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

Stroke therapy trials have historically allowed for late patient entry (ie, within 24 to 48 hours from stroke onset) despite evidence suggesting the importance of early intervention. Experimental studies of cerebral infarction suggest treatment may be most effective when begun within three hours and may be only marginally effective when begun after 12 hours. Lysis of an acute intra-arterial thrombus in the setting of thrombolytic therapy is also time dependent. We describe an ongoing dose-escalation study of tissue plasminogen activator (tPA) as ultra-early therapy for cerebral infarction. The protocol requires that hemorrhage be ruled out by computed tomography scan of the brain prior to tPA infusion, and the infusion must begin within 90 minutes of symptom onset. The two primary goals of the study are to assess safety and potential efficacy. Preliminary results from the study and the future of ultra-early stroke intervention are discussed.
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PMID:The investigational use of tPA for stroke. 314 18

Two patients with acute major, disabling cerebral infarction with presumed middle cerebral artery occlusion were treated with the clot specific thrombolytic agent tissue plasminogen activator roughly three and a half hours after the onset of symptoms. Both patients had a normal computed tomography (CT) scan before treatment. No appreciable systemic bleeding complications occurred, apart from bruising. One patient had bleeding into the subarachnoid space from a microscopic angioma, which was found at necropsy. Haematological monitoring of the two patients showed pronounced fibrinogenolysis and alpha 2 antiplasmin consumption in one. One patient showed transient improvement during the infusion. In both cases extensive infarction, partly haemorrhagic in one, with massive concomitant oedema was found on repeated CT. Both patients deteriorated and eventually died as a consequence of transtentorial herniation. In the one patient who came to necropsy a moderate, probably pre-existing smooth stenosis of the ipsilateral carotid artery was found, all cerebral vessels being patent. It is concluded that thrombolytic treatment with a clot specific agent such as tissue plasminogen activator started three to four hours after a major ischaemic stroke may be hazardous, not because of haemorrhagic transformation of the original ischaemia but because early reperfusion may promote massive, potentially fatal cerebral oedema.
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PMID:Fatal ischaemic brain oedema after early thrombolysis with tissue plasminogen activator in acute stroke. 314 80

Intravenous administration of tissue plasminogen activator immediately after the injection of numerous small blood clots into the carotid circulation in rabbit embolic stroke model animals caused a significant reduction in neurological damage. In vitro studies indicate that tissue plasminogen activator produced substantial lysis of clots at concentrations comparable to those expected in vivo, suggesting that this may be the mechanism of action of this drug. Drug-induced hemorrhages were not demonstrable. Tissue plasminogen activator may be of value for the immediate treatment of embolic stroke.
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PMID:Tissue plasminogen activator reduces neurological damage after cerebral embolism. 393 54

Thrombolytic therapy mimics and enhances physiological fibrinolysis. The following substances are presently available for clinical use: the nonphysiological thrombolytics streptokinase, the APSAC (acylated plasminogen-streptokinase activator complex), the physiological plasminogen activators urokinase and tissue plasminogen activator (t-PA). Whereas the first three systematically activate the fibrinolytic system, t-PA possesses relative fibrin selectivity. The fibrin-selective active pro-urokinase has not yet been officially approved for the treatment of thromboembolic diseases, but it is being clinically tested. Fibrinolytic therapy has an established place in the management of acute myocardial infarction and of massive pulmonary embolism. When an acute deep venous thrombosis is diagnosed with a proximal extension into the popliteal vein, thrombolytic therapy is clearly superior to heparin. The lysis has proven to be an effective form of treatment of peripheral occlusive arterial disease. Local thrombolytic therapy is an option for acute and chronic femoro-popliteal occlusions involving the trifurcation into the calf arteries and for embolic occlusions of the same segment in patients with contraindications to surgical therapy. First study results of thrombolytic therapy of stroke are promising.
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PMID:[Fibrinolytic agents--who benefits when?]. 748 76

Cerebrovascular disease is one of the major causes of morbidity and mortality in the developed world. A number of important risk factors have been identified with the occurrence of stroke, including advancing age, hypertension, smoking and diabetes mellitus, but the mechanisms that link these risk factors to the development of cerebrovascular disease are unclear. The pathogenesis of cerebrovascular disease includes syndromes of atherothrombotic brain infarction and intracerebral hemorrhage. The role of abnormalities of the coagulation and fibrinolytic systems in these processes has not been properly evaluated with regard to clinical outcome, although there is evidence that raised concentrations of fibrinogen are associated with an increased risk of stroke. Smaller studies have identified increases in FVIII/vWF in association with acute stroke and raised levels of tissue plasminogen activator. Although factor VII is considered a risk factor for coronary artery disease, little is known regarding its role in the development of cerebrovascular disease. Improved understanding of the pathogenesis of stroke and the potential to predict patients at risk of stroke should herald the beginning of new approaches in stroke management.
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PMID:Risk factors for cerebrovascular disease and the role of coagulation and fibrinolysis. 757 90

The authors investigated the behaviour of some markers of the haemostatic balance in a group of patients with acute focal cerebral vasculopathy. The series consists of 70 female patients (mean age: 61 +/- 5), 25 of whom suffering from TIA and 45 from thrombotic stroke; 40 normal controls (mean age 43 +/- 5) were also considered. For each patient after an overnight fasting a withdrawal of venous blood was done within 24-36 hours after the admission. For each sample the determination of seven prothrombotic markers [(fibrinogen (F), factor VII (F VII), antithrombin III (AT III), protein C (PC), protein S (PS) (coagulometric method IL), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) (ELISA method Boehringer)] and of three prethrombotic markers [(fibrinopeptide A (FPA), beta-thromboglobulin (BTG) and D-dimer (D-D) (ELISA method, Boehringer)] was performed. The results obtained in the group of the cerebrovasculopathic patients compared to the controls showed a significant increase of F (p < 0.001), F VII (p < 0.005), BTG (p < 0.05) and D-D (p < 0.01), whereas significant differences regarding AT III, PC, PS, t-PA, PAI and FPA were not observed. The authors hypothesized that the increased levels of fibrinogen and factor VII in the cerebrovascular subjects, globally considered, may depend on a marked prothrombotic state, linked in a pathogenetic sense to the vascular disease; the existence of a prethrombotic state is also documented by the increase of betathromboglobulin and D-dimer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Haemostatic balance in patients with acute focal cerebral vasculopathy. 760 35

Platelet function and fibrinolytic activity was studied during rest and after ergometric exercise in 13 hypertensive or normotensive patients with obstructive sleep apnea (OSA) and in 10 sex- and weight-matched controls. All patients had undergone a complete polysomnography for the diagnosis of OSA. The controls did not undergo any sleep investigation but had no history of snoring or witnessed apneas during sleep. On antihypertensive drug wash-out, two of the patients were normotensive, whereas 11 had mild to moderate hypertension. Platelet aggregation measured by adenosine 5'-diphosphate- or adrenaline-induced aggregation, platelet factor-4 or beta-thromboglobulin did not differ between patients and controls. During exercise beta-thromboglobulin decreased significantly in both OSA patients and controls. Plasma tissue plasminogen activator activity was similar in OSA patients and controls and increased significantly in both groups after exercise. Plasminogen activator inhibitor type 1 (PAI-1) was 18.4 +/- 3.6 IU/ml in OSA patients compared with 8.2 +/- 1.7 IU/ml in controls (p < 0.029) during rest, indicating decreased fibrinolytic activity. The difference between groups remained after exercise (p < 0.017). Blood pressure elevation was more common and body mass index (BMI) was higher in patients with OSA, but there was no direct relation between blood pressure level or BMI and PAI-1. Nevertheless, differences between groups were smaller when blood pressure and obesity were accounted for. It is concluded that patients with OSA may exhibit decreased fibrinolytic activity. Low fibrinolytic activity may represent a confounding pathophysiological mechanism behind the high incidence of myocardial infarction and stroke in patients with OSA.
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PMID:Platelet function and fibrinolytic activity in hypertensive and normotensive sleep apnea patients. 761 Mar 15

The relevance of coagulation abnormalities in ischemic stroke remains uncertain. The purpose of this study was to identify abnormal patterns of coagulation in established ischemic stroke. We measured coagulation parameters in 86 patients with acute ischemic stroke: 10 lacunar, 55 atherothrombotic and 21 cardioembolic. Statistical comparisons were made between different stroke groups and between all stroke patients and 60 healthy controls. A decrease in functional antithrombin III and plasminogen and an increase in thrombin-antithrombin III complexes, total protein S, tissue plasminogen activator, plasminogen activator inhibitor and D-dimer were observed in the stroke group (p < 0.05). A positive correlation was found between tissue plasminogen activator and thrombin-antithrombin III levels in cardioembolic stroke (p < 0.05). Protein C levels showed significant differences between the three groups, and in the cardioembolic group they were lower than in controls (p < 0.05). Antiphospholipid antibodies were positive in two cases. We conclude that activation of coagulation and fibrinolytic pathways was observed during the acute phase of ischemic stroke. Protein C activity is different in the three types of strokes analyzed, and higher levels seem to be associated with lacunar lesions. Antiphospholipid antibodies do not seem to play an important role in the pathogenesis of stroke in a nonselected population.
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PMID:Hemostatic disturbances in acute ischemic stroke: a study of 86 patients. 765 7

To clarify the efficacy and limitations of the intra-arterial local infusion of a high-dose fibrinolytic agent for acute embolic stroke, we analyzed the results of 44 patients and compared them with those of 51 patients treated with intracarotid (18 patients) or intravenous (33 patients) infusion therapy. Ten megaunits of recombinant tissue plasminogen activator or 24 x 10(4) IU of urokinase were administered through a microcatheter placed into or proximal to an embolus for 20 minutes. When arterial recanalization was not achieved, a second or third infusion was performed. The rates of complete and partial recanalization just after the local infusion were 52 and 32%, respectively. They were high in middle cerebral and basilar artery occlusion and low in internal carotid artery occlusion (69, 78, and 20%, respectively). In our use, there was no difference between tissue plasminogen activator and urokinase in restoring blood flow. The mean time interval from onset to recanalization in patients with middle cerebral artery occlusion showing marked improvement was 4.8 hours, and it was 5.8 hours with basilar artery occlusion. The size of infarction was reduced, and the outcome was good in patients with complete recanalization achieved. The incidence of hemorrhagic infarction within 24 hours was 22%, and only one patient clinically deteriorated. In the intracarotid infusion group (20 x 10(4) IU of urokinase for 30 min), only two patients showed partial recanalization without clinical improvement. The incidence of hemorrhagic infarction was 28%. The outcome in this group and the intravenous infusion group (18 x 10(4) IU of urokinase a day for 1 wk) was poor compared with that in the local infusion group showing complete recanalization. This preliminary study appears to suggest that intra-arterial local fibrinolytic therapy could be a new strategy for acute embolic stroke.
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PMID:Fibrinolytic therapy for acute embolic stroke: intravenous, intracarotid, and intra-arterial local approaches. 773 3

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


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