Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 39-year-old female presented to the Emergency Department during the fourth day of menstruation and within 2 hours of the onset of chest pain associated with dyspnea, diaphoresis, and emesis. An electrocardiogram showed acute inferior myocardial infarction and serial CPK enzyme levels peaked at 958 IU/L with 9% MB fraction. Along with aspirin and intravenous nitroglycerin, the patient was given thrombolytic therapy consisting of tPA with an initial bolus of 35 units, followed by 65 units infused within 60 minutes together with heparin 5000 units intravenous bolus, and 1000 units/hour maintenance infusion for 5 days. The menses were prolonged 1 day longer than her usual 5 days; however, there was no increase in the amount of bleeding during any day. The hemoglobin dropped from 12.5 G/dl to 11.3 G/dl in the first 6 hours, but remained stable thereafter. This initial drop in hemoglobin was considered a dilutional effect of 1.5 L of normal saline the patient received intravenously during that period. Although no available guidelines exist regarding the safety of thrombolytic agents during active menstruation, this case report and a few others reported in the literature suggest that normal menstruation is not a contraindication to thrombolytic therapy during acute myocardial infarction.
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PMID:Is thrombolytic therapy safe during active menstruation? 767 27

A blinded, randomized trial compared the effects of front-loaded streptokinase with those of the conventional dose of intravenous recombinant tissue-type plasminogen activator (rt-PA) on left ventricular (LV) function after acute myocardial infarction (AMI). Thrombolytic therapy was administered in the emergency departments of 30 community hospitals in central Illinois, and subsequent studies were performed at 1 tertiary referral center. Patients aged < or = 75 years with a first AMI who could be treated within 4 hours of the onset of chest pain were randomly assigned to receive either streptokinase (375,000 IU bolus, followed by 1,125,000 IU over 1 hour) or rt-PA (10 mg bolus, followed by 50 mg in the first hour, and 20 mg/hour for the next 2 hours). All patients were treated with aspirin (325 mg) and intravenous heparin. Patients were transferred for angiography within 24 hours. During the 30-month study, 253 patients were treated with intravenous thrombolytic therapy 2.4 +/- 1.0 hour after the onset of AMI. In patients with anterior wall AMI (n = 90), global LV ejection fraction measured by angiography within 24 hours was 45 +/- 12% with rt-PA, and 39 +/- 13% with streptokinase (p < 0.03). Convalescent radionuclide angiography documented a persistent beneficial effect of rt-PA on LV regional wall contractility, but not global ejection fraction. There were no differences between rt-PA and streptokinase in preserving global or regional LV function in patients with inferior wall AMI.
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PMID:A difference between front-loaded streptokinase and standard-dose recombinant tissue-type plasminogen activator in preserving left ventricular function after acute myocardial infarction (the Central Illinois Thrombolytic Therapy Study). 821 79

We randomized 352 patients with pain suggestive of acute myocardial infarction who were seen less than 3 h after onset of symptoms to either tissue plasminogen activator or placebo. The impact of treatment on chest pain score was assessed during the first 24 h and related to limitation of final myocardial damage as assessed by various indirect markers. The most marked effect of tissue plasminogen activator was observed in the chest pain score being reduced by 43% in the tissue plasminogen activator group as compared with placebo. Limitation of infarct size with tissue plasminogen activator reached the following percentage values when various methods were used: maximum serum lactate dehydrogenase I activity, 32%; vectorcardiography (QRS vector difference), 20%; electrocardiography (Palmeri score), 20%; ejection fraction, 9%. We conclude that early thrombolysis in acute myocardial infarction reduces the severity of chest pain by nearly 50%. The effect on chest pain is much more marked as compared with the effect on various markers of the final ischemic damage.
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PMID:Impact of early thrombolysis on chest pain score reflecting myocardial ischemia in relation to various markers of ischemic damage. TEAHAT Study Group. 828 35

We report the use of centrally administered tissue-type plasminogen activator for three patients who presented with massive pulmonary embolism to the emergency department. In all patients, rapid improvement of pulmonary arterial pressures ensued by the end of the drug infusion, while the presenting symptoms of chest pain and shortness of breath subsided.
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PMID:Treatment of massive pulmonary embolism with centrally administered tissue-type plasminogen activator. 833 42

We describe an autopsy case of severe intracranial hemorrhage which occurred during the infusion of tissue plasminogen activator (t-PA) for acute myocardial infarction. A 75-year-old man was admitted with substernal chest pain of 3-h duration and electrocardiographic changes consistent with an acute inferior myocardial infarction. Physical examination was unremarkable, except for an initial blood pressure reading of 160/96 mmHg. The patient received 3,000 IU intravenous heparin followed by a 2.4 x 10(6) IU bolus dose of tissue plasminogen activator (t-PA) (Alteplase). This was followed by a drip infusion of 21.6 x 10(6) IU of t-PA over 1 h (total dose 41 mg). Thirty minutes after the infusion of t-PA was initiated, the patient suddenly lost consciousness and began to have violent convulsions, followed by cardiac arrest. Autopsy revealed massive hemorrhage in the bilateral cerebrum and brain stem. To our knowledge, this is the first case of sudden death during t-PA infusion therapy.
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PMID:An autopsy case of intracranial hemorrhage during tissue plasminogen activator infusion. 840 27

Recurrent chest pain with new ST-segment elevation was observed in 26 of 652 patients (4%) with myocardial infarction in a clinical trial of alteplase (recombinant tissue-type plasminogen activator; 100 mg) and aspirin with or without heparin. Clinical and electrocardiographic signs of reocclusion were treated with a second dose of alteplase: 50 mg in 20 patients with signs of reocclusion < or = 24 hours after initial therapy, and 100 mg in 5 patients with signs between 24 and 77 hours, and in 1 patient with early signs of reocclusion. Pain and ST changes disappeared within 100 minutes (median 50). D-dimer determinations in 15 patients were increased, indicating activation of the coagulation system. Signs of reocclusion occurred despite adequate anticoagulation with heparin in 5 of 11 patients in whom coagulation measurements were available. No excess bleeding was observed in patients who received a second dose of alteplase. Retreatment with alteplase is feasible and provides an alternative for angioplasty in patients with clinical and electrocardiographic signs of reocclusion early after thrombolytic therapy.
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PMID:Retreatment with alteplase for early signs of reocclusion after thrombolysis. The European Cooperative Study Group. 843 37

Although coronary thrombosis is thought to play a pivotal role in the pathogenesis of unstable angina and non-Q wave myocardial infarction and antithrombotic therapy is a mainstay in the early management of these patients, the relation between measures of systemic anticoagulation and clinical events has not been defined clearly. In the Thrombolysis in Myocardial Ischemia III trial, 1473 patients with ischemic chest pain at rest evaluated within 24 hours of symptom onset were randomized to (1) tissue plasminogen activator (TPA) or placebo and (2) an early invasive or an early conservative strategy. All patients received a full complement of anti-ischemic medication, aspirin, and continuous intravenous heparin titrated to an activated partial thromboplastin time (aPTT) of 1.5 to 2.0 times control for 72 to 96 hours. The median aPTT in all study groups exceeded the minimum threshold (45 seconds) by 24 hours and remained within the designated range during the protocol-directed heparin infusion. No differences in median aPTT values for the 72- to 96-hour study period were observed between groups (p=not significant). Median 12-hour heparin concentrations were >0.2 U/ml in all groups; however, values <0.2 U/ml were common thereafter, particularly in TPA-treated patients. Time-dependent covariate analyses failed to identify statistically significant differences in either aPTT or heparin levels between patients with in-hospital clinical events (spontaneous ischemia, myocardial infarction, or death) and those without events (p=0.27). Furthermore, early clinical events occurred in a similar percentage of patients with optimal anticoagulation (all aPTTs >60 seconds, all heparin levels>0.2 U/ml), and those with aPTTs or heparin levels below these thresholds. Aggressive (high-intensity) anticoagulation with heparin to achieve aPTTs >2.0 times control does not appear to offer additional clinical benefit to lower levels (1.5 to 2.0 times control) among patients with unstable angina and non-Q wave myocardial infarction receiving intravenous heparin and oral aspirin. Therefore, the optimal level of anticoagulation in this common clinical setting is between 45 and 60 seconds when heparin is included in the treatment strategy. Direct plasma heparin measurement does not offer an advantage to routine aPTT monitoring. The occurrence of spontaneous ischemia, myocardial infarction, and death in spite of antischemic therapy and optimal anticoagulation (as it is currently defined) with heparin supports ongoing efforts to develop more effective antithrombotic agents.
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PMID:Relation between systemic anticoagulation as determined by activated partial thromboplastin time and heparin measurements and in-hospital clinical events in unstable angina and non-Q wave myocardiaL infarction. Thrombolysis in Myocardial Ischemia III B Investigators. 860 20

To characterize the vasospastic angina patients with exercise-induced ischemia, we measured hemostasis (platelet factor 4; PF4, fibrinopeptide A; FPA) and fibrinolytic parameters (tissue plasminogen activator antigen; t-PA, free plasminogen activator inhibitor-1 antigen; free PAI-1) in 15 normal subjects and 33 vasospastic angina patients without significant coronary artery stenosis (less than 50% stenosis). All of the vasospastic angina patients began to feel chest pain within 3 months before diagnostic coronary angiography. Blood samples were obtained from all of the study patients at 8:30-9:30 am before exercise 201Tl emission computed tomography. Vasospastic angina patients were divided into 2 groups; 15 patients with exercise-induced ischemia (group 1) and 18 patients without exercise-induced ischemia (group 2). On coronary angiography, the severity of coronary artery stenosis at the site of spasm in group 1 (34 +/- 5%) was greater than that in group 2 (18 +/- 3%). Plasma FPA and PF 4 levels in group 1 were also significantly higher than those in normal subjects and group 2. Plasma t-PA and free PAI-1 levels in group 1 were significantly higher than those in normal subjects and group 2. Plasma levels of free PAI-1 group 2 were also significantly higher than those in normal subjects. The present study demonstrated that all of the patients with vasospastic angina had impaired fibrinolysis, and these patients with exercise-induced ischemia showed enhanced platelet activation, an enhanced coagulation system, and advanced atherosclerotic lesions. These results suggest that vasospastic angina with exercise-induced ischemia puts patients at increased risk for thrombus formation.
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PMID:Characteristics of vasospastic angina with exercised-induced ischemia--analysis of parameters of hemostasis and fibrinolysis. 880 21

This study assesses the effects of invasive procedures, hemostatic and clinical variables, and doses of recombinant tissue plasminogen activator (t-PA) on hemorrhagic events in the thrombolysis in myocardial ischemia (TIMI), phase 1B clinical trial (n = 1,425). Patients seen within 24 hours of the onset of ischemic chest pain at rest were randomized using a 2 x 2 factorial design for comparison of: (1) t-PA versus placebo as initial therapy, and (2) an early invasive (coronary arteriography with percutaneous angioplasty, if feasible) versus an early conservative strategy (coronary arteriography followed by revascularization if initial medical therapy failed). All patients received conventional medication for acute ischemic syndromes, including heparin, aspirin, beta blockers, nitrates, and calcium antagonists. The total dose of t-PA or placebo was 0.8 mg/kg, up to a maximum dose of 80 mg. In patients treated with t-PA, major and minor hemorrhagic events were more common than among those assigned to placebo (p < 0.001). Patients assigned to the invasive strategy arm had a higher hemorrhagic event rate than the noninvasive strategy, although the difference was not significant (p = 0.026). Patients > 75 years of age had higher intracranial hemorrhage rates than those < 75 years of age (6.7% vs 0.2%, respectively, p = 0.01). Major hemorrhagic events were more common in patients with higher heparin levels (p < 0.001), higher peak D-dimer levels (p = 0.007), and lower nadir fibrinogen levels (p = 0.005). Thus, increased morbidity due to hemorrhagic complications is associated with the use of t-PA, increased age, and selected hemostatic measures. Comparison to TIMI II demonstrates a significant association between the dose of t-PA and hemorrhagic complications.
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PMID:Hemorrhagic events during therapy with recombinant tissue plasminogen activator, heparin, and aspirin for unstable angina (Thrombolysis in Myocardial Ischemia, phase IIIB trial). 905 37

There are several opinions asserting that the accelerated t-PA is more efficient than the standard protocol of streptokinase (SK) administration in acute myocardial infarction (AMI). One hundred patients admitted within the first 6 hrs after the onset of the symptoms revealing AMI were divided in two subgroups, as follows: subgroup A (50 patients) in whom a dose of 1.5 M.U. SK was infused in 20 min (accelerated protocol) and subgroup B (50 patients) in whom the same dose was infused in 60 min (standard protocol). In order to assess the efficiency of thrombolytic therapy (TT), we used three noninvasive criteria: the rapid resolution of the chest pain, the rapid decreasing of the ST segment elevation by more than 50% from the initial value, and the rapid increasing of enzymes revealing necrosis. Using the above-mentioned criteria, we considered that coronary reperfusion appeared in 40 patients from subgroup A (80%) and in 29 patients from subgroup B (58%). The speed of coronary reperfusion was 40 +/- 26 min in patients with accelerated SK and this time was significantly shorter than the time of 60 +/- 24 min registered in the control group. No major hemorrhagic events appeared in both subgroups. Although hypotension appeared more frequently in subgroup A, this minor complication was well supported by our patients. The rapid infusion of the standard dose of SK was followed by a higher rate and speed of coronary reperfusion as compared to the standard protocol.
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PMID:Rapid infusion of streptokinase standard dose in acute myocardial infarction is followed by a higher rate of coronary reperfusion than standard protocol. 956 52


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