was subsequently performed in 1863 of 3491 patients receiving fibrinolysis randomized to a 300-mg clopidogrel loading dose and maintenance therapy versus matching placebo.…”

Section: Adjunctive Antiplatelet and Antithrombin Pharmacologymentioning

confidence: 99%

Angioplasty Strategies in ST-Segment–Elevation Myocardial Infarction

Stone

2008

Circulation

View full text Add to dashboard Cite

ardiovascular disease is the most common cause of mortality in most developed nations; Ϸ838 000 inhospital discharges in the United States in 2005 were for acute myocardial infarction, 29% to 47% of which were acute ST-segment-elevation myocardial infarction (STEMI). 1 The case fatality rate of STEMI has fallen dramatically in the last 3 decades, in part because of the widespread use of reperfusion therapy. 1-4 STEMI is in most cases due to rupture of an inflamed thin-capped fibroatheroma containing a lipid-rich necrotic core with superimposed secondary thrombosis resulting in coronary artery occlusion. 5,6 From the seminal demonstration by Reimer et al 7 that canine coronary occlusion results in a several-hour wave front of necrosis spreading from the subendocardial to the subepicardial myocardium arose the hypothesis that timely restoration of flow in the occluded coronary artery would salvage jeopardized myocardium and enhance survival. Effective reperfusion in STEMI can be achieved by either fibrinolytic therapy or primary percutaneous coronary intervention (PCI) without antecedent fibrinolysis (also generally known as primary angioplasty). Fibrinolysis and PCI also may be combined in a variety of ways, depending on the timing of PCI after fibrinolytic administration, the clinical condition of the patient, and whether PCI is applied routinely or selectively after lytic therapy. Randomized trials have collectively demonstrated enhanced survival and freedom from major adverse cardiovascular events with primary PCI compared with fibrinolysis, and as a result, the expeditious performance of primary PCI has become the preferred reperfusion modality for patients with STEMI presenting at appropriately equipped centers.The introduction of new devices such as bare metal stents (BMS) and drug-eluting stents (DES) and novel potent antiplatelet and antithrombotic agents have transformed the interventional approach to the patient with STEMI. Important studies have been completed that have addressed previously unsettled issues such as the importance of time to intervention and the utility of late reperfusion. It is thus appropriate and timely to review the data underlying the contemporary interventional approach to STEMI. The first part of this 2-part series will review the essentials of primary PCI in STEMI, including comparison with fibrinolytic therapy, the impact of PCI-related delays, the evidence for and against delayed infarct artery intervention, the role of BMS and DES, appropriate use of adjunctive antiplatelet and antithrombotic agents, and strategies to expand access to primary PCI, including angioplasty without surgical backup and interhospital transfer. Part 2 reviews interventional strategies after fibrinolytic therapy, discusses volume-quality relationships for PCI outcomes, offers summary recommendations for the patient presenting with STEMI at hospitals with and without interventional facilities, and reviews recent and ongoing investigations to further improve outcomes after catheterbased reperfusion the...

show abstract

Human platelet activation by thrombolytic agents: Effects of tissue-type plasminogen activator and urokinase on platelet surface P-selectin expression

Cited by 21 publications

References 24 publications

Identification of Diagnostic Biomarkers for Infection in Premature Neonates

Identification of Diagnostic Biomarkers for Infection in Premature Neonates

Platelet GPIIb/IIIa Receptor Antagonists in Human Ischemic Brain Disease

Angioplasty Strategies in ST-Segment–Elevation Myocardial Infarction

Contact Info

Product

Resources

About