Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subsequent to publication of the NINDS t-PA Stroke Study results, we sought to determine the proportion of patients eligible for and receiving intravenous tissue plasminogen activator (t-PA) at an active acute stroke treatment center. Over a 12-month period there were 185 stroke code activations. Of these, 134 involved patients with ischemic stroke, and 48 of these (36%) were potentially eligible for treatment with t-PA by the time criterion (i.e., interval from stroke onset to hospital presentation < 3 hours). Nine of the 48 potentially eligible patients (19%) and 9 of 134 ischemic stroke patients (7%) overall received t-PA. In our patient population only a small proportion of all patients with acute ischemic stroke presently are eligible for treatment with t-PA.
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PMID:Intravenous t-PA for acute ischemic stroke: therapeutic yield of a stroke code system. 948 80

Thrombotic risk factors may be important in determining cardiovascular outcome in patients with symptomatic peripheral arterial disease. A cohort study with a 6-year follow-up period was established to determine the relationships between haemostatic and rheological factors and incident ischaemic heart disease (IHD) and stroke events in patients with peripheral arterial disease. A consecutive series of 607 patients with intermittent claudication was examined between 1989 and 1990 at the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. Main outcome measures were combined fatal and non-fatal stroke, non-fatal myocardial infarction (MI), coronary death and total coronary events. A total of 210 patients died during follow-up. 203 patients did not experience a vascular event or deterioration of limb ischaemia. Median levels of fibrinogen, von Willebrand factor (VWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer and whole blood viscosity were significantly higher in those who experienced an event compared with those who did not. After adjusting for age and sex, fibrin D-dimer was significantly associated with risk of non-fatal myocardial infarction (RR 1.50, 95% CI 1.09-2.06, P < or = 0.01). Both fibrinogen and fibrin D-dimer were associated with risk of total coronary events (P < or = 0.05). The risk of stroke was related to baseline levels of t-PA antigen (RR 1.87, 95% CI 1.04-3.34, P < or = 0.05) and whole blood viscosity (RR 1.33, 95% CI 1.07-1.65, P < or = 0.01). All the relationships became weaker and statistically non-significant after further adjustment for cigarette smoking, systolic blood pressure, glucose and baseline IHD. The associations of these factors to IHD and stroke may therefore be partly related to cardiovascular risk factors, but are likely to be important in the pathogenesis of future atherothrombotic events in subjects with peripheral arterial disease.
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PMID:Haemostatic factors and prediction of ischaemic heart disease and stroke in claudicants. 953 45

Arterial thrombosis is the underlying cause of a wide variety of cardiovascular diseases such as myocardial infarction, stroke and pulmonary thromboembolism. All the currently used thrombolytic agents are plasminogen activators, which are very efficient in restoring the blood flow. The fibrinolytic system comprises an inactive proenzyme plasminogen, that is converted by plasminogen activators to the enzyme plasmin, that degrades fibrin. Despite the widespread use of established thrombolytic agents such as streptokinase, tissue-plasminogen activator and urokinase, all these agents suffer from a number of inadequacies including resistance to reperfusion, occurrence of acute coronary reocclusion and bleeding complications. The quest continues for thrombolytic agents with a higher potency, specific thrombolytic activity and fibrin selectivity. Several lines of research towards improvement of thrombolytic agents are being explored including the construction of mutants and variants of plasminogen activators, chimeric plasminogen activators and conjugates of plasminogen activators with monoclonal antibodies. Newer molecules such as pro-urokinase, saruplase, alteplase, K1K2Pu and staphylokinase have shown promise in animal models of arterial and venous thrombosis and also in pilot scale clinical studies in patients with myocardial infarction. However, more clinical trials are needed to determine whether these novel recombinant thrombolytic agents shows improved efficacy and fibrin specificity with minimal bleeding tendencies.
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PMID:Newer thrombolytic drugs for acute myocardial infarction. 953 45

Thromboembolic complications such as ischemic stroke and myocardial infarction are significantly more frequent in patients with arterial hypertension. From the available intervention studies, it appears that pharmacologic treatment of hypertension-at least with diuretics and beta-blockers-may more effectively protect against cerebrovascular as compared to coronary thromboembolic events. Whether other antihypertensive substances provide a more effective protection with respect to cardiac morbidity and mortality is the subject of numerous studies presently underway. These studies will help to answer the question of whether the extent of protection from coronary events during antihypertensive treatment depends on factors beyond blood pressure control. The fibrinolytic system is crucially involved in the pathogenesis of thromboembolic events. One determinant of this system is the balance between plasminogen activators (tissue-type plasminogen activator [t-PA]) and inhibitors (plasminogen activator inhibitor 1 [PAI-1]). Experimental and clinical evidence suggests that at least some of the drugs used in the treatment of hypertension may alter the activity of the fibrinolytic system. Scarce and controversial data with respect to such an interaction exist with respect to diuretics, beta-blockers, and calcium antagonists. In addition, experimental evidence demonstrates that PAI-1 is stimulated by angiotensin II (A II), whereas t-PA is activated by bradykinin. Thus, antihypertensive drugs acting within the renin angiotensin system should exert effects also within the fibrinolytic system. However, results from clinical studies with angiotensin converting enzyme (ACE) inhibitors and A II receptor antagonists do not unequivocally support such a concept. The discrepancy in the results may, at least in part, be explained by studies performed in healthy volunteer subjects showing that ACE inhibition profoundly affected fibrinolysis only during stimulation of the renin angiotensin system by NaCL restriction.
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PMID:Antihypertensive drug treatment and fibrinolytic function. 979 46

The effective treatment of acute ischemic stroke remains an important goal of modern medicine and substantive advances are occurring. Recently, thrombolytic therapy with tissue-type plasminogen activator was approved for selected patients with acute ischemic stroke when therapy is started within 3 hours of onset. Streptokinase therapy for acute ischemic stroke has not been shown to be effective and is associated with an increased risk of hemorrhage, although it was not evaluated as early after stroke onset as tissue-type plasminogen activator. Various types of neuroprotective interventions are effective in animal models, but none has yet been proven effective in patients. In the future, combinations of thrombolytic and neuroprotective drugs may be used to attempt maximum rates of recovery after acute ischemic stroke. For combination therapy to achieve its maximum potential, patients with acute ischemic stroke will have to be carefully selected and treated.
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PMID:Further evolution toward effective therapy for acute ischemic stroke. 956 13

Strong evidence from large observational epidemiological studies links haemostatic variables to the future risk of myocardial infarction and stroke. Recent data provide further evidence for an early involvement of haemostatic parameters in atherosclerosis. So far, a variety of markers of a procoagulatory tendency e.g. elevated fibrinogen, coagulation factor VII, factor VIII and von Willebrand factor, platelet hyperaggregation, increased plasma levels of D-dimer, and decreased fibrinolytic capacity, e.g. characterized by increased levels of PAI-1 activity and decreased t-PA concentrations have been identified prospectively. Thus, a complex disturbed haemostatic system plays an important role in the development of atherothrombotic events in several vascular beds. This review discusses the epidemiologic evidence of the association between the haemostatic system and cardiovascular disease.
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PMID:Haemostatic risk factors for cardiovascular diseases. 959 24

Prosthetic valve thrombosis can determine different degrees of valvular insufficiency or obstruction, with a potentially fatal course. The current literature has not established whether the best treatment is thrombolysis or surgery (thrombectomy or valvular replacement). However, both treatments expose the patient to the risk of serious sequelae or death. Here we describe a case of acute thrombosis in a prosthetic mitral valve. At presentation, the patient was in pulmonary edema and had a low cardiac output. She was treated with recombinant tissue-type plasminogen activator infusion (rt-PA 100 mg in 2 hours). Both clinically as well as echocardiographically, we observed a quick regression of the obstruction, but after the treatment, the patient developed an ischemic stroke with aphasia and hemiplegia. The authors conclude that thrombolysis is a highly effective treatment in resolving prosthetic thrombosis. However, because it carries a significant risk of embolization, it should be limited to patients with hemodynamic deterioration in whom surgery could also entail a significant risk of death.
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PMID:[Acute disfunction from thrombosis of a prosthetic mitral valve: thrombolysis with rt-PA in the clinical emergency phase]. 961 54

Drug therapies that inhibit or reverse thrombus formation are important components of the management of acute ischemic stroke. The role of antiplatelet and anticoagulant therapies in stroke prevention has been defined, but further research is needed to confirm the possible benefits of aspirin, heparin, and low-molecular-weight heparin products in acute ischemic stroke. Recently, double-blind, placebo-controlled studies have evaluated the role of the thrombolytic agents streptokinase and tissue plasminogen activator (t-PA) in patients with acute ischemic stroke. Intravenous t-PA, administered within 3 hours of symptom onset at a dose of 0.9 mg/kg, is safe and effective in carefully selected patients.
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PMID:The stroke pharmacopeia: current medical therapies. 961 93

Strategies directed against activated neutrophils have reduced ischemia-induced brain injury. However, therapies targeted specially against the neutrophil adhesion protein L-selectin have not yet been examined in stroke. This study therefore examined the effects of a monoclonal antibody directed against L-selectin in a rabbit model of thromboembolic stroke with (n = 16) or without (n = 10) concomitant t-PA therapy. Rabbits received either the humanized monoclonal antibody DREG200 directed against the L-selectin receptor or humanized control monoclonal antibody HuDREG55 which does not bind to rabbit L-selectin in addition to t-PA therapy (n = 8, each group). HuDREG200 (2 mg kg-1 i.v.) was given as a bolus 3 h following clot embolization, followed immediately by a 2 h intravenous infusion of t-PA (6.3 mg kg-1. Without t-PA therapy rabbits received HuDREG200 (2 mgkg-1, i.v.; n = 5) or HuDREG55 (n = 5) 1 h following clot embolization. The group receiving HuDREG200 in addition to t-PA demonstrated a moderate improvement in brain infarct size (8.4 +/- 2.4 vs. 13.5 +/- 3.5, %hemisphere, mean +/- sem), ICP (final reading 10.0 +/- 1.6 vs. 12.4 +/- 3.0 torr) and restoration in regional cerebral blood flow (30.2 +/- 7.8 vs. 21.6 +/- 10.9 cc 100 g-1 min-1) when compared to t-PA therapy alone although statistical significance was not achieved. No efficacy was demonstrated in the group receiving HUDREG200 without concomitant t-PA therapy. The results suggest the addition of a humanized anti-L-selectin monoclonal antibody HuDREG200 in combination with t-PA may further improve outcome in acute thromboembolic stroke, although future studies are necessary to support these findings.
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PMID:Humanized anti-L-selectin monoclonal antibody DREG200 therapy in acute thromboembolic stroke. 966 85

It is widely recognized that thrombosis is the major event in the evolution of stable vascular disease to unstable ischaemic syndromes including myocardial infarction and stroke. The purpose of this case-control study was to establish clinical and laboratory data on the possible relationship between specific components of the haemostatic system and coronary heart disease. The procoagulant activity (PCA) of peripheral monocytes and polymorphonuclear neutrophils was assessed in 21 males who had suffered a myocardial infarction (MI) and in age-matched controls. In addition, total factor VII activity, fibrinogen, tissue factor pathway inhibitor (TFPI). D-dimers, tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), tumour necrosis factor-alpha (TNF-alpha) and full blood counts were measured. Post MI patients had significantly higher monocyte PCA, higher plasma concentrations of TFPI, fibrinogen, t-PA, T/P100 and also higher total white blood cell and neutrophil counts compared to age-matched controls. This elevated procoagulant state in post MI patients could further exacerbate the disease process and increase the risk of subsequent acute ischaemic events.
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PMID:Monocyte tissue factor-like activity in post myocardial infarction patients. 969 80


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