Mechanisms of fibrinolysis and clinical use of thrombolytic agents

Margaglione, Maurizio; Grandone, E.; Minno, G. Di

doi:10.1007/978-3-0348-7144-0_6

Cited by 2 publications

(5 citation statements)

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“…20 In addition to high levels of PAI-1, major variations in plasma levels of TPA have been found in subjects with coronary artery disease 11 ' 14 ; recent reports 21 -22 have confirmed these findings. Because we have found raised plasma levels of PAI-1 in subjects with a history of ischemic stroke, we have evaluated whether TPA plasma levels are also abnormally high in this setting.…”

supporting

confidence: 72%

“…31 To clarify the apparently paradoxical association of ischemic events with the plasma levels of a factor that promotes fibrinorysis, one should consider that TPA covalently binds to a series of inhibitors of fibrinorysis including PAI-1, a 2 -antiplasmin, and a 2 -macroglobuhn. 20 The enzymaticaUy active fraction of TPA (TPA activity) is the portion of this enzyme that is not bound to PAI-1 or to any other inhibitor. 20 Concentrations of TPA antigen above normal ranges have been reported in subjects with high plasma PAI-1 levels.…”

Section: Discussionmentioning

confidence: 99%

“…20 The enzymaticaUy active fraction of TPA (TPA activity) is the portion of this enzyme that is not bound to PAI-1 or to any other inhibitor. 20 Concentrations of TPA antigen above normal ranges have been reported in subjects with high plasma PAI-1 levels. 36 There is a negative correlation between TPA antigen and TPA activity in plasma samples.…”

Section: Discussionmentioning

confidence: 99%

“…However, despite these uncertainties, the abnormally high levels of fibrin associated with hypofibrinofytic states may greatly amplify an inflammatory and proliferate response. 20 These data show that in a group of subjects attending a metabolic ward, TPA plasma levels-whether alone or in combination with PAI-1 or certain vascular risk factors -identify subjects with a history of cerebral episodes. They also indicate that other factors (PAI-1, positive family history, and age) significantly affect this clinical condition.…”

mentioning

confidence: 99%

“…- 20 Especially when combined, risk factors may trigger a vascular injury that in turn leads to inflammatory and proliferate events. 15 TPA has been suggested as a marker of preclinical atherosclerosis in apparently healthy individuals.…”

mentioning

confidence: 99%

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Abnormally high circulation levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with a history of ischemic stroke.

Margaglione

Minno

Vecchione

et al. 1994

Arterioscler Thromb

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We evaluated 106 subjects with and 109 subjects without a history of ischemic stroke. All were attending a metabolic ward. The two groups were compared for major risk factors for ischemic events. A positive family history for ischemic complications of atherosclerosis was more common in subjects with a history of stroke than in those without; moreover, plasma levels of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (TPA) were higher in patients with documented previous events. A strong positive significant correlation was found between TPA and PAI-1 levels, and an interaction between age and TPA was observed when the sample was stratified according to ages S troke is a major thrombotic complication of atherosclerosis and a leading cause of morbidity and mortality in Western countries. Individuals who smoke, who have high plasma levels of cholesterol or glucose or high blood pressure, or who are obese are all at risk for this event.15 However, such established risk factors account for only about one third of the future ischemic episodes. 68 The involvement of hemostasis in arterial thrombosis has been suspected for many years, but only recently has it been supported by clinical observations and intervention studies.910 Crosssectional and prospective studies 1115 have documented that the impaired fibrinolysis of patients with angina pectoris or previous myocardial infarction is related to elevated plasma levels of the principal inhibitor of the fibrinorytic system, plasminogen activator inhibitor-1 (PAI-1). High levels of PAI-1 have also been reported in myocardial reinfarction, 16 in the juvenile myocardial ischemia of patients with diabetes mellirus and/or hypertrigh/ceridemia, 17 in hyperinsulinemia, 18 and in anReceived April 6, 1994; revision accepted August 31, 1994. From the Qinica Medica, Istituto di Medicina Interna e Malattie Dismetaboliche, Universita di Napoli, and Unita di Trombosi e Aterosclerosi, I.R.C.C.S. "Casa Sollievo della Sofferenza," S. Giovanni Rotondo, Italy.Presented in part at the XIV Congress of the International Society on Thrombosis and Haemostasis, New York, NY, July 4-9, 1993, and published in abstract form (Thromb Haemost. 1993;69:820).Reprint requests to Giovanni Di Minno, MD, Clinica Medica, Istituto di Medicina, Interna e Malattie Dismetaboliche, Via S. Pansini, 5, 80131, Napoli, Italy.O 1994 American Heart Association, Inc.being above or below 70 years. When the patient population was analyzed according to the number of ischemic events, it was found that 62 of the 106 subjects with a history of stroke had experienced more than one ischemic event. Under these conditions, the levels of TPA and PAI-1 still correlated with the occurrence of previous ischemic episodes. As in the whole patient sample, TPA was the strongest discriminator. We conclude that in subjects attending a metabolic ward, TPA and PAI-1 levels consistently help identify subjects with a history of cerebral ischemic episodes and that TPA is the strongest discriminator. (Ar...

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confidence: 72%