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

The choice of antithrombotic agent in cerebral ischemia depends on the pathogenesis: thrombosis, embolism, or hemorrhage. Antiplatelet agents are considered most beneficial in thrombotic stroke, anticoagulants are most effective in cardioembolic stroke; antithrombotic agents are generally contraindicated in hemorrhagic stroke. A meta-analysis of 18 trials documented a 23% reduction in stroke risk with antiplatelet agents; aspirin is typically the antiplatelet agent of choice for stroke prevention. There are no definitive data regarding the optimal aspirin dose for stroke prevention and this issue remains controversial. Ticlopidine is the most effective antiplatelet agent, but its adverse effect profile restricts its use. Anticoagulants are highly effective for preventing cardioembolic stroke, but their effectiveness in non-cardioembolic stroke is uncertain because of lack of trial data. Results of the ongoing Warfarin/Aspirin Recurrent Stroke Study (warfarin [INR 1.8-2.8] vs aspirin [325 mg/day]) may clarify this issue. There is renewed interest in thrombolytics because recent data indicate that reperfusion within a few hours of stroke onset appears to be effective in preventing neuronal damage. In addition, when given within 6 hours of stroke onset, thrombolytics appear to be relatively safe. Several direct thrombin inhibitors are being evaluated. Experimentally, hirudin, hirulog, D-Phe-L-Pro-L-Arg-CH2Cl (PPACK), and argatroban are clearly more effective than heparin in inhibiting platelet deposition and thrombus formation, and also show promise in preventing reocclusion after thrombolysis for both experimental thrombotic and embolic stroke. However, the risk of hemorrhage in patients with cerebrovascular disease is unknown for these agents.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antithrombotic agents in cerebral ischemia. 786 71

Haemostatic measurements were undertaken in 132 patients diagnosed with heat stroke during the pilgrimage to Makkah, in two successive summers of 1989-90. The control group comprised 49 patients, all pilgrims, with a wide range of clinical conditions, but without hyperpyrexia or deranged haemostasis. Heat stroke patients showed (i) significant prolongation of the prothrombin (PT), activated partial thromboplastin (aPTT) and thrombin times (TT) but normal reptilase time (RT); (ii) significant reduction in plasma levels of antithrombin III (AT-III), factor V, proteins C and S, plasminogen activator inhibitor (PAI) and platelet count; (iii) increase in plasma factor VIII, tissue plasminogen activator (t-PA) and serum FDP; (iv) no significant changes in plasma fibrinogen, plasminogen, alpha 2-antiplasmin and factors VII and X. Heat stroke patients were then grouped into those with and those without bleeding symptoms. Bleeders showed greater prolongation of the PT, aPTT and TT and significant reductions in fibrinogen, AT-III, factors V, VIII and X, plasminogen, alpha 2-antiplasmin and platelet count. Logistic regression and discriminant analysis showed that AT-III was the parameter associated most with heat stroke and reliable enough to predict its occurrence, whether or not bleeding occurred. The results indicate that activation of the haemostatic mechanism, consumptive in nature, regularly accompanies heat stroke and highlights the physiological role of AT-III in checking this activation process.
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PMID:The coagulopathy of heat stroke: alterations in coagulation and fibrinolysis in heat stroke patients during the pilgrimage (Haj) to Makkah. 786 79

Lipopolysaccharide (LPS)-induced (i.v. or i.c.v., 1.8 mg/kg) release of von Willebrand factor (vWF) was examined in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. SHR rats released significantly (P < 0.05) more vWF than WKY rats in response to LPS. LPS also inhibited factor VIII procoagulant activity (FVIII:c) which may indicate an increase in thrombin activity. Cultured cerebrovascular endothelial cells (EC) derived from both SHR and WKY rats, as well as human umbilical vein EC (HUVEC) cultures constitutively released vWF. Treatment with agonists including LPS, thrombin and tumor necrosis factor-alpha (TNF alpha) did not affect the in vitro secretion of vWF by cerebrovascular EC cultures but significantly upregulated vWF release by HUVEC cultures. Preincubation of cerebrovascular EC cultures with interleukin-1 (IL-1) +/- TNF alpha or co-culturing in the presence of LPS-activated syngeneic monocytes had no effect on vWF secretion. The findings demonstrate that conditions of hypertension may affect endothelial cells and make them more responsive to agonist stimulation and thereby increase secretion of vWF, an important factor in hemostasis as well as thrombosis. The capacity of LPS to significantly affect the in vivo secretion of vWF in SHR and WKY rats but not cultured cerebrovascular EC indicates that observed elevations in plasma vWF were not derived from cerebrovascular EC. It is suggested that hypertension may function as a risk factor for thrombotic stroke by influencing factors involved in coagulation processes, such as vWF and factor VIII:c.
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PMID:Agonist-stimulated release of von Willebrand factor and procoagulant factor VIII in rats with and without risk factors for stroke. 792 3

In the natural history of patients with peripheral obliterative arterial disease (POAD) the prognosis of the complaint "intermittent claudication" is relatively good and the amputation rate is presently only about 3%. However, POAD patients carry a high risk of cardiovascular events and their cumultative mortality rate within 10 years is as high as 40-50%. Atherothrombotic events in the coronary and, less frequently, cerebral arteries are by far the first cause of death and disability in these patients. The rationale for antithrombotic drugs in the treatment of POAD lies in the pivotal role of platelet activation and thrombin formation in the evolution of the atherothrombotic lesions, but also in the effect of some of these drugs on the regulation of microcirculatory responses. In acute thrombotic arterial occlusion, Heparin is the "first application" drug, especially in support of interventional revascularisation procedures. Regional thrombolysis often coupled with angioplasty (PTA), or systemic thrombolysis, are effective in revascularisation of especially infrainguinal-supra popliteal occlusions. However, controlled clinical trials are needed. In chronic POAD, intermittent claudication can be improved with a rational walking exercise programme, but, besides pentoxyphilline, especially ticlopidine significantly adds to the benefits of exercise. Regarding districtual progression of atherothrombosis and especially cardiovascular events, both aspirin and ticlopidine have been shown effective in single studies or meta-analyses. In a recent observational study of pooled data the cumulative endpoint including myocardial infarction, stroke and vascular death was reduced by 25 +/- 10% in the generality of patients treated with antiplatelet drugs. Finally, in critical limbs ischemia (CLI), some prostanoid compounds as Iloprost and Prostaglandin E1 favourably influence rest pain and ulcer healing, but less evidence is available on their effects on hard events as amputation and death. In conclusion, following the general indication to "be conservative" in the treatment of these patients, it seems clear that antithrombotic drugs have become by far a key medication in all different phases of POAD.
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PMID:Antithrombotic drugs in peripheral obliterative arterial diseases. 795 59

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

Intracellular free Ca2+, [Ca2+]i, levels were measured in platelets from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) using fura-2AM. In the presence of extracellular Ca2+ (1 mM), [Ca2+]i levels in unstimulated platelets of 2- and 9-month-old SHRSP were both significantly higher than those of the age matched WKY. In the absence of extracellular Ca2+, the levels in platelets from 9-month-old SHRSP were also higher than any other groups examined. Receptor-linked Ca2+ influxes of old SHRSP were smaller when thrombin or collagen was given to the platelets. Phorbol 12-myristate 13-acetate (TPA) enhanced more prominently the Ca2+ influx into old SHRSP platelets than into old WKY platelets. These results strongly suggest that the Ca2+ permeability across plasma membrane is increased in young as well as old SHRSP platelets, where the resting [Ca2+]i level is highly sustained because of an impaired Ca2+ uptake mechanism and possible enhancement of protein kinase C activity.
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PMID:Changes in Ca2+ mobilization in platelets from stroke-prone spontaneously hypertensive rats. 813 78

Epidemiological studies have consistently correlated plasma fibrinogen level to the risk of coronary heart disease (CHD) and acute ischemic stroke. Several mechanisms have been proposed such as the role of fibrinogen in the viscosity of blood, the participation of fibrinogen in both fibrin clot formation and platelet aggregation. However, there is no evidence that the increase in fibrinogen is directly responsible for the vascular disease since the cytokines which participate to the synthesis of fibrinogen by the hepatocytes, such as interleukin 6, could also induce an endothelial cell damage by increasing tumor necrotic factor (TNF) production. In these conditions fibrinogen increase could therefore only represent a marker of cytokine production which in turn is responsible for vascular injury. In addition, for the pathogenesis of atherosclerosis, the influence of fibrinogen is not only mediated by way of increased fibrinogen concentration but could be due to a structurally variant fibrinogen. The recent epidemiological studies have shown that the variation at the beta locus of fibrinogen is associated with an increase risk of peripheral atherosclerosis. The finding concerning dysfibrinogenemia and thrombosis (Dusart and Tampere) create further opportunities to enrich knowledge of the link between the association of abnormal gel structure and thrombotic diseases such as myocardial infarction or stroke at young age. This abnormal clot structure could contribute to thrombogenicity by decreasing the capacity of these clots to be degraded by fibrinolytic enzymes or by decreasing thrombin binding since fibrin is considered as a "thrombin trap".(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Fibrinogen, a vascular risk factor]. 819 48

A highly sensitive automated method, fluorogenic prothrombin time (FPT) method, was developed by a combination of a fluorogenic peptide substrate for thrombin and a centrifugal autoanalyzer (Cobas Bio). Using plasmas from stroke patients, we showed that the second reagent containing fluorogenic peptide substrate should be mixed after the first reagent containing tissue factor and plasma were mixed, that is, two steps method, in order to detect hypercoagulable state. When the first and the second reagent were mixed with plasma at the same time, that is, one step method, FPT was not sensitive to hypercoagulable state. We also showed that patient plasmas should be stored at -80 degrees C and subjected to FPT analysis immediately after thawing, not leaving at 4 degrees C or room temperature. Good correlation was observed on FPT of stroke patients using human tissue factor and bovine tissue factor. Another fluorogenic method was developed by the same principle for the evaluation of factors X and VII concentrations in plasma using deficient plasma of factor X or factor VII. Good correlation was observed on factors X and VII concentrations of stroke patients using human tissue factor and bovine tissue factor.
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PMID:[A basic study on a highly sensitive automated method for hypercoagulable state in plasma, fluorogenic prothrombin time (FPT) method]. 825 61

The relationship between a hypercoagulable state and intracardiac thrombus formation is reviewed, with reference to the pathophysiology of intracardiac thrombus in patients with acute cardioembolic stroke, and those with mitral stenosis. When the development or enlargement of intracardiac thrombus is followed serially by echocardiography, the diameter of the inferior vena cava is seen to decrease as the hematocrit increases, particularly in patients with negative water balance taking diuretics. These findings strongly suggest that dehydration could play an important role in the formation of thrombus. A hypercoagulable and secondarily enhanced fibrinolytic state exists in the cardiac chamber of patients with acute cardioembolic stroke or with intracardiac thrombus. This can be evaluated by plasma levels of fibrinopeptide A, fibrinopeptide B beta 15-42, thrombin-antithrombin III complex and D-dimer. Anticoagulant treatment suppresses thrombin activity in the cardiac chamber, allowing plasma fibrinolytic activity to predominate and reduce the size of the intracardiac thrombus.
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PMID:Hypercoagulability in the left atrium: Part II: Coagulation factors. 826 1

Efficacy and safety of combined alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor blockade and thrombolytic therapy with human recombinant tissue plasminogen activator (TPA) was tested in a rat embolic stroke model. Sixty-three rats were embolized in the right internal carotid territory with a 200 microliters suspension of microclots formed by alternate moving of 150 microliters whole blood and 50 microliters of thrombin between two interconnected syringes for 4 min. Sixteen embolized rats served as controls, and 16 rats were treated with NBQX immediately after embolization. Thirty-one rats were treated with TPA 2 h following embolization, and in 16 of these rats additional NBQX treatments were initiated 90 min following embolization. Hemispheric cerebral blood flow (CBF) was measured by an intraarterial 133Xenon injection method before and after embolization. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed after 2 days, evaluated neuropathologically, and infarct volumes were measured. Median CBF was reduced by 70-77% in the affected hemispheres following embolization. Significant recanalization occurred in all groups except those treated with NBQX. TPA-treated rats had significantly better reperfusion compared to controls judged by angiography 3 h following embolization (P = 0.04). NBQX alone and TPA alone caused insignificant reduction in infarct volume but, when combined, total infarct volume was reduced by 77% compared to controls (P = 0.02). Separate measurement of cortical infarct revealed significantly smaller infarcts (P = 0.05) in the combined treatment group compared to the TPA treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhancing the efficacy of thrombolysis by AMPA receptor blockade with NBQX in a rat embolic stroke model. 827 37


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