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The Rational Basis of Thrombosis Models
Published in Josef Hladovec, Antithrombotic Drugs in Thrombosis Models, 2020
A large group of secondary platelet activation states as indicated by hypersensitivity to various aggregating agents, or more appropriately, the release of platelet factors and constituents as in complicated atherosclerosis,41, 42 diabetes mellitus,43–45 smoking,46, 47 advanced age,48, 49 and perhaps even in hypertension50 and emotional stress,51 is characterized by a previous vascular lesion. Nevertheless, some studies were negative.52, 53 Platelets and the vascular wall have very close functional relations and platelet activation may be considered one of the most sensitive indicators of endothelial dysfunction. A large number of tests have been devised to detect platelet activation (Table 4).
Haemostasis
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Platelet activation is critical for platelet aggregation. Platelet surface integrins, especially αIIbβ3, are activated, and these bind to fibrinogen, VWF, fibronectin and vitronectin to promote platelet aggregation. Activated GPIIb/IIIa receptors bind soluble fibrinogen resulting in platelet-to-platelet binding or aggregation. Thromboxane A2 is a potent stimulant for platelet aggregation.
Phospholipids and the Clotting Process
Published in E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson, Phospholipid-Binding Antibodies, 2020
Robert F. A. Zwaal, Edouard M. Bevers, Jan Rosing
In most if not all cells, lipid asymmetry is maintained during the lifetime of the cell. Apparently, platelets are no exception to this rule unless they become activated. Two regulatory mechanisms have been proposed for the maintenance of phospholipid asymmetry in biological membranes, and it seems likely that loss of membrane lipid asymmetry involves alterations in these regulatory systems. The two mechanisms which are usually considered are (1) binding of amino-phospholipids to cytoskeletal proteins at the cytoplasmic surface of the membrane,103-106 and (2) pumping of amino-phospholipids from the outside to the inside of the cell membrane by an ATP-dependent lipid flip-flop catalyst in the membrane, usually referred to as amino-phospholipid translocase.106-110 Alterations in these mechanisms may occur during platelet activation as will be discussed below.
Swimming improves platelet dysfunction in mice fed with a high-fat diet
Published in Archives of Physiology and Biochemistry, 2023
Xinyong Su, Xiao Yu, Ruzhuan Chen, Weihua Bian
Platelets are an important component of mammalian blood and are small pieces of cytoplasm derived from mature megakaryocytes (Fu et al.2019). They can not only participate in normal physiological hemostasis but also play an important role in immunity and tissue repair (Rayes et al. 2019). Excessive aggregation of platelets will occur when their reactivity is increased, leading to the formation of a thrombus (Salamah et al.2018, Cardenas et al.2019). Platelet activation is related to a variety of intracellular signalling pathways. The level of pAKT, the activated form of AKT, increases when the platelet is activated (Li et al.2019). pAKT can promote the formation of platelet pseudopodia, the adhesion and spread of platelets, the release of α-granules and adenosine triphosphate in dense granules, and the binding of fibrinogen with the αIIb/β3 receptor on the surface of platelets. Inhibiting pAKT activity can inhibit the activation of the αIIb/β3 receptor, thereby inhibiting platelet reactivity (Chen et al.2004, Kwon, 2019).
Platelet-HIV: interactions and their implications
Published in Platelets, 2022
A corollary to the questions about platelet activation, is where does it initiate? Viruses may bind to surface proteins and directly activate platelets via specific signaling cascades. Potential receptors such as CLEC2 or β3 integrins do initiate signaling cascades, albeit different ones. Alternatively, Ig-coated virions could activate platelets via engagement of surface Fc receptors (i.e., FcRγIIA) using a tyrosine kinase pathway similar to CLEC2. Platelets also contain most of the TLR family members with some on the surface (i.e., TLR 2 and 4) and others in endosomal compartments (i.e., TLR7 and 9) [17]. TLR7 is important for responses to Encephalomyocarditis Virus (EMCV) [26] and deletion of TLR7/9 disrupted platelet responses to HIV-pseudovirions [17]. We further showed that endocytosis was required for pseudovirion-induced platelet activation, thus in mice, activation by virions was not occurring solely at the cell surface. Further analysis is required to determine the relative importance of virion-induced activation of receptors at the platelet surface or in an endosome. However, it should be noted, activation of endosomal TLRs has been thought to be a specific response to virus genomes that helps the innate immune system discriminate between self and pathogen genetic material (discussed in [27]).
Heparin-induced thrombocytopenia: pathophysiology, diagnosis and treatment
Published in Expert Review of Hematology, 2021
Anne-Mette Hvas, Emmanuel J Favaloro, Maja Hellfritzsch
While thrombocytopenia is the cardinal presentation of HIT, 30–50% of HIT patients also experience thromboembolic disease, termed thrombotic HIT. When suspecting HIT a 4Ts probability score (ranging from 0–8) should be made and followed by laboratory diagnostics in patients with 4Ts score at 4 or above. In cases where rapid immunoassay tests are positive, functional platelet activation assays should also be performed. In parallel, heparin treatment should be immediately suspended and replaced by a non-heparin anticoagulant therapy in patients with suspected HIT as indicated by the 4Ts score. Argatroban is the only anticoagulant holding regulatory approval for HIT in both the U.S. and Europe, but based on current evidence, also danaparoid, fondaparinux or DOACs can be chosen as anticoagulants in acute HIT depending on availability and patient characteristics. After platelet counts normalization, treatment can be continued with an oral anticoagulant agent, possibly a DOAC, among which most evidence has accumulated on the use of rivaroxaban, so far. Duration of anticoagulant therapy is 3 months in thrombotic HIT whereas it can be discontinued earlier in isolated HIT depending on patient risk factors.