Platelet adhesion to collagen

Nuyttens, Benedicte P.; Thijs, Tim; Deckmyn, Hans; Broos, Katrijn

doi:10.1016/s0049-3848(10)70151-1

Cited by 132 publications

(96 citation statements)

References 46 publications

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“…In situations with normally functioning platelets, the collagen component of PCC rapidly induces coagulation through direct binding of platelets via the platelet receptor GPVI and integrin α2β1, and indirect binding of platelets through binding of von Willebrand factor which, in turn, binds the platelet receptor GPIb-IX-V and integrin αIIbβIII [24,25]. Receptor and integrin binding results in intracellular signaling events that reinforce platelet adhesion and mediate platelet activation, leading to platelet aggregation and a growing clot.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Severe Aortic Bleeding Using Hemopatch in Swine on Dual Antiplatelet Therapy

Baumgartner

Draxler

Lewis

2016

Journal of Investigative Surgery

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Purpose: The perioperative management of patients on antithrombotic therapy is currently an unresolved problem as these therapies pose a considerable risk for perioperative hemorrhagic complications. The presented studies investigated the efficacy of a new collagen technology to achieve hemostasis. A polyethylene glycol-coated collagen pad (PCC) was compared to a marketed fibrinogen-thrombin coated collagen pad (FTC) for the treatment of an aortotomy incision in heparinized swine on dual antiplatelet therapy. Materials and Methods: Twenty-eight 3-mm aortotomy incisions were created in nine heparinized pigs without antiplatelet therapy and treated with PCC. Sixty-eight aortotomy incisions were created in ten heparinized pigs that received clopidogrel (10-11 mg/kg) and acetylsalicylic acid (8-11 mg/kg) orally for 5 days, and treated with either PCC or FTC (N = 34/group). Dual antiplatelet therapy resulted in significantly reduced platelet function. Aortotomy incisions resulted in lifethreatening bleeding of 35-292 ml/min. Results: In animals without antiplatelet treatment, PCC provided 96% immediate hemostatic success. In animals with antiplatelet treatment, FTC provided 18% immediate hemostatic success increasing to 74% after 10 min. Strikingly, PCC provided 94% immediate success increasing to 100% after 10 min. Controlling for differences in pretreatment bleeding rates, statistical model-estimated time to hemostasis was 12 times shorter in PCC-treated lesions (p < .02). Conclusion: The combination of a procoagulant collagen pad with a synthetic sealing component provides excellent hemostatic properties under a worst-case scenario. PCC rapidly and firmly adheres to tissue, thereby controlling severe arterial bleeding, even when platelet function is significantly reduced. Treatment with PCC provided superior time to hemostasis compared to FTC.

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Section: Discussionmentioning

confidence: 99%

Treatment of Severe Aortic Bleeding Using Hemopatch in Swine on Dual Antiplatelet Therapy

Baumgartner

Draxler

Lewis

2016

Journal of Investigative Surgery

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“…The rapid response of platelets to vascular injury is mediated by a diverse repertoire of tyrosine kinase-linked receptors, including the von Willibrand factor (VWF) receptor complex GPIb-IX-V that mediates tethering to sites of vascular injury 1 ; the immunoreceptor tyrosine-based activation motif (ITAM)-containing collagen receptor complex GPVI-FcR g-chain that mediates platelet activation 2 ; the integrins a2b1 and aIIbb3 that mediate firm adhesion and aggregation to exposed extracellular matrix 3 ; the hemi-ITAMcontaining podoplanin receptor CLEC-2 4 ; and the ITAM-containing low-affinity immunoglobulin receptor FcgRIIA (Figure 1). 5 Ligandmediated clustering of these receptors triggers transmission of primary activation signals through the phosphorylation of downstream tyrosine residues in proteins.…”

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confidence: 99%

Src family kinases: at the forefront of platelet activation

Senis

Mazharian

Mori

2014

Blood

245

214

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Src family kinases (SFKs) play a central role in mediating the rapid response of platelets to vascular injury. They transmit activation signals from a diverse repertoire of platelet surface receptors, including the integrin αIIbβ3, the immunoreceptor tyrosine–based activation motif–containing collagen receptor complex GPVI-FcR γ-chain, and the von Willebrand factor receptor complex GPIb-IX-V, which are essential for thrombus growth and stability. Ligand-mediated clustering of these receptors triggers an increase in SFK activity and downstream tyrosine phosphorylation of enzymes, adaptors, and cytoskeletal proteins that collectively propagate the signal and coordinate platelet activation. A growing body of evidence has established that SFKs also contribute to Gq- and Gi-coupled receptor signaling that synergizes with primary activation signals to maximally activate platelets and render them prothrombotic. Interestingly, SFKs concomitantly activate inhibitory pathways that limit platelet activation and thrombus size. In this review, we discuss past discoveries that laid the foundation for this fundamental area of platelet signal transduction, recent progress in our understanding of the distinct and overlapping functions of SFKs in platelets, and new avenues of research into mechanisms of SFK regulation. We also highlight the thrombotic and hemostatic consequences of targeting platelet SFKs.

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“…28 In addition to αIIbβ3, other platelet integrins, α2β1, α5β1, and α6β1 that bind collagen, fibronectin, or laminin, respectively, also become functional on activated platelets and promote firm platelet adhesion to collagenous subendothelial matrix. 29,30 This amplification of platelet activation through release of secondary agonists is critical in stabilizing the thrombus and augmenting the thrombus volume. In cases of unrestrained growth, which can result in occlusion and ischemia, inhibition of secondary messengers, such as TxA2, by aspirin or platelet adhesion integrins assists in controlling thrombus size on the vessel wall.…”

Section: Platelet Activation and Thrombus Formation At The Vessel Wallmentioning

confidence: 99%

Current State and Novel Approaches of Antiplatelet Therapy

Metharom

Berndt

Baker

et al. 2015

ATVB

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Abstract-An unresolved problem with clinical use of antiplatelet therapy is that a significant number of individuals either still get thrombosis or run the risk of life-threatening bleeding. Antiplatelet drugs are widely used clinically, either chronically for people at risk of athero/thrombotic disease or to prevent thrombus formation during surgery. However, a subpopulation may be resistant to standard doses, while the platelet targets of these drugs are also critical for the normal hemostatic function of platelets. In this review, we will briefly examine current antiplatelet therapy and existing targets while focusing on new potential approaches for antiplatelet therapy and improved monitoring of effects on platelet reactivity in individuals, ultimately to improve antithrombosis with minimal bleeding. Primary platelet adhesion-signaling receptors, glycoprotein (

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Platelet adhesion to collagen

Cited by 132 publications

References 46 publications

Treatment of Severe Aortic Bleeding Using Hemopatch in Swine on Dual Antiplatelet Therapy

Treatment of Severe Aortic Bleeding Using Hemopatch in Swine on Dual Antiplatelet Therapy

Src family kinases: at the forefront of platelet activation

Current State and Novel Approaches of Antiplatelet Therapy

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