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Platelets

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https://www.readbyqxmd.com/read/28532218/flow-chamber-and-microfluidic-approaches-for-measuring-thrombus-formation-in-genetic-bleeding-disorders
#1
Rogier M Schoeman, Marcus Lehmann, Keith B Neeves
Platelet adhesion and aggregation, coagulation, fibrin formation, and fibrinolysis are regulated by the forces and flows imposed by blood at the site of a vascular injury. Flow chambers designed to observe these events are an indispensable part of doing hemostasis and thrombosis research, especially with human blood. Microfluidic methods have provided the flexibility to design flow chambers with complex geometries and features that more closely mimic the anatomy and physiology of blood vessels. Additionally, microfluidic systems with integrated optics and/or pressure sensors and on-board signal processing could transform what have been primarily research tools into clinical assays...
May 22, 2017: Platelets
https://www.readbyqxmd.com/read/28524712/p2y12-receptor-gene-mutations-associated-with-bleeding
#2
Mariangela Scavone, Eti A Femia, Marco Cattaneo
No abstract text is available yet for this article.
May 19, 2017: Platelets
https://www.readbyqxmd.com/read/28523956/pathogen-reduction-technologies-the-pros-and-cons-for-platelet-transfusion
#3
Audrey Magron, Jonathan Laugier, Patrick Provost, Eric Boilard
The transfusion of platelets is essential for diverse pathological conditions associated with thrombocytopenia or platelet disorders. To maintain optimal platelet quality and functions, platelets are stored as platelet concentrates (PCs) at room temperature under continuous agitation-conditions that are permissive for microbial proliferation. In order to reduce these contaminants, pathogen reduction technologies (PRTs) were developed by the pharmaceutical industry and subsequently implemented by blood banks...
May 19, 2017: Platelets
https://www.readbyqxmd.com/read/28523947/potentiation-of-trap-6-induced-platelet-dense-granule-release-by-blockade-of-p2y12-signaling-with-mrs2395
#4
Annachiara Mitrugno, Rachel A Rigg, Nicole B Laschober, Anh T P Ngo, Jiaqing Pang, Craig D Williams, Joseph E Aslan, Owen J T McCarty
The release of ADP from platelet dense granules and its binding to platelet P2Y12 receptors is key to amplifying the initial hemostatic response and propagating thrombus formation. P2Y12 has thus emerged as a therapeutic target to safely and effectively prevent secondary thrombotic events in patients with acute coronary syndrome or a history of myocardial infarction. Pharmacological inhibition of P2Y12 receptors represents a useful approach to better understand the signaling mediated by these receptors and to elucidate the role of these receptors in a multitude of platelet hemostatic and thrombotic responses...
May 19, 2017: Platelets
https://www.readbyqxmd.com/read/28504079/a-novel-nonsense-nbeal2-gene-mutation-causing-severe-bleeding-in-a-patient-with-gray-platelet-syndrome
#5
Lijuan Cao, Jian Su, Jiaming Li, Ziqiang Yu, Xia Bai, Zhaoyue Wang, Lijun Xia, Changgeng Ruan
Gray platelet syndrome (GPS) is a rare, inherited bleeding disorder characterized by the defect of platelet α-granule. Up to date, these are only four studies identifying NBEAL2 gene correlated with GPS. In the current report, we present a Chinese GPS patient who had severe bleeding tendency, abnormalities of platelet functions, and absence of platelet α-granules. Genomic DNA sequencing for the patient identified a nonsense mutation (g.27713C>A) of NBEAL2 gene (g.NG_031914.1) resulting in a premature protein (p...
May 15, 2017: Platelets
https://www.readbyqxmd.com/read/28504052/adenosine-a2a-receptor-agonists-with-potent-antiplatelet-activity
#6
Eduardo Fuentes, Manuel Fuentes, Julio Caballero, Iván Palomo, Sonja Hinz, Ali El-Tayeb, Christa E Müller
Selected adenosine A2A receptor agonists (PSB-15826, PSB-12404, and PSB-16301) have been evaluated as new antiplatelet agents. In addition, radioligand-binding studies and receptor-docking experiments were performed in order to explain their differential biological effects on a molecular level. Among the tested adenosine derivatives, PSB-15826 was the most potent compound to inhibit platelet aggregation (EC50 0.32 ± 0.05 µmol/L) and platelet P-selectin cell-surface localization (EC50 0.062 ± 0.2 µmol/L), and to increase intraplatelets cAMP levels (EC50 0...
May 15, 2017: Platelets
https://www.readbyqxmd.com/read/28503993/dual-inhibition-of-pi3k-and-mtor-by-vs-5584-suppresses-thrombus-formation
#7
Thomas Später, Isabelle Müller, Hermann Eichler, Michael D Menger, Matthias W Laschke, Emmanuel Ampofo
VS-5584 is a highly selective dual kinase inhibitor which suppresses phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) activity. Because these kinases are crucially involved in primary hemostasis, we herein investigated the effect of this compound on thrombus formation in vitro and in vivo. Pretreatment of washed platelets (WP) or platelet-rich plasma (PRP) with VS-5584 inhibited the agonist-induced activation of surface glycoprotein complex (GP)IIb/IIIa and the upregulation of P-selectin...
May 15, 2017: Platelets
https://www.readbyqxmd.com/read/28503991/platelet-concentrates-modulate-myeloid-dendritic-cell-immune-responses
#8
Katrina K Ki, Helen M Faddy, Robert L Flower, Melinda M Dean
Platelet transfusion has been reported to modulate the recipients' immune system. To date, the precise mechanism(s) driving poor patient outcomes (e.g., increased rate of mortality, morbidity, infectious complications and prolonged hospital stays) following platelet transfusion are largely undefined. To determine the potential for platelet concentrates (PC) to modulate responses of crucial immune regulatory cells, a human in vitro whole blood model of transfusion was established. Maturation and activation of human myeloid dendritic cells (mDC) and the specialized subset blood DC antigen (BDCA)3(+) DC were assessed following exposure to buffy-coat derived PC at day (D)2 (fresh) and D5 (date-of-expiry)...
May 15, 2017: Platelets
https://www.readbyqxmd.com/read/28503981/platelet-reactivity-influences-clot-structure-as-assessed-by-fractal-analysis-of-viscoelastic-properties
#9
Rebecca B Knowles, Matthew J Lawrence, Plinio M Ferreira, Melissa A Hayman, Lindsay A D'Silva, Sophie N Stanford, Ahmed Sabra, Arthur T Tucker, Karl M Hawkins, Phylip R Williams, Timothy D Warner, Phillip A Evans
Despite the interwoven nature of platelet activation and the coagulation system in thrombosis, few studies relate both analysis of protein and cellular parts of coagulation in the same population. In the present study, we use matched ex vivo samples to determine the influences of standard antiplatelet therapies on platelet function and use advanced rheological analyses to assess clot formation. Healthy volunteers were recruited following fully informed consent then treated for 7 days with single antiplatelet therapy of aspirin (75 mg) or prasugrel (10 mg) or with dual antiplatelet therapy (DAPT) using aspirin (75 mg) plus prasugrel (10 mg) or aspirin (75 mg) plus ticagrelor (90 mg)...
May 15, 2017: Platelets
https://www.readbyqxmd.com/read/28437133/the-impact-of-the-centrifuge-characteristics-and-centrifugation-protocols-on-the-cells-growth-factors-and-fibrin-architecture-of-a-leukocyte-and-platelet-rich-fibrin-l-prf-clot-and-membrane
#10
David M Dohan Ehrenfest, Nelson R Pinto, Andrea Pereda, Paula Jiménez, Marco Del Corso, Byung-Soo Kang, Mauricio Nally, Nicole Lanata, Hom-Lay Wang, Marc Quirynen
L-PRF (leukocyte- and platelet-rich fibrin) is one of the four families of platelet concentrates for surgical use and is widely used in oral and maxillofacial regenerative therapies. The first objective of this article was to evaluate the mechanical vibrations appearing during centrifugation in four models of commercially available table-top centrifuges used to produce L-PRF and the impact of the centrifuge characteristics on the cell and fibrin architecture of a L-PRF clot and membrane. The second objective of this article was to evaluate how changing some parameters of the L-PRF protocol may influence its biological signature, independently from the characteristics of the centrifuge...
April 24, 2017: Platelets
https://www.readbyqxmd.com/read/28436749/differential-diagnosis-of-neonatal-alloimmune-thrombocytopenia-type-2b-von-willebrand-disease
#11
Mathilde Penel-Page, Sandrine Meunier, Mathilde Fretigny, Sandra Le Quellec, Pierre Boisseau, Christine Vinciguerra, Catherine Ternisien, Lucia Rugeri
At birth, severe thrombocytopenia without context of infection should mainly suggest neonatal alloimmune thrombocytopenia (NAIT), especially in case of a platelet count below 20 GL(-1). We report two cases of severe neonatal thrombocytopenia, first suspected as being NAIT. Both had a platelet count below 20 GL(-1) with platelet clumps. The absence of alloantibodies and failure of platelet transfusion and intravenous immunoglobulins to improve the platelet count led to question the diagnosis and to evoke inherited bleeding disorders...
April 24, 2017: Platelets
https://www.readbyqxmd.com/read/28436258/thrombopoietin-and-platelet-aggregation-in-patients-with-stable-coronary-artery-disease
#12
Sanne Bøjet Larsen, Erik Lerkevang Grove, Søs Neergaard-Petersen, Morten Würtz, Anne-Mette Hvas, Steen Dalby Kristensen
Thrombopoietin (TPO) may facilitate platelet activation and aggregation. However, data on the impact of TPO on platelet aggregation in patients with stable coronary artery disease (CAD) are scarce. We aimed to investigate associations between TPO and platelet aggregation and activation in patients with stable coronary artery disease (CAD). We studied 900 stable CAD patients. Serum TPO was assessed by ELISA. Platelet aggregation was evaluated using the Multiplate Analyzer (agonists: arachidonic acid [AA] and collagen) and the VerifyNow Aspirin Assay...
April 24, 2017: Platelets
https://www.readbyqxmd.com/read/28409645/evaluation-of-platelet-function-in-thrombocytopenia
#13
Mette Tiedemann Skipper, Peter Rubak, Jesper Stentoft, Anne-Mette Hvas, Ole Halfdan Larsen
Whole blood aggregometry is a functional assay for determination of platelet function. Until now, whole blood aggregometry has not been considered feasible at low platelet counts. Hence, the objectives of the present study were to explore platelet function in thrombocytopenia using a novel index of impedance aggregometry adjusted for platelet count and evaluate the association to platelet function assessed by flow cytometry. Hirudin anticoagulated blood was collected from 20 healthy volunteers, 20 patients with primary immune thrombocytopenia (ITP), and 17 hematological cancer patients...
April 14, 2017: Platelets
https://www.readbyqxmd.com/read/28406726/role-of-heterotrimeric-g-proteins-in-platelet-activation-and-clot-formation-in-platelets-treated-with-integrin-%C3%AE-iib%C3%AE-3-inhibitor
#14
Ivan Budnik, Boris Shenkman, Hagit Hauschner, Isaac Zilinsky, Naphtali Savion
Mechanisms of platelet activation are triggered by thrombin, adenosine diphosphate (ADP), epinephrine, thromboxane A2, and other soluble agonists which induce signaling via heterotrimeric Gαq, Gαi, and Gα12/13 proteins. We have undertaken a study addressing the contribution of these G proteins to platelet activation and clot formation in the presence of eptifibatide, thus excluding outside-in signaling provided by integrin αIIbβ3-fibrinogen engagement. Selective and combined activation of the G proteins was achieved by using combinations of platelet agonists and inhibitors...
April 13, 2017: Platelets
https://www.readbyqxmd.com/read/28406722/development-of-quantitative-monoclonal-antibody-specific-immobilization-of-platelet-antigens-assay-for-antibodies-against-human-platelet-antigen-1a-3a-and-5b
#15
R S Li, B Ling, P Lu
Human platelet antigens (HPAs) are platelet-specific alloantigens that cause alloimmunization. Alloantibodies induced via pregnancy and transfusion may result in various clinical syndromes. The monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay is the gold standard for the detection and identification of HPA antibodies. The present study aimed to develop standardized quantitative MAIPA assays for antibodies against HPA-1a, 3a, and 5b. MAIPA protocol was applied on serial dilutions of standard or reference reagents containing antibodies against HPA-1a, 3a, and 5b...
April 13, 2017: Platelets
https://www.readbyqxmd.com/read/28406717/young-steady-state-rabbit-platelets-do-not-have-an-enhanced-capacity-to-expose-procoagulant-phosphatidylserine
#16
Emily C Reddy, Hong Wang, K W Annie Bang, Marian A Packham, Margaret L Rand
Platelets are recognized to be physiologically and functionally heterogeneous. An example of the diversity in reactivity is the formation of a distinct subpopulation of procoagulant phosphatidylserine (PS)-exposing platelets upon activation. Platelet age has been proposed as a determinant of platelet function, and it has been reported that young platelets are more reactive in exposing PS; using the same methodology of thiazole orange (TO) staining to distinguish young and old platelets, the percentages of procoagulant platelets produced by thrombin plus collagen activation of platelets from healthy controls were examined by flow cytometry...
April 13, 2017: Platelets
https://www.readbyqxmd.com/read/28399723/germline-heterozygous-variants-in-genes-associated-with-familial-hemophagocytic-lymphohistiocytosis-as-a-cause-of-increased-bleeding
#17
Marcus Fager Ferrari, Eva Leinoe, Maria Rossing, Eva Norström, Karin Strandberg, Tobias Steen Sejersen, Klaus Qvortrup, Eva Zetterberg
Familial hemophagocytic lymphohistiocytosis (FHL) is caused by biallelic variants in genes regulating granule secretion in cytotoxic lymphocytes. In FHL3-5, the affected genes UNC13D, STX11 and STXBP2 have further been shown to regulate the secretion of platelet granules, giving rise to compromised platelet function. Therefore, we aimed to investigate platelet degranulation in patients heterozygous for variants in UNC13D, STX11 and STXBP2. During the work-up of patients referred to the Coagulation Unit, Skåne University Hospital, Malmö, Sweden and the Department of Hematology, Rigshospitalet, Copenhagen, Denmark due to bleeding tendencies, 12 patients harboring heterozygous variants in UNC13D, STX11 or STXBP2 were identified using targeted whole exome sequencing...
April 11, 2017: Platelets
https://www.readbyqxmd.com/read/28374642/value-of-platelet-count-in-the-early-diagnosis-of-nosocomial-invasive-fungal-infections-in-premature-infants
#18
Yu-Chen Yang, Jian Mao
The aim of this study was to investigate the value of a platelet count (PLT) in the early diagnosis of nosocomial invasive fungal infections in premature infants. Based on clinical diagnosis combined with blood culture results, 72 premature infants of 5354 pediatric patients who were hospitalized in the neonatal ward of our hospital between September 2009 and February 2013 were diagnosed with nosocomial invasive fungal infections (fungal infection group). There were 58 premature infants diagnosed with bacterial infections during the same period (bacterial infection group)...
April 4, 2017: Platelets
https://www.readbyqxmd.com/read/28374620/thrombin-generation-test-for-evaluation-of-antiplatelet-treatment-in-patients-with-coronary-artery-disease-after-percutaneous-coronary-intervention
#19
Gelena Berezovskaya, Olga Smirnova, Eduard Malev, Nikita Khromov-Borisov, Elena Klokova, Mikhail Karpenko, Lyudmila Papayan, Nikolay Petrishchev
To study the possibility of using thrombin generation tests in platelet-rich and platelet-poor plasma for evaluation of dual antiplatelet therapy efficacy in patients with coronary artery disease (CAD), following percutaneous coronary intervention. Venous blood was analyzed from CAD patients aged 53-75 years who had undergone percutaneous coronary intervention with stenting within one year and had been receiving standard doses of clopidogrel and aspirin (75 and 75-100 mg per day, respectively). The control group comprised age- and sex-matched subjects without clinical signs of CAD who were not receiving these drugs...
April 4, 2017: Platelets
https://www.readbyqxmd.com/read/28358995/use-of-microfluidics-to-assess-the-platelet-based-control-of-coagulation
#20
Magdolna Nagy, Johan W M Heemskerk, Frauke Swieringa
This paper provides an overview of the various types of microfluidic devices that are employed to study the complex processes of platelet activation and blood coagulation in whole blood under flow conditions. We elaborate on how these devices are used to detect impaired platelet-dependent fibrin formation in blood from mice or patients with specific bleeding disorders. We provide a practical guide on how to assess formation of a platelet-fibrin thrombus under flow, using equipment that is present in most laboratories...
March 30, 2017: Platelets
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