Inherited traits affecting platelet function

Salles, Isabelle I.; Feys, Hendrik B.; Iserbyt, Brecht; Meyer, Simon F. De; Vanhoorelbeke, Karen; Deckmyn, Hans

doi:10.1016/j.blre.2007.11.002

Cited by 104 publications

(81 citation statements)

References 203 publications

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“…Few patients have been identified with hemorrhagic diathesis associated to P2Y12 congenital defects, whereas so far there has been no report of patients with a P2Y1 deficiency. 49 Together with results from in vitro studies using specific inhibitors, such data identify P2Y12 as the major receptor to amplify and sustain ADP-mediated platelet activation initiated via P2Y1. Indeed, P2Y12 is the target of thienopyridine drugs (ticlopidine, clopidogrel, prasugrel) widely used and with probed efficacy in the prevention of vascular events in patients with cardiovascular disease, specially those having stent insertion.…”

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confidence: 84%

“…48,58 Several homozygous and heterozygous patients suffering from lifelong mucosal bleeding due to genetic changes in TP or in other elements of the TxA2 signaling pathway have also been reported. 49 All these data, in addition to the compelling evidence about the benefit of aspirin in the prevention/therapy of cardiovascular diseases, fully demonstrate the major contribution of TxA2 in platelet plug formation.It is well established that thrombin rapidly generated at sites of vascular injury plays a major role in promoting and stabilizing thrombi under all shear conditions. …”

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confidence: 89%

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Platelet receptors and signaling in the dynamics of thrombus formation

Rivera¹,

Lozano²,

et al. 2009

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Hemostasis and pathological thrombus formation are dynamic processes that require a co-ordinated series of events involving platelet membrane receptors, bidirectional intracellular signals, and release of platelet proteins and inflammatory substances. This review aims to summarize current knowledge in the key steps in the dynamics of thrombus formation, with special emphasis on the crucial participation of platelet receptors and signaling in this process. Initial tethering and firm adhesion of platelets to the exposed subendothelium is mediated by glycoprotein (GP) Ib/IX/V complex and collagen receptors, GP VI and α2β1 integrin, in the platelet surface, and by VWF and fibrillar collagen in the vascular site. Interactions between these elements are largely influenced by flow and trigger signaling events that reinforce adhesion and promote platelet activation. Thereafter, soluble agonists, ADP, thrombin, TxA2, produced/released at the site of vascular injury act in autocrine and paracrine mode to amplify platelet activation and to recruit circulating platelets to the developing thrombus. Specific interactions of these agonists with their G-protein coupled receptors generate inside-out signaling leading to conformational activation of integrins, in particular αIIbβ3, increasing their ligand affinity. Binding of αIIbβ3 to its ligands, mainly fibrinogen, supports processes such as clot retraction and platelet aggregation. Stabilization of thrombi is supported by the late wave of signaling events promoted by close contact between aggregated platelets. The best known contact-dependent signaling is outside-in signaling through αIIbβ3, but new ones are being clarified such as those mediated by interaction of Eph receptors with ephrins, or by Sema 4D and Gas-6 binding to their receptors. Finally, newly identified mechanisms appear to control thrombus growth, including back-shifting of activated integrins and actuation of compensatory molecules such as ESAM or PECAM-1. The expanding knowledge of thrombotic disease is expected to translate into the development of new drugs to help management and prevention of thrombosis.Key words: platelet, receptors, thrombus formation.Citation: Rivera J, Lozano ML, Navarro-Núñez L, Vicente V. Platelet receptors and signaling in the dynamics of thrombus formation. Haematologica 2009; 94:700-711. doi:10.3324/haematol.2008 This is an open-access paper. ABSTRACT Platelet receptors and signaling in the dynamics of thrombus formationJosé Rivera, María Luisa Lozano, Leyre Navarro-Núñez, and Vicente Vicente Unit of Hematology and Clinical Oncology, Centro Regional de Hemodonación, University of Murcia, Spain © F e r r a t a S t o r t i F o u n d a t i o nand metastasis, or immunological host defense. 1Internally, platelets contain a cytoskeleton, a dense tubular system, few mitochondrias, glycogen granules, dense (δ) and α storage granules and peroxisomes. The α-granules retain relevant proteins for the hemostatic function of platelets, such as von Willebrand factor (VWF), fibrinogen, P-selectin,...

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confidence: 84%

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confidence: 89%

Platelet receptors and signaling in the dynamics of thrombus formation

Rivera¹,

Lozano²,

et al. 2009

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“…At the molecular level, two important platelet surface glycoprotein are implicated in the disease, GPIIb (CD41) and GPIIIa (CD61). These two glycoproteins form a complex that functions as a receptor for fibrinogen and other molecules included in platelet functions, leading eventually to platelet aggregation and formation of platelet plug (3)(4)(5) . Genetically, two genes responsible for the biosynthesis of GPIIb, IIIa complex, both are located on chromosome no.…”

Section: Introductionmentioning

confidence: 99%

“…(2,3) . In this disease, where either one or both glycoproteins are absent or have defective function, this will render the other glycoprotein also either absent or defective in its function causing no binding between platelet and fibrinogen, no platelet aggregation, leading to a defect in primary hemostasis and hemorrhagic manifestations will appear (4,6) . Patients with Glanzmann thrombosthenia presents with normal platelet count and morphology, normal PT, PTT, TT, normal level of clotting factors and VWF.…”

Section: Introductionmentioning

confidence: 99%

Expression of Cd41 (Gpiib) and Cd61 (Gpiiia) in Patients With Glanzmann Thrombasthenia Using Flow Cytometry

2016

IJMS

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“…Могут быть повреждены различные структуры и нарушены разнообразные процессы в тром-боцитах: мембранные рецепторы, внутритромбоцитар-ная сигнализация, гранулы и др. Это приводит к раз-личным клиническим проявлениям кровоточивости [2][3][4]. Тромбоцитопатии характеризуются в первую очередь развитием спонтанных и посттравматических кожно-слизистых кровотечений.…”

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