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

Plasma fibrinogen chromatography is a method for quantification of high molecular weight fibrinogen complexes (HMWFC), native fibrinogen and other fibrinogen derivatives in plasma. Enchanced formation of fibrin, intravascular coagulation, thrombus formation, etc., are reflected by elevation of plasma HMWFC, and the method distinguishes between subjects with normal and pathological rates of fibrin formation. Serial standard blood coagulation assays, including plasma fibrinogen chromatography, and neurological studies were performed on 220 patients admitted to a stroke unit. Findings from patients with cerebral infarction were compared against those of three control groups: (1)normals, (2)a stroke control group and(3)a stroke risk factor group. Plasma HMWFC findings were significantly (p less than 0.001) higher in the stroke risk factor group than in the normals. Plasma HMWFC values were significantly higher (p less than 0.001) in the cerebral infarction patients than in any of the control groups, and plasma fibrinogen, plasminogen, alpha1-antitrypsin and alpha2-macroglobulin also were significiantly higher (p less than 0.001) in the patients. The greater the degree of initial neurological deficit, the greater were plasma HMWFC values (p less than 0.001), and high HMWFC values were associated with poor clinical outcome. Plasma HMWFC values were significantly higher (p less than 0.001) in patients with intracerebral hemorrhage, subarachnoid hemorrhage and cerebral embolism. These findings docunment the fact that a high proportion of stroke patients have coagulopathy, characterized by pathological enhancement of fibrin formation.
Stroke
PMID:Blood coagulation and plasma fibrinolytic enzyme system pathophysiology in stroke. 6 Aug 7

A new model of internal carotid artery embolism was developed using autologous clot. The clot was prepared by incubating blood at room temperature for 2 hours to inactivate plasminogen activators and then refrigerating it at 4 degrees C for 22 hours. The purpose of the experiment was to devise a model of the intravascular lesion and not of stroke itself. The dog was chosen as the experimental animal since it has a maxillocarotid artery which permits collateral flow beyond proximal internal carotid artery occlusions. A volume of clot measuring 0.25 to 0.30 cc was sufficient to occlude the artery for 48 hours in 80% of the animals without causing major strokes. We have used this model to study clot radiolabeling and suggest it may also have application for evaluating thrombolytic drugs.
Stroke
PMID:A new canine model of proximal internal carotid embolism. 50 78

In accordance with the clinical and coagulographic data on 172 patients with ischemic brain stroke (IBS), the authors developed a method of the use of some medicamentous agents (heparin, platelet inhibitors, fresh-frozen blood plasma, plasminogen activators, proteolytic enzymes), adapted to concrete characteristics of the coagulation status at different stages of brain infarction formation and permitting the rate of lethal outcomes to be reduced. In disseminated intravascular coagulation seen in patients with the gravest patterns of IBS, heparin may be indicated.
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PMID:[Revising the principles and improving the methods of differential therapy of ischemic stroke]. 131 50

41,299 patients entering 914 hospitals up to 24 h (median 4 h) after the onset of suspected acute myocardial infarction were randomised between streptokinase (SK: 1.5 MU infused over about 1 h), tissue plasminogen activator (tPA, duteplase: 0.60 MU/kg infused over about 4 h), or anisoylated plasminogen-streptokinase activator complex (APSAC), anistreplase: 30 U over about 3 min). All patients were to receive aspirin (162 mg/day enteric-coated), with the first tablet chewed for rapid and full antiplatelet effect. Half of all patients were randomly allocated subcutaneous calcium heparin (12,500 IU starting at 4 h and given twice daily for 7 days or until prior discharge) in addition to aspirin, and the other half were to receive aspirin alone. ASPIRIN PLUS HEPARIN VERSUS ASPIRIN ALONE--The addition of heparin to aspirin was associated with an excess of transfused or other major non-cerebral bleeds (1.0% aspirin plus heparin vs 0.8% aspirin alone; 2p < 0.01) and of definite or probable cerebral haemorrhage (0.56% vs 0.40%; 2p < 0.05), but with no significnat differences in total stroke (1.28% vs 1.18%). Reinfarctions were slightly less common among those allocated aspirin plus heparin (3.16% vs 3.47%; 2p = 0.09). There was no signficant difference in the pre-specified endpoint of 35-day mortality (2132 [10.3%] aspirin plus heparin vs 2189 [10.6%] aspirin alone). During the scheduled heparin treatment period there were slightly fewer deaths in the aspirin plus heparin group (days 0-7 in hospital: 1534 [7.4%] vs 1633 [7.9%]; 2 p = 0.06), with a slight convergence by day 35 (598 further deaths [3.1% of survivors] vs 556 [2.9%]). The pattern was similar to that observed in the GISSI-2 trial, so that in both trials combined there was a significant reduction in mortality during the scheduled treatment period (2071 [6.8%] vs 2239 [7.3%]; 2p < 0.01). This indicates avoidance of 5 deaths (SD 2) per 1000 patients allocated this high-dose subcutaneous heparin regimen in addition to aspirin, but some of any early benefit may be lost after heparin ceases, with no significant mortality advantage in days 0-35 (both trials: 3100 [10.0%] vs 3172 [10.2%]) or during follow-up to 6 months. SK VERSUS APSAC--APSAC was associated with significantly more reports of allergy causing persistent symptoms and of non-cerebral bleeds, but not of transfused bleeds or of reinfarctions. There was a slight excess of strokes with APSAC (1.04% SK vs 1.26% APSAC; 2p = 0.08), much of it appearing soon after treatment started (strokes during days 0-1: 0.50% SK vs 0.73% APSAC; 2p < 0.02) and being attributed to cerebral haemorrhage (0.24% SK vs 0.55% APSAC; 2p < 0.0001). No significant difference was observed in reinfarction (3.47% SK vs 3.55% APSAC). There was no significant mortality difference during days 0-35, either among all randomised patients (1455 [10.6%] SK vs 1448 [10.5%] APSAC) or among the pre-specified subset presenting within 0-6 h of pain onset and with ST elevation on the electrocardiogram in whom fibrinolytic treatment may have most to offer (861 [10.0%] SK vs 855 [9.9%] APSAC). No significant difference in 6-month survival was apparent overall or in the subset.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41,299 cases of suspected acute myocardial infarction. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group. 1111 34

Plasma crosslinked fibrin polymers (XLFP) are formed as a result of in vivo hemostatic activation and are elevated in thrombotic disease. We have investigated the plasmic degradation of plasma XLFP in vitro to provide information regarding the pattern of crosslinking and the composition of degradation products. Plasma XLFP were identified by sodium dodecyl sulfate (SDS)-agarose electrophoresis and Western blotting and quantitated by gel scanning. D-dimer was measured by enzyme-linked immunosorbent assay and the results were verified by SDS-polyacrylamide gel electrophoresis and Western blotting of the digests. Complete degradation of XLFP occurred only after supplementation of plasma with plasminogen (5 U/mL) and incubation with recombinant tissue plasminogen activator (rt-PA), indicating that the normal plasma plasminogen concentration limits plasmic degradation in vitro. Gel electrophoresis showed that the principal terminal degradation products of XLDP were fragments D, DD, and E, indicating that crosslinking occurred primarily through gamma chain dimers. After adding a low concentration of thrombin to plasma in vitro, XLFP increased progressively before clotting, and the concentration correlated with the increase in the D-dimer concentration after degradation (r = .98). Plasma XLFP and D-dimer concentrations in plasmic digests were significantly elevated in patients with stroke (150 +/- 83 micrograms/mL and 88 +/- 32 micrograms/mL), myocardial infarction (217 +/- 110 micrograms/mL and 84 +/- 30 micrograms/mL), and venous thrombosis (187 +/- 80 micrograms/mL and 86 +/- 19 micrograms/mL) compared with normals (28 +/- 12 micrograms/mL and 25 +/- 7 micrograms/mL). There was a strong correlation between the plasma concentration of XLFP and the D-dimer immunoreactivity of plasma after plasmic degradation (r = .87). The results indicate that XLFP in plasma are crosslinked primarily through gamma chains and degrade to fragment DD with plasminogen activation. Also, the immunoreactivity of in vitro plasmic digests of plasma reflects the concentration of XLFP and may provide a useful indirect measure of in vivo hemostatic activation in patients with thrombotic disease.
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PMID:Plasma crosslinked fibrin polymers: quantitation based on tissue plasminogen activator conversion to D-dimer and measurement in normal and patients with acute thrombotic disorders. 138 60

Elevated plasma levels of the lipoprotein Lp(a) are associated with increased risk for atherosclerosis and its manifestations, myocardial infarction, stroke and restenosis (for reviews, see refs 1-3). Lp(a) differs from low-density lipoprotein by the addition of the glycoprotein apolipoprotein(a), a homologue of plasminogen that contains many tandemly repeated units which resemble the fourth kringle domain of plasminogen, and single homologues of its kringle-5 and protease domain. As plasma Lp(a) concentration is strongly influenced by heritable factors and is refractory to most drug and dietary manipulation, the effects of modulating it are difficult to mimic experimentally. In addition, the absence of apolipoprotein(a) from virtually all species other than primates precludes the use of convenient animal models. Here we show that transgenic mice expressing human apolipoprotein(a) are more susceptible than control mice to the development of lipid-staining lesions in the aorta, and that apolipoprotein(a) co-localizes with lipid deposition in the artery walls.
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PMID:Atherogenesis in transgenic mice expressing human apolipoprotein(a) 146 21

The relative efficacy and safety of individual thrombolytic agents, administered alone and with antiplatelet and antithrombotic drugs, in the treatment of acute myocardial infarction are presented. The clinical benefits and risks of treatment choices are discussed in relation to the mechanisms of the formation and prevention of thrombus and thrombolysis. It is concluded that streptokinase, tissue plasminogen activator (t-PA), and anisoylated plasminogen-streptokinase activator complex (APSAC) significantly reduce mortality and improve left ventricular function equally, despite differences in the rate at which they achieve vascular patency, their durations of action, and the extent to which their use is associated with adverse events. The questions of how best to minimize reocclusion/reinfarction, bleeding, and stroke are discussed, with particular focus on the beneficial use of aspirin and the unresolved issue of how best to use heparin.
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PMID:Thrombolytic, antiplatelet, and antithrombotic agents. 147 1

Disseminated intravascular coagulation (DIC) may cause multiple organ failure. Although DIC may cause capillary occlusion in any and all organs, the lungs, liver, kidneys, gut, heart and brain are particularly affected. Focal brain necrosis can also be caused by DIC. Fibrinolytic therapy will often restore significant blood flow to the capillaries of the lungs. This results in significant increase in lung function because the lung is more resistant to actual necrosis and will resume function once circulation is restored. Administration of fibrinolytic therapy will also prevent liver and kidney failure if started within four hours after trauma. This therapy, when given in low doses intravenously over a twenty-four hour period, has little effect on the coagulation mechanism, and abnormal bleeding, therefore, has not been a concern. It is speculated that if plasminogen activators are effective and safe for treating the intravascular clots of DIC, then perhaps they would be effective in treating other types of intravascular coagulation in the brain, such as various types and degrees of stroke.
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PMID:Organ damage in shock, disseminated intravascular coagulation, and stroke. 147 53

Thrombotic and thromboembolic occlusions of arteries and veins represent acute and often life threatening complications requiring immediate therapeutic intervention. The most important clinical manifestations of vascular occlusions are myocardial infarction, peripheral arterial occlusion, pulmonary embolism, deep vein thrombosis and ischemic stroke. The logical approach for the treatment in these indications is the early restoration of blood circulation in order to preserve the organ deprived from oxygen supply and to prevent chronic sequelae. Recanalization by surgical intervention is only possible in some indications and is restricted to special clinics. Thrombolysis induced by agents activating plasminogen imitates the physiologic way of dissolving an occlusive clot by shifting the balance of the hemostatic and fibrinolytic system towards fibrinolysis. Streptokinase was the first effective thrombolytic drug used in patients. In the first years of its usage the identification of the appropriate indication and the dosage and application regimens used were based on little pharmacological knowledge and lack of appropriate dose finding. This resulted in suboptimal therapeutic efficacy and severe bleeding. Development of advanced diagnostic methods, more appropriate dose and application regimens and the development of more specific fibrinolytic drugs like rt-PA led to a remarkable improvement of its benefit-risk ratio and made thrombolysis to a widely accepted form of therapy in thrombotic and thromboembolic diseases. Early restoration of blood flow however is only the starting point of a therapeutic strategy, aiming at minimizing the risk of recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombolysis: the logical approach for the treatment of vascular occlusions. 152 9

The plasminogen-plasmin enzyme system and its therapeutic manipulation provide the substrate for an assessment of the clinical use of thrombolytic agents. Proven effective in acute MI and its complications, such agents have other potential applications--e.g., in stroke or pulmonary embolism--and are being investigated in those contexts.
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PMID:Thrombolytic therapy: a state of the art review. 152 55


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