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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic fibrinolytic therapy for acute stroke is no longer recommended because of resulting systemic fibrinolysis and the risk of intracerebral hemorrhage. Human tissue-type plasminogen activator (TPA) is a native enzyme that converts plasminogen to plasmin with subsequent clot lysis. The affinity for plasminogen is increased several-fold when the substrate is bound to fibrin. At appropriate dosage, "clot-specific" thrombolysis may be achieved at the surface of the thrombus without creating systemic fibrinolysis. The authors designed a study to evaluate the effect of intravenous TPA administered 2 hours after acute thromboembolic stroke in rats. This time course was chosen to simulate an analogous clinical situation. Middle cerebral artery embolic stroke was caused by intracarotid injection of 0.025 cc of human blood clot in 16 rats. Regional cerebral blood flow, measured by the hydrogen clearance technique, and electroencephalographic (EEG) recordings were obtained every 30 minutes for 5 hours after thromboembolism. Eight rats received a 1-hour infusion of intravenous TPA (1.5 mg/kg) 2 hours after injection of emboli. Ipsilateral blood flow increased significantly within 30 minutes after intravenous TPA and reached preembolic levels within 60 minutes. Blood flow did not improve in the eight control rats throughout the experiment. Power spectral analysis of the EEG recordings showed improvement in the treated group compared to the control group. Postmortem angiography revealed proximal middle cerebral artery occlusion in control animals and patent middle cerebral arteries in TPA-treated animals. Serum fibrinogen and fibrin split products were unchanged in both groups, indicating the absence of systemic fibrinolysis. There were no intracerebral hemorrhages. It is concluded that, in this rat model, TPA increases blood flow with subsequent improvement in the EEG recording after thromboembolic stroke without evidence of systemic fibrinolysis. Intravenous TPA may be useful in the treatment of acute stroke in man.
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PMID:Recombinant human tissue-type plasminogen activator therapy in acute thromboembolic stroke. 311 28

When the human blood coagulation and fibrinolytic systems are activated thrombin cleaves fibrinopeptide A (FPA) and plasmin cleaves b beta1 leads to 42 from fibrin(ogen). Elevated plasma concentrations of FPA and B beta 1 leads to 42 are evidence for enhanced thrombin and plasma activities in plasma. We have determined the plasma concentrations of FPA and B beta 1 leads to 42 in patients who have had thrombotic stroke. Patients who were studied immediately following stroke were found to have greatly elevated plasma FPA and B beta 1 leads to 42 levels, but these decreased to the concentrations found in an apparently healthy age-matched control group 1 month after the infarct. In contrast, the plasma concentrations of the platelet release product beta-thromboglobulin (beta TG) were slightly, but significantly, elevated immediately following the stroke and these did not alter with time after the infarct. It is concluded that following thrombotic stroke increased thrombin and plasmin activities are to be found in plasma. These increased protease activities are probably not directly associated with an increased in vivo platelet release reaction and may be useful in deciding which patients are at risk of reinfarction or stroke progression.
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PMID:Activation of coagulation and fibrinolytic systems following stroke. 621 94

The purpose of this study was to clarify differences in coagulation and fibrinolytic activation between the various subtypes and phases of ischaemic stroke. Haemostatic activation markers were measured in 52 patients with cardioembolic stroke, 32 with atherothrombotic stroke and 54 with lacunar stroke and compared with 23 age-matched controls. Data were obtained in the acute (< or = 7 days after onset), subacute (8-28 days) and chronic (> or = 29 days) phases of stroke. In patients with cardioembolic stroke, D-dimer and alpha 2-antiplasmin-plasmin complex levels were higher during the acute and subacute phases, while thrombin-antithrombin III complex levels were higher during the acute phase than in patients with lacunar stroke and controls. In cardioembolic stroke, fibrinopeptide A was increased during the acute and subacute phases, thrombin-antithrombin III complexes were higher during the subacute phase and D-dimer levels were higher during the chronic phase. Protein C activity was lower during the acute phase than in atherothrombotic stroke, lacunar stroke and controls. Protein C antigen was lower during the acute phase than in lacunar stroke and controls and during the chronic phase than in lacunar stroke. In contrast, only D-dimer levels were higher in atherothrombotic stroke patients than controls during the acute and chronic phases and no significant alterations in these markers were observed in the patients with lacunar stroke. These findings suggest that measurement of molecular markers of coagulation and fibrinolysis may be useful for detecting intracardiac thrombin and plasmin generation in patients with cardioembolic stroke.
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PMID:Alterations of haemostatic markers in various subtypes and phases of stroke. 750 62

Alteplase (recombinant tissue-type plasminogen activator) stimulates the fibrinolysis of blood clots by converting plasminogen to plasmin. The efficacy of intravenous alteplase in the early treatment of patients with acute myocardial infarction has been unequivocally proven, and recent results from the GUSTO trial indicate a significant advantage in 30-day survival for alteplase in an accelerated dosage regimen (< or = 100mg infused over 90 minutes rather than 3 hours) over streptokinase. The advantage of the accelerated alteplase dosage regimen seems to be maintained for at least 1 year. The role of heparin as adjunctive therapy to thrombolysis remains to be fully defined but heparin administration appears to be more important in conjunction with alteplase than with streptokinase. Ideally, patients should receive alteplase as soon as possible after the onset of symptoms of acute myocardial infarction and, while therapy is most beneficial when administered early, survival is improved when the drug is administered up to 12 hours after symptom onset. The accelerated regimen of alteplase used in the GUSTO trial demonstrated a survival advantage in patients < or = 75 as well as those > 75 years of age which was at least as great as that seen with streptokinase. Similarly, alteplase reduces mortality in patients with both anterior and inferior infarctions; however, those with anterior wall infarctions show an improved outcome over those with inferior infarcts. On the basis of pharmacoeconomic analysis of GUSTO data, the accelerated alteplase regimen cost an estimated additional $US32,678 per year of life saved compared with a conventional streptokinase regimen. Cumulative 1-year costs were greater in patients who received the accelerated alteplase regimen but survival was significantly greater than in patients who received streptokinase. No difference in quality of life was evident in patients who received either treatment. The incidence of major haemorrhage associated with alteplase therapy appears to be similar to that seen with other fibrinolytic agents, increasing with increasing dose; however, the risk of stroke, particularly haemorrhagic stroke, is higher with alteplase than with streptokinase. Thus, alteplase has become firmly established as a first-line option in the management of acute myocardial infarction. On the basis of accumulated evidence, the greatest risk reduction with alteplase therapy may be in certain high risk groups, such as those with anterior infarcts, selected elderly patients and those who present late after symptom onset.
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PMID:Alteplase. A reappraisal of its pharmacological properties and therapeutic use in acute myocardial infarction. 758 83

Intracerebral hemorrhagic transformation is one of the most important complications of thrombolytic therapy for acute ischemic stroke. The relationship between changes in markers for the coagulation and fibrinolytic systems and occurrence of hemorrhagic transformation was determined after local intra-arterial thrombolytic therapy using urokinase (UK) (24 patients) or recombinant tissue plasminogen activator (t-PA) (10 patients) within 6 hours of onset. All 34 patients had no hypodensity areas on initial computed tomography scans. Plasma concentrations of fibrinogen-fibrin degradation products (FDP), fibrinogen, alpha 2-plasmin inhibitor (alpha 2-PI), plasmin-alpha 2 plasmin inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), and D-dimer were measured. Hemorrhagic transformation occurred in seven patients (21%) with complete or partial recanalization; four in the UK group and three in the t-PA group. Doses of the thrombolytic agents did not correlate with the incidence of hemorrhagic transformation. The FDP levels in the hemorrhagic transformation group treated with UK significantly increased immediately and 1 hour after the therapy. The alpha 2-PI activities decreased and PIC levels increased in both the hemorrhagic transformation and the nonhemorrhagic groups after the therapy. The TAT levels in both groups tended to be higher than the normal range, but there was no significant difference from the pretreatment levels. The D-dimer levels in the hemorrhagic transformation group were higher than those in the nonhemorrhagic group at 24 hours after the therapy. Furthermore, the D-dimer levels were significantly higher in patients with complete recanalization compared with those with none or partial recanalization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in coagulation and fibrinolytic system after local intra-arterial thrombolysis for acute ischemic stroke. 777 Jan 6

The carbohydrate deficient glycoprotein (CDG) syndrome is a newly described disorder characterized by impaired glycosylated molecules. It has been reported that transient stroke-like episodes appear in half of the patients. We performed hemostatic studies on three CDG syndrome patients belonging to two unrelated families. The most characteristic findings were decreases in antithrombin III (AT III), protein C and alpha 2 plasmin inhibitor to nearly half normal levels. Protein S was reduced in two (siblings) patients. Isoelectric focusing of AT III in native plasma revealed decreased intensity of the major band and increased intensity of a minor cathodal band. These minor AT III molecules were considered to lack an oligosaccharide sidechain. A 12-year-old girl defective not only for AT III but also protein C and protein S developed disseminated intravascular coagulation accompanied by arterial thrombosis in her left hand following dyspnea associated with bronchial asthma. These findings suggest that thrombotic predisposition in patients with CDG syndrome is due to decreased levels of major coagulation inhibitors, particularly as a result of impaired glycosylation of AT III.
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PMID:Hemostatic studies in patients with carbohydrate-deficient glycoprotein syndrome. 786 68

We studied the effect of antiplatelet therapy not only on the secondary prevention of stroke but also on the suppression of vascular damages in patients with cerebral thrombosis at the chronic phase. We measured von Willebrand factor (vWF) as a marker for the endothelial system, and coagulation and fibrinolytic parameters in addition to platelet functions. The platelet aggregation and markers for platelet activation were monitored for the adequate inhibition of platelets. Twenty-one patients were treated with 200 mg ticlopidine. 9 patients with 100 mg ticlopidine and 60-150 mg acetylsalicylic acid, and 18 patients with 200 mg cilostazol daily. The mean duration of follow up was 8.4 +/- 3.0 months. A patient was attacked by a recurrent stroke, but no fatal vascular events occurred during the period. A significant decrease was observed in the collagen- and ADP-induced platelet aggregation and markers for platelet activation such as platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) by the antiplatelet therapy. In addition, the activities of coagulation factor VIII (FVIII) and vWF, markers for vascular damages, showed a significant decrease. The results suggest that the antiplatelet therapy could ameliorate the vascular damage through the inhibition of platelet function. Moreover, thrombin-antithrombin III complex (TAT) and alpha 2-plasmin inhibitor-plasmin complex (PIC), markers for the activation of coagulation and fibrinolytic systems, decreased significantly, suggesting that the treatment inhibits the activation of coagulation and fibrinolytic systems induced by the platelet activation. The activities of FVIII and vWF decreased significantly when the level of beta TG or that of PF4 lowered sufficiently by the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Antiplatelet therapy in patients with cerebral thrombosis at the chronic phase--assessment of its effect on coagulation and fibrinolytic parameters]. 799 82

The prophylactic use of aprotinin has recently been reported to be associated with a significant decrease in blood loss in patients undergoing cardiopulmonary bypass procedures. One of the primary effects of aprotinin is prevention of plasmin degradation of platelet function. Because aprotinin is commercially unavailable in the United States at this time, we evaluated epsilon-aminocaproic acid with respect to decreased perioperative blood loss. We prospectively randomized 40 patients undergoing first-time coronary artery bypass grafting without prior sternotomy into two groups: one group (n = 21) received prophylactic and preincision epsilon-aminocaproic acid and the other (n = 19) received a placebo. No significant differences existed between patient groups with respect to age, body surface area, cardiopulmonary bypass time, and aortic crossclamp time. Cumulative blood loss at 4, 8, 12, and 24 hours after chest closure was significantly less in the epsilon-aminocaproic acid group (426 +/- 242 ml versus 634 +/- 224 ml, p = 0.002, at 12 hours). Only one patient receiving epsilon-aminocaproic acid was given blood or blood components compared to five patients in the placebo group (p < 0.02). D-dimers and fibrin split products were significantly less prevalent in the epsilon-aminocaproic acid group (at 4 hours: 0/20 versus 7/16, p < 0.002 and 5/20 versus 12/19, p < 0.05, respectively). None of the patients had a perioperative myocardial infarction or cerebrovascular accident. The prophylactic administration of epsilon-aminocaproic acid results in a significant decrease in blood loss in patients undergoing first-time coronary artery bypass grafting, and blood transfusion requirements are significantly less. It may be important to administer epsilon-aminocaproic acid before skin incision to be optimally effective.
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PMID:Effect of prophylactic epsilon-aminocaproic acid on blood loss and transfusion requirements in patients undergoing first-time coronary artery bypass grafting. A randomized, prospective, double-blind study. 802 87

The use of first generation plasminogen activators, urokinase, streptokinase and tissue plasminogen activator has revolutionized thrombolytic therapy for myocardial infarction and ischaemia, and potentially stroke. However, thrombolytic therapy employing these activators is limited by reocclusion of the very arteries being opened, which follows in a small but significant number of patients. The development of second generation plasminogen activators, e.g. staphylokinase and anisoylated plasminogen streptokinase activator complex, has not alleviated the problems encountered with classical plasminogen activators. It is now widely recognized that aberrant platelet aggregation induced primarily by thrombin, rather than plasmin, is one of the major causes of recurrent thrombosis following pharmacologic thrombolysis. Agents that (a) inhibit enzymatic and/or coagulant activity of thrombin, (b) block binding of thrombin to its receptor, and (c) interfere with the generation of thrombin by the prothrombinase complex may compromise haemostasis resulting in haemorrhage. We recently demonstrated that thrombin-induced platelet aggregation is accompanied by cleavage of aggregin, a putative ADP-receptor on the platelet surface, and that these events are indirectly mediated by intracellularly activated calpain expressed on the surface. In this review, we discuss the known mechanisms of thrombin-induced platelet aggregation and suggest relative advantages of potential pharmacological agents, being developed in our laboratory, over those that have been previously developed and tested. These inhibitors selectively prevent aggregation of platelets induced by thrombin by inhibiting calpain expressed on the surface. Moreover, one of these inhibitors which blocks thrombin-induced platelet aggregation does not interfere with other platelet responses mediated by thrombin or platelet aggregation induced by other agonists, such as, ADP, collagen, phorbol myristate acetate and thromboxane A2 mimetics. This selectivity could reduce the chances of perturbing the formation of a haemostatic plug.
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PMID:Reocclusion after thrombolytic therapy: strategies for inhibiting thrombin-induced platelet aggregation. 832 74

Alteplase is the product of recombinant DNA technology and is chemically identical to endogenous tissue-type plasminogen activator: Plasminogen is converted to plasmin by alteplase, and fibrinolysis of blood thrombi is subsequently stimulated. Alteplase is now firmly established as a treatment of choice in the management of acute myocardial infarction. The efficacy of intravenous alteplase in the treatment of pulmonary thromboembolism has also been established and appears to be similar to that of streptokinase and urokinase in this indication and in arterial thrombotic occlusion. However, its use in this latter indication and in other vascular disorders has not been as extensively documented. Although trials demonstrating the efficacy of intravenous alteplase in patients with deep vein thrombosis and intra-arterial alteplase in patients with arterial thrombotic occlusion exist, reliable data on the efficacy of the fibrinolytic in ischaemic stroke and intracranial haemorrhage are scarce. Little clinical benefit is apparent in patients with unstable angina, although careful use may be warranted in those with definite pretreatment coronary thrombi. Of concern, there is a suggestion that general use of alteplase in patients with unstable angina may be associated with increased incidence of myocardial infarction. The incidence of major haemorrhage associated with alteplase therapy increases with increasing dose and appears to be similar to that seen with other fibrinolytic agents. Thus, further well-designed studies of the use of alteplase in ischaemic stroke and cerebral haemorrhage are required. However, a small subset of patients with unstable angina and definite pretreatment coronary thrombi may benefit from alteplase therapy. Further, preliminary data suggest efficacy in the therapy of deep vein thrombosis and arterial thrombotic occlusion, and alteplase has a proven place in the fibrinolytic treatment of pulmonary thromboembolism.
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PMID:Alteplase. A reappraisal of its pharmacology and therapeutic use in vascular disorders other than acute myocardial infarction. 852 60


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