Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial infarction (MI) is the result of acute coronary occlusion and the prognosis depends on the infarct size. In experimental studies, infarct size is reduced by early coronary reperfusion which may be obtained by intravenous thrombolytic therapy. This simple, rapid and widely used technique is the clinical treatment of choice. The diagnosis of MI must be confirmed by clinical and electrocardiographic findings. The clinical history is important because the value of reperfusion when started after the 6th hour after the onset of chest pain is questionable. However, it is often difficult to determine the beginning of MI when preceded by unstable angina. Contraindications to thrombolytic therapy must be carefully excluded irrespective of the thrombolytic agent because of the risk of haemorrhage. This must be weighed up against the risk of the MI itself. Therefore, age is not a systematic exclusion criterion. The choice of thrombolytic is based on the efficacy, mode of administration and cost. Heparin therapy at effective doses is associated in all cases to prevent reocclusion. Aspirin is given orally. The association of a calcium inhibitor or a betablocker may also be considered. Reperfusion and ischaemia may give rise to arrhythmias and haemodynamic changes which have to be rapidly corrected. Haemorrhagic complications during thrombolysis are treated according to the severity and time of onset by blood transfusion sometimes associated with a plasmin inhibitor. Reocclusion is an indication for emergency coronary angioplasty but in some cases repeat thrombolytic therapy may be beneficial. When the MI is extensive, rapid transfer to a cardiological centre with catheter facilities is advisable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Thrombolytic therapy of myocardial infarction: practical management]. 153 Apr 12

Unstable angina is a clinical syndrome of recurrent myocardial ischemia. In some cases, this reflects episodic platelet activation and coronary thrombosis. Thus, the biosynthesis of thromboxane A2, which is largely derived from activated platelets, is increased, often coincident with chest pain. The major role of platelets in unstable angina may influence the response to plasminogen activators. Platelets increase the resistance of thrombi to lysis, by inducing clot retraction and cross-linking and by releasing inhibitors. Thus, coronary thrombi in unstable angina may be resistant to lysis. Furthermore, both t-PA and streptokinase cause platelet activation and thrombin formation in vivo, possibly via plasmin. Plasmin can activate platelets and factor V directly. These prothrombotic effects of plasminogen activators may limit their activity in unstable angina. At the very least, their therapeutic efficacy may be highly dependent on the coadministration of potent antiplatelet agents and anticoagulants.
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PMID:Platelet activation in the pathogenesis of unstable angina: importance in determining the response to plasminogen activators. 189 67

All thrombolytic agents convert plasminogen to plasmin, either directly, as in the case of urokinase, saruplase, and alteplase, or indirectly, as in the case of streptokinase. In the majority of recent clinical trials with streptokinase, a high-dose (0.7-1.5 million units), brief-duration (30-90 minutes) drug regimen has been used. After a mean interval of 4.2 hours from onset of chest pain to intravenous infusion of streptokinase, repeat angiography performed 60-90 minutes after the start of thrombolytic treatment gave a reperfusion rate of 43%; the corresponding figures for anistreplase, saruplase, and alteplase are 56%, 67%, and 69%. The patency rates obtained in similar studies with the same end point are 56% for streptokinase, 77% for anistreplase, 62% for urokinase, 71% for saruplase, and 75% for alteplase. The in-hospital mortality in randomized trials (six large studies in a total of 31,713 randomized patients) with intravenous high-dose streptokinase decreased from 12.0% in the control group to 9.47% in the streptokinase group. In a mortality study involving 1,258 patients randomized to intravenous anistreplase or placebo, the 30-day mortality was reduced by 47%, from 12.2% to 6.4%. In a large trial in which 5,011 patients were randomized to alteplase or placebo, the 30-day mortality was 7.2% compared with 9.8% in controls, a reduction of 27% by alteplase. In another trial, 721 patients were randomized to placebo or alteplase; all patients received acetylsalicylic acid and intravenous heparin. The 14-day mortality was only 2.8% in the alteplase group, 51% less than that in the control group. It is most important that the favorable impact on hospital survival be maintained at 1 year for any thrombolytic drug. Large-scale trials directly comparing mortality after alteplase, streptokinase, or anistreplase are being performed or are in the planning phase. The risk of bleeding exists with any thrombolytic agent; intracranial bleeding is the most serious risk. In a large trial in 5,011 patients with acute myocardial infarction, stroke occurred in 1.1% of alteplase-treated patients compared with 1.0% in placebo-treated controls. Haunting problems are residual stenosis of the coronary artery and reocclusion. Urgent angioplasty does not seem to be the right answer; more effective antithrombotic strategies have yet to be developed.
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PMID:Thrombolytic treatment in acute myocardial infarction. 211 32

Recombinant tissue plasminogen activator (t-PA) is a synthetic fibrinolytic protein which activates plasminogen or converts plasminogen to plasmin specifically in the presence of fibrin. With its "clot-selectivity", t-PA is capable of lysing clots without having a significant effect on circulating plasminogen. In contrast, activation by streptokinase and urokinase is non-specific and affects circulating as well as thrombus plasminogen. These agents, therefore, have a greater potential to induce bleeding than does t-PA. Plasma levels of t-PA following intravenous administration are generally proportional to the dose, but there can be significant interpatient variation. The drug is eliminated primarily by hepatic metabolism and is then excreted in the urine. Half-life of circulating t-PA ranges from 2-8 minutes. Most clinical trials of t-PA have evaluated its use in acute myocardial infarction. Indeed, its current indication is for thrombolysis in evolving MI. Short-term benefits of t-PA administration include a prompt reperfusion and restoration of coronary artery patency in patients with total coronary artery occlusion. The degree to which the heart benefits from thrombolysis is unknown, but electrocardiographic changes, changes in cardiac enzymes and alterations in the pattern of chest pain indicate that rapid reperfusion may limit the size of the infarct. Overall, t-PA appears to be a relatively safe thrombolytic agent. Bleeding is the most significant adverse effect reported with t-PA administration. In most cases, however, bleeding has been minor. Other reported adverse effects include reperfusion arrhythmias, bradycardia, and chest pain. Allergic reactions were not observed in clinical trials.
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PMID:Tissue plasminogen activator: an evaluation of clinical efficacy in acute myocardial infarction. 312 Jan 60

We examined activities or levels of plasmin and thrombin inhibitors in essentially untreated patients with angiographically documented coronary artery spasm. The patients received the ergonovine malate provocation test and were classified into two groups: (a) those with significant coronary artery spasm that produced reduction of the internal luminal diameter of 50% or greater with chest pain and change of electrocardiography (n = 18), and (b) those without coronary artery spasm (n = 17). There was no significant differences in alpha 1-antitrypsin and alpha 2-macroglobulin levels, and C1-inactivator activity between the control and patients with coronary artery spasm. On the other hand, the lower antithrombin III and alpha 2-plasmin inhibitor activities were noted in patients with coronary artery spasm than the control. Thrombin/antithrombin III complex and alpha 2-plasmin inhibitor/plasmin complex levels were significantly higher in coronary artery spasm patients. These results suggest that the coagulation and fibrinolytic systems may maintain their equilibrium in untreated patients with coronary artery spasm.
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PMID:Plasmin and thrombin inhibitors in essentially untreated patients with coronary artery spasm. 751 Nov 30

Uncontrolled hypereosinophilic syndrome is frequently associated with cardiovascular consequences that cause significant morbidity and mortality. The present article reports on a patient with hypereosinophilic syndrome in whom recurrent, recalcitrant coronary artery spasm and associated cardiac arrest were the predominant cardiac manifestations. No valvular abnormalities, evidence of mural thrombi or other cardiac findings commonly associated with hypereosinophilic syndrome were detected, and cardiac function remained normal. The serum tryptase level was normal, cysteine-rich hydrophobic domain 2 (CHIC2) deletion analysis of bone marrow cells was negative and no evidence of mastocytosis or other hematological disorder was found in the bone marrow. To allow for the reduction of prednisone, interferon-alpha-2b was added to the patient's program, but caused aggravation of chest pain and was discontinued. However, a combination of reduced prednisone dosage, imatinib mesylate and hydroxyurea successfully controlled the eosinophilia, and thereafter, episodes of coronary artery spasm did not recur. The clinical features of the present case suggest that, in some patients, hypereosinophilia may manifest as resistant coronary artery spasm and that aggressive control of eosinophilia is necessary.
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PMID:Control of hypereosinophilic syndrome-associated recalcitrant coronary artery spasm by combined treatment with prednisone, imatinib mesylate and hydroxyurea. 1865 Oct 15

A 38-year-old cocaine abuser was admitted to the Emergency Department with a one hour history of precordial chest pain associated with shortness of breath and extreme discomfort. On admission his blood pressure was 90/60 mmHg, the resting 12-lead ECG showed ventricular tachycardia at about 300 beats per minute, and oxygen saturation was 86 percent in room air. After electrical cardioversion, the 12-lead ECG revealed sinusal rhythm and a significative ST segment elevation in leads I, aVL and V1-V6, that was about 0.5 mV in leads I and aVL and more than 1 mV in leads V2, V3 and V4. Laboratory determinations showed elevated creatine-chinase MB (CK-MB) and troponin I. An emergency coronary angiogram was normal. Cocaine use is a major cause of acute myocardial infarction in patients with normal epicardial coronary arteries but the exact mechanism still remains unclear. We hypothesize a non-IgE mediated mast-cell activation, with a direct action played by cocaine, and consequent massive expression of several factors effecting the microcirculatory system, including pro-inflammatory cytokines and chemokines. Our hypothesis is supported by an elevated serum tryptase levels in the patient.
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PMID:High serum tryptase value in massive acute myocardial infarction with ventricular arrhythmia exortion in a cocaine abuser. 1950 5

Kounis syndrome (KS) is characterized by concurrent acute coronary syndrome and allergic reaction, in which acute inflammatory mediators cause spasm and/or erosion and rupture of coronary atheromatous plaque. In this report, we remind clinicians to consider KS in patients who are subjected to allergenic substances and demonstrate acute chest pain. A 36-year-old woman had chest pain, severe dyspnea, hypotension, and symmetrical negative T waves on the anterior leads during electrocardiography approximately two hours after the use of clarithromycin. KS was considered as a possible diagnosis based on the presentation. Laboratory tests revealed an elevated level of troponin I, suggesting myocardial infarction, and an elevated level of serum tryptase level, suggesting an allergic reaction. The patient promptly underwent coronary angiography, which revealed only plaques in all main coronary arteries without any obstructive lesion. To the best of our knowledge, we report herein the first case in the literature describing an association between clarithromycin and KS.
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PMID:Acute coronary syndrome secondary to clarithromycin: the first case and review of the literature. 2508 Sep 53

d-dimers are cleavage products of fibrin that occur during plasmin-mediated fibrinolysis of blood clots. In the emergency department, d-dimer measurement represents a valuable and cost-effective tool in the differential diagnosis of acute chest pain including the main life-threatening entities: acute coronary syndrome, pulmonary embolism, and acute aortic syndrome. Whereas the diagnostic and prognostic values of d-dimer testing in acute coronary syndrome is of less priority, increases of d-dimers are frequently found in venous thromboembolism and acute aortic syndromes, especially acute aortic dissection. As to the high negative predictive value of d-dimer in those disorders, patients with low to intermediate pretest probability may profit in terms of less necessity of further non-invasive or even invasive imaging, simultaneously reducing potential complications and healthcare-related costs. However, because of the low specificity of the different d-dimer tests in contrast to its frequent usage, adequate interpretation is required. Age-related adjustment of d-dimer levels may be used to increase its diagnostic power.
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PMID:Impact of d-Dimers on the Differential Diagnosis of Acute Chest Pain: Current Aspects Besides the Widely Known. 2539