-
Clinical Laboratory 2004Heart failure is a common disease in aging western populations. Not only severe but even mild to moderate heart failure is associated with increasing risk for stroke.... (Review)
Review
Heart failure is a common disease in aging western populations. Not only severe but even mild to moderate heart failure is associated with increasing risk for stroke. This can partly be attributed to concomitant atrial fibrillation, a well-known risk factor for stroke. Furthermore, the increased risk for thromboembolic events in congestive heart failure has been attributed to a hypercoagulable state including formation of intraventricular thrombi. However, more recently, enhanced platelet activation has been described in patients with heart failure in sinus rhythm. Vascular endothelial dysfunction and reduced formation of the platelet inhibitor nitric oxide appear to contribute to platelet activation in heart failure. This review article summarizes the historical knowledge of abnormal platelet function in heart failure, focuses on pathophysiological changes in heart failure which could influence platelet activation, and discusses drug regimens investigated in heart failure to reduce platelet activation either by direct anti-platelet effects or by modulating the release of platelet inhibiting substances.
Topics: Anticoagulants; Blood Platelets; Endothelium, Vascular; Heart Failure; Humans; Platelet Activation; Thrombophilia
PubMed: 15481631
DOI: No ID Found -
Advances in Clinical Chemistry 2020The main function of blood platelets is to form hemostatic plugs and enable thrombosis. These properties, however, can be greatly influenced by dietary components which... (Review)
Review
The main function of blood platelets is to form hemostatic plugs and enable thrombosis. These properties, however, can be greatly influenced by dietary components which may inhibit certain steps of platelet activation, including platelet aggregation. Such inhibition can play a role in the prophylaxis and treatment of cardiovascular diseases associated with blood platelet hyperactivation. In fact, plant and fish oils have been identified and specifically used for this purpose. Numerous in vivo and in vitro experiments have explored the potential use of these oils to inhibit platelet activation as well as their role in reducing oxidative stress and blood pressure, and lowering triglyceride and cholesterol. This chapter presents and compares the anti-platelet effects of fish and plant oils and their constituents, especially fatty acids. Studies on healthy subjects and patients with various cardiovascular diseases are also examined. Findings indicate that both fish and plant oils contain protective components with anti-platelet activity having clearly defined mechanisms of action. Although both are excellent sources of omega fatty acids and vitamins, plant oils contain components with cardioprotective benefit in hypercholesterolemics, i.e., phytosterols. Plant oils may hence play a key role in strategies for preventing and treating cardiovascular diseases associated with platelet hyperactivation. Further studies are clearly needed to determine the precise dose of these components needed for effective prophylaxis and treatment.
Topics: Animals; Blood Platelets; Cardiotonic Agents; Cardiovascular Diseases; Humans; Plant Oils; Platelet Activation
PubMed: 32122524
DOI: 10.1016/bs.acc.2019.08.006 -
Current Pharmaceutical Design 2009The prevention of excessive blood loss to avoid fatal haemorrhage is a pivotal process for all organisms possessing a circulatory system. Increased circulating blood... (Review)
Review
The prevention of excessive blood loss to avoid fatal haemorrhage is a pivotal process for all organisms possessing a circulatory system. Increased circulating blood volume and pressure, as required in larger animals, make this process all the more important and challenging. It is essential to have a powerful and rapid system to detect damage and generate an effective seal, and which is also exquisitely regulated to prevent unwanted, excessive or systemic activation so as to avoid blockage of vessels. Thus, a highly specialised and efficient haemostatic system has evolved that consists of cellular (platelets) and protein (coagulation factors) components. Importantly, this is able to support haemostasis in both the low shear environment of the venous system and the high shear environment of the arterial system. Endothelial cells, lining the entire circulation system, play a crucial role in the delicate balance between activation and inhibition of the haemostatic system. An intact and healthy endothelium supports blood flow by preventing attachment of cells and proteins which is required for initiation of coagulation and platelet activation. Endothelial cells produce and release the two powerful soluble inhibitors of platelet activation, nitric oxide and prostacyclin, and express high levels of CD39 which rapidly metabolises the major platelet feedback agonist, ADP. This antithrombotic environment however can rapidly change following activation or removal of endothelial cells through injury or rupture of atherosclerotic plaques. Loss of endothelial cells exposes the subendothelial extracellular matrix which creates strong signals for activation of the haemostatic system including powerful platelet adhesion and activation. Quantitative and qualitative changes in the composition of the subendothelial extracellular matrix influence these prothrombotic characteristics with life threatening thrombotic and bleeding complications, as illustrated by formation of atherosclerotic plaques or the disorder Ehler-Danlos syndrome, which is caused by a defect in collagen synthesis and is associated with fragile blood vessels. This review will focus on the role of the subendothelial matrix in haemostasis and thrombosis, highlighting its potential as a target for novel antithrombotics.
Topics: Animals; Extracellular Matrix; Extracellular Matrix Proteins; Fibrinolytic Agents; Hemostasis; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Thrombosis
PubMed: 19355974
DOI: 10.2174/138161209787846702 -
Platelets Feb 2022Left-ventricular assist devices (LVADs) improve outcomes in end-stage heart failure patients. Two centrifugal-flow LVAD systems are currently approved, HeartMate 3 (HM3)...
Left-ventricular assist devices (LVADs) improve outcomes in end-stage heart failure patients. Two centrifugal-flow LVAD systems are currently approved, HeartMate 3 (HM3) and Medtronic/Heartware HVAD (HVAD). Clinical findings suggest differences in thrombogenicity between both systems. We compared markers of platelet activation and aggregation between HM3 and HVAD. We prospectively included 59 LVAD patients (40 HM3, 19 HVAD). Platelet -selectin expression, activated glycoprotein (GP) IIb/IIIa and monocyte-platelet aggregates (MPA) were assessed by flow-cytometry. Platelet aggregation was measured by light-transmission aggregometry (LTA) and multiple-electrode aggregometry (MEA). Von-Willebrand factor (VWF) antigen (VWF:Ag), VWF activity (VWF:Ac), and VWF multimer pattern analysis were determined. Soluble -selectin (sP-selectin) was measured with an enzyme-linked immunoassay. -selectin, GPIIb/IIIa and MPA levels and in response to arachidonic acid, adenosine diphosphate, and thrombin receptor activating peptide were similar between HM3 and HVAD (all > .05). Likewise, agonist-inducible platelet aggregation by LTA and MEA did not differ between HM3 and HVAD (all > .05). VWF:Ag levels and FVIII:C were similar between both systems (both > .05), but patients with HVAD had significantly lower VWF:Ac ( = .011) and reduced large VWF multimers ( = .013). Finally, sP-selectin levels were similar in patients with HVAD and HM3 ( = .845). In conclusion, on-treatment platelet activation and aggregation are similar in HM3 and HVAD patients. Potential clinical implications of observed differences in VWF profiles between both LVAD systems need to be addressed in future clinical trials.
Topics: Aged; Female; Heart-Assist Devices; Humans; Male; Middle Aged; Platelet Activation; Platelet Aggregation; Prospective Studies
PubMed: 33760697
DOI: 10.1080/09537104.2021.1881950 -
European Heart Journal Sep 2001
Review
Topics: Humans; Platelet Activation; Platelet Aggregation Inhibitors; Thrombosis
PubMed: 11492985
DOI: 10.1053/euhj.2000.2515 -
Pharmacology & Therapeutics 1996Experimental and clinical observations of the involvement of platelets in the pathophysiology of myocardial ischaemia indicate the importance of interactions between... (Review)
Review
Experimental and clinical observations of the involvement of platelets in the pathophysiology of myocardial ischaemia indicate the importance of interactions between these formed elements and the heart. The aim of this review is to outline evidence linking platelet activation, myocardial ischaemia and infarction, and to present evidence for a link between platelet activation, arrhythmogenesis and sudden death. A brief review of platelet physiology and pharmacology is provided, with a review of the cardiac electrophysiological effects of ischaemia and the electrophysiological effects of platelet-derived substances. The concept that platelet activation during myocardial ischaemia is a contributory arrhythmogenic mechanism is discussed.
Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Humans; Myocardial Infarction; Myocardial Ischemia; Platelet Activation
PubMed: 8981572
DOI: 10.1016/s0163-7258(96)00100-3 -
Interventional Cardiology Clinics Jan 2017Hemostasis requires tightly regulated interaction of the coagulation system, platelets, blood cells, and vessel wall components at a site of vascular injury.... (Review)
Review
Hemostasis requires tightly regulated interaction of the coagulation system, platelets, blood cells, and vessel wall components at a site of vascular injury. Dysregulation of this response may result in excessive bleeding if the response is impaired, and pathologic thrombosis with vessel occlusion and tissue ischemia if the response is robust. Studies have elucidated the major molecular signaling pathways responsible for platelet activation and aggregation. Antithrombotic agents targeting these pathways are in clinical use. This review summarizes research examining mechanisms by which these multiple platelet signaling pathways are integrated at a site of vascular injury to produce an optimal hemostatic response.
Topics: Animals; Blood Coagulation; Blood Platelets; Humans; Platelet Activation; Platelet Aggregation; Thrombosis; Vascular System Injuries
PubMed: 27886814
DOI: 10.1016/j.iccl.2016.08.001 -
Blood Reviews Jul 2011When platelet numbers are low or when their function is disabled, the risk of bleeding is high, which on the one hand indicates that in normal life vascular damage is a... (Review)
Review
When platelet numbers are low or when their function is disabled, the risk of bleeding is high, which on the one hand indicates that in normal life vascular damage is a rather common event and that hence the role of platelets in maintaining a normal hemostasis is a continuously ongoing physiological process. Upon vascular injury, platelets instantly adhere to the exposed extracellular matrix resulting in platelet activation and aggregation to form a hemostatic plug. This self-amplifying mechanism nevertheless requires a tight control to prevent uncontrolled platelet aggregate formation that eventually would occlude the vessel. Therefore endothelial cells produce inhibitory compounds such as prostacyclin and nitric oxide that limit the growth of the platelet thrombus to the damaged area. With this review, we intend to give an integrated survey of the platelet response to vascular injury in normal hemostasis.
Topics: Animals; Blood Platelets; Endothelium, Vascular; Hemostasis; Humans; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation; Signal Transduction
PubMed: 21496978
DOI: 10.1016/j.blre.2011.03.002 -
Drugs 2008Platelets play a key role in thrombosis and haemostasis, which can be either beneficial or deleterious depending on the circumstances. Multiple factors, such as genetic... (Review)
Review
Platelets play a key role in thrombosis and haemostasis, which can be either beneficial or deleterious depending on the circumstances. Multiple factors, such as genetic polymorphisms, pathological state and lifestyle, are thought to be associated with platelet hyperreactivity. Platelet activation occurs through the complex process of transmembrane signalling, with a cascade of biochemical interactions leading to platelet activation. Transmembrane signalling involves many different molecules with different enzymatic activity and/or function. Based on the signalling pathways involved in platelet activation, there are four possible targets of antiplatelet drugs: (i) inhibition of agonist generation; (ii) receptor inhibition; (iii) G-protein inhibition; and (iv) inhibition of enzymatic cascades. However, both established and novel antiplatelet drugs have their own advantages and disadvantages. Because of the problems associated with the use of current antiplatelet drugs, such as resistance, optimal dosage and safety, future strategies for the development of new antiplatelet drugs and new treatment regimens may include consideration of the following: (i) a shift from single targets within the signalling cascade to multiple targets; (ii) a shift from therapy with a single drug to combination therapy; and (iii) investigating drugs in current clinical use for novel antiplatelet properties.
Topics: Drug Design; Humans; Meta-Analysis as Topic; Models, Biological; Platelet Activation; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Signal Transduction
PubMed: 18681489
DOI: 10.2165/00003495-200868120-00004 -
Circulation Research Dec 2006Because of their ability to become rapidly activated at places of vascular injury, platelets are important players in primary hemostasis as well as in arterial... (Review)
Review
Because of their ability to become rapidly activated at places of vascular injury, platelets are important players in primary hemostasis as well as in arterial thrombosis. In addition, they are also involved in chronic pathological processes including the atherosclerotic remodeling of the vascular system. Although primary adhesion of platelets to the vessel wall is largely independent of G protein-mediated signaling, the subsequent recruitment of additional platelets into a growing platelet thrombus requires mediators such as ADP, thromboxane A(2), or thrombin, which act through G protein-coupled receptors. Platelet activation via G protein-coupled receptors involves 3 major G protein-mediated signaling pathways that are initiated by the activation of the G proteins G(q), G(13), and G(i). This review summarizes recent progress in understanding the mechanisms underlying platelet activation and thrombus extension via G protein-mediated signaling pathways.
Topics: Animals; Blood Platelets; Humans; Platelet Activation; Receptors, G-Protein-Coupled; Thrombosis
PubMed: 17158345
DOI: 10.1161/01.RES.0000251742.71301.16