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

In vitro abnormalities of platelet behaviour have been described in patients with ischemic cerebrovascular disease (ICD) suggesting that changes in platelet receptors and/or platelet a granules may occur in the circulation. We investigated the frequency of such alterations in 95 patients that were studied within a few days after acute stroke. Using specific antibodies to two intrinsic plasma membrane glycoproteins (GPs), the GPIIb-IIIa complex and GPIV, and to thrombospondin (TSP), a a-granular protein that becomes expressed on the platelet surface upon activation, we were able to distinguish two groups of patients: 16 patients presented an increased concentration of TSP on their platelets demonstrating in vivo platelet secretion. These patients could constitute a group with increased risk of thrombosis. In contrast, 20 patients presented a decreased concentration of GPIIb-IIIa and GPIV. This decrease in intrinsic plasma membrane GPs was associated with a decrease in mean platelet volume and may suggest the occurrence of platelet fragmentation in the circulation.
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PMID:Platelet surface glycoprotein changes in patients with cerebral ischemia. 181 6

Antiplatelet therapy has become a useful means of preventing acute thromboembolic artery occlusions in cardiovascular diseases. The rationale for this is an enhanced activity of circulating platelets and release of platelet-derived vasoactive mediators, probably due to endothelial dysfunction. This review discusses the current status of 4 major classes of antiplatelet compounds: (i) aspirin and related drugs active via cyclo-oxygenase product formation; (ii) thienopyridines (ticlopidine and clopidogrel); (iii) direct thrombin inhibitors (e.g. hirudin); and (iv) GPIIb/IIIa receptor antagonists [e.g. abciximab (c7E3 Fab)]. It is concluded that aspirin is the drug of choice for long term oral treatment, specifically for secondary prevention of myocardial infarction, and is also a suitable basic but not maximally efficient drug in percutaneous transluminal coronary angioplasty (PTCA) and platelet activation during clot lysis. Ticlopidine has a similar indication and may be superior to aspirin in prevention of ischaemic stroke and peripheral arterial occlusion. Direct thrombin inhibitors and glycoprotein GPIIb/IIIa receptor antagonists need further investigation in clinical trials. To date, these compounds have a higher bleeding risk and currently they are available only for short term parenteral application. They are superior to aspirin in acute platelet-dependent ischaemic syndromes, such as unstable angina, and in connection with therapeutic PTCA because of their high potency in preventing platelet-dependent reocclusion. Future developments include more selective thromboxane inhibitors, i.e. combined-mode agents; nonpeptide clot-specific thrombin inhibitors with longer lasting action and nonpeptide fibrinogen receptor antagonists.
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PMID:Antiplatelet drugs. A comparative review. 758 91

MK-852 is a newly developed low molecular weight inhibitor of fibrinogen binding to platelets. Platelet aggregation and adhesion of platelets to damaged vessel walls are critical events in haemostasis, and uncontrolled aggregation may cause arterial thrombus formation. Depending on the location of the occluded vessel, this may result in unstable angina, myocardial infarction or stroke. Platelet aggregation requires binding of fibrinogen to the GPIIb/IIIa receptor on the platelet surface. Thus, inhibitors of fibrinogen binding to the receptor may constitute an efficient way of preventing thrombus formation. We have used flow cytometry and FITC-labelled chicken anti-human fibrinogen antibodies to study the in vitro inhibitory effects of MK-852 on fibrinogen binding to platelets. We show that MK-852 is a very efficient fibrinogen receptor antagonist in vitro. Flow cytometry is well suited for clinical use and may be used to monitor treatment with MK-852 or other fibrinogen receptor antagonists.
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PMID:Inhibition of fibrinogen binding to platelets by MK-852, a new GPIIb/IIIa antagonist. 771 23

During the past decade, many significant developments in the clinical management of thrombotic and vascular disorders have occurred. In particular, several newer approaches for the prophylactic and therapeutic management of such disorders as venous thrombosis, acute myocardial infarction, and stroke have been introduced. This has been possible because of the understanding of the molecular mechanisms involved in the thrombogenic process, which plays a key role in the pathophysiology of thrombotic and vascular disorders. With the increased knowledge of the pathophysiology of thrombosis have come advances in drug treatment possibilities. Advances in biotechnology and separation techniques have contributed to the development of many newer antithrombotic, anticoagulant, and thrombolytic drugs. Many new drugs and devices based on newer concepts are currently being tested in various clinical trials. Hirudin, hirulog, GPIIb/IIIa targeting antibodies, and tissue factor pathway inhibitor are some examples. From these current developments, it can be appreciated that antithrombotic drugs represent a wide spectrum of natural, synthetic, semisynthetic, and biotechnology-produced agents with marked differences in chemical composition, physicochemical properties, biochemical actions, and pharmacologic effects. The use of physical means to treat thrombotic disorders and advanced means of drug delivery add to the expanding nature of treatment. The endogenous actions of the antithrombotic drugs are quite complex. It is no longer valid to assume that an antithrombotic drug must produce an anticoagulant action in blood, as do the classical heparin and oral anticoagulants. Many of these new drugs do not produce any alteration of currently measurable blood-clotting parameters, yet they are effective therapeutic agents because of their interactions with the elements of the blood and the vasculature. Another perspective is that several of these agents require endogenous transformation to become active products. Therefore, it becomes important to rely on the pharmacodynamic actions of these agents rather than on other in vitro characteristics to assess potency or efficacy. Hematologic and vascular modulation play a key role in the mediation of the antithrombotic actions of these drugs, involving red cells, white cells, platelets, endothelial cells, and blood proteins. Thus, an optimal antithrombotic drug approach will include the targeting of all possible sites involved in thrombogenesis. Antithrombotic and anticoagulant drugs will also be useful in the development of such biomedical devices as stents and other vascular support material. Polytherapeutic approaches utilizing combinations of drugs may turn out to be the most effective in the management of thrombotic disorders.
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PMID:Current trends in antithrombotic drug and device development. 880 21

Appreciation of the critical role of platelets in cardiovascular disease came when it was shown that aspirin, by virtue of its ability to block platelet aggregation, reduced the combined incidence of MI, stroke, and vascular death by 25%. Understanding the key role played by platelets in acute thrombotic vascular events prompted the development of a new class of drugs to control platelet action. Platelet aggregation is mediated exclusively by the platelet fibrinogen receptor GP IIb/IIIa. The binding of the receptor with fibrinogen is the final common pathway leading to platelet aggregation and thrombus formation. Abciximab, the first GP IIb/IIIa platelet receptor inhibitor, effectively reduces the thrombotic complications in acute coronary vascular events. The newer GP IIb/IIIa inhibitors, the synthetic peptide antagonists, have been shown to be more specific, to be nonimmunogenic, and to cause less bleeding. It is predictable that an oral GP IIb/IIIa inhibitor will become part of the standard repertoire in patients with unstable angina. The platelet has taken center stage in the battle against arterial thrombosis. The direction of our medical attack on acute coronary events is clear: harness the platelet.
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PMID:Harnessing the platelet. 928 79

The IST, CAPRIE and ESPS-2 have shown that large collaborative randomised trials can be conducted in stroke medicine and can provide statistically and clinically significant results. They, and other concurrent studies, have highlighted the potential hazards of early anticoagulation, and the effectiveness and safety of early (and continuous) antiplatelet therapy in limiting early stroke recurrence and its consequences. In addition, they have shown that antiplatelet agents with differing mechanisms of action can have different effects, and perhaps additive effects when combined. The ESPRIT trial should delineate the roles of oral anticoagulant therapy, and the combination of aspirin and dipyridamole, in the prevention of stroke due to arterial disease. Future trials will hopefully determine the role in secondary stroke prevention of inhibitors of the platelet GPIIb/IIIa complex (the final common pathway of platelet aggregation), the combination of anitplatelet agents with different mechanisms of action (e.g. aspirin and clopidogrel, aspirin and IIb/IIIa inhibitors), the combination of antiplatelet agents and oral anticoagulants (which may simultaneously modify platelet function and fibrin production), and the combination of antithrombotic and cholesterol-lowering (statin) medications.
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PMID:One year after CAPRIE, IST and ESPS 2. Any changes in concepts? 976 93

Mechanical revascularization in the acute myocardial infarction by primary angioplasty has several advantages over thrombolytic therapy. The short-term patency rates of the infarct-related artery range from 95 to 99% and a normal flow is achieved in more than 90% of the cases. This prompt and effective reperfusion is probably responsible for the improved prognosis with primary angioplasty. The better outcome after primary angioplasty is observed both in low- and in high-risk patients, in all ages and in patients presenting late (>6 h) after the chest pain. Pooled analysis of randomized studies, show that primary angioplasty as compared to thrombolysis, has a lower incidence of death, stroke and reinfarction. Additional advantages of primary PTCA include the possibility of reperfusion in patients in whom lysis is contraindicated or less effective (e.g. patients in cardiogenic shock, or with prior coronary artery bypass surgery) and the ability to provide prognostic information helpful in the patient triage. Thus, primary PTCA results in better outcome than thrombolysis when performed in centers with success rates comparable to those achieved in the randomized trials. Further studies are still needed to assess its long-term efficacy. Several randomized trials are underway to assess the role of stents and the use of more potent antiplatelet drugs, as the GPIIb/IIIa receptor blockers, in adjunct to balloon angioplasty in the treatment of acute myocardial infarction.
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PMID:Update on mechanical revascularization in acute myocardial infarction: which role and when? 1032 5

Ticlopidine has become an established therapy in patients with stroke, and during stenting in patients with coronary artery disease. Clopidogrel, another thienopyridine, is a safe and promising alternative, that irreversibly inhibits ADP-induced platelet aggregation, and reduces formation of both arterial and venous thrombi. In a recent, large, well-controlled trial (CAPRIE), clopidogrel has been shown to be superior to aspirin in terms of prevention of ischaemic stroke, myocardial infarction and death in patients with atherosclerotic vascular disease. Clopidogrel provides a safe opportunity to enhance reperfusion when administered during stent placement, by protecting platelets from excessive activation. However, the ability of clopidogrel to be superior to ticlopidine in terms of its antiplatelet properties in the clinical setting of coronary stenting, is unknown. The effects of clopidogrel versus ticlopidine on platelet and endothelial function are yet to be determined and may strongly affect the outcome, benefits, and complications following coronary stent placement. Further clinical trials, well-designed, and carefully conducted, should elucidate possible benefits of clopidogrel during coronary interventions, especially in conjunction with new and aggressive reperfusion techniques. The benefits of clopidogrel in an expanding array of clinical conditions, including myocardial infarction, may be directly related to platelet inhibition. Moreover, marginal clinical benefits, and recently reported severe bleeding events in some patients after oral platelet glycoprotein IIb/IIIa therapy, may advance clopidogrel as a safe, and efficient alternative during coronary interventions. This review summarises the latest, and often confusing data on the effects of thienopyridines on certain haemostatic characteristics in interventional cardiology. 1999 Academic Press.
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PMID:Clopidogrel: the future choice for preventing platelet activation during coronary stenting? 1043 68

Platelet active drugs are part of the antithrombotics. Their biological effect is not assessed in current practice. Their clinical efficacy has been firmly established in randomised controlled trials. Aspirin has been the most widely tested drug and is effective in various forms of coronary artery disease and in the secondary prevention after a first ischaemic stroke; in these settings, aspirin reduces the incidence of myocardial infarction, stroke and cardiac death; aspirin has been tested in various daily doses from 30 to 1300 mg: best evidence has been gathered for dosages between 75 and 300 mg; good clinical practice is to use the lowest effective dose. Ticlopidine and clopidogrel have been shown to be superior to aspirin in 2 trials where the incidence of myocardial infarction has been lowered by the new drugs; nevertheless the superiority is apparent only in patients with lower limb atherosclerosis and after stroke. The combination of dipyridamole and aspirin has been proven to be superior to aspirin in the secondary prevention of stroke in one trial contrasting with the other trials performed with other combinations of those two drugs. Glycoprotein GP IIb/IIIa antagonists have been tested in coronary angioplasty and in acute coronary syndromes and only in short intravenous administration; these drugs reduce the incidence of myocardial infarction without any effect on 6-month mortality.
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PMID:[Indications for antiplatelet medications]. 1058 93

Ischemic mechanisms in pa2000Mar;58(1)1-10 studied for more than 150 years. Antiplatelet agents did show benefit in secondary prevention. Aspirin is the most common antiaggregant in clinical use today. However, the benefit produced by the "best" antiplatelet regimen in stroke prevention is lower than 40%. The adherence of circulating platelets to the subendothelium is mediated by glycoprotein (GP) residing on the cell's surface. GPIIb/IIIa is the most important platelet membrane receptor that mediates the process of platelet aggregation, and thrombus formation. Thus, new drugs that block the GPIIb/IIIa receptor have recently emerged. Clinical trials using these agents have shown effectiveness in acute coronary syndromes. However, the absence of studies in cerebrovascular disease and the potential hemorrhagic complications questioned their use in stroke prevention. We review the clinical trials using the new GPIIb/IIIa agents in myocardial ischemia, and consider the potential implications for cerebrovascular disease.
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PMID:Arteriosclerosis and the promise of GPIIb/IIIa inhibitors in stroke. 1077 Aug 59


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