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Sample records for bk070044 platelet pgd

  1. PGD-ens paradokser

    Directory of Open Access Journals (Sweden)

    Bjørn Hofmann

    2011-10-01

    Full Text Available Bakgrunn: Preimplantasjonsgenetisk diagnostikk (PGD er en genetisk undersøkelse av befruktede egg før de settes inn i livmoren i forbindelse med assistert reproduksjon. Hensikten med PGD er å unngå at det fremtidige barnet får en alvorlig arvelig sykdom, og at par som på grunn av arvelig sykdom har vansker med å få barn, kan få avkom. PGD er kontroversielt og et sentralt tema for den pågående vurderingen og revisjonen av bioteknologiloven.Metode: Paradoksteori anvendes for å identifisere og analysere noen av kontroversene ved PGD. Det skilles mellom tilsynelatende paradokser, antinomier og aporier. Materialet er offentlige dokumenter, debattinnlegg og faglitteratur.Resultater: Det finnes en rekke tilsynelatende paradokser på PGD-ens område, slik som at PGD gjøres selv om det er svært liten sannsynlighet for at det blir født et alvorlig sykt barn, og at det gjøres PGD for mindre alvorlige sykdommer når forutsetningen for PGD er alvorlig arvelig sykdom. Samtidig finnes det også antinomier: At PGD gir rett til helsehjelp uten at det eksisterer noen pasient, og at PGD gjennomføres selv ved høye kostnader og lav suksessrate. Om embryoet og fosteret har moralsk status og rett på beskyttelse, synes å utgjøre en apori.Konklusjon: Å formulere moralske utfordringer som paradokser kan være en fruktbar måte å tydeliggjøre utfordringer og motsetninger på. Dessuten kan det styre innsatsen: Vi bør bestrebe oss på å rydde opp i tilsynelatende paradokser, jobbe hardere med grunnlagsutfordringene ved antinomier og til en viss grad akseptere motsetningene ved aporiene.Nøkkelord: Preimplantasjonsgenetisk diagnostikk, paradoks, antinomi, aporiEnglish summary: PGD's ParadoxesBackground: Pre-implantation genetic diagnosis (PGD is a genetic test of embryos before implantation as part of in vitro fertilization. The purpose of using PGD is to help people avoid having children with serious genetic disease and to help those with

  2. Quality control standards in PGD and PGS.

    Science.gov (United States)

    SenGupta, S B; Dhanjal, S; Harper, J C

    2016-03-01

    Preimplantation genetic diagnosis (PGD) aims to test the embryo for specific conditions before implantation in couples at risk of transmitting genetic abnormality to their offspring. The couple must undergo IVF procedures to generate embryos in vitro. The embryos can be biopsied at either the zygote, cleavage or blastocyst stage. Preimplantation genetic screening uses the same technology to screen for chromosome abnormalities in embryos from patients undergoing IVF procedures as a method of embryo selection. Fluorescence in-situ hybridization was originally used for chromosome analysis, but has now been replaced by array comparative genomic hybridization or next generation sequencing. For the diagnosis of single gene defects, polymerase chain reaction is used and has become highly developed; however, single nucleotide polymorphism arrays for karyomapping have recently been introduced. A partnership between IVF laboratories and diagnostic centres is required to carry out PGD and preimplantation genetic screening. Accreditation of PGD diagnostic laboratories is important. Accreditation gives IVF centres an assurance that the diagnostic tests conform to specified standards. ISO 15189 is an international laboratory standard specific for medical laboratories. A requirement for accreditation is to participate in external quality assessment schemes. PMID:26776824

  3. Gender eugenics? The ethics of PGD for intersex conditions.

    Science.gov (United States)

    Sparrow, Robert

    2013-01-01

    This article discusses the ethics of the use of preimplantation genetic diagnosis (PGD) to prevent the birth of children with intersex conditions/disorders of sex development (DSDs), such as congenital adrenal hyperplasia (CAH) and androgen insensitivity syndrome (AIS). While pediatric surgeries performed on children with ambiguous genitalia have been the topic of intense bioethical controversy, there has been almost no discussion to date of the ethics of the use of PGD to reduce the prevalence of these conditions. I suggest that PGD for those conditions that involve serious medical risks for those born with them is morally permissible and that PGD for other "cosmetic" variations in sexual anatomy is more defensible than might first appear. However, importantly, the arguments that establish the latter claim have radical and disturbing implications for our attitude toward diversity more generally. PMID:24024804

  4. ESHRE PGD Consortium/Embryology Special Interest Group--best practice guidelines for polar body and embryo biopsy for preimplantation genetic diagnosis/screening (PGD/PGS)

    DEFF Research Database (Denmark)

    Harton, G L; Magli, M C; Lundin, K;

    2011-01-01

    than one document that covers all of PGD as in the original publication, these guidelines are separated into four new documents that apply to different aspects of a PGD programme; Organization of a PGD centre, fluorescence in situ hybridization-based testing, amplification-based testing and polar body...

  5. Critical Issues for Dentistry: PGD Program Directors Respond.

    Science.gov (United States)

    Atchison, Kathryn A.; Cheffetz, Susan E.

    2002-01-01

    Surveyed directors of programs in postgraduate education in general dentistry (PGD) about critical issues facing their programs. Identified 12 themes: lack of postdoctoral applicants; student quality; professionalism and attitudes; number of postdoctoral positions; lack of funding; quality of facilities; special patient care; program curriculum;…

  6. Centrifuge modeling of PGD response of buried pipe

    Institute of Scientific and Technical Information of China (English)

    Michael O'Rourke; Vikram Gadicherla; Tarek Abdoun

    2005-01-01

    A new centrifuge based method for determining the response of continuous buried pipe to PGD is presented.The physical characteristics of the RPI's 100 g-ton geotechnical centrifuge and the current lifeline experiment split-box are described: The split-box contains the model pipeline and surrounding soil and is manufactured such that half can be offset, in flight, simulating PGD. In addition, governing similitude relations which allow one to determine the physical characteristics,(diameter, wall thickness and material modulus of elasticity) of the model pipeline are presented. Finally, recorded strains induced in two buried pipes with prototype diameters of 0.63 m and 0.95 m (24 and 36 inch) subject to 0.6 and 2.0 meters (2and 6 feet) of full scale fault offsets and presented and compared to corresponding FE results.

  7. PGD: a pangolin genome hub for the research community

    Science.gov (United States)

    Tan, Tze King; Tan, Ka Yun; Hari, Ranjeev; Mohamed Yusoff, Aini; Wong, Guat Jah; Siow, Cheuk Chuen; Mutha, Naresh V.R.; Rayko, Mike; Komissarov, Aleksey; Dobrynin, Pavel; Krasheninnikova, Ksenia; Tamazian, Gaik; Paterson, Ian C.; Warren, Wesley C.; Johnson, Warren E.; O'Brien, Stephen J.; Choo, Siew Woh

    2016-01-01

    Pangolins (order Pholidota) are the only mammals covered by scales. We have recently sequenced and analyzed the genomes of two critically endangered Asian pangolin species, namely the Malayan pangolin (Manis javanica) and the Chinese pangolin (Manis pentadactyla). These complete genome sequences will serve as reference sequences for future research to address issues of species conservation and to advance knowledge in mammalian biology and evolution. To further facilitate the global research effort in pangolin biology, we developed the Pangolin Genome Database (PGD), as a future hub for hosting pangolin genomic and transcriptomic data and annotations, and with useful analysis tools for the research community. Currently, the PGD provides the reference pangolin genome and transcriptome data, gene sequences and functional information, expressed transcripts, pseudogenes, genomic variations, organ-specific expression data and other useful annotations. We anticipate that the PGD will be an invaluable platform for researchers who are interested in pangolin and mammalian research. We will continue updating this hub by including more data, annotation and analysis tools particularly from our research consortium. Database URL: http://pangolin-genome.um.edu.my PMID:27616775

  8. PGD: a pangolin genome hub for the research community.

    Science.gov (United States)

    Tan, Tze King; Tan, Ka Yun; Hari, Ranjeev; Mohamed Yusoff, Aini; Wong, Guat Jah; Siow, Cheuk Chuen; Mutha, Naresh V R; Rayko, Mike; Komissarov, Aleksey; Dobrynin, Pavel; Krasheninnikova, Ksenia; Tamazian, Gaik; Paterson, Ian C; Warren, Wesley C; Johnson, Warren E; O'Brien, Stephen J; Choo, Siew Woh

    2016-01-01

    Pangolins (order Pholidota) are the only mammals covered by scales. We have recently sequenced and analyzed the genomes of two critically endangered Asian pangolin species, namely the Malayan pangolin (Manis javanica) and the Chinese pangolin (Manis pentadactyla). These complete genome sequences will serve as reference sequences for future research to address issues of species conservation and to advance knowledge in mammalian biology and evolution. To further facilitate the global research effort in pangolin biology, we developed the Pangolin Genome Database (PGD), as a future hub for hosting pangolin genomic and transcriptomic data and annotations, and with useful analysis tools for the research community. Currently, the PGD provides the reference pangolin genome and transcriptome data, gene sequences and functional information, expressed transcripts, pseudogenes, genomic variations, organ-specific expression data and other useful annotations. We anticipate that the PGD will be an invaluable platform for researchers who are interested in pangolin and mammalian research. We will continue updating this hub by including more data, annotation and analysis tools particularly from our research consortium.Database URL: http://pangolin-genome.um.edu.my. PMID:27616775

  9. Ethics of PGD: thoughts on the consequences of typing HLA in embryos.

    Science.gov (United States)

    Edwards, R G

    2004-08-01

    As with so many fields of study associated with assisted human reproduction, many ethical issues are raised by the practice of preimplantation diagnosis of inherited disease (PGD). Some are part and parcel of assisted conception, e.g.the rights of human embryos in vitro and of embryologists to establish them, carry out research and discard them. Others unique to clinical PGD were discussed at an earlier meeting on PGD (Edwards et al., 2003). Recent developments in PGD are discussed briefly in this Commentary, especially the ethics of designer babies.

  10. On the relation between moral, legal and evaluative justifications of pre-implantation genetic diagnosis (PGD).

    Science.gov (United States)

    Lohmann, Georg

    2003-01-01

    In Germany the question whether to uphold or repeal the judicial prohibition on Pre-implantation Genetic Diagnosis (PGD) is being debated from quite different standpoints. This paper differentiates the major arguments according to their reasons as a) moral, b) evaluative (i.e. cultural/religious), and c) legal. The arguments for and against PGD can be divided by content into three groups: arguments relating to the status of the embryo, focusing on individual actions in the implementation of PGD, and relating to the foreseeable or probable consequences of PGD. In Germany, from a legal perspective, the status of the embryo does not permit the intervention of PGD; from a purely moral perspective, a prohibition on PGD does not appear defensible. It remains an open question, however, whether the moral argument permitting PGD should be restricted for evaluative (cultural) reasons. The paper discusses the species-ethical reasons, for which Jurgen Habermas sees worrisome consequences in the wake of PGD to the extent that we comprehend it as the forerunner of a 'positive eugenics'. It would so disrupt the natural preconditions of our universal morality. The question of whether to prohibit or allow PGD is not merely a question of simple moral and/or legal arguments, but demands a choice between evaluative, moral and (still to be specified) species-ethical arguments, and the question remains open. PMID:16206459

  11. On the relation between moral, legal and evaluative justifications of pre-implantation genetic diagnosis (PGD).

    Science.gov (United States)

    Lohmann, Georg

    2003-01-01

    In Germany the question whether to uphold or repeal the judicial prohibition on Pre-implantation Genetic Diagnosis (PGD) is being debated from quite different standpoints. This paper differentiates the major arguments according to their reasons as a) moral, b) evaluative (i.e. cultural/religious), and c) legal. The arguments for and against PGD can be divided by content into three groups: arguments relating to the status of the embryo, focusing on individual actions in the implementation of PGD, and relating to the foreseeable or probable consequences of PGD. In Germany, from a legal perspective, the status of the embryo does not permit the intervention of PGD; from a purely moral perspective, a prohibition on PGD does not appear defensible. It remains an open question, however, whether the moral argument permitting PGD should be restricted for evaluative (cultural) reasons. The paper discusses the species-ethical reasons, for which Jurgen Habermas sees worrisome consequences in the wake of PGD to the extent that we comprehend it as the forerunner of a 'positive eugenics'. It would so disrupt the natural preconditions of our universal morality. The question of whether to prohibit or allow PGD is not merely a question of simple moral and/or legal arguments, but demands a choice between evaluative, moral and (still to be specified) species-ethical arguments, and the question remains open.

  12. PGD-based modeling of materials, structures and processes

    CERN Document Server

    Chinesta, Francisco

    2014-01-01

    This book focuses on the development of a new simulation paradigm allowing for the solution of models that up to now have never been resolved and which result in spectacular CPU time savings (in the order of millions) that, combined with supercomputing, could revolutionize future ICT (information and communication technologies) at the heart of science and technology. The authors have recently proposed a new paradigm for simulation-based engineering sciences called Proper Generalized Decomposition, PGD, which has proved a tremendous potential in many aspects of forming process simulation. In this book a review of the basics of the technique is made, together with different examples of application.

  13. Modulation of platelet aggregation by areca nut and betel leaf ingredients: roles of reactive oxygen species and cyclooxygenase.

    Science.gov (United States)

    Jeng, Jiiang-Huei; Chen, Shiao-Yun; Liao, Chang-Hui; Tung, Yuan-Yii; Lin, Bor-Ru; Hahn, Liang-Jiunn; Chang, Mei-Chi

    2002-05-01

    There are 2 to 6 billion betel quid (BQ) chewers in the world. Areca nut (AN), a BQ component, modulates arachidonic acid (AA) metabolism, which is crucial for platelet function. AN extract (1 and 2 mg/ml) stimulated rabbit platelet aggregation, with induction of thromboxane B2 (TXB2) production. Contrastingly, Piper betle leaf (PBL) extract inhibited AA-, collagen-, and U46619-induced platelet aggregation, and TXB2 and prostaglandin-D2 (PGD2) production. PBL extract also inhibited platelet TXB2 and PGD2 production triggered by thrombin, platelet activating factor (PAF), and adenosine diphosphate (ADP), whereas little effect on platelet aggregation was noted. Moreover, PBL is a scavenger of O2(*-) and *OH, and inhibits xanthine oxidase activity and the (*)OH-induced PUC18 DNA breaks. Deferoxamine, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and neomycin prevented AN-induced platelet aggregation and TXB2 production. Indomethacin, genistein, and PBL extract inhibited only TXB2 production, but not platelet aggregation. Catalase, superoxide dismutase, and dimethylthiourea (DMT) showed little effect on AN-induced platelet aggregation, whereas catalase and DMT inhibited the AN-induced TXB2 production. These results suggest that AN-induced platelet aggregation is associated with iron-mediated reactive oxygen species production, calcium mobilization, phospholipase C activation, and TXB2 production. PBL inhibited platelet aggregation via both its antioxidative effects and effects on TXB2 and PGD2 production. Effects of AN and PBL on platelet aggregation and AA metabolism is crucial for platelet activation in the oral mucosa and cardiovascular system in BQ chewers. PMID:11978487

  14. Platelet kinetics

    International Nuclear Information System (INIS)

    Recently, the in vivo processes of platelet function and the reaction and interaction of platelets with components of the blood vessel wall and artificial surfaces have received increasing attention. In this article the focus is placed on two aspects of platelet function and kinetics as revealed by 111In-labelled platelets. First the interaction of platelets with foreign prosthetic surfaces is discussed and some interesting facets of platelet functions that have come to light, are pointed out. Secondly, experiences with the development and refinement of an improved technique, namely the dual-isotope subtraction method, which increases the sensitivity of platelet imaging and allows the detection of relatively small areas of platelet deposition with accuracy, are described

  15. Accuracy of preimplantation genetic diagnosis (PGD) of single gene and chromosomal disorders

    Energy Technology Data Exchange (ETDEWEB)

    Verlinsky, Y.; Strom, C.; Rechitsky, S. [Reproductive Genetics Institute, Chicage, IL (United States)] [and others

    1994-09-01

    We have developed a polar body inferred approach for preconception diagnosis of single gene and chromosomal disorders. Preconception PCR or FISH analysis was performed in a total of 310 first polar bodies for the following genetic conditions: cystic fibrosis, hemophilia A, alpha-1-antitrypsin deficiency, Tay Sachs disease, retinitis pigmentosa and common chromosomal trisomies. An important advantage of this approach is the avoidance of sperm (DNA) contamination, which is the major problem of PGD. We are currently applying FISH analysis of biopsied blastomeres, in combination with PCR or separately, and have demonstrated a significant improvement of the accuracy of PGD of X-linked disorders at this stage. Our data have also demonstrated feasibility of the application of FISH technique for PGD of chromosomal disorders. It was possible to detect chromosomal non-disjunctions and chromatid malsegregations in the first meiotic division, as well as to evaluate chromosomal mutations originating from the second meiotic nondisjunction.

  16. An efficient reduced-order method with PGD for solving journal bearing hydrodynamic lubrication problems

    Science.gov (United States)

    Cherabi, Bilal; Hamrani, Abderrachid; Belaidi, Idir; Khelladi, Sofiane; Bakir, Farid

    2016-10-01

    In the present work, a reduced-order method, "Proper Generalized Decomposition (PGD)" is extended and applied to the resolution of the Reynolds equation describing the behavior of the lubricant in hydrodynamic journal bearing. The PGD model is employed to solve the characteristic 'Reynolds' partial differential equation using the separation technique through the alternating direction strategy. The resulting separated-dimension system has a low computation cost compared to classical finite-difference resolution. Several numerical benchmark examples are investigated to verify the validity and accuracy of the proposed method. It has been found that numerical results obtained by the PGD method can achieve an improved convergence rate with a very low computation cost.

  17. Platelet proteomics.

    Science.gov (United States)

    Zufferey, Anne; Fontana, Pierre; Reny, Jean-Luc; Nolli, Severine; Sanchez, Jean-Charles

    2012-01-01

    Platelets are small cell fragments, produced by megakaryocytes, in the bone marrow. They play an important role in hemostasis and diverse thrombotic disorders. They are therefore primary targets of antithrombotic therapies. They are implicated in several pathophysiological pathways, such as inflammation or wound repair. In blood circulation, platelets are activated by several pathways including subendothelial matrix and thrombin, triggering the formation of the platelet plug. Studying their proteome is a powerful approach to understand their biology and function. However, particular attention must be paid to different experimental parameters, such as platelet quality and purity. Several technologies are involved during the platelet proteome processing, yielding information on protein identification, characterization, localization, and quantification. Recent technical improvements in proteomics combined with inter-disciplinary strategies, such as metabolomic, transcriptomics, and bioinformatics, will help to understand platelets biological mechanisms. Therefore, a comprehensive analysis of the platelet proteome under different environmental conditions may contribute to elucidate complex processes relevant to platelet function regarding bleeding disorders or platelet hyperreactivity and identify new targets for antiplatelet therapy.

  18. PGD for hereditary breast and ovarian cancer : the route to universal tests for BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    Drusedau, Marion; Dreesen, Jos C.; Derks-Smeets, Inge; Coonen, Edith; van Golde, Ron; van Echten-Arends, Jannie; Kastrop, Peter M. M.; Blok, Marinus J.; Gomez-Garcia, Encarna; Geraedts, Joep P.; Smeets, Hubert J.; de Die-Smulders, Christine E.; Paulussen, Aimee D.

    2013-01-01

    Preimplantation Genetic Diagnosis (PGD) is a method of testing in vitro embryos as an alternative to prenatal diagnosis with possible termination of pregnancy in case of an affected child. Recently, PGD for hereditary breast and ovarian cancer caused by BRCA1 and BRCA2 mutations has found its way in

  19. Platelet lipidomic.

    Science.gov (United States)

    Dolegowska, B; Lubkowska, A; De Girolamo, L

    2012-01-01

    Lipids account for 16-19 percent dry platelet matter and includes 65 percent phospholipids, 25 percent neutral lipids and about 8 percent glycosphingolipids. The cell membrane that surrounds platelets is a bilayer that contains different types phospholipids symmetrically distributed in resting platelets, such as phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylcholine, and sphingomyelin. The collapse of lipid asymmetry is exposure of phosphatidylserine in the external leaflet of the plasma bilayer, where it is known to serve at least two major functions: providing a platform for development of the blood coagulation cascade and presenting the signal that induces phagocytosis of apoptotic cells. During activation, this asymmetrical distribution becomes disrupted, and PS and PE become exposed on the cell surface. The transbilayer movement of phosphatidylserine is responsible for the platelet procoagulant activity. Exposure of phosphatidylserine is a flag for macrophage recognition and clearance from the circulation. Platelets, stored at room temperature for transfusion for more than 5 days, undergo changes collectively known as platelet storage lesions. Thus, the platelet lipid composition and its possible modifications over time are crucial for efficacy of platelet rich plasma therapy. Moreover, a number of substances derived from lipids are contained into platelets. Eicosanoids are lipid signaling mediators generated by the action of lipoxygenase and include prostaglandins, thromboxane A2, 12-hydroxyeicosatetraenoic acid. Isoprostanes have a chemical structure similar to this of prostanoids, but are differently produced into the particle, and are ligands for prostaglandins receptors, exhibiting biological activity like thromboxane A2. Endocannabinoids are derivatives from arachidonic acid which could reduce local pain. Phospholipids growth factors (sphingolipids, lysophosphatidic acid, platelet-activating factor) are involved in tissue

  20. BLOCKADE OF PGE2, PGD2 RECEPTORS CONFERS PROTECTION AGAINST PREPATENT SCHISTOSOMIASIS MANSONI IN MICE.

    Science.gov (United States)

    Abdel-Ghany, Rasha; Rabia, Ibrahim; El-Ahwany, Eman; Saber, Sameh; Gamal, Rasha; Nagy, Faten; Mahmoud, Olaa; Hamad, Rabab Salem; Barakat, Walled

    2015-12-01

    Schistosomiasis is a chronic disease with considerable social impact. Despite the availability of affordable chemotherapy, drug treatment has not significantly reduced the overall number of disease cases. Among other mechanisms, the parasite produces PGE2 and PGD2 to evade host immune defenses. To investigate the role of PGE2 and PGD2 in schistosomiasis, we evaluated the effects of L-161,982, Ah6809 (PGE2 receptor antagonists alone of combined with each other) and MK-0524 (PGD2 receptor antagonist) during prepatent Schistosoma mansoni infection. Drugs were administered intraperitoneally an hour before and 24 hours after infection of C57BL/6 mice with 100 Schistosoma mansoni cercariae. L-161,982, Ah6809, their combination and MK-0524 caused partial protection against pre-patent S. mansoni infection which was mediated by biasing the immune response towards Th1 phenotype. These results showed that blockade of PGE2 and PGD2 receptors confers partial protection against pre-patent S. mansoni infection in mice and that they may be useful as adjunctive therapy to current anti-schistosomal drugs or vaccines. PMID:26939228

  1. Prostaglandin D2 (PGD2) and its Receptor's Biological Function%前列腺素D2(PGD2)及其受体的生物学功能

    Institute of Scientific and Technical Information of China (English)

    任雪平

    2014-01-01

    前列腺素D2(Prostaglandin D2,PGD2)是哺乳动物脑内含量最丰富的一种前列腺素。研究表明PGD2是最强效的内源性睡眠促进物质,诱导生理性睡眠;哮喘的慢性炎症反应过程中有PGD2参与;并且前列腺素D2及其受体与哺乳动物的生殖密切相关。%Prostaglandin D2 (Prostaglandin D2, PGD2) is the most abundant in mammalian brain a prostaglandin PGD2 study showed the most potent endogenous sleep-promoting substance to induce physiological sleep; asthma, chronic inflammatory reaction there PGD2 participation;and are closely related to prostaglandin D2 and its receptors in mammalian germ.

  2. Cultural Concerns when Counseling Orthodox Jewish Couples for Genetic Screening and PGD.

    Science.gov (United States)

    Grazi, Richard V; Wolowelsky, Joel B

    2015-12-01

    There is a spectrum of attitudes within the Orthodox Jewish community towards genetic testing and PGD. Increased understanding of the belief systems of the Orthodox Jewish population will enhance the genetic counselors' ability to better serve this unique group of patients. By improving cultural competence, genetic counselors can help patients choose the testing options that they deem appropriate, while simultaneously respecting the patient's belief system.

  3. Failure mode and effects analysis of witnessing protocols for ensuring traceability during PGD/PGS cycles.

    Science.gov (United States)

    Cimadomo, Danilo; Ubaldi, Filippo Maria; Capalbo, Antonio; Maggiulli, Roberta; Scarica, Catello; Romano, Stefania; Poggiana, Cristina; Zuccarello, Daniela; Giancani, Adriano; Vaiarelli, Alberto; Rienzi, Laura

    2016-09-01

    Preimplantation genetic diagnosis and aneuploidy testing (PGD/PGS) use is constantly growing in IVF, and embryo/biopsy traceability during the additional laboratory procedures needed is pivotal. An electronic witnessing system (EWS), which showed a significant value in decreasing mismatch occurrence and increasing detection possibilities during standard care IVF, still does not guarantee the same level of efficiency during PGD/PGS cycles. Specifically, EWS cannot follow single embryos throughout the procedure. This is however critical when an unambiguous diagnosis corresponds to each embryo. Failure Mode and Effects Analysis (FMEA) is a proactive method generally adopted to define tools ensuring safety along a procedure. Due to the implementation of a large quantitative PCR (qPCR)-based blastocyst stage PGD/PGS programme in our centre, and to evaluate the potential procedural risks, a FMEA was performed in September 2014. Forty-four failure modes were identified, among which six were given a moderate risk priority number (>15) (RPN; product of estimated occurrence, severity and detection). Specific corrective measures were then introduced and implemented, and a second evaluation performed six months later. The meticulous and careful application of such measures allowed the risks to be decreased along the whole protocol, by reducing their estimated occurrence and/or increasing detection possibilities. PMID:27372783

  4. Can Characteristics of Reciprocal Translocations Predict the Chance of Transferable Embryos in PGD Cycles?

    Directory of Open Access Journals (Sweden)

    Elsbeth Dul

    2014-04-01

    Full Text Available Translocation carriers have an increased risk of miscarriage or the birth of a child with congenital anomalies. Preimplantation genetic diagnosis (PGD is performed in translocation carriers to select for balanced embryos and, thus, increase the chance of an ongoing pregnancy. However, a common experience is that reciprocal translocation carriers produce a high percentage of unbalanced embryos, which cannot be transferred. Therefore, the pregnancy rates in PGD in this patient group are low. In a cohort of 85 reciprocal translocation carriers undergoing PGD we have searched for cytogenetic characteristics of the translocations that can predict the percentage of balanced embryos. Using shape algorithms, the most likely segregation mode per translocation was determined. Shape algorithm, breakpoint location, and relative chromosome segment sizes proved not to be independent predictors of the percentage of balanced embryos. The ratio of the relative sizes of the translocated segments of both translocation chromosomes can give some insight into the chance of transferable embryos: Very asymmetrical translocations have a higher risk of unbalanced products (p = 0.048. Counseling of the couples on the pros and cons of all their reproductive options remains very important.

  5. Enzymatic and mRNA Transcript Response of Ovine 6-Phosphogluconate Dehydrogenase (6PGD in Respect to Different Milk Yield

    Directory of Open Access Journals (Sweden)

    Stamatina Trivizaki

    2010-01-01

    Full Text Available Ovine 6-phosphogluconate dehydrogenase (6PGD is an enzyme of the pentose phosphate pathway, providing the necessary compounds of NADPH for the synthesis of fatty acids. Much of research has been conducted both on enzymatic level and on molecular level. However, to our knowledge, any correlation between enzymatic activity and 6PGD gene expression pattern related to different physiological stages has not been yet reported. With this report, we tried to highlight if any correlation between enzymatic activity and expression of ovine 6PGD gene exists, in respect to different milk yield. According to the determined enzymatic activities and adipocytes characteristics, ewes with low milk production possessed a greater (P≤.001 6PGD activity and larger adipocytes than the highly productive ewes. Although 6PGD expression pattern was higher in low milk yield ewes than in ewes with high milk production, this difference was not found statistically significant. Thus, 6PGD gene expression pattern was not followed by so rapid and great/sizeable changes as it was observed for its respective enzymatic activity, suggesting that other mechanisms such as post translation regulation may be involved in the regulation of the respective gene.

  6. Characterization of human PGD blastocysts with unbalanced chromosomal translocations and human embryonic stem cell line derivation?

    Science.gov (United States)

    Frydman, N; Féraud, O; Bas, C; Amit, M; Frydman, R; Bennaceur-Griscelli, A; Tachdjian, G

    2009-01-01

    Novel embryonic stem cell lines derived from embryos carrying structural chromosomal abnormalities obtained after preimplantation genetic diagnosis (PGD) are of interest to study in terms of the influence of abnormalities on further development. A total of 22 unbalanced blastocysts obtained after PGD were analysed for structural chromosomal defects. Morphological description and chromosomal status of these blastocysts was established and they were used to derive human embryonic stem cell (ESC) lines. An outgrowth of cells was observed for six blastocysts (6/22; 27%). For two blastocysts, the exact morphology was unknown since they were at early stage, and for four blastocysts, the inner cell mass was clearly visible. Fifteen blastocysts carried an unbalanced chromosomal defect linked to a reciprocal translocation, resulting in a positive outgrowth of cells for five blastocysts. One human ESC line was obtained from a blastocyst carrying a partial chromosome-21 monosomy and a partial chromosome-1 trisomy. Six blastocysts carried an unbalanced chromosomal defect linked to a Robertsonian translocation, and one showed a positive outgrowth of cells. One blastocyst carried an unbalanced chromosomal defect linked to an insertion and no outgrowth was observed. The efficiency of deriving human ESC lines with constitutional chromosomal disorders was low and probably depends on the initial morphological aspect of the blastocysts and/or the type of the chromosomal disorders.

  7. Religious Scholars' Attitudes and Views on Ethical Issues Pertaining to Pre-Implantation Genetic Diagnosis (PGD) in Malaysia.

    Science.gov (United States)

    Olesen, A; Nor, S N; Amin, L

    2016-09-01

    Pre-Implantation Genetic Diagnosis (PGD) represents the first fusion of genomics and assisted reproduction and the first reproductive technology that allows prospective parents to screen and select the genetic characteristics of their potential offspring. However, for some, the idea that we can intervene in the mechanisms of human existence at such a fundamental level can be, at a minimum, worrying and, at most, repugnant. Religious doctrines particularly are likely to collide with the rapidly advancing capability for science to make such interventions. This paper focuses on opinions and arguments of selected religious scholars regarding ethical issues pertaining to PGD. In-depth interviews were conducted with religious scholars from three different religious organizations in the Klang Valley, Malaysia. Findings showed that Christian scholars are very sceptical of the long-term use of PGD because of its possible effect on the value of humanity and the parent-children relationship. This differs from Islamic scholars, who view PGD as God-given knowledge in medical science to further help humans understand medical genetics. For Buddhist scholars, PGD is considered to be new medical technology that can be used to save lives, avoid suffering, and bring happiness to those who need it. Our results suggest that it is important to include the opinions and views of religious scholars when it comes to new medical technologies such as PGD, as their opinions will have a significant impact on people from various faiths, particularly in a multi-religious country like Malaysia where society places high value on marital relationships and on the traditional concepts of family. PMID:27365102

  8. Religious Scholars' Attitudes and Views on Ethical Issues Pertaining to Pre-Implantation Genetic Diagnosis (PGD) in Malaysia.

    Science.gov (United States)

    Olesen, A; Nor, S N; Amin, L

    2016-09-01

    Pre-Implantation Genetic Diagnosis (PGD) represents the first fusion of genomics and assisted reproduction and the first reproductive technology that allows prospective parents to screen and select the genetic characteristics of their potential offspring. However, for some, the idea that we can intervene in the mechanisms of human existence at such a fundamental level can be, at a minimum, worrying and, at most, repugnant. Religious doctrines particularly are likely to collide with the rapidly advancing capability for science to make such interventions. This paper focuses on opinions and arguments of selected religious scholars regarding ethical issues pertaining to PGD. In-depth interviews were conducted with religious scholars from three different religious organizations in the Klang Valley, Malaysia. Findings showed that Christian scholars are very sceptical of the long-term use of PGD because of its possible effect on the value of humanity and the parent-children relationship. This differs from Islamic scholars, who view PGD as God-given knowledge in medical science to further help humans understand medical genetics. For Buddhist scholars, PGD is considered to be new medical technology that can be used to save lives, avoid suffering, and bring happiness to those who need it. Our results suggest that it is important to include the opinions and views of religious scholars when it comes to new medical technologies such as PGD, as their opinions will have a significant impact on people from various faiths, particularly in a multi-religious country like Malaysia where society places high value on marital relationships and on the traditional concepts of family.

  9. Media debates and 'ethical publicity' on social sex selection through preimplantation genetic diagnosis (PGD) technology in Australia.

    Science.gov (United States)

    Whittaker, Andrea

    2015-01-01

    This paper offers a critical discourse analysis of media debate over social sex selection in the Australian media from 2008 to 2014. This period coincides with a review of the National Health and Medical Research Council's Ethical Guidelines on the Use of Assisted Reproductive Technology in Clinical Practice and Research (2007), which underlie the regulation of assisted reproductive clinics and practice in Australia. I examine the discussion of the ethics of pre-implatation genetic diagnosis (PGD) within the media as 'ethical publicity' to the lay public. Sex selection through PGD is both exemplary of and interconnected with a range of debates in Australia about the legitimacy of certain reproductive choices and the extent to which procreative liberties should be restricted. Major themes emerging from media reports on PGD sex selection in Australia are described. These include: the spectre of science out of control; ramifications for the contestation over the public funding of abortion in Australia; private choices versus public authorities regulating reproduction; and the ethics of travelling overseas for the technology. It is concluded that within Australia, the issue of PGD sex selection is framed in terms of questions of individual freedom against the principle of sex discrimination - a principle enshrined in legislation - and a commitment to publically-funded medical care. PMID:25803702

  10. Platelets and galectins

    OpenAIRE

    Schattner, Mirta

    2014-01-01

    A major function of platelets is keeping the vascular system intact. Platelet activation at sites of vascular injury leads to the formation of a hemostatic plug. Activation of platelets is therefore crucial for normal hemostasis; however, uncontrolled platelet activation may also lead to the formation of occlusive thrombi that can cause ischemic events. Although they are essential for proper hemostasis, platelet function extends to physiologic processes such as tissue repair, wound remodeling...

  11. Platelets in Lung Biology

    Science.gov (United States)

    Weyrich, Andrew S.; Zimmerman, Guy A.

    2013-01-01

    Platelets and the lungs have an intimate relationship. Platelets are anucleate mammalian blood cells that continuously circulate through pulmonary vessels and that have major effector activities in hemostasis and inflammation. The lungs are reservoirs for megakaryocytes, the requisite precursor cell in thrombopoiesis, which is the intricate process by which platelets are generated. Platelets contribute to basal barrier integrity of the alveolar capillaries, which selectively restricts the transfer of water, proteins, and red blood cells out of the vessels. Platelets also contribute to pulmonary vascular repair. Although platelets bolster hemostatic and inflammatory defense of the healthy lung, experimental evidence and clinical evidence indicate that these blood cells are effectors of injury in a variety of pulmonary disorders and syndromes. Newly discovered biological capacities of platelets are being explored in the context of lung defense, disease, and remodeling. PMID:23043249

  12. Platelets enhance neutrophil transendothelial migration

    Science.gov (United States)

    Platelets are increasingly recognized as important mediators of inflammation in addition to thrombosis. While platelets have been shown to promote neutrophil (PMN) adhesion to endothelium in various inflammatory models, it is unclear whether platelets enhance neutrophil transmigration across inflame...

  13. Reactive oxygen species (ROS) production triggered by prostaglandin D2 (PGD2) regulates lactate dehydrogenase (LDH) expression/activity in TM4 Sertoli cells.

    Science.gov (United States)

    Rossi, Soledad P; Windschüttl, Stefanie; Matzkin, María E; Rey-Ares, Verónica; Terradas, Claudio; Ponzio, Roberto; Puigdomenech, Elisa; Levalle, Oscar; Calandra, Ricardo S; Mayerhofer, Artur; Frungieri, Mónica B

    2016-10-15

    Reactive oxygen species (ROS) regulate testicular function in health and disease. We previously described a prostaglandin D2 (PGD2) system in Sertoli cells. Now, we found that PGD2 increases ROS and hydrogen peroxide (H2O2) generation in murine TM4 Sertoli cells, and also induces antioxidant enzymes expression suggesting that defense systems are triggered as an adaptive stress mechanism that guarantees cell survival. ROS and specially H2O2 may act as second messengers regulating signal transduction pathways and gene expression. We describe a stimulatory effect of PGD2 on lactate dehydrogenase (LDH) expression via DP1/DP2 receptors, which is prevented by the antioxidant N-acetyl-L-cysteine and the PI3K/Akt pathway inhibitor LY 294002. PGD2 also enhances Akt and CREB/ATF-1 phosphorylation. Our results provide evidence for a role of PGD2 in the regulation of the oxidant/antioxidant status in Sertoli cells and, more importantly, in the modulation of LDH expression which takes place through ROS generation and the Akt-CREB/ATF-1 pathway. PMID:27329155

  14. Reproductive Endocrinologists' Utilization of Genetic Counselors for Oncofertility and Preimplantation Genetic Diagnosis (PGD) Treatment of BRCA1/2 Mutation Carriers.

    Science.gov (United States)

    Goetsch, Allison L; Wicklund, Catherine; Clayman, Marla L; Woodruff, Teresa K

    2016-06-01

    Genetic counselors believe fertility preservation and preimplantation genetic diagnosis (PGD) discussions to be a part of their role when counseling BRCA1/2 mutation-positive patients. This study is the first to explore reproductive endocrinologists' (REI) practices and attitudes regarding involvement of genetic counselors in the care of BRCA1/2 mutation carriers seeking fertility preservation and PGD. A survey was mailed to 1000 REIs from Reproductive Endocrinology & Infertility (SREI), an American Society for Reproductive Medicine (ASRM) affiliate group. A 14.5 % response rate was achieved; data was analyzed using SPSS software. The majority of participating REIs were found to recommend genetic counseling to cancer patients considering fertility preservation (82 %) and consult with a genetic counselor regarding PGD for hereditary cancer syndromes (92 %). Additionally, REIs consult genetic counselors regarding PGD patient counseling (88 %), genetic testing (78 %), and general genetics questions (66 %). Two areas genetic counselors may further aid REIs are: elicitation of family history, which is useful to determine fertility preservation and PGD intervention timing (32 % of REIs utilize a cancer family history to determine intervention timing); and, interpretation of variants of uncertain significance (VOUS) as cancer panel genetic testing becomes more common (36 % of REIs are unfamiliar with VOUS). Given our findings, the Oncofertility Consortium® created an online resource for genetic counselors focused on fertility preservation education and communication strategies.

  15. Reproductive Endocrinologists' Utilization of Genetic Counselors for Oncofertility and Preimplantation Genetic Diagnosis (PGD) Treatment of BRCA1/2 Mutation Carriers.

    Science.gov (United States)

    Goetsch, Allison L; Wicklund, Catherine; Clayman, Marla L; Woodruff, Teresa K

    2016-06-01

    Genetic counselors believe fertility preservation and preimplantation genetic diagnosis (PGD) discussions to be a part of their role when counseling BRCA1/2 mutation-positive patients. This study is the first to explore reproductive endocrinologists' (REI) practices and attitudes regarding involvement of genetic counselors in the care of BRCA1/2 mutation carriers seeking fertility preservation and PGD. A survey was mailed to 1000 REIs from Reproductive Endocrinology & Infertility (SREI), an American Society for Reproductive Medicine (ASRM) affiliate group. A 14.5 % response rate was achieved; data was analyzed using SPSS software. The majority of participating REIs were found to recommend genetic counseling to cancer patients considering fertility preservation (82 %) and consult with a genetic counselor regarding PGD for hereditary cancer syndromes (92 %). Additionally, REIs consult genetic counselors regarding PGD patient counseling (88 %), genetic testing (78 %), and general genetics questions (66 %). Two areas genetic counselors may further aid REIs are: elicitation of family history, which is useful to determine fertility preservation and PGD intervention timing (32 % of REIs utilize a cancer family history to determine intervention timing); and, interpretation of variants of uncertain significance (VOUS) as cancer panel genetic testing becomes more common (36 % of REIs are unfamiliar with VOUS). Given our findings, the Oncofertility Consortium® created an online resource for genetic counselors focused on fertility preservation education and communication strategies. PMID:26567039

  16. Platelet Function Tests

    Science.gov (United States)

    ... of the clotting process in the body ( in vivo ). A person with normal platelet function test results may still experience excessive bleeding or inappropriate clotting during and after a surgery. Most samples for platelet function testing are only stable for a very short period ...

  17. Gasotransmitters and platelets.

    Science.gov (United States)

    Truss, Nicola J; Warner, Timothy D

    2011-11-01

    Platelets are essential to prevent blood loss and promote wound healing. Their activation comprises of several complex steps which are regulated by a range of mediators. Over the last few decades there has been intense interest in a group of gaseous mediators known as gasotransmitters; currently comprising nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H(2)S). Here we consider the action of gasotransmitters on platelet activity. NO is a well established platelet inhibitor which mediates its effects predominantly through activation of soluble guanylyl cyclase leading to a decrease in intraplatelet calcium. More recently CO has been identified as a gasotransmitter with inhibitory actions on platelets; CO acts through the same mechanism as NO but is less potent. The in vivo and platelet functions of the most recently identified gasotransmitter, H(2)S, are still the subject of investigations, but they appear generally inhibitory. Whilst there is evidence for the individual action of these mediators, it is also likely that combinations of these mediators are more relevant regulators of platelets. Furthermore, current evidence suggests that these mediators in combination alter the production of each other, and so modify the circulating levels of gasotransmitters. The use of gasotransmitters as therapeutic agents is also being explored for a range of indications. In conclusion, the importance of NO in the regulation of vascular tone and platelet activity has long been understood. Other gasotransmitters are now establishing themselves as mediators of vascular tone, and recent evidence suggests that these other gasotransmitters may also modulate platelet function.

  18. Platelet function in dogs

    DEFF Research Database (Denmark)

    Nielsen, Line A.; Zois, Nora Elisabeth; Pedersen, Henrik D.;

    2007-01-01

    Background: Clinical studies investigating platelet function in dogs have had conflicting results that may be caused by normal physiologic variation in platelet response to agonists. Objectives: The objective of this study was to investigate platelet function in clinically healthy dogs of 4...... different breeds by whole-blood aggregometry and with a point-of-care platelet function analyzer (PFA-100), and to evaluate the effect of acetylsalicylic acid (ASA) administration on the results from both methods. Methods: Forty-five clinically healthy dogs (12 Cavalier King Charles Spaniels [CKCS], 12...... applied. However, the importance of these breed differences remains to be investigated. The PFA-100 method with Col + Epi as agonists, and ADP-induced platelet aggregation appear to be sensitive to ASA in dogs....

  19. Platelet alloimmunization after transfusion

    DEFF Research Database (Denmark)

    Taaning, E; Simonsen, A C; Hjelms, E;

    1997-01-01

    BACKGROUND AND OBJECTIVES: The frequency of platelet-specific antibodies after one series of blood transfusions has not been reported, and in multiply transfused patients is controversial. MATERIALS AND METHODS: We studied the frequency of alloimmunization against platelet antigens in 117 patients...... who received a single series of blood transfusions. They received mostly saline-adenine-glucose+mannitol red blood cell components (poor in leukocytes and platelets) in connection with cardiac surgery. Platelet-specific antibodies were detected with the platelet ELISA and the monoclonal...... (17.9%), of whom 18 (15.4%) had had no detectable antibodies before transfusion. There was a positive correlation between the transfused load of immunogenic materials and the frequency of alloimmunization against HLA antigens. In one third of the immunized patients, there was no history of previous...

  20. Platelet activation and aggregation

    DEFF Research Database (Denmark)

    Jensen, Maria Sander; Larsen, O H; Christiansen, Kirsten;

    2013-01-01

    This study introduces a new laboratory model of whole blood platelet aggregation stimulated by endogenously generated thrombin, and explores this aspect in haemophilia A in which impaired thrombin generation is a major hallmark. The method was established to measure platelet aggregation initiated...... by tissue factor evaluated by means of impedance aggregometry. Citrated whole blood from healthy volunteers and haemophilia A patients with the addition of inhibitors of the contact pathway and fibrin polymerization was evaluated. In healthy persons, a second wave of platelet aggregation was found...

  1. Nanotechnology: Platelet mimicry

    Science.gov (United States)

    Farokhzad, Omid C.

    2015-10-01

    Cloaking drug-loaded nanoparticles with platelet membranes enhances the drugs' abilities to target desired cells and tissues. This technology might improve treatments for cardiovascular and infectious diseases. See Letter p.118

  2. Platelet preservation: agitation and containers.

    Science.gov (United States)

    van der Meer, Pieter F; de Korte, Dirk

    2011-06-01

    For platelets to maintain their in vitro quality and in vivo effectiveness, they need to be stored at room temperature with gentle agitation in gas-permeable containers. The mode of agitation affects the quality of the platelets, and a gentle method of agitation, either a circular or a flat bed movement, provides the best results. Tumblers or elliptical agitators induce platelet activation and subsequent damage. As long as the platelets remain in suspension, the agitation speed is not important. Agitation of the platelet concentrates ensures that the platelets are continuously oxygenated, that sufficient oxygen can enter the storage container and that excess carbon dioxide can be expelled. During transportation of platelet concentrates, nowadays over long distances where they are held without controlled agitation, platelets may tolerate a certain period without agitation. However, evidence is accumulating that during the time without agitation, local hypoxia surrounding the platelets may induce irreversible harm to the platelets. Over the decades, more gas-permeable plastics have been used to manufacture platelet containers. The use of different plastics and their influence on the platelet quality both in vitro and in vivo is discussed. The improved gas-permeability has allowed the extension of platelet storage from 3 days in the early 1980s, to currently at least 7 days. In the light of new developments, particularly the introduction of pathogen reduction techniques, the use of platelet additive solutions and the availability of improved automated separators, further (renewed) research in this area is warranted.

  3. Platelets and cardiac arrhythmia

    Directory of Open Access Journals (Sweden)

    Jonas S De Jong

    2010-12-01

    Full Text Available Sudden cardiac death remains one of the most prevalent modes of death in industrialized countries, and myocardial ischemia due to thrombotic coronary occlusion is its primary cause. The role of platelets in the occurrence of SCD extends beyond coronary flow impairment by clot formation. Here we review the substances released by platelets during clot formation and their arrhythmic properties. Platelet products are released from three types of platelet granules: dense core granules, alpha-granules, and platelet lysosomes. The physiologic properties of dense granule products are of special interest as a potential source of arrhythmic substances. They are released readily upon activation and contain high concentrations of serotonin, histamine, purines, pyrimidines, and ions such as calcium and magnesium. Potential arrhythmic mechanisms of these substances, e.g. serotonin and high energy phosphates, include induction of coronary constriction, calcium overloading, and induction of delayed after-depolarizations. Alpha-granules produce thromboxanes and other arachidonic acid products with many potential arrhythmic effects mediated by interference with cardiac sodium, calcium and potassium channels. Alpha-granules also contain hundreds of proteins that could potentially serve as ligands to receptors on cardiomyocytes. Lysosomal products probably do not have an important arrhythmic effect. Platelet products and ischemia can induce coronary permeability, thereby enhancing interaction with surrounding cardiomyocytes. Antiplatelet therapy is known to improve survival after myocardial infarction. Although an important part of this effect results from prevention of coronary clot formation, there is evidence to suggest that antiplatelet therapy also induces anti-arrhythmic effects during ischemia by preventing the release of platelet activation products.

  4. Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Dong Ju Son

    2014-08-01

    Full Text Available PURPOSE: Piperine, a major alkaloid of black pepper (Piper nigrum and long pepper (Piper longum, was shown to have anti-inflammatory activity through the suppression of cyclooxygenase (COX-2 gene expression and enzyme activity. It is also reported to exhibit anti-platelet activity, but the mechanism underlying this action remains unknown. In this study, we investigated a putative anti-platelet aggregation mechanism involving arachidonic acid (AA metabolism and how this compares with the mechanism by which it inhibits macrophage inflammatory responses; METHODS: Rabbit platelets and murine macrophage RAW264.7 cells were treated with piperine, and the effect of piperine on the activity of AA-metabolizing enzymes, including cytosolic phospholipase A2 (cPLA2, COX-1, COX-2, and thromboxane A2 (TXA2 synthase, as well as its effect on AA liberation from the plasma membrane components, were assessed using isotopic labeling methods and enzyme immunoassay kit; RESULTS: Piperine significantly suppressed AA liberation by attenuating cPLA2 activity in collagen-stimulated platelets. It also significantly inhibited the activity of TXA2 synthase, but not of COX-1, in platelets. These results suggest that piperine inhibits platelet aggregation by attenuating cPLA2 and TXA2 synthase activities, rather than through the inhibition of COX-1 activity. On the other hand, piperine significantly inhibited lipopolysaccharide-induced generation of prostaglandin (PGE2 and PGD2 in RAW264.7 cells by suppressing the activity of COX-2, without effect on cPLA2; CONCLUSION: Our findings indicate that piperine inhibits platelet aggregation and macrophage inflammatory response by different mechanisms.

  5. Prophylactic platelets in dengue

    DEFF Research Database (Denmark)

    Whitehorn, James; Rodriguez Roche, Rosmari; Guzman, Maria G;

    2012-01-01

    Dengue is the most important arboviral infection of humans. Thrombocytopenia is frequently observed in the course of infection and haemorrhage may occur in severe disease. The degree of thrombocytopenia correlates with the severity of infection, and may contribute to the risk of haemorrhage....... As a result of this prophylactic platelet transfusions are sometimes advocated for the prevention of haemorrhage. There is currently no evidence to support this practice, and platelet transfusions are costly and sometimes harmful. We conducted a global survey to assess the different approaches to the use...... of platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received responses from 306 physicians from 20 different countries. The heterogeneity...

  6. Platelet serotonin in systemic sclerosis.

    OpenAIRE

    Klimiuk, P S; Grennan, A; Weinkove, C.; Jayson, M I

    1989-01-01

    Platelet serotonin concentrations were measured in 43 patients with systemic sclerosis, in 11 patients with primary Raynaud's phenomenon, and in 38 normal controls. Patients with the CREST variant (calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia) had significantly lower platelet serotonin concentrations than normal controls. Patients with diffuse systemic sclerosis had normal platelet serotonin concentrations. In patients with CREST treatment with keta...

  7. Approaches to synthetic platelet analogs.

    Science.gov (United States)

    Modery-Pawlowski, Christa L; Tian, Lewis L; Pan, Victor; McCrae, Keith R; Mitragotri, Samir; Sen Gupta, Anirban

    2013-01-01

    Platelet transfusion is routinely used for treating bleeding complications in patients with hematologic or oncologic clotting disorders, chemo/radiotherapy-induced myelosuppression, trauma and surgery. Currently, these transfusions mostly use allogeneic platelet concentrates, while products like lyophilized platelets, cold-stored platelets and infusible platelet membranes are under investigation. These natural platelet-based products pose considerable risks of contamination, resulting in short shelf-life (3-5 days). Recent advances in pathogen reduction technologies have increased shelf-life to ~7 days. Furthermore, natural platelets are short in supply and also cause several biological side effects. Hence, there is significant clinical interest in platelet-mimetic synthetic analogs that can allow long storage-life and minimum side effects. Accordingly, several designs have been studied which decorate synthetic particles with motifs that promote platelet-mimetic adhesion or aggregation. Recent refinement in this design involves combining the adhesion and aggregation functionalities on a single particle platform. Further refinement is being focused on constructing particles that also mimic natural platelet's shape, size and elasticity, to influence margination and wall-interaction. The optimum design of a synthetic platelet analog would require efficient integration of platelet's physico-mechanical properties and biological functionalities. We present a comprehensive review of these approaches and provide our opinion regarding the future directions of this research. PMID:23092864

  8. Inhibition of human platelet function in vitro and ex vivo by acetaminophen.

    Science.gov (United States)

    Lages, B; Weiss, H J

    1989-03-15

    The effects of acetaminophen (APAP) in vitro, or ex vivo following APAP ingestion, on human platelet aggregation, 14C-5HT secretion, and thromboxane B2 (TxB2) formation were assessed. APAP added in vitro to citrated platelet-rich plasma (PRP) inhibited aggregation, secretion, and TxB2 formation induced by collagen, epinephrine, arachidonate, and the ionophore A23187, but had no effect on the responses induced by the endoperoxide analog U44069. Arachidonate-induced responses were inhibited by lower concentrations of APAP than were the responses to the other agonists. In PRP obtained 1 hour after ingestion of 650 mg or 1000 mg APAP, arachidonate-induced TxB2 formation was inhibited by 40-99% in five subjects tested, whereas inhibition of collagen- or epinephrine-induced TxB2 formation was less consistent. Aggregation and secretion responses were not altered by APAP ingestion in 4 of the 5 subjects, but were inhibited in the remaining subject, who had the highest plasma APAP levels. In contrast to aspirin and indomethacin, APAP-induced inhibition of collagen-stimulated TxB2 formation could be partially overcome with increasing collagen concentrations. No such partial correction occurred with epinephrine, however. In washed platelet suspensions labeled with 3H-arachidonate, both APAP and aspirin inhibited the formation of labeled PGD2 and PGE2, as well as TxB2. These results suggest that APAP acts in human platelets as a reversible inhibitor of cyclo-oxygenase, as found previously in other tissues, and that recent APAP ingestion can, on occasion, produce inhibition of platelet functional responses measured in vitro. PMID:2499947

  9. Effects of platelet inhibitors on propyl gallate-induced platelet aggregation, protein tyrosine phosphorylation, and platelet factor 3 activation.

    Science.gov (United States)

    Xiao, Hongyan; Kovics, Richard; Jackson, Van; Remick, Daniel G

    2004-04-01

    Propyl gallate (PG) is a platelet agonist characterized by inducing platelet aggregation, protein tyrosine phosphorylation, and platelet factor 3 activity. The mechanisms of platelet activation following PG stimulation were examined by pre-incubating platelets with well-defined platelet inhibitors using platelet aggregation, protein tyrosine phosphorylation, activated plasma clotting time, and annexin V binding by flow cytometry. PG-induced platelet aggregation and tyrosine phosphorylation of multiple proteins were substantially abolished by aspirin, apyrase, and abciximab (c7E3), suggesting that PG is associated with activation of platelet cyclooxygenase 1, adenosine phosphate receptors, and glycoprotein IIb/IIIa, respectively. The phosphorylation of the cytoskeletal enzyme pp60(c-src) increased following PG stimulation, but was blunted by pre-incubation of platelets with aspirin, apyrase, and c7E3, suggesting that tyrosine kinase is important for the signal transduction of platelet aggregation. Propyl gallate also activates platelet factor 3 by decreasing the platelet coagulation time and increasing platelet annexin V binding. Platelet incubation with aspirin, apyrase, and c7E3 did not alter PG-induced platelet coagulation and annexin V binding. The results suggest that platelet factor 3 activation and membrane phosphotidylserine expression were not involved with activation of platelet cyclooxygenase, adenosine phosphate receptors, and glycoprotein IIb/IIIa. PG is unique in its ability to stimulate platelet aggregation and coagulation simultaneously, and platelet inhibitors in this study affect only platelet aggregation but not platelet coagulation. PMID:15060414

  10. Analysis of the APX, PGD1 and R1G1B constitutive gene promoters in various organs over three homozygous generations of transgenic rice plants.

    Science.gov (United States)

    Park, Su-Hyun; Bang, Seung Woon; Jeong, Jin Seo; Jung, Harin; Redillas, Mark Christian Felipe Reveche; Kim, Hyung Il; Lee, Kang Hyun; Kim, Youn Shic; Kim, Ju-Kon

    2012-06-01

    We have previously characterized the constitutively active promoters of the APX, PGD1 and R1G1B genes in rice (Park et al. 2010 in J Exp Bot 61:2459-2467). To have potential crop biotechnology applications, gene promoters must be stably active over many generations. In our current study, we report our further detailed analysis of the APX, PGD1 and R1G1B gene promoters in various organs and tissues of transgenic rice plants for three (T₃₋₅) homozygous generations. The copy numbers in 37 transgenic lines that harbor promoter:gfp constructs were determined and promoter activities were measured by real-time qPCR. Analysis of the 37 lines revealed that 15 contained a single copy of one of the three promoter:gfp chimeric constructs. The promoter activity levels were generally higher in multi-copy lines, whereas variations in these levels over the T₃₋₅ generations studied were observed to be smaller in single-copy than in multi-copy lines. The three promoters were further found to be highly active in the whole plant body at both the vegetative and reproductive stages of plant growth, with the exception of the APX in the ovary and R1G1B in the pistil and filaments where zero or very low levels of activity were detected. Of note, the spatial activities of the PGD1 promoter were found to be strikingly similar to those of the ZmUbi1, a widely used constitutive promoter. Our comparison of promoter activities between T₃, T₄ and T₅ plants revealed that the APX, PGD1 and R1G1B promoters maintained their activities at comparable levels in leaves and roots over three homozygous generations and are therefore potentially viable alternative promoters for crop biotechnology applications.

  11. PREGNANCY WITH PLATELET FUNCTION DISORDER

    Directory of Open Access Journals (Sweden)

    Sheila K

    2014-01-01

    Full Text Available latelets play a vital role in haemostasis . Antenatal patients with platelet function disorders should be managed in tertiary care centres that are well equipped to tackle any obstetric haemorrhage that can ensue during labour and delivery . Primi gravida was admitted for safe confinement . She had been evaluated earlier for complaints of multiple episodes of mucosal bleeding . On evaluation she had nor mal platelet counts and coagulation factor assay was normal . Platelet aggregometry revealed mild disorder of platelet aggregation . She was planned for induction of labour after arranging enough blood and blood products . She got into active labour and was p ut on syntocinon augmentation . She had emergency Caesarean section for foetal distress . Oxytocics were given proactively . Intraoperatively platelet transfusions and tranexamic acid infusion were given . Complete haemostasis was achieved . She had an uneventf ul postoperative period . Patients with functional platelet disorders can be successfully managed with local application of antifibrinolytic agents like tranexamic acid , in case of minor bleeds . Platelet transfusions are very effective in tackling major ble eds , especially during surgeries and for obstetric indications . If a patient has the history of clinically significant bleeding suggestive of platelet dysfunction , appropriate platelet function tests should be obtained so that the risk of bleeding can be adequately assessed and therapy chosen more rationally . . In obstetric practice the response of such patients to platelet transfusions has been excellent

  12. Effect of some saturated and unsaturated fatty acids on prostaglandin biosynthesis in washed human blood platelets from (1-/sup 14/ C)arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, K.C.; Awasthi, K.K.; Lindegard, P.; Tiwari, K.P.

    1982-03-01

    The effects of some saturated (lauric, palmitic and stearic) an unsaturated (linoleic, gamma-linolenic, alpha-linolenic and oleic) fatty acids at 0.1. 0.25 and 0.5 mM concentrations on the in vitro metabolization of (1-14 C) arachidonic acid by washed human blood platelets have been studied. Effects of these fatty acids were studied with intact as well as lysed platelet preparations. With intact platelet preparations it was found that (i) all unsaturated fatty acids enhanced the biosynthesis of TxB2, PGE2, PGD2 and PGF2 alpha, (ii) unsaturated fatty acids reduced the formation of HHT and HETE with the exception of oleic acid which showed very little effect, (iii) unsaturated fatty acids reduced the formation of MDA, whereas palmitic and stearic acids increased its formation and (iv) all unsaturated fatty acids reduced the synthesis of prostaglandin endoperoxides. These results support our previous observations where effects of fatty acids were examined at higher concentrations (10). At 0.1 mM FA concentration, inconsistent results were obtained. With lysed platelet preparations all cyclooxygenase products were reduced in presence of unsaturated fatty acids, whereas HETE formation was reduced only in presence of linoleic and gamma-linolenic acids. Electron micrographs of washed platelet suspensions were obtained with untreated platelet preparations and platelet preparations treated with 0.25 and 0.5 mM linoleic acid concentrations. The results are discussed in the light of a possible soap-like effect of FA salt on platelets.

  13. Platelet aggregation following trauma

    DEFF Research Database (Denmark)

    Windeløv, Nis A; Sørensen, Anne M; Perner, Anders;

    2014-01-01

    We aimed to elucidate platelet function in trauma patients, as it is pivotal for hemostasis yet remains scarcely investigated in this population. We conducted a prospective observational study of platelet aggregation capacity in 213 adult trauma patients on admission to an emergency department (ED......). Inclusion criteria were trauma team activation and arterial cannula insertion on arrival. Blood samples were analyzed by multiple electrode aggregometry initiated by thrombin receptor agonist peptide 6 (TRAP) or collagen using a Multiplate device. Blood was sampled median 65 min after injury; median injury...... severity score (ISS) was 17; 14 (7%) patients received 10 or more units of red blood cells in the ED (massive transfusion); 24 (11%) patients died within 28 days of trauma: 17 due to cerebral injuries, four due to exsanguination, and three from other causes. No significant association was found between...

  14. Platelets actively sequester angiogenesis regulators

    OpenAIRE

    Lakka Klement, Giannoula; Yip, Tai-Tung; Cassiola, Flavia; Kikuchi, Lena; Cervi, David; Podust, Vladimir; Italiano, Joseph E.; Wheatley, Erin; Abou-Slaybi, Abdo; Bender, Elise; Almog, Nava; Kieran, Mark W.; Folkman, Judah

    2009-01-01

    Clinical trials with antiangiogenic agents have not been able to validate plasma or serum levels of angiogenesis regulators as reliable markers of cancer presence or therapeutic response. We recently reported that platelets contain numerous proteins that regulate angiogenesis. We now show that accumulation of angiogenesis regulators in platelets of animals bearing malignant tumors exceeds significantly their concentration in plasma or serum, as well as their levels in platelets from non–tumor...

  15. Novel aspects of platelet aggregation

    Directory of Open Access Journals (Sweden)

    Roka-Moya Y. M.

    2014-01-01

    Full Text Available The platelet aggregation is an important process, which is critical for the hemostatic plug formation and thrombosis. Recent studies have shown that the platelet aggregation is more complex and dynamic than it was previously thought. There are several mechanisms that can initiate the platelet aggregation and each of them operates under specific conditions in vivo. At the same time, the influence of certain plasma proteins on this process should be considered. This review intends to summarize the recent data concerning the adhesive molecules and their receptors, which provide the platelet aggregation under different conditions.

  16. Subpopulations in purified platelets adhering on glass.

    Science.gov (United States)

    Donati, Alessia; Gupta, Swati; Reviakine, Ilya

    2016-01-01

    Understanding how platelet activation is regulated is important in the context of cardiovascular disorders and their management with antiplatelet therapy. Recent evidence points to different platelet subpopulations performing different functions. In particular, procoagulant and aggregating subpopulations have been reported in the literature in platelets treated with the GPVI agonists. How the formation of platelet subpopulations upon activation is regulated remains unclear. Here, it is shown that procoagulant and aggregating platelet subpopulations arise spontaneously upon adhesion of purified platelets on clean glass surfaces. Calcium ionophore treatment of the adhering platelets resulted in one platelet population expressing both the procoagulant and the adherent population markers phosphatidylserine and the activated form of GPIIb/IIIa, while all of the platelets expressed CD62P independently of the ionophore treatment. Therefore, all platelets have the capacity to express all three activation markers. It is concluded that platelet subpopulations observed in various studies reflect the dynamics of the platelet activation process. PMID:27338300

  17. Genomics of platelet disorders.

    Science.gov (United States)

    Westbury, S K; Mumford, A D

    2016-07-01

    Genetic diagnosis in families with inherited platelet disorders (IPD) is not performed widely because of the genetic heterogeneity of this group of disorders and because in most cases, it is not possible to select single candidate genes for analysis using clinical and laboratory phenotypes. Next-generation sequencing (NGS) technology has revolutionized the scale and cost-effectiveness of genetic testing, and has emerged as a valuable tool for IPD. This review examines the potential utility of NGS as a diagnostic tool to streamline detection of causal variants in known IPD genes and as a vehicle for new gene discovery. PMID:27405671

  18. Platelets, inflammation and tissue regeneration.

    Science.gov (United States)

    Nurden, Alan T

    2011-05-01

    Blood platelets have long been recognised to bring about primary haemostasis with deficiencies in platelet production and function manifesting in bleeding while upregulated function favourises arterial thrombosis. Yet increasing evidence indicates that platelets fulfil a much wider role in health and disease. First, they store and release a wide range of biologically active substances including the panoply of growth factors, chemokines and cytokines released from a-granules. Membrane budding gives rise to microparticles (MPs), another active participant within the blood stream. Platelets are essential for the innate immune response and combat infection (viruses, bacteria, micro-organisms). They help maintain and modulate inflammation and are a major source of pro-inflammatory molecules (e.g. P-selectin, tissue factor, CD40L, metalloproteinases). As well as promoting coagulation, they are active in fibrinolysis; wound healing, angiogenesis and bone formation as well as in maternal tissue and foetal vascular remodelling. Activated platelets and MPs intervene in the propagation of major diseases. They are major players in atherosclerosis and related diseases, pathologies of the central nervous system (Alzheimers disease, multiple sclerosis), cancer and tumour growth. They participate in other tissue-related acquired pathologies such as skin diseases and allergy, rheumatoid arthritis, liver disease; while, paradoxically, autologous platelet-rich plasma and platelet releasate are being used as an aid to promote tissue repair and cellular growth. The above mentioned roles of platelets are now discussed.

  19. Derivation of HVR1, HVR2 and HVR3 human embryonic stem cell lines from IVF embryos after preimplantation genetic diagnosis (PGD for monogenic disorder

    Directory of Open Access Journals (Sweden)

    Abdelkrim Hmadcha

    2016-05-01

    Full Text Available From 106 human blastocyts donate for research after in vitro fertilization (IVF and preimplantation genetic diagnosis (PGD for monogenetic disorder, 3 human embryonic stem cells (hESCs HVR1, HVR2 and HVR3 were successfully derived. HVR1 was assumed to be genetically normal, HVR2 carrying Becker muscular dystrophy and HVR3 Hemophilia B. Despite the translocation t(9;15(q34.3;q14 detected in HVR2, all the 3 cell lines were characterised in vitro and in vivo as normal hESCs lines and were registered in the Spanish Stem Cell Bank.

  20. Derivation of HVR1, HVR2 and HVR3 human embryonic stem cell lines from IVF embryos after preimplantation genetic diagnosis (PGD) for monogenic disorder.

    Science.gov (United States)

    Hmadcha, Abdelkrim; Aguilera, Yolanda; Lozano-Arana, Maria Dolores; Mellado, Nuria; Sánchez, Javier; Moya, Cristina; Sánchez-Palazón, Luis; Palacios, Jose; Antiñolo, Guillermo; Soria, Bernat

    2016-05-01

    From 106 human blastocyts donate for research after in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD) for monogenetic disorder, 3 human embryonic stem cells (hESCs) HVR1, HVR2 and HVR3 were successfully derived. HVR1 was assumed to be genetically normal, HVR2 carrying Becker muscular dystrophy and HVR3 Hemophilia B. Despite the translocation t(9;15)(q34.3;q14) detected in HVR2, all the 3 cell lines were characterised in vitro and in vivo as normal hESCs lines and were registered in the Spanish Stem Cell Bank. PMID:27346196

  1. Platelets in inflammation and infection.

    Science.gov (United States)

    Jenne, Craig N; Kubes, Paul

    2015-01-01

    Although platelets are traditionally recognized for their central role in hemostasis, many lines of research clearly demonstrate these rather ubiquitous blood components are potent immune modulators and effectors. Platelets have been shown to directly recognize, sequester and kill pathogens, to activated and recruit leukocytes to sites of infection and inflammation, and to modulate leukocyte behavior, enhancing their ability to phagocytose and kill pathogens and inducing unique effector functions, such as the production of Neutrophil Extracellular Traps (NETs). This multifaceted response to infection and inflammation is due, in part, to the huge array of soluble mediators and cell surface molecules expressed by platelets. From their earliest origins as primordial hemocytes in invertebrates to their current form as megakaryocyte-derived cytoplasts, platelets have evolved to be one of the key regulators of host intravascular immunity and inflammation. In this review, we present the diverse roles platelets play in immunity and inflammation associated with autoimmune diseases and infection. Additionally, we highlight recent advances in our understanding of platelet behavior made possible through the use of advanced imaging techniques that allow us to visualize platelets and their interactions, in real-time, within the intact blood vessels of a living host.

  2. Platelet mechanosensing of collagen matrices.

    Directory of Open Access Journals (Sweden)

    Matthew F Kee

    Full Text Available During vascular injury, platelets adhere to exposed subendothelial proteins, such as collagen, on the blood vessel walls to trigger clot formation. Although the biochemical signalings of platelet-collagen interactions have been well characterized, little is known about the role microenvironmental biomechanical properties, such as vascular wall stiffness, may have on clot formation. To that end, we investigated how substrates of varying stiffness conjugated with the same concentration of Type I collagen affect platelet adhesion, spreading, and activation. Using collagen-conjugated polyacrylamide (PA gels of different stiffnesses, we observed that platelets do in fact mechanotransduce the stiffness cues of collagen substrates, manifesting in increased platelet spreading on stiffer substrates. In addition, increasing substrate stiffness also increases phosphatidylserine exposure, a key aspect of platelet activation that initiates coagulation on the platelet surface. Mechanistically, these collagen substrate stiffness effects are mediated by extracellular calcium levels and actomyosin pathways driven by myosin light chain kinase but not Rho-associated protein kinase. Overall, our results improve our understanding of how the mechanics of different tissues and stroma affect clot formation, what role the increased vessel wall stiffness in atherosclerosis may directly have on thrombosis leading to heart attacks and strokes, and how age-related increased vessel wall stiffness affects hemostasis and thrombosis.

  3. Cyclosporine A enhances platelet aggregation.

    Science.gov (United States)

    Grace, A A; Barradas, M A; Mikhailidis, D P; Jeremy, J Y; Moorhead, J F; Sweny, P; Dandona, P

    1987-12-01

    In view of the reported increase in thromboembolic episodes following cyclosporine A (CyA) therapy, the effect of this drug on platelet aggregation and thromboxane A2 release was investigated. The addition of CyA, at therapeutic concentrations to platelet rich plasma from normal subjects in vitro was found to increase aggregation in response to adrenaline, collagen and ADP. Ingestion of CyA by healthy volunteers was also associated with enhanced platelet aggregation. The CyA-mediated enhancement of aggregation was further enhanced by the addition in vitro of therapeutic concentrations of heparin. Platelets from renal allograft recipients treated with CyA also showed hyperaggregability and increased thromboxane A2 release, which were most marked at "peak" plasma CyA concentration and less so at "trough" concentrations. Platelet hyperaggregability in renal allograft patients on long-term CyA therapy tended to revert towards normal following the replacement of CyA with azathioprine. Hypertensive patients with renal allografts on nifedipine therapy had normal platelet function and thromboxane release in spite of CyA therapy. These observations suggest that CyA-mediated platelet activation may contribute to the pathogenesis of the thromboembolic phenomena associated with the use of this drug. The increased release of thromboxane A2 (a vasoconstrictor) may also play a role in mediating CyA-related nephrotoxicity.

  4. Hormonal contraception and platelet function.

    Science.gov (United States)

    Saleh, A A; Ginsburg, K A; Duchon, T A; Dorey, L G; Hirata, J; Alshameeri, R S; Dombrowski, M P; Mammen, E F

    1995-05-15

    73 healthy women (29 controls, 25 using OCs, and 19 using Norplant) were selected from the clinic population at North Oakland Medical Center for inclusion in this study after obtaining informed consent. Age, race, height, weight, blood pressure, and cigarette smoking were recorded for each subject. 12 patients were on monophasic OCs while 13 were on triphasic preparations. Both hormonal contraceptive groups had used their particular contraceptive for at least 3 months prior to blood drawing. Platelet tests were performed within 2 hours of sample collection: platelet counts (PLC) and mean platelet volume (MPV) were determined on an Automated Platelet Counter (Baker 810 Platelet Analyzer). Whole blood aggregation was performed on a platelet aggregometer (Chrono-Log, Model 550) using both ADP (ADP, 5 mM) and collagen (COLL, 2 mcg/ml) as inducing agents. Demographic differences were not significant (p 0.05) among the 3 treatment groups, whose average age was 25.3-25.8 years old. Furthermore, no significant differences (p 0.05) in platelet function were detected among controls or subjects receiving either oral contraceptives or Norplant, compared to control patients. The mean platelet counts (X 10/9/L) were 223 for OC users, 231 for Norplant users, and 232 for controls. The respective platelet aggregation (ADP, ohms) values were 12.5, 18.0, and 19.2 as well as (COLL, ohms) 35.6, 40.7, and 39.0. These results demonstrated that there is no evidence for altered platelet function, with the testing methods employed, in women using either Norplant or combination low dose oral contraceptives. To date, several studies have examined this issue, with contradictory reports about the effects of hormonal contraceptives in platelet function. After controlling for differences between various steroid preparations and other such confounding variables, some of these conflicting conclusions could be the result of a lack of uniformity among the methods used to evaluate platelet aggregation

  5. [Protein kinase C activation induces platelet apoptosis].

    Science.gov (United States)

    Zhao, Li-Li; Chen, Meng-Xing; Zhang, Ming-Yi; Dai, Ke-Sheng

    2013-10-01

    Platelet apoptosis elucidated by either physical or chemical compound or platelet storage occurs wildly, which might play important roles in controlling the numbers and functions of circulated platelets, or in the development of some platelet-related diseases. However, up to now, a little is known about the regulatory mechanisms of platelet apoptosis. Protein kinase C (PKC) is highly expressed in platelets and plays central roles in regulating platelet functions. Although there is evidence indicating that PKC is involved in the regulation of apoptosis of nucleated cells, it is still unclear whether PKC plays a role in platelet apoptosis. The aim of this study was to investigate the role of PKC in platelet apoptosis. The effects of PKC on mitochondrial membrane potential (ΔΨm), phosphatidylserine (PS) exposure, and caspase-3 activation of platelets were analyzed by flow cytometry and Western blot. The results showed that the ΔΨm depolarization in platelets was induced by PKC activator in time-dependent manner, and the caspase-3 activation in platelets was induced by PKC in concentration-dependent manner. However, the platelets incubated with PKC inhibitor did not results in ΔΨm depolarization and PS exposure. It is concluded that the PKC activation induces platelet apoptosis through influencing the mitochondrial functions and activating caspase 3. The finds suggest a novel mechanism for PKC in regulating platelet numbers and functions, which has important pathophysiological implications for thrombosis and hemostasis.

  6. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features.

    Science.gov (United States)

    Dohan, David M; Choukroun, Joseph; Diss, Antoine; Dohan, Steve L; Dohan, Anthony J J; Mouhyi, Jaafar; Gogly, Bruno

    2006-03-01

    Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this second article, we investigate the platelet-associated features of this biomaterial. During PRF processing by centrifugation, platelets are activated and their massive degranulation implies a very significant cytokine release. Concentrated platelet-rich plasma platelet cytokines have already been quantified in many technologic configurations. To carry out a comparative study, we therefore undertook to quantify PDGF-BB, TGFbeta-1, and IGF-I within PPP (platelet-poor plasma) supernatant and PRF clot exudate serum. These initial analyses revealed that slow fibrin polymerization during PRF processing leads to the intrinsic incorporation of platelet cytokines and glycanic chains in the fibrin meshes. This result would imply that PRF, unlike the other platelet concentrates, would be able to progressively release cytokines during fibrin matrix remodeling; such a mechanism might explain the clinically observed healing properties of PRF.

  7. Myeloperoxidase induces the priming of platelets.

    Science.gov (United States)

    Kolarova, H; Klinke, A; Kremserova, S; Adam, M; Pekarova, M; Baldus, S; Eiserich, J P; Kubala, L

    2013-08-01

    The release of myeloperoxidase (MPO) from polymorphonuclear neutrophils is a hallmark of vascular inflammation and contributes to the pathogenesis of vascular inflammatory processes. However, the effects of MPO on platelets as a contributory mechanism in vascular inflammatory diseases remain unknown. Thus, MPO interaction with platelets and its effects on platelet function were examined. First, dose-dependent binding of MPO (between 1.7 and 13.8nM) to both human and mouse platelets was observed. This was in direct contrast to the absence of MPO in megakaryocytes. MPO was localized both on the surface of and inside platelets. Cytoskeleton inhibition did not prevent MPO localization inside the three-dimensional platelet structure. MPO peroxidase activity was preserved upon the MPO binding to platelets. MPO sequestered in platelets catabolized NO, documented by the decreased production of NO (on average, an approximately 2-fold decrease). MPO treatment did not affect the viability of platelets during short incubations; however, it decreased platelet viability after long-term storage for 7 days (an approximately 2-fold decrease). The activation of platelets by MPO was documented by an MPO-mediated increase in the expression of surface platelet receptors P-selectin and PECAM-1 (of about 5 to 20%) and the increased formation of reactive oxygen species (of about 15 to 200%). However, the activation was only partial, as MPO did not induce the aggregation of platelets nor potentiate platelet response to classical activators. Nor did MPO induce a significant release of the content of granules. The activation of platelets by MPO was connected with increased MPO-treated platelet interaction with polymorphonuclear leukocytes (an approximately 1.2-fold increase) in vitro. In conclusion, it can be suggested that MPO can interact with and activate platelets, which can induce priming of platelets, rather than the classical robust activation of platelets. This can contribute to the

  8. In vitro function of random donor platelets stored for 7 days in composol platelet additive solution

    Directory of Open Access Journals (Sweden)

    Gupta Ashish

    2011-01-01

    Full Text Available Background and Aim: Platelets are routinely isolated from whole blood and stored in plasma for 5 days. The present study was done to assess the in vitro function of random donor platelets stored for 7 days in composol platelet additive solution at 22°C. Materials and Methods: The study sample included 30 blood donors of both sex in State Blood Bank, CSM Medical University, Lucknow. Random donor platelets were prepared by platelet rich plasma method. Whole blood (350 ml was collected in anticoagulant Citrate Phosphate Dextrose Adenine triple blood bags. Random donor platelets were stored for 7 days at 22°C in platelet incubators and agitators, with and without additive solution. Results: Platelet swirling was present in all the units at 22°C on day 7, with no evidence of bacterial contamination. Comparison of the mean values of platelet count, platelet factor 3, lactate dehydrogenase, pH, glucose and platelet aggregation showed no significant difference in additive solution, whereas platelet factor 3, glucose and platelet aggregation showed significant difference (P < 0.001 on day 7 without additive solution at 22°C. Conclusion: Our study infers that platelet viability and aggregation were best maintained within normal levels on day 7 of storage in platelet additive solution at 22°C. Thus, we may conclude that in vitro storage of random donor platelets with an extended shelf life of 7 days using platelet additive solution may be advocated to improve the inventory of platelets.

  9. Evidence of platelet activation in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Alexander J Steven

    2008-06-01

    Full Text Available Abstract Objective A fatality in one multiple sclerosis (MS patient due to acute idiopathic thrombocytopenic purpura (ITP and a near fatality in another stimulated our interest in platelet function abnormalities in MS. Previously, we presented evidence of platelet activation in a small cohort of treatment-naive MS patients. Methods In this report, 92 normal controls and 33 stable, untreated MS patients were studied. Platelet counts, measures of platelet activation [plasma platelet microparticles (PMP, P-selectin expression (CD62p, circulating platelet microaggragtes (PAg], as well as platelet-associated IgG/IgM, were carried out. In addition, plasma protein S activity was measured. Results Compared to controls, PMP were significantly elevated in MS (p Conclusion Platelets are significantly activated in MS patients. The mechanisms underlying this activation and its significance to MS are unknown. Additional study of platelet activation and function in MS patients is warranted.

  10. Platelets and infection — an emerging role of platelets in viral infection

    Directory of Open Access Journals (Sweden)

    Alice eAssinger

    2014-12-01

    Full Text Available Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia and several platelet function disorders increase the risk of bleeding. Over the last years more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients.Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favours platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen-antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies.All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count, but also shapes immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation and platelet-mediated modulations of innate and adaptive immune responses.

  11. Platelets and infection - an emerging role of platelets in viral infection.

    Science.gov (United States)

    Assinger, Alice

    2014-01-01

    Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis) are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia) and several platelet function disorders increase the risk of bleeding. Over the last years, more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients. Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favors platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen-antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies. All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count but also shape immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation, and platelet-mediated modulations of innate and adaptive immune responses.

  12. CD8+ T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia

    Science.gov (United States)

    Qiu, Jihua; Liu, Xuena; Li, Xiaoqing; Zhang, Xu; Han, Panpan; Zhou, Hai; Shao, Linlin; Hou, Yu; Min, Yanan; Kong, Zhangyuan; Wang, Yawen; Wei, Yu; Liu, Xinguang; Ni, Heyu; Peng, Jun; Hou, Ming

    2016-01-01

    In addition to antiplatelet autoantibodies, CD8+ cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8+ T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8+ T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8+ T cells than those without cytotoxicity and controls. In vitro, CD8+ T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8+ splenocytes were used. Platelets co-cultured with these CD8+ splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8+ splenocytes. These findings suggest that CD8+ T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP. PMID:27321376

  13. CD8(+) T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia.

    Science.gov (United States)

    Qiu, Jihua; Liu, Xuena; Li, Xiaoqing; Zhang, Xu; Han, Panpan; Zhou, Hai; Shao, Linlin; Hou, Yu; Min, Yanan; Kong, Zhangyuan; Wang, Yawen; Wei, Yu; Liu, Xinguang; Ni, Heyu; Peng, Jun; Hou, Ming

    2016-01-01

    In addition to antiplatelet autoantibodies, CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8(+) T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8(+) T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8(+) T cells than those without cytotoxicity and controls. In vitro, CD8(+) T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8(+) splenocytes were used. Platelets co-cultured with these CD8(+) splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8(+) splenocytes. These findings suggest that CD8(+) T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP. PMID:27321376

  14. An overview of platelet indices and methods for evaluating platelet function in thrombocytopenic patients

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Hvas, Anne-Mette; Nybo, Mads

    2014-01-01

    in thrombocytopenia. Flow cytometry, platelet aggregometry and platelet secretion tests are used to diagnose specific platelet function defects. The flow cytometric activation marker P-selectin and surface coverage by the Cone and Plate[let] analyser™ predict bleeding in selected thrombocytopenic populations...

  15. Prolonged platelet preservation by transient metabolic suppression

    NARCIS (Netherlands)

    Badlou, Bahram Alamdary

    2006-01-01

    Introduction: Different clinical studies have shown that transfusion of stored platelets results in better haemostasis in patients with thrombocytopenia with and without a platelet function defect. Objectives: Current preservation procedures aim to optimally preserve the metabolic status of platel

  16. Establishing biological reference intervals for novel platelet parameters (immature platelet fraction, high immature platelet fraction, platelet distribution width, platelet large cell ratio, platelet-X, plateletcrit, and platelet distribution width and their correlations among each other

    Directory of Open Access Journals (Sweden)

    Ritesh Sachdev

    2014-01-01

    Full Text Available Aims: This study aims to establish biological reference interval for novel platelet parameters. Settings and Design: A total of 945 healthy individuals, age ranges from 18 to 64 years (881 males and 64 females coming for voluntary blood donation from June to August 2012 (3 months were enrolled after exclusion of rejection criteria. Materials and Methods: The samples were assayed by running in complete blood count + reticulocyte mode on the Sysmex XE-2100 hematology analyzer and the reference interval for the population was calculated using Clinical and Laboratory Standards Institute guidelines. Statistical analysis used: Tests were performed using SPSS (Statistical Product and Service Solutions , developed by IBM corporation, version 13. Student t test and pearsons correlation analysis were also used. Results: The normal range for various parameters was platelet count: 150-520 × 10 3 /cu mm, immature platelet fraction (IPF: 0.3-8.7%, platelet distribution width (PDW: 8.3-25.0 fL, mean platelet volume (MPV: 8.6-15.5 fL, plateletcrit (PCT: 0.15-0.62%, high immature platelet fraction (H-IPF: 0.1-2.7%, platelet large cell ratio (P-LCR: 11.9-66.9% and platelet-X (PLT-X (ch: 11.0-22.0. Negative correlation was observed between platelet count (r = −0.468 to r = −0.531; P < 0.001 and PCT (r = −0.080 to r = −0.235; P < 0.05 to P < 0.001 with IPF, PDW, MPV, H-IPF, P-LCR, and platelet-X. IPF/H-IPF showed a positive correlation among them and also with PDW, MPV, P-LCR, platelet-X (r = +0.662 to r = +0.925; P < 0.001. Conclusions: These novel platelet parameters offer newer avenues in research and clinical use. Establishing biological reference interval for different platelet parameters would help determine true high and low values and help guide treatment decisions.

  17. New treatment for low platelets.

    Science.gov (United States)

    Grodeck, B

    1995-01-01

    The Food and Drug Administration (FDA) recently approved WinRho SD, a new treatment for immune thrombocytopenic purpura (ITP). A clinical trial in children with acute ITP found that WinRho SD is as effective as IVIG or prednisone, but less expensive and dramatically easier to administer. WinRho SD is the first polyclonal antibody product shown to increase platelets in ITP patients. Platelets usually rise within one to two days and peak within seven to fourteen days after initial therapy. On average, platelet levels are maintained for approximately thirty days. Each year, 50,000 people nationally suffer from ITP as a complication of HIV infection, while another 18,000 manifest the disease as a primary condition. PMID:11362579

  18. Platelets: Covert Regulators of Lymphatic Development

    OpenAIRE

    Bertozzi, Cara C.; Hess, Paul R.; Kahn, Mark L.

    2010-01-01

    The field of platelet biology has rapidly expanded beyond the classical role of platelets in preventing blood loss and orchestrating clot formation. Despite the lack of transcriptional ability of these anuclear cell fragments, platelet function is now thought to encompass such diverse contexts as tissue repair, immune activation, primary tumor formation, and metastasis. Recent studies from multiple groups have turned the spotlight on an exciting new role for platelets in the formation of lymp...

  19. Molecular Basis Linking Platelet to Inflammation

    Institute of Scientific and Technical Information of China (English)

    马丽萍

    2010-01-01

    @@ Introduction Blood platelets not only play an important role in hemostasis and thrombosis,but increasing evidence show that they participate in the induction of inflammation.Firstly,platelets contain and release cytokines and immune mediators.And platelets are able to modulate and regulate the function of surrounding cells by adhesion molecules or by the release of various factors.

  20. Image analysis of blood platelets adhesion.

    Science.gov (United States)

    Krízová, P; Rysavá, J; Vanícková, M; Cieslar, P; Dyr, J E

    2003-01-01

    Adhesion of blood platelets is one of the major events in haemostatic and thrombotic processes. We studied adhesion of blood platelets on fibrinogen and fibrin dimer sorbed on solid support material (glass, polystyrene). Adhesion was carried on under static and dynamic conditions and measured as percentage of the surface covered with platelets. Within a range of platelet counts in normal and in thrombocytopenic blood we observed a very significant decrease in platelet adhesion on fibrin dimer with bounded active thrombin with decreasing platelet count. Our results show the imperative use of platelet poor blood preparations as control samples in experiments with thrombocytopenic blood. Experiments carried on adhesive surfaces sorbed on polystyrene showed lower relative inaccuracy than on glass. Markedly different behaviour of platelets adhered on the same adhesive surface, which differed only in support material (glass or polystyrene) suggest that adhesion and mainly spreading of platelets depends on physical quality of the surface. While on polystyrene there were no significant differences between fibrin dimer and fibrinogen, adhesion measured on glass support material markedly differed between fibrin dimer and fibrinogen. We compared two methods of thresholding in image analysis of adhered platelets. Results obtained by image analysis of spreaded platelets showed higher relative inaccuracy than results obtained by image analysis of platelets centres and aggregates.

  1. Dengue platelets meet Sir Arthur Conan Doyle.

    Science.gov (United States)

    Bray, Paul F

    2013-11-14

    In this issue of Blood, Hottz et al provide compelling evidence that dengue virus (DV) induces (1) platelet synthesis of interleukin-1b (IL-1b); (2) platelet-derived IL-1b–containing microvesicles (MVs) that increase vascular permeability; and (3) DV-triggered inflammasome activation in platelets.

  2. Pooled platelet concentrates: an alternative to single donor apheresis platelets?

    Science.gov (United States)

    Pietersz, R N I

    2009-10-01

    Three types of platelet concentrates (PC) are compared: PC either processed with the platelet-rich plasma (PRP) or the Buffy coat (BC) method from whole blood units and PC obtained by apheresis. Leuko-reduction (LR) pre-storage is advocated to improve quality of the PC during storage and reduce adverse reactions in recipients. Standardization of methods allow preparation of PC with comparable yields of approximately 400 x 10(9) platelets in pooled non-LR-PRP, approximately 370 x 10(9) in pooled LR-BC-PC and in LR apheresis PC the number of platelets can be targeted on 350 x 10(9) or more with devices of various manufacturers. While viral transmission can be prevented by outstanding laboratory tests, the risk of bacterial contamination should be reduced by improved arm disinfection, deviation of the first 20-30 ml of blood and culture or rapid detection assays of the PC pre-issue. In a large prospective multicenter trial no significant difference was observed between cultures of apheresis PC (n = 15,198): 0.09% confirmed positive units versus 0.06% in pooled BC-PC (n = 37,045), respectively. Though platelet activation as measured by CD62 expression may differ in vitro in PC obtained with various apheresis equipment, and also between PC processed with the two whole blood methods there is scarce literature about the clinical impact of these findings. In conclusion the final products of LR-PC derived from whole blood or obtained by apheresis can be comparable, provided the critical steps of the processing method are identified and covered and the process is in control.

  3. Platelets: crossroads of immunity and hemostasis.

    Science.gov (United States)

    Jenne, Craig N

    2014-07-31

    In this issue of Blood, Koupenova and colleagues report that platelets express functional TOLL-like receptor 7 (TLR7) and contribute to host survival during viral infection. Through a series of experiments utilizing mice deficient for TLR7 together with adoptive transfer of wild-type platelets, Koupenova et al demonstrate that platelets specifically respond to viral analogs and intact virus, leading to platelet activation and binding to various leukocyte subsets. Perhaps most importantly, this platelet activation appears absolutely essential for host survival during infection with some viral pathogens such as encephalomyocarditis virus (EMCV).

  4. Evidence that platelet buoyant density, but not size, correlates with platelet age in man

    Energy Technology Data Exchange (ETDEWEB)

    Mezzano, D.; Hwang, K.; Catalano, P.; Aster, R.H.

    1981-01-01

    Following infusion of 51Cr-labeled autologous platelets into normal subjects, high-density (HD) and low-density (LD) platelet cohorts were isolated by prolonged centrifugation in isosmotic arabino-galactan (Stractan). Specific radio-activity of LD platelets declined rapidly post-infusion (T1/2 . 1.5 days), but specific radioactivity of HD platelets remained constant or increased over a 3--4-day period and gradually declined for 6--7 days thereafter. These differences were exaggerated when platelet cohorts enriched in LD or HD cells by slow centrifugation in high-density albumin were labeled and transfused. Mean survival of a platelet cohort enriched with HD cells was significantly (P less than 0.02) shorter (7.73 days) than that of a cohort enriched with LD cells (9.33) days). In normal subjects treated with aspirin, capacity for thromboxane synthesis was regained more rapidly (P less than 0.05) in LD than in HD platelets. HD and LD platelets differed only slightly in mean volume (HD platelets . 7.57 mu3, LD platelets . 6.87 mu3, 0.05 less than P less than 0.01). We believe the most logical interpretation of these findings is that under normal conditions in man, newly formed platelets are less dense on the average than total platelets and become more dense as they age in the circulation. Thus, specific radioactivity of LD platelets declines rapidly as these platelets move into a more dense compartment and are replaced by newly formed, unlabelled cells; specific radioactivity of HD platelets remains constant or increases as labelled platelets enter this compartment in numbers equal to or greater than the number leaving it at the end of their life span. The similarity in mean volumes of LD and HD platelets suggests that platelet size is unrelated to platelet age under normal conditions.

  5. Platelets: bridging hemostasis, inflammation, and immunity.

    Science.gov (United States)

    Jenne, C N; Urrutia, R; Kubes, P

    2013-06-01

    Although the function of platelets in the maintenance of hemostasis has been studied in great detail, more recent evidence has highlighted a central role for platelets in the host inflammatory and immune responses. Platelets by virtue of their large numbers and their ability to rapidly release a broad spectrum of immunomodulatory cytokines, chemokines, and other mediators act as circulating sentinels. Upon detection of a pathogen, platelets quickly activate and begin to drive the ensuing inflammatory response. Platelets have the ability to directly modulate the activity of neutrophils (phagocytosis, oxidative burst), endothelium (adhesion molecule and chemokine expression), and lymphocytes. Due to their diverse array of adhesion molecules and preformed chemokines, platelets are able to adhere to leukocytes and facilitate their recruitment to sites of tissue damage or infection. Furthermore, platelets directly participate in the capture and sequestration of pathogens within the vasculature. Platelet-neutrophil interactions are known to induce the release of neutrophil extracellular traps (NETs) in response to either bacterial or viral infection, and platelets have been shown to internalize pathogens, sequestering them in engulfment vacuoles. Finally, emerging data indicate that platelets also participate in the host immune response by directly killing infected cells. This review will highlight the central role platelets play in the initiation and modulation of the host inflammatory and immune responses.

  6. Calpain Activator Dibucaine Induces Platelet Apoptosis

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2011-03-01

    Full Text Available Calcium-dependent calpains are a family of cysteine proteases that have been demonstrated to play key roles in both platelet glycoprotein Ibα shedding and platelet activation and altered calpain activity is associated with thrombotic thrombocytopenic purpura. Calpain activators induce apoptosis in several types of nucleated cells. However, it is not clear whether calpain activators induce platelet apoptosis. Here we show that the calpain activator dibucaine induced several platelet apoptotic events including depolarization of the mitochondrial inner transmembrane potential, up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation and phosphatidylserine exposure. Platelet apoptosis elicited by dibucaine was not affected by the broad spectrum metalloproteinase inhibitor GM6001. Furthermore, dibucaine did not induce platelet activation as detected by P-selectin expression and PAC-1 binding. However, platelet aggregation induced by ristocetin or α-thrombin, platelet adhesion and spreading on von Willebrand factor were significantly inhibited in platelets treated with dibucaine. Taken together, these data indicate that dibucaine induces platelet apoptosis and platelet dysfunction.

  7. Role of platelets in allergic airway inflammation.

    Science.gov (United States)

    Idzko, Marco; Pitchford, Simon; Page, Clive

    2015-06-01

    Increasing evidence suggests an important role for platelets and their products (e.g., platelet factor 4, β-thromboglobulin, RANTES, thromboxane, or serotonin) in the pathogenesis of allergic diseases. A variety of changes in platelet function have been observed in patients with asthma, such as alterations in platelet secretion, expression of surface molecules, aggregation, and adhesion. Moreover, platelets have been found to actively contribute to most of the characteristic features of asthma, including bronchial hyperresponsiveness, bronchoconstriction, airway inflammation, and airway remodeling. This review brings together the current available data from both experimental and clinical studies that have investigated the role of platelets in allergic airway inflammation and asthma. It is anticipated that a better understanding of the role of platelets in the pathogenesis of asthma might lead to novel promising therapeutic approaches in the treatment of allergic airway diseases. PMID:26051948

  8. Platelet Function Tests in Bleeding Disorders.

    Science.gov (United States)

    Lassila, Riitta

    2016-04-01

    Functional disorders of platelets can involve any aspect of platelet physiology, with many different effects or outcomes. These include platelet numbers (thrombocytosis or thrombocytopenia); changes in platelet production or destruction, or capture to the liver (Ashwell receptor); altered adhesion to vascular injury sites and/or influence on hemostasis and wound healing; and altered activation or receptor functions, shape change, spreading and release reactions, procoagulant and antifibrinolytic activity. Procoagulant membrane alterations, and generation of thrombin and fibrin, also affect platelet aggregation. The above parameters can all be studied, but standardization and quality control of assay methods have been limited despite several efforts. Only after a comprehensive clinical bleeding assessment, including family history, information on drug use affecting platelets, and exclusion of coagulation factor, and tissue deficits, should platelet function testing be undertaken to confirm an abnormality. Current diagnostic tools include blood cell counts, platelet characteristics according to the cell counter parameters, peripheral blood smear, exclusion of pseudothrombocytopenia, whole blood aggregometry (WBA) or light transmission aggregometry (LTA) in platelet-rich plasma, luminescence, platelet function analysis (PFA-100) for platelet adhesion and deposition to collagen cartridges under blood flow, and finally transmission electron microscopy to exclude rare structural defects leading to functional deficits. The most validated test panels are included in WBA, LTA, and PFA. Because platelets are isolated from their natural environment, many simplifications occur, as circulating blood and interaction with vascular wall are omitted in these assays. The target to reach a highly specific platelet disorder diagnosis in routine clinical management can be exhaustive, unless needed for genetic counseling. The elective overall assessment of platelet function disorder

  9. In vitro function of random donor platelets stored for 7 days in composol platelet additive solution

    Directory of Open Access Journals (Sweden)

    Gupta Ashish

    2011-01-01

    Full Text Available Background and Aim: Platelets are routinely isolated from whole blood and stored in plasma for 5 days. This study was done to assess the in vitro function of random donor platelets stored for 7 days in composol platelet additive solution at 22°C. Materials and Methods: The study sample included 30 blood donors of both sex in State Blood Bank, C S M Medical University, Lucknow. Random donor platelets were prepared by the platelet-rich plasma method. Whole blood (350 ml was collected in anticoagulant Citrate Phosphate Dextrose Adenine triple blood bags. Random donor platelets were stored for 7 days at 22°C in platelet incubators and agitators with and without additive solution. Results: Platelet swirling was present in all the units at 22°C on day 7 with no evidence of bacterial contamination. Comparison of the mean values of platelet count, platelet factor 3, lactate dehydrogenase, pH, glucose and platelet aggregation showed no significant difference in additive solution while platelet factor 3, glucose and platelet aggregation showed significant difference (P < 0.001 on day 7 without additive solution at 22°C. Conclusion: Our study infers that the platelet viability and aggregation were the best maintained within normal levels on day 7 of storage in platelet additive solution at 22°C. Thus, we may conclude that in vitro storage of random donor platelets with an extended shelf life of 7 days using platelet additive solution may be advocated to improve the inventory of platelets.

  10. Platelet receptors and patient responses: The contributions of Professor Stan Heptinstall to platelet research.

    Science.gov (United States)

    Clemetson, Kenneth J

    2015-01-01

    Stan Heptinstall's contributions to platelet research covered organising meetings at the national and European level as well as starting and maintaining the journal "Platelets". The major part of his research addressed problems of inhibition of platelet receptors and the effects of this on patient health. In particular, the effects of P2Y12 inhibitors on patients with acute cardiovascular problems were a major focus. Other studies included the effects of feverfew (Tanacetum parthenium) extracts on platelets, of direct anti-IIb/IIIa receptor (αIIbβ3) inhibitors and of prostanoids on platelet function. Recently, methods for assessing the effectiveness of platelet inhibition were investigated.

  11. Effects of Physical (Inactivity on Platelet Function

    Directory of Open Access Journals (Sweden)

    Stefan Heber

    2015-01-01

    Full Text Available As platelet activation is closely related to the liberation of growth factors and inflammatory mediators, platelets play a central role in the development of CVD. Virtually all cardiovascular risk factors favor platelet hyperreactivity and, accordingly, also physical (inactivity affects platelet function. Within this paper, we will summarize and discuss the current knowledge on the impact of acute and habitual exercise on platelet function. Although there are apparent discrepancies regarding the reported effects of acute, strenuous exercise on platelet activation, a deeper analysis of the available literature reveals that the applied exercise intensity and the subjects’ cardiorespiratory fitness represent critical determinants for the observed effects. Consideration of these factors leads to the summary that (i acute, strenuous exercise can lead to platelet activation, (ii regular physical activity and/or physical fitness diminish or prevent platelet activation in response to acute exercise, and (iii habitual physical activity and/or physical fitness also favorably modulate platelet function at physical rest. Notably, these effects of exercise on platelet function show obvious similarities to the well-recognized relation between exercise and the risk for cardiovascular events where vigorous exercise transiently increases the risk for myocardial infarction and a physically active lifestyle dramatically reduces cardiovascular mortality.

  12. Platelet MicroRNAs: An Overview.

    Science.gov (United States)

    Dahiya, Neetu; Sarachana, Tewarit; Vu, Long; Becker, Kevin G; Wood, William H; Zhang, Yongqing; Atreya, Chintamani D

    2015-10-01

    MicroRNAs (miRNAs) are short ~22-nucleotide noncoding RNA that have been found to influence the expression of many genes and cellular processes by either repressing translation or degrading messenger RNA transcripts. Platelet miRNA expression has been shown to be perturbed during ex vivo storage of platelets and in platelet-associated disorders. Although bioinformatics-based miRNA target predictions have been established, direct experimental validation of the role of miRNAs in platelet biology has been rather slow. Target prediction studies are, nonetheless, valuable in directing the design of appropriate experiments to test specific miRNA:messenger RNA interactions relevant to the underlying mechanisms of platelet function in general and in disease as well as in ex vivo storage-associated "storage lesions," a collective term used to include physiologic, biochemical, and morphologic changes that occur in stored platelets. This brief review will focus on emerging human platelet miRNA studies to emphasize their potential role relevant to transfusion medicine field in terms of regulating platelet signaling pathways, markers of platelet associated disorders, and remote impactors of gene expression (intercellular biomodulators) as well as potential platelet quality markers of storage and pathogen reduction treatments.

  13. Reference intervals for platelet aggregation assessed by multiple electrode platelet aggregometry

    DEFF Research Database (Denmark)

    Rubak, Peter; Villadsen, Kirsten; Hvas, Anne-Mette

    2012-01-01

    Abstract Introduction Analyses of platelet aggregation in hirudin whole blood using Multiplate® was validated. Reference intervals for the most commonly used agonists were established, and the association between platelet aggregation, age, gender and haematological values was analysed. Material...

  14. Laboratory testing for platelet function disorders.

    Science.gov (United States)

    Israels, S J

    2015-05-01

    Platelet function testing is both complex and labor intensive. A stepwise approach to the evaluation of patients with suspected platelet disorders will optimize the use of laboratory resources, beginning with an appropriate clinical evaluation to determine whether the bleeding is consistent with a defect of primary hemostasis. Bleeding assessment tools, evaluation of platelet counts, and review of peripheral blood cell morphology can aid the initial assessment. For patients requiring further laboratory testing, platelet aggregometry, secretion assays, and von Willebrand factor assays are the most useful next steps and will direct further specialized testing including flow cytometry, electron microscopy, and molecular diagnostics. Guidelines and recommendations for standardizing platelet function testing, with a particular focus on light transmission aggregometry, are available and can provide a template for clinical laboratories in establishing procedures that will optimize diagnosis and assure quality results. This review outlines an approach to platelet function testing and reviews testing methods available to clinical laboratories.

  15. Does bipolar pacemaker current activate blood platelets?

    DEFF Research Database (Denmark)

    Gjesdal, Grunde; Hansen, Annebirthe Bo; Brandes, Axel

    2009-01-01

    platelets and muscle cells contain actin and myosin filaments, and both cells are activated following calcium influx. Muscle cells open their calcium channels and contract when exposed to an electric current. Current through a bipolar pacemaker lead will expose a small volume of blood, including platelets...... to the pacemaker can. METHODS: Platelet-rich plasma was prepared from two healthy subjects. Platelet reactivity to the agonist ADP was tested in paired samples in an aggregometer in a case/control setup. RESULTS: Eighteen of 46 tested pairs of platelet-rich plasma showed increased reactivity in the paced sample......; 26 were unchanged while two showed decreased reactivity in the paced sample. Using a two-sided sign test, the null hypothesis was rejected (P = 0.0004). CONCLUSIONS: The study demonstrates increased reactivity to ADP in platelets exposed in vitro to stimulation by pacemaker current. The clinical...

  16. Autologous Platelet Gel: An In Vitro Analysis of Platelet-Rich Plasma Using Multiple Cycles

    OpenAIRE

    Christensen, Kevin; Vang, See; Brady, Chad; Isler, Jack; Allen, Keith; Anderson, John; Holt, David

    2006-01-01

    Autologous platelet gel (APG) has become an expanding field for perfusionists. By mixing platelet-rich plasma (PRP) with thrombin and calcium, platelet gel is prepared and used in many surgical settings. There are many devices used to produce PRP. This study evaluates the Medtronic Magellan Autologous Platelet Separator. The purpose of this study was to show that processing two cycles of the same syringe could reduce the amount of blood required to produce a specific volume of PRP. Three 60-m...

  17. Differential Dynamics of Platelet Contact and Spreading

    OpenAIRE

    Lee, Dooyoung; Fong, Karen P.; King, Michael R.; Brass, Lawrence F.; Hammer, Daniel A.

    2012-01-01

    Platelet spreading is critical for hemostatic plug formation and thrombosis. However, the detailed dynamics of platelet spreading as a function of receptor-ligand adhesive interactions has not been thoroughly investigated. Using reflection interference contrast microscopy, we found that both adhesive interactions and PAR4 activation affect the dynamics of platelet membrane contact formation during spreading. The initial growth of close contact area during spreading was controlled by the combi...

  18. Extending The Shelf Life Of Blood Platelets

    Science.gov (United States)

    Surgenor, Douglas M.

    1988-01-01

    New method of storing human blood platelets extends vitality for transfusions. Packaged as suspension in sterile liquid in plastic blood bags. Each bag placed between pair of plastic grids, and rubberbands placed around sandwich thus formed to hold together. Stored upright in open air or in container through which air pumped at rate of at least 45 L/min. Ensures that platelets receive ample oxygen and expiratory carbon dioxide form platelets removed before pH drops to harmful levels.

  19. The effects of selective serotonin reuptake inhibitors on platelet function in whole blood and platelet concentrates.

    Science.gov (United States)

    Reikvam, Anne-Grete; Hustad, Steinar; Reikvam, Håkon; Apelseth, Torunn Oveland; Nepstad, Ina; Hervig, Tor Audun

    2012-01-01

    Several studies report that patients who are treated with selective serotonin reuptake inhibitors (SSRIs) for depression may have increased risk of bleeding, particularly from the gastrointestinal tract. This may be related to low intraplatelet serotonin concentrations. Several blood banks do not store platelets from donors using SSRIs for transfusion, although the possible effects of SSRIs on platelet storage are not documented. We conducted a case-control pilot study of apheresis platelet concentrates prepared from donors using SSRIs (n=8) and from donors without medication (n=10). The platelet concentrates were stored for 5 days. Light transmission aggregometry (LTA), thrombelastography (TEG), and flow cytometric analyses were preformed for in vitro measurements of platelet function. Platelet function and platelet serotonin content were investigated in whole blood and in platelet concentrates stored for up to 5 days. LTA, TEG, and flow cytometric analysis of glycoprotein expression did not reveal any significant differences between the two groups. All 18 platelet concentrates performed well according to the standards set for platelet quality in relation to transfusion. Blood donors using SSRIs had significantly lower platelet serotonin compared to blood donors without medication. The results from our pilot study indicate that platelets from donors using SSRIs may be suitable for transfusion after storage for 5 days, but further laboratory and clinical studies are necessary to confirm this.

  20. Platelet aggregation and quality control of platelet concentrates produced in the Amazon Blood Bank

    Directory of Open Access Journals (Sweden)

    Maria José Dantas Coêlho

    2011-01-01

    Full Text Available BACKGROUND: The study of platelet aggregation is essential to assess in vitro platelet function by different platelet activation pathways. OBJECTIVE: To assess aggregation and biochemical parameters of random platelet concentrates produced at the Fundação HEMOAM using the quality control tests defined by law. METHODS: Whole blood samples from 80 donors and the respective platelet concentrate units were tested. Platelet concentrates were tested (platelet count, aggregation and pH on days 1, 3 and 5 of storage. Additionally a leukocyte count was done only on day 1 and microbiological tests on day 5 of storage. Collagen and adenosine diphosphate were used as inducing agonists for platelet aggregation testing. RESULTS: Donor whole blood had normal aggregation (aggregation with adenosine diphosphate = 67% and with collagen = 78%. The median aggregation in platelet concentrates with adenosine diphosphate was low throughout storage (18% on day 1, 7% on day 3 and 6% on day 5 and the median aggregation with collagen was normal only on day 1 and low thereafter (54.4% on day 1, 20.5% on day 3 and 9% on day 5. CONCLUSION: Although the results were within the norms required by law, platelet concentrates had low aggregation rates. We suggest the inclusion of a functional assessment test for the quality control of platelet concentrates for a more effective response to platelet replacement therapy.

  1. Platelets: covert regulators of lymphatic development.

    Science.gov (United States)

    Bertozzi, Cara C; Hess, Paul R; Kahn, Mark L

    2010-12-01

    The field of platelet biology has rapidly expanded beyond the classical role of platelets in preventing blood loss and orchestrating clot formation. Despite the lack of transcriptional ability of these anuclear cell fragments, platelet function is now thought to encompass such diverse contexts as tissue repair, immune activation, primary tumor formation, and metastasis. Recent studies from multiple groups have turned the spotlight on an exciting new role for platelets in the formation of lymphatic vessels during embryonic development. Genetic experiments demonstrate that podoplanin, a transmembrane protein expressed on lymphatic endothelial cells, engages the platelet C-type lectin-like receptor 2 (CLEC-2) when exposed to blood, leading to SYK-SLP-76-dependent platelet activation. When components of this pathway are disrupted, aberrant vascular connections form, resulting in blood-lymphatic mixing. Furthermore, platelet-null embryos manifest identical blood-lymphatic mixing. The identification of platelets as the critical cell type mediating blood-lymphatic vascular separation raises new questions in our understanding of lymphatic development and platelet biology. PMID:21071706

  2. Platelet cytoskeleton and its hemostatic role.

    Science.gov (United States)

    Cerecedo, Doris

    2013-12-01

    Upon vascular injury, platelets adhere to the exposed extracellular matrix, which triggers the platelet activation and aggregation to form a hemostatic plug to seal the wound. All of these events involve dramatic changes in shape because of the cytoskeleton reorganization. The versatility of the cytoskeleton's main elements depends on the biochemical nature of the elements, as well as on the associated proteins that confer multiple functions within the cell. The list of these associated proteins grows actively, increasing our knowledge concerning the complexity of platelet cytoskeleton machinery. The present review evidences the recently described platelet proteins that promote characteristic modifications in their cytoskeleton organization, with special focus on the dystrophin-glycoprotein complex.

  3. Platelet interactions with viruses and parasites.

    Science.gov (United States)

    Alonso, Ana Lopez; Cox, Dermot

    2015-01-01

    While the interactions between Gram-positive bacteria and platelets have been well characterized, there is a paucity of data on the interaction between other pathogens and platelets. However, thrombocytopenia is a common feature with many infections especially viral hemorrhagic fever. The little available data on these interactions indicate a similarity with bacteria-platelet interactions with receptors such as FcγRIIa and Toll-Like Receptors (TLR) playing key roles with many pathogens. This review summarizes the known interactions between platelets and pathogens such as viruses, fungi and parasites.

  4. The Study of Platelet Volume Indices in Platelet Aphaeresis Procedure: An Experience Of 271 Platelet Aphaeresis Procedures

    Directory of Open Access Journals (Sweden)

    Arpit C Patel

    2015-09-01

    Full Text Available Background: Platelet activity can be assessed by platelet volume indices like MPV, PDW and P-LCR. Aim: To develop an approach in blood bank professional, a habit of looking at platelet indices in hematology analyzer report of aphaeresis donors and QC samples of platelet aphaeresis products. Methods and materials: A retrospective data analysis was done for 271 platelet aphaeresis procedures conducted on CS3000 plus with AMS cell separator, Fenwal, USA and COM.TEC, Fresenius Kabi, Germany. Samples of the donors were collected before aphaeresis and 1 to 2 ml sample from each bag was collected in the satellite pouch attached to bag and analysis was done on day 0 and day 7. Platelet parameters were measured on automated hematology analyzers SYSMEX KX-21 and Horiba Micros 60.Statistical analysis: Statistical analysis was done by calculating and lsquo;r value' and a paired t test at 95 % confidence interval. A P value of <0.05 was taken as significant. Results: The mean platelet yield was 3.39+/-0.88 x 1011/unit. The platelet yield correlated negatively with MPV, PDW and PLCR (r value -0.224, -0.045 and -0.159 respectively for correlation between MPV, PDW and PLCR with the yield, P <0.0001.The mean values of PVI of SDP were significantly smaller than that of donor pre-donation samples (paired t test P value < 0.05.The size of stored single donor platelet on day 7 were significantly larger than that of day 0 (P value < 0.05. Conclusion: The platelet indices are useful to study - selectively smaller platelet separation by automated cell separators, storage lesions and yield prediction. [Natl J Med Res 2015; 5(3.000: 207-210

  5. Platelet function alterations in dengue are associated with plasma leakage

    NARCIS (Netherlands)

    Michels, M.; Alisjahbana, B.; Groot, P.G. de; Indrati, A.R.; Fijnheer, R.; Puspita, M.; Dewi, I.M.; Wijer, L. van de; Boer, E.M. de; Roest, M.; Ven, A.J. van der; Mast, Q. de

    2014-01-01

    Severe dengue is characterised by thrombocytopenia, plasma leakage and bleeding. Platelets are important for preservation of endothelial integrity. We hypothesised that platelet activation with secondary platelet dysfunction contribute to plasma leakage. In adult Indonesian patients with acute dengu

  6. Platelet-rich fibrin: Evolution of a second-generation platelet concentrate

    Directory of Open Access Journals (Sweden)

    Sunitha Raja V

    2008-01-01

    Full Text Available Platelet-rich plasma (PRP is a platelet concentrate that has been used widely to accelerate soft-tissue and hard-tissue healing. The preparation of PRP has been described by several authors. Platelet-rich fibrin (PRF was first described by Choukroun et al. in France. It has been referred to as a second-generation platelet concentrate, which has been shown to have several advantages over traditionally prepared PRP. Its chief advantages include ease of preparation and lack of biochemical handling of blood, which makes this preparation strictly autologous. This article describes the evolution of this novel platelet concentrate, referred to as PRF.

  7. Novel agents for anti-platelet therapy

    Directory of Open Access Journals (Sweden)

    Ji Xuebin

    2011-11-01

    Full Text Available Abstract Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti-platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12 receptor antagonists (e.g., clopidogrel, prasugrel, cangrelor, and ticagrelor are being used in clinical settings for their pronounced protective effects. The new protease-activated receptor antagonists, vorapaxar and atopaxar, potentially decrease the risk of ischemic events without significantly increasing the rate of bleeding. Some other new anti-platelet drugs undergoing clinical trials have also been introduced. Indeed, the number of new anti-platelet drugs is increasing. Consequently, the efficacy of these anti-platelet agents in actual patients warrants scrutiny, especially in terms of the hemorrhagic risks. Hopefully, new selective platelet inhibitors with high anti-thrombotic efficiencies and low hemorrhagic side effects can be developed.

  8. Fractal and Euclidean descriptors of platelet shape.

    Science.gov (United States)

    Kraus, Max-Joseph; Neeb, Heiko; Strasser, Erwin F

    2014-01-01

    Platelet shape change is a dynamic membrane surface process that exhibits remarkable morphological heterogeneity. Once the outline of an irregular shape is identified and segmented from a digital image, several mathematical descriptors can be applied to numerical characterize the irregularity of the shapes surface. 13072 platelet outlines (PLO) were segmented automatically from 1928 microscopic images using a newly developed algorithm for the software product Matlab R2012b. The fractal dimension (FD), circularity, eccentricity, area and perimeter of each PLO were determined. 972 PLO were randomly assigned for computer-assisted manual measurement of platelet diameter as well as number, width and length of filopodia per platelet. FD can be used as a surrogate parameter for determining the roughness of the PLO and circularity can be used as a surrogate to estimate the number and length of filopodia. The relationship between FD and perimeter of the PLO reveals the existence of distinct groups of platelets with significant structural differences which may be caused by platelet activation. This new method allows for the standardized continuous numerical classification of platelet shape and its dynamic change, which is useful for the analysis of altered platelet activity (e.g. inflammatory diseases, contact activation, drug testing). PMID:24224894

  9. Titanium surface hydrophilicity enhances platelet activation.

    Science.gov (United States)

    Alfarsi, Mohammed A; Hamlet, Stephen M; Ivanovski, Saso

    2014-01-01

    Titanium implant surface modification is a key strategy used to enhance osseointegration. Platelets are the first cells that interact with the implant surface whereupon they release a wide array of proteins that influence the subsequent healing process. This study therefore investigated the effect of titanium surface modification on the attachment and activation of human platelets. The surface characteristics of three titanium surfaces: smooth (SMO), micro-rough (SLA) and hydrophilic micro-rough (SLActive) and the subsequent attachment and activation of platelets following exposure to these surfaces were determined. The SLActive surface showed the presence of significant nanoscale topographical features. While attached platelets appeared to be morphologically similar, significantly fewer platelets attached to the SLActive surface compared to both the SMO and SLA surfaces. The SLActive surface however induced the release of the higher levels of chemokines β-thromboglobulin and platelet factor 4 from platelets. This study shows that titanium surface topography and chemistry have a significant effect on platelet activation and chemokine release.

  10. The origin and function of platelet glycosyltransferases

    DEFF Research Database (Denmark)

    Wandall, Hans H; Rumjantseva, Viktoria; Sørensen, Anne Louise Tølbøll;

    2012-01-01

    Platelets are megakaryocyte subfragments that participate in hemostatic and host defense reactions and deliver pro- and anti-angiogenic factors throughout the vascular system. Platelets are anucleated cells and lack a complex secretory apparatus with distinct Golgi/endoplasmic reticulum compartme...

  11. Performance evaluation of PL-11 platelet analyzer

    Institute of Scientific and Technical Information of China (English)

    张有涛

    2013-01-01

    Objective To evaluate and report the performance of PL-11 platelet analyzer. Methods Intravenous blood sam-ples anticoagulated with EDTA-K2 and sodium citrate were tested by the PL-11 platelet analyzer to evaluate the intra-assay and interassay coefficient of variation(CV),

  12. Platelets and fibrin strands during clot retraction.

    Science.gov (United States)

    Morgenstern, E; Korell, U; Richter, J

    1984-03-15

    The ultrastructure of platelet fibrin contacts (PFC) and the course of the strands was investigated in serial sections of retracted clots with the help of specimen tilting. We found after retraction in a test tube as well as under isometric conditions in the resonance thrombograph, after HARTERT, an uniform type of PFC. The side to side contact between platelet surface and fibrin strands displayed a 15 nm wide space which was bridged of 10 - 30 nm by filamentary structure. In each case the direction of the fibrin strands changed on contact with the platelet surface (bend). These bends recurred if the adhering strands ran over a longer distance on the platelet surface. The bends can be explained by non-directional movement of the platelets or of their pseudopodia. Microfilaments (actomyosin) which run straight in pseudopodia and often also twisted in the platelet body support this assumption. The described mechanism - contact of the thrombin activated platelets with fibrin strands and simultaneous nondirectional movement of the platelets which bind further sections of the adhering strands to their surface - would provide a more satisfactory explanation for the retraction of the clot to 1/10 of its original volume. PMID:6539004

  13. Fractal and Euclidean descriptors of platelet shape.

    Science.gov (United States)

    Kraus, Max-Joseph; Neeb, Heiko; Strasser, Erwin F

    2014-01-01

    Platelet shape change is a dynamic membrane surface process that exhibits remarkable morphological heterogeneity. Once the outline of an irregular shape is identified and segmented from a digital image, several mathematical descriptors can be applied to numerical characterize the irregularity of the shapes surface. 13072 platelet outlines (PLO) were segmented automatically from 1928 microscopic images using a newly developed algorithm for the software product Matlab R2012b. The fractal dimension (FD), circularity, eccentricity, area and perimeter of each PLO were determined. 972 PLO were randomly assigned for computer-assisted manual measurement of platelet diameter as well as number, width and length of filopodia per platelet. FD can be used as a surrogate parameter for determining the roughness of the PLO and circularity can be used as a surrogate to estimate the number and length of filopodia. The relationship between FD and perimeter of the PLO reveals the existence of distinct groups of platelets with significant structural differences which may be caused by platelet activation. This new method allows for the standardized continuous numerical classification of platelet shape and its dynamic change, which is useful for the analysis of altered platelet activity (e.g. inflammatory diseases, contact activation, drug testing).

  14. Platelets as immune cells in infectious diseases.

    Science.gov (United States)

    Speth, Cornelia; Löffler, Jürgen; Krappmann, Sven; Lass-Flörl, Cornelia; Rambach, Günter

    2013-11-01

    Platelets have been shown to cover a broad range of functions. Besides their role in hemostasis, they have immunological functions and thus participate in the interaction between pathogens and host defense. Platelets have a broad repertoire of receptor molecules that enable them to sense invading pathogens and infection-induced inflammation. Consequently, platelets exert antimicrobial effector mechanisms, but also initiate an intense crosstalk with other arms of the innate and adaptive immunity, including neutrophils, monocytes/macrophages, dendritic cells, B cells and T cells. There is a fragile balance between beneficial antimicrobial effects and detrimental reactions that contribute to the pathogenesis, and many pathogens have developed mechanisms to influence these two outcomes. This review aims to highlight aspects of the interaction strategies between platelets and pathogenic bacteria, viruses, fungi and parasites, in addition to the subsequent networking between platelets and other immune cells, and the relevance of these processes for the pathogenesis of infections.

  15. Breaking the mold: transcription factors in the anucleate platelet and platelet-derived microparticles

    Directory of Open Access Journals (Sweden)

    Katie L Lannan

    2015-02-01

    Full Text Available Platelets are small anucleate blood cells derived from megakaryocytes. In addition to their pivotal roles in hemostasis, platelets are the smallest, yet most abundant, immune cell and regulate inflammation, immunity, and disease progression. Although platelets lack DNA, and thus no functional transcriptional activities, they are nonetheless rich sources of RNAs, possess an intact spliceosome, and are thus capable of synthesizing proteins. Previously, it was thought that platelet RNAs and translational machinery were remnants from the megakaryocyte. We now know that the initial description of platelets as cellular fragments is an antiquated notion, as mounting evidence suggests otherwise. Therefore, it is reasonable to hypothesize that platelet transcription factors are not vestigial remnants from megakaryoctes, but have important, if only partly understood functions. Proteins play multiple cellular roles to minimize energy expenditure for maximum cellular function; thus, the same can be expected for transcription factors. In fact, numerous transcription factors have non-genomic roles, both in platelets and in nucleated cells. Our lab and others have discovered the presence and nongenomic roles of transcription factors in platelets, such as the nuclear factor kappa β (NFκB family of proteins and peroxisome proliferator activated receptor gamma (PPARγ. In addition to numerous roles in regulating platelet activation, functional transcription factors can be transferred to vascular and immune cells through platelet microparticles. This method of transcellular delivery of key immune molecules may be a vital mechanism by which platelet transcription factors regulate inflammation and immunity. At the very least, platelets are an ideal model cell to dissect out the nongenomic roles of transcription factors in nucleated cells. There is abundant evidence to suggest that transcription factors in platelets play key roles in regulating inflammatory and

  16. Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis.

    Science.gov (United States)

    Koupenova, Milka; Vitseva, Olga; MacKay, Christopher R; Beaulieu, Lea M; Benjamin, Emelia J; Mick, Eric; Kurt-Jones, Evelyn A; Ravid, Katya; Freedman, Jane E

    2014-07-31

    Viral infections have been associated with reduced platelet counts, the biological significance of which has remained elusive. Here, we show that infection with encephalomyocarditis virus (EMCV) rapidly reduces platelet count, and this response is attributed to platelet Toll-like receptor 7 (TLR7). Platelet-TLR7 stimulation mediates formation of large platelet-neutrophil aggregates, both in mouse and human blood. Intriguingly, this process results in internalization of platelet CD41-fragments by neutrophils, as assessed biochemically and visualized by microscopy, with no influence on platelet prothrombotic properties. The mechanism includes TLR7-mediated platelet granule release, translocation of P-selectin to the cell surface, and a consequent increase in platelet-neutrophil adhesion. Viral infection of platelet-depleted mice also led to increased mortality. Transfusion of wild-type, TLR7-expressing platelets into TLR7-deficient mice caused a drop in platelet count and increased survival post EMCV infection. Thus, this study identifies a new link between platelets and their response to single-stranded RNA viruses that involves activation of TLR7. Finally, platelet-TLR7 stimulation is independent of thrombosis and has implications to the host immune response and survival.

  17. Quality assessment of platelet concentrates prepared by platelet rich plasma-platelet concentrate, buffy coat poor-platelet concentrate (BC-PC and apheresis-PC methods

    Directory of Open Access Journals (Sweden)

    Singh Ravindra

    2009-01-01

    Full Text Available Background: Platelet rich plasma-platelet concentrate (PRP-PC, buffy coat poor-platelet concentrate (BC-PC, and apheresis-PC were prepared and their quality parameters were assessed. Study Design: In this study, the following platelet products were prepared: from random donor platelets (i platelet rich plasma - platelet concentrate (PRP-PC, and (ii buffy coat poor- platelet concentrate (BC-PC and (iii single donor platelets (apheresis-PC by different methods. Their quality was assessed using the following parameters: swirling, volume of the platelet concentrate, platelet count, WBC count and pH. Results: A total of 146 platelet concentrates (64 of PRP-PC, 62 of BC-PC and 20 of apheresis-PC were enrolled in this study. The mean volume of PRP-PC, BC-PC and apheresis-PC was 62.30±22.68 ml, 68.81±22.95 ml and 214.05±9.91 ml and ranged from 22-135 ml, 32-133 ml and 200-251 ml respectively. The mean platelet count of PRP-PC, BC-PC and apheresis-PC was 7.6±2.97 x 1010/unit, 7.3±2.98 x 1010/unit and 4.13±1.32 x 1011/unit and ranged from 3.2-16.2 x 1010/unit, 0.6-16.4 x 1010/unit and 1.22-8.9 x 1011/unit respectively. The mean WBC count in PRP-PC (n = 10, BC-PC (n = 10 and apheresis-PC (n = 6 units was 4.05±0.48 x 107/unit, 2.08±0.39 x 107/unit and 4.8±0.8 x 106/unit and ranged from 3.4 -4.77 x 107/unit, 1.6-2.7 x 107/unit and 3.2 - 5.2 x 106/unit respectively. A total of 26 units were analyzed for pH changes. Out of these units, 10 each were PRP-PC and BC-PC and 6 units were apheresis-PC. Their mean pH was 6.7±0.26 (mean±SD and ranged from 6.5 - 7.0 and no difference was observed among all three types of platelet concentrate. Conclusion: PRP-PC and BC-PC units were comparable in terms of swirling, platelet count per unit and pH. As expected, we found WBC contamination to be less in BC-PC than PRP-PC units. Variation in volume was more in BC-PC than PRP-PC units and this suggests that further standardization is required for preparation of BC

  18. Platelet thrombosis in cardiac-valve prostheses

    International Nuclear Information System (INIS)

    The contribution of platelets and clotting factors in thrombosis on cardiovascular prostheses had been quantified with several tracers. Thrombus formation in vivo could be measured semiquantitatively in animal models and patients with indium-111, Technetium-99m labeled platelets, iodine-123, iodine-131 labeled fibrinogen, and In-111 and Tc-99m labeled antibody to the fibrinogen-receptor on the platelet- membrane, or fibrin. The early studies demonstrated that certain platelet-inhibitors, e.g. sulfinpyrazone, aspirin or aspirin- persantine increased platelet survival time with mechanical valves implanted in the baboon model and patients. Thrombus localization by imaging is possible for large thrombus on thrombogenic surface of prosthesis in the acute phase. The majority of thrombus was found in the sewing ring (Dacron) in the acute phase in both the mechanical and tissue valves. The amount of retained thrombus in both mechanical and tissue valves in our one-day study in the dog model was similar (< 1% if injected In-111 platelets = 5 billion platelets). As the fibrous ingrowth covered the sewing ring, the thrombus formation decreased significantly. Only a small amount of thrombus was found on the leaflets at one month in both the dog and calf models. 38 refs., 9 figs., 5 tabs

  19. Platelet thrombosis in cardiac-valve prostheses

    Energy Technology Data Exchange (ETDEWEB)

    Dewanjee, M.K.

    1989-01-01

    The contribution of platelets and clotting factors in thrombosis on cardiovascular prostheses had been quantified with several tracers. Thrombus formation in vivo could be measured semiquantitatively in animal models and patients with indium-111, Technetium-99m labeled platelets, iodine-123, iodine-131 labeled fibrinogen, and In-111 and Tc-99m labeled antibody to the fibrinogen-receptor on the platelet- membrane, or fibrin. The early studies demonstrated that certain platelet-inhibitors, e.g. sulfinpyrazone, aspirin or aspirin- persantine increased platelet survival time with mechanical valves implanted in the baboon model and patients. Thrombus localization by imaging is possible for large thrombus on thrombogenic surface of prosthesis in the acute phase. The majority of thrombus was found in the sewing ring (Dacron) in the acute phase in both the mechanical and tissue valves. The amount of retained thrombus in both mechanical and tissue valves in our one-day study in the dog model was similar (< 1% if injected In-111 platelets = 5 billion platelets). As the fibrous ingrowth covered the sewing ring, the thrombus formation decreased significantly. Only a small amount of thrombus was found on the leaflets at one month in both the dog and calf models. 38 refs., 9 figs., 5 tabs.

  20. Analysis of aggregation of platelets in thrombosis

    Science.gov (United States)

    Ahuja, Suresh

    Platelets are key players in thrombus formation by first rolling over collagen bound von Willebrand factor followed by formation of a stable interaction with collagen. The first adhered platelets bind additional platelets until the whole injury is sealed off by a platelet aggregate. The coagulation system stabilizes the formed platelet plug by creating a tight fibrin network, and then wound contraction takes place because of morphological changes in platelets. Coagulation takes place by platelet activation and aggregation mainly through fibrinogen polymerization into fibrin fibers. The process includes multiple factors, such as thrombin, plasmin, and local shear-rate which regulate and control the process. Coagulation can be divided into two pathways: the intrinsic pathway and the extrinsic pathway. The intrinsic pathway is initiated by the exposure of a negatively charged. It is able to activate factor XII, using a complex reaction that includes prekallikrein and high-molecular-weight kininogen as cofactors.. Thrombin is the final enzyme that is needed to convert fibrinogen into fibrin. The extrinsic pathway starts with the exposure of tissue factor to the circulating blood, which is the major initiator of coagulation. There are several feedback loops that reinforce the coagulation cascade, resulting in large amounts of thrombin. It is dependent on the presence of pro-coagulant surfaces of cells expressing negatively charged phospholipids--which include phosphatidylserine (PS)--on their outer membrane. PS-bearing surfaces are able to increase the efficiency of the reactions by concentrating and co-localizing coagulation factors.. Aggregation of platelets are analyzed and compared to adhesion of platelet to erythrocyte and to endothelial cells. This abstract is replacing MAR16-2015-020003.

  1. Platelets: at the nexus of antimicrobial defence.

    Science.gov (United States)

    Yeaman, Michael R

    2014-06-01

    Platelets have traditionally been viewed as fragmentary mediators of coagulation. However, recent molecular and cellular evidence suggests that they have multiple roles in host defence against infection. From first-responders that detect pathogens and rapidly deploy host-defence peptides, to beacons that recruit and enhance leukocyte functions in the context of infection, to liaisons that facilitate the T cell-B cell crosstalk that is required in adaptive immunity, platelets represent a nexus at the intersection of haemostasis and antimicrobial host defence. In this Review, I consider recent insights into the antimicrobial roles of platelets, which are mediated both directly and indirectly to integrate innate and adaptive immune responses to pathogens.

  2. Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs

    OpenAIRE

    Jungbluth, P; Grassmann, JP; Thelen, S; Wild, M.; Sager, M; Windolf, J.; M Hakimi

    2014-01-01

    In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP) preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of a...

  3. Platelet endothelial cell adhesion molecule-1 signaling inhibits the activation of human platelets

    OpenAIRE

    Cicmil, Milenko; Stevens, Jo; Leduc, Mireille; Bon, Cassian; Gibbins, Jonathan M.

    2002-01-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a 130-kd transmembrane glycoprotein and a member of the growing family of receptors with immunoreceptor tyrosine-based inhibitory motifs (ITIMs). PECAM-1 is expressed on platelets, certain T cells, monocytes, neutrophils, and vascular endothelial cells and is involved in a range of cellular processes, though the role of PECAM-1 in platelets is unclear. Cross-linking of PECAM-1 results in phosphorylation of the ITIM allowing the r...

  4. Platelet-rich fibrin matrix for facial plastic surgery.

    Science.gov (United States)

    Sclafani, Anthony P; Saman, Masoud

    2012-05-01

    Platelets are known primarily for their role in hemostasis, but there is increasing interest in the effect of platelets on wound healing. Platelet isolates such as platelet-rich plasma have been advocated to enhance and accelerate wound healing. This article describes the use of a novel preparation, platelet-rich fibrin matrix (PRFM), for facial plastic surgery applications such as volume augmentation, fat transfer supplementation, and as an adjunct to open surgical procedures.

  5. Evaluation of platelet thromboxane radioimmunoassay method to measure platelet life-span: Comparison with /sup 111/indium-platelet method

    Energy Technology Data Exchange (ETDEWEB)

    Vallabhajosula, S.; Machac, J.; Badimon, L.; Lipszyc, H.; Goldsmith, S.J.; Fuster, V.

    1985-05-01

    The platelet activation during radiolabeling in vitro with Cr-51 and In-111 may affect the platelet life-span (PLS) in vivo. A new RIA method to measure PLS is being evaluated. Aspirin inhibits platelet thromboxane (TxA/sub 2/) by acetylating cyclooxygenase. The time required for the TxA/sub 2/ levels to return towards control values depends on the rate of new platelets entering circulation and is a measure of PLS. A single dose of aspirin (150mg) was given to 5 normal human subjects. Blood samples were collected for 2 days before aspirin and daily for 10 days. TxA/sub 2/ production in response to endogenous thrombin was studied by allowing 1 ml blood sample to clot at 37/sup 0/C for 90 min. Serum TxB/sub 2/ (stable breakdown product of Tx-A/sub 2/) levels determined by RIA technique. The plot of TxB/sub 2/ levels (% control) against time showed a gradual increase. The PLS calculated by linear regression analysis assuming a 2-day lag period before cyclooxygenase recovery is 9.7 +- 2.37. In the same 5 subjects, platelets from a 50ml blood sample were labeled with /sup 111/In-tropolone in 2 ml autologous plasma. Starting at 1 hr after injection of labeled platelets, 10 blood samples were obtained over a 8 day period. The PLS calculated based on a linear regression analysis is 10.2 +. 1.4. The PLS measured from the rate of platelet disappearance from circulation and the rate of platelet regeneration into circulation are quite comparable in normal subjects. TxA/sub 2/ regeneration RIA may provide a method to measure PLS without administering radioactivity to patient.

  6. Platelets and erythrocyte-bound platelets bind infectious HIV-1 in plasma of chronically infected patients.

    Science.gov (United States)

    Beck, Zoltan; Jagodzinski, Linda L; Eller, Michael A; Thelian, Doris; Matyas, Gary R; Kunz, Anjali N; Alving, Carl R

    2013-01-01

    Chronic HIV-1 infection is associated with persistent viremia in most patients, but it remains unclear how free virus may survive the potential hostile effects of plasma. We investigated whether sites might exist on the surfaces of circulating blood cells for protection of infectious HIV-1 particles. Red blood cells (RBC) either from blood of uninfected normal individuals, or from blood obtained without EDTA from chronically infected HIV-1 patients, invariably contained a small number of RBC having attached platelets as determined by flow cytometry, light microscopy, and immunofluorescence microscopy. After mixing normal RBC with platelet-rich plasma, discrete populations of RBC, platelets, and complexes of platelets attached to RBC were purified by fluorescence-activated cell sorting. Upon incubation of purified cells or platelets with HIV-1 followed by washing and co-incubation with CD4-positive peripheral blood mononuclear cells (PBMC), platelets, and platelet-RBC complexes, but not platelet-free RBC, caused infection of PBMC. Infection was prevented by pre-treating the platelet-RBC complexes with EDTA. Plasma and RBC (comprising a RBC/platelet-RBC mixture) from chronically infected patients with low viral loads were also co-incubated with PBMC ex vivo to determine the presence of infectious HIV-1. All freshly isolated plasmas from the HIV-1-infected donors, obtained in the absence of anticoagulant, were noninfectious. Interestingly, the RBC from most of the patients caused cell-cell infection of PBMC that was prevented by stripping the RBC with EDTA. A monoclonal antibody to DC-SIGN partially inhibited cell-cell HIV-1 infection of PBMC by normal RBC pre-incubated with platelets and HIV-1. We conclude: (a) platelet-free EDTA-free plasma from chronically infected HIV-1 patients, although containing viral RNA, is an environment that lacks detectable infectious HIV-1; (b) platelets and platelet-RBC complexes, but not purified RBC, bind infectious HIV-1; (c) DC

  7. Platelets and erythrocyte-bound platelets bind infectious HIV-1 in plasma of chronically infected patients.

    Directory of Open Access Journals (Sweden)

    Zoltan Beck

    Full Text Available Chronic HIV-1 infection is associated with persistent viremia in most patients, but it remains unclear how free virus may survive the potential hostile effects of plasma. We investigated whether sites might exist on the surfaces of circulating blood cells for protection of infectious HIV-1 particles. Red blood cells (RBC either from blood of uninfected normal individuals, or from blood obtained without EDTA from chronically infected HIV-1 patients, invariably contained a small number of RBC having attached platelets as determined by flow cytometry, light microscopy, and immunofluorescence microscopy. After mixing normal RBC with platelet-rich plasma, discrete populations of RBC, platelets, and complexes of platelets attached to RBC were purified by fluorescence-activated cell sorting. Upon incubation of purified cells or platelets with HIV-1 followed by washing and co-incubation with CD4-positive peripheral blood mononuclear cells (PBMC, platelets, and platelet-RBC complexes, but not platelet-free RBC, caused infection of PBMC. Infection was prevented by pre-treating the platelet-RBC complexes with EDTA. Plasma and RBC (comprising a RBC/platelet-RBC mixture from chronically infected patients with low viral loads were also co-incubated with PBMC ex vivo to determine the presence of infectious HIV-1. All freshly isolated plasmas from the HIV-1-infected donors, obtained in the absence of anticoagulant, were noninfectious. Interestingly, the RBC from most of the patients caused cell-cell infection of PBMC that was prevented by stripping the RBC with EDTA. A monoclonal antibody to DC-SIGN partially inhibited cell-cell HIV-1 infection of PBMC by normal RBC pre-incubated with platelets and HIV-1. We conclude: (a platelet-free EDTA-free plasma from chronically infected HIV-1 patients, although containing viral RNA, is an environment that lacks detectable infectious HIV-1; (b platelets and platelet-RBC complexes, but not purified RBC, bind infectious HIV

  8. Anticoagulation inhibits tumor cell-mediated release of platelet angiogenic proteins and diminishes platelet angiogenic response.

    Science.gov (United States)

    Battinelli, Elisabeth M; Markens, Beth A; Kulenthirarajan, Rajesh A; Machlus, Kellie R; Flaumenhaft, Robert; Italiano, Joseph E

    2014-01-01

    Platelets are a reservoir for angiogenic proteins that are secreted in a differentially regulated process. Because of the propensity for clotting, patients with malignancy are often anticoagulated with heparin products, which paradoxically offer a survival benefit by an unknown mechanism. We hypothesized that antithrombotic agents alter the release of angiogenesis regulatory proteins from platelets. Our data revealed that platelets exposed to heparins released significantly decreased vascular endothelial growth factor (VEGF) in response to adenosine 5'-diphosphate or tumor cells (MCF-7 cells) and exhibited a decreased angiogenic potential. The releasate from these platelets contained decreased proangiogenic proteins. The novel anticoagulant fondaparinux (Xa inhibitor) demonstrated a similar impact on the platelet angiogenic potential. Because these anticoagulants decrease thrombin generation, we hypothesized that they disrupt signaling through the platelet protease-activated receptor 1 (PAR1) receptor. Addition of PAR1 antagonists to platelets decreased VEGF release and angiogenic potential. Exposure to a PAR1 agonist in the presence of anticoagulants rescued the angiogenic potential. In vivo studies demonstrated that platelets from anticoagulated patients had decreased VEGF release and angiogenic potential. Our data suggest that the mechanism by which antithrombotic agents increase survival and decrease metastasis in cancer patients is through attenuation of platelet angiogenic potential. PMID:24065244

  9. The expression levels of platelet adhesive receptors in PRP derived platelet concentrates during storage

    Directory of Open Access Journals (Sweden)

    Fatemeh Nassaji

    2016-04-01

    Full Text Available Background: Major platelet adhesive receptors that contribute significantly to thrombus formation include platelet receptor glycoprotein Ibα (GPIbα of the GPIb-IX-V complex and platelet glycoprotein VI (GPVI. GPIbα plays a crucial role in platelet tethering to sub-endothelial matrix, which initiates thrombus formation at arterial shear rates, whereas GPVI is critically involved in platelets firm adhesion to the site of injury regardless of shear condition. During storage, platelets experience some changes that deleteriously affect the expression levels of platelet receptors, which in turn can alter platelet functional behaviors. Considering the important roles of GPIbα and GPVI in platelet adhesion, it seems that any dramatic changes in the expression levels of these receptors can influence adhesive function of transfused platelets. Thereby examining GPIbα and GPVI expression during the storage of platelet concentrates may provide some useful information about the functional quality of these products after transfusion. Methods: In our experimental study, 5 PRP-platelet concentrates were randomly obtained from Iranian Blood Transfusion Organization (IBTO. All the platelet products met the standard quality assessment based on AABB (American Association of Blood Banks guidelines. Washed platelets were subjected to flowcytometry analysis for the evaluation of GPIbα and GPVI receptor expression in day 1, 3 and 5 after storage. Data were presented as mean fluorescence intensity (MFI and analyzed by Kruskal-Wallis test with Dunn’s multiple comparison test. Results: The GPIbα expression on first day (MFI=86±5.9 was reduced three days after storage (MFI= 69±6.9. The expression levels continued to reduce until day 5 in which GPIbα expression was markedly decreased to (MFI= 61±7.7 (P= 0.0094. GPVI expression on the days 1, 3 and 5 after storage were 20.6±3.3, 24±2.5 and 14±4.9, respectively. The results showed a significant decrease of

  10. Understanding platelet generation from megakaryocytes: implications for in vitro-derived platelets.

    Science.gov (United States)

    Sim, Xiuli; Poncz, Mortimer; Gadue, Paul; French, Deborah L

    2016-03-10

    Platelets are anucleate cytoplasmic discs derived from megakaryocytes that circulate in the blood and have major roles in hemostasis, thrombosis, inflammation, and vascular biology. Platelet transfusions are required to prevent the potentially life-threatening complications of severe thrombocytopenia seen in a variety of medical settings including cancer therapy, trauma, and sepsis. Platelets used in the clinic are currently donor-derived which is associated with concerns over sufficient availability, quality, and complications due to immunologic and/or infectious issues. To overcome our dependence on donor-derived platelets for transfusion, efforts have been made to generate in vitro-based platelets. Work in this area has advanced our understanding of the complex processes that megakaryocytes must undergo to generate platelets both in vivo and in vitro. This knowledge has also defined the challenges that must be overcome to bring in vitro-based platelet manufacturing to a clinical reality. This review will focus on our understanding of committed megakaryocytes and platelet release in vivo and in vitro, and how this knowledge can guide the development of in vitro-derived platelets for clinical application.

  11. Donor demographic and laboratory predictors of single donor platelet yield

    Directory of Open Access Journals (Sweden)

    R. Arun

    2013-10-01

    Full Text Available Background: Platelet transfusions are essential to prevent morbidity and mortality in patients who are severely thrombocytopenic and are at risk of spontaneous bleeding. Platelets are currently obtained either by fractionation of whole blood or by platelet apheresis. The quality of single donor platelets (SDP in terms of yield influences platelet recovery in the recipient and allows prolonging intervals between transfusions. Material and Methods: Donor demographic and laboratory data were analyzed prior to performing plateletpheresis to identify donor factors that influence platelet yield. The study was conducted on 130 healthy, first-time plateletpheresis donors over a period of 4 years. The plateletpheresis procedures were performed using Fresenius Kabi COM.TEC and Hemonetics MCS plus separator. A relationship between pre-donation donor variables and yield of platelets was studied using the Pearson correlation. Results: The mean platelet yield was 3.160.62x1011 per unit. A positive correlation was observed between platelet yield and pre-donation platelet count, body mass index (BMI; Kg/m2 of the donor, while a negative correlation was observed between age and the platelet yield. Conclusion: Donor pre-donation platelet count, BMI and donor age influence platelet yield. Young healthy donors with a high platelet count and better BMI can give a better platelet yield in the SDP.

  12. Mapuche Herbal Medicine Inhibits Blood Platelet Aggregation

    Directory of Open Access Journals (Sweden)

    Susan Skanderup Falkenberg

    2012-01-01

    Full Text Available 12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM and collagen- (2.0 μg/mL induced aggregations in human blood. These four species in respective extracts (in brackets were Blechnum chilense (MeOH, Luma apiculata (H2O, Amomyrtus luma (DCM : MeOH 1 : 1 and Cestrum parqui (DCM : MeOH 1 : 1. The platelet aggregating inhibitory effects of A. luma (DCM : MeOH 1 : 1, and L. apiculata (H2O were substantial and confirmed by inhibition of platelet surface activation markers.

  13. Physiopathology of blood platelets and development of platelet substitutes. Progress report, August 1, 1975--July 31, 1976

    Energy Technology Data Exchange (ETDEWEB)

    Baldini, M G

    1976-04-28

    Progress is reported on studies on the physiology of blood platelets in thrombocytopenic patients and rabbits. Methods for the detection of platelet antibodies and the preservation of platelets in vitro were investigated. Studies on the effect of low doses of x irradiation (up to 1000 R) on platelet function indicate that platelets exposed to ionizing radiation have increased functional activity. A list is included of publications that report the results of the studies in detail.

  14. Dengue virus binding and replication by platelets.

    Science.gov (United States)

    Simon, Ayo Y; Sutherland, Michael R; Pryzdial, Edward L G

    2015-07-16

    Dengue virus (DENV) infection causes ∼200 million cases of severe flulike illness annually, escalating to life-threatening hemorrhagic fever or shock syndrome in ∼500,000. Although thrombocytopenia is typical of both mild and severe diseases, the mechanism triggering platelet reduction is incompletely understood. As a probable initiating event, direct purified DENV-platelet binding was followed in the current study by quantitative reverse transcription-polymerase chain reaction and confirmed antigenically. Approximately 800 viruses specifically bound per platelet at 37°C. Fewer sites were observed at 25°C, the blood bank storage temperature (∼350 sites), or 4°C, known to attenuate virus cell entry (∼200 sites). Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and heparan sulfate proteoglycan were implicated as coreceptors because only the combination of anti-DC-SIGN and low-molecular-weight heparin prevented binding. Interestingly, at 37°C and 25°C, platelets replicated the positive sense single-stranded RNA genome of DENV by up to ∼4-fold over 7 days. Further time course experiments demonstrated production of viral NS1 protein, which is known to be highly antigenic in patient serum. The infectivity of DENV intrinsically decayed in vitro, which was moderated by platelet-mediated generation of viable progeny. This was shown using a transcription inhibitor and confirmed by freeze-denatured platelets being incapable of replicating the DENV genome. For the first time, these data demonstrate that platelets directly bind DENV saturably and produce infectious virus. Thus, expression of antigen encoded by DENV is a novel consideration in the pathogen-induced thrombocytopenia mechanism. These results furthermore draw attention to the possibility that platelets may produce permissive RNA viruses in addition to DENV.

  15. Anaphylactic actions of platelet-activating factor.

    OpenAIRE

    Stimler, N. P.; Bloor, C. M.; Hugli, T E; Wykle, R. L.; McCall, C E; O'Flaherty, J. T.

    1981-01-01

    Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) is a potent inducer of systemic anaphylactoid reactions in animals. It was found to be similarly potent in contracting smooth muscle of guinea pig ileum and lung and in enhancing vascular permeability when injected subcutaneously into these animals. This factor, therefore, possesses in vitro and in vivo bioactions that resemble those of C3a and C5a anaphylatoxins. However, platelet-activating factor induces a slowl...

  16. Influence of mental stress on platelet bioactivity

    OpenAIRE

    Koudouovoh-Tripp, Pia; Sperner-Unterweger, Barbara

    2012-01-01

    It is well established that various mental stress conditions contribute, or at least influence, underlying pathophysiological mechanisms in somatic, as well as in psychiatric disorders; blood platelets are supposed to represent a possible link in this respect. The anculeated platelets are the smallest corpuscular elements circulating in the human blood. They display different serotonergic markers which seem to reflect the central nervous serotonin metabolism. They are known as main effectors ...

  17. [The role of blood platelets in infections].

    Science.gov (United States)

    Micota, Bartłomiej; Sadowska, Beata; Różalska, Barbara

    2015-05-17

    Platelets are primarily associated with their main function, hemostasis, although it is known that these cells also exhibit biological activity in cancer progression, inflammation and infectious processes. During infection platelets, due to the expression of specific receptors - Toll-like receptors (TLRs) - which recognize molecular patterns associated with pathogens - pathogen-associated molecular patterns (PAMPs) - are activated by the presence of microorganism components and/or substances released from damaged cells/tissue. Further antimicrobial activity of platelets is based on their capacity for phagocytosis, generation of reactive oxygen species (ROS), and the synthesis, storage and release of proteins/peptides with antimicrobial activity. Another mechanism of platelet action is their immunomodulatory activity. It is based mainly on the ability to secrete chemotactic factors allowing the accumulation of professional immunocompetent cells at the site of infection, thus enhancing the effective eradication of an infectious agent. In chronic infections, platelets, due to release of numerous growth factors and various cytokines, support mechanisms of acquired immunity. They accelerate the maturation of dendritic cells, stimulate B cells to be immunoglobulin-producing plasma cells and potentiate the activity of T cells. Unfortunately, in certain situations (the existence of specific risk factors) the interaction of microorganisms with activated platelets may also be the cause of pathology within the cardiovascular system.

  18. The genetics of normal platelet reactivity.

    Science.gov (United States)

    Kunicki, Thomas J; Nugent, Diane J

    2010-10-14

    Genetic and environmental factors contribute to a substantial variation in platelet function seen among normal persons. Candidate gene association studies represent a valiant effort to define the genetic component in an era where genetic tools were limited, but the single nucleotide polymorphisms identified in those studies need to be validated by more objective, comprehensive approaches, such as genome-wide association studies (GWASs) of quantitative functional traits in much larger cohorts of more carefully selected normal subjects. During the past year, platelet count and mean platelet volume, which indirectly affect platelet function, were the subjects of GWAS. The majority of the GWAS signals were located to noncoding regions, a consistent outcome of all GWAS to date, suggesting a major role for mechanisms that alter phenotype at the level of transcription or posttranscriptional modifications. Of 15 quantitative trait loci associated with mean platelet volume and platelet count, one located at 12q24 is also a risk locus for coronary artery disease. In most cases, the effect sizes of individual quantitative trait loci are admittedly small, but the results of these studies have led to new insight into regulators of hematopoiesis and megakaryopoiesis that would otherwise be unapparent and difficult to define. PMID:20610812

  19. Glycoprotein biosynthesis by human normal platelets

    International Nuclear Information System (INIS)

    Incorporation of radioactive Man, Gal, Fuc, Glc-N, and NANA into washed human normal platelets and endogenous glycoproteins has been found. Both parameters were time dependent. Analysis of hydrolyzed labeled glycoproteins by paper chromatography revealed that the radioactive monosaccharide incubated with the platelets had not been converted into other sugars. Acid hydrolysis demonstrates the presence of a glycosidic linkage. All the effort directed to the demonstration of the existence of a lipid-sugar intermediate in intact human platelets yielded negative results for Man and Glc-N used as precursors. The incorporation of these sugars into glycoproteins is insensitive to bacitracin, suggesting no involvement of lipid-linked saccharides in the synthesis of glycoproteins in human blood platelets. The absence of inhibition of the glycosylation process in the presence of cycloheximide suggests that the sugars are added to proteins present in the intact platelets. These results support the contention that glycoprotein biosynthesis in human blood platelets observed under our experimental conditions is effected through direct sugar nucleotide glycosylation

  20. Treatment of osteochondral injuries with platelet gel

    Directory of Open Access Journals (Sweden)

    Marcus Vinicius Danieli

    2014-12-01

    Full Text Available OBJECTIVES: Treatments for injured articular cartilage have not advanced to the point that efficient regeneration is possible. However, there has been an increase in the use of platelet-rich plasma for the treatment of several orthopedic disorders, including chondral injuries. Our hypothesis is that the treatment of chondral injuries with platelet gel results in higher-quality repair tissue after 180 days compared with chondral injuries not treated with gel. METHODS: A controlled experimental laboratory study was performed on 30 male rabbits to evaluate osteochondral injury repair after treatment with or without platelet gel. Osteochondral injuries were surgically induced in both knees of each rabbit at the medial femoral condyle. The left knee injury was filled with the platelet gel, and the right knee was not treated. Microscopic analysis of both knee samples was performed after 180 days using a histological grading scale. RESULTS: The only histological evaluation criterion that was not significantly different between treatments was metachromasia. The group that was treated with platelet gel exhibited superior results in all other criteria (cell morphology, surface regularity, chondral thickness and repair tissue integration and in the total score. CONCLUSION: The repair tissue was histologically superior after 180 days in the study group treated with platelet gel compared with the group of untreated injuries.

  1. Assessment of quality of platelets preserved in plasma and platelet additive solution: A Malaysian experience

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    Munirah Binti Mokhtar

    2016-01-01

    Full Text Available Background: A use of platelet additives solution (PAS improves storage conditions so as to give increased shelf life to platelets and to maintain hemostatic function. Objective: The present study was aimed to compare in vitro quality of platelet rich plasma (PRP-derived platelet concentrate (PC during extended period of storage in plasma and in additive solution (Composol PS and Fresenius. Study Design: Randomized 19 PCs each were used in the study for plasma and PAS as the storage medium. The measurement parameters, including pH, total white blood cell (WBC count, total platelet count, and platelet activation rate, were studied on day 1, day 5, and day 8 of the storage period. The sterility test was carried out on the eighth day of storage. Results: pH of PC suspended in PAS was significantly lower as compared to that in plasma (P < 0.001 for all the three days of sampling. The WBC count, both in plasma and in PAS, showed an acceptable values of being <0.2 Χ 10 9 /unit during the storage period. Platelet count in PAS was higher as compared to that in plasma, though it was not statistically significant. While both the groups showed increased platelet activation rate during the storage, the PCs suspended in PAS showed significantly higher platelet activation rate (p0.001. Results from sterility test showed no bacterial growth in the PCs in both the groups. Conclusion: Most parameters studied on platelet storage in suspending medium of native plasma and PAS remained well within the acceptable limits. However, the pH values and platelet activation rate significantly differed in PAS as compared with plasma.

  2. Strange bedfellows: the Bundestag’s free vote on pre-implantation genetic diagnosis (PGD reveals how Germany’s restrictive bioethics legislation is shaped by a Christian Democratic/New Left issue-coalition

    Directory of Open Access Journals (Sweden)

    Kai Arzheimer

    2015-08-01

    Full Text Available Germany’s bioethical legislation presents a puzzle: given structural factors, the country should be at the forefront of reproductive medicine, but its embryology regime remains one of the strictest in Western Europe. Past research has linked this fact to an unusual coalition of Christian and New Left groups, which both draw a connection from modern embryology to eugenics under the Nazis. In this article, the workings of this alleged alliance are demonstrated at the micro-level for the first time. The behaviour of individual MPs in a crucial free vote on pre-implantation genetic diagnosis (PGD is modelled using data on their political, sectoral and religious affiliations. Identifying as a Catholic and membership in Christian organisations are strong predictors of resistance to PGD. Even more importantly, net of religious and professional ties, affiliation with either the Christian Democrats or the left-libertarian Green party is closely linked to restrictive bioethical preferences. The modest liberalisation in 2011 was contingent on external factors and the overwhelming support of the historically unusually large FDP delegation. With the FDP no longer represented in parliament and the Christian Democratic/New Left issue coalition even stronger than before, further liberalisation is unlikely.

  3. Platelets kill intraerythrocytic malarial parasites and mediate survival to infection.

    Science.gov (United States)

    McMorran, Brendan J; Marshall, Vikki M; de Graaf, Carolyn; Drysdale, Karen E; Shabbar, Meriam; Smyth, Gordon K; Corbin, Jason E; Alexander, Warren S; Foote, Simon J

    2009-02-01

    Platelets play a critical role in the pathogenesis of malarial infections by encouraging the sequestration of infected red blood cells within the cerebral vasculature. But platelets also have well-established roles in innate protection against microbial infections. We found that purified human platelets killed Plasmodium falciparum parasites cultured in red blood cells. Inhibition of platelet function by aspirin and other platelet inhibitors abrogated the lethal effect human platelets exert on P. falciparum parasites. Likewise, platelet-deficient and aspirin-treated mice were more susceptible to death during erythrocytic infection with Plasmodium chabaudi. Both mouse and human platelets bind malarial-infected red cells and kill the parasite within. These results indicate a protective function for platelets in the early stages of erythrocytic infection distinct from their role in cerebral malaria.

  4. Resveratrol preserves the function of human platelets stored for transfusion.

    Science.gov (United States)

    Lannan, Katie L; Refaai, Majed A; Ture, Sara K; Morrell, Craig N; Blumberg, Neil; Phipps, Richard P; Spinelli, Sherry L

    2016-03-01

    Stored platelets undergo biochemical, structural and functional changes that lead to decreased efficacy and safety of platelet transfusions. Not only do platelets acquire markers of activation during storage, but they also fail to respond normally to agonists post-storage. We hypothesized that resveratrol, a cardioprotective antioxidant, could act as a novel platelet storage additive to safely prevent unwanted platelet activation during storage, while simultaneously preserving normal haemostatic function. Human platelets treated with resveratrol and stored for 5 d released less thromboxane B2 and prostaglandin E2 compared to control platelets. Resveratrol preserved the ability of platelets to aggregate, spread and respond to thrombin, suggesting an improved ability to activate post-storage. Utilizing an in vitro model of transfusion and thromboelastography, clot strength was improved with resveratrol treatment compared to conventionally stored platelets. The mechanism of resveratrol's beneficial actions on stored platelets was partly mediated through decreased platelet apoptosis in storage, resulting in a longer half-life following transfusion. Lastly, an in vivo mouse model of transfusion demonstrated that stored platelets are prothrombotic and that resveratrol delayed vessel occlusion time to a level similar to transfusion with fresh platelets. We show resveratrol has a dual ability to reduce unwanted platelet activation during storage, while preserving critical haemostatic function. PMID:26683619

  5. Stability of lyophilized human platelets loaded with small molecule carbohydrates.

    Science.gov (United States)

    Wang, J X; Yang, C; Wan, W; Liu, M X; Ren, S P; Quan, G B; Han, Y

    2011-01-01

    Long-term preservation of platelets is a great challenge for blood transfusion centers, due to the required narrow storage temperature arange (22 ± 2 degree C). Short shelf life and potential bacterial growth often lead to the shortage of high-quality platelets. Freeze-dried preservation is thus believed to be a potential solution for long-term platelet storage without losing the hemostasis function. Here we report a new platelet preservation method, which uses small molecule carbohydrates to extend storage time and to maintain platelet function. The activities of lyophilized platelets that were stabilized with small molecule carbohydrate (e.g., cell viability, mean platelet volume, activation characteristics, and aggregation kinetics) were maintained after storage of 30, 60, and 90 days at room temperature, 4 degree C, and -20 degree C. The recovery of freeze-dried platelets was 87 percent in comparison to fresh platelets. The mean platelet volume of rehydrated platelets increased (from 6.8 fl to 8.0 fl). About 40 percent of rehydrated platelets was in the early-activated stage (PCA-1 positive) and 30 percent was in the terminal-activated stage (CD62P positive). The cell viability was about 60 percent as measured with CMFDA vital probes. The aggregation rate of rehydrated platelets after 90-day storage was similar to fresh platelets stored at 22 degree C ± 2 degree C.

  6. Platelet inhibition by nitrite is dependent on erythrocytes and deoxygenation.

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    Sirada Srihirun

    Full Text Available BACKGROUND: Nitrite is a nitric oxide (NO metabolite in tissues and blood, which can be converted to NO under hypoxia to facilitate tissue perfusion. Although nitrite is known to cause vasodilation following its reduction to NO, the effect of nitrite on platelet activity remains unclear. In this study, the effect of nitrite and nitrite+erythrocytes, with and without deoxygenation, on platelet activity was investigated. METHODOLOGY/FINDING: Platelet aggregation was studied in platelet-rich plasma (PRP and PRP+erythrocytes by turbidimetric and impedance aggregometry, respectively. In PRP, DEANONOate inhibited platelet aggregation induced by ADP while nitrite had no effect on platelets. In PRP+erythrocytes, the inhibitory effect of DEANONOate on platelets decreased whereas nitrite at physiologic concentration (0.1 µM inhibited platelet aggregation and ATP release. The effect of nitrite+erythrocytes on platelets was abrogated by C-PTIO (a membrane-impermeable NO scavenger, suggesting an NO-mediated action. Furthermore, deoxygenation enhanced the effect of nitrite as observed from a decrease of P-selectin expression and increase of the cGMP levels in platelets. The ADP-induced platelet aggregation in whole blood showed inverse correlations with the nitrite levels in whole blood and erythrocytes. CONCLUSION: Nitrite alone at physiological levels has no effect on platelets in plasma. Nitrite in the presence of erythrocytes inhibits platelets through its reduction to NO, which is promoted by deoxygenation. Nitrite may have role in modulating platelet activity in the circulation, especially during hypoxia.

  7. Nephropathy in type 1 diabetes is associated with increased circulating activated platelets and platelet hyperreactivity

    DEFF Research Database (Denmark)

    Tarnow, Inge; Michelson, Alan D.; Barnard, Marc R.;

    2009-01-01

    controls (P = 0.0075). There were no differences between groups in activated GPIIb/IIIa or in response to TRAP at any end-point. More patients with nephropathy received aspirin (71.4%) compared to normoalbuminuric patients (27.4%) (P diabetic nephropathy, as compared with normoalbuminuria......Patients with diabetes mellitus (DM) have increased platelet activation compared to non-diabetic controls. Platelet hyperreactivity has been associated with adverse cardiovascular outcomes in Type 2 DM, and with diabetic nephropathy. We investigated the relationship between platelet activation...... and nephropathy in Type 1 DM. Patients with Type 1 DM and diabetic nephropathy (n = 35), age- and sex-matched Type 1 DM patients with persistent normoalbuminuria (n = 51), and healthy age- and sex-matched controls (n = 30) were studied. Platelet surface P-selectin, platelet surface activated GPIIb/IIIa, monocyte...

  8. Spurious automated platelet count. Enumeration of yeast forms as platelets by the cell-DYN 4000.

    Science.gov (United States)

    Latif, Shahnila; Veillon, Diana M; Brown, Donald; Kaltenbach, Jenny; Curry, Sherry; Linscott, Andrea J; Oberle, Arnold; Cotelingam, James D

    2003-12-01

    We recently encountered a patient with thrombocytopenia secondary to multiple drug therapy, disseminated prostatic adenocarcinoma, and sepsis who had a sudden decrease in his platelet count as enumerated by the Cell-DYN 4000 hematology analyzer (Abbott Diagnostics, Santa Clara, CA). A manual platelet count performed thereafter was even lower. The etiology of the spurious platelet count was clarified when numerous yeast forms were observed on routine microscopy of the peripheral blood smear. Subsequently, these organisms were identified as Candida glabrata from a positive blood culture (BACTEC 9240, Becton Dickinson, Cockeysville, MD). To our knowledge, this is the first report of spurious enumeration of yeast forms as platelets in an automated hematology system. The principle underlying platelet enumeration by the Cell-DYN 4000 system and other hematology analyzers and the value of microscopy on peripheral smears with unexpected CBC count results are discussed. PMID:14671977

  9. A General Aspect of Platelet Rich Plasma

    Directory of Open Access Journals (Sweden)

    Onur ORAL

    2015-08-01

    Full Text Available The aim of this scientific paper is to introduce Platelet Rich Plasma (PRP cure method by people who never heard about it. People can hurt their selves, thus they can have damaged tissue; for instance broken bone, a scar or a wounded area. Furthe rmore damaged tissue can be a cartilage tissue, which takes very long time to heal. Platelets, those exist in the veins as thrombus, come up to repair those damaged tissues. However, platelets would be insufficient to cure damaged area in a short time. At this point PRP cure method give a hand to the healing process. By centrifuging people’s own blood via special kits, platelets can be separated from blood cells as plasma. That plasma’s platelet density is 3 - 5 times greater than that blood’s platelet densit y. Afterwards PRP method is implemented by injection of plasma to the damaged area or tissue. After implementation of 2 - 4 sessions per week, damaged tissue can be regenerated. It is fast healing method because densified platelet plasma is used; and it is s afe because that plasma is obtained from people’s own blood. PRP can be implemented on many areas; for instance on dentistry, sports medicine, different kind of surgeries such as plastic, vascular or orthopedic and so on. When soccer players brake their le gs, their sports life come to the end, but what if their broken legs was healed better and faster than general healing process? To sum up, PRP is very safe and the future of healing process.

  10. Platelet receptor polymorphisms do not influence Staphylococcus aureus-platelet interactions or infective endocarditis.

    Science.gov (United States)

    Daga, Shruti; Shepherd, James G; Callaghan, J Garreth S; Hung, Rachel K Y; Dawson, Dana K; Padfield, Gareth J; Hey, Shi Y; Cartwright, Robyn A; Newby, David E; Fitzgerald, J Ross

    2011-03-01

    Cardiac vegetations result from bacterium-platelet adherence, activation and aggregation, and are associated with increased morbidity and mortality in infective endocarditis. The GPIIb/IIIa and FcγRIIa platelet receptors play a central role in platelet adhesion, activation and aggregation induced by endocarditis pathogens such as Staphylococcus aureus, but the influence of known polymorphisms of these receptors on the pathogenesis of infective endocarditis is unknown. We determined the GPIIIa platelet antigen Pl(A1/A2) and FcγRIIa H131R genotype of healthy volunteers (n = 160) and patients with infective endocarditis (n = 40), and investigated the influence of these polymorphisms on clinical outcome in infective endocarditis and S. aureus-platelet interactions in vitro. Platelet receptor genotype did not correlate with development of infective endocarditis, vegetation characteristics on echocardiogram or the composite clinical end-point of embolism, heart failure, need for surgery or mortality (P > 0.05 for all), even though patients with the GPIIIa Pl(A1/A1) genotype had increased in vivo platelet activation (P = 0.001). Furthermore, neither GPIIIa Pl(A1/A2) nor FcγRIIa H131R genotype influenced S. aureus-induced platelet adhesion, activation or aggregation in vitro (P > 0.05). Taken together, our data suggest that the GPIIIa and FcγRIIa platelet receptor polymorphisms do not influence S. aureus-platelet interactions in vitro or the clinical course of infective endocarditis.

  11. Platelets of patients with chronic kidney disease demonstrate deficient platelet reactivity in vitro

    Directory of Open Access Journals (Sweden)

    van Bladel Esther R

    2012-09-01

    Full Text Available Abstract Background In patients with chronic kidney disease studies focusing on platelet function and properties often are non-conclusive whereas only few studies use functional platelet tests. In this study we evaluated a recently developed functional flow cytometry based assay for the analysis of platelet function in chronic kidney disease. Methods Platelet reactivity was measured using flow cytometric analysis. Platelets in whole blood were triggered with different concentrations of agonists (TRAP, ADP, CRP. Platelet activation was quantified with staining for P-selectin, measuring the mean fluorescence intensity. Area under the curve and the concentration of half-maximal response were determined. Results We studied 23 patients with chronic kidney disease (9 patients with cardiorenal failure and 14 patients with end stage renal disease and 19 healthy controls. Expression of P-selectin on the platelet surface measured as mean fluorescence intensity was significantly less in chronic kidney disease patients compared to controls after maximal stimulation with TRAP (9.7 (7.9-10.8 vs. 11.4 (9.2-12.2, P = 0.032, ADP (1.6 (1.2-2.1 vs. 2.6 (1.9-3.5, P = 0.002 and CRP (9.2 (8.5-10.8 vs. 11.5 (9.5-12.9, P = 0.004. Also the area under the curve was significantly different. There was no significant difference in half-maximal response between both groups. Conclusion In this study we found that patients with chronic kidney disease show reduced platelet reactivity in response of ADP, TRAP and CRP compared to controls. These results contribute to our understanding of the aberrant platelet function observed in patients with chronic kidney disease and emphasize the significance of using functional whole blood platelet activation assays.

  12. Exogenous modification of platelet membranes with the omega-3 fatty acids EPA and DHA reduces platelet procoagulant activity and thrombus formation

    OpenAIRE

    Larson, Mark K.; Tormoen, Garth W.; Weaver, Lucinda J.; Luepke, Kristen J.; Patel, Ishan A.; Hjelmen, Carl E.; Ensz, Nicole M.; McComas, Leah S.; McCarty, Owen J. T.

    2012-01-01

    Several studies have implicated the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in inhibition of normal platelet function, suggesting a role for platelets in EPA- and DHA-mediated cardioprotection. However, it is unclear whether the cardioprotective mechanisms arise from alterations to platelet-platelet, platelet-matrix, or platelet-coagulation factor interactions. Our previous results led us to hypothesize that EPA and DHA alter the ability of platelets to ...

  13. Hypersensitivity to thrombin of platelets from hypercholesterolemic rats

    International Nuclear Information System (INIS)

    Hypersensitivity of platelets to thrombin has been associated with hypercholesterolemia. The authors have examined the mechanisms involved in this hypersensitivity. Rats were given diets rich in milk fat and containing added cholesterol and taurocholate to produce hypercholesterolemia (HC) (262 +/- 25 mg%) or added sitosterol as a normocholesterolemic control (NC) (89 +/- 6 mg%). Washed platelets were prelabelled with 14C-serotonin. In the presence of acetylsalicyclic acid (ASA) (to inhibit thromboxane A2 (TXA2) formation) and creatine phosphate/creatine phosphokinase (CP/CPK) (to remove released ADP), HC platelets aggregated more (26 +/- 1%) and released more 14C (9.1 +/- 2.0%) than NC platelets (aggregation: 0%, p 14C release: 1.5 +/- 0.5%, p 2 formation is involved in the hypersensitivity of HC platelets to thrombin. Total binding of 125I-thrombin to HC platelets was less than that to NC platelets but HC platelets were smaller and had less protein than NC platelets; the thrombin binding per mg platelet protein was the same for HC and NC platelets, indicating that hypersensitivity to thrombin of HC platelets does not result from increased thrombin binding. Thus, hypersensitivity of HC platelets to thrombin is not due to TXA2 formation, the action of released ADP or increased thrombin binding

  14. Decreased mean platelet volume in panic disorder

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    Göğçegöz Gül I

    2014-09-01

    Full Text Available Işil Göğçegöz Gül, Gül Eryilmaz, Eylem Özten, Gökben Hizli Sayar Neuropsychiatry Health, Practice, and Research Center, Uskudar University, Istanbul, Turkey Aim: The relationship between psychological stress and platelet activation has been widely studied. It is well known that platelets may reflect certain biochemical changes that occur in the brain when different mental conditions occur. Platelet 5-hydroxytryptamine (5-HT is also extensively studied in psychiatry. The mean platelet volume (MPV, the accurate measure of platelet size, has been considered a marker and determinant of platelet function. The aim of the present study was to search for any probable difference in the MPV of subjects with panic disorder (PD.Methods: A total of 37 drug-free subjects, aged 18 to 65 years, diagnosed with PD, with or without agoraphobia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition (DSM-IV criteria and 45 healthy control subjects were included in the study. Platelet count and MPV were measured and recorded for each subject.Results: There were no statistically significant differences between groups in terms of female/male ratio, age, or body mass index between the PD group and control group (P=0.91, P=0.82, and P=0.93, respectively. The MPV was found to be significantly lower in the PD group compared with the control group (8.8±0.9 fL vs 9.2±0.8 fL; P=0.02. All the participants had MPV values in the standard range of 6.9–10.8 fL.Conclusion: We concluded that abnormalities of the 5-HT1A receptor function in the central nervous system of subjects with a diagnosis of PD are also mirrored in as an alteration in platelet activity. Measurements of platelet activity may be used as a tool for neuropsychiatric and psychopharmacological research and for studying how certain mental diseases and medications affect the central nervous system. Keywords: 5-HT, thrombocyte, anxiety 

  15. Equid herpesvirus type 1 activates platelets.

    Science.gov (United States)

    Stokol, Tracy; Yeo, Wee Ming; Burnett, Deborah; DeAngelis, Nicole; Huang, Teng; Osterrieder, Nikolaus; Catalfamo, James

    2015-01-01

    Equid herpesvirus type 1 (EHV-1) causes outbreaks of abortion and neurological disease in horses. One of the main causes of these clinical syndromes is thrombosis in placental and spinal cord vessels, however the mechanism for thrombus formation is unknown. Platelets form part of the thrombus and amplify and propagate thrombin generation. Here, we tested the hypothesis that EHV-1 activates platelets. We found that two EHV-1 strains, RacL11 and Ab4 at 0.5 or higher plaque forming unit/cell, activate platelets within 10 minutes, causing α-granule secretion (surface P-selectin expression) and platelet microvesiculation (increased small events double positive for CD41 and Annexin V). Microvesiculation was more pronounced with the RacL11 strain. Virus-induced P-selectin expression required plasma and 1.0 mM exogenous calcium. P-selectin expression was abolished and microvesiculation was significantly reduced in factor VII- or X-deficient human plasma. Both P-selectin expression and microvesiculation were re-established in factor VII-deficient human plasma with added purified human factor VIIa (1 nM). A glycoprotein C-deficient mutant of the Ab4 strain activated platelets as effectively as non-mutated Ab4. P-selectin expression was abolished and microvesiculation was significantly reduced by preincubation of virus with a goat polyclonal anti-rabbit tissue factor antibody. Infectious virus could be retrieved from washed EHV-1-exposed platelets, suggesting a direct platelet-virus interaction. Our results indicate that EHV-1 activates equine platelets and that α-granule secretion is a consequence of virus-associated tissue factor triggering factor X activation and thrombin generation. Microvesiculation was only partly tissue factor and thrombin-dependent, suggesting the virus causes microvesiculation through other mechanisms, potentially through direct binding. These findings suggest that EHV-1-induced platelet activation could contribute to the thrombosis that occurs in

  16. Equid herpesvirus type 1 activates platelets.

    Directory of Open Access Journals (Sweden)

    Tracy Stokol

    Full Text Available Equid herpesvirus type 1 (EHV-1 causes outbreaks of abortion and neurological disease in horses. One of the main causes of these clinical syndromes is thrombosis in placental and spinal cord vessels, however the mechanism for thrombus formation is unknown. Platelets form part of the thrombus and amplify and propagate thrombin generation. Here, we tested the hypothesis that EHV-1 activates platelets. We found that two EHV-1 strains, RacL11 and Ab4 at 0.5 or higher plaque forming unit/cell, activate platelets within 10 minutes, causing α-granule secretion (surface P-selectin expression and platelet microvesiculation (increased small events double positive for CD41 and Annexin V. Microvesiculation was more pronounced with the RacL11 strain. Virus-induced P-selectin expression required plasma and 1.0 mM exogenous calcium. P-selectin expression was abolished and microvesiculation was significantly reduced in factor VII- or X-deficient human plasma. Both P-selectin expression and microvesiculation were re-established in factor VII-deficient human plasma with added purified human factor VIIa (1 nM. A glycoprotein C-deficient mutant of the Ab4 strain activated platelets as effectively as non-mutated Ab4. P-selectin expression was abolished and microvesiculation was significantly reduced by preincubation of virus with a goat polyclonal anti-rabbit tissue factor antibody. Infectious virus could be retrieved from washed EHV-1-exposed platelets, suggesting a direct platelet-virus interaction. Our results indicate that EHV-1 activates equine platelets and that α-granule secretion is a consequence of virus-associated tissue factor triggering factor X activation and thrombin generation. Microvesiculation was only partly tissue factor and thrombin-dependent, suggesting the virus causes microvesiculation through other mechanisms, potentially through direct binding. These findings suggest that EHV-1-induced platelet activation could contribute to the thrombosis

  17. Lea blood group antigen on human platelets

    International Nuclear Information System (INIS)

    One- and two-stage radioligand assays were used to determine if human platelets possess the Lea antigen. Goat IgG anti-Lea antibody was purified by multiple adsorptions with Le(a-b-) human red blood cells, followed by affinity chromatography with synthetic Lea substance and labeling with 125I. Human IgG anti-Lea antibody was used either in a two stage radioassay with 125I-labeled mouse monoclonal IgG anti-human IgG as the second antibody or, alternatively, purified by Staph protein A chromatography, labeled with 125I, and used in a one-stage radioassay. Platelets from donors of appropriate red blood cell phenotypes were incubated with the antisera, centrifuged through phthalate esters, and assayed in a gamma scintillation counter. Dose response and saturation curve analysis demonstrate the presence of Lewis a antigen on platelets from Lea+ donors. Furthermore, platelets from an Le(a-b-) donor incubated in Le (a+b-) plasma adsorb Lea antigen in a similar manner to red blood cells. The clinical significance of these antigens in platelet transfusion remains undefined

  18. The prowess of platelets in immunity and inflammation.

    Science.gov (United States)

    Koenen, Rory R

    2016-09-27

    Platelets not only serve as essential haemostatic cells, they also have important roles in immune defence and inflammation. Despite not having a nucleus, platelets contain physiologically relevant amounts of RNA, which can be spliced and translated into functional proteins. In addition, platelets have the ability to bind to numerous other cells, such as leukocytes and vascular cells. During those interactions, platelets can modulate cellular responses, resulting in e. g. inflammatory activation or apoptosis. Recent studies have demonstrated that platelets can influence the outcomes of bacterial and viral infection, as well as the extent of tissue injury after ischaemia. Platelets also carry considerable amounts of cytokines and growth factors in their secretory granules, preformed for rapid secretion. Those properties in combination with the sheer amount of platelets circulating in the blood stream make them an important force in the immune response during health and disease. In this overview, recent findings concerning those interesting properties of platelets beyond haemostasis are discussed.

  19. LIPOPOLYSACCHARIDE INDUCES EXPOSURE OF FIBRINOGEN RECEPTORS ON HUMAN PLATELETS

    Institute of Scientific and Technical Information of China (English)

    于希春; 吴其夏

    1995-01-01

    The effect of lipopolysaccharide (LPS) on the exposure of platelet fibrinogen receptors was investigated.The results showed that:1)LPS increased the binding of fibrinogen-gold complexes to platelets and the labels were primarily limited to shape-changed platelets;2)LPS caused a dose-dependent rise in intracellular Ca2+ concentration in platelets;3)LPS induced the activation of platelet protein kinase C(PKC) and the phosphorylation of glycoprotein llla (GP llla) which was inhibited by H-7.All these results suggest that stimulation of platelets with LPS causes a conformational change in glycoprotein llb/Illa (GPllb/llla) through platelet shape change and/or phosphorylation of GPllla via PKC,which serves to expose the fibrinogen binding sites of GPllb/llla on human platelets.

  20. Platelet concentrates, from whole blood or collected by apheresis?

    Science.gov (United States)

    van der Meer, Pieter F

    2013-04-01

    Platelet concentrates can be isolated from donated whole blood with the platelet-rich plasma-method or the buffy coat-method. Alternatively, platelets can be obtained by apheresis, harvesting the platelets but returning all other cells to the donor. The quality and characteristics of platelets during storage are affected by a number of factors, such as anticoagulant, centrifugation and processing after collection, and pre- or post storage pooling, but when comparing literature on the various methods, most differences balance out. To have sufficient platelets to treat an adult patient, whole-blood-derived platelet concentrates need pooling of multiple donations, thereby increasing the risk of infectious agent transmission at least two-fold as compared with apheresis units. Allo immunization rates, acute reaction rates, and transfusion related acute lung injury rates are not different. Apheresis donation procedures have fewer adverse events. All these factors need to be considered and weighed when selecting a method of platelet collection for a blood center.

  1. Platelet-activating factor increases platelet-dependent glycoconjugate secretion from tracheal submucosal gland

    International Nuclear Information System (INIS)

    Using isolated glands from feline trachea, we examined the effect of platelet-activating factor (PAF) on radiolabeled glycoconjugate release and glandular contraction by measuring induced tension in the absence or presence of platelets. PAF alone did not produce any significant glandular contraction nor any significant change in glycoconjugate release from isolated glands. In the presence of purified platelets containing no plasma, PAF (10(-8) to 10(-5) M) produced significant glycoconjugate secretion in a dose-dependent fashion, but it produced no significant glandular contraction. PAF-evoked glycoconjugate secretion was time dependent, reaching a peak response of 277% of control 15-30 min after the exposure of isolated glands to 10(-5) M PAF in the presence of platelets and returning to 135% of controls at 2 h. Platelets alone did not produce any significant stimulation in glycoconjugate release. CV-3988, a known PAF antagonist, inhibited the secretory response to PAF. Methysergide, a known antagonist to receptors for 5-hydroxytryptamine, did not alter PAF-evoked glycoconjugate secretion. Both indomethacin and SQ 29,548, a thromboxane receptor antagonist, abolished the PAF-evoked glycoconjugate secretion from isolated submucosal glands. Epithiomethanothromboxane A2, a stable thromboxane A2 analogue, produced a significant increase in glycoconjugate secretion in a dose-dependent fashion. These findings indicate that PAF increases glycoconjugate release in the presence of platelets and that the increase is dependent on some aspect of platelet function, namely thromboxane generation

  2. Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus, Prevents Platelet Activation in Human Platelets

    Directory of Open Access Journals (Sweden)

    Ye-Ming Lee

    2012-01-01

    Full Text Available Xanthohumol is the principal prenylated flavonoid in the hop plant (Humulus lupulus L.. Xanthohumol was found to be a very potent cancer chemopreventive agent through regulation of diverse mechanisms. However, no data are available concerning the effects of xanthohumol on platelet activation. The aim of this paper was to examine the antiplatelet effect of xanthohumol in washed human platelets. In the present paper, xanthohumol exhibited more-potent activity in inhibiting platelet aggregation stimulated by collagen. Xanthohumol inhibited platelet activation accompanied by relative [Ca2+]i mobilization, thromboxane A2 formation, hydroxyl radical (OH● formation, and phospholipase C (PLCγ2, protein kinase C (PKC, mitogen-activated protein kinase (MAPK, and Akt phosphorylation. Neither SQ22536, an inhibitor of adenylate cyclase, nor ODQ, an inhibitor of guanylate cyclase, reversed the xanthohumol-mediated inhibitory effect on platelet aggregation. Furthermore, xanthohumol did not significantly increase nitrate formation in platelets. This study demonstrates for the first time that xanthohumol possesses potent antiplatelet activity which may initially inhibit the PI3-kinase/Akt, p38 MAPK, and PLCγ2-PKC cascades, followed by inhibition of the thromboxane A2 formation, thereby leading to inhibition of [Ca2+]i and finally inhibition of platelet aggregation. Therefore, this novel role of xanthohumol may represent a high therapeutic potential for treatment or prevention of cardiovascular diseases.

  3. Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting

    Science.gov (United States)

    Zhu, Yuanjun; Li, Ruyi; Lin, Yuan; Shui, Mengyang; Liu, Xiaoyan; Chen, Huan; Wang, Yinye

    2016-01-01

    Targeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets, and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency. PMID:27432161

  4. Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting.

    Science.gov (United States)

    Zhu, Yuanjun; Li, Ruyi; Lin, Yuan; Shui, Mengyang; Liu, Xiaoyan; Chen, Huan; Wang, Yinye

    2016-01-01

    Targeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets, and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency. PMID:27432161

  5. A more practical therapy for low platelets.

    Science.gov (United States)

    Torres, G

    1996-01-01

    The Food and Drug Administration (FDA) approved WinRho as a new treatment for ITP or thrombocytopenic purpura (low blood platelet count) in people with HIV. Current treatment options for ITP include AZT, corticosteroids, immunoglobulin therapy, and splenectomy. Clinical evaluation rates AZT as the best of the options. WinRho treatment will not work on Rh-negative patients or patients with no spleen. The largest WinRho study to date, involving 267 patients, shows a mean platelet increase of 76,000 cells with no adverse effect on CD4 counts or evidence of an acceleration of HIV disease progression. HIV-positive patients had a poorer platelet increase response than HIV-negative patients. PMID:11363379

  6. Platelet concentration in platelet concentrates and periodontal regeneration-unscrambling the ambiguity

    Directory of Open Access Journals (Sweden)

    A Suchetha

    2015-01-01

    Full Text Available Context: Platelet-rich-plasma (PRP and Platelet-rich-fibrin (PRF are extensively used autologous platelet concentrates in periodontal regeneration, and PRF has a better efficacy as compared to PRP. The rationale for this difference has often been attributed to the difference in the structure of the fibrin matrix. However, the effect of concentration of platelets on the regenerative potential of these concentrates is obscure. Aims: The study was conducted to evaluate and compare, clinically and radiographically, the efficacy of PRF and PRP in the treatment of periodontal endosseous defects and to assess the effect of platelet concentration on periodontal regeneration. Materials and Methods: Twenty intrabony defects were selected and divided into two groups randomly by the coin toss method. Group I received PRP and Group II subjects were treated with PRF. The platelet counts in PRP and PRF were analyzed. Clinical and radiological parameters were assessed at baseline and 3, 6, and 9 months postoperatively. Statistical Analysis: Kruskal–Wallis Chi-square test, Wilcoxon signed rank test, t-test, and Spearman's rank correlation were used for statistical analysis of data. Results: There was statistically significant improvement in all the parameters in the two groups except in relation to gingival recession. There was a statistically significant difference between the platelet count in Group I and Group II (P = 0.002. Conclusion: PRP and PRF appear to have nearly comparable effects in terms of periodontal regeneration. The concentration of platelets appears to play a paradoxical role in regeneration. The regenerative potential of platelets appears to be optimal within a limited range.

  7. Platelet Transfusion – The New Immunology of an Old Therapy

    OpenAIRE

    Stolla, Moritz; Refaai, Majed A.; Heal, Joanna M.; Spinelli, Sherry L.; Garraud, Olivier; Phipps, Richard P.; Blumberg, Neil

    2015-01-01

    Platelet transfusion has been a vital therapeutic approach in patients with hematologic malignancies for close to half a century. Randomized trials show that prophylactic platelet transfusions mitigate bleeding in patients with acute myeloid leukemia. However, even with prophylactic transfusions, as many as 75% of patients, experience hemorrhage. While platelet transfusion efficacy is modest, questions and concerns have arisen about the risks of platelet transfusion therapy. The acknowledged ...

  8. Exosomes: novel effectors of human platelet lysate activity

    OpenAIRE

    E Torreggiani; F Perut; Roncuzzi, L; N Zini; SR Baglìo; N Baldini

    2014-01-01

    Despite the popularity of platelet-rich plasma (PRP) and platelet lysate (PL) in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF) released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one...

  9. Enhancement of mononuclear procoagulant activity by platelet 12-hydroxyeicosatetraenoic acid.

    OpenAIRE

    Lorenzet, R; Niemetz, J; Marcus, A J; Broekman, M J

    1986-01-01

    Platelets induce generation of procoagulant tissue factor activity (TFa) by mononuclear leukocytes, and also enhance the TFa induced by endotoxin. Our present investigation demonstrated that arachidonic acid, which by itself had no effect on mononuclear TFa, greatly enhanced platelet-induced TFa. The effect was concentration dependent for both platelets and arachidonate (1-20 microM); other fatty acids tested were inactive. The enhancing effect of arachidonate was more pronounced if platelets...

  10. Platelets promote allergic asthma through the expression of CD154

    OpenAIRE

    Tian, Jun; ZHU, TIANYI; Liu, Juan; Guo, Zhenhong; Cao, Xuetao

    2014-01-01

    Platelet activation is associated with multiple immune responses and the pathogenesis of various immune-related diseases. However, the exact role and the underlying mechanism of platelets in the progression of allergic asthma remain largely unclear. In this study, we demonstrate that during antigen sensitization, platelets can be activated by ovalbumin (OVA) aerosol via the upregulation of CD154 (CD40L) expression. Platelet transfer promoted allergic asthma progression by inducing more severe...

  11. Metabolomic analysis of platelets during storage

    DEFF Research Database (Denmark)

    Paglia, Giuseppe; Sigurjónsson, Ólafur E; Rolfsson, Óttar;

    2015-01-01

    BACKGROUND: Platelet concentrates (PCs) can be prepared using three methods: platelet (PLT)-rich plasma, apheresis, and buffy coat. The aim of this study was to obtain a comprehensive data set that describes metabolism of buffy coat-derived PLTs during storage and to compare it with a previously...... measurements. This data set was obtained by combining a series of standard quality control assays to monitor the quality of stored PLTs and a deep coverage metabolomics study using liquid chromatography coupled with mass spectrometry. RESULTS: Stored PLTs showed a distinct metabolic transition occurring 4 days...

  12. Platelets contribute to growth and metastasis in hepatocellular carcinoma.

    Science.gov (United States)

    Bihari, Chhagan; Rastogi, Archana; Shasthry, Saggere Muralikrishna; Bajpai, Meenu; Bhadoria, Ajeet Singh; Rajesh, S; Mukund, Amar; Kumar, Anupam; Sarin, Shiv K

    2016-09-01

    To determine the association of platelets with hepatocellular carcinoma (HCC) growth and its metastasis. We examined platelets, laboratory, and radiological data of consecutive 420 HCC and 1008 cirrhosis cases. Follow-up information of platelet count in cirrhosis to HCC, pre- to post-therapy, and post-therapy to HCC outcome was analyzed. Cytokine profiling was performed in HCC and cirrhosis (n = 10 each). On the basis of imaging, HCC was divided into six subgroups. Cytosmears of HCC were assessed for platelet clustering around tumor cells. An in vitro Matrigel invasion assay was performed on human HCC cell lines using graded concentration of platelets. Baseline platelet numbers and platelet/lymphocyte ratios (PLRs) were significantly higher (p AFP, PIVKAII, platelets, and PLR increase (p AFP (p < 0.001) associated with distant metastasis. Platelet clustering seen in 75.7% of HCC group 3, 45% in group 2, and 12.5% in group 1 cases (p < 0.001). Invaded cells in Matrigel assay positively correlated with platelet concentration. Platelets can contribute to the development, growth, invasion, and metastasis of HCC. Rising platelet count after HCC therapy is indicative of incomplete response or recurrence. PMID:27457354

  13. Platelet function and HIV: a case-control study.

    LENUS (Irish Health Repository)

    Satchell, Claudette S

    2010-03-13

    Cardiovascular disease and myocardial infarction are of increasing concern in HIV-infected populations. Although platelets mediate arterial thrombosis, central to myocardial infarction, data on platelet function in HIV infection are lacking. We hypothesized that HIV-infected patients would have altered platelet reactivity.

  14. Glycoprotein Ibα clustering in platelet storage and function

    NARCIS (Netherlands)

    Gitz, E.

    2013-01-01

    Platelets are anucleated, discoid-shaped cells that play an essential role in the formation of a hemostatic plug to prevent blood loss from injured vessels. Initial platelet arrest at the damaged arterial vessel wall is mediated through the interaction between the platelet receptor glycoprotein (GP)

  15. Insights into Platelet Storage and the Need for Multiple Approaches.

    Science.gov (United States)

    Handigund, Mallikarjun; Cho, Yong Gon

    2015-01-01

    Upon accidental injury and the treatment of many diseases, patients may need a transfusion of blood components in order to achieve hemostasis. Platelets are small enucleated cells derived from bone marrow megakaryocytes that undergo change upon activation at sites of vascular injury and play a vital role in vascular repair and antimicrobial host defense, collectively contributing to hemostasis. They are the common blood components transfused whenever there is need, but supplies do not equal the demand as platelets are required in many medical and surgical procedures. In addition, surplus supplies of platelet concentrate are often discarded as they have a short shelf life. Currently, platelet concentrates are stored at room temperature for a maximum of 5 days from the date of collection; the temporal aspect is an added hurdle in the growing demand for platelet concentrates. Many investigations have been carried out in attempt to improve the quality and lengthen the shelf life of platelets, but the few that have succeeded are not commercially viable. Moreover, currently there is a declining trend in platelet research, quelling the hope of platelet storage improvement. Successful strategies would be a boon for medicine in particular and humanity in general. This review deals with past and current efforts toward improving the quality of platelet concentrates by reducing platelet storage lesions and increasing the viable storage period for platelets. Also presented are new perspectives based on past and current efforts, which should be investigated for platelet research in this decade.

  16. Biochemical and functional abnormalities in hypercholesterolemic rabbit platelets

    Energy Technology Data Exchange (ETDEWEB)

    Dalal, K.B.; Ebbe, S.; Mazoyer, E.; Carpenter, D.; Yee, T. (Lawrence Berkeley Laboratory, CA (USA))

    1990-02-01

    This study was designed to elucidate changes in rabbit platelet lipids induced by a cholesterol rich diet and to explore the possible correlation of these lipid changes with platelet abnormalities. Pronounced biochemical alterations were observed when serum cholesterol levels of 700-1000 mg% were reached. Hypercholesterolemic (HC) platelets contained 37% more neutral lipids and 16% less phospholipids than the controls. Lysolecithin, cholesterol esters and phosphatidylinositol (PI) levels were increased in HC platelets, and the levels of phosphatidylcholine (PC) were decreased. The cholesterol/phospholipid molar ratio of lipidemic platelets increased from 0.55 +/- 0.011 to 0.89 +/- 0.016 (P less than 0.01) in eight weeks. HC platelets had 90% more arachidonic acid (AA) in the PI than normal platelets. No significant changes in AA of PC were observed. Platelet function was monitored by the uptake and release of (14C)serotonin in platelet rich plasma (PRP), using varying concentrations of collagen as an aggregating agent. The uptake of (14C)serotonin in HC and normal platelets ranged from 78-94%. The percent of (14C)serotonin released from normal and HC platelets was proportional to the concentration of collagen. However, lipidemic platelets were hyperreactive to low concentrations of collagen. Incorporation of 50 microM acetylsalicylic acid into the aggregating medium suppressed the release of (14C)serotonin in normal PRP by more than 90%, but had only a partial effect on lipidemic PRP.

  17. Reduced platelet hyperreactivity and platelet-monocyte aggregation in HIV-infected individuals receiving a raltegravir-based regimen

    NARCIS (Netherlands)

    Tunjungputri, R.N.; Ven, A.J. van der; Schonsberg, A.; Mathan, T.S.M.; Koopmans, P.P.; Roest, M.; Fijnheer, R.; Groot, P.G. de; Mast, Q. de

    2014-01-01

    OBJECTIVE: Platelets are key cells in atherosclerosis and acute cardiovascular events. Platelet hyperreactivity and increased platelet-monocyte aggregation (PMA) are found in HIV-infected patients and may contribute to the excess cardiovascular risk. The integrase inhibitor raltegravir (RAL) has bee

  18. Physiopathology of blood platelets and development of platelets substitutes. Progress report, August 1, 1976--October 31, 1977. [/sup 51/Cr

    Energy Technology Data Exchange (ETDEWEB)

    Baldini, M G

    1977-07-31

    Progress is reported on the following research projects: the effect of estrogen on platelet aggregability and thrombus formation; the antithrombotic effect of platelet inhibiting agents in a bench model of artificial kidney; the arrest of hemorrhage in severely alloimmunized thrombocytopenic patients; and in vivo elution of /sup 51/Cr from labeled platelets induced by antibody. (HLW)

  19. Indium-111-labeled platelets: Applications in human platelet imaging and survival studies

    International Nuclear Information System (INIS)

    Clinical indications for the use of platelets labeled with indium-111 are not well established at this time, and the procedure should be considered an investigational tool. The procedure is used to study platelet kinetics, platelet distribution, and organ uptake. Although the /sup 51/Cr technique is still the reference procedure, the indium label has advantages that make it a more useful tool for clinical studies. Like the /sup 51/Cr method, /sup 111/In-oxine is a random label, that is, a mixed population (with respect to age) of circulating platelets is labeled in vitro and reinjected. Other random labels such as /sup 14/C-serotonin and diisopropylfluorophosphate (DFP) labeled with /sup 32/P or /sup 3/H have been used in research applications but are not well suited as clinical test procedures. Efforts to use cohort labeling with /sup 32/P, /sup 35/S, and /sup 75/Se-methionine have not resulted in a generally accepted procedure

  20. Evaluation of different sized blood sampling tubes for thromboelastometry, platelet function, and platelet count

    DEFF Research Database (Denmark)

    Andreasen, Jo Bønding; Pistor-Riebold, Thea Unger; Knudsen, Ingrid Hell;

    2014-01-01

    and compared three blood sampling tubes of different size: 1.8, 2.7, and 3.6 mL. All tubes were made of plastic and contained 3.2% sodium-citrate as anticoagulant. Platelet aggregation was investigated in 12 healthy individuals employing the Multiplate® Analyser comparing tubes of 3.6 mL and 1.8 mL. Platelet...... be preferred for RoTEM® analyses in order to minimise the volume of blood drawn. With regard to platelet aggregation analysed by impedance aggregometry tubes of different size cannot be used interchangeably. If platelet count is determined later than 10 min after blood sampling using tubes containing citrate...

  1. Circulating Endothelial Progenitor Cell and Platelet Microparticle Impact on Platelet Activation in Hypertension Associated with Hypercholesterolemia

    OpenAIRE

    Nicoleta Alexandru; Doina Popov; Emanuel Dragan; Eugen Andrei; Adriana Georgescu

    2013-01-01

    AIM: The purpose of this project was to evaluate the influence of circulating endothelial progenitor cells (EPCs) and platelet microparticles (PMPs) on blood platelet function in experimental hypertension associated with hypercholesterolemia. METHODS: Golden Syrian hamsters were divided in six groups: (i) control, C; (ii) hypertensive-hypercholesterolemic, HH; (iii) 'prevention', HHin-EPCs, HH animals fed a HH diet and treated with EPCs; (iv) 'regression', HHfin-EPCs, HH treated with EPCs aft...

  2. Platelet activation: ultrastructure and morphometry in platelet-rich plasma of horses

    Directory of Open Access Journals (Sweden)

    Bruna M. Zandim

    2012-01-01

    Full Text Available This study was conducted to investigate the activation ability of the platelet-rich plasma (PRP by pharmacological agents, as well as to verify the need or not of this activation for therapeutic use. The PRP was obtained from four healthy crossbred geldings aged 13 to 16 years (15±1years, and was processed for observation and quantification of the platelet morphology by using the transmission electron microscopy. All PRP samples were activated with 10% calcium chloride (CaCl2 solution, pure bovine thrombin or associated with CaCl2. The control (pure PRP was not pharmacologically activated. In the pure PRP samples, 49% of the platelets were classified as state of activation uncertain, 41% as resting, 9% as fully activated and 1% as irreversibly damaged. Treatment with 10% CaCl2 provided a distribution of 54% platelets in state of activation uncertain, 24% as fully activated, 20% as resting, and 2% as irreversibly damaged. The platelet morphology of the bovine thrombin treated samples did not fit into classification adopted, as showing irregular shape with emission of large filamentous pseudopods, appearance of ruptured and whole granules in the remaining cytoplasm and extracellular environment. There was effect of the treatment on the platelet morphology (P=0.03. The 10% CaCl2 is an adequate platelet-activating agent. However, in cases the use of PRP under its liquid form is necessary, the use of pure PRP is recommended, since besides presenting an adequate percentage of fully activated platelets it also has significant amount of the resting type, which can be activated by substances found in the injured tissue.

  3. Point-of-care platelet function tests: detection of platelet inhibition induced by nonopioid analgesic drugs.

    Science.gov (United States)

    Scharbert, Gisela; Gebhardt, Kristina; Sow, Zacharia; Duris, Monika; Deusch, Engelbert; Kozek-Langenecker, Sibylle

    2007-12-01

    Detection of platelet inhibition is of clinical relevance in the preinterventional risk-benefit assessment in chronic low-back-pain patients scheduled for invasive pain therapy. We evaluated the sensitivity of various point-of-care platelet function tests for the detection of platelet inhibition induced by nonopioid analgesic drugs. After Institutional Review Board approval and informed consent, citrated whole blood from 40 patients with chronic unspecific low back pain was investigated before and 30 min after intravenous infusion of the study medication consisting of diclofenac 75 mg (plus orphenadrin 30 mg; Neodolpasse; Fresenius Kabi Austria GmbH, Austria), parecoxib 40 mg (Dynastat; Pharmacia Europe EEIG, UK), paracetamol 1 g (Perfalgan; Bieffe Medital S.P.A., Italy), or normal saline in a randomized, cross-over, double-blinded, placebo-controlled study. Platelet function was assessed using the PFA-100 platelet function analyzer and thromboelastometry, as well as impedance aggregometry (in the last 17 patients recruited after it became commercially available). Sensitivity for detecting diclofenac-induced platelet inhibition was 85% for the PFA-100 using epinephrine as agonist and 94% for arachidonic acid-induced impedance aggregometry. ADP-induced platelet function tests, as well as cytochalasin D-modified thromboelastometry were unreliable. All tests had a low incidence of false-positive test results after normal saline. Paracetamol and parecoxib had no significant platelet inhibiting effect. The PFA-100 using epinephrine as agonist and arachidonic acid-induced impedance aggregometry are recommended for the detection of cyclooxygenase-I-inhibiting effects of nonsteroidal anti-inflammatory drugs such as diclofenac. Our findings confirm that a single rescue dose of paracetamol and parecoxib has no antiplatelet effect. PMID:17982319

  4. Platelet transfusions in platelet consumptive disorders are associated with arterial thrombosis and in-hospital mortality.

    Science.gov (United States)

    Goel, Ruchika; Ness, Paul M; Takemoto, Clifford M; Krishnamurti, Lakshmanan; King, Karen E; Tobian, Aaron A R

    2015-02-26

    While platelets are primary mediators of hemostasis, there is emerging evidence to show that they may also mediate pathologic thrombogenesis. Little data are available on risks and benefits associated with platelet transfusions in thrombotic thrombocytopenic purpura (TTP), heparin-induced thrombocytopenia (HIT) and immune thrombocytopenic purpura (ITP). This study utilized the Nationwide Inpatient Sample to evaluate the current in-hospital platelet transfusion practices and their association with arterial/venous thrombosis, acute myocardial infarction (AMI), stroke, and in-hospital mortality over 5 years (2007-2011). Age and gender-adjusted odds ratios (adjOR) associated with platelet transfusions were calculated. There were 10 624 hospitalizations with TTP; 6332 with HIT and 79 980 with ITP. Platelet transfusions were reported in 10.1% TTP, 7.1% HIT, and 25.8% ITP admissions. Platelet transfusions in TTP were associated with higher odds of arterial thrombosis (adjOR = 5.8, 95%CI = 1.3-26.6), AMI (adjOR = 2.0, 95%CI = 1.2-3.3) and mortality (adjOR = 2.0,95%CI = 1.3-3.0), but not venous thrombosis. Platelet transfusions in HIT were associated with higher odds of arterial thrombosis (adjOR = 3.4, 95%CI = 1.2-9.5) and mortality (adjOR = 5.2, 95%CI = 2.6-10.5) but not venous thrombosis. Except for AMI, all relationships remained significant after adjusting for clinical severity and acuity. No associations were significant for ITP. Platelet transfusions are associated with higher odds of arterial thrombosis and mortality among TTP and HIT patients.

  5. Acidosis downregulates platelet haemostatic functions and promotes neutrophil proinflammatory responses mediated by platelets.

    Science.gov (United States)

    Etulain, Julia; Negrotto, Soledad; Carestia, Agostina; Pozner, Roberto Gabriel; Romaniuk, María Albertina; D'Atri, Lina Paola; Klement, Giannoula Lakka; Schattner, Mirta

    2012-01-01

    Acidosis is one of the hallmarks of tissue injury such as trauma, infection, inflammation, and tumour growth. Although platelets participate in the pathophysiology of all these processes, the impact of acidosis on platelet biology has not been studied outside of the quality control of laboratory aggregation assays or platelet transfusion optimization. Herein, we evaluate the effect of physiologically relevant changes in extracellular acidosis on the biological function of platelets, placing particular emphasis on haemostatic and secretory functions. Platelet haemostatic responses such as adhesion, spreading, activation of αIIbβ3 integrin, ATP release, aggregation, thromboxane B2 generation, clot retraction and procoagulant activity including phosphatidilserine exposure and microparticle formation, showed a statistically significant inhibition of thrombin-induced changes at pH of 7.0 and 6.5 compared to the physiological pH (7.4). The release of alpha granule content was differentially regulated by acidosis. At low pH, thrombin or collagen-induced secretion of vascular endothelial growth factor and endostatin were dramatically reduced. The release of von Willebrand factor and stromal derived factor-1α followed a similar, albeit less dramatic pattern. In contrast, the induction of CD40L was not changed by low pH, and P-selectin exposure was significantly increased. While the generation of mixed platelet-leukocyte aggregates and the increased chemotaxis of neutrophils mediated by platelets were further augmented under acidic conditions in a P-selectin dependent manner, the increased neutrophil survival was independent of P-selectin expression. In conclusion, our results indicate that extracellular acidosis downregulates most of the haemostatic platelet functions, and promotes those involved in amplifying the neutrophil-mediated inflammatory response.

  6. Platelet activation and platelet-leukocyte interaction in dogs naturally infected with Babesia rossi.

    Science.gov (United States)

    Goddard, Amelia; Leisewitz, Andrew L; Kristensen, Annemarie T; Schoeman, Johan P

    2015-09-01

    Using flow cytometry, platelet-leukocyte aggregate (PLA) formation has previously been documented in dogs with a variety of systemic inflammatory disorders and immune-mediated haemolytic anaemia. Platelet activation and subsequent interaction between platelets and leukocytes are important for regulating innate immunity and systemic inflammation. The objective of this study was to investigate PLA formation in canine babesiosis and to determine whether it was associated with outcome. Blood was collected from 36 client-owned dogs diagnosed with Babesia rossi infection and 15 healthy controls using EDTA as anticoagulant. Activated platelets and PLA formation were detected by measuring surface expression of P-selectin (CD62P) on platelets, monocytes and neutrophils. Of the Babesia-infected dogs, 29 survived and seven died. The percentage of CD62P-positive monocytes was significantly higher (P = 0.036) in the Babesia-infected dogs (54%) than in healthy control dogs (35.3%). However, there were no significant differences between the Babesia-infected and control groups for CD62P-positive platelets (4.9% and 1.2%, respectively) and CD62P-positive neutrophils (28.3% and 17.9%, respectively). The percentage of CD62P-positive monocytes was significantly higher (P = 0.019) in the survivors (58.9%) than in healthy control dogs; however, there were no significant differences between the non-survivors (39.2%) and the controls or between survivors and non-survivors. There were no significant differences between groups for the percentage of CD62P-positive platelets (survivors 4.8%; non-survivors 5.3%; controls 1.2%) or CD62P-positive neutrophils (survivors 31.6%; non-survivors 5.6%; controls 17.9%). In conclusion, Babesia-infected dogs, specifically dogs that survived, had a significantly increased percentage of platelet-monocyte aggregates compared to healthy control dogs. PMID:26088270

  7. The Effect of Butanolides from Cinnamomum tenuifolium on Platelet Aggregation

    OpenAIRE

    Chung-Yi Chen; Sheue-Jiun Chen; Hui-Ming Wu; Huei-Ping Dong

    2013-01-01

    This study investigated the effects of isotenuifolide and tenuifolide B from the stems of Cinnamomum tenuifolium on adenosine diphosphate (ADP)-induced human platelet aggregation. Treatment of human platelet-rich plasma with isotenuifolide (1 and 2 μg/μL) and tenuifolide B (1, 2 and 4 μg/μL) did not have any significant effect on human platelet aggregation in vitro, however, treatment of human platelet-rich plasma with isotenuifolide (4 μg/μL) resulted in an inhibitory effect on platelet aggr...

  8. P-selectin-mediated platelet adhesion promotes tumor growth.

    Science.gov (United States)

    Qi, Cuiling; Wei, Bo; Zhou, Weijie; Yang, Yang; Li, Bin; Guo, Simei; Li, Jialin; Ye, Jie; Li, Jiangchao; Zhang, Qianqian; Lan, Tian; He, Xiaodong; Cao, Liu; Zhou, Jia; Geng, Jianguo; Wang, Lijing

    2015-03-30

    Blood platelets foster carcinogenesis. We found that platelets are accumulated in human tumors. P-selectin deficiency and soluble P-selectin abolish platelet deposition within tumors, decreasing secretion of vascular endothelial growth factor and angiogenesis, thereby suppressing tumor growth. Binding of the P-selectin cytoplasmic tail to talin1 triggers the talin1 N-terminal head to interact with the β3 cytoplasmic tail. This activates αIIbβ3 and recruits platelets into tumors. Platelet infiltration into solid tumors occurs through a P-selectin-dependent mechanism.

  9. Insulin resistance in platelets and monocytes

    NARCIS (Netherlands)

    Gerrits, A.J.

    2010-01-01

    Patients with type 2 diabetes have an increased risk of cardiovascular disease and suffer from thrombotic complications. The aim of the studies presented in this thesis is to elucidate the cause of the prothrombotic situation in type 2 diabetes patients. The studies were focused on platelets and mon

  10. A computerized multichannel platelet aggregometer system.

    Science.gov (United States)

    Kuzara, D; Zoltan, B J; Greathouse, S L; Jordan, C W; Kohler, C A

    1986-08-01

    Commercially available instrumentation for conducting platelet aggregation studies in clinical and research laboratories consists of one-, two-, or four-channel aggregometers used in conjunction with strip chart recorders. These instruments have limited utility in large-scale drug screening and evaluation of the mode of action of drugs or in the clinical diagnosis of platelet disorders. A new instrument, a computerized multichannel aggregometer system (CMPAS) has been developed to collect, display, and analyze platelet aggregation data. The system is comprised of a 24-channel Born-type aggregometer, interfaced to a Rockwell AIM-65 microcomputer through an analogue-to-digital converter and an Epson dot-matrix printer. Each channel is individually calibrated, and aggregation data can be collected on up to 24 different platelet-rich plasma samples simultaneously. Conversational programs written in BASIC prompt the user for the addition of agonists and inhibitors. The tracings for each channel are displayed simultaneously, and a program automatically analyzes the data to generate the following parameters: baseline optical density, maximum aggregation response, positive and negative slopes, time to peak aggregation, and percentage response. Computerized multichannel aggregometer system data outputs are comparable to data generated by a standard Chronolog aggregometer unit. The advantages of the system include multichannel capability, simultaneous display of all channels allowing relative comparisons between control and experimental groups, and time savings and improved efficiency in conducting and analyzing aggregation experiments. PMID:3755779

  11. Platelet-Leukocyte Interaction and Thrombosis

    Institute of Scientific and Technical Information of China (English)

    贺石林; 范金茹

    2007-01-01

    @@ Cerebrocardiac thrombotic disease such as acute myocardial infarction and acute ischemic stroke cause signifieant morbidity and mortality.Present therapies for these diseases besides anticoagulation and fibrinolysis mainly aim toward limiting platelet adhesion and aggregation processes.However,their incomplete effectiveness suggests that other mechanisms may be important.

  12. Mean platelet volume measurement, EDTA or citrate?

    Science.gov (United States)

    Dastjerdi, Mansour Siavash; Emami, Tajolmolouk; Najafian, Alireza; Amini, Masoud

    2006-10-01

    Most laboratories use EDTA for anticoagulation of whole blood prior to automated cell counting but due to platelet swelling, mean platelet volume (MPV) values may increase with its use. MPV changes may be less with acid citrate based anticoagulation. As MPV is a marker of platelet function and its precise measurement is important in a number of clinical situations, this study was performed to assess if EDTA and citrate based anticoagulated blood samples can be used interchangeably for MPV measurement. In this cross sectional descriptive study, EDTA and citrate based anticoagulated blood samples of the same patients were assessed by auto-analyzer within 1 h of sampling. In the 61 evaluated patients, there was a close correlation between MPV as measured by EDTA and citrate, but mean MPV measured from EDTA samples was 0.66 fL (9%) more than citrate. There was also a significant negative correlation between platelets count and MPV by both methods. The results of our study reveal that MPV can be measured accurately by both methods of anticoagulation; EDTA and citrate if analysis be performed within 1 h of sampling. PMID:17607580

  13. Epithelial sodium channel modulates platelet collagen activation.

    Science.gov (United States)

    Cerecedo, Doris; Martínez-Vieyra, Ivette; Alonso-Rangel, Lea; Benítez-Cardoza, Claudia; Ortega, Arturo

    2014-03-01

    Activated platelets adhere to the exposed subendothelial extracellular matrix and undergo a rapid cytoskeletal rearrangement resulting in shape change and release of their intracellular dense and alpha granule contents to avoid hemorrhage. A central step in this process is the elevation of the intracellular Ca(2+) concentration through its release from intracellular stores and on throughout its influx from the extracellular space. The Epithelial sodium channel (ENaC) is a highly selective Na(+) channel involved in mechanosensation, nociception, fluid volume homeostasis, and control of arterial blood pressure. The present study describes the expression, distribution, and participation of ENaC in platelet migration and granule secretion using pharmacological inhibition with amiloride. Our biochemical and confocal analysis in suspended and adhered platelets suggests that ENaC is associated with Intermediate filaments (IF) and with Dystrophin-associated proteins (DAP) via α-syntrophin and β-dystroglycan. Migration assays, quantification of soluble P-selectin, and serotonin release suggest that ENaC is dispensable for migration and alpha and dense granule secretion, whereas Na(+) influx through this channel is fundamental for platelet collagen activation.

  14. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF).

    Science.gov (United States)

    Dohan Ehrenfest, David M; Rasmusson, Lars; Albrektsson, Tomas

    2009-03-01

    The topical use of platelet concentrates is recent and its efficiency remains controversial. Several techniques for platelet concentrates are available; however, their applications have been confusing because each method leads to a different product with different biology and potential uses. Here, we present classification of the different platelet concentrates into four categories, depending on their leucocyte and fibrin content: pure platelet-rich plasma (P-PRP), such as cell separator PRP, Vivostat PRF or Anitua's PRGF; leucocyte- and platelet-rich plasma (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan or GPS PRP; pure plaletet-rich fibrin (P-PRF), such as Fibrinet; and leucocyte- and platelet-rich fibrin (L-PRF), such as Choukroun's PRF. This classification should help to elucidate successes and failures that have occurred so far, as well as providing an objective approach for the further development of these techniques.

  15. Unaltered Angiogenesis-Regulating Activities of Platelets in Mild Type 2 Diabetes Mellitus despite a Marked Platelet Hyperreactivity

    Science.gov (United States)

    Miao, Xinyan; Zhang, Wei; Huang, Zhangsen

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is associated with platelet dysfunction and impaired angiogenesis. Aim of the study is to investigate if platelet dysfunction might hamper platelet angiogenic activities in T2DM patients. Sixteen T2DM patients and gender/age-matched non-diabetic controls were studied. Flow cytometry and endothelial colony forming cell (ECFC) tube formation on matrigel were used to assess platelet reactivity and angiogenic activity, respectively. Thrombin receptor PAR1-activating peptide (PAR1-AP) induced higher platelet P-selectin expression, and evoked more rapid and intense platelet annexin V binding in T2DM patients, seen as a more rapid increase of annexin V+ platelets (24.3±6.4% vs 12.6±3.8% in control at 2 min) and a higher elevation (30.9±5.1% vs 24.3±3.0% at 8 min). However, PAR1-AP and PAR4-AP induced similar releases of angiogenic regulators from platelets, and both stimuli evoked platelet release of platelet angiogenic regulators to similar extents in T2DM and control subjects. Thus, PAR1-stimulated platelet releasate (PAR1-PR) and PAR4-PR similarly enhanced capillary-like network/tube formation of ECFCs, and the enhancements did not differ between T2DM and control subjects. Direct supplementation of platelets to ECFCs at the ratio of 1:200 enhanced ECFC tube formation even more markedly, leading to approximately 100% increases of the total branch points of ECFC tube formation, for which the enhancements were also similar between patients and controls. In conclusion, platelets from T2DM subjects are hyperreactive. Platelet activation induced by high doses of PAR1-AP, however, results in similar releases of angiogenic regulators in mild T2DM and control subjects. Platelets from T2DM and control subjects also demonstrate similar enhancements on ECFC angiogenic activities. PMID:27612088

  16. Detection of dengue virus in platelets isolated from dengue patients.

    Science.gov (United States)

    Noisakran, Sansanee; Gibbons, Robert V; Songprakhon, Pucharee; Jairungsri, Aroonroong; Ajariyakhajorn, Chuanpis; Nisalak, Ananda; Jarman, Richard G; Malasit, Prida; Chokephaibulkit, Kulkanya; Perng, Guey Chuen

    2009-03-01

    Though thrombocytopenia or dysfunction of platelets is common in dengue virus infection, the role of platelets has not been established. We enrolled 33 hospitalized children with serologically confirmed dengue virus infection. Blood specimens were collected during hospitalization. Platelets and plasma were isolated from the whole blood. Detection of dengue virus in plasma and platelets was carried out by RT-PCR with primers that can differentiate different dengue serotypes simultaneously, and by electron transmission microscopy (EM). Dengue viral RNA was detected in the platelets and plasma by conventional RT-PCR. A significantly higher percentage of dengue viral RNA was detected in platelets than in plasma (p = 0.03). Platelets isolated 5 days after onset of fever were most likely positive for viral RNA. Concurrent infection or co-circulation with multiple dengue serotypes was observed in 12% of patients. Infrequently, negative-stranded dengue viral RNA was detected in platelets and in plasma. Importantly, EM confirmed the presence of dengue viral-like particles inside platelets prepared from dengue patients. Our findings suggest the presence of dengue virus in platelets may be associated with the dysfunction of platelets observed in dengue patients.

  17. Generation of Anti-platelet Autoantibody During Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Huan-Yao Lei

    2008-01-01

    Full Text Available Dengue virus infection causes dengue fever, Dengue Hemorrhagic Fever (DHF and Dengue Shock Syndrome (DSS. Thrombocytopenia is common in dengue fever and is always found in DHF/DSS. The pathogenesis of thrombocytopenia is poorly understood. To further understand the relationship between anti-dengue virus antibody and anti-platelet antibody, we generated monoclonal anti-dengue virus antibodies from the dengue virus infected mice that developed transient thrombocytopenia post dengue infection. The analysis of a panel of monoclonal anti-NS-1 antibodies reveals three different patterns of platelet binding: strong, intermediate, or dull. Their isotypes are different, some are IgM while others are IgG1. Most of anti-platelet antibodies are cross-reactive with NS-1 of dengue virus and can be competitively inhibited by recombinant NS-1 protein, suggesting a molecular mimicry between dengue virus NS-1 protein and platelet. A clone, 13-F4-G5, preferentially bound activated platelets, can recognize two or three proteins around 150 kD on platelets. The binding to platelet would lyse the platelet in the presence of complement or enhance the ADP-induced platelet aggregation. Furthermore, some of these monoclonal antibodies would also react with the cellular antigens of BHK. Based on the data, we conclude that dengue virus infection induces auto anti-platelet antibodies which thereafter may involve in the manifestation of thrombocytopenia. A molecular mimicry between NS-1 and platelet is demonstrated.

  18. Emerging roles for platelets as immune and inflammatory cells.

    Science.gov (United States)

    Morrell, Craig N; Aggrey, Angela A; Chapman, Lesley M; Modjeski, Kristina L

    2014-05-01

    Despite their small size and anucleate status, platelets have diverse roles in vascular biology. Not only are platelets the cellular mediator of thrombosis, but platelets are also immune cells that initiate and accelerate many vascular inflammatory conditions. Platelets are linked to the pathogenesis of inflammatory diseases such as atherosclerosis, malaria infection, transplant rejection, and rheumatoid arthritis. In some contexts, platelet immune functions are protective, whereas in others platelets contribute to adverse inflammatory outcomes. In this review, we will discuss platelet and platelet-derived mediator interactions with the innate and acquired arms of the immune system and platelet-vessel wall interactions that drive inflammatory disease. There have been many recent publications indicating both important protective and adverse roles for platelets in infectious disease. Because of this new accumulating data, and the fact that infectious disease continues to be a leading cause of death globally, we will also focus on new and emerging concepts related to platelet immune and inflammatory functions in the context of infectious disease.

  19. Improving platelet transfusion safety: biomedical and technical considerations.

    Science.gov (United States)

    Garraud, Olivier; Cognasse, Fabrice; Tissot, Jean-Daniel; Chavarin, Patricia; Laperche, Syria; Morel, Pascal; Lefrère, Jean-Jacques; Pozzetto, Bruno; Lozano, Miguel; Blumberg, Neil; Osselaer, Jean-Claude

    2016-03-01

    Platelet concentrates account for near 10% of all labile blood components but are responsible for more than 25% of the reported adverse events. Besides factors related to patients themselves, who may be particularly at risk of side effects because of their underlying illness, there are aspects of platelet collection and storage that predispose to adverse events. Platelets for transfusion are strongly activated by collection through disposal equipment, which can stress the cells, and by preservation at 22 °C with rotation or rocking, which likewise leads to platelet activation, perhaps more so than storage at 4 °C. Lastly, platelets constitutively possess a very large number of bioactive components that may elicit pro-inflammatory reactions when infused into a patient. This review aims to describe approaches that may be crucial to minimising side effects while optimising safety and quality. We suggest that platelet transfusion is complex, in part because of the complexity of the "material" itself: platelets are highly versatile cells and the transfusion process adds a myriad of variables that present many challenges for preserving basal platelet function and preventing dysfunctional activation of the platelets. The review also presents information showing--after years of exhaustive haemovigilance--that whole blood buffy coat pooled platelet components are extremely safe compared to the gold standard (i.e. apheresis platelet components), both in terms of acquired infections and of immunological/inflammatory hazards. PMID:26674828

  20. Current and emerging approaches for evaluating platelet disorders.

    Science.gov (United States)

    Podda, G; Femia, E A; Cattaneo, M

    2016-05-01

    Platelets play a central role in physiological hemostasis and also in pathological thrombosis. It is well established that congenital or acquired abnormalities of platelet function are associated with a heightened risk of bleeding of variable severity and excessive hemorrhage after surgery or trauma. Several kinds of different platelet function tests have been developed over the years to identify or diagnose platelet function disorders. The use of these tests for the assessment of thrombotic risk or for monitoring the effects of drugs inhibiting platelet function is not well established. Light transmission aggregometry (LTA) is the gold standard for the study of patients with defects of platelet function. Its results are affected by several pre-analytical and analytical variables. The Subcommittee on Platelet Physiology of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis published official guidelines for the standardization of the variables affecting LTA, which should be followed to harmonize the procedures across different laboratories worldwide. The lumi-aggregometer, a modification of LTA that measures platelet secretion in parallel with aggregation, is preferable to LTA for diagnosing inherited defects of platelet function, because it is more sensitive to the most common disorders, which are characterized by abnormalities of platelet secretion. LTA (or lumi-aggregometry) is useful as a first screening test of patients with the clinical suspicion of defects of platelet function, because it helps to provide an interim diagnostic hypothesis, which can then be confirmed or discounted using appropriate and specific tests. PMID:27426860

  1. Indium-111-labeled platelet scintigraphy in carotid atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Minar, E.; Ehringer, H.; Dudczak, R.; Schoefl, R.J.; Jung, M.; Koppensteiner, R.; Ahmadi, R.; Kretschmer, G.

    1989-01-01

    We evaluated platelet accumulation in carotid arteries by means of a dual-radiotracer method, using indium-111-labeled platelets and technetium-99m-labeled human serum albumin, in 123 patients (92 men, 31 women; median age 60 years). Sixty patients had symptoms of transient ischemic carotid artery disease, and 63 patients with peripheral arterial occlusive disease served as controls. Antiplatelet treatment with acetylsalicylic acid was taken by 53 of the 123 patients. In 36 of the 60 symptomatic patients, platelet scintigraphy was repeated 3-4 days after carotid endarterectomy. Comparison of different scintigraphic parameters (platelet accumulation index and percent of the injected dose of labeled platelets at the carotid bifurcation) showed no significant differences between symptomatic and asymptomatic patients, and the severity of stenosis and the presence of plaque ulceration also had no influence on the parameters. There was no difference between patients with a short (less than 4 weeks) or long (greater than 4 weeks) interval from the last transient ischemic attack to scintigraphy and no difference between patients with or without antiplatelet treatment. Classifying the patients according to plaque morphology judged by high-resolution real-time ultrasonography also demonstrated no differences. No significant correlation was found between any scintigraphic parameter and other platelet function parameters such as platelet survival time, platelet turnover rate, and concentration of platelet-specific proteins. Quantification of platelet deposition after carotid endarterectomy in 36 patients demonstrated a significant increase of the median platelet accumulation index and the percent injected dose index.

  2. Human platelets efficiently kill IgG-opsonized E. coli.

    Science.gov (United States)

    Riaz, Anum H; Tasma, Brian E; Woodman, Michael E; Wooten, R Mark; Worth, Randall G

    2012-06-01

    Platelets are known contributors of hemostasis but have recently been shown to be important in inflammation and infectious diseases. Moreover, thrombocytopenia is often observed in patients with sepsis. We previously reported that platelets actively phagocytosed IgG-coated latex beads. In this study, the capacity of human platelets to participate in host defense against bacterial infections was determined by assessing their ability to kill Escherichia coli. Washed human platelets were incubated with unopsonized or IgG-opsonized E. coli and evaluated for binding and killing of E. coli. We found that although both unopsonized and IgG-opsonized E. coli were associated with platelets, only IgG-opsonized E. coli were efficiently killed unless platelets were activated by a potent agonist. The bactericidal activity was dependent on FcγRIIA, was sensitive to cytochalasin D, but was not due to reactive oxygen metabolites. These data suggest that platelets may play an important role in protection against infection.

  3. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk.

    Science.gov (United States)

    Zhu, Weifei; Gregory, Jill C; Org, Elin; Buffa, Jennifer A; Gupta, Nilaksh; Wang, Zeneng; Li, Lin; Fu, Xiaoming; Wu, Yuping; Mehrabian, Margarete; Sartor, R Balfour; McIntyre, Thomas M; Silverstein, Roy L; Tang, W H Wilson; DiDonato, Joseph A; Brown, J Mark; Lusis, Aldons J; Hazen, Stanley L

    2016-03-24

    Normal platelet function is critical to blood hemostasis and maintenance of a closed circulatory system. Heightened platelet reactivity, however, is associated with cardiometabolic diseases and enhanced potential for thrombotic events. We now show gut microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to platelet hyperreactivity and enhanced thrombosis potential. Plasma TMAO levels in subjects (n > 4,000) independently predicted incident (3 years) thrombosis (heart attack, stroke) risk. Direct exposure of platelets to TMAO enhanced sub-maximal stimulus-dependent platelet activation from multiple agonists through augmented Ca(2+) release from intracellular stores. Animal model studies employing dietary choline or TMAO, germ-free mice, and microbial transplantation collectively confirm a role for gut microbiota and TMAO in modulating platelet hyperresponsiveness and thrombosis potential and identify microbial taxa associated with plasma TMAO and thrombosis potential. Collectively, the present results reveal a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thrombosis risk. PMID:26972052

  4. Blood platelet counts, morphology and morphometry in lions, Panthera leo

    Directory of Open Access Journals (Sweden)

    L. Du Plessis

    2009-09-01

    Full Text Available Due to logistical problems in obtaining sufficient blood samples from apparently healthy animals in the wild in order to establish normal haematological reference values, only limited information regarding the blood platelet count and morphology of free-living lions (Panthera leo is available. This study provides information on platelet counts and describes their morphology with particular reference to size in two normal, healthy and free-ranging lion populations. Blood samples were collected from a total of 16 lions. Platelet counts, determined manually, ranged between 218 and 358 x 109/ℓ. Light microscopy showed mostly activated platelets of various sizes with prominent granules. At the ultrastructural level the platelets revealed typical mammalian platelet morphology. However, morphometricanalysis revealed a significant difference (P < 0.001 in platelet size between the two groups of animals. Basic haematological information obtained in this study may be helpful in future comparative studies between animals of the same species as well as in other felids.

  5. The Effect of Hematocrit on Platelet Adhesion: Experiments and Simulations.

    Science.gov (United States)

    Spann, Andrew P; Campbell, James E; Fitzgibbon, Sean R; Rodriguez, Armando; Cap, Andrew P; Blackbourne, Lorne H; Shaqfeh, Eric S G

    2016-08-01

    The volume fraction of red blood cells (RBCs) in a capillary affects the degree to which platelets are promoted to marginate to near a vessel wall and form blood clots. In this work we investigate the relationship between RBC hematocrit and platelet adhesion activity. We perform experiments flowing blood samples through a microfluidic channel coated with type 1 collagen and observe the rate at which platelets adhere to the wall. We compare these results with three-dimensional boundary integral simulations of a suspension of RBCs and platelets in a periodic channel where platelets can adhere to the wall. In both cases, we find that the rate of platelet adhesion varies greatly with the RBC hematocrit. We observe that the relative decrease in platelet activity as hematocrit falls shows a similar profile for simulation and experiment. PMID:27508441

  6. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk.

    Science.gov (United States)

    Zhu, Weifei; Gregory, Jill C; Org, Elin; Buffa, Jennifer A; Gupta, Nilaksh; Wang, Zeneng; Li, Lin; Fu, Xiaoming; Wu, Yuping; Mehrabian, Margarete; Sartor, R Balfour; McIntyre, Thomas M; Silverstein, Roy L; Tang, W H Wilson; DiDonato, Joseph A; Brown, J Mark; Lusis, Aldons J; Hazen, Stanley L

    2016-03-24

    Normal platelet function is critical to blood hemostasis and maintenance of a closed circulatory system. Heightened platelet reactivity, however, is associated with cardiometabolic diseases and enhanced potential for thrombotic events. We now show gut microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to platelet hyperreactivity and enhanced thrombosis potential. Plasma TMAO levels in subjects (n > 4,000) independently predicted incident (3 years) thrombosis (heart attack, stroke) risk. Direct exposure of platelets to TMAO enhanced sub-maximal stimulus-dependent platelet activation from multiple agonists through augmented Ca(2+) release from intracellular stores. Animal model studies employing dietary choline or TMAO, germ-free mice, and microbial transplantation collectively confirm a role for gut microbiota and TMAO in modulating platelet hyperresponsiveness and thrombosis potential and identify microbial taxa associated with plasma TMAO and thrombosis potential. Collectively, the present results reveal a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thrombosis risk.

  7. Role of platelet function and platelet membrane glycoproteins in children with primary immune thrombocytopenia.

    Science.gov (United States)

    Liu, Wen-Jun; Bai, Jing; Guo, Qu-Lian; Huang, Zhe; Yang, Hong; Bai, Yong-Qi

    2016-09-01

    The aim of the present study was to examine and understand changes in platelet functions prior to and after the treatment of primary immune thrombocytopenia (ITP) in children. An automatic hematology analyzer and whole blood flow cytometry were used to detect immature platelet fraction (IPF), IPC and membrane glycoproteins (CD62p, PAC-1 and CD42b) in ITP children (ITP group), children with complete response after ITP treatment (ITP-CR group) and children with elective surgery (normal control group). The results showed that, levels of platelet count (PLT) and plateletcrit in the ITP group were lower alhtough the levels of mean platelet volume, platelet distribution width and platelet-large cell ratio (P-LCR) were higher than those in the normal control and ITP-CR groups. PLT in the ITP-CR group was lower than that in the normal controls. Additionally, IPF% was higher in the normal control and ITP-CR groups, IPC was lower in the ITP group compared to the normal control and ITP-CR groups. Furthermore, prior to ADP activation, the expression levels of CD62p, PAC-1 and CD42b in the ITP group were lower in ITP group than those in the normal control and ITP-CR groups. The expression level of PAC-1 was lower in the ITP-CR and normal control groups. No differences were identified in CD62p and CD42b expression levels. Following ATP activation, CD62p, PAC-1 and CD42b expression in the ITP group was lower than that in the normal control and ITP-CR groups. PAC-1 expression was lower while CD62p expression was higher in the ITP-CR group compared to the normal control group. In conclusion, the activation of platelets in ITP children was low. Decreased platelet function, platelet parameters and platelet glycoproteins may be used as markers for monitoring the treatment efficacy in ITP children. PMID:27431926

  8. Platelet-derived ERp57 mediates platelet incorporation into a growing thrombus by regulation of the αIIbβ3 integrin.

    Science.gov (United States)

    Wang, Lu; Wu, Yi; Zhou, Junsong; Ahmad, Syed S; Mutus, Bulent; Garbi, Natalio; Hämmerling, Günter; Liu, Junling; Essex, David W

    2013-11-21

    The platelet protein disulfide isomerase called ERp57 mediates platelet aggregation, but its role in thrombus formation is unknown. To determine the specific role of platelet-derived ERp57 in hemostasis and thrombosis, we generated a megakaryocyte/platelet-specific knockout. Despite normal platelet counts and platelet glycoprotein expression, mice with ERp57-deficient platelets had prolonged tail-bleeding times and thrombus occlusion times with FeCl3-induced carotid artery injury. Using a mesenteric artery thrombosis model, we found decreased incorporation of ERp57-deficient platelets into a growing thrombus. Platelets lacking ERp57 have defective activation of the αIIbβ3 integrin and platelet aggregation. The defect in aggregation was corrected by the addition of exogenous ERp57, implicating surface ERp57 in platelet aggregation. Using mutants of ERp57, we demonstrate the second active site targets a platelet surface substrate to potentiate platelet aggregation. Binding of Alexa 488-labeled ERp57 to thrombin-activated and Mn(2+)-treated platelets lacking β3 was decreased substantially, suggesting a direct interaction of ERp57 with αIIbβ3. Surface expression of ERp57 protein and activity in human platelets increased with platelet activation, with protein expression occurring in a physiologically relevant time frame. In conclusion, platelet-derived ERp57 directly interacts with αIIbβ3 during activation of this receptor and is required for incorporation of platelets into a growing thrombus. PMID:24030382

  9. Circulating endothelial progenitor cell and platelet microparticle impact on platelet activation in hypertension associated with hypercholesterolemia.

    Directory of Open Access Journals (Sweden)

    Nicoleta Alexandru

    Full Text Available AIM: The purpose of this project was to evaluate the influence of circulating endothelial progenitor cells (EPCs and platelet microparticles (PMPs on blood platelet function in experimental hypertension associated with hypercholesterolemia. METHODS: Golden Syrian hamsters were divided in six groups: (i control, C; (ii hypertensive-hypercholesterolemic, HH; (iii 'prevention', HHin-EPCs, HH animals fed a HH diet and treated with EPCs; (iv 'regression', HHfin-EPCs, HH treated with EPCs after HH feeding; (v HH treated with PMPs, HH-PMPs, and (vi HH treated with EPCs and PMPs, HH-EPCs-PMPs. RESULTS: Compared to HH group, the platelets from HHin-EPCs and HHfin-EPCs groups showed a reduction of: (i activation, reflected by decreased integrin 3β, FAK, PI3K, src protein expression; (ii secreted molecules as: SDF-1, MCP-1, RANTES, VEGF, PF4, PDGF and (iii expression of pro-inflammatory molecules as: SDF-1, MCP-1, RANTES, IL-6, IL-1β; TFPI secretion was increased. Compared to HH group, platelets of HH-PMPs group showed increased activation, molecules release and proteins expression. Compared to HH-PMPs group the combination EPCs with PMPs treatment induced a decrease of all investigated platelet molecules, however not comparable with that recorded when EPC individual treatment was applied. CONCLUSION: EPCs have the ability to reduce platelet activation and to modulate their pro-inflammatory and anti-thrombogenic properties in hypertension associated with hypercholesterolemia. Although, PMPs have several beneficial effects in combination with EPCs, these did not improve the EPC effects. These findings reveal a new biological role of circulating EPCs in platelet function regulation, and may contribute to understand their cross talk, and the mechanisms of atherosclerosis.

  10. Genetic engineering of platelets to neutralize circulating tumor cells.

    Science.gov (United States)

    Li, Jiahe; Sharkey, Charles C; Wun, Brittany; Liesveld, Jane L; King, Michael R

    2016-04-28

    Mounting experimental evidence demonstrates that platelets support cancer metastasis. Within the circulatory system, platelets guard circulating tumor cells (CTCs) from immune elimination and promote their arrest at the endothelium, supporting CTC extravasation into secondary sites. Neutralization of CTCs in blood circulation can potentially attenuate metastases to distant organs. Therefore, extensive studies have explored the blockade of platelet-CTC interactions as an anti-metastatic strategy. Such an intervention approach, however, may cause bleeding disorders since the platelet-CTC interactions inherently rely on the blood coagulation cascade including platelet activation. On the other hand, platelets have been genetically engineered to correct inherited bleeding disorders in both animal models and human clinical trials. In this study, inspired by the physical association between platelets and CTCs, platelets were genetically modified to express surface-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a cytokine known to induce apoptosis specifically in tumor cells. The TRAIL-expressing platelets were demonstrated to kill cancer cells in vitro and significantly reduce metastases in a mouse model of prostate cancer metastasis. Our results suggest that using platelets to produce and deliver cancer-specific therapeutics can provide a Trojan-horse strategy of neutralizing CTCs to attenuate metastasis.

  11. Platelets, immune-mediated thrombocytopenias, and fetal hemorrhage.

    Science.gov (United States)

    Xu, Xiaohong Ruby; Gallant, Reid C; Ni, Heyu

    2016-05-01

    Platelets are small versatile blood cells generated from megakaryocytes in the bone marrow and cleared in the reticuloendothelial system. Platelet accumulation (adhesion and aggregation) at the site of injury has been considered the first wave of hemostasis. Interestingly, although fibrinogen and von Willebrand factor (VWF) are documented to be essential for hemostasis, fibrinogen/VWF-independent platelet aggregation and thrombosis still occur. Following platelet activation and phosphatidylserine expression, platelets also contribute to cell-based thrombin generation and blood coagulation - the second wave of hemostasis. Most recently, deposition of fibronectin and other plasma proteins onto the injured vessel wall was identified as a "protein wave" of hemostasis, in which platelets may release their granule proteins and thus also contribute to this very early hemostatic event. Due to the central roles of platelets in hemostasis, excessive platelet clearance may lead to bleeding disorders as observed in auto- and alloimmune-mediated thrombocytopenias. In this review, we will introduce several new pathways of thrombosis and hemostasis as well as antibody Fc-independent platelet clearance, which may play an important role in immune-mediated thrombocytopenias. We will also discuss the roles of platelets in fetal hemostasis that may deserve further investigation. PMID:27207432

  12. Platelets promote allergic asthma through the expression of CD154.

    Science.gov (United States)

    Tian, Jun; Zhu, Tianyi; Liu, Juan; Guo, Zhenhong; Cao, Xuetao

    2015-11-01

    Platelet activation is associated with multiple immune responses and the pathogenesis of various immune-related diseases. However, the exact role and the underlying mechanism of platelets in the progression of allergic asthma remain largely unclear. In this study, we demonstrate that during antigen sensitization, platelets can be activated by ovalbumin (OVA) aerosol via the upregulation of CD154 (CD40L) expression. Platelet transfer promoted allergic asthma progression by inducing more severe leukocyte infiltration and lung inflammation, elevated IgE production and strengthened T helper 2 (Th2) responses in asthma-induced mice. Accordingly, platelet depletion compromised allergic asthma progression. Cd154-deficient platelets failed to promote asthma development, indicating the requirement of CD154 for platelets to promote asthma progression. The mechanistic study showed that platelets inhibited the induction of Foxp3(+) regulatory T cells both in vivo and in vitro at least partially through CD154, providing an explanation for the increase of Th2 responses by platelet transfer. Our study reveals the previously unknown role of platelet CD154 in the promotion of asthma progression by polarizing Th2 responses and inhibiting regulatory T-cell generation and thus provides a potential clue for allergic disease interventions. PMID:25418472

  13. Formulation and Storage of Platelet-Rich Plasma Homemade Product

    Science.gov (United States)

    Giraudo, Laurent; Veran, Julie; Magalon, Jeremy; Coudreuse, Jean-Marie; Magalon, Guy; Dubois, Christophe; Serratrice, Nicolas; Dignat-George, Françoise; Sabatier, Florence

    2012-01-01

    Abstract The platelet-rich plasma (PRP) is an autologous biotherapy based on platelet-healing properties. Here, we developed a simple and reproducible PRP purification protocol based on two successive centrifugations. We evaluated different centrifugation speeds and time-storage durations on the platelet quantity and quality. Sterility and stability of our PRP homemade product were also performed. We prepared PRP from 54 healthy volunteers. We tested activation state, reactivity, and stability of platelets by flow cytometry using basal and adenosine diphosphate (ADP)-induced P-selectin expression markers; growth factor release after platelet activation by an enzyme-linked immunosorbent assay (ELISA); platelet aggregation capacity by aggregrometry assays; clot formation and retraction by thromboelastography; and platelet morphology by ultrastructural analysis. About 130 and 250 g successive speed centrifugations further concentrated platelets while preserving their bioactivity during 6 h (after that, platelet functions were significantly altered). In these conditions, we obtained a highly concentrated pure PRP product (with a low leukocyte count) suitable to study platelet properties. To avoid the loss of efficacy, we recommend injecting PRP under 3 h after preparation. PMID:23516671

  14. Genetic engineering of platelets to neutralize circulating tumor cells.

    Science.gov (United States)

    Li, Jiahe; Sharkey, Charles C; Wun, Brittany; Liesveld, Jane L; King, Michael R

    2016-04-28

    Mounting experimental evidence demonstrates that platelets support cancer metastasis. Within the circulatory system, platelets guard circulating tumor cells (CTCs) from immune elimination and promote their arrest at the endothelium, supporting CTC extravasation into secondary sites. Neutralization of CTCs in blood circulation can potentially attenuate metastases to distant organs. Therefore, extensive studies have explored the blockade of platelet-CTC interactions as an anti-metastatic strategy. Such an intervention approach, however, may cause bleeding disorders since the platelet-CTC interactions inherently rely on the blood coagulation cascade including platelet activation. On the other hand, platelets have been genetically engineered to correct inherited bleeding disorders in both animal models and human clinical trials. In this study, inspired by the physical association between platelets and CTCs, platelets were genetically modified to express surface-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a cytokine known to induce apoptosis specifically in tumor cells. The TRAIL-expressing platelets were demonstrated to kill cancer cells in vitro and significantly reduce metastases in a mouse model of prostate cancer metastasis. Our results suggest that using platelets to produce and deliver cancer-specific therapeutics can provide a Trojan-horse strategy of neutralizing CTCs to attenuate metastasis. PMID:26921521

  15. Platelets promote bacterial dissemination in a mouse model of streptococcal sepsis.

    Science.gov (United States)

    Kahn, Fredrik; Hurley, Sinead; Shannon, Oonagh

    2013-01-01

    Platelets have been reported to contribute to inflammation and inflammatory disorders. In the present study, we demonstrate that platelets contribute to the acute response to bacterial infection in a mouse model of invasive Streptococcus pyogenes infection. Thrombocytopenia occurred rapidly in infected animals and this was associated with platelet activation, formation of platelet-neutrophil complexes and neutrophil activation. In order to assess the role of platelets during infection, platelets were depleted prior to infection. Platelet-depleted animals had significantly decreased platelet-neutrophil complex formation and neutrophil activation in response to infection. Importantly, significantly fewer bacteria disseminated to the blood, lungs, and spleen of platelet-depleted animals. Platelet-depleted animals did not decrease as significantly in weight as the infected control animals. The results demonstrate a previously unappreciated role for platelets during the pathophysiological response to infection, whereby S. pyogenes bacteria bind to platelets and platelets facilitate bacterial dissemination.

  16. Cardiac and vascular imaging with labeled platelets and leukocytes

    International Nuclear Information System (INIS)

    The contribution of platelets in atherosclerosis and thrombosis in animal models and in clinical studies has been quantified with 111In-platelet scintigraphy. New in vitro quantitative techniques have been developed using 111In-labeled platelets to determine the number of adherent platelets on deendothelialized surfaces of damaged vessel walls and synthetic vascular grafts. In vivo imaging techniques are semi-quantitative in nature; in these studies 111In radioactivity on thrombotic vessels or graft surfaces of iliac, femoral, or popliteal arteries is compared with contralateral vessels. Background 111In radioactivity in the circulating blood pool of venous and capillary networks and radioactivity in marrow decreases the sensitivity of these techniques. Subtraction of blood pool radioactivity with 99mTc-labeled autologous red cells and calculation of 111In radioactivity associated with platelet thrombus on vessel walls also have been performed for coronary, carotid, and femoral arteries. Although platelet concentrates are used frequently after open heart surgery (one to six per patient), consumption of platelets in the artificial lung or oxygenator, lysis of platelets during pumping, and suction of blood only recently have been quantified with the use of 111In-labeled platelets. These studies also demonstrated far less trauma to platelets with the use of a membrane rather than a bubble oxygenator. Further reduction in platelet consumption and trauma was observed with the use of prostacyclin, a short-acting drug with significant beneficial effect on platelet thrombus reduction and disaggregation of aggregated platelets. The role of polymorphonuclear leukocytes in inflammation, infection and myocardial infarction, and in vivo evaluation with 111In-leukocyte scintigraphy in animals and humans has been described

  17. Platelet transfusion—the new immunology of an old therapy

    Directory of Open Access Journals (Sweden)

    Moritz eStolla

    2015-02-01

    Full Text Available Platelet transfusion has been a vital therapeutic approach in patients with hematologic malignancies for close to half a century. Randomized trials show that prophylactic platelet transfusions mitigate bleeding in patients with acute myeloid leukemia. However, even with prophylactic transfusions, as many as 75% of patients experience hemorrhage. While platelet transfusion efficacy is modest, questions and concerns have arisen about the risks of platelet transfusion therapy. The acknowledged serious risks of platelet transfusion include viral transmission, bacterial sepsis, and acute lung injury. Less serious adverse effects include allergic and non-hemolytic febrile reactions. Rare hemolytic reactions have occurred due to a common policy of transfusing without regard to ABO type. In the last decade or so, new concerns have arisen; platelet derived lipids are implicated in transfusion related acute lung injury after transfusion. With the recognition that platelets are immune cells came the discoveries that supernatant IL-6, IL-27 sCD40L, and OX40L are closely linked to febrile reactions and sCD40L with acute lung injury. Platelet transfusions are pro-inflammatory, and may be pro-thrombotic. Anti-A and anti-B can bind to incompatible recipient or donor platelets and soluble antigens, impair hemostasis and thus increase bleeding. Finally, stored platelet supernatants contain biological mediators such as VEGF and TGF-β1 that may compromise the host versus tumor response. This is particularly of concern in patients receiving many platelet transfusions, as for acute leukemia. New evidence suggests that removing stored supernatant will improve clinical outcomes.This new view of platelets as pro-inflammatory and immunomodulatory agents suggests that innovative approaches to improving platelet storage and pre-transfusion manipulations to reduce toxicity could substantially improve the efficacy and safety of this long employed therapy.

  18. Platelet transfusion - the new immunology of an old therapy.

    Science.gov (United States)

    Stolla, Moritz; Refaai, Majed A; Heal, Joanna M; Spinelli, Sherry L; Garraud, Olivier; Phipps, Richard P; Blumberg, Neil

    2015-01-01

    Platelet transfusion has been a vital therapeutic approach in patients with hematologic malignancies for close to half a century. Randomized trials show that prophylactic platelet transfusions mitigate bleeding in patients with acute myeloid leukemia. However, even with prophylactic transfusions, as many as 75% of patients, experience hemorrhage. While platelet transfusion efficacy is modest, questions and concerns have arisen about the risks of platelet transfusion therapy. The acknowledged serious risks of platelet transfusion include viral transmission, bacterial sepsis, and acute lung injury. Less serious adverse effects include allergic and non-hemolytic febrile reactions. Rare hemolytic reactions have occurred due to a common policy of transfusing without regard to ABO type. In the last decade or so, new concerns have arisen; platelet-derived lipids are implicated in transfusion-related acute lung injury after transfusion. With the recognition that platelets are immune cells came the discoveries that supernatant IL-6, IL-27 sCD40L, and OX40L are closely linked to febrile reactions and sCD40L with acute lung injury. Platelet transfusions are pro-inflammatory, and may be pro-thrombotic. Anti-A and anti-B can bind to incompatible recipient or donor platelets and soluble antigens, impair hemostasis and thus increase bleeding. Finally, stored platelet supernatants contain biological mediators such as VEGF and TGF-β1 that may compromise the host versus tumor response. This is particularly of concern in patients receiving many platelet transfusions, as for acute leukemia. New evidence suggests that removing stored supernatant will improve clinical outcomes. This new view of platelets as pro-inflammatory and immunomodulatory agents suggests that innovative approaches to improving platelet storage and pre-transfusion manipulations to reduce toxicity could substantially improve the efficacy and safety of this long-employed therapy. PMID:25699046

  19. Platelet Rich Plasma for Treating Chronic Tendinopathy

    OpenAIRE

    Kaux, Jean-François

    2016-01-01

    Tendinopathy is a major problem in medicine and sports traumatology. It is due, inter alia, to mechanical overload. It remains a challenge for the medical world to the extent that its frequent resistance to conventional treatments never promises the patient a favourable response following therapeutic management. The development of platelet-rich plasma (PRP) is a new hope when therapeutic treatments such as NSAIDs, corticosteroid injections, eccentric rehabilitation, shock waves, etc. have sho...

  20. Mean Platelet Volume and Vitamin D Level

    OpenAIRE

    Cumhur Cure, Medine; Cure, Erkan; Yuce, Suleyman; Yazici, Tarkan; Karakoyun, Inanc; EFE, Hasan

    2014-01-01

    Background Vitamin D deficiency and a high mean platelet volume (MPV) are related to cardiovascular disease. We investigated whether vitamin D deficiency is associated with high MPV. Methods This study included 434 patients without chronic disease who were not taking vitamin D or calcium supplements. Vitamin D was measured by chemiluminescent microparticle immunoassay on the Architect-I2000 system (Abbott Diagnostics, USA), and MPV was measured on the Cell-Dyn Ruby analyzer (Abbott Diagnostic...

  1. EVALUATION OF PLATELET COUNTS AND PLATELET INDICES AND THEIR SIGNIFICANT ROLE IN PRE-ECLAMPSIA AND ECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Vijaya

    2014-03-01

    Full Text Available BACKGROUND: Preeclampsia and eclampsia are the most leading cause of maternal mortality in developing countries like ours. The aim of our study is to find out the relation between platelet indices and platelet counts with preeclampsia and eclampsia and their significance as prognostic indicator. MATERIALS AND METHOD: 82 cases of preeclampsia and 63 cases of eclampsia diagnosed between September 2010 to December 2013 were evaluated prospectively. One hundred healthy pregnant women with similar demographic features and gestational age without diagnosis of preeclampsia were included in the study of control group. Blood samples were analyzed by automated hematology analyzer. The platelet count, mean platelet volume and platelet distribution width were compared. RESULTS: The platelet counts were lower while mean platelet volume, platelet distribution width were increased in preeclampsia and eclampsia as compared to control group. CONCLUSION: We found an association between platelet indices and severity of preeclampsia. The estimation of platelet indices can be considered as an early, simple and rapid procedure in the assessment of severity of preeclampsia and eclampsia which can be used as a prognostic marker.

  2. Sticky platelet syndrome: history and future perspectives.

    Science.gov (United States)

    Kubisz, Peter; Ruiz-Argüelles, Guillermo J; Stasko, Jan; Holly, Pavol; Ruiz-Delgado, Guillermo J

    2014-07-01

    The sticky platelet syndrome (SPS) is a thrombophilic qualitative platelet disorder with familial occurrence and autosomal dominant trait, characterized by increased in vitro platelet aggregation after low concentrations of adenosine diphosphate and/or epinephrine. Its clinical manifestation includes arterial thrombosis, pregnancy complications (fetal growth retardation and fetal loss), and less often venous thromboembolism. SPS was considered to be a rare thrombophilic disorder, but it can be found relatively often as a cause of unexplained thrombosis, particularly among patients with arterial thrombosis such as stroke. The syndrome was recognized as a distinct disorder in 1983 by Holiday and further characterized in the 1980s and 1990s, with Mammen and Bick providing the key findings. Although recognized for more than 30 years, significant issues, namely the syndrome's etiology, inheritance, and epidemiology, remain unclear. The aim of the first part of this review is to summarize the previous 35 years of the research into, and to provide a brief historical account of, SPS. The history section is focused particularly on the work of two most prominent investigators: Eberhard F. Mammen and Rodger L. Bick. The second part summarizes the present understanding of the syndrome and outlines unresolved issues and the trends in which the future research is likely to continue. PMID:24911675

  3. Platelet indices in dogs with Babesia rossi infection

    DEFF Research Database (Denmark)

    Goddard, Amelia; Leisewitz, Andrew L; Kristensen, Annemarie Thuri;

    2015-01-01

    BACKGROUND: Thrombocytopenia without clinical bleeding is a consistent finding in virulent canine babesiosis. OBJECTIVES: The purpose of the study was to investigate the platelet index phenotype in Babesia rossi-infected dogs and the association with disease outcome. We hypothesized that an incre......BACKGROUND: Thrombocytopenia without clinical bleeding is a consistent finding in virulent canine babesiosis. OBJECTIVES: The purpose of the study was to investigate the platelet index phenotype in Babesia rossi-infected dogs and the association with disease outcome. We hypothesized...... that an increased proportion of large, activated platelets would be present. METHODS: Ninety-six infected and 15 control dogs were included. Babesia-infected dogs were further divided into survivors and nonsurvivors. Platelet count, mean platelet volume (MPV), platelet volume distribution width (PDW), plateletcrit...

  4. Feasibility of Using Multilayer Platelets as Toughening Agents

    Directory of Open Access Journals (Sweden)

    Yuan-Liang Chin

    2009-12-01

    Full Text Available It is known that the toughness of brittle ceramics can be improved significantly with the addition of hard platelets. In the present study, platelet-shape multilayer ceramic laminates are utilized as a toughening agent for alumina ceramics. They are prepared by laminating the BaTiO3-based ceramic tapes. Although the elastic modulus of the BaTiO3-based platelets is lower than that of the alumina matrix, and the platelets are also reactive to alumina at elevated temperatures, the weak platelets are found to exhibit the ability to deflect major matrix cracks by forming a large number of microcrack branches within the platelets, thus achieving the desired toughening effect.

  5. Platelet Function Tests: A Review of Progresses in Clinical Application

    Directory of Open Access Journals (Sweden)

    Jae-Lim Choi

    2014-01-01

    Full Text Available The major goal of traditional platelet function tests has been to screen and diagnose patients who present with bleeding problems. However, as the central role of platelets implicated in the etiology of arterial thrombotic diseases such as myocardial infarction and stroke became widely known, platelet function tests are now being promoted to monitor the efficacy of antiplatelet drugs and also to potentially identify patients at increased risk of thrombosis. Beyond hemostasis and thrombosis, an increasing number of studies indicate that platelets play an integral role in intercellular communication, are mediators of inflammation, and have immunomodulatory activity. As new potential biomarkers and technologies arrive at the horizon, platelet functions testing appears to take on a new aspect. This review article discusses currently available clinical application of platelet function tests, placing emphasis on essential characteristics.

  6. Platelet function testing: methods of assessment and clinical utility.

    LENUS (Irish Health Repository)

    Mylotte, Darren

    2012-02-01

    Platelets play a central role in the regulation of both thrombosis and haemostasis yet tests of platelet function have, until recently, been exclusively used in the diagnosis and management of bleeding disorders. Recent advances have demonstrated the clinical utility of platelet function testing in patients with cardiovascular disease. The ex vivo measurement of response to antiplatelet therapies (aspirin and clopidogrel), by an ever-increasing array of platelet function tests, is with some assays, predictive of adverse clinical events and thus, represents an emerging area of interest for both the clinician and basic scientist. This review article will describe the advantages and disadvantages of the currently available methods of measuring platelet function and discuss both the limitations and emerging data supporting the role of platelet function studies in clinical practice.

  7. Platelet function testing: methods of assessment and clinical utility.

    LENUS (Irish Health Repository)

    Mylotte, Darren

    2011-01-01

    Platelets play a central role in the regulation of both thrombosis and haemostasis yet tests of platelet function have, until recently, been exclusively used in the diagnosis and management of bleeding disorders. Recent advances have demonstrated the clinical utility of platelet function testing in patients with cardiovascular disease. The ex vivo measurement of response to antiplatelet therapies (aspirin and clopidogrel), by an ever-increasing array of platelet function tests, is with some assays, predictive of adverse clinical events and thus, represents an emerging area of interest for both the clinician and basic scientist. This review article will describe the advantages and disadvantages of the currently available methods of measuring platelet function and discuss both the limitations and emerging data supporting the role of platelet function studies in clinical practice.

  8. Platelet and other hemostatic characteristics in patients with chronic urticaria.

    Science.gov (United States)

    Isiksacan, Nilgun; Koser, Murat; Cemsitoglu, Ferhan; Kucuksezer, Umut C; Gurdol, Figen

    2015-04-01

    Several publications have pointed out the importance of coagulation and fibrinolysis in the occurrence of chronic urticaria (CU), but only a few indicated the direct role of platelets. We assessed platelet aggregation and evaluated parameters of coagulation and fibrinolysis in patients with CU. Patients (n = 34) diagnosed as having CU and 36 healthy controls were enrolled. Platelet aggregation was assayed using an impedance aggregometer and adenosine diphosphate, arachidonic acid, thrombin receptor-activating peptide (TRAP), and ristocetin as agonists. In patients with CU, significantly decreased platelet aggregation to some agonists (ristocetin and TRAP) was observed. The D-dimer levels were elevated, mean platelet volume was decreased, but no alteration was observed in other coagulation assays. Elevated D-dimer levels indicated that coagulation and fibrinolysis are activated in the patients with CU. Evaluation of platelet function may contribute to identify the role of these cells in the pathogenesis of CU.

  9. Platelet activation risk index as a prognostic thrombosis indicator.

    Science.gov (United States)

    Zlobina, K E; Guria, G Th

    2016-01-01

    Platelet activation in blood flow under high, overcritical shear rates is initiated by Von Willebrand factor. Despite the large amount of experimental data that have been obtained, the value of the critical shear rate, above which von Willebrand factor starts to activate platelets, is still controversial. Here, we recommend a theoretical approach to elucidate how the critical blood shear rate is dependent on von Willebrand factor size. We derived a diagram of platelet activation according to the shear rate and von Willebrand factor multimer size. We succeeded in deriving an explicit formula for the dependence of the critical shear rate on von Willebrand factor molecule size. The platelet activation risk index was introduced. This index is dependent on the flow conditions, number of monomers in von Willebrand factor, and platelet sensitivity. Probable medical applications of the platelet activation risk index as a universal prognostic index are discussed. PMID:27461235

  10. Characterization of canine platelet adhesion to extracellular matrix proteins.

    Science.gov (United States)

    Pelagalli, Alessandra; Pero, Maria Elena; Mastellone, Vincenzo; Cestaro, Anna; Signoriello, Simona; Lombardi, Pietro; Avallone, Luigi

    2011-07-01

    Canine platelets have been extensively studied but little is known about specific aspects such as adhesion. Platelet adhesion is a critical step during haemostasis and thrombosis as well as during inflammatory and immunopathogenic responses. The aim of this study was to evaluate the adhesive properties of canine platelets using fibrinogen and collagen as substrates immobilized on plates. Adhesion was monitored for 120 min and the effect of adenosine 5'-diphosphate (ADP) was assayed. The results showed that canine platelets displayed good adhesion activity that was significantly time-dependent. Moreover, ADP was able to enhance platelet adhesion in a dose-dependent manner. The findings aid knowledge of the adhesion process and suggest a specific role of surface platelet receptors in mediating the interaction with extracellular matrix proteins.

  11. Metabolic Plasticity in Resting and Thrombin Activated Platelets

    OpenAIRE

    Ravi, Saranya; Chacko, Balu; Sawada, Hirotaka; Kramer, Philip A.; Johnson, Michelle S.; Benavides, Gloria A.; O’DONNELL, Valerie; Marques, Marisa B.; Darley-Usmar, Victor M.

    2015-01-01

    Platelet thrombus formation includes several integrated processes involving aggregation, secretion of granules, release of arachidonic acid and clot retraction, but it is not clear which metabolic fuels are required to support these events. We hypothesized that there is flexibility in the fuels that can be utilized to serve the energetic and metabolic needs for resting and thrombin-dependent platelet aggregation. Using platelets from healthy human donors, we found that there was a rapid throm...

  12. Topographic Cues Reveal Two Distinct Spreading Mechanisms in Blood Platelets

    OpenAIRE

    Rabea Sandmann; Sarah Köster

    2016-01-01

    Blood platelets are instrumental in blood clotting and are thus heavily involved in early wound closure. After adhering to a substrate they spread by forming protrusions like lamellipodia and filopodia. However, the interaction of these protrusions with the physical environment of platelets while spreading is not fully understood. Here we dynamically image platelets during this spreading process and compare their behavior on smooth and on structured substrates. In particular we analyze the te...

  13. Slow Coronary Flow Phenomenon and Increased Platelet Volume Indices

    OpenAIRE

    Seyyed-Mohammadzad, Mir Hossein; Khademvatani, Kamal; Kerachian, Abdollah; Eskandari, Ramin; Rezaei, Yousef

    2014-01-01

    Background and Objectives We sought to determine the relationship between mean platelet volume (MPV), platelet distribution width (PDW), and platelet larger cell ratio (P-LCR) with slow coronary flow (SCF). Subjects and Methods Eighty participants who underwent coronary angiography were divided into two groups, 50 participants with SCF as case group, and 30 with normal coronary flow (NCF) as control group. Baseline characteristics and laboratory data were collected before angiography. Results...

  14. /sup 111/In-oxine platelet survivals in thrombocytopenic infants

    Energy Technology Data Exchange (ETDEWEB)

    Castle, V.; Coates, G.; Kelton, J.G.; Andrew, M.

    1987-09-01

    Thrombocytopenia is a common occurrence (20%) in sick neonates, but the causes have not been well studied. In this report we demonstrate that thrombocytopenia in the neonate is characterized by increased platelet destruction as shown by shortened homologous /sup 111/In-oxine-labeled platelet life spans. Thirty-one prospectively studied thrombocytopenic neonates were investigated by measuring the /sup 111/In-labeled platelet life span, platelet-associated IgG (PAIgG), and coagulation screening tests. In every infant, the thrombocytopenia was shown to have a destructive component since the mean platelet life span was significantly shortened to 65 +/- 6 (mean +/- SEM) hours with a range of one to 128 hours compared with adult values (212 +/- 8; range, 140 to 260; gamma function analysis). The platelet survival was directly related to the lowest platelet count and inversely related to both the highest mean platelet volume and duration of the thrombocytopenia. In 22 infants the percent recovery of the radiolabeled platelets was less than 50%, which suggested that increased sequestration also contributed to the thrombocytopenia. Infants with laboratory evidence of disseminated intravascular coagulation (n = 8) or immune platelet destruction evidenced by elevated levels of PAIgG (n = 13) had even shorter platelet survivals and a more severe thrombocytopenia compared with the ten infants in whom an underlying cause for the thrombocytopenia was not apparent. Full-body scintigraphic images obtained in 11 infants showed an increased uptake in the spleen and liver, with a spleen-to-liver ratio of 3:1. This study indicates that thrombocytopenia in sick neonates is primarily destructive, with a subgroup having evidence of increased platelet sequestration.

  15. Clinical Applications of Platelet-Rich Plasma in Patellar Tendinopathy

    OpenAIRE

    D. U. Jeong; C.-R. Lee; Lee, J.H.; Pak, J.; L.-W. Kang; B. C. Jeong; Lee, S. H.

    2014-01-01

    Platelet-rich plasma (PRP), a blood derivative with high concentrations of platelets, has been found to have high levels of autologous growth factors (GFs), such as transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), fibroblastic growth factor (FGF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). These GFs and other biological active proteins of PRP can promote tissue healing through the regulation of fibrosis and angiogenesis. Moreover,...

  16. Platelet-Rich Plasma in a Patient with Cerebral Palsy

    OpenAIRE

    Alcaraz, Jesús; Oliver, Antonio; Sánchez, Juana María

    2015-01-01

    Patient: Male, 6 Final Diagnosis: Cerebral palsy secundary perinatal hypoxia Symptoms: Cognitive impairment • epilectic seizure Medication: Platelet rich plasma Clinical Procedure: Cognitive improvement with neuroestimulator and neuroregenerator power of platelet rich plasma injection Specialty: Hematology Objective: Unusual clinical course Background: The use of platelet-rich plasma is a now a common medical technique known as regenerative medicine, through power cell activation and differen...

  17. Inhibition of angiogenesis by platelets in systemic sclerosis patients

    OpenAIRE

    Hirigoyen, Daniela; Burgos, Paula I.; Mezzano, Veronica; Duran, Josefina; Barrientos, Magaly; Saez, Claudia G.; Panes, Olga; Mezzano, Diego; Iruretagoyena, Mirentxu

    2015-01-01

    Introduction Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvascular damage, inflammation, and fibrosis. It has become increasingly evident that platelets, beyond regulating hemostasis, are important in inflammation and innate immunity. Platelets may be an important source of proinflammatory and profibrotic cytokines in the vascular microenvironment. In this study, we sought to assess the contribution of platelet-derived factors in patients with SSc to the angi...

  18. Platelet Activation and Inhibition in Connection with Vascular Stents

    OpenAIRE

    Christensen, Kjeld

    2007-01-01

    This thesis describes the Chandler loop, which makes it possible to conduct studies in vitro of molecular and cellular interactions between whole blood and stents. It was possible to monitor activation and inhibition of the cascades systems, leukocytes and platelets by combining different platelet inhibitors and heparin coating of stents. The clinical study was performed on patients with ACS undergoing PCI and stent implantation. In this study platelet activation markers P-selectin, and αIIb/...

  19. Imaging thrombus with radiolabelled monoclonal antibody to platelets

    International Nuclear Information System (INIS)

    Indium-111-hydroxyquinoline labelled platelets, though useful in the detection of thrombus, have not gained widespread use owing to the time and technical skill required for their preparation. A study was therefore conducted evaluating a new method of imaging thrombus with platelets radiolabelled with a 111In labelled monoclonal antibody, P256, directed to the platelet surface glycoprotein complex IIb/IIIa. When the number of receptors occupied by P256 was less than 3% of the total available on the platelet surface platelet function, as assessed by platelet aggregometry, was undisturbed. P256 was radiolabelled with 111In using diethylenetriaminepenta-acetic acid, which achieved a specific activity of 185 MBq (5 mCi)/mg. No impairment of immunoreactivity was detected at this specific activity. Platelets were labelled with radiolabelled monoclonal antibody in vitro in two patients at a receptor occupancy of 6% and in vivo - that is, by direct intravenous injection of P256 - in six patients at a receptor occupancy of 1%. In vivo recovery and biodistribution kinetics suggested that after in vitro labelling platelets were minimally activated. The 111In kinetics recorded after intravenous P256 suggested rapid and efficient radiolabelling of platelets and gave no indication of platelet activation. Of the six patients who received intravenous P256, three had documented thrombus, tow of whom gave positive results on P256 platelet scintigraphy. The third subject had chromic deep venous thrombosis and was scintigraphically negative. Imaging thrombus using a radiolabelled monoclonal antibody directed to platelets appears to offer great potential as a simple, non-invasive approach to the diagnosis of thrombosis. 3 refs. (Author)

  20. Platelets and infections—complex interactions with bacteria

    Directory of Open Access Journals (Sweden)

    Hind eHAMZEH-COGNASSE

    2015-02-01

    Full Text Available Platelets can be considered sentinels of vascular system due to their high number in the circulation and to the range of functional immunoreceptors they express. Platelets express a wide range of potential bacterial receptors, including complement receptors, FcγRII, Toll-Like Receptors but also integrins conventionally described in the hemostatic response, such as GPIIb-IIIa or GPIb. Bacteria bind these receptors either directly, or indirectly via fibrinogen, fibronectin, the first complement C1q, the von Willebrand Factor, etc. The fate of platelet bound bacteria is questioned. Several studies reported the ability of activated platelets to internalize bacteria such as Staphylococcus aureus or Porphyromonas gingivalis, though there is no clue on what happens thereafter. Are they sheltered from the immune system in the cytoplasm of platelets or are they lysed? Indeed, while the presence of phagolysosome has not been demonstrated in platelets, they contain antimicrobial peptides that were shown to be efficient on S. aureus. Besides, the fact that bacteria can bind to platelets via receptors involved in hemostasis suggests that they may induce aggregation; this has indeed been described for Streptococcus sanguinis, S. epidermidis or C. pneumoniae. On the other hand, platelets are able to display an inflammatory response to an infectious triggering. We, and others, have shown that platelet release soluble immunomodulatory factors upon stimulation by bacterial components. Moreover, interactions between bacteria and platelets are not limited to only these two partners. Indeed, platelets are also essential for the formation of Neutrophil Extracellular Traps by neutrophils, resulting in bacterial clearance by trapping bacteria and concentrating antibacterial factors but in enhancing thrombosis. In conclusion, the platelet-bacteria interplay is a complex game; its fine analysis is complicated by the fact that the inflammatory component adds to the

  1. Platelet monoamine uptake in relatives of patients with Huntington's chorea.

    OpenAIRE

    Ehsanullah, R S; Turner, P.

    1981-01-01

    Uptake of dopamine and 5-hydroxytryptamine (5-HT) by the platelets of 25 symptom-free relatives of patients with established Huntington's chorea (HC) was not significantly different from that of control subjects. Platelet uptake of 5-HT in 3 subjects with early signs of the disease showed increased Km and Vmax values. Increased platelet uptake of 5-HT in patients with established HC was confirmed in a further 3 patients. It seems that this phenomenon appears with the clinical evidence of the ...

  2. Platelet satellitism: an Infrequent cause of spurious thrombocytopenia

    International Nuclear Information System (INIS)

    Platelet adherence to Neutrophilic leucocytes or so called 'Platelet satellitism' is an infrequent phenomenon. This finding was observed in a healthy person undergoing routine checkup. Multiple blood smears prepared from peripheral blood collected in Ethylene Diamine Tetra acetic Acid (EDTA) showed evidence of platelet satellitism with the Neutrophils only. Adherence was not observed with any other cell type. Platlet satellitism totally disappeared when samples were collected in heparin or tri-sodium citrate. (author)

  3. Regulation of fibrinogen receptor expression on human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Shattil, S.J.; Motulsky, H.J.; Insel, P.A.; Brass, L.F.

    1986-03-01

    Platelet aggregation requires the binding of fibrinogen to specific receptors on the plasma membrane glycoprotein IIb-IIIa complex. Although the IIb-IIIa complex is identifiable on the surface of resting platelets, the fibrinogen receptor is expressed only after platelet activation. The authors have developed a monoclonal anti-IIb-IIIa antibody (PAC-1) that binds only to stimulated platelets and only in the presence of Ca. In order to better understand the steps leading to platelet aggregation, the authors used radiolabeled PAC-1 and fibrinogen to examine the effect of the ..cap alpha../sub 2/-adrenergic agonist, epinephrine, on the expression and function of the fibrinogen receptor. The addition of epinephrine to unstirred platelets caused and immediate increase in PAC-1 and fibrinogen binding that was associated with platelet aggregation once the platelets were stirred. Even after prolonged incubation of the platelets with epinephrine, fibrinogen receptor expression could be reversed by adding EGTA, PGl/sub 2/, or the ..cap alpha../sub 2/-adrenergic antagonist, phentolamine. When unstirred platelets were exposed to epinephrine for more than 10 min, the extent of aggregation caused by subsequent stirring was decreased by 70%. Surprisingly, these desensitized platelets bound PAC-1 and fibrinogen normally, indicating that the loss of aggregation was not due to a decrease in fibrinogen receptor expression or function. These studies demonstrate that: (1) fibrinogen receptor expression is dependent on extracellular CA; (2) induction of the fibrinogen receptor by epinephrine requires the continued presence of the agonist; and (3) prolonged stimulation of the platelet by epinephrine can lead to a reduced aggregation response by a mechanism that does not involve a loss of either fibrinogen recepor expression or fibrinogen binding.

  4. Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs

    Directory of Open Access Journals (Sweden)

    Jungbluth, Pascal

    2014-11-01

    Full Text Available In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of all growth factors tested was observed in the PRP in comparison to the corresponding plasma or serum. Five of the plasma samples examined contained detectable levels of bone morphogenic protein 2 (BMP-2 whereas eleven of the plasma or serum samples contained minimal amounts of vascular endothelial growth factor (VEGF and platelet-derived growth factor (PDGF-bb respectively. On the other hand variable concentrations of bone morphogenic protein 7 (BMP-7 and transforming growth factor β1 (TGF-β1 were measured in all plasma samples. In contrast, all PRP samples contained significantly increased amounts of growth factors. The level of BMP-2, BMP-7, TGF-β1, VEGF and PDGF-bb increased by 17.6, 1.5, 7.1, 7.2 and 103.3 fold, in comparison to the corresponding non-enriched preparations. Moreover significant positive correlations were found between platelet count and the concentrations of BMP-2 (r=0.62, p<0.001, TGF-β1 (r=0.85, p<0.001, VEGF (r=0.46, p<0.01 and PDGF-bb (r=0.9, p<0.001. Our results demonstrate that selected growth factors are present in the platelet-rich plasma of minipigs which might thus serve as a source of autologous growth factors.

  5. An overview of platelet indices for evaluating platelet function in children with scorpion envenomation.

    Science.gov (United States)

    Konca, Capan; Tekin, Mehmet; Colak, Pinar; Uckardes, Fatih; Turgut, Mehmet

    2014-01-01

    The aim of this study was to assess the correlation between platelet indices and scorpion envenomations (SE). Medical records of 76 children who were hospitalised for scorpion stings in the paediatric intensive care unit (PICU) between February 2013 and November 2013, and 55 healthy children who were similar to the patient group in terms of age and sex, were analysed retrospectively. The leucocyte (WBC), thrombocyte (PLT), plateletcrit (PCT), platelet distribution width (PDW) and mean platelet volume (MPV) values of the 76 children with SE were recorded. These values were compared with the healthy control group. Significantly higher WBC and PDW values were noted in patients with SE in comparison to the controls. Patients with SE had significantly lower mean MPV values compared to the healthy controls (9.03 ± 1.26 compared to 10.43 ± 1.44 fL, respectively; p < 0.001). Although the mean platelet count was slightly elevated in the SE group, no statistically significant difference existed between the two groups (p = 0.097). Furthermore, the mean PCT values in the SE group compared to the control group were slightly decreased, but this decrease was not statistically significant (p = 0.141). A significant inverse correlation existed between the MPV values and the WBC (r = -0.450, p < 0.01) and PLT counts (r = -0.420, p < 0.01). The PLT values were significantly correlated with the PCT values (r = 0.687, p < 0.01). This study demonstrated that SE may lead to several alterations in platelet indices. Significantly lower values of MPV and higher values of PDW were detected in SE patients. However, the increase in the platelet counts and the decrease in the PCT values were not significant. PMID:26417303

  6. Association of Adiposity Indices with Platelet Distribution Width and Mean Platelet Volume in Chinese Adults.

    Directory of Open Access Journals (Sweden)

    Jian Hou

    Full Text Available Hypoxia is a prominent characteristic of inflammatory tissue lesions. It can affect platelet function. While mean platelet volume (MPV and platelet distribution width (PDW are sample platelet indices, they may reflect subcinical platelet activation. To investigated associations between adiposity indices and platelet indices, 17327 eligible individuals (7677 males and 9650 females from the Dongfeng-Tongji Cohort Study (DFTJ-Cohort Study, n=27009 were included in this study, except for 9682 individuals with missing data on demographical, lifestyle, physical indicators and diseases relative to PDW and MPV. Associations between adiposity indices including waist circumstance (WC, waist-to-height ratio (WHtR, body mass index (BMI, and MPV or PDW in the participants were analyzed using multiple logistic regressions. There were significantly negative associations between abnormal PDW and WC or WHtR for both sexes (ptrend<0.001 for all, as well as abnormal MPV and WC or WHtR among female participants (ptrend<0.05 for all. In the highest BMI groups, only females with low MPV or PDW were at greater risk for having low MPV (OR=1.33, 95% CI=1.10, 1.62 ptrend<0.001 or PDW (OR=1.34, 95% CI=1.14, 1.58, ptrend<0.001 than those who had low MPV or PDW in the corresponding lowest BMI group. The change of PDW seems more sensitive than MPV to oxidative stress and hypoxia. Associations between reduced PDW and MPV values and WC, WHtR and BMI values in Chinese female adults may help us to further investigate early changes in human body.

  7. Platelet production and platelet destruction: assessing mechanisms of treatment effect in immune thrombocytopenia

    OpenAIRE

    Barsam, Sarah J.; Psaila, Bethan; Forestier, Marc; Page, Lemke K.; Sloane, Peter A.; Geyer, Julia T.; Villarica, Glynis O.; Ruisi, Mary M.; Gernsheimer, Terry B.; Beer, Juerg H.; Bussel, James B.

    2011-01-01

    This study investigated the immature platelet fraction (IPF) in assessing treatment effects in immune thrombocytopenia (ITP). IPF was measured on the Sysmex XE2100 autoanalyzer. The mean absolute-IPF (A-IPF) was lower for ITP patients than for healthy controls (3.2 vs 7.8 × 109/L, P < .01), whereas IPF percentage was greater (29.2% vs 3.2%, P < .01). All 5 patients with a platelet response to Eltrombopag, a thrombopoietic agent, but none responding to an anti-FcγRIII antibody, had correspondi...

  8. Platelet activation: ultrastructure and morphometry in platelet-rich plasma of horses

    OpenAIRE

    Bruna M. Zandim; Maria V. de Souza; Pablo C. Magalhães; Laércio dos A. Benjamin; Leandro Maia; Aécio C. de Oliveira; José de O. Pinto; José I. Ribeiro Júnior

    2012-01-01

    This study was conducted to investigate the activation ability of the platelet-rich plasma (PRP) by pharmacological agents, as well as to verify the need or not of this activation for therapeutic use. The PRP was obtained from four healthy crossbred geldings aged 13 to 16 years (15±1years), and was processed for observation and quantification of the platelet morphology by using the transmission electron microscopy. All PRP samples were activated with 10% calcium chloride (CaCl2) solution, pur...

  9. Platelets and HIV-1 infection: old and new aspects.

    Science.gov (United States)

    Torre, Donato; Pugliese, Agostino

    2008-09-01

    In this review we summarize the data on interaction of platelets with HIV-1 infection. Thrombocytopenia is a common finding among HIV-1 infected patients; several combined factors contribute to low peripheral platelet counts, which are present during all the stages of the disease. In addition, a relationship between platelet count, plasma viral load and disease progression has been reported, and this shows the potential influence platelets may have on the natural history of HIV-1 disease. Several lines of evidence have shown that platelets are an integral part of inflammation, and can be also potent effector cells of innate immune response as well as of adaptive immunity. Thus, we rewieved the role of inflammatory cytokines, and chemokines as activators of platelets during HIV-1 infection. Moreover, platelets show a direct interaction with HIV-1 itself, through different pathogenic mechanisms as binding, engulfment, internalisation of HIV-1, playing a role in host defence during HIV-1 infection, by limiting viral spread and probably by inactivating viral particles. Platelets may also play an intriguing role on endothelial dysfunction present in HIV-1 infection, and this topic begins to receive systematic study, inasmuch as interaction between platelets and endothelial cells is important in the pathogenesis of atherosclerosis in HIV-1 infected patients, especially in those patients treated with antiretroviral drugs. Finally, this review attempts to better define the state of this emerging issue, to focus areas of potential clinical relevance, and to suggest several directions for future research.

  10. Effects of Suilysin on Streptococcus suis-Induced Platelet Aggregation

    Science.gov (United States)

    Zhang, Shengwei; Wang, Junping; Chen, Shaolong; Yin, Jiye; Pan, Zhiyuan; Liu, Keke; Li, Lin; Zheng, Yuling; Yuan, Yuan; Jiang, Yongqiang

    2016-01-01

    Blood platelets play important roles during pathological thrombocytopenia in streptococcal toxic shock syndrome (STSS). Streptococcus suis (S. suis) an emerging human pathogen, can cause STSS similarly to S. pyogenes. However, S. suis interactions with platelets are poorly understood. Here, we found that suilysin (SLY), different from other bacterial cholesterol-dependent cytolysins (CDCs), was the sole stimulus that induced platelet aggregation. Furthermore, the inside-out activation of GPIIb/IIIa of platelets mediated SLY-induced platelet aggregation. This process was triggered by Ca2+ influx that depend on the pore forming on platelets by SLY. Additionally, although SLY induced α-granule release occurred via the MLCK-dependent pathway, PLC-β-IP3/DAG-MLCK and Rho-ROCK-MLCK signaling were not involved in SLY-induced platelet aggregation. Interestingly, the pore dependent Ca2+ influx was also found to participate in the induction of platelet aggregation with pneumolysin (PLY) and streptolysin O (SLO), two other CDCs. It is possible that the CDC-mediated platelet aggregation we observed in S. suis is a similar response mechanism to that used by a wide range of bacteria. These findings might lead to the discovery of potential therapeutic targets for S. suis-associated STSS. PMID:27800304

  11. High doses of recombinant erythropoietin stimulate platelet production in mice

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, T.P.; Cottrell, M.B.; Clift, R.E.; Cullen, W.C.; Lin, F.K.

    1987-07-01

    Previously, recombinant erythropoietin (rEpo) was shown to increase the number and size of megakaryocytic colonies in vitro, and in vivo it elevates the number of megakaryocytes in mouse spleens. To test the hypothesis that rEpo would stimulate platelet production in mice, both normal mice and mice in rebound-thrombocytosis were injected with rEpo and the %35S incorporation into platelets was measured. A thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) was used as a positive control. rEpo increased isotopic incorporation into platelets of both normal mice and mice in rebound-thrombocytosis, as did TSF, but required large doses (15 U rEpo/mouse). In other mice, hematocrits, platelet counts, platelet sizes, and 24-hr %35S incorporation into platelets were measured 2 days after injection of two equally divided doses of either rEpo or TSF. Significant increases in both platelet sizes and %35S incorporation into platelets were found after injections of 15 U rEpo/mouse or 2.3 U TSF/mouse. These data indicate that rEpo, at high doses, will stimulate platelet production in mice, and may suggest molecular similarities between rEpo and TSF and their ability to compete for common receptor sites on megakaryocytes and their progenitor cells.

  12. Platelet adhesion studies on dipyridamole coated polyurethane surfaces

    Directory of Open Access Journals (Sweden)

    Aldenhoff Y. B.J.

    2003-06-01

    Full Text Available Surface modification of polyurethanes (PUs by covalent attachment of dipyridamole (Persantinregistered is known to reduce adherence of blood platelets upon exposure to human platelet rich plasma (PRP. This effect was investigated in further detail. First platelet adhesion under static conditions was studied with four different biomaterial surfaces: untreated PU, PU immobilised with conjugate molecule 1, PU immobilised with conjugate molecule 2, and PU immobilised with conjugate molecule 3. In PU immobilised with 1 dipyridamole is directly linked to the surface, in PU immobilised with 2 there is a short hydrophilic spacer chain in between the surface and the dipyridamole, while conjugate molecule 3 is merely the spacer chain. Scanning electron microscopy (SEM was used to characterise platelet adhesion from human PRP under static conditions, and fluorescence imaging microscopy was used to study platelet adhesion from whole blood under flow. SEM experiments encompassed both density measurements and analysis of the morphology of adherent platelets. In the static experiments the surface immobilised with 2 showed the lowest platelet adherence. No difference between the three modified surfaces emerged from the flow experiments. The surfaces were also incubated with washed blood platelets and labeled with Oregon-Green Annexin V. No capture of Oregon-Green Annexin V was seen, implying that the adhered platelets did not expose any phosphatidyl serine at their exteriour surface.

  13. Interaction of platelets with collagen substrate: role of platelet prostaglandin endoperoxides and thromboxane A/sub 2/

    Energy Technology Data Exchange (ETDEWEB)

    Mazurov, A.B.; Leitin, V.L.; Repin, V.S.

    1985-04-01

    In this investigation, the role of PG-endoperoxides and TA/sub 2/ in interaction of platelets and a collagen-coated surface was studied. For this purpose, the effects of exogenous AA, of U46619, a stable analog of PG endoperoxides, which simulates the action of PG endoperoxides and TA/sub 2/ on platelets at the receptor level, and of aspirin, a cyclooxygenase inhibitor, on platelet-surface interaction were investigated. The quantity of TA/sub 2/ synthesized in the platelets was determined by measuring accumulation of its stable product TB/sub 2/. After adhesion of the platelets the incubation medium was removed, nonadherent platelets were destroyed by freezing and thawing, and TB/sub 2/ was determined by radioimmunoassay.

  14. Mean platelet volume and the risk of periprocedural myocardial infarction in patients undergoing coronary angioplasty

    NARCIS (Netherlands)

    Verdoia, M.; Camaro, C.; Barbieri, L.; Schaffer, A.; Marino, P.; Bellomo, G.; Suryapranata, H.; Luca, G. De

    2013-01-01

    BACKGROUND: Periprocedural myocardial infarction (PMI) represents a relatively common complication of percutaneous coronary intervention (PCI). Mean platelet volume (MPV) has been proposed as a marker for platelet activation, as larger sized platelets have been associated with higher pro-thrombotic

  15. Platelet-Rich Fibrin Promotes an Accelerated Healing of Achilles Tendon When Compared to Platelet-Rich Plasma in Rat

    OpenAIRE

    Dietrich, Franciele; L. Duré, Gustavo; P. Klein, Caroline; F. Bampi, Vinícius; V. Padoin, Alexandre; D. Silva, Vinícius; Braga-Silva, Jefferson

    2015-01-01

    BACKGROUND Autologous platelet concentrate has been used to improve the function and regeneration of injured tissues. Tendinopathies are common in clinical practice, although long-term treatment is required. On the basis of lead time, we compared the effect of using platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in repairing rat Achilles tendon. METHODS The effectiveness of using PRP and PRF was evaluated after 14 and 28 postoperative days by histological analysis. The quantificati...

  16. Platelet and growth factor concentrations in activated platelet-rich plasma: a comparison of seven commercial separation systems.

    Science.gov (United States)

    Kushida, Satoshi; Kakudo, Natsuko; Morimoto, Naoki; Hara, Tomoya; Ogawa, Takeshi; Mitsui, Toshihito; Kusumoto, Kenji

    2014-06-01

    Platelet-rich plasma (PRP) is blood plasma that has been enriched with platelets. It holds promise for clinical use in areas such as wound healing and regenerative medicine, including bone regeneration. This study characterized the composition of PRP produced by seven commercially available separation systems (JP200, GLO PRP, Magellan Autologous Platelet Separator System, KYOCERA Medical PRP Kit, SELPHYL, MyCells, and Dr. Shin's System THROMBO KIT) to evaluate the platelet, white blood cell, red blood cell, and growth factor concentrations, as well as platelet-derived growth factor-AB (PDGF-AB), transforming growth factor beta-1 (TGF-β1), and vascular endothelial growth factor (VEGF) concentrations. PRP prepared using the Magellan Autologous Platelet Separator System and the KYOCERA Medical PRP Kit contained the highest platelet concentrations. The mean PDGF-AB concentration of activated PRP was the highest from JP200, followed by the KYOCERA Medical PRP Kit, Magellan Autologous Platelet Separator System, MyCells, and GLO PRP. TGF-β1 and VEGF concentrations varied greatly among individual samples, and there was almost no significant difference among the different systems, unlike for PDGF. The SELPHYL system produced PRP with low concentrations of both platelets and growth factors. Commercial PRP separation systems vary widely, and familiarity with their individual advantages is important to extend their clinical application to a wide variety of conditions. PMID:24748436

  17. p38 mitogen-activated protein kinase activation during platelet storage: consequences for platelet recovery and hemostatic function in vivo.

    Science.gov (United States)

    Canault, Matthias; Duerschmied, Daniel; Brill, Alexander; Stefanini, Lucia; Schatzberg, Daphne; Cifuni, Stephen M; Bergmeier, Wolfgang; Wagner, Denisa D

    2010-03-01

    Platelets undergo several modifications during storage that reduce their posttransfusion survival and functionality. One important feature of these changes, which are known as platelet storage lesion, is the shedding of the surface glycoproteins GPIb-alpha and GPV. We recently demonstrated that tumor necrosis factor-alpha converting enzyme (TACE/ADAM17) mediates mitochondrial injury-induced shedding of adhesion receptors and that TACE activity correlates with reduced posttransfusion survival of these cells. We now confirm that TACE mediates receptor shedding and clearance of platelets stored for 16 hours at 37 degrees C or 22 degrees C. We further demonstrate that both storage and mitochondrial injury lead to the phosphorylation of p38 mitogen-activated kinase (MAPK) in platelets and that TACE-mediated receptor shedding from mouse and human platelets requires p38 MAP kinase signaling. Protein kinase C, extracellular regulated-signal kinase MAPK, and caspases were not involved in TACE activation. Both inhibition of p38 MAPK and inactivation of TACE during platelet storage led to a markedly improved posttransfusion recovery and hemostatic function of platelets in mice. p38 MAPK inhibitors had only minor effects on the aggregation of fresh platelets under static or flow conditions in vitro. In summary, our data suggest that inhibition of p38 MAPK or TACE during storage may significantly improve the quality of stored platelets.

  18. Reduction of CTRP9, a novel anti-platelet adipokine, contributes to abnormal platelet activity in diabetic animals.

    Science.gov (United States)

    Wang, Wenqing; Lau, Wayne Bond; Wang, Yajing; Ma, Xinliang; Li, Rong

    2016-01-11

    Platelet hyper-reactivity is a crucial cause of accelerated atherosclerosis increasing risk of thrombotic vascular events in diabetic patients. The mechanisms leading to abnormal platelet activity during diabetes are complex and not fully defined. The current study attempted to clarify the role of CTRP9, a novel adiponectin paralog, in enhanced platelet activity and determined whether CTRP9 may inhibit platelet activity. Adult male C57BL/6 J mice were randomized to receive high-fat diet (HFD) or normal diet (ND). 8 weeks after HFD, animals were sacrificed, and both plasma CTRP9 and platelet aggregation were determined. HFD-fed animals increased weight gain significantly, and became hyperglycemic and hyperinsulinemic 8 weeks post-HFD. Compared to ND animals, HFD animals exhibited significantly decreased plasma CTRP9 concentration and increased platelet response to ADP, evidenced by augmented aggregation amplitude, steeper aggregation slope, larger area under the curve, and shorter lag time (P animals. Taken together, our results suggest reduced plasma CTRP9 concentration during diabetes plays a causative role in platelet hyper-activity, contributing to platelet-induced cardiovascular damage during this pathologic condition. Enhancing CTRP9 production and/or exogenous supplementation of CTRP9 may protect against diabetic cardiovascular injury via inhibition of abnormal platelet activity.

  19. Are Platelets Cells? And if Yes, Are They Immune Cells?

    Directory of Open Access Journals (Sweden)

    Fabrice eCOGNASSE

    2015-02-01

    Full Text Available Small fragments circulating in the blood were formally identified by the end of the 19th century, and it was suggested that they assisted coagulation via interactions with vessel endothelia. Wright, at the beginning of the 20th century, identified their bone-marrow origin. For long, platelets have been considered sticky assistants of hemostasis and pollutants of blood or tissue samples; they were just cell fragments. As such however, they were acknowledged as immunizing (to specific HPA and HLA markers: the platelet’s dark face. The enlightened face showed that besides hemostasis, platelets contained factors involved in healing. As early as the 1930s, platelets entered the arsenal of medicines; were transfused, and were soon manipulated to become a kind of glue to repair damaged tissues. Some gladly categorized platelets as cells but they were certainly not fully licensed as such for cell physiologists. Actually, platelets possess almost every characteristic of cells, apart from being capable of organizing their genes: they have neither a nucleus nor genes. This view prevailed until it became evident that platelets play a role in homeostasis and interact with cells other than with vascular endothelial cells; then began the era of physiological and also pathological inflammation. Platelets have now entered the field of immunity as inflammatory cells. Does assistance to immune cells itself suffice to license a cell as an immune cell? Platelets prove capable of sensing different types of signals and organizing an appropriate response. Many cells can do that. However, platelets can use a complete signalosome (apart from the last transcription step, though it is likely that this step can be circumvented by retrotranscribing RNA messages. The question has also arisen as to whether platelets can present antigen via their abundantly expressed MHC class I molecules. In combination, these properties argue in favor of allowing platelets the title of

  20. Platelets and Infections – Complex Interactions with Bacteria

    Science.gov (United States)

    Hamzeh-Cognasse, Hind; Damien, Pauline; Chabert, Adrien; Pozzetto, Bruno; Cognasse, Fabrice; Garraud, Olivier

    2015-01-01

    Platelets can be considered sentinels of vascular system due to their high number in the circulation and to the range of functional immunoreceptors they express. Platelets express a wide range of potential bacterial receptors, including complement receptors, FcγRII, Toll-like receptors but also integrins conventionally described in the hemostatic response, such as GPIIb–IIIa or GPIb. Bacteria bind these receptors either directly, or indirectly via fibrinogen, fibronectin, the first complement C1q, the von Willebrand Factor, etc. The fate of platelet-bound bacteria is questioned. Several studies reported the ability of activated platelets to internalize bacteria such as Staphylococcus aureus or Porphyromonas gingivalis, though there is no clue on what happens thereafter. Are they sheltered from the immune system in the cytoplasm of platelets or are they lysed? Indeed, while the presence of phagolysosome has not been demonstrated in platelets, they contain antimicrobial peptides that were shown to be efficient on S. aureus. Besides, the fact that bacteria can bind to platelets via receptors involved in hemostasis suggests that they may induce aggregation; this has indeed been described for Streptococcus sanguinis, S. epidermidis, or C. pneumoniae. On the other hand, platelets are able to display an inflammatory response to an infectious triggering. We, and others, have shown that platelet release soluble immunomodulatory factors upon stimulation by bacterial components. Moreover, interactions between bacteria and platelets are not limited to only these two partners. Indeed, platelets are also essential for the formation of neutrophil extracellular traps by neutrophils, resulting in bacterial clearance by trapping bacteria and concentrating antibacterial factors but in enhancing thrombosis. In conclusion, the platelet–bacteria interplay is a complex game; its fine analysis is complicated by the fact that the inflammatory component adds to the aggregation response

  1. Are Platelets Cells? And if Yes, are They Immune Cells?

    Science.gov (United States)

    Garraud, Olivier; Cognasse, Fabrice

    2015-01-01

    Small fragments circulating in the blood were formally identified by the end of the nineteenth century, and it was suggested that they assisted coagulation via interactions with vessel endothelia. Wright, at the beginning of the twentieth century, identified their bone-marrow origin. For long, platelets have been considered sticky assistants of hemostasis and pollutants of blood or tissue samples; they were just cell fragments. As such, however, they were acknowledged as immunizing (to specific HPA and HLA markers): the platelet’s dark face. The enlightened face showed that besides hemostasis, platelets contained factors involved in healing. As early as 1930s, platelets entered the arsenal of medicines were transfused, and were soon manipulated to become a kind of glue to repair damaged tissues. Some gladly categorized platelets as cells but they were certainly not fully licensed as such for cell physiologists. Actually, platelets possess almost every characteristic of cells, apart from being capable of organizing their genes: they have neither a nucleus nor genes. This view prevailed until it became evident that platelets play a role in homeostasis and interact with cells other than with vascular endothelial cells; then began the era of physiological and also pathological inflammation. Platelets have now entered the field of immunity as inflammatory cells. Does assistance to immune cells itself suffice to license a cell as an “immune cell”? Platelets prove capable of sensing different types of signals and organizing an appropriate response. Many cells can do that. However, platelets can use a complete signalosome (apart from the last transcription step, though it is likely that this step can be circumvented by retrotranscribing RNA messages). The question has also arisen as to whether platelets can present antigen via their abundantly expressed MHC class I molecules. In combination, these properties argue in favor of allowing platelets the title of immune

  2. The platelet indices in pediatric patients with acute appendicitis

    Directory of Open Access Journals (Sweden)

    Yunus Yilmaz

    2015-06-01

    Full Text Available Background: The diagnosis of Acute Appendicitis (AA remains a problem in pediatric population. It has been suggested that Mean Platelet Volume (MPV is lower in the patients with AA. The purpose of this study was to investigate the diagnostic value of platelet indices in pediatric AA cases. Methods: A retrospective case-controlled study was designed: 224 subjects were included in this study. All patients had been operated on in division of pediatric surgery at the Kars Government Hospital with the preliminary diagnosis of AA. 204 and 20 of these patients were pathologically diagnosed as AA (group 1 and normal appendix vermiformis (group 2, respectively. Platelet indices had been studied in the biochemistry laboratory of the hospital, before the surgery. Results: In group 1, platelet count, mean platelet volume, plateletcrit and platelet distribution width were 305 +/- 94x103/ and micro;L; 7.37 +/- 0.90 fL; 0,220 +/- 0.057 % and 16.3 +/- 0.5%, respectively. In group 2, platelet count, mean platelet volume, plateletcrit and platelet distribution width were 283 +/- 85 103/ and micro;L; 7.60 +/- 1.24 fL; 0.208 +/- 0.045 % and 16.4 +/- 0.7%, respectively. There was no statistically significant difference between the groups studied with regard to platelet indices (P>0.05. Conclusions: Our study showed that platelet indices have no diagnostic value in the diagnosis of AA at pediatric age group. [Int J Res Med Sci 2015; 3(6.000: 1388-1391

  3. Posttransfusion platelet increments after different platelet products in neonates : a retrospective cohort study

    NARCIS (Netherlands)

    Honohan, Aine; van't Ende, Ella; Hulzebos, Christian; Lopriore, Enrico; van't Verlaat, Ellen; Govaert, Paul; Brand, Anneke; van der Bom, Johanna

    2013-01-01

    BackgroundIn the Netherlands different platelet (PLT) products are used for neonatal transfusions: volume-reduced PLTs, PLT additive solution (PAS) II PLTs, and plasma PLTs. These are standard products at three different neonatal intensive care units where local transfusion guidelines apply. Here we

  4. Platelet activation and platelet-leukocyte interaction in dogs naturally infected with Babesia rossi

    DEFF Research Database (Denmark)

    Goddard, Amelia; Leisewitz, Andrew L; Kristensen, Annemarie Thuri;

    2015-01-01

    EDTA as anticoagulant. Activated platelets and PLA formation were detected by measuring surface expression of P-selectin (CD62P) on platelets, monocytes and neutrophils. Of the Babesia-infected dogs, 29 survived and seven died. The percentage of CD62P-positive monocytes was significantly higher (P = 0.......036) in the Babesia-infected dogs (54%) than in healthy control dogs (35.3%). However, there were no significant differences between the Babesia-infected and control groups for CD62P-positive platelets (4.9% and 1.2%, respectively) and CD62P-positive neutrophils (28.3% and 17.9%, respectively). The percentage of CD62...... groups for the percentage of CD62P-positive platelets (survivors 4.8%; non-survivors 5.3%; controls 1.2%) or CD62P-positive neutrophils (survivors 31.6%; non-survivors 5.6%; controls 17.9%). In conclusion, Babesia-infected dogs, specifically dogs that survived, had a significantly increased percentage...

  5. The influence of environmental variables on platelet concentration in horse platelet-rich plasma.

    Science.gov (United States)

    Rinnovati, Riccardo; Romagnoli, Noemi; Gentilini, Fabio; Lambertini, Carlotta; Spadari, Alessandro

    2016-01-01

    Platelet-rich plasma (PRP) commonly refers to blood products which contain a higher platelet (PLT) concentration as compared to normal plasma. Autologous PRP has been shown to be safe and effective in promoting the natural processes of soft tissue healing or reconstruction in humans and horses. Variability in PLT concentration has been observed in practice between PRP preparations from different patients or from the same individual under different conditions. A change in PLT concentration could modify PRP efficacy in routine applications. The aim of this study was to test the influence of environmental, individual and agonistic variables on the PLT concentration of PRP in horses. Six healthy Standardbred mares were exposed to six different variables with a one-week washout period between variables, and PRP was subsequently obtained from each horse. The variables were time of withdrawal during the day (morning/evening), hydration status (overhydration/dehydration) treatment with anti-inflammatory drugs and training periods on a treadmill. The platelet concentration was significantly higher in horses treated with a non-steroidal anti-inflammatory drug (P = 0.03). The leukocyte concentration increased 2-9 fold with respect to whole blood in the PRP which was obtained after exposure to all the variable considered. Environmental variation in platelet concentration should be taken into consideration during PRP preparation. PMID:27377748

  6. Platelet Concentration in Platelet-Rich Plasma Affects Tenocyte Behavior In Vitro

    Directory of Open Access Journals (Sweden)

    Ilaria Giusti

    2014-01-01

    Full Text Available Since tendon injuries and tendinopathy are a growing problem, sometimes requiring surgery, new strategies that improve conservative therapies are needed. Platelet-rich plasma (PRP seems to be a good candidate by virtue of its high content of growth factors, most of which are involved in tendon healing. This study aimed to evaluate if different concentrations of platelets in PRP have different effects on the biological features of normal human tenocytes that are usually required during tendon healing. The different platelet concentrations tested (up to 5 × 106 plt/µL stimulated differently tenocytes behavior; intermediate concentrations (0.5 × 106, 1 × 106 plt/µL strongly induced all tested processes (proliferation, migration, collagen, and MMPs production if compared to untreated cells; on the contrary, the highest concentration had inhibitory effects on proliferation and strongly reduced migration abilities and overall collagen production but, at the same time, induced increasing MMP production, which could be counterproductive because excessive proteolysis could impair tendon mechanical stability. Thus, these in vitro data strongly suggest the need for a compromise between extremely high and low platelet concentrations to obtain an optimal global effect when inducing in vivo tendon healing.

  7. Reticulated platelets as a marker of platelet recovery after allogeneic stem cell transplantation.

    Science.gov (United States)

    Michur, H; Maślanka, K; Szczepiński, A; Mariańska, B

    2008-12-01

    Reticulated platelets (RP) are the youngest forms of platelets in blood and reflect the rate of bone marrow platelet production. In the present study, we used flow cytometric analysis to determine the percentage of RPs in patients undergoing allogeneic stem cell transplantation. We investigated 10 patients after transplantation from HLA identical siblings: five with acute myeloid leukemia (AML), four with chronic myeloid leukemia (CML), and one patient with myelodysplastic syndrome (MDS). Of the patients examined, four patients underwent allogeneic bone marrow transplantation and six patients underwent peripheral blood stem cell transplantation. It was observed that the initially reduced percentage of RPs (2.9 +/- 1.7%; mean +/- SD) was significantly higher (P = 0.0109) in all patients (13.6 +/- 6.4%) in the following 10-26 days. The RP percentage peak preceded the recovery of peripheral platelet count up to 45.6 x 10(9)/l on average by 3 days. We found no difference in RP% between the AML and CML patients but we did observe that in CML patients the RP percentage increased on average 7 days earlier than in AML patients. The elevated RP percentage reflects increased bone marrow regeneration and can be considered an additional marker of thrombopoietic recovery in the patients undergoing allogeneic stem cell transplantation. PMID:18983304

  8. Effect of platelet orientation on the properties of alumina platelet zirconia matrix composites

    DEFF Research Database (Denmark)

    Toft Sørensen, O.; Li, W.-Y.

    1996-01-01

    alignment. The results also indicated that there was a trend of higher K-IC value when cracks were propagating parallel to the platelet surface (nor delamination). Thermal shock resistance of the injection moulded composite has been characterized by water quench test. Delta T-c for the composite was between...

  9. Transfused stored platelets have the same haemostatic function as circulating native platelets

    NARCIS (Netherlands)

    Roeloffzen, W. W. H.; Kluin-Nelemans, H. C.; Veeger, N. J. G. M.; de Wolf, J. Th. M.

    2010-01-01

    Background and objectives As thrombelastography (R) (TEG) measures haemostasis in whole blood, we used this instrument to study whether transfused platelets (PLTs) have the same haemostatic function compared to native circulating PLTs. Further, we studied the effect of storage time on the haemostati

  10. Pressure-aided transfusion of platelets: does it affect the platelets?

    DEFF Research Database (Denmark)

    Fischer-Nielsen, Anne; Stissing, Trine; Maansson, Charlotte;

    2010-01-01

    In massively bleeding patients, pressure infusers are used for transfusion of red blood cells and plasma but not for platelets (PLTs) due to an assumed negative effect on the PLTs. This study examined whether pressure-aided in vitro transfusion affected the number, activation state, and/or function...

  11. Mean platelet volume, neutrophil to lyphocyte ratio and platelet to lymphocyte ratio in psoriasis

    Directory of Open Access Journals (Sweden)

    Mehmet Ünal

    2015-06-01

    Full Text Available Background and Design: It has been demonstrated that ratio of neutrophil and platelet count systemic inflammation and is associated with prognosis of many cardiovascular diseases, malignates and chronic inflammatory diseases.As far as it is known, there are no studies investigating neutrophil/lymphocyeratio(NLR, platelet/lymphocyte ratio(PLR and mean platelet volume(MPV values together within the context of psoriasis, a chronic and systemic inflammatory disease. Materials and Methods: 320 patients followed up in our polyclinic with psoriasis vulgaris and 200 healthy persons were evaluated in the study. Results: Leukocyte, neutrophil, platelet, MPV, NLR and PLR values in patients with psoriasis were significantly higher, and lymphocyte count, on the other hand, was significantly lower than those of the control group. No significant difference was found between MPV, NLR and PLR values of patients with or without a family history, nail and joint involvement. Conclusions: These parameters may be made use of as cheap and easily applicable methods in predicting which psoriasis patients are under the risk of cardiovascular disease. PLR is a better inflammation marker than MPV and NLR in patients with psoriasis. We did not observe a significant relationship between MPV, NLR and PLR values and such disease characteristics as severity of disease, joint involvement, nail involvement and duration of disease in patients with psoriasis. So, we believe that there is little information on the extent to which MPV,NLR and PLR might be useful regarding these characteristics.

  12. Inhibitors of platelet lipoxygenase from Ponkan fruit.

    Science.gov (United States)

    Nogata, Y; Sekiya, K; Ohta, H; Kusumoto, K; Ishizu, T

    2001-04-01

    An activity-guided separation for inhibitors of rat platelet 12-lipoxygenase led to the isolation of two compounds, 4-O-feruloyl-5-O-caffeoylquinic acid (IC50; 5.5 microM) and methyl 4-O-feruloyl-5-O-caffeoylquinate (IC50; 1.9 microM) from the peel of Ponkan fruit (Citrus reticulata). The complete structure of each phenolic ester was determined by NMR spectroscopy [1H and 13C NMR spectra, 1H-1H correlation spectroscopy (COSY), 1H-detected heteronuclear multiple quantum coherence (HMQC), and heteronuclear multiple bond connectivity (HMBC) spectroscopies] and other spectral methods. PMID:11314960

  13. Platelet-rich plasma in regenerative medicine

    Directory of Open Access Journals (Sweden)

    Guhta Ra Hara and Thaha Basu

    2014-01-01

    Full Text Available Platelet-rich plasma (PRP contains at least seven growth factors including epidermal, plateletderived, transforming, vascular endothelial, fibroblast, insulin-like and keratinocyte growth factor. The therapeutic effect of PRP occurs because of the high concentration of these growth factors compared with those found in normal plasma. In recent years, PRP is widely used across many clinical fields, especially in regenerative medicine. This review aimed at presenting an overview of the applications of PRP in regenerative medicine. The mechanisms of PRP effects on healing are also stated in this review. [Biomed Res Ther 2014; 1(1.000: 25-31

  14. Platelet peripheral benzodiazepine receptors in repeated stress

    Energy Technology Data Exchange (ETDEWEB)

    Dar, D.E.; Bidder, M.; Gavish, M. (Technion-Israel Institute of Technology, Haifa (Israel)); Weizman, A.; Karp, L.; Tyano, S. (Tel Aviv Univ. (Israel)); Grinshpoon, A.; Bleich, A.

    1991-01-01

    ({sup 3}H)PK 11195 binding to platelet membranes and plasma stress hormones were studied in soldiers at the beginning of a parachute training course, following 6 days of preparatory exercises, and after the fourth actual parachute jump. A slight reduction (15%; NS) in the number of peripheral benzodiazepine receptors (PBR) was detected at the end of the exercise period, prior to the first jump. Reduced density of PBR was observed immediately after the repeated actual jumps. Equilibrium dissociation constants were not affected by the stressful situation. Plasma cortisol and prolactin levels remained unaltered during the entire study period.

  15. Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs.

    Science.gov (United States)

    Jungbluth, Pascal; Grassmann, Jan-Peter; Thelen, Simon; Wild, Michael; Sager, Martin; Windolf, Joachim; Hakimi, Mohssen

    2014-01-01

    In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP) preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of all growth factors tested was observed in the PRP in comparison to the corresponding plasma or serum. Five of the plasma samples examined contained detectable levels of bone morphogenic protein 2 (BMP-2) whereas eleven of the plasma or serum samples contained minimal amounts of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-bb) respectively. On the other hand variable concentrations of bone morphogenic protein 7 (BMP-7) and transforming growth factor β1 (TGF-β1) were measured in all plasma samples. In contrast, all PRP samples contained significantly increased amounts of growth factors. The level of BMP-2, BMP-7, TGF-β1, VEGF and PDGF-bb increased by 17.6, 1.5, 7.1, 7.2 and 103.3 fold, in comparison to the corresponding non-enriched preparations. Moreover significant positive correlations were found between platelet count and the concentrations of BMP-2 (r=0.62, pVEGF (r=0.46, pplatelet-rich plasma of minipigs which might thus serve as a source of autologous growth factors. PMID:26504722

  16. Rapid in vitro biocompatibility assay of endovascular stents by flow cytometry using platelet activation and platelet-leukocyte aggregation.

    Science.gov (United States)

    Tárnok, A; Mahnke, A; Müller, M; Zotz, R J

    1999-02-15

    Clinical studies suggest that stent design and surface texture are responsible for differences in biocompatibility of metallic endovascular stents. A simple in vitro experimental setup was established to test stent-induced degree of platelet and leukocyte activation and platelet-leukocyte aggregation by flow cytometry. Heparin-coated tantalum stents and gold-coated and uncoated stainless steel stents were tested. Stents were implanted into silicone tubes and exposed to blood from healthy volunteers. Platelet and leukocyte activation and percentage of leukocyte-platelet aggregates were determined in a whole-blood assay by subsequent staining for activation-associated antigens (CD41a, CD42b, CD62p, and fibrinogen binding) and leukocyte antigens (CD14 and CD45) and flow cytometric analysis. Blood taken directly after venous puncture or exposed to the silicone tube alone was used as negative controls. Positive control was in vitro stimulation with thrombin receptor activating peptide (TRAP-6). Low degree of platelet activation and significant increase in monocyte- and neutrophil-platelet aggregation were observed in blood exposed to stents (P coated stents continuously induced less platelet activation and leukocyte-platelet aggregation than uncoated stainless steel stents of the same length and shorter stents of the same structure. Stent surface coating and texture plays a role in platelet and leukocyte activation and leukocyte-platelet aggregation. Using this simple in vitro assay and whole blood and flow cytometry, it seems possible to differentiate stents by their potency to activate platelets and/or leukocytes. This assay could be applied for improving the biocompatibility of coronary stents. PMID:10088974

  17. The repertoire and features of human platelet microRNAs.

    Directory of Open Access Journals (Sweden)

    Hélène Plé

    Full Text Available Playing a central role in the maintenance of hemostasis as well as in thrombotic disorders, platelets contain a relatively diverse messenger RNA (mRNA transcriptome as well as functional mRNA-regulatory microRNAs, suggesting that platelet mRNAs may be regulated by microRNAs. Here, we elucidated the complete repertoire and features of human platelet microRNAs by high-throughput sequencing. More than 492 different mature microRNAs were detected in human platelets, whereas the list of known human microRNAs was expanded further by the discovery of 40 novel microRNA sequences. As in nucleated cells, platelet microRNAs bear signs of post-transcriptional modifications, mainly terminal adenylation and uridylation. In vitro enzymatic assays demonstrated the ability of human platelets to uridylate microRNAs, which correlated with the presence of the uridyltransferase enzyme TUT4. We also detected numerous microRNA isoforms (isomiRs resulting from imprecise Drosha and/or Dicer processing, in some cases more frequently than the reference microRNA sequence, including 5' shifted isomiRs with redirected mRNA targeting abilities. This study unveils the existence of a relatively diverse and complex microRNA repertoire in human platelets, and represents a mandatory step towards elucidating the intraplatelet and extraplatelet role, function and importance of platelet microRNAs.

  18. Flow Cytometric Investigation of Classical and Alternative Platelet Activation Markers

    Science.gov (United States)

    Debreceni, Ildikó Beke; Kappelmayer, János

    2013-01-01

    Platelets show a substantial role in the maintenance of vascular integrity when these cells after a rapid activation adhere to the vessel wall lesion, aggregate with other platelets and leukocytes resulting in an arterial thrombosis. Analysis of in vivo platelet activation at an early time point is crucial in the detection of developing thrombotic events. In addition, the forecast of future complications as well as the evaluation of the efficacy of anti- platelet medication are also essential in a large group of patients. Changes in the levels of platelet receptors or alteration in other surface properties due to intra- and extracellular responses to a stimulus can be measurable primarily by flow cytometry with specific antibodies via the assessment of classical and alternative platelet activation markers. Some of these biomarkers have been already used in routine laboratory settings in many cases, while others still stand in the phase of research applications. Deficiency in platelet receptors is also accessible with this technique for the diagnosis of certain bleeding disorders. We here describe the most important types of platelet activation markers, and give an overview how the levels of these markers are altered in different diseases.

  19. Platelet function in brown bear (Ursus arctos compared to man

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    Särndahl Eva

    2010-06-01

    Full Text Available Abstract Background Information on hemostasis and platelet function in brown bear (Ursus arctos is of importance for understanding the physiological, protective changes during hibernation. Objective The study objective was to document platelet activity values in brown bears shortly after leaving the den and compare them to platelet function in healthy humans. Methods Blood was drawn from immobilized wild brown bears 7-10 days after leaving the den in mid April. Blood samples from healthy human adults before and after clopidogrel and acetylsalicylic acid administration served as control. We analyzed blood samples by standard blood testing and platelet aggregation was quantified after stimulation with various agonists using multiple electrode aggregometry within 3 hours of sampling. Results Blood samples were collected from 6 bears (3 females between 1 and 16 years old and from 10 healthy humans. Results of adenosine diphosphate, aspirin, and thrombin receptor activating peptide tests in bears were all half or less of those in humans. Platelet and white blood cell counts did not differ between species but brown bears had more and smaller red blood cells compared with humans. Conclusion Using three different tests, we conclude that platelet function is lower in brown bears compared to humans. Our findings represent the first descriptive study on platelet function in brown bears and may contribute to explain how bears can endure denning without obvious thrombus building. However, the possibility that our findings reflect test-dependent and not true biological variations in platelet reactivity needs further studies.

  20. Anti-platelet therapy in small animal medicine.

    Science.gov (United States)

    Thomason, J; Lunsford, K; Mackin, A

    2016-08-01

    Thromboembolism is a significant complication in many commonly encountered diseases, and can be a devastating sequel to otherwise treatable conditions. Platelets play an essential role in the hemostatic process and, consequently, are associated with thrombus formation. Platelets adhere to denuded vascular subendothelium, recruit additional platelets and cells, aggregate, and provide the catalytic surface for thrombin production and fibrin formation. Therapy to prevent unwanted thrombus formation and thromboembolic crises is essential in the management of hypercoagulable patients. Unfortunately, many of the medications used in veterinary medicine that inhibit or modulate coagulation factors, such as the heparins, are cost prohibitive, only effective when administered by injection or require frequent drug monitoring, and are therefore poor choices for long term at home therapy. While the role of the platelet in pathologic thrombus formation is not fully understood, veterinarians often resort to anti-platelet therapy in the management of patients at risk for thromboembolic complications, because many anti-platelet medications are inexpensive, require minimal drug monitoring, and can be given orally. The aim of this review is to discuss the anti-platelet therapies that are currently being used or being considered for use to inhibit platelet function and reduce thromboembolic complications in hypercoagulable dogs and cats. PMID:26969126

  1. Platelets: versatile effector cells in pneumonia and sepsis

    NARCIS (Netherlands)

    S.F. de Stoppelaar

    2015-01-01

    The role of platelets in infection and immunity is an exciting new theme, which is rapidly evolving. In this thesis we studied the involvement of platelets in the host response to pneumonia and sepsis. We made use of well established mouse models in which mice were infected with a bacterial inoculum

  2. Survival curves study of platelet labelling with 51Cr

    International Nuclear Information System (INIS)

    Platelet kinetics and idiopathic thrombocytopenic purpura were researched in the literature. An 'in vitro' platelet labelling with 51Cr procedure in implementation has been evaluated in human beings. Functions used for fitting considered the cases whether the curve was linear or exponential as well as the presence of hematies. (author)

  3. Indium-111 labelled platelets: experimental and clinical studies

    International Nuclear Information System (INIS)

    The object of the present study became to develop a method of effective and gentle isolation and 111-In labelling of human platelets, as well as to employ these platelets in human clinical studies with the object of elucidating a number of physiological and pathophysiological mechanisms and processes in which platelets take part. 111-In-oxine presents obvious advantages over 51-Cr-sodium chromate; a high labelling efficiency, and more advantageous physical properties (a half life of 68 hours (against the half life of 28 days for 51-Cr) and considerably more effective gamma emission), making external registration by means of a gamma camera possible. Considering the role played by platelets in the development of atherosclerosis and its thromboembolic complications, in the early phases of deep venous thrombosis, and in graft rejection, it is natural that attempts have been made to use 111-In-labelled platelets for scintigraphic and kinetic evaluation of thromboembolic processes. Accumulation of 111-In-labelled platelets at sites of vessel wall injury, on pulmonary emboli (presumably on deep vein thrombi as well), and on catheter material has been demonstrated. Beyond this, the number of publications concerning the use of 111-In-labelled platelets for visualization of atherosclerosis, venous thromboembolism, arterial grafts, intracardiac thrombi, aortic aneurysms, renal allograft rejection, and other situations in which platelet thromboembolism takes place, provides evidence that a tool has finally been found for the study of their nature and response to therapeutic intervention. (eg)

  4. [A method for studying intravascular platelet aggregation in vitro].

    Science.gov (United States)

    Ikonnikova, E I; Chernousova, L A; Moshkina, I R

    1999-06-01

    A simple available method for evaluating intravascular platelet aggregation is proposed. It consists in graphic recording of disaggregation of platelet-rich citrate plasma, which indicates the degree of intravascular aggregation. Intravascular aggregation is notably increased in coronary patients and negligible in normal subjects. The method may be used for the diagnosis of diseases with a high thrombogenic risk.

  5. Platelets in Pulmonary Immune Responses and Inflammatory Lung Diseases.

    Science.gov (United States)

    Middleton, Elizabeth A; Weyrich, Andrew S; Zimmerman, Guy A

    2016-10-01

    Platelets are essential for physiological hemostasis and are central in pathological thrombosis. These are their traditional and best known activities in health and disease. In addition, however, platelets have specializations that broaden their functional repertoire considerably. These functional capabilities, some of which are recently discovered, include the ability to sense and respond to infectious and immune signals and to act as inflammatory effector cells. Human platelets and platelets from mice and other experimental animals can link the innate and adaptive limbs of the immune system and act across the immune continuum, often also linking immune and hemostatic functions. Traditional and newly recognized facets of the biology of platelets are relevant to defensive, physiological immune responses of the lungs and to inflammatory lung diseases. The emerging view of platelets as blood cells that are much more diverse and versatile than previously thought further predicts that additional features of the biology of platelets and of megakaryocytes, the precursors of platelets, will be discovered and that some of these will also influence pulmonary immune defenses and inflammatory injury. PMID:27489307

  6. Platelet transfusion and alloimmunization : clinical and laboratory studies

    NARCIS (Netherlands)

    K. Sintnicolaas (Krijn)

    1996-01-01

    textabstractThrombocytopenia as a result of decreased platelet production may be treated with platelet transfusions. Decreased bone marrow function resulting in thrombocytopenia may be seen in hematopoietic diseases as leukemia, myelodysplastic syndrome or conditions of infiltration of bone marrow w

  7. Platelet serotonin transporter function predicts default-mode network activity.

    Directory of Open Access Journals (Sweden)

    Christian Scharinger

    Full Text Available The serotonin transporter (5-HTT is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence.A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax was assessed in blood platelets. We used a mixed-effects multilevel analysis technique (MEMA to test for linear relationships between whole-brain, blood-oxygen-level dependent (BOLD activity and platelet Vmax.The present study demonstrates that increases in platelet Vmax significantly predict default-mode network (DMN suppression in healthy subjects independent of genetic variation within SLC6A4. Furthermore, functional connectivity analyses indicate that platelet Vmax is related to global DMN activation and not intrinsic DMN connectivity.This study provides evidence that platelet Vmax predicts global DMN activation changes in healthy subjects. Given previous reports on platelet-synaptosomal Vmax coupling, results further suggest an important role of neuronal 5-HT reuptake in DMN regulation.

  8. Platelet counts and outcome in the pediatric intensive care unit

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    Agrawal Shruti

    2008-01-01

    Full Text Available Objectives: Thrombocytopenia is commonly observed in critically ill patients. This study was undertaken to evaluate the variation in platelet counts and the risk factors associated with thrombocytopenia and mortality in pediatric intensive care patients. In addition, prognostic value of platelet counts for outcome in pediatric intensive care unit was studied. Study Design: Prospective, observational cohort analysis. Setting: 8- bedded pediatric intensive care unit of a tertiary care teaching hospital. Patients: All consecutively admitted patients (n=138 staying in the pediatric intensive care unit (PICU for at least 48h over a 7 months period were studied. Measurements and Main Results: Thrombocytopenia was defined as platelet counts < 150.0/nL. Median 1 st day Pediatric Risk of Mortality Score (PRISM was 5 (range 0-30 and median ICU stay was 4 days (range 2-98 days. Twenty five percent patients had at least one episode of thrombocytopenia during the stay. Twenty percent of these patients had thrombocytopenia on admission and rest (80% developed it during the PICU stay. Seventy one percent (19 of the patients developed thrombocytopenia by fourth day of admission. Patients with PICU acquired thrombocytopenia had statistically significant lower baseline, nadir and 4th day platelet counts and a significantly higher drop in platelet counts (56% vs. 6% P< 0.001 as compared to non thrombocytopenic patients. PRISM score, long PICU stay, sepsis, coagulopathy, and creatinine levels were significantly associated with occurrence of thrombocytopenia. Patients with thrombocytopenia had higher probability of bleeding (34% vs. 15%, P=0.01. Higher platelet counts on admission were associated with significantly reduced risk of thrombocytopenia (P=0.00 Baseline, nadir and day-4 platelet counts, presence of thrombocytopenia on admission, sepsis, coagulopathy and a higher mean PRISM score on univariate analysis were significantly associated with mortality

  9. Role of blood platelets in infection and inflammation.

    Science.gov (United States)

    Klinger, Matthias H F; Jelkmann, Wolfgang

    2002-09-01

    Blood platelets are here presented as active players in antimicrobial host defense and the induction of inflammation and tissue repair in addition to their participation in hemostasis. Megakaryopoiesis is inhibited after acute infection with viruses or bacteria. In contrast, chronic inflammation is often associated with reactive thrombocytosis. Platelets can bind and internalize pathogens and release microbicidal proteins that kill certain bacteria and fungi. By making cell-cell contacts with leukocytes and endothelial cells, platelets assist white blood cells in rolling, arrest and transmigration. On stimulation by bacteria or thrombin, platelets release the content of their alpha-granules, which include an arsenal of bioactive peptides, such as CC-chemokines and CXC-chemokines and growth factors for endothelial cells, smooth muscle cells and fibroblasts. Thus, integral to innate immunity, the tiny little platelets may become bombshells when irritated by pathogens.

  10. Low platelet monoamine oxidase activity in pathological gambling

    International Nuclear Information System (INIS)

    Decreased platelet monoamine oxidase (MAO) activity has been reported in association with sensation-seeking personality type and in some mental disorders associated with a lack of impulse control. Pathological gambling itself has been related with both sensation-seeking and reduced impulse control. Platelet MAO activity was investigated in 15 DSM-III-R pathological gamblers from our outpatient clinic. Gamblers had a significantly lower platelet MAO activity than a group of 25 healthy controls. The range of MAO levels in gamblers was also significantly shorter than in controls. In controls, platelet MAO levels showed the previously described negative correlations with sensation-seeking scores but not in gamblers. The findings are consistent with previous studies showing an association of low platelet MAO activity with impulse control disorders and raise some interesting therapeutic alternatives for pathological gambling. (au) (40 refs.)

  11. Low platelet monoamine oxidase activity in pathological gambling

    Energy Technology Data Exchange (ETDEWEB)

    Carrasco, J.L. [Department of Psychiatry, Centro de Salud Mental, Parla Madrid (Spain); Saiz-Ruiz, J. [Department of Psychiatry and Haematology, Hospital Ramon y Cajal, Madrid (Spain); Hollander, E. [Department of Psychiatry, Mount Sinai School of Medicine, Queens Hospital Center, New York (United States); Cesar, J. [Department of Haematology, Hospital Ramon y Cajal, Madrid (Spain); Lopez-Ibor, J.J. Jr. [Department of Psychiatry, Hospital San Carlos, Complutense University, Madrid (Spain)

    1994-12-01

    Decreased platelet monoamine oxidase (MAO) activity has been reported in association with sensation-seeking personality type and in some mental disorders associated with a lack of impulse control. Pathological gambling itself has been related with both sensation-seeking and reduced impulse control. Platelet MAO activity was investigated in 15 DSM-III-R pathological gamblers from our outpatient clinic. Gamblers had a significantly lower platelet MAO activity than a group of 25 healthy controls. The range of MAO levels in gamblers was also significantly shorter than in controls. In controls, platelet MAO levels showed the previously described negative correlations with sensation-seeking scores but not in gamblers. The findings are consistent with previous studies showing an association of low platelet MAO activity with impulse control disorders and raise some interesting therapeutic alternatives for pathological gambling. (au) (40 refs.).

  12. Platelet content of nitric oxide synthase 3 phosphorylated at Serine 1177 is associated with the functional response of platelets to aspirin.

    Directory of Open Access Journals (Sweden)

    Javier Modrego

    Full Text Available OBJECTIVE: To analyse if platelet responsiveness to aspirin (ASA may be associated with a different ability of platelets to generate nitric oxide (NO. PATIENTS/METHODS: Platelets were obtained from 50 patients with stable coronary ischemia and were divided into ASA-sensitive (n = 26 and ASA-resistant (n = 24 using a platelet functionality test (PFA-100. RESULTS: ASA-sensitive platelets tended to release more NO (determined as nitrite + nitrate than ASA-resistant platelets but it did not reach statistical significance. Protein expression of nitric oxide synthase 3 (NOS3 was higher in ASA-sensitive than in ASA-resistant platelets but there were no differences in the platelet expression of nitric oxide synthase 2 (NOS2 isoform. The highest NOS3 expression in ASA-sensitive platelets was independent of the presence of T-to-C mutation at nucleotide position -786 (T(-786 → C in the NOS3-coding gene. However, platelet content of phosphorylated NOS3 at Serine (Ser(1177, an active form of NOS3, was higher in ASA-sensitive than in ASA-resistant platelets. The level of platelet NOS3 Ser(1177 phosphorylation was positively associated with the closure time in the PFA-100 test. In vitro, collagen failed to stimulate the aggregation of ASA-sensitive platelets, determined by lumiaggregometry, and it was associated with a significant increase (p = 0.018 of NOS3 phosphorylation at Ser(1177. On the contrary, collagen stimulated the aggregation of ASA-resistant platelets but did not significantly modify the platelet content of phosphorylated NOS3 Ser(1177. During collagen stimulation the release of NO from ASA-sensitive platelets was significantly enhanced but it was not modified in ASA-resistant platelets. CONCLUSIONS: Functional platelet responsiveness to ASA was associated with the platelet content of phosphorylated NOS3 at Ser(1177.

  13. Multiwavelength UV/visible spectroscopy for the quantitative investigation of platelet quality

    Science.gov (United States)

    Mattley, Yvette D.; Leparc, German F.; Potter, Robert L.; Garcia-Rubio, Luis H.

    1998-04-01

    The quality of platelets transfused is vital to the effectiveness of the transfusion. Freshly prepared, discoid platelets are the most effective treatment for preventing spontaneous hemorrhage or for stopping an abnormal bleeding event. Current methodology for the routine testing of platelet quality involves random pH testing of platelet rich plasma and visual inspection of platelet rich plasma for a swirling pattern indicative of the discoid shape of the cells. The drawback to these methods is that they do not provide a quantitative and objective assay for platelet functionality that can be used on each platelet unit prior to transfusion. As part of a larger project aimed at characterizing whole blood and blood components with multiwavelength UV/vis spectroscopy, isolated platelets and platelet in platelet rich plasma have been investigated. Models based on Mie theory have been developed which allow for the extraction of quantitative information on platelet size, number and quality from multi-wavelength UV/vis spectra. These models have been used to quantify changes in platelet rich plasma during storage. The overall goal of this work is to develop a simple, rapid quantitative assay for platelet quality that can be used prior to platelet transfusion to ensure the effectiveness of the treatment. As a result of this work, the optical properties for isolated platelets, platelet rich plasma and leukodepleted platelet rich plasma have been determined.

  14. Platelets stimulate fibroblast-mediated contraction of collagen gels

    Directory of Open Access Journals (Sweden)

    Lundahl Joachim

    2003-10-01

    Full Text Available Abstract Background Platelets are thought to play a role in a variety of inflammatory conditions in the lung, some of which may lead to fibrosis. In the current study we tested the hypothesis that whole platelets and platelet lysate can mediate remodelling of extracellular matrix in vitro by affecting fibroblast-mediated contraction of a collagen gel. We also sought to determine to what extent platelet-derived growth factor (PDGF and transforming growth factor-β (TGF-β contribute to this effect. Methods Washed platelets, isolated from healthy blood donors, and platelet lysate (freezing and thawing, were cast together with human lung fibroblasts in three-dimensional collagen gels. The gels were then released and cultured for four days. PDGF and TGF-β1 concentrations were measured in culture supernatants by ELISA. Results Both platelets and platelet lysate augmented fibroblast-mediated gel contraction in a time and concentration dependent manner (19.9% ± 0.1 (mean ± SEM of initial area vs. 48.0% ± 0.4 at 48 hours; P 1 and PDGF-AA/AB were released in co-culture. PDGF-AA/AB had a maximum release at 24 hours whereas TGF-β1 release increased with longer culture periods. Neutralising antibodies to these mediators partially inhibited platelet-induced gel contraction. Conclusion We conclude that platelets may promote remodelling of extracellular matrix in vitro and that PDGF and TGF-β partially mediate this effect, also indicating a role for other mediators. The findings may be an important mechanism in regulating repair processes after injury.

  15. Thioredoxin Inhibitors Attenuate Platelet Function and Thrombus Formation

    Science.gov (United States)

    Metcalfe, Clive; Ramasubramoni, Anjana; Pula, Giordano; Harper, Matthew T.; Mundell, Stuart J.; Coxon, Carmen H.

    2016-01-01

    Thioredoxin (Trx) is an oxidoreductase with important physiological function. Imbalances in the NADPH/thioredoxin reductase/thioredoxin system are associated with a number of pathologies, particularly cancer, and a number of clinical trials for thioredoxin and thioredoxin reductase inhibitors have been carried out or are underway. Due to the emerging role and importance of oxidoreductases for haemostasis and the current interest in developing inhibitors for clinical use, we thought it pertinent to assess whether inhibition of the NADPH/thioredoxin reductase/thioredoxin system affects platelet function and thrombosis. We used small molecule inhibitors of Trx (PMX 464 and PX-12) to determine whether Trx activity influences platelet function, as well as an unbiased proteomics approach to identify potential Trx substrates on the surface of platelets that might contribute to platelet reactivity and function. Using LC-MS/MS we found that PMX 464 and PX-12 affected the oxidation state of thiols in a number of cell surface proteins. Key surface receptors for platelet adhesion and activation were affected, including the collagen receptor GPVI and the von Willebrand factor receptor, GPIb. To experimentally validate these findings we assessed platelet function in the presence of PMX 464, PX-12, and rutin (a selective inhibitor of the related protein disulphide isomerase). In agreement with the proteomics data, small molecule inhibitors of thioredoxin selectively inhibited GPVI-mediated platelet activation, and attenuated ristocetin-induced GPIb-vWF-mediated platelet agglutination, thus validating the findings of the proteomics study. These data reveal a novel role for thioredoxin in regulating platelet reactivity via proteins required for early platelet responses at sites of vessel injury (GPVI and GPIb). This work also highlights a potential opportunity for repurposing of PMX 464 and PX-12 as antiplatelet agents. PMID:27716777

  16. Platelet kinetics and scintigraphic imaging in thrombocytopenic malaria patients.

    Science.gov (United States)

    Karanikas, Georgios; Zedwitz-Liebenstein, Konstantin; Eidherr, Harald; Schuetz, Matthias; Sauerman, Robert; Dudczak, Robert; Winkler, Stefan; Pabinger, Ingrid; Kletter, Kurt

    2004-03-01

    Thrombocytopenia is a common occurrence in acute malaria. It is attributed, among other factors, to excessive splenic platelet pooling and a shortened platelet lifespan. The aim of our study was to evaluate the platelet kinetics and sequestration site by isotopic studies in uncomplicated malaria-induced thrombocytopenia. Seven thrombocytopenic malaria patients (74,000+/-36,000 platelets/ micro l) were included in the study. Autologous (111)In-labeled platelet scintigraphy was performed up to 96 hours (h) post injection (p.i.) to evaluate the platelet sequestration site. Late sequestration for the spleen (S) and the liver (L) was analyzed according to the following activity ratios: S (spleen count on the last day of the platelet lifespan / spleen count at 30 min) and L (liver count on the last day of the platelet lifespan / liver count at 30 min). Additionally, platelet survival studies were performed. A normal late sequestration (S: 0.95+/-0.06 and L: 1.04+/-0.08; normal values, S and L: 1+/-0.2.) was observed in all of our patients. The platelet lifespan was reduced (1 to 4 days; normal range, 7-9 days), recovery was normal (mean, 63+/-6%; normal range, 55-75%), and the turnover rate was enhanced (mean, 95,000+/-80,000/ micro l/day; normal value, 35,000+/-4,500/ micro l/ day). According to the results of scintigraphy, the sequestration site by uncomplicated malaria-induced thrombocytopenia appears to be non-splenic and/or hepatic, yet diffuse. PMID:14983232

  17. A novel thrombopoietin signaling defect in polycythemia vera platelets.

    Science.gov (United States)

    Moliterno, A R; Siebel, K E; Sun, A Y; Hankins, W D; Spivak, J L

    1998-01-01

    The pathogenesis of polycythemia vera (PV), a disease involving a multipotent hematopoietic progenitor cell, is unknown. Thrombopoietin (TPO) is a newly characterized hematopoietic growth factor which regulates the production of multipotent hematopoietic progenitor cells as well as platelets. To evaluate the possibility that an abnormality in TPO-mediated signal transduction might be involved in the pathogenesis of PV, we examined TPO-induced protein tyrosine phosphorylation using platelets as a surrogate model system. Platelets were isolated from the blood of patients with PV as well as from patients with other chronic myeloproliferative disorders and control subjects. Impaired TPO-mediated platelet protein tyrosine phosphorylation was a consistent observation in patients with PV as well as those with idiopathic myelofibrosis (IMF), in contrast to patients with essential thrombocytosis, chronic myelogenous leukemia, secondary erythrocytosis, iron deficiency anemia, hemochromatosis, or normal volunteers. Thrombin-mediated platelet protein tyrosine phosphorylation was intact in PV platelets as was expression of the appropriate tyrosine kinases and their cognate substrates. However, expression of the platelet TPO receptor, Mpl, as determined by immunoblotting, chemical crosslinking or flow cytometry was markedly reduced or absent in 34 of 34 PV patients and also in 13 of 14 IMF patients. Impaired TPO-induced protein tyrosine phosphorylation in PV and IMF platelets was uniformly associated with markedly reduced or absent expression of Mpl. We conclude that reduced expression of Mpl is a phenotypic characteristic of platelets from patients with PV and IMF. The abnormality appears to distinguish PV from other forms of erythrocytosis and may be involved in the platelet function defect associated with PV.

  18. Platelets surrounding primary tumor cells are related to chemoresistance.

    Science.gov (United States)

    Ishikawa, Satoko; Miyashita, Tomoharu; Inokuchi, Masafumi; Hayashi, Hironori; Oyama, Katsunobu; Tajima, Hidehiro; Takamura, Hironori; Ninomiya, Itasu; Ahmed, A Karim; Harman, John W; Fushida, Sachio; Ohta, Tetsuo

    2016-08-01

    Platelets are crucial components of the tumor microenvironment that function to promote tumor progression and metastasis. In the circulation, the interaction between tumor cells and platelets increases invasiveness, protects tumor cells from shear stress and immune surveillance, and facilitates tumor cell extravasation to distant sites. However, the role and presence of platelets in the primary tumor have not been fully determined. Here, we investigated the presence of platelets around breast cancer primary tumor cells and the associations between these cells. We further investigated the associations among platelets, tumor cells, chemoresistance, and epithelial-mesenchymal transition (EMT). We retrospectively analyzed data from 74 patients with human epidermal growth factor receptor 2 (HER2)‑negative breast cancer who underwent biopsies before treatment and subsequent neo-adjuvant chemotherapy. In biopsy specimens, we evaluated the expression of platelet-specific markers and EMT markers using immunohistochemistry. The associations among the expression of platelet‑specific markers in biopsy specimens, EMT, response to neo‑adjuvant chemotherapy, and survival were analyzed. The presence of platelets was observed in 44 out of 74 (59%) primary breast cancer biopsy specimens. Platelet‑positive tumor cells showed EMT‑like morphological changes and EMT marker expression. Primary tumor cells associated with platelets were less responsive to neo‑adjuvant chemotherapy (pCR rate: 10 vs. 50%, respectively; p=0.0001). Platelets were an independent predictor of the response to chemotherapy upon multivariable analysis (pbreast cancer. Platelets surrounding primary tumor cells may represent novel predictors of chemotherapeutic responses. PMID:27349611

  19. Platelet Composite Coatings for Tin Whisker Mitigation

    Science.gov (United States)

    Rohwer, Lauren E. S.; Martin, James E.

    2015-11-01

    Reliable methods for tin whisker mitigation are needed for applications that utilize tin-plated commercial components. Tin can grow whiskers that can lead to electrical shorting, possibly causing critical systems to fail catastrophically. The mechanisms of tin whisker growth are unclear and this makes prediction of the lifetimes of critical components uncertain. The development of robust methods for tin whisker mitigation is currently the best approach to eliminating the risk of shorting. Current mitigation methods are based on unfilled polymer coatings that are not impenetrable to tin whiskers. In this paper we report tin whisker mitigation results for several filled polymer coatings. The whisker-penetration resistance of the coatings was evaluated at elevated temperature and high humidity and under temperature cycling conditions. The composite coatings comprised Ni and MgF2-coated Al/Ni/Al platelets in epoxy resin or silicone rubber. In addition to improved whisker mitigation, these platelet composites have enhanced thermal conductivity and dielectric constant compared with unfilled polymers.

  20. Plasma rico en plaquetas Platelet -rich plasma

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    J. González Lagunas

    2006-04-01

    Full Text Available El Plasma Rico en Plaquetas es una suspensión concentrada de la sangre centrifugada que contiene elevadas concentraciones de trombocitos. Durante los últimos años, este producto ha aparecido de forma repetida en publicaciones científicas y en medios de comunicación generales como un producto que por sus características induce la curación y regeneración de los tejidos. La premisa de su uso es que las elevadas concentraciones de plaquetas en el PRP, liberan cantidades significativas de factores de crecimiento. En este artículo se van a recoger las evidencias científicas que se han presentado en la literatura médica con respecto al PRP y a la curación ósea, así como las diferentes aplicaciones clínicas que se han sugerido.Platelet-rich plasma is a by-product of centrifuged whole blood that contains high levels of thrombocytes. In the last decade, scientific and media interest has been generated by this product that apparently has the capacity of inducing and promoting tissue healing and regeneration. The premise of its use is that the large number of platelets in PRP release significant amounts of growth factors. In this paper, a critical review of the medical literature regarding PRP and bone healing will be presented. Also, the suggested clinical applications of the product will be addressed.

  1. [Platelets, atherothrombosis, antiplatelet drugs and cerebral ischemia].

    Science.gov (United States)

    Bousser, Marie-Germaine

    2013-02-01

    Platelets play a much more important role in myocardial ischemia than in cerebral ischemia, because atherothrombosis - the underlying cause of the vast majority of myocardial infarcts - is responsible for only 25-30% of cerebral infarcts. Aspirin is the only effective antiplatelet drug for primary prevention of ischemic events, especially those affecting the heart. For secondary prevention of cerebral infarction, clopidogrel and the combination of aspirin with extended-release dipyridamole are both marginally better than aspirin alone, but aspirin remains the gold standard worldwide because of its remarkable cost/benefit/tolerability ratio. The clopidogrel-aspirin combination is to be avoided because of the risk of hemorrhage, particularly in the brain and gastrointestinal tract. Revascularization strategies and the choice of antiplatelet drugs for the acute phase of myocardial and cerebral ischemia are very different, consisting of endovascular treatment and aggressive platelet inhibition for coronary infarcts, versus intravenous thrombolysis and / or aspirin for cerebral infarcts. None of the new antiplatelet drugs used in acute coronary syndromes has so far been studied in acute cerebral ischemia. PMID:24919368

  2. Indium-111 platelet scintigraphy in carotid disease

    Energy Technology Data Exchange (ETDEWEB)

    Branchereau, A.; Bernard, P.J.; Ciosi, G.; Bazan, M.; de Laforte, C.; Elias, A.; Bouvier, J.L.

    1988-07-01

    Forty-five patients (35 men, 10 women) undergoing carotid surgery had Indium-111 platelet scintigraphy as part of their preoperative work-up. Imaging was performed within three hours after injection of the Indium-111. A second series of views was obtained 24 hours later and repeated at 24 hour intervals for two days. Of 54 scintigrams, 22 were positive and 32 negative. Positive results were defined as a twofold or more increase in local activity on a visualized carotid after 24 hours. The sensitivity of the method was 41%, intraoperatively, and the specificity, 100%. The low sensitivity places this method behind sonography and duplex-scanning for screening patients for surgery. We believe that indications for platelet scintigraphy are limited to: 1. Repeated transient ischemic attacks in the same territory with minimal lesions on arteriography and non-homogeneous plaque on duplex scan; 2. Symptomatic patients being treated medically as a possible argument for surgery; 3. Determining therapeutic policy for patients having experienced a transient ischemic attack with a coexisting intracardiac thrombus.

  3. Common variants in the human platelet PAR4 thrombin receptor alter platelet function and differ by race

    Science.gov (United States)

    Edelstein, Leonard C.; Simon, Lukas M.; Lindsay, Cory R.; Kong, Xianguo; Teruel-Montoya, Raúl; Tourdot, Benjamin E.; Chen, Edward S.; Ma, Lin; Coughlin, Shaun; Nieman, Marvin; Holinstat, Michael; Shaw, Chad A.

    2014-01-01

    Human platelets express 2 thrombin receptors: protease-activated receptor (PAR)-1 and PAR4. Recently, we reported 3.7-fold increased PAR4-mediated aggregation kinetics in platelets from black subjects compared with white subjects. We now show that platelets from blacks (n = 70) express 14% more PAR4 protein than those from whites (n = 84), but this difference is not associated with platelet PAR4 function. Quantitative trait locus analysis identified 3 common single nucleotide polymorphisms in the PAR4 gene (F2RL3) associated with PAR4-induced platelet aggregation. Among these single nucleotide polymorphisms, rs773902 determines whether residue 120 in transmembrane domain 2 is an alanine (Ala) or threonine (Thr). Compared with the Ala120 variant, Thr120 was more common in black subjects than in white subjects (63% vs 19%), was associated with higher PAR4-induced human platelet aggregation and Ca2+ flux, and generated greater inositol 1,4,5-triphosphate in transfected cells. A second, less frequent F2RL3 variant, Phe296Val, was only observed in blacks and abolished the enhanced PAR4-induced platelet aggregation and 1,4,5-triphosphate generation associated with PAR4-Thr120. PAR4 genotype did not affect vorapaxar inhibition of platelet PAR1 function, but a strong pharmacogenetic effect was observed with the PAR4-specific antagonist YD-3 [1-benzyl-3(ethoxycarbonylphenyl)-indazole]. These findings may have an important pharmacogenetic effect on the development of new PAR antagonists. PMID:25293779

  4. Effect of combined anti-platelets drugs on platelet activation in the elderly patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    黄大海

    2012-01-01

    Objective To investigate the effect of combined anti-platelets drugs on platelet activation in the elderly patients with acute coronary syndrome(ACS).Methods Totally 72 elderly patients with ACS were divided randomly into two groups according to age ≤80 years and>80 years.

  5. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin.

    Science.gov (United States)

    Bozzi, Laura M; Mitchell, Braxton D; Lewis, Joshua P; Ryan, Kathy A; Herzog, William R; O'Connell, Jeffrey R; Horenstein, Richard B; Shuldiner, Alan R; Yerges-Armstrong, Laura M

    2016-01-01

    Clopidogrel and aspirin are commonly prescribed anti-platelet medications indicated for patients who have experienced, or are at risk for, ischemic cardiovascular events. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study was designed to characterize determinants of clopidogrel and dual anti-platelet therapy (DAPT) response in a healthy cohort of Old Order Amish from Lancaster, PA. Following a loading dose, clopidogrel was taken once a day for 7 days. One hour after the last dose of clopidogrel, 325 mg of aspirin was given. Ex vivo platelet aggregometry was performed at baseline, post-clopidogrel, and post-DAPT. Platelet aggregation measurements were significantly lower after both interventions for all agonists tested (p pharmacogenomics studies.

  6. Incidence of platelet dysfunction by thromboelastography-platelet mapping in children supported with ECMO: A Pilot Retrospective Study.

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    Arun eSaini

    2016-01-01

    Full Text Available Background: Bleeding complications are common and decrease the odds of survival in children supported with extracorporeal membrane oxygenation (ECMO. The role of platelet dysfunction on ECMO-induced coagulopathy and resultant bleeding complications is not well understood. The primary objective of this pilot study was to determine the incidence and magnitude of platelet dysfunction according to thromboelastography (TEG®-platelet mapping (PM testing. Methods: Retrospective chart review of children <18 years old who required ECMO at a tertiary level hospital. We collected TEG®-PM and conventional coagulation tests data. We also collected demographic, medications, blood products administered, and clinical outcome data. We defined severe platelet dysfunction as less than 50 % aggregation in response to an agonist. Results: We identified 24 out of 46 children on ECMO, who had TEG®-PM performed during the study period. We found the incidence of severe bleeding was 42%, and mortality was 54% in our study cohort. In all samples measured, severe qualitative platelet dysfunction was more common for adenosine diphosphate (ADP-mediated aggregation (92% compared to arachidonic acid (AA-mediated aggregation (75%, (p=0.001. Also, ADP-mediated percent of platelet aggregation was significant lower than AA-mediated platelet aggregation (15% [IQR 2.8-48] vs 49% [IQR 22-82.5], p<0.001. There was no difference in kaolin-activated heparinase TEG® parameters between the bleeding group and the non-bleeding group. Only absolute platelet count and TEG®-PM had increased predictive value on receiver operating characteristics analyses for severe bleeding and mortality compared to ACT. Conclusions: We found frequent and severe qualitative platelet dysfunction on TEG®-PM testing in children on ECMO. Larger studies are needed to determine if the assessment of qualitative platelet function by TEG®-PM can improve prediction of bleeding complications for children on ECMO.

  7. Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis

    OpenAIRE

    Battinelli, Elisabeth M.; Markens, Beth A.; Italiano, Joseph E.

    2011-01-01

    An association between platelets, angiogenesis, and cancer has long been recognized, but the mechanisms linking them remains unclear. Platelets regulate new blood vessel growth through numerous stimulators and inhibitors of angiogenesis by several pathways, including differential exocytosis of angiogenesis regulators. Herein, we investigated the differential release of angiogenesis stimulators and inhibitors from platelets. Activation of human platelets with adenosine diphosphate (ADP) stimul...

  8. Prognostic significance of early platelet count decline in preterm newborns

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    Abeer Abd Elmoneim

    2015-01-01

    Full Text Available Objectives: Decline of platelets with or without thrombocytopenia is observed in critically ill preterm newborns. Prognostic significance of platelets count in Neonatal Intensive Care Unit focused on outcome after thrombocytopenia. We aimed to estimate the changes in platelets count within the first 7 days of life in preterm newborns and its relation to final outcomes. Methods: Retrospectively, the platelets count during the first 7 days of life, and its association with mortality, length of stay among survivors (LOS, and later severe morbidities were determined. Appropriate regression analyses were used to examine possible relations between studied variables. Results and Discussion: Platelets drop that did not reach thrombocytopenia level in the first 7 days of life happened in 61.7%. Platelets count drop in the first 7 days of life was a predictor of mortality, LOS, and major morbidities such as intraventricular hemorrhage and necrotizing enterocolitis. Conclusions: Platelets count drop within the first 7 days of life independent of thrombocytopenia can be used to predict increased mortality, LOS, and the development of later severe morbidities in critically ill preterm neonates.

  9. Regulating VEGF signaling in platelet concentrates via specific VEGF sequestering.

    Science.gov (United States)

    Belair, David G; Le, Ngoc Nhi; Murphy, William L

    2016-05-26

    Platelets contain an abundance of growth factors that mimic the composition of the wound healing milieu, and platelet-derived VEGF in particular can negatively influence wound healing if unregulated. Here, we sought to capture and regulate the activity of VEGF factor from human platelets using poly(ethylene glycol) microspheres. In this communication, we demonstrate that platelet freeze/thaw produced significantly higher levels of Vascular Endothelial Growth Factor (VEGF) than either calcium chloride treatment, protease activated receptor 1 activating peptide (PAR1AP) treatment, or thrombin treatment. PEG microspheres containing a VEGF-binding peptide (VBP), derived from VEGFR2, sequestered VEGF from platelet concentrate, prepared via freeze/thaw, and reduced the bioactivity of platelet concentrate in HUVEC culture, which suggests that VBP microspheres sequestered and reduced the activity of VEGF from patient-derived platelets. Here, we demonstrate the ability of VEGF sequestering microspheres to regulate the activity of VEGF derived from a growth factor-rich autologous human blood product. PMID:27010034

  10. Individual dosing of ASA prophylaxis by controlling platelet aggregation.

    Science.gov (United States)

    Syrbe, G; Redlich, H; Weidlich, B; Ludwig, J; Kopitzsch, S; Göckefitz, A; Herzog, T

    2001-07-01

    Acetylsalicylic acid is widely used in the primary and secondary prevention of cardiovascular diseases. In the current study, we used platelet aggregation ex vivo in platelet-rich plasma induced with arachidonic acid as a routine method for the determination of the individual dose of acetylsalicylic acid necessary to inhibit platelet aggregation in 108 patients with cardiovascular diseases. In 40% of all patients studied, a dose of 30 mg/day was sufficient to block the arachidonic acid-induced platelet aggregation nearly completely. In 50% of all patients, a dose of 100 mg/day was necessary. In 10% of all patients, the dose had to be further increased to 300 mg/day or even to 500 mg/day to inhibit platelet aggregation nearly completely. These results demonstrate that platelet aggregation can be used as a simple routine laboratory method to control acetylsalicylic acid treatment in patients with cardiovascular diseases and to determine individual doses of acetylsalicylic acid for a nearly complete inhibition of platelet aggregation. With a standard dose of 100 mg/day, 10% of the patients were nonresponders. PMID:11441981

  11. Dabigatran and rivaroxaban do not affect AA- and ADP-induced platelet aggregation in patients receiving concomitant platelet inhibitors.

    Science.gov (United States)

    Olivier, Christoph B; Weik, Patrick; Meyer, Melanie; Weber, Susanne; Diehl, Philipp; Bode, Christoph; Moser, Martin; Zhou, Qian

    2016-08-01

    Dabigatran and rivaroxaban are novel, vitamin K-independent oral anticoagulants (NOACs) and act via antagonism of the coagulation factor (F) IIa (dabigatran) or FXa (rivaroxaban), respectively. Compared to vitamin-K-antagonists, NOACs have shown non-inferiority of risk and benefit in patients with non valvular atrial fibrillation (AF). In clinical practice there is increasing use of NOACs combined with platelet inhibitors in patients with AF and coronary artery disease. However, whether NOACs affect the function of platelet inhibitors remains incompletely known. This observational study aimed to assess the platelet function in patients receiving dabigatran or rivaroxaban and concomitant platelet inhibitors. A single centre observational study was performed analysing the platelet aggregation of patients treated with dabigatran or rivaroxaban with or without concomitant platelet inhibitors. Measurements before the initiation of NOAC therapy served as the respective control group. Platelet aggregation was measured by multiple electrode aggregometry and was induced with adenosine diphosphate (ADP, 6.5 µM) and arachidonic acid (AA, 0.5 mM), respectively. In order to evaluate whether NOACs interact with platelet inhibition by ASA or the P2Y12-antagonist clopidogrel, 87 patients were grouped according to their concomitant antiplatelet medication. Comparing the ADP- and AA-induced platelet aggregation in patients without concomitant platelet inhibitors (n = 45) no significant differences under therapy with dabigatran (d) or rivaroxaban (r) compared to the control group (c) were observed. In patients taking clopidogrel as a concomitant platelet inhibitor (n = 21), neither dabigatran nor rivaroxaban affected the ADP-induced platelet aggregation (c 20 ± 11, d 21 ± 14, r 18 ± 8 AU*min, p = 0.200). Patients receiving dabigatran or rivaroxaban in combination with ASA (n = 42; 21 ASA only, 21 ASA + clopidogrel) showed no significant differences of the AA

  12. A meta-analysis and genome-wide association study of platelet count and mean platelet volume in african americans.

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    Rehan Qayyum

    Full Text Available Several genetic variants associated with platelet count and mean platelet volume (MPV were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388 with p<5×10(-8 of which 5 have not been associated with platelet count in previous GWAS. The novel genetic variants associated with platelet count were in the following regions (the most significant SNP, closest gene, and p-value: 6p22 (rs12526480, LRRC16A, p = 9.1×10(-9, 7q11 (rs13236689, CD36, p = 2.8×10(-9, 10q21 (rs7896518, JMJD1C, p = 2.3×10(-12, 11q13 (rs477895, BAD, p = 4.9×10(-8, and 20q13 (rs151361, SLMO2, p = 9.4×10(-9. Three of these loci (10q21, 11q13, and 20q13 were replicated in European Americans (N = 14,909 and one (11q13 in Hispanic Americans (N = 3,462. For MPV (N = 4,531, genetic variants in 3 regions were significant at p<5×10(-8, two of which were also associated with platelet count. Previously reported regions that were also significant in this study were 6p21, 6q23, 7q22, 12q24, and 19p13 for platelet count and 7q22, 17q11, and 19p13 for MPV. The most significant SNP in 1 region was also associated with ADP-induced maximal platelet aggregation in whole blood (12q24. Thus through a meta-analysis of GWAS enrolling African Americans, we have identified 5 novel regions associated with platelet count of which 3 were replicated in other ethnic

  13. Human platelet calmodulin-binding proteins: Ca/sup 2 +/-dependent proteolysis upon platelet activation

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    Wallace, R.W.; Tallant, E.A.; McManus, M.C.

    1986-05-01

    Calmodulin (CaM)-binding proteins have been identified in human platelets using Western blotting techniques and /sup 125/I-CaM. Ten distinct proteins with molecular weights of 245, 225K, 175K, 150K, 90K, 82K(2), 60K and 41K(2) bound /sup 125/I-CaM in a Ca/sup 2 +/-dependent manner; the binding was blocked by both trifluoperazine and nonradiolabeled CaM. The 225K and 90K proteins were labeled by antisera against myosin light chain kinase (MLCK); the 60K and one of the 82K proteins were identified as the CaM-dependent phosphatase and caldesmon. The remaining proteins have not yet been identified. Most of the CaM-binding proteins were degraded upon addition of Ca/sup 2 +/ to a platelet homogenate; the degradation could be blocked by either EGTA, leupeptin or N-ethyl-maleimide which suggests that it was due to a Ca/sup 2 +/-dependent protease. Activation of intact platelets by thrombin, ADP, collagen and the Ca/sup 2 +/-ionophores A23187 and ionomycin under conditions which promote platelet aggregation (i.e. stirring with extracellular Ca/sup 2 +/) also resulted in limited proteolysis of CaM-binding proteins including those labeled with anti-MLCK and the phosphatase. Many Ca/sup 2 +//CaM-regulated enzymes have been shown to be irreversibly activated in vitro by limited proteolysis. Their data indicates that limited proteolysis also occurs in vivo; under certain conditions proteolysis may be an important physiological mechanism for irreversibly activating Ca/sup 2 +//CaM-regulated enzymes.

  14. Sulfatides partition disabled-2 in response to platelet activation.

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    Karen E Drahos

    Full Text Available BACKGROUND: Platelets contact each other at the site of vascular injury to stop bleeding. One negative regulator of platelet aggregation is Disabled-2 (Dab2, which is released to the extracellular surface upon platelet activation. Dab2 inhibits platelet aggregation through its phosphotyrosine-binding (PTB domain by competing with fibrinogen for alphaIIbbeta3 integrin receptor binding by an unknown mechanism. METHODOLOGY/PRINCIPAL FINDINGS: Using protein-lipid overlay and liposome-binding assays, we identified that the N-terminal region of Dab2, including its PTB domain (N-PTB, specifically interacts with sulfatides. Moreover, we determined that such interaction is mediated by two conserved basic motifs with a dissociation constant (K(d of 0.6 microM as estimated by surface plasmon resonance (SPR analysis. In addition, liposome-binding assays combined with mass spectroscopy studies revealed that thrombin, a strong platelet agonist, cleaved N-PTB at a site located between the basic motifs, a region that becomes protected from thrombin cleavage when bound to sulfatides. Sulfatides on the platelet surface interact with coagulation proteins, playing a major role in haemostasis. Our results show that sulfatides recruit N-PTB to the platelet surface, sequestering it from integrin receptor binding during platelet activation. This is a transient recruitment that follows N-PTB internalization by an actin-dependent process. CONCLUSIONS/SIGNIFICANCE: Our experimental data support a model where two pools of Dab2 co-exist at the platelet surface, in both sulfatide- and integrin receptor-bound states, and their balance controls the extent of the clotting response.

  15. Managing pregnancy with HIV, HELLP syndrome and low platelets.

    Science.gov (United States)

    Onyangunga, O A; Moodley, J

    2012-02-01

    Management of pregnancies with human immunodeficiency virus, haemolytic anaemia, elevated liver enzymes, low platelets (HELLP) syndrome, and low platelets presents complexities in investigations and treatments, because these conditions and their treatment affect the mother and baby. Low platelets in severe pre-eclampsia, eclampsia and HELLP syndrome are relatively common, and should be detected early once the diagnosis of pre-eclampsia, HELLP syndrome, or both, are made. The mainstay of treatment is lowering of high blood pressure with rapid-acting antihypertensive agents, prevention of convulsions or further seizures with MgSO(4), use of steroids for fetal lung maturity if necessary, followed by delivery of the baby. The use of high-dose steroids for the rapid recovery of maternal platelet counts is controversial, and should not be used routinely in women with HELLP syndrome. The use of platelet transfusion in women with severe pre-eclampsia, eclampsia and HELLP syndrome is a temporising measure, and should only be justified if the clinical circumstances warrant their use (e.g. before caesarean section when the woman has a low platelet count with evidence of bruising or bleeding from venepuncture sites). Low platelets may be an isolated finding in asymptomatic pregnant women and warrant the offer of a human immunodeficiency virus test, as it may be the first sign of this infection. Isolated low platelets may also indicate gestational thrombocytopaenia or idiothrombocytopaenic purpura. Gestational thrombocytopaenia is a benign condition and a diagnosis of exclusion. All clinicians should be aware that low platelets warrant further investigations because of the above-mentioned issues.

  16. Thrombocytopenia in leptospirosis and role of platelet transfusion

    Directory of Open Access Journals (Sweden)

    Sharma Jayashree

    2007-01-01

    Full Text Available Aim : The study was designed to find out the incidence of thrombocytopenia in leptospirosis and to correlate thrombocytopenia with other parameters like renal failure, hepatic failure and bleeding manifestation like adult respiratory distress syndrome and to assess the role of platelet transfusion. Materials and Methods : 50 cases of leptospirosis during the month of July and August 2005 were retrospectively analyzed. Criteria for selection were Lepto Tek Dri - dot test positive cases of the clinically suspected cases of Leptospirosis. Degree of thrombocytopenia was categorized as severe, moderate and mild. Presence of thrombocytopenia was clinically correlated with parameters like renal dysfunction, hepatic dysfunction and hemorrhagic manifestations (mainly ARDS. Role of platelet transfusion was assessed with reference to presence and degree of thrombcytopenia and hemorrhagic manifestations. Results : Out of total 50 patients 26 were male and 24 were females. Major bleeding manifestation in the form of ARDS was seen in 15 (30% of patients. 28 (56% patients had thrombocytopenia and 22 (44% patients had normal platelet counts. Total number of patients with renal dysfunction was 24 (48%. Only four (18.18% patients with normal platelet counts had renal dysfunction while 20 (71.42% patients with thrombocytopenia had renal dysfunction. Only two (9.09% patients with normal platelet counts and 48 (46.42% patients with thrombocytopenia had hepatorenal dysfunction. Total number of patients with ARDS was 15 (30%. Of these two (13.33% had normal platelet count while 13 (86.6% patients were thrombocytopenic. Total 47 units of platelets were transfused to 12 patients in our study. Of these seven patients with severe thrombocytopenia required total 28 units, two patients with moderate thrombocytopenia required total seven units and patients with mild thrombocytopenia were transfused total 12 units of platelets. Conclusion : It is important to anticipate and

  17. Plasma and platelet serotonin levels in patients with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To analyze the relationship between plasmaand platelet serotonin levels and the degree of liverinsufficiency.METHODS: The prospective study included 30 patients with liver cirrhosis and 30 healthy controls. The degree of liver failure was assessed according to the Child-Pugh classification. Platelet and platelet poor plasma serotonin levels were determined.RESULTS: The mean plasma serotonin level was higher in liver cirrhosis patients than in healthy subjects (215.0± 26.1 vs 63.1 ± 18.1 nmol/L; P < 0.0001). The mean platelet serotonin content was not significantly different in patients with liver cirrhosis compared with healthy individuals (4.8 ± 0.6; 4.2 ± 0.3 nmol/platelet; P > 0.05).Plasma serotonin levels were significantly higher in ChildPugh grade A/B than in grade C patients (246.8 ± 35.0vs132.3 ± 30.7 nmol/L; P < 0.05). However, platelet serotonin content was not significantly different between Child-Pugh grade C and grade A/B (4.6 ± 0.7 vs 5.2 ± 0.8nmol/platelet; P > 0.05).CONCLUSION: Plasma serotonin levels are significantly higher in patients with cirrhosis than in the controls and represent the degree of liver insufficiency. In addition,platelet poor plasma serotonin estimation is a better marker for liver insufficiency than platelet serotonin content.

  18. Systems Biology of Platelet-Vessel Wall Interactions.

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    Scott L. Diamond

    2013-08-01

    Full Text Available Blood Systems Biology seeks to quantify outside-in signaling as platelets respond to numerous external stimuli, typically under flow conditions. Platelets can activate via GPVI collagen receptor and numerous G-protein coupled receptors (GPCRs responsive to ADP, thromboxane, thrombin, and prostacyclin. A bottom-up ODE approach allowed prediction of platelet calcium and phosphoinositides following P2Y1 activation with ADP, either for a population average or single cell stochastic behavior. The homeostasis assumption (i.e. a resting platelet stays resting until activated was particularly useful in finding global steady states for these large metabolic networks. Alternatively, a top-down approach involving Pairwise Agonist Scanning allowed large data sets of measured calcium mobilization to predict an individual’s platelet responses. The data was used to train Neural Network (NN models of signaling to predict patient-specific responses to combinatorial stimulation. A kinetic description of platelet signaling then allows prediction of inside-out activation of platelets as they experience the complex biochemical milieu at the site of thrombosis. Multiscale lattice kinetic Monte Carlo (LKMC utilizes these detailed descriptions of platelet signaling under flow conditions where released soluble species are solved by finite element method and the flow field around the growing thrombus is updated using computational fluid dynamics or lattice Boltzmann method. Since hemodynamic effects are included in a multiscale approach, thrombosis can then be predicted under arterial and venous thrombotic conditions for various anatomical geometries. Such systems biology approaches accommodate the effect of anti-platelet pharmacological intervention where COX1 pathways or ADP signaling are modulated in a patient-specific manner.

  19. Intracranial hemorrhage and platelet transfusion after administration of anti-platelets agents: Fukushima Prefecture.

    Science.gov (United States)

    Suzuki, Yuhko; Sato, Taku; Sakuma, Jun; Ichikawa, Masahiro; Kishida, Yugo; Oda, Keiko; Watanabe, Yoichi; Goto, Takeshi; Sato, Masahiro; Nollet, Kenneth E; Saito, Kiyoshi; Ohto, Hitoshi

    2016-06-01

    We conducted a case series study to assess intracerebral hemorrhage (ICH) in the context of anti-platelets agents (APAs) and platelet (PLT) transfusion in Fukushima Prefecture.This study included patients who were newly diagnosed with ICH between January 2008 and June 2014 in the neurosurgical hospitals of Fukushima Prefecture. Four of ten neurosurgical hospitals responded to our questionnaire. Of 287 ICH patients, 51 (20.6%) were on APA therapy, of whom PLT transfusion was given to only one persistently bleeding patient who was on dual anti-platelet therapy. In a follow-up survey, 30 out of 51 ICH patients on APA therapy, average age 75 years, were analyzed, of whom 21 (70%) were male. The predominant underlying disease was diabetes mellitus. It is interesting to note that peripheral artery disease and aortic aneurysm were among the indications for APAs. ICH was mainly observed supratentorially. Hematoma enlargement was observed in 13 (44.8%) cases. By day 7, 3 patients (10%) had died from complications of ICH. In this study, we show that ICH during APA therapy matched what was observed in Kanagawa Prefecture. Whether or not a national survey differs, we anticipate greater statistical validity and an opportunity to improve patient outcomes in Japan and around the world. PMID:27210309

  20. Revascularization of Immature Necrotic Teeth: Platelet rich Fibrin an Edge over Platelet rich Plasma

    Directory of Open Access Journals (Sweden)

    Neelam Mittal

    2012-03-01

    Full Text Available Introduction: Revascularization is one such entity that has found its clinical application in the field of endodontics for the manage-ment of immature permanent necrotic teeth. The protocols for revascularization of such teeth focus especially on delivery of stem cells and scaffolds in a nonsurgical manner rather than concentrated growth micro molecules.The hypothesis: This article proposes the role of platelet concentrates such as platelet rich fibrin (PRF and platelet rich plasma (PRP in accelerating the regenerative process in such teeth. PRF unlike PRP is associated with slow, continuous and substantial re-lease of morphogens. It is hypothesized further if PRF instead of PRP when placed through immature apices in an orthograde manner can open newer gates for fast and controlled growth in young, ne-crotic, non-infected teeth.Evaluation of the hypothesis: Enhancement of the healing kinetics can be evaluated by change in size of periapical radiolucency, thickness of the dentinal walls, root elongation and apical closure compared between preoperative and postoperative standardized two dimensional/three dimensional radiographs taken on regular follow ups.

  1. Glycans and glycosylation of platelets: current concepts and implications for transfusion

    DEFF Research Database (Denmark)

    Sørensen, Anne Louise; Hoffmeister, Karin M; Wandall, Hans H

    2008-01-01

    the risk of transfusion-mediated sepsis and accelerates platelet deterioration, limiting platelet shelf life. Recent evidence suggests that glycoengineering of platelets might allow for their cold storage, significantly improving the quality of platelet products.......PURPOSE OF REVIEW: Platelet products are currently stored at room temperature, because refrigeration causes their rapid clearance from the circulation upon transfusion. Glycans have recently been emphasized as important determinants for the clearance of refrigerated platelets. The present review...... addresses the current knowledge of platelet glycans and the potential of glycosylation for improving platelet storage. RECENT FINDINGS: Removal of refrigerated platelets from the circulation is partly mediated by recognition of clustered beta-N-acetylglucosamine on platelet surface glycoproteins...

  2. Changes in platelet parameters and secondary brain injury in acute craniocerebral trauma

    Institute of Scientific and Technical Information of China (English)

    Xiaoping Tang; Zhangyang Gou; Junwei Duan; Shun Li; Chao You; Hua Peng; Tao Zhang; Wenguo Tang; Jian Qi; Renguo Luo; Yuanchuan Wang; Ling Feng

    2011-01-01

    Changes in platelet parameters are important in secondary brain injury in acute craniocerebral trauma. We selected 163 patients with craniocerebral trauma who were admitted within 24 hours with nonoperative therapy. Platelet parameters of 40 healthy subjects served as controls. Platelet number was decreased, while mean platelet volume and platelet distribution width values were increased, at 1 and 3 days after injury. Platelet number was lower and mean platelet volume and platelet distribution width were larger in patients with traumatic cerebral infarction and those in Glasgow Coma Scale score < 8 group. Platelet number was negatively correlated to volume of cerebral edema, but positively correlated to Glasgow Outcome Scale score. These data indicate that changes in platelet parameters may be utilized to indicate the state of central nervous system injury and patient prognosis.

  3. Emerging Evidence for Platelets as Immune and Inflammatory Effector Cells

    Directory of Open Access Journals (Sweden)

    Matthew Thomas Rondina

    2014-12-01

    Full Text Available While traditionally recognized for their roles in hemostatic pathways, emerging evidence demonstrates that platelets have previously unrecognized, dynamic roles that span the immune continuum. These newly-recognized platelet functions, including the secretion of immune mediators, interactions with endothelial cells, monocytes, and neutrophils, toll-like receptor (TLR mediated responses, and induction of neutrophil extracellular trap (NET formation, bridge thrombotic and inflammatory pathways and contribute to host defense mechanisms against invading pathogens. In this focused review, we highlight several of these emerging aspects of platelet biology and their implications in clinical infectious syndromes.

  4. Acidic preparations of platelet concentrates release bone morphogenetic protein-2.

    OpenAIRE

    Wahlström, Ola; Linder, Cecilia; Kalén, Anders; Magnusson, Per

    2008-01-01

    BACKGROUND AND PURPOSE: Growth factors released from platelets have potent effects on fracture and wound healing. The acidic tide of wound healing, i.e. the pH within wounds and fractures, changes from acidic pH to neutral and alkaline pH as the healing process progresses. We investigated the influence of pH on lysed platelet concentrates regarding the release of growth factors. MATERIAL AND METHODS: Platelet concentrates free of leukocyte components were lysed and incubated in buffers with p...

  5. PLATELET COUNT, ITS SIGNIFICANCE IN BURN INJURY MANAGEMENT

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    Shanti Prakash

    2015-07-01

    Full Text Available INTRODUCTION: Platelet count evaluation in a burn trauma patient has much significance because it has been studied in literature that decrease i n platelet count is an indicator of septicaemia in the patient and vice versa thus knowing the count level of platelets, the treatment of burn patients can be done accordingly. Septicaemia is most important cause of mortality in burn patients, the survival of the patients can only be assured if septicaemia is detected early and controlled. Platelet s play an important role in haemostaticdisorder and immune response impairment in burn patient . [1] The aim of study is to see the significance of platelet count i nvestigation in burn patient and then their outcome, whether survival or not survival. MATERIAL METHODS: We investigated 480 burn patients within the ages of 18 and 60 Years and the percentage of the burn was between 20% and 70%. Platelet count was investi gated by visual method in all patients. The investigation of the platelet count was done on day 1, 3, 7, 14 & 21 of the patients. Other parameters TLC , neutrophil count was done by visual methods. Serum creatinine estimation was also done in all patients. RESULT: In our study we found that the platelet count gradually increased towards normal count and maintained till the discharge in survival patients, and in non - survival the platelet count gradually declined. The statistical significant of difference in m ean platelet counts on different post burn days in survivors and non survivors were studied by using standard t test. It was observed that the actual difference between two means is more than double of the SED between two means in different post burn days – i . e. , (Day 1, 3, 7, 14 &, 21. So difference is significant (P<0.05. CONCLUSION: It can be concluded that platelet count decreases initially in all cases of burn sepsis. It gradually rises to normal in case of survivors and declines gradually in non surv ivors. So serial declining

  6. Platelet-rich plasma for osteoarthritis treatment

    Directory of Open Access Journals (Sweden)

    Eduardo Knop

    2016-04-01

    Full Text Available ABSTRACT We conducted a comprehensive and systematic search of the literature on the use of platelet-rich plasma (PRP in the treatment of osteoarthritis, using the Medline, Lilacs, Cochrane and SciELO databases, from May 2012 to October 2013. A total of 23 studies were selected, with nine being controlled trials and, of these, seven randomized, which included 725 patients. In this series, the group receiving PRP showed improvement in pain and joint function compared to placebo and hyaluronic acid. The response lasted up to two years and was better in milder cases. However it was found that there is no standardization in the PRP production method, neither in the number, timing, and volume of applications. Furthermore, the populations studied were not clearly described in many studies. Thus, these results should be analyzed with caution, and further studies with more standardized methods would be necessary for a more consistent conclusion about the PRP role in osteoarthritis.

  7. Effects of platelet-poor plasma, platelet-rich plasma, and platelet-rich fibrin on healing of extraction sockets with buccal dehiscence in dogs.

    Science.gov (United States)

    Hatakeyama, Ichiro; Marukawa, Eriko; Takahashi, Yukinobu; Omura, Ken

    2014-02-01

    Alveolar bone resorption generally occurs during healing after tooth extraction. This study aimed to evaluate the effects of platelet-poor plasma (PPP), platelet-rich plasma (PRP), and platelet-rich fibrin (PRF) on healing in a ridge-augmentation model of the canine socket with dehiscence of the buccal wall. The third mandibular premolars of 12 beagle dogs were extracted and a 3 mm buccal dehiscence from the alveolar crest to the buccal wall of the extraction socket was created. These sockets were then divided into four groups on the basis of the material used to fill the sockets: PPP, PRP, PRF, and control (no graft material) groups. Results were evaluated at 4 and 8 weeks after surgery. The ultrastructural morphology and constructs of each blood product were studied by a scanning electron microscope (SEM) or calculating concentrations of platelets, fibrinogen, platelet-derived growth factor, and transforming growth factor-β. A total of five microcomputed tomography images of specimens were selected for measurement, and the area occupied by the newly formed bone as well as the horizontal bone width were measured. Moreover, decalcified tissue specimens from each defect were analyzed histologically. The median area of new bone at 4 and 8 weeks and median horizontal bone width at 8 weeks were the highest in the PPP group. However, bone maturation in the PRF and the PRP groups was more progressed than that in the PPP and control groups. By SEM findings, the PRF group showed a more highly condensed fibrin fiber network that was regularly arranged when compared with the PPP and PRP groups. The growth factors released from platelets in PRP indicated higher concentrations than that in PRF. Under more severe conditions for bone formation, as in this experiment, the growth factors released from platelets had a negative effect on bone formation. This study showed that PPP is an effective material for the preservation of sockets with buccal dehiscence.

  8. Mechanisms of andrographolide-induced platelet apoptosis in human platelets: regulatory roles of the extrinsic apoptotic pathway.

    Science.gov (United States)

    Lien, Li-Ming; Su, Cheng-Chen; Hsu, Wen-Hsien; Lu, Wan-Jung; Chung, Chi-Li; Yen, Ting-Lin; Chiu, Hou-Chang; Sheu, Joen-Rong; Lin, Kuan-Hung

    2013-11-01

    Andrographolide, a novel nuclear factor-κB (NF-κB) inhibitor, is isolated from the leaves of Andrographis paniculata. Platelet activation is relevant to a variety of coronary heart diseases. Our recent studies revealed that andrographolide possesses potent antiplatelet activity by inhibition of the p38 MAPK/(●) HO-NF-κB-ERK2 cascade. Although platelets are anucleated cells, apoptotic machinery apparatus recently has been found to regulate platelet activation and limit platelet lifespan. Therefore, we further investigated the regulatory effects of andrographolide on platelet apoptotic events. In this study, apoptotic signaling events for caspase-3, -8, and Bid were time (10-60 min)- and dose (25-100 μΜ)-dependently activated by andrographolide in human platelets. Andrographolide could also disrupt mitrochondrial membrane potential. In addition, caspase-8 inhibitor (z-IETD-fmk, 50 μΜ) was found to reverse andrographolide-induced caspase-8 activation, whereas the antagonistic anti-Fas receptor (ZB4, 500 ng/mL) and anti-tumor necrosis factor-R1 (H398, 10 µg/mL) monoclonal antibodies did not. In conclusion, this study for the first time demonstrated that andrographolide might limit platelet lifespan by initiating the caspase-8-dependent extrinsic apoptotic pathway, in spite of no direct evidence that death receptors are involved in this process proved. Overall, the various medicinal properties of andrographolide suggest its potential value in treating patients with thromboembolic disorders. PMID:23292890

  9. Role of platelet transfusion in children with bleeding in dengue fever

    Directory of Open Access Journals (Sweden)

    Sriram Pothapregada

    2015-01-01

    Interpretation & conclusion: Platelet transfusion was required in children with severe dengue infection in the form of significant spontaneous bleed, shock and severe thrombocytopenia. Bleeding should not be considered only indicator to transfuse platelets as it occurred in children even with normal platelet counts. The community and treating physicians should be educated regarding the judicious transfusion of platelets. Unnecessary and empirical use of platelets should be completely avoided especially during an epidemic when there is scarcity in its availability.

  10. [Isoenzyme fractions of serum and platelet lactate dehydrogenase in normal subjects].

    Science.gov (United States)

    Perna, M P; Palmucci, Z; Saccone, A; Rossi, M; Tresca, E; Nubile, G

    1984-04-30

    We determined the isoenzymatic fractions of platelets and seric LDH in off healthy people (50 males and 50 females). We broken the platelets by triton X 100 (octylphenoxypolyethoxyethanol) in order to obtain the release of platelet LDH. The seric and platelet LDH isoenzymes were then separated by electrophoresis (Gelman sistem). We confirm the prevalence of LDH2 and LDH3 fractions in human platelets. PMID:6732960

  11. Platelets as immune mediators: Their role in host defense responses and sepsis

    OpenAIRE

    Li, Zhenyu; Yang, Fanmuyi; Dunn, Steve; Gross, A. Kendall; Smyth, Susan S.

    2010-01-01

    Platelets occupy a central role at the interface between thrombosis and inflammation. At sites of vascular damage, adherent platelets physically and functionally interact with circulating leukocytes. Activated platelets release soluble factors into circulation that may have local and systemic effects on blood and vascular cells. Platelets can also interact with a wide variety of microbial pathogens. Emerging evidence from animal models suggests that platelets may participate in a wide variety...

  12. Platelet Surface-Associated Activation and Secretion-Mediated Inhibition of Coagulation Factor XII

    OpenAIRE

    Zakharova, Natalia V.; Artemenko, Elena O.; Podoplelova, Nadezhda A.; Anastasia N Sveshnikova; Demina, Irina A.; Ataullakhanov, Fazly I.; Panteleev, Mikhail A.

    2015-01-01

    Coagulation factor XII (fXII) is important for arterial thrombosis, but its physiological activation mechanisms are unclear. In this study, we elucidated the role of platelets and platelet-derived material in fXII activation. FXII activation was only observed upon potent platelet stimulation (with thrombin, collagen-related peptide, or calcium ionophore, but not ADP) accompanied by phosphatidylserine exposure and was localised to the platelet surface. Platelets from three patients with grey p...

  13. OP9 Bone Marrow Stroma Cells Differentiate into Megakaryocytes and Platelets

    OpenAIRE

    Yumiko Matsubara; Yukako Ono; Hidenori Suzuki; Fumio Arai; Toshio Suda; Mitsuru Murata; Yasuo Ikeda

    2013-01-01

    Platelets are essential for hemostatic plug formation and thrombosis. The mechanisms of megakaryocyte (MK) differentiation and subsequent platelet production from stem cells remain only partially understood. The manufacture of megakaryocytes (MKs) and platelets from cell sources including hematopoietic stem cells and pluripotent stem cells have been highlighted for studying the platelet production mechanisms as well as for the development of new strategies for platelet transfusion. The mouse ...

  14. Platelet Count and Mean Platelet Volume in Patients with Nasal Polyposis

    Directory of Open Access Journals (Sweden)

    Asli Tanrivermis Sayit

    2014-12-01

    Full Text Available Aim: Nasal polyps (NPs are the most common reason for nasal obstruction, with a prevalence of 1-4%. Although the etiology is not clearly known, chronic infections and mechanical, immunological, and biochemical factors can play a role in the etiology. Recently, mean platelet volume (MPV was recognized as a simple inflammatory marker in the inflammatory disease. In this study, we aimed to evaluate platelet (PLT and MPV in patients with NPs. Material and Method: This study included 80 histopathologically proven patients with NPs and 80 age- and sex-matched healthy subjects as controls. The Lund-Mackay staging system was used to evalute paranasal sinus CT scans, in patients with NPs, and paranasal sinus CT scores were recorded. Values of MPV, platelet (PLT, platelet crit (PCT and platelet distribution width (PDW were assessed in NP and control groups. Results: MPV and PLT values were found to be low in patients with NPs, at 8.57±1.62 fL and 259.99±62.03 x103/µL, respectively, compared with the control groups, at 8.79±1.49fL and 270.29±61.82 x103/µL. These findings were not statistically significant. PDW values were found to be slightly high in patients with NPs, at 17.1±1.36 fL, compared with the control group, at 16.78±1.04 fL (p=0.075. But PCT values were found to be low in patients with NPs, at 0.21±0.065, compared with the control group, at 0.23±0.069 (p=0.044. This finding was statistically significant. Discussion: In our study, the MPV and PLT values were lower in patients with NPs, but the difference was not statistically significant. According to our findings, the use of MPV as an inflammation marker in patients with NPs does not seem to be reliable.

  15. Pneumococcal association to platelets is mediated by soluble fibrin and supported by thrombospondin-1.

    Science.gov (United States)

    Niemann, Silke; Kehrel, Beate E; Heilmann, Christine; Rennemeier, Claudia; Peters, Georg; Hammerschmidt, Sven

    2009-10-01

    Platelets and coagulation are involved in bacterial colonisation of the host. Streptocococcus pneumoniae (pneumococcus) are important etiologic agents of respiratory tract infections in humans. The formation of pneumococci-platelet associations may facilitate haematogenous dissemination of pneumococci by providing an adhesive surface on damaged endothelium. However, the formation of platelet-pneumococci associations and the factors involved in this process have not been described so far. The formation of platelet-pneumococci associates was analysed and quantified using flow cytometry. Binding of pneumococci to platelets was significantly increased after activation of platelets with thrombin, while platelet activation by ADP or collagen did not promote formation of platelet-pneumococci associates. In addition to be a platelet agonist, thrombin cleaves fibrinogen, which results in the generation of fibrin. The simultaneous formation of fibrin and activation of platelets was shown to be a prerequisite for a high number of platelet-pneumococci associates. Moreover, exogenously added human thrombospondin-1 (TSP-1) significantly enhanced the association of pneumococci with activated platelets. Soluble fibrin and TSP-1 are key co-factors of platelet-pneumococci-association. Similar results were recently demonstrated for S. aureus-platelet adhesion. Consequently, we hypothesise that the described mechanism of platelet-bacteria-association might represent a general and important strategy of Gram-positive bacteria during development of invasive diseases.

  16. [The use of platelet concentrates: platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in bone reconstruction prior to dental implant surgery].

    Science.gov (United States)

    Baeyens, W; Glineur, R; Evrard, L

    2010-01-01

    The autologous platelet concentrates--Platelet-Rich Plasma (PRP) and Platelet-Rich Fibrin (PRF)--are used in various medical fields, particularly in oral and maxillofacial surgery. These concentrates contain high levels of growth factors, including the 3 isomers of PDGF (platelet-derived growth factor), 2 of the numerous transforming growth factors (TGF-beta), the insulinlike growth factor (IGF), the epithelial growth factor (EGF) and the vascular endothelial growth factor (VEGF), which are the key elements in wound healing, particularly in bone regeneration. Platelet concentrates are easy to apply in clinical practice and offer potential benefits including rapid wound healing and bone regeneration, and can therefore be considered to be new therapeutic adjuvants. In dental implant surgery they are used in bone reconstruction prior or concomitant to implant procedures, and also for dental extraction socket preservation. Their use result in enhanced bone graft density and maturation. A literature review on the use of PRP/PRF in maxillofacial and dental implant surgery is proposed.

  17. Inhibition of uptake of adenosine into human blood platelets

    NARCIS (Netherlands)

    Lips, J.P.M.; Sixma, J.J.; Trieschnigg, A.C.

    1980-01-01

    Adenosine transport into human blood platelets is mediated by two independent systems with different affinities. Both systems transport only purine nucleosides and no pyrimidine nucleosides. In experiments with differently substituted purine nucleosides, purines and analogues, differences in carrier

  18. Comparison of platelets characteristics according to various processing methods

    Directory of Open Access Journals (Sweden)

    O. V. Karpova

    2015-01-01

    Full Text Available To date different techniques of platelet concentrates (PC preparation and processing are proposed to achieve the best efficiency of transfusions and to minimize the risks post-transfusion reactions. However, data on the impact of different approaches to PC preparation and processing on morphological and functional characteristics of platelets and, as a consequence, the clinical efficacy of transfusions is controversial. In this paper we analyzed the impact of the platelet storage solution and different methods of pathogen inactivation (X-rays, UV-irradiation after photosensitization with riboflavin on morphological and functional parameters of platelets. Our findings allow optimizing the technology of preparation and processing of PC to achieve greater effectiveness of transfusion therapy.

  19. Cellular origin of platelet-derived microparticles in vivo

    NARCIS (Netherlands)

    A. Rank; R. Nieuwland; R. Delker; A. Köhler; B. Toth; V. Pihusch; R. Wilkowski; R. Pihusch

    2010-01-01

    Introduction: Microparticles (MP), presumably of platelet origin, are the most abundant microparticles in blood. To which extent such MP may also directly originate from megakaryocytes, however, is unknown. During hematopoietic stem cell transplantation, patients undergo total body irradiation which

  20. Characterization of Leukocyte-platelet Rich Fibrin, A Novel Biomaterial.

    Science.gov (United States)

    Madurantakam, Parthasarathy; Yoganarasimha, Suyog; Hasan, Fadi K

    2015-09-29

    Autologous platelet concentrates represent promising innovative tools in the field of regenerative medicine and have been extensively used in oral surgery. Unlike platelet rich plasma (PRP) that is a gel or a suspension, Leukocyte-Platelet Rich Fibrin (L-PRF) is a solid 3D fibrin membrane generated chair-side from whole blood containing no anti-coagulant. The membrane has a dense three dimensional fibrin matrix with enriched platelets and abundant growth factors. L-PRF is a popular adjunct in surgeries because of its superior handling characteristics as well as its suturability to the wound bed. The goal of the study is to demonstrate generation as well as provide detailed characterization of relevant properties of L-PRF that underlie its clinical success.

  1. Pathogen sensing, subsequent signalling, and signalosome in human platelets.

    Science.gov (United States)

    Garraud, Olivier; Berthet, Julien; Hamzeh-Cognasse, Hind; Cognasse, Fabrice

    2011-04-01

    Beyond haemostasis, platelets exert a potent role in innate immunity and particularly in its inflammatory arm. The extent of this action remains however debatable, despite clear - and old - evidence of a link between platelets and infection. Platelets can sense infectious pathogens by pathogen recognition receptors and they can even discriminate between various types of infectious signatures. In reply, they can shape their capacity to respond by activating a signalosome and by producing different profiles of pro-inflammatory cytokines and related products. The links between pathogen sensing, signalosome activation and protein production, and their finely tuned regulation are still under investigation since platelets lack a nucleus and thus, canonical molecular biology and genomics apparati.

  2. Invasive pneumococcal disease leads to activation and hyperreactivity of platelets

    NARCIS (Netherlands)

    Tunjungputri, Rahajeng N.; De Jonge, Marien I.; De Greeff, Astrid; Van Selm, Saskia; Buys, Herma; Harders-Westerveen, Jose F.; Stockhofe-Zurwieden, Norbert; Urbanus, Rolf T.; de Groot, Phillip G.; Smith, Hilde E.; Van Der Ven, Andre J.; De Mast, Quirijn

    2016-01-01

    Using a novel porcine model of intravenous Streptococcus pneumoniae infection, we showed that invasive pneumococcal infections induce marked platelet activation and hyperreactivity. This may contribute to the vascular complications seen in pneumococcal infection.

  3. Invasive pneumococcal disease leads to activation and hyperreactivity of platelets

    NARCIS (Netherlands)

    Tunjungputri, Rahajeng N.; Jonge, de Marien I.; Greeff, de Astrid; Selm, van Saskia; Buys-Bergen, Herma; Harders-Westerveen, Jose F.; Stockhofe-Zurwieden, Norbert; Urbanus, Rolf T.; Groot, De Phillip G.; Smith, Hilde E.; Ven, van der Andre J.; Mast, de Quirijn

    2016-01-01

    Using a novel porcine model of intravenous Streptococcus pneumoniae infection, we showed that invasive pneumococcal infections induce marked platelet activation and hyperreactivity. This may contribute to the vascular complications seen in pneumococcal infection.

  4. Using the Platelet Function Analyzer-100 for monitoring aspirin therapy

    DEFF Research Database (Denmark)

    Poulsen, Tina Svenstrup; Mickley, Hans; Korsholm, Lars;

    2007-01-01

    INTRODUCTION: The aim of the study was to evaluate the test characteristics of the Platelet Function Analyzer-100 (PFA-100) in patients treated with aspirin. METHODS AND RESULTS: The study consisted of two sub-studies. In study 1, 10 patients with ischemic heart disease (IHD) and 10 controls had...... platelet function assessed by optical platelet aggregation and the PFA-100 method in two 5-week periods. Patients with IHD were treated with aspirin 150 mg/day (first 5-week period), and 300 mg/day (second 5-week period), whereas the controls only received aspirin (150 mg/day) during the second 5-week...... period. From the results of study 1, we found that a cut-off value for the PFA-100 collagen/epinephrine cartridge <165 s identified patients not taking aspirin (sensitivity 0.91, specificity 1.00). A good agreement between the PFA-100 method and optical platelet aggregation was found. Within...

  5. Platelet Transfusion and Thrombosis: More Questions than Answers.

    Science.gov (United States)

    Schmidt, Amy E; Refaai, Majed A; Blumberg, Neil

    2016-03-01

    Platelets perform a vital role in hemostasis and their role in inflammation is becoming increasingly evident. Blood transfusion is the most common procedure performed in hospitals and platelet transfusions comprise a significant proportion. Over the past few decades, retrospective studies and randomized clinical trials have demonstrated that blood transfusion is more harmful than previously thought and is associated with numerous complications, such as transfusion-associated lung injury, transfusion-associated cardiac overload, transfusion-associated immune modulation, and infectious diseases such as human immunodeficiency virus, hepatitis C virus, and hepatitis B virus. Recent data suggest an association between platelet transfusion and thrombosis. This review will highlight the mechanistic issues that may be relevant to the epidemiologic associations of platelet transfusion with thrombosis and mortality in critically ill patients. PMID:26716501

  6. Value of detection of atherosclerotic lesions using autologous labelled platelets

    Energy Technology Data Exchange (ETDEWEB)

    Sinzinger, H.; Silberbauer, K.; Fitscha, P.; Kaliman, J. (Vienna Univ. (Austria). 2. Medizinische Klinik; Vienna Univ. (Austria). Kardiologische Abt.; Allgem. Poliklinik, Vienna (Austria). 2. Medizinische Abteilung)

    1982-01-01

    In 44 patients with clinical signs of carotid artery stenosis a positive Doppler-ultrasound was obtained. In all patients the lesions were confirmed by angiography. In the patients labelling of autologous platelets with 111 Indium-oxine-sulphate was done in order to calculate the platelet half-life. In addition we tried to visualize the verified atherosclerotic lesions under a gamma-camera. In all patients the platelet half-life was significantly shortened in comparison to the controls. In none of the patients studied a visualization of the angiographically verified atherosclerotic lesions could be obtained. These findings point out, that only in recently developed and very severe atherosclerotic lesions the number of platelets deposed on the vascular surface is enough to allow gamma-camera imaging.

  7. Comparison of platelets characteristics according to various processing methods

    Directory of Open Access Journals (Sweden)

    O. V. Karpova

    2014-01-01

    Full Text Available To date different techniques of platelet concentrates (PC preparation and processing are proposed to achieve the best efficiency of transfusions and to minimize the risks post-transfusion reactions. However, data on the impact of different approaches to PC preparation and processing on morphological and functional characteristics of platelets and, as a consequence, the clinical efficacy of transfusions is controversial. In this paper we analyzed the impact of the platelet storage solution and different methods of pathogen inactivation (X-rays, UV-irradiation after photosensitization with riboflavin on morphological and functional parameters of platelets. Our findings allow optimizing the technology of preparation and processing of PC to achieve greater effectiveness of transfusion therapy.

  8. Thrombocytopenia in Plasmodium vivax malaria is related to platelets phagocytosis.

    Directory of Open Access Journals (Sweden)

    Helena Cristina C Coelho

    Full Text Available BACKGROUND: Although thrombocytopenia is a hematological disorder commonly reported in malarial patients, its mechanisms are still poorly understood, with only a few studies focusing on the role of platelets phagocytosis. METHODS AND FINDINGS: Thirty-five malaria vivax patients and eight healthy volunteers (HV were enrolled in the study. Among vivax malaria patients, thrombocytopenia (<150,000 platelets/µL was found in 62.9% (22/35. Mean platelet volume (MPV was higher in thrombocytopenic patients as compared to non-thrombocytopenic patients (p = 0.017 and a negative correlation was found between platelet count and MPV (r = -0.483; p = 0.003. Platelets from HV or patients were labeled with 5-chloromethyl fluorescein diacetate (CMFDA, incubated with human monocytic cell line (THP-1 and platelet phagocytosis index was analyzed by flow cytometry. The phagocytosis index was higher in thrombocytopenic patients compared to non-thrombocytopenic patients (p = 0.042 and HV (p = 0.048. A negative correlation was observed between platelet count and phagocytosis index (r = -0.402; p = 0.016. Platelet activation was assessed measuring the expression of P-selectin (CD62-P in platelets' surface by flow cytometry. No significant difference was found in the expression of P-selectin between thrombocytopenic patients and HV (p = 0.092. After evaluating the cytokine profile (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17 in the patients' sera, levels of IL-6, IL-10 and IFN-γ were elevated in malaria patients compared to HV. Moreover, IL-6 and IL-10 values were higher in thrombocytopenic patients than non-thrombocytopenic ones (p = 0.044 and p = 0.017, respectively. In contrast, TNF-α levels were not different between the three groups, but a positive correlation was found between TNF-α and phagocytosis index (r = -0.305; p = 0.037. CONCLUSION/SIGNIFICANCE: Collectively, our findings indicate that platelet

  9. Selective inhibition of the platelet phosphoinositide 3-kinase p110beta as promising new strategy for platelet protection during extracorporeal circulation.

    Science.gov (United States)

    Straub, Andreas; Wendel, Hans Peter; Dietz, Klaus; Schiebold, Daniela; Peter, Karlheinz; Schoenwaelder, Simone M; Ziemer, Gerhard

    2008-03-01

    Extracorporeal circulation (ECC) is used in cardiac surgery for cardiopulmonary bypass as well as in ventricular assist devices and for extracorporeal membrane oxygenation. Blood contact with the artificial surface and shear stress of ECC activates platelets and leukocytes resulting in a coagulopathy and proinflammatory events. Blockers of the platelet glycoprotein (GP) IIb/IIIa (CD41/CD61) can protect platelet function during ECC, a phenomenon called "platelet anaesthesia", but may be involved in post-ECC bleeding. We hypothesized that the new selective phosphoinositide 3-kinase p110beta inhibitor TGX-221 that inhibits shear-induced platelet activation without prolonging the bleeding time in vivo may also protect platelet function during ECC. Heparinized blood of healthy volunteers (n = 6) was treated in vitro with either the GP IIb/IIIa blocker tirofiban, TGX-221 or as control and circulated in an ECC model. Before and after 30 minutes circulation CD41 expression on the ECC-tubing as measure for platelet-ECC binding and generation of the platelet activation marker beta-thromboglobulin were determined using ELISA. Platelet aggregation and platelet-granulocyte binding were analysed in flow cytometry. After log-transforming the data statistical evaluation was performed using multifactor ANOVA in combination with Tukey's HSD test (global alpha = 5%). Tirofiban and TGX-221 inhibited platelet-ECC interaction, platelet aggregation and platelet-granulocyte binding. Tirofiban also inhibited ECC-induced beta-thromboglobulin release. The observed inhibition of platelet-ECC interaction and platelet activation by tirofiban contributes to explain the mechanism of "platelet anaesthesia". TGX-221 represents a promising alternative to GP IIb/IIIa blockade and should be further investigated for use during ECC in vivo.

  10. Wdr1-Dependent Actin Reorganization in Platelet Activation.

    Science.gov (United States)

    Dasgupta, Swapan K; Le, Anhquyen; Da, Qi; Cruz, Miguel; Rumbaut, Rolando E; Thiagarajan, Perumal

    2016-01-01

    In resting platelets, the integrin αIIbβ3 is present in a low-affinity "bent" state. During platelet aggregation, intracytoplasmic signals induce conformational changes (inside-out signaling) that result in a "swung-out" conformation competent to bind ligands such as fibrinogen. The cytoskeleton plays an essential role in αIIbβ3 activation. We investigated the role of the actin interacting protein Wdr1 in αIIbβ3 activation. Wdr1-hypomorphic mice had a prolonged bleeding time (> 10 minutes) compared to that of wild-type mice (2.1 ± 0.7 minutes). Their platelets had impaired aggregation to collagen and thrombin. In a FeCl3 induced carotid artery thrombosis model, vessel occlusion in Wdr1-hypomorphic mice was prolonged significantly compared to wild-type mice (9.0 ± 10.5 minutes versus 5.8 ± 12.6 minutes (p = 0.041). Activation-induced binding of JON/A (a conformation-specific antibody to activated αIIbβ3) was significantly less in Wdr1-hypomorphic platelets at various concentrations of collagen, indicating impaired inside-out activation of αIIbβ3, despite a normal calcium response. Actin turnover, assessed by measuring F-actin and G-actin ratios during collagen- and thrombin-induced platelet aggregation, was highly impaired in Wdr1-hypomorphic platelets. Furthermore, talin failed to redistribute and translocate to the cytoskeleton following activation in Wdr1-hypomorphic platelets. These studies show that Wdr1 is essential for talin-induced activation of αIIbβ3 during platelet activation. PMID:27627652

  11. Hemodynamic aspects of reduced platelet adhesion on bioinspired microstructured surfaces.

    Science.gov (United States)

    Pham, Tam Thanh; Wiedemeier, Stefan; Maenz, Stefan; Gastrock, Gunter; Settmacher, Utz; Jandt, Klaus D; Zanow, Jürgen; Lüdecke, Claudia; Bossert, Jörg

    2016-09-01

    Occlusion by thrombosis due to the absence of the endothelial cell layer is one of the most frequent causes of failure of artificial vascular grafts. Bioinspired surface structures may have a potential to reduce the adhesion of platelets contributing to hemostasis. The aim of this study was to investigate the hemodynamic aspects of platelet adhesion, the main cause of thrombosis, on bioinspired microstructured surfaces mimicking the endothelial cell morphology. We tested the hypothesis that platelet adhesion is statistically significantly reduced on bioinspired microstructured surfaces compared to unstructured surfaces. Platelet adhesion as a function of the microstructure dimensions was investigated under flow conditions on polydimethylsiloxane (PDMS) surfaces by a combined experimental and theoretical approach. Platelet adhesion was statistically significantly reduced (by up to 78%; p≤0.05) on the microstructured PDMS surfaces compared to that on the unstructured control surface. Finite element method (FEM) simulations of blood flow dynamic revealed a micro shear gradient on the microstructure surfaces which plays a pivotal role in reducing platelet adhesion. On the surfaces with the highest differences of the shear stress between the top of the microstructures and the ground areas, platelet adhesion was reduced most. In addition, the microstructures help to reduce the interaction strength between fluid and surfaces, resulting in a larger water contact angle but no higher resistance to flow compared to the unstructured surface. These findings provide new insight into the fundamental mechanisms of reducing platelet adhesion on microstructured bioinspired surfaces and may lay the basis for the development of innovative next generation artificial vascular grafts with reduced risk of thrombosis. PMID:27239904

  12. Transmission matrix of a uniaxial optically active crystal platelet

    OpenAIRE

    Zomer, Fabian

    2005-01-01

    Expressions corresponding to the transmission of a uniaxial optically active crystal platelet are provided for an optical axis parallel and perpendicular to the plane of interface. The optical activity is taken into account by a consistent multipolar expansion of the crystal medium response due to the path of an electromagnetic wave. Numerical examples of the effect of the optical activity are given for quartz platelets of chosen thicknesses. The optical activity's effects on the variations o...

  13. Platelet Serotonin Transporter Function Predicts Default-Mode Network Activity

    OpenAIRE

    Christian Scharinger; Ulrich Rabl; Christian H. Kasess; Meyer, Bernhard M.; Tina Hofmaier; Kersten Diers; Lucie Bartova; Gerald Pail; Wolfgang Huf; Zeljko Uzelac; Beate Hartinger; Klaudius Kalcher; Thomas Perkmann; Helmuth Haslacher; Andreas Meyer-Lindenberg

    2014-01-01

    Background The serotonin transporter (5-HTT) is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT) from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence. Methods A functional magnetic resonance study was performed in 48 healthy...

  14. A recently developed bifacial platelet-rich fibrin matrix

    OpenAIRE

    Lucarelli, E

    2010-01-01

    Platelet-rich plasma (PRP) is used clinically in liquid or gel form to promote tissue repair. Because of the poor mechanical properties, conventional PRP is often difficult to handle when used in clinical settings and requires secure implantation in a specific site, otherwise when released growth factors could be washed out during an operation. In this study, we analyzed the end product of a recently developed commercially available system (FIBRINET®), which is a dense pliable, platelet-rich ...

  15. Tendon lesion and platelet-rich plasma (PRP) injection

    OpenAIRE

    Kaux, Jean-François; Drion, Pierre; Renouf, Julien; Pascon, Frédéric; Libertiaux, Vincent; Colige, Alain; Le Goff, Caroline; Lambert, Charles; Nusgens, Betty; Gothot, André; CESCOTTO, Serge; Defraigne, Jean-Olivier; Rickert, Markus; Crielaard, Jean-Michel

    2010-01-01

    Introduction: For a few years, the positive effects of platelets on the healing process of different tissues (skin, bones...) were demonstrated. In fact platelets contain lots of growth factors which can be release locally and enhance the healing process. Thus the aim of our experiment was to ascertain by an original mechanical measure whether the use of PRP was of interest for accelerating the healing process of rats’ Achilles tendons after surgical induced lesion. Methods: A 5mm defect w...

  16. The platelet indices in pediatric patients with acute appendicitis

    OpenAIRE

    Yunus Yilmaz; Fatih Kara; Musa Gumusdere; Hasan Arslan; Sefer Ustebay

    2015-01-01

    Background: The diagnosis of Acute Appendicitis (AA) remains a problem in pediatric population. It has been suggested that Mean Platelet Volume (MPV) is lower in the patients with AA. The purpose of this study was to investigate the diagnostic value of platelet indices in pediatric AA cases. Methods: A retrospective case-controlled study was designed: 224 subjects were included in this study. All patients had been operated on in division of pediatric surgery at the Kars Government Hospita...

  17. Sports medicine and platelet-rich plasma: nonsurgical therapy.

    Science.gov (United States)

    Grambart, Sean T

    2015-01-01

    A Cochrane Review was performed to assess the effects of platelet-rich therapies for treating musculoskeletal soft tissue injuries. Selection criteria were randomized and quasirandomized controlled trials (RCTs) that compared platelet-rich therapy with either placebo, autologous whole blood, dry needling, or no platelet-rich therapy for people with acute or chronic musculoskeletal soft tissue injuries. Primary outcomes were functional status, pain, and adverse effects. The investigators found 19 studies that compared platelet-rich therapy with placebo, autologous whole blood, dry needling, or no platelet-rich therapy. Disorders included rotator cuff tears (arthroscopic repair; 6 trials); shoulder impingement syndrome surgery (1 trial); elbow epicondylitis (3 trials); anterior cruciate ligament (ACL) reconstruction (4 trials), ACL reconstruction (donor graft site application; 2 trials), patellar tendinopathy (1 trial), Achilles tendinopathy (1 trial), and acute Achilles rupture surgical repair (1 trial). They further subdivided the studies based on type of treatment, including tendinopathies in which platelet-rich therapy injections were the main treatment (5 trials), and surgical augmentation procedures in which platelet-rich therapy was applied during surgery (14 trials). The conclusion was that there is currently insufficient evidence to support the use of platelet-rich therapy for treating musculoskeletal soft tissue injuries. Researchers contemplating RCTs should consider the coverage of currently ongoing trials when assessing the need for future RCTs on specific conditions. There is a need for standardization of PRP preparation methods. At this time, the use of PRP in foot and ankle surgery as an orthobiologic does not have an absolute indication. Many of the studies are lower evidence-based from surgical techniques. Several in vitro studies have shown that growth factors promote the regeneration of bone, cartilage, and tendons. More clinical studies are

  18. Platelet transfusion and alloimmunization : clinical and laboratory studies

    OpenAIRE

    Sintnicolaas, Krijn

    1996-01-01

    textabstractThrombocytopenia as a result of decreased platelet production may be treated with platelet transfusions. Decreased bone marrow function resulting in thrombocytopenia may be seen in hematopoietic diseases as leukemia, myelodysplastic syndrome or conditions of infiltration of bone marrow with solid tumor metastases. Thrombocytopenia also is a frequent side effect of cancer therapy. The application of high doses of chemotherapy and/or radiotherapy may result in periods of severe bone...

  19. Clopidogrel discontinuation and platelet reactivity following coronary stenting

    LENUS (Irish Health Repository)

    2011-01-01

    Summary. Aims: Antiplatelet therapy with aspirin and clopidogrel is recommended for 1 year after drug-eluting stent (DES) implantation or myocardial infarction. However, the discontinuation of antiplatelet therapy has become an important issue as recent studies have suggested a clustering of ischemic events within 90 days of clopidogrel withdrawal. The objective of this investigation was to explore the hypothesis that there is a transient ‘rebound’ increase in platelet reactivity within 3 months of clopidogrel discontinuation. Methods and Results: In this prospective study, platelet function was assessed in patients taking aspirin and clopidogrel for at least 1 year following DES implantation. Platelet aggregation was measured using a modification of light transmission aggregometry in response to multiple concentrations of adenosine diphosphate (ADP), epinephrine, arachidonic acid, thrombin receptor activating peptide and collagen. Clopidogrel was stopped and platelet function was reassessed 1 week, 1 month and 3 months later. Thirty-two patients on dual antiplatelet therapy were recruited. Discontinuation of clopidogrel increased platelet aggregation to all agonists, except arachidonic acid. Platelet aggregation in response to ADP (2.5, 5, 10, and 20 μm) and epinephrine (5 and 20 μm) was significantly increased at 1 month compared with 3 months following clopidogrel withdrawal. Thus, a transient period of increased platelet reactivity to both ADP and epinephrine was observed 1 month after clopidogrel discontinuation. Conclusions: This study demonstrates a transient increase in platelet reactivity 1 month after clopidogrel withdrawal. This phenomenon may, in part, explain the known clustering of thrombotic events observed after clopidogrel discontinuation. This observation requires confirmation in larger populations.

  20. Complex formation of platelet thrombospondin with histidine-rich glycoprotein.

    OpenAIRE

    Leung, L L; Nachman, R L; Harpel, P C

    1984-01-01

    Thrombospondin and histidine-rich glycoprotein are two proteins with diverse biological activities which have been associated with human platelets and other cell systems. Using an enzyme-linked immunosorbent assay, we have demonstrated that purified human platelet thrombospondin formed a complex with purified human plasma histidine-rich glycoprotein. The formation of the thrombospondin-histidine-rich glycoprotein complex was specific, concentration dependent, and saturable. Significant bindin...

  1. Use of Autologous Platelet Gel in Bariatric Surgery

    OpenAIRE

    Brady, Chad; Vang, See; Christensen, Kevin; Isler, Jack; Vollstedt, Keith; Holt, David

    2006-01-01

    Gastric bypass surgery is a common corrective procedure for obesity that is associated with many risks. Recent studies describing the use of autologous platelet gel (APG) have shown promise in preventing certain operative complications and improved healing processes. These improvements have been credited to the concentrated platelets and growth factors present in APG, as well as the native concentrations of fibrinogen. There are numerous applications for the use of APG in surgery, and the lis...

  2. STIMULATED PLATELETS RELEASE AMYLOID β–PROTEIN PRECURSOR

    OpenAIRE

    Cole, Gregory M.; Galasko, Douglas; Shapiro, I. Paul; Saitoh, Tsunao

    1990-01-01

    Human platelets can be stimulated by thrombin or ionomycin to secrete soluble truncated amyloid β–protein precursor and particulate membrane fragments which contain C-terminal and N-terminal immunoreactive amyloid β–protein precursor. This suggests a possible circulating source of β–protein in serum which may play a role in the formation of amyloid deposits. The release of soluble amyloid β-protein precursor could be involved in normal platelet physiology.

  3. Platelet turnover in stable coronary artery disease - influence of thrombopoietin and low-grade inflammation.

    Directory of Open Access Journals (Sweden)

    Sanne Bøjet Larsen

    Full Text Available BACKGROUND: Newly formed platelets are associated with increased aggregation and adverse outcomes in patients with coronary artery disease (CAD. The mechanisms involved in the regulation of platelet turnover in patients with CAD are largely unknown. AIM: To investigate associations between platelet turnover parameters, thrombopoietin and markers of low-grade inflammation in patients with stable CAD. Furthermore, to explore the relationship between platelet turnover parameters and type 2 diabetes, prior myocardial infarction, smoking, age, gender and renal insufficiency. METHODS: We studied 581 stable CAD patients. Platelet turnover parameters (immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell-ratio were determined using automated flow cytometry (Sysmex XE-2100. Furthermore, we measured thrombopoietin and evaluated low-grade inflammation by measurement of high-sensitive CRP and interleukin-6. RESULTS: We found strong associations between the immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell ratio (r = 0.61-0.99, p<0.0001. Thrombopoietin levels were inversely related to all of the platelet turnover parameters (r = -0.17--0.25, p<0.0001. Moreover, thrombopoietin levels were significantly increased in patients with diabetes (p = 0.03 and in smokers (p = 0.003. Low-grade inflammation evaluated by high-sensitive CRP correlated significantly, yet weakly, with immature platelet count (r = 0.10, p = 0.03 and thrombopoietin (r = 0.16, p<0.001. Also interleukin-6 correlated with thrombopoietin (r = 0.10, p = 0.02. CONCLUSION: In stable CAD patients, thrombopoietin was inversely associated with platelet turnover parameters. Furthermore, thrombopoietin levels were increased in patients with diabetes and in smokers. However, low-grade inflammation did not seem to have a

  4. Platelet reactivity changes significantly throughout all trimesters of pregnancy compared with the nonpregnant state: a prospective study.

    LENUS (Irish Health Repository)

    Burke, N

    2013-12-01

    Platelets play an important role in the pathophysiology of uteroplacental disease and platelet reactivity may be an important marker of uteroplacental disease activity. However, platelet reactivity has not been evaluated comprehensively in normal pregnancy. We sought to evaluate platelet reactivity using a number of agonists at defined time points in pregnancy using a novel platelet assay and compare these with a nonpregnant cohort.

  5. Endothelial and platelet markers in diabetes mellitus type 2

    Institute of Scientific and Technical Information of China (English)

    Peter Kubisz; Lucia Stanciaková; Ján Stasko; Peter Galajda; Marián Mokáň

    2015-01-01

    Diabetes mellitus (DM) is an extremely common disorder which carries a risk of vascular impairment. DM type2 (DM2) can be characterized by the dysfunction ofhaemostasis manifesting by stimulated coagulation process,disorder of platelet function and decreased fibrinolyticactivity. These all are the reasons why DM2 is the mostcommon acquired thrombophilia. Endothelial dysfunctionalong with platelet hyperactivity are unquestionablyinvolved in the hyperactivation of platelets and clottingfactors in DM. As a natural consequence of continuousinvestigation, many markers of endothelial dysfunctionand diabetic thrombocytopathy have been identifiedand considered for implementation in clinical practice.Endothelial function can be assessed by the evaluationof endothelial markers, circulating molecules synthesisedin various amounts by the endothelium. These markersprecede the signs of evident microangiopathy. Plateletshave an ethiopathogenic relation to the microangiopathy inDM. Their increased activity was confirmed in both typesof DM. Predictors of endothelial and platelet disorder couldimprove the screening of individuals at increased risk, thusleading to the early diagnosis, appropriate treatment, aswell as to the effective prevention of the complications ofDM2. In the article we deal with the mechanisms involvedin the pathogenesis of endothelial and platelet functionalabnormalities, endothelial and platelet markers of DM2considered for implementation in clinical practice andpossibilities of their detection.

  6. Automated platelet counters: a comparative evaluation of latest instrumentation.

    Science.gov (United States)

    Mayer, K; Chin, B; Magnes, J; Thaler, H T; Lotspeich, C; Baisley, A

    1980-08-01

    An extensive evaluation of performance characteristics and accuracy of clinical results for two automated multiparameter whole-blood cell counters (the Coulter Counter Model S-Plus and the Ortho ELT-8) and two single-parameter semiautomated platelet counters (the J. T. Baker MK-4/HC and the Clay-Adams Ultra-Flo 100) is described. Results of comparative assays performed on more than 1,200 clinical specimens are analyzed. These results are compared with manual determinations where appropriate. Particular attention is accorded to the accuracy of platelet counts, especially at abnormal levels below 70 X 10(3)/cu mm, where falsely elevated platelet counts may lead to serious clinical consequences. Both multiparameter instruments yielded accurate results, with the exception of low values reported by the ELT-8 for mean corpuscular volumes above 100 cu micrometer. Results for platelet counts were accurate for most specimens on all four instruments; the ELT-8 was the most reliable (P < 0.01), especially for the critically low counts. Although no instrument is infallible in determining platelet counts at all levels, the authors conclude that addition of platelet-counting capability represents a significant advancement over existing instrumentation. PMID:7405891

  7. PLATELET RICH FIBRIN: A PROMISING INNOVATION IN REGENERATIVE THERAPY

    Directory of Open Access Journals (Sweden)

    Arun

    2015-04-01

    Full Text Available Platelets can play a crucial role in regenerative therapy as they are reservoirs of growth factors and cytokines which are the key factors for regeneration of the bone and maturation of the soft tissue. Platelet - rich fibr in (PRF was first described by Choukroun et al. in France. It has been referred to as a second - generation platelet concentrate, which has been shown to have several advantages over traditionally prepared PRP. Platelet - rich fibrin (PRF is autologous plate let concentrates prepared from patient’s own blood. It is a natural fibrin - based biomaterial prepared from an anticoagulant - free blood harvest without any artificial biochemical modification that allows obtaining fibrin membranes enriched with platelets a nd growth factors. Evidence from the literature suggests the potential role of PRF in regeneration and tissue engineering. The slow polymerisation during centrifugation and fibrin - based structure makes PRF a better healing biomaterial than PRP and other fi brin adhesives. The purpose of this review article is to describe the novel second - generation platelet concentrate PRF, which is an improvement over the traditionally prepared PRP for use in regenerative dentistry.

  8. Exosomes: novel effectors of human platelet lysate activity

    Directory of Open Access Journals (Sweden)

    E Torreggiani

    2014-09-01

    Full Text Available Despite the popularity of platelet-rich plasma (PRP and platelet lysate (PL in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one of the effectors of PL activity. Exosomes were isolated from human PL by differential ultracentrifugation, and analysed by electron microscopy and Western blotting. Bone marrow stromal cells (MSC treated with three different exosome concentrations (0.6 μg, 5 μg and 50 μg showed a significant, dose-dependent increase in cell proliferation and migration compared to the control. In addition, osteogenic differentiation assays demonstrated that exosome concentration differently affected the ability of MSC to deposit mineralised matrix. Finally, the analysis of exosome protein content revealed a higher amount of basic fibroblast growth factor (bFGF, vascular endothelial growth factor (VEGF, platelet-derived growth factor (PDGF-BB and transforming growth factor beta 1 (TGF-β1 as compared to PL. In regards to RNA content, an enrichment of small RNAs in exosomes as compared to donor platelets has been found. These results suggest that exosomes consistently contribute to PL activity and could represent an advantageous nanodelivery system for cell-free regeneration therapies.

  9. Exosomes: novel effectors of human platelet lysate activity.

    Science.gov (United States)

    Torreggiani, E; Perut, F; Roncuzzi, L; Zini, N; Baglìo, S R; Baldini, N

    2014-01-01

    Despite the popularity of platelet-rich plasma (PRP) and platelet lysate (PL) in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF) released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one of the effectors of PL activity. Exosomes were isolated from human PL by differential ultracentrifugation, and analysed by electron microscopy and Western blotting. Bone marrow stromal cells (MSC) treated with three different exosome concentrations (0.6 μg, 5 μg and 50 μg) showed a significant, dose-dependent increase in cell proliferation and migration compared to the control. In addition, osteogenic differentiation assays demonstrated that exosome concentration differently affected the ability of MSC to deposit mineralised matrix. Finally, the analysis of exosome protein content revealed a higher amount of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) as compared to PL. In regards to RNA content, an enrichment of small RNAs in exosomes as compared to donor platelets has been found. These results suggest that exosomes consistently contribute to PL activity and could represent an advantageous nanodelivery system for cell-free regeneration therapies. PMID:25241964

  10. Crosstalk between platelets and PBMC: New evidence in wound healing.

    Science.gov (United States)

    Nami, Niccolò; Feci, Luca; Napoliello, Luca; Giordano, Antonio; Lorenzini, Sauro; Galeazzi, Mauro; Rubegni, Pietro; Fimiani, Michele

    2016-01-01

    Platelet-derived products have proven useful in accelerating healing processes and tissue regeneration. However, despite their widespread use in clinical practice, the cellular and molecular mechanisms involved have not yet been completely clarified. Recent studies show that interaction between platelet gel (PG) and peripheral blood mononuclear cells (PBMC) can result in activation of PBMC and production of several cytokines involved in wound healing and tissue repair. The aim of our study was to analyze whether crosstalk between platelets and PBMC can influence wound healing by modulating release of VEGF, bFGF and IL-10 by PBMC. Cultures of PBMC alone and co-cultures with autologous PG of 24 healthy volunteers were incubated under normoxia for 24 h. VEGF, bFGF and IL-10 concentration and expression were then analyzed in supernatants by ELISA and by real-time RT-PCR. We observed a down-regulation of VEGF and bFGF release and an up-regulation of IL-10 release in co-cultures of PBMC and PG. Platelets are not only important in the early stages of the healing process (clot formation, direct release of growth factors), but also can influence the whole process of tissue regeneration by modulating synthesis and release of VEGF, bFGF and IL-10 by PBMC. These effects could give platelets a new key role in the control of healing processes and provide insights into the clinical success of platelet-derived products in many medical fields. PMID:26030799

  11. Inherited Platelet Function Disorders: Algorithms for Phenotypic and Genetic Investigation.

    Science.gov (United States)

    Gresele, Paolo; Bury, Loredana; Falcinelli, Emanuela

    2016-04-01

    Inherited platelet function disorders (IPFDs) manifest with mucocutaneous bleeding and are frequently difficult to diagnose due to their heterogeneity, the complexity of the platelet activation pathways and a lack of standardization of the platelet function laboratory assays and of their use for this purpose. A rational diagnostic approach to IPFDs should follow an algorithm where clinical examination and a stepwise laboratory evaluation play a crucial role. A streamlined panel of laboratory tests, with consecutive steps of increasing level of complexity, allows the phenotypic characterization of most IPFDs. A first-line diagnosis of a significant fraction of the IPFD may be made also at nonspecialized centers by using relatively simple tests, including platelet count, peripheral blood smear, light transmission aggregometry, measurement of platelet granule content and release, and the expression of glycoproteins by flow cytometry. Some of the most complex, second- and third-step tests may be performed only in highly specialized laboratories. Genotyping, including the widespread application of next-generation sequencing, has enabled discovery in the last few years of several novel genes associated with platelet disorders and this method may eventually become a first-line diagnostic approach; however, a preliminary clinical and laboratory phenotypic characterization nowadays still remains crucial for diagnosis of IPFDs. PMID:26962877

  12. Metabolic plasticity in resting and thrombin activated platelets.

    Directory of Open Access Journals (Sweden)

    Saranya Ravi

    Full Text Available Platelet thrombus formation includes several integrated processes involving aggregation, secretion of granules, release of arachidonic acid and clot retraction, but it is not clear which metabolic fuels are required to support these events. We hypothesized that there is flexibility in the fuels that can be utilized to serve the energetic and metabolic needs for resting and thrombin-dependent platelet aggregation. Using platelets from healthy human donors, we found that there was a rapid thrombin-dependent increase in oxidative phosphorylation which required both glutamine and fatty acids but not glucose. Inhibition of fatty acid oxidation or glutamine utilization could be compensated for by increased glycolytic flux. No evidence for significant mitochondrial dysfunction was found, and ATP/ADP ratios were maintained following the addition of thrombin, indicating the presence of functional and active mitochondrial oxidative phosphorylation during the early stages of aggregation. Interestingly, inhibition of fatty acid oxidation and glutaminolysis alone or in combination is not sufficient to prevent platelet aggregation, due to compensation from glycolysis, whereas inhibitors of glycolysis inhibited aggregation approximately 50%. The combined effects of inhibitors of glycolysis and oxidative phosphorylation were synergistic in the inhibition of platelet aggregation. In summary, both glycolysis and oxidative phosphorylation contribute to platelet metabolism in the resting and activated state, with fatty acid oxidation and to a smaller extent glutaminolysis contributing to the increased energy demand.

  13. Platelet function and hemolysis in centrifugal pumps: in vitro investigations.

    Science.gov (United States)

    Steines, D; Westphal, D; Göbel, C; Reul, H; Rau, G

    1999-08-01

    The effects of centrifugal pumps on blood components other than erythrocytes, namely platelets and their interaction with the coagulation system, are not very well known. In a comparative study with three centrifugal pumps (BioMedicus BP-80, St. Jude Isoflow, and Sarns Delphin) and the Stockert roller pump hemolysis, platelet counts, thromboplastin and partial thromboplastin times, as well as resonance thrombography (RTG) parameters for the assessment of platelet and coagulation function were evaluated in vitro. Normalized indices of hemolysis (NIH) with ACD anticoagulation after 360 minutes were 0.008+/-0.004 (Isoflow), 0.018+/-0.017 (BP-80), 0.085+/-0.051 (Delphin), and 0.049+/-0.010 g/1001 (roller pump). Plasmatic coagulation was activated in all circuits. Platelet function was severely inhibited by the BP-80, indicated by increase in RTG platelet time to 358%+/-150% of initial values compared to 42%+/-29% (Isoflow), 40%+/-20% (Delphin), and 12%+/-10% (roller pump). Fibrin polymerization was affected similarly. The large surface area of the BP-80 leads to an extensive activation of platelets and plasminogen.

  14. Aluminum induces lipid peroxidation and aggregation of human blood platelets

    Directory of Open Access Journals (Sweden)

    Neiva T.J.C.

    1997-01-01

    Full Text Available Aluminum (Al3+ intoxication is thought to play a major role in the development of Alzheimer's disease and in certain pathologic manifestations arising from long-term hemodialysis. Although the metal does not present redox capacity, it can stimulate tissue lipid peroxidation in animal models. Furthermore, in vitro studies have revealed that the fluoroaluminate complex induces diacylglycerol formation, 43-kDa protein phosphorylation and aggregation. Based on these observations, we postulated that Al3+-induced blood platelet aggregation was mediated by lipid peroxidation. Using chemiluminescence (CL of luminol as an index of total lipid peroxidation capacity, we established a correlation between lipid peroxidation capacity and platelet aggregation. Al3+ (20-100 µM stimulated CL production by human blood platelets as well as their aggregation. Incubation of the platelets with the antioxidants nor-dihydroguaiaretic acid (NDGA (100 µM and n-propyl gallate (NPG (100 µM, inhibitors of the lipoxygenase pathway, completely prevented CL and platelet aggregation. Acetyl salicylic acid (ASA (100 µM, an inhibitor of the cyclooxygenase pathway, was a weaker inhibitor of both events. These findings suggest that Al3+ stimulates lipid peroxidation and the lipoxygenase pathway in human blood platelets thereby causing their aggregation

  15. Increased platelet count and leucocyte-platelet complex formation in acute symptomatic compared with asymptomatic severe carotid stenosis.

    LENUS (Irish Health Repository)

    McCabe, D J H

    2005-09-01

    The risk of stroke in patients with recently symptomatic carotid stenosis is considerably higher than in patients with asymptomatic stenosis. In the present study it was hypothesised that excessive platelet activation might partly contribute to this difference.

  16. Clopidogrel resistance of patients with coronary artery disease and its correlation with platelet count and mean platelet volume

    Institute of Scientific and Technical Information of China (English)

    李蕾

    2013-01-01

    Objective To explore the association between clopidogrel resistance(CR)as assessed by whole blood electrical impedance aggregometry(EIA) and platelet parameters.Methods The prospective study comprised 152 patients

  17. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part III: leucocyte activation: a new feature for platelet concentrates?

    Science.gov (United States)

    Dohan, David M; Choukroun, Joseph; Diss, Antoine; Dohan, Steve L; Dohan, Anthony J J; Mouhyi, Jaafar; Gogly, Bruno

    2006-03-01

    Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this third article, we investigate the immune features of this biomaterial. During PRF processing, leucocytes could also secrete cytokines in reaction to the hemostatic and inflammatory phenomena artificially induced in the centrifuged tube. We therefore undertook to quantify 5 significant cell mediators within platelet poor plasma supernatant and PRF clot exudate serum: 3 proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), an antiinflammatory cytokine (IL-4), and a key growth promoter of angiogenesis (VEGF). Our data are correlated with that obtained in plasma (nonactivated blood) and in sera (activated blood). These initial analyses revealed that PRF could be an immune regulation node with inflammation retrocontrol abilities. This concept could explain the reduction of postoperative infections when PRF is used as surgical additive.

  18. Fluorescence Nanoscopy of Platelets Resolves Platelet-State Specific Storage, Release and Uptake of Proteins, Opening up Future Diagnostic Applications

    OpenAIRE

    Rönnlund, Daniel; Yang, Yang; Blom, Hans; Auer, Gert; Widengren, Jerker

    2012-01-01

    Dysregulation of how platelets store, sequester and release specific proteins seems to be implicated in many disease states, including cancer. Dual-color immunofluorescence stimulated emission depletion (STED) microscopy with 40 nm resolution is used to map pro-angiogenic VEGF, anti-angiogenic PF-4 and fibrinogen in >300 individual platelets. This reveals that these proteins are stored in a segmented, zonal manner within regional clusters, significantly smaller than the size of an alpha-gr...

  19. Can mean platelet component be used as an index of platelet activity in stable coronary artery disease?

    LENUS (Irish Health Repository)

    Cooke, John

    2009-04-01

    Acute coronary syndrome is associated with intracoronary thrombosis secondary to platelet activation. Previous groups have investigated platelet activation in both stable and unstable vascular disease. Most measures of platelet activation are not routinely available or easily adaptable to large scale clinical use. Recently, measurement of the mean platelet component (MPC) has become part of the routine data provided by an automated full blood count analyser, the Advia 120. MPC measures platelet density which changes on platelet activation. Our objectives were to determine if platelet activation, as measured by MPC, is increased in patients with stable coronary artery disease (CAD) and to determine if MPC could be useful in differentiating people with stable CAD from controls on an everyday clinical basis. Three hundred and forty-five consecutive patients attending for elective coronary angiography had full blood count analysis and MPC measurement performed using an ADVIA-120 analyser. Three hundred and twenty-four were analysed in our final dataset. Two hundred and fifty-three (78%) had CAD. Patients with CAD were significantly (p<0.001) older than those without (63.8 versus 56.0 years). Results failed to demonstrate a difference (p=0.467) in MPC between patients with CAD and those with normal coronary arteries (25.8 versus 26.0). Likewise, there was no correlation between MPC and the severity of CAD (Kendall\\'s tau b=-0.086, p=0.04). MPC is not a useful index of platelet activity in stable CAD when used in everyday clinical practice.

  20. Can mean platelet component be used as an index of platelet activity in stable coronary artery disease?

    LENUS (Irish Health Repository)

    Cooke, John

    2012-01-31

    Acute coronary syndrome is associated with intracoronary thrombosis secondary to platelet activation. Previous groups have investigated platelet activation in both stable and unstable vascular disease. Most measures of platelet activation are not routinely available or easily adaptable to large scale clinical use. Recently, measurement of the mean platelet component (MPC) has become part of the routine data provided by an automated full blood count analyser, the Advia 120. MPC measures platelet density which changes on platelet activation. Our objectives were to determine if platelet activation, as measured by MPC, is increased in patients with stable coronary artery disease (CAD) and to determine if MPC could be useful in differentiating people with stable CAD from controls on an everyday clinical basis. Three hundred and forty-five consecutive patients attending for elective coronary angiography had full blood count analysis and MPC measurement performed using an ADVIA-120 analyser. Three hundred and twenty-four were analysed in our final dataset. Two hundred and fifty-three (78%) had CAD. Patients with CAD were significantly (p<0.001) older than those without (63.8 versus 56.0 years). Results failed to demonstrate a difference (p=0.467) in MPC between patients with CAD and those with normal coronary arteries (25.8 versus 26.0). Likewise, there was no correlation between MPC and the severity of CAD (Kendall\\'s tau b=-0.086, p=0.04). MPC is not a useful index of platelet activity in stable CAD when used in everyday clinical practice.

  1. Dose response of surfactants to attenuate gas embolism related platelet aggregation

    Science.gov (United States)

    Eckmann, David M.; Eckmann, Yonaton Y.; Tomczyk, Nancy

    2014-03-01

    Intravascular gas embolism promotes blood clot formation, cellular activation, and adhesion events, particularly with platelets. Populating the interface with surfactants is a chemical-based intervention to reduce injury from gas embolism. We studied platelet activation and platelet aggregation, prominent adverse responses to blood contact with bubbles. We examined dose-response relationships for two chemically distinct surfactants to attenuate the rise in platelet function stimulated by exposure to microbubbles. Significant reduction in platelet aggregation and platelet activation occurred with increasing concentration of the surfactants, indicating presence of a saturable system. A population balance model for platelet aggregation in the presence of embolism bubbles and surfactants was developed. Monte Carlo simulations for platelet aggregation were performed. Results agree qualitatively with experimental findings. Surfactant dose-dependent reductions in platelet activation and aggregation indicate inhibition of the gas/liquid interface's ability to stimulate cellular activation mechanically.

  2. In-vitro model for the ultrastructural study of the formation of thrombi in human platelets.

    Science.gov (United States)

    Cerecedo, Doris; González, Sirenia; Mondragón, Mónica; Reyes, Elba; Mondragón, Ricardo

    2006-03-01

    Platelets are cell fragments with dynamic properties involved in clot formation after tissue damage. Platelet activation causes a change in shape, secretion of intracellular granules and aggregation with each other through the cytoskeleton components and biochemical changes. Platelet adhesion, considered as the major event in haemostasis, has been studied in several in-vitro and in-vivo models to evaluate the feasible thrombogenicity of some materials, the dynamics of specific receptors, as well as the effect of different buffers and inhibitors in this process. In spite of the numerous reports about platelet activation, to date there is no information available about the fine structure of the platelet-platelet and platelet-substrate interactions. In the present report we describe an in-vitro system that allows the visualization of these interactions: platelets are adhered to an inert substrate, and interactions with suspended platelets as a process to initiate the formation of thrombi was followed by ultramicrotomy and transmission electron microscopy.

  3. Platelet protein disulfide isomerase is required for thrombus formation but not for hemostasis in mice.

    Science.gov (United States)

    Kim, Kyungho; Hahm, Eunsil; Li, Jing; Holbrook, Lisa-Marie; Sasikumar, Parvathy; Stanley, Ronald G; Ushio-Fukai, Masuko; Gibbins, Jonathan M; Cho, Jaehyung

    2013-08-01

    Protein disulfide isomerase (PDI) derived from intravascular cells is required for thrombus formation. However, it remains unclear whether platelet PDI contributes to the process. Using platelet-specific PDI-deficient mice, we demonstrate that PDI-null platelets have defects in aggregation and adenosine triphosphate secretion induced by thrombin, collagen, and adenosine diphosphate. Such defects were rescued by wild-type but not mutant PDI, indicating that the isomerase activity of platelet surface PDI is critical for the regulatory effect. PDI-deficient platelets expressed increased levels of intracellular ER protein 57 (ERp57) and ERp72. Platelet PDI regulated αIIbβ3 integrin activation but not P-selectin exposure, Ca(2+) mobilization, β3-talin1 interaction, or platelet spreading on immobilized fibrinogen. Inhibition of ERp57 further diminished αIIbβ3 integrin activation and aggregation of activated PDI-deficient platelets, suggesting distinct roles of PDI and ERp57 in platelet functions. We found that platelet PDI is important for thrombus formation on collagen-coated surfaces under shear. Intravital microscopy demonstrates that platelet PDI is important for platelet accumulation but not initial adhesion and fibrin generation following laser-induced arteriolar injury. Tail bleeding time in platelet-specific PDI-deficient mice were not significantly increased. Our results provide important evidence that platelet PDI is essential for thrombus formation but not for hemostasis in mice. PMID:23788140

  4. Challenges and promises for the development of donor-independent platelet transfusions.

    Science.gov (United States)

    Lambert, Michele P; Sullivan, Spencer K; Fuentes, Rudy; French, Deborah L; Poncz, Mortimer

    2013-04-25

    Platelet transfusions are often a life-saving intervention, and the use of platelet transfusions has been increasing. Donor-derived platelet availability can be challenging. Compounding this concern are additional limitations of donor-derived platelets, including variability in product unit quality and quantity, limited shelf life and the risks of product bacterial contamination, other transfusion-transmitted infections, and immunologic reactions. Because of these issues, there has been an effort to develop strategies to generate platelets from exogenously generated precursor cells. If successful, such platelets have the potential to be a safer, more consistent platelet product, while reducing the necessity for human donations. Moreover, ex vivo-generated autologous platelets or precursors may be beneficial for patients who are refractory to allogeneic platelets. For patients with inherited platelet disorders, ex vivo-generated platelets offer the promise of a treatment via the generation of autologous gene-corrected platelets. Theoretically, ex vivo-generated platelets also offer targeted delivery of ectopic proteins to sites of vascular injury. This review summarizes the current, state-of-the-art methodologies in delivering a clinically relevant ex vivo-derived platelet product, and it discusses significant challenges that must be overcome for this approach to become a clinical reality.

  5. Influence of platelet-derived growth factor-AB on tissue development in autologous platelet-rich plasma gels.

    Science.gov (United States)

    Wirz, Simone; Dietrich, Maren; Flanagan, Thomas C; Bokermann, Gudrun; Wagner, Wolfgang; Schmitz-Rode, Thomas; Jockenhoevel, Stefan

    2011-07-01

    Fibrin-based scaffolds are widely used in tissue engineering. We postulated that the use of platelet-rich plasma (PRP) in contrast to platelet-poor plasma and pure fibrinogen as the basic material leads to an increased release of autologous platelet-derived growth factor (PDGF)-AB, which may have a consequent positive effect on tissue development. Therefore, we evaluated the release of PDGF-AB during the production process and the course of PDGF release during cultivation of plasma gels with and w/o platelets. The influence of PDGF-AB on the proliferation rate of human umbilical cord artery smooth muscle cells (HUASMCs) was studied using XTT assay. The synthesis of extracellular matrix by HUASMCs in plasma- and fibrin gels was measured using hydroxyproline assay. The use of PRP led to an increase in autologous PDGF-AB release. Further, the platelet-containing plasma gels showed a prolonged release of growth factor during cultivation. Both PRP and platelet-poor plasma gels had a positive effect on the production of collagen. However, PDGF-AB as a supplement in medium and in pure fibrin gel had neither an effect on cell proliferation nor on the collagen synthesis rate. This observation may be due to an absence of PDGF receptors in HUASMCs as determined by flow cytometry. In conclusion, although the prolonged autologous production of PDGF-AB in PRP gels is possible, the enhanced tissue development by HUASMCs within such gels is not PDGF related.

  6. Contribution of blood platelets to vascular pathology in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Zhang W

    2013-11-01

    Full Text Available Wei Zhang,1,2 Wei Huang,1 Fang Jing11Department of Pharmacology, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, People's Republic of China; 2Shanghai Engineering Research Center of Molecular Therapy and Pharmaceutical Innovation, Shanghai, People's Republic of ChinaAbstract: Cerebral amyloid angiopathy (CAA is a critical factor in the pathogenesis of Alzheimer's disease (AD. In the clinical setting, nearly 98% AD patients have CAA, and 75% of these patients are rated as severe CAA. It is characterized by the deposition of the β-amyloid peptide (mainly Aβ40 in the walls of cerebral vessels, which induces the degeneration of vessel wall components, reduces cerebral blood flow, and aggravates cognitive decline. Platelets are anuclear cell fragments from bone marrow megakaryocytes and their function in hemostasis and thrombosis has long been recognized. Recently, increasing evidence suggests that platelet activation can also mediate the onset and development of CAA. First, platelet activation and adhesion to a vessel wall is the initial step of vascular injury. Activated platelets contribute to more than 90% circulating Aß (mainly Aβ1-40, which in turn activates platelets and results in the vicious cycle of Aβ overproduction in damaged vessel. Second, the uncontrolled activation of platelets leads to a chronic inflammatory reaction by secretion of chemokines (eg, platelet factor 4 [PF4], regulated upon activation normal T-cell expressed and presumably secreted [RANTES], and macrophage inflammatory protein [MIP-1α], interleukins (IL-1 β, IL-7, and IL-8, prostaglandins, and CD40 ligand (CD40L. The interaction of these biological response modulators with platelets, endothelial cells, and leukocytes establishes a localized inflammatory response that contributes to CAA formation. Finally, activated platelets are the upholder of fibrin clots, which are structurally abnormal and resistant to degradation

  7. A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of artificial platelet nanoconstructs without interfering with VWF-adhesion of natural platelets.

    Science.gov (United States)

    Haji-Valizadeh, Hassan; Modery-Pawlowski, Christa L; Sen Gupta, Anirban

    2014-05-01

    There is substantial clinical interest in synthetic platelet analogs for potential application in transfusion medicine. To this end, our research is focused on self-assembled peptide-lipid nanoconstructs that can undergo injury site-selective adhesion and subsequently promote site-directed active platelet aggregation, thus mimicking platelet's primary hemostatic actions. For injury site-selective adhesion, we have utilized a coagulation factor FVIII-derived VWF-binding peptide (VBP). FVIII binds to VWF's D'-D3 domain while natural platelet GPIbα binds to VWF's A1 domain. Therefore, we hypothesized that the VBP-decorated nanoconstructs will adhere to VWF without mutual competition with natural platelets. We further hypothesized that the adherent VBP-decorated constructs can enhance platelet aggregation when co-decorated with a fibrinogen-mimetic peptide (FMP). To test these hypotheses, we used glycocalicin to selectively block VWF's A1 domain and, using fluorescence microscopy, studied the binding of fluorescently labeled VBP-decorated nanoconstructs versus platelets to ristocetin-treated VWF. Subsequently, we co-decorated the nanoconstructs with VBP and FMP and incubated them with human platelets to study construct-mediated enhancement of platelet aggregation. Decoration with VBP resulted in substantial construct adhesion to ristocetin-treated VWF even if the A1-domain was blocked by glycocalicin. In comparison, such A1-blocking resulted in significant reduction of platelet adhesion. Without A1-blocking, the VBP-decorated constructs and natural platelets could adhere to VWF concomitantly. Furthermore, the constructs co-decorated with VBP and FMP enhanced active platelet aggregation. The results indicate significant promise in utilizing the FVIII-derived VBP in developing synthetic platelet analogs that do not interfere with VWF-binding of natural platelets but allow site-directed enhancement of platelet aggregation when combined with FMP.

  8. Era of blood component therapy: time for mandatory pre-donation platelet count for maximizing donor safety and optimizing quality of platelets.

    Science.gov (United States)

    Das, Sudipta Sekhar; Zaman, R U; Biswas, Dipak

    2013-12-01

    Blood bank regulatory agencies including the Drug and Cosmetics Act (DCA) of India do not mandate a predonation platelet count in whole blood donation. Mandating such practice will definitely optimize the quality of random donor platelets (RDP) in terms of platelet yield and patient therapeutic benefit. We observed poor platelet yield in RDP concentrates prepared at our center with a significant number not meeting the DCA guideline of ≥ 4.5 × 10(10) per bag processed from 450 ml of whole blood. Therefore we planned this study to evaluate the pre-donation hematological values in our blood donor population and effect of these values on the quality of platelet concentrates. The prospective study included 221 blood donors eligible for donating 450 ml of whole blood (WB). Following the departmental standard operating procedure (SOP) RDPs were prepared using the 'Top & Bottom' quadruple bag system and automated component extractor. Quality of RDP was assessed as per departmental protocol. All results were recorded and subsequently transcribed to SPSS working sheet. A significant (pplatelets reduced by 0.72 g/dl and 22.1 × 10(6)/ml respectively. Quality of RDPs in terms of platelet yield was significantly better (pplatelet count was >200 × 10(6)/ml. Although platelet yield significantly correlated with the donor platelet count however quality of RDPs in terms of red cell contamination showed no correlation with the donor hematocrit. Platelet yield in random donor platelets is a concern in Eastern India. A platelet yield of 4.5 × 10(10) per bag as mandated by the DCA of India was only achieved when the donor platelet count was >200 × 10(6)/ml. Posttransfusion platelet recovery (PPR) was unsatisfactory in the transfused patient. Introduction of pre-donation platelet count in whole blood donation will maximize donor safety and optimize patient platelet transfusion management.

  9. Effects of Recombinant Human Megakaryocyte Growth and Development Factor (rHuMGDF) on Platelet Production, Platelet Aggregation, and Thrombosis.

    Science.gov (United States)

    Lott; Nelson; Toombs

    1998-01-01

    Recombinant human megakaryocyte growth and development factor (rHuMGDF) is a c-mpl ligand that promotes the differentiation of CD34+ precursor cells into megakaryocyte, and then platelets. In experimental animals, injection of this and other c-mpl ligands leads to profound increases in the circulating platelet count in a matter of days. However, c-mpl ligands have also been shown to sensitize platelets to aggregating agents in vitro, raising the possibility that c-mpI ligands may have prothrombotic effects in vivo. Therefore, characterizing rHuMGDF in an in vivo model of thrombosis is a necessary and critical step in defining the in vivo pharmacology of this novel and important hernatopoietic factor, a pegylated form of which is currently in clinical trials. To determine the biologically effective doses in the rabbit, daily subcutaneous injections of rHuMGDF at 0.1, 1.0, or 10 µg/kg were administered ever 7 days. Daily injection of 10 µ/kg produced an approximate fourfold increase in platelet count and 1.0 µ/kg doubled platelet count over the injection period, both of which were statistically significant. The serum concentrations of rHuMGDF were determined 10 minutes following a single intravenous injection with 0.1, 1.0, and 10 µ/kg, and were 0.05 +/- 0.02, 0.98 +/- 0.07, and 21.32 +/- 21.35 ng/ml. To determine whether rHuMGDF can sensitize platelets in vivo, platelet aggregometry was performed on platelets isolated from animals immediately before and 10 minutes after they had been injected intravenously with rHuMGDF (0.1, 1.0, and 10 µ/kg). Intravenous injection of 10 µ/kg produced measurable changes in platelet aggregometry ex vivo, as evidenced by an increased sensitivity of platelets to adenosine diphosphate (ADP). To assess. the in vivo prothrombotic potential of rHuMGDF, a rabbit carotid artery model of cyclic flow reduction (CFR) was used to measure the effect of intravenous rHuMGDF administration on the rate of thrombus formation as assessed by CFR

  10. Platelet rich fibrin in jaw defects

    Science.gov (United States)

    Nica, Diana; Ianes, Emilia; Pricop, Marius

    2016-03-01

    Platelet rich fibrin (PRF) is a tissue product of autologous origin abundant in growth factors, widely used in regenerative procedures. Aim of the study: Evaluation of the regenerative effect of PRF added in the bony defects (after tooth removal or after cystectomy) Material and methods: The comparative nonrandomized study included 22 patients divided into 2 groups. The first group (the test group) included 10 patients where the bony defects were treated without any harvesting material. The second group included 12 patients where the bony defects were filled with PRF. The bony defect design was not critical, with one to two walls missing. After the surgeries, a close clinically monitoring was carried out. The selected cases were investigated using both cone beam computer tomography (CBCT) and radiographic techniques after 10 weeks postoperatively. Results: Faster bone regeneration was observed in the bony defects filled with PRF comparing with the not grafted bony defects. Conclusions: PRF added in the bony defects accelerates the bone regeneration. This simplifies the surgical procedures and decreases the economic costs.

  11. Increased mean platelet volume in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ezgi Coşkun Yenigün

    2014-03-01

    Full Text Available Objective: Platelet functions have important roles in the development of vascular complications in diabetic patients. Platelets with increased volume have increased activity compared to smaller ones; therefore, mean platelet volume (MPV is used as a marker for platelet activity. In the present study, we evaluated MPV in patients with type II diabetes mellitus (DM and its associations with diabetic microvascular and macrovascular complications. Methods: Consecutive type II diabetic patients were screened from outpatient clinic of Internal Medicine Department of Diskapı Yıldırım Beyazıt Education and Researsch Hospital, Ankara, Turkey. A total of 48 patients with type II DM and 30 age and gender matched healthy subjects constituted the study population. For all subjects a complete blood count including MPV, fasting blood glucose level and lipid parameters were studied. In diabetic patients, duration of diabetes and HbA1C level, presence of microvascular and macrovascular complications were noted additively. Mean platelet volume was compared between diabetic patients and healthy counterparents. Then, among diabetic patients, MPV was compared between the ones with and without microvascular and macrovascular complications. Results: Mean platelet volume was found significantly higher in diabetic patients compared to non-diabetic healthy subjects. Diabetic patients with at least one of the microvascular complications had significantly higher MPV than those without microvascular damage.Higher MPV levels have also been shown in diabetics with macrovascular complications compared to the ones without macrovascular disease. Conclusion: Mean platelet volume was found to be higher in type II diabetics and those having any of microvascular or macrovascular diabetic complications.

  12. Formed platelet combustor liner construction feasibility, phase A

    Science.gov (United States)

    Hayes, W. A.; Janke, D. E.

    1992-09-01

    Environments generated in high pressure liquid rocket engines impose severe requirements on regeneratively cooled combustor liners. Liners fabricated for use in high chamber pressures using conventional processes suffer from limitations that can impair operational cycle life and can adversely affect wall compatibility. Chamber liners fabricated using formed platelet technology provide an alternative to conventional regeneratively cooled liners (an alternative that has many attractive benefits). A formed platelet liner is made from a stacked assembly of platelets with channel features. The assembly is diffusion bonded into a flat panel and then three-dimensionally formed into a section of a chamber. Platelet technology permits the liner to have very precisely controlled and thin hot gas walls and therefore increased heat transfer efficiency. Further cooling efficiencies can be obtained through enhanced design flexibility. These advantages translate into increased cycle life and enhanced wall compatibility. The increased heat transfer efficiency can alternately be used to increase engine performance or turbopump life as a result of pressure drop reductions within the regeneratively cooled liner. Other benefits can be obtained by varying the materials of construction within the platelet liner to enhance material compatibility with operating environment or with adjoining components. Manufacturing cost savings are an additional benefit of a formed platelet liner. This is because of reduced touch labor and reduced schedule when compared to conventional methods of manufacture. The formed platelet technology is not only compatible with current state-of-the art combustion chamber structural support and manifolding schemes, it is also an enabling technology that allows the use of other high performance and potentially low cost methods of construction for the entire combustion chamber assembly. The contract under which this report is submitted contains three phases: (1) phase

  13. Timing of Platelet Rich Plasma Injections During Antithrombotic Therapy.

    Science.gov (United States)

    Ramsook, Ryan Ravi; Danesh, Houman

    2016-01-01

    The use of platelet rich plasma (PRP) spans across many fields owing to its role in healing and as a natural alternative to surgery. PRP continues to grow however much of the literature is anecdotal or case report based and there is a lack of controlled trials to evaluate standards for PRP. The International Cellular Medical Society (ICMS) has developed guidelines to help with the safe advancement of PRP; however there remains a gap in literature concerning the timing of PRP injections in patients who are on antithrombotic therapy. The importance of an intact platelet surface membrane allows for the appropriate release of the healing bioproteins and growth factors granting PRP therapy its efficacy. This along with the proliferation of differentiated cells, enhancement of collagen synthesis, early angiogenesis and revascularization help promote the benefits of regeneration. The intrinsic and extrinsic pathways of the coagulation cascade are valuable in that disruption of this mechanism or prematurely activated platelets may result in limited efficacy. Anticoagulants and antiplatelet drugs are commonly used in patients who are candidates for PRP. As antithrombotic agents affect platelet stability, they will have an effect on PRP efficacy and must be discontinued at an appropriate time frame prior to injection therapy. Understanding the pharmacokinetics and platelet effects can help guide discussion on the proper timing of discontinuation and resumption of a particular antithrombotic agent. With future research, the establishment of clinical practice guidelines concerning PRP and antithrombotic therapy can help structure safe and efficacious means in which to promote healing and regeneration in a growing patient population. Platelet rich plasma, antithrombotic therapy, coagulation, platelet activation, regenerative medicine, growth factors. PMID:27676677

  14. The platelet proaggregating and potentiating effects of unfractionated heparin, low molecular weight heparin and heparinoid in intensive care patients and healthy controls

    NARCIS (Netherlands)

    Burgess, J K; Chong, B H

    1997-01-01

    Heparin binds to platelets and can cause platelet proaggregating and potentiating effects, possibly causing thrombocytopenia, particularly in patients in intensive care with hyperaggregable platelets. In this study we compared the platelet proaggregating and potentiating effects of unfractionated he

  15. Correlation between Platelet Gelsolin and Platelet Activation Level in Acute Myocardial Infarction Rats and Intervention Effect of Effective Components of Chuanxiong Rhizome and Red Peony Root

    Directory of Open Access Journals (Sweden)

    Yue Liu

    2013-01-01

    Full Text Available The biological role of platelet gelsolin in platelet activation of acute myocardial infarction is not defined. In order to provide a potential new antiplatelet target for Chinese medicine and to elucidate the contribution of Xiongshao capsule, the effective components of Chuanxiong rhizome and red peony root, in this study, we randomly allocated Sprague Dawley rats to left anterior descending coronary artery ligation or sham surgery and different drug prophylaxis as control. We found that gelsolin is highly expressed in platelet rich plasma and lowly expressed in platelet poor plasma, accompanied by the high platelet activation level in model rats; plasma actin filaments and mean fluorescence intensity (MFI of platelet calcium ion increased and plasma vitamin D binding protein decreased in model rats. Xiongshao capsule could inhibit the gelsolin expression in platelet rich plasma and ischemic heart tissue simultaneously and reduce the level of plasma F-actin and MFI of platelet calcium ion. Our study concludes that platelet gelsolin is an important contributor to platelet activation, and platelet gelsolin inhibition may form a novel target for antiplatelet therapy. Xiongshao capsule may be a promising Chinese medicine drug for antiplatelet and aspirin-like cardioprotection effect.

  16. Human platelet glycoprotein Ia. One component is only expressed on the surface of activated platelets and may be a granule constituent

    Energy Technology Data Exchange (ETDEWEB)

    Bienz, D.; Clemetson, K.J.

    1989-01-05

    Glycoprotein Ia (GP Ia) is a relatively minor component of human blood platelets thought to be a receptor involved in collagen-induced platelet activation. However, some difficulties exist with the definition of this glycoprotein. The expression of GP Ia on resting (prostacyclin analogue-treated) and thrombin-activated platelets was compared by surface labeling with /sup 125/I-lactoperoxidase. Intact platelets or platelets solubilized in sodium dodecyl sulfate were labeled with periodate/(/sup 3/H)NaBH/sub 4/. Analysis on two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels showed that GP Ia is very poorly labeled in resting platelets. After activation a new spot (GP Ia*) appears with the same relative molecular mass as GP Ia under reducing conditions. GP Ia and Ia* can be clearly separated by two-dimensional nonreduced/reduced gel electrophoresis. Therefore, two glycoproteins which have been termed GP Ia exist in platelets with similar molecular weight and pI under reducing conditions. One of these (GP Ia*) is only surface-labeled when platelets are activated, indicating that it is only exposed on the surface of activated platelets. Supernatant from activated platelets contains this glycoprotein as well as other granule components. This glycoprotein is missing in platelets from two patients with collagen-response defects.

  17. Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation.

    Science.gov (United States)

    Rigg, Rachel A; Healy, Laura D; Nowak, Marie S; Mallet, Jérémy; Thierheimer, Marisa L D; Pang, Jiaqing; McCarty, Owen J T; Aslan, Joseph E

    2016-04-01

    Molecular chaperones that support protein quality control, including heat shock protein 70 (Hsp70), participate in diverse aspects of cellular and physiological function. Recent studies have reported roles for specific chaperone activities in blood platelets in maintaining hemostasis; however, the functions of Hsp70 in platelet physiology remain uninvestigated. Here we characterize roles for Hsp70 activity in platelet activation and function. In vitro biochemical, microscopy, flow cytometry, and aggregometry assays of platelet function, as well as ex vivo analyses of platelet aggregate formation in whole blood under shear, were carried out under Hsp70-inhibited conditions. Inhibition of platelet Hsp70 blocked platelet aggregation and granule secretion in response to collagen-related peptide (CRP), which engages the immunoreceptor tyrosine-based activation motif-bearing collagen receptor glycoprotein VI (GPVI)-Fc receptor-γ chain complex. Hsp70 inhibition also reduced platelet integrin-αIIbβ3 activation downstream of GPVI, as Hsp70-inhibited platelets showed reduced PAC-1 and fibrinogen binding. Ex vivo, pharmacological inhibition of Hsp70 in human whole blood prevented the formation of platelet aggregates on collagen under shear. Biochemical studies supported a role for Hsp70 in maintaining the assembly of the linker for activation of T cells signalosome, which couples GPVI-initiated signaling to integrin activation, secretion, and platelet function. Together, our results suggest that Hsp70 regulates platelet activation and function by supporting linker for activation of T cells-associated signaling events downstream of platelet GPVI engagement, suggesting a role for Hsp70 in the intracellular organization of signaling systems that mediate platelet secretion, "inside-out" activation of platelet integrin-αIIbβ3, platelet-platelet aggregation, and, ultimately, hemostatic plug and thrombus formation.

  18. Platelets, acting in part via P-selectin, mediate cytomegalovirus-induced microvascular dysfunction.

    Science.gov (United States)

    Khoretonenko, Mikhail V; Brunson, Jerry L; Senchenkov, Evgeny; Leskov, Igor L; Marks, Christian R; Stokes, Karen Y

    2014-12-15

    Cytomegalovirus (CMV) infects a majority of the population worldwide. It has been implicated in cardiovascular disease, induces microvascular dysfunction, and synergizes with hypercholesterolemia to promote leukocyte and platelet recruitment in venules. Although platelets and platelet-associated P-selectin contribute to cardiovascular disease inflammation, their role in CMV-induced vascular responses is unknown. We assessed the role of platelets in CMV-induced microvascular dysfunction by depleting platelets and developing bone marrow chimeric mice deficient in platelet P-selectin. Wild-type and chimeric mice received mock or murine (m)CMV intraperitoneally. Five weeks later, some mice were switched to a high-cholesterol diet (HC) to investigate the synergism between mCMV and HC. Arteriolar vasodilation and recruitment of leukocytes and donor platelets in venules were measured at 11wk. mCMV with or without HC caused significant endothelial dysfunction in arterioles. Platelet depletion restored normal vasodilation in mCMV-HC but not mCMV-ND mice, whereas protection was seen in both groups for platelet P-selectin chimeras. Only mCMV + HC elevated leukocyte and platelet recruitment in venules. Leukocyte adhesion was reduced to mock levels by acute platelet depletion but was only partially decreased in platelet P-selectin chimeras. Platelets from mCMV-HC mice and, to a lesser extent, mCMV-ND but not mock-HC mice showed significant adhesion in mCMV-HC recipients. Our findings implicate a role for platelets, acting through P-selectin, in CMV-induced arteriolar dysfunction and suggest that the addition of HC leads to a platelet-dependent, inflammatory infiltrate that is only partly platelet P-selectin dependent. CMV appeared to have a stronger activating influence than HC on platelets and may represent an additional therapeutic target in vulnerable patients.

  19. Characterization of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction.

    Science.gov (United States)

    Eicher, John D; Wakabayashi, Yoshiyuki; Vitseva, Olga; Esa, Nada; Yang, Yanqin; Zhu, Jun; Freedman, Jane E; McManus, David D; Johnson, Andrew D

    2016-01-01

    Transcripts in platelets are largely produced in precursor megakaryocytes but remain physiologically active as platelets translate RNAs and regulate protein/RNA levels. Recent studies using transcriptome sequencing (RNA-seq) characterized the platelet transcriptome in limited number of non-diseased individuals. Here, we expand upon these RNA-seq studies by completing RNA-seq in platelets from 32 patients with acute myocardial infarction (MI). Our goals were to characterize the platelet transcriptome using a population of patients with acute MI and relate gene expression to platelet aggregation measures and ST-segment elevation MI (STEMI) (n = 16) vs. non-STEMI (NSTEMI) (n = 16) subtypes. Similar to other studies, we detected 9565 expressed transcripts, including several known platelet-enriched markers (e.g. PPBP, OST4). Our RNA-seq data strongly correlated with independently ascertained platelet expression data and showed enrichment for platelet-related pathways (e.g. wound response, hemostasis, and platelet activation), as well as actin-related and post-transcriptional processes. Several transcripts displayed suggestively higher (FBXL4, ECHDC3, KCNE1, TAOK2, AURKB, ERG, and FKBP5) and lower (MIAT, PVRL3, and PZP) expression in STEMI platelets compared to NSTEMI. We also identified transcripts correlated with platelet aggregation to TRAP (ATP6V1G2, SLC2A3), collagen (CEACAM1, ITGA2), and ADP (PDGFB, PDGFC, ST3GAL6). Our study adds to current platelet gene expression resources by providing transcriptome-wide analyses in platelets isolated from patients with acute MI. In concert with prior studies, we identify various genes for further study in regards to platelet function and acute MI. Future platelet RNA-seq studies examining more diverse sets of healthy and diseased samples will add to our understanding of platelet thrombotic and non-thrombotic functions.

  20. Mice lacking the SLAM family member CD84 display unaltered platelet function in hemostasis and thrombosis.

    Directory of Open Access Journals (Sweden)

    Sebastian Hofmann

    Full Text Available BACKGROUND: Platelets are anuclear cell fragments derived from bone marrow megakaryocytes that safeguard vascular integrity by forming thrombi at sites of vascular injury. Although the early events of thrombus formation--platelet adhesion and aggregation--have been intensively studied, less is known about the mechanisms and receptors that stabilize platelet-platelet interactions once a thrombus has formed. One receptor that has been implicated in this process is the signaling lymphocyte activation molecule (SLAM family member CD84, which can undergo homophilic interactions and becomes phosphorylated upon platelet aggregation. OBJECTIVE: The role of CD84 in platelet physiology and thrombus formation was investigated in CD84-deficient mice. METHODS AND RESULTS: We generated CD84-deficient mice and analyzed their platelets in vitro and in vivo. Cd84(-/- platelets exhibited normal activation and aggregation responses to classical platelet agonists. Furthermore, CD84 deficiency did not affect integrin-mediated clot retraction and spreading of activated platelets on fibrinogen. Notably, also the formation of stable three-dimensional thrombi on collagen-coated surfaces under flow ex vivo was unaltered in the blood of Cd84(-/- mice. In vivo, Cd84(-/- mice exhibited unaltered hemostatic function and arterial thrombus formation. CONCLUSION: These results show that CD84 is dispensable for thrombus formation and stabilization, indicating that its deficiency may be functionally compensated by other receptors or that it may be important for platelet functions different from platelet-platelet interactions.

  1. Platelet functions in relation to dietary fats in farmers from two regions of France.

    Science.gov (United States)

    Renaud, S; Dumont, E; Godsey, F; Suplisson, A; Thevenon, C

    1979-02-15

    To determine whether the long-term feeding of dietary fats affect platelet functions in man, platelet aggregation (to thrombin ADP, collagen, epinephrine) and clotting activity of platelet-rich plasma (PRP), platelet-poor plasma and of washed platelets were studied in a mobile-laboratory in 44 healthy male farmers (40--45 years) from two French regions Var and Moselle, in relation to lipemia, glycemia, dietary nutriments, and platelet phospholipid composition. In the Moselle subjects, the platelet clotting activity of PRP and of washed platelets, the platelet aggregation to thrombin and ADP, were highly significantly (p less than 0.001) increased as compared to those of Var, but not the plasma cholesterol, which was identical in the two regions. In Moselle, the intake of total calories, total lipids and saturated fats was higher than in the Var. However, it was only with the saturated fat intake (mostly stearic acid) that the platelet clotting activity (p less than 0.01) and the platelet aggregation (p less than 0.001) were highly significantly correlated. The platelet clotting activity was also significantly (p less than 0.001) correlated with the fatty acid composition of the platelet phospholipid fractions phosphatidyl serine + phosphatidyl inositol.

  2. Amorphous silica nanoparticles aggregate human platelets: potential implications for vascular homeostasis

    Science.gov (United States)

    Corbalan, J Jose; Medina, Carlos; Jacoby, Adam; Malinski, Tadeusz; Radomski, Marek W

    2012-01-01

    Background Amorphous silica nanoparticles (SiNP) can be used in medical technologies and other industries leading to human exposure. However, an increased number of studies indicate that this exposure may result in cardiovascular inflammation and damage. A high ratio of nitric oxide to peroxynitrite concentrations ([NO]/[ONOO−]) is crucial for cardiovascular homeostasis and platelet hemostasis. Therefore, we studied the influence of SiNP on the platelet [NO]/[ONOO−] balance and platelet aggregation. Methods Nanoparticle–platelet interaction was examined using transmission electron microscopy. Electrochemical nanosensors were used to measure the levels of NO and ONOO− released by platelets upon nanoparticle stimulation. Platelet aggregation was studied using light aggregometry, flow cytometry, and phase contrast microscopy. Results Amorphous SiNP induced NO release from platelets followed by a massive stimulation of ONOO− leading to an unfavorably low [NO]/[ONOO−] ratio. In addition, SiNP induced an upregulation of selectin P expression and glycoprotein IIb/IIIa activation on the platelet surface membrane, and led to platelet aggregation via adenosine diphosphate and matrix metalloproteinase 2-dependent mechanisms. Importantly, all the effects on platelet aggregation were inversely proportional to nanoparticle size. Conclusions The exposure of platelets to amorphous SiNP induces a critically low [NO]/[ONOO−] ratio leading to platelet aggregation. These findings provide new insights into the pharmacological profile of SiNP in platelets. PMID:22334785

  3. Platelet-derived HMGB1 is a critical mediator of thrombosis.

    Science.gov (United States)

    Vogel, Sebastian; Bodenstein, Rebecca; Chen, Qiwei; Feil, Susanne; Feil, Robert; Rheinlaender, Johannes; Schäffer, Tilman E; Bohn, Erwin; Frick, Julia-Stefanie; Borst, Oliver; Münzer, Patrick; Walker, Britta; Markel, Justin; Csanyi, Gabor; Pagano, Patrick J; Loughran, Patricia; Jessup, Morgan E; Watkins, Simon C; Bullock, Grant C; Sperry, Jason L; Zuckerbraun, Brian S; Billiar, Timothy R; Lotze, Michael T; Gawaz, Meinrad; Neal, Matthew D

    2015-12-01

    Thrombosis and inflammation are intricately linked in several major clinical disorders, including disseminated intravascular coagulation and acute ischemic events. The damage-associated molecular pattern molecule high-mobility group box 1 (HMGB1) is upregulated by activated platelets in multiple inflammatory diseases; however, the contribution of platelet-derived HMGB1 in thrombosis remains unexplored. Here, we generated transgenic mice with platelet-specific ablation of HMGB1 and determined that platelet-derived HMGB1 is a critical mediator of thrombosis. Mice lacking HMGB1 in platelets exhibited increased bleeding times as well as reduced thrombus formation, platelet aggregation, inflammation, and organ damage during experimental trauma/hemorrhagic shock. Platelets were the major source of HMGB1 within thrombi. In trauma patients, HMGB1 expression on the surface of circulating platelets was markedly upregulated. Moreover, evaluation of isolated platelets revealed that HMGB1 is critical for regulating platelet activation, granule secretion, adhesion, and spreading. These effects were mediated via TLR4- and MyD88-dependent recruitment of platelet guanylyl cyclase (GC) toward the plasma membrane, followed by MyD88/GC complex formation and activation of the cGMP-dependent protein kinase I (cGKI). Thus, we establish platelet-derived HMGB1 as an important mediator of thrombosis and identify a HMGB1-driven link between MyD88 and GC/cGKI in platelets. Additionally, these findings suggest a potential therapeutic target for patients sustaining trauma and other inflammatory disorders associated with abnormal coagulation.

  4. Platelet receptor expression and shedding: glycoprotein Ib-IX-V and glycoprotein VI.

    Science.gov (United States)

    Gardiner, Elizabeth E; Andrews, Robert K

    2014-04-01

    Quantity, quality, and lifespan are 3 important factors in the physiology, pathology, and transfusion of human blood platelets. The aim of this review is to discuss the proteolytic regulation of key platelet-specific receptors, glycoprotein(GP)Ib and GPVI, involved in the function of platelets in hemostasis and thrombosis, and nonimmune or immune thrombocytopenia. The scope of the review encompasses the basic science of platelet receptor shedding, practical aspects related to laboratory analysis of platelet receptor expression/shedding, and clinical implications of using the proteolytic fragments as platelet-specific biomarkers in vivo in terms of platelet function and clearance. These topics can be relevant to platelet transfusion regarding both changes in platelet receptor expression occurring ex vivo during platelet storage and/or clinical use of platelets for transfusion. In this regard, quantitative analysis of platelet receptor profiles on blood samples from individuals could ultimately enable stratification of bleeding risk, discrimination between causes of thrombocytopenia due to impaired production vs enhanced clearance, and monitoring of response to treatment prior to change in platelet count.

  5. Platelet Function During Hypothermia in Experimental Mock Circulation.

    Science.gov (United States)

    Van Poucke, Sven; Stevens, Kris; Kicken, Cécile; Simons, Antoine; Marcus, Abraham; Lancé, Marcus

    2016-03-01

    Alterations in platelet function are a common finding in surgical procedures involving cardiopulmonary bypass and hypothermia. Although the combined impact of hypothermia and artificial circulation on platelets has been studied before, the ultimate strategy to safely minimize the risk for bleeding and thrombosis is yet unknown. The aim of this study was to evaluate the use of a mock circulation loop to study the impact of hypothermia for platelet-related hemostatic changes. Venous blood was collected from healthy adult humans (n = 3). Closed mock circulation loops were assembled, each consisting of a centrifugal pump, an oxygenator with integrated heat exchanger, and a hardshell venous reservoir. The experiment started with the mock circulation temperature set at 37°C (T0 [0 h]). Cooling was then initiated at T1 (+2 h), where temperature was adjusted from 37°C to 32°C. Hypothermia was maintained from T2 (+4 h) to T3 (+28 h). From that point in time, rewarming from 32°C to 37°C was initiated with similar speed as cooling. From time point T4 (+30 h), normothermia (37°C) was maintained until the experiment ended at T5 (+32 h). Blood samples were analyzed in standard hematological tests: light transmission aggregometry (LTA) (arachidonic acid [AA], adenosine diphosphate [ADP], collagen [COL], thrombin-receptor-activating-peptide-14 [TRAP]), multiple electrode aggregometry (MEA) (AA, ADP, COL, TRAP), and rotational thromboelastometry (ROTEM) (EXTEM, FIBTEM, PLTEM). Hemoglobin, hematocrit, and platelet count decrease more substantially during temperature drop (37-32°C) than during hypothermia maintenance. Hb and Hct continue to follow this trend during active rewarming (32-37°C). PC increase from the moment active rewarming was initiated. None of the values return to the initial values. LTA values demonstrate a similar decrease in aggregation after stimulation with the platelet agonists between the start of the mock circulation and the start of cooling. Except

  6. HMGB1 binds to activated platelets via the receptor for advanced glycation end products and is present in platelet rich human coronary artery thrombi.

    Science.gov (United States)

    Ahrens, Ingo; Chen, Yung-Chih; Topcic, Danijal; Bode, Michael; Haenel, David; Hagemeyer, Christoph E; Seeba, Hannah; Duerschmied, Daniel; Bassler, Nicole; Jandeleit-Dahm, Karin A; Sweet, Matthew J; Agrotis, Alex; Bobik, Alex; Peter, Karlheinz

    2015-11-01

    High mobility group box 1 (HMGB1) acts as both a nuclear protein that regulates gene expression, as well as a pro-inflammatory alarmin that is released from necrotic or activated cells. Recently, HMGB1-expression in human atherosclerotic plaques was identified. Therapeutic blockade of HMGB1 reduced the development of diet-induced atherosclerosis in ApoE knockout mice. Thus, we hypothesised an interaction between HMGB1 and activated platelets. Binding of recombinant HMGB1 to platelets was assessed by flow cytometry. HMGB1 bound to thrombin-activated human platelets (MFI 2.49 vs 25.01, p=0.0079). Blood from wild-type, TLR4 and RAGE knockout mice was used to determine potential HMGB1 receptors on platelets. HMGB1 bound to platelets from wild type C57Bl6 (MFI 2.64 vs 20.3, p 0.05). RAGE expression on human platelets was detected by RT-PCR with mRNA extracted from highly purified platelets and confirmed by Western blot and immunofluorescence microscopy. Platelet activation increased RAGE surface expression (MFI 4.85 vs 6.74, p< 0.05). Expression of HMGB1 in human coronary artery thrombi was demonstrated by immunohistochemistry and revealed high expression levels. Platelets bind HMGB1 upon thrombin-induced activation. Platelet specific expression of RAGE could be detected at the mRNA and protein level and is involved in the binding of HMGB1. Furthermore, platelet activation up-regulates platelet surface expression of RAGE. HMGB1 is highly expressed in platelet-rich human coronary artery thrombi pointing towards a central role for HMGB1 in atherothrombosis, thereby suggesting the possibility of platelet targeted anti-inflammatory therapies for atherothrombosis.

  7. Sgk1 Sensitive Pendrin Expression in Murine Platelets

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    Lisann Pelzl

    2013-12-01

    Full Text Available Background: The anion exchanger pendrin (SLC26A4 is required for proper development of the inner ear, and contributes to iodide organification in thyroid glands as well as anion transport in various epithelia, such as airways and renal tubules. SLC26A4 deficiency leads to Pendred syndrome, which is characterized by hearing loss with enlarged vestibular aqueducts and variable hypothyroidism and goiter. Pendrin expression in kidney, heart, lung and thyroid is up-regulated by the mineralocorticoid deoxycorticosterone (DOCA. Platelets express anion exchangers but virtually nothing is known about the molecular identity and regulation of those carriers. Other carriers such as the Na+/H+ exchanger are regulated by the mineralocorticoid-sensitive serum and glucocorticoid inducible kinase SGK1. Methods: The present study utilized i quantitative reverse transcription polymerase chain reaction (RT-qPCR to quantify the transcript levels of Slc26a4 as compared to Gapdh and ii western blotting to assess Slc26a4 protein abundance in murine platelets from gene-targeted mice lacking Sgk1 (sgk1-/- and respective wild type animals (sgk1+/+ treated without or with a subcutaneous injection of 2.5 mg DOCA for 3 h, or in sgk1+/+ platelets with or without in vitro treatment for 1 h with 10 µg/ml DOCA. Results: Slc26a4 was expressed in platelets, and in vitro DOCA treatment increased Slc26a4 mRNA levels in platelets isolated from sgk1+/+ mice. Moreover, in vivo DOCA treatment significantly up-regulated Slc26a4 mRNA levels in platelets isolated from sgk1+/+ but not sgk1-/- mice. An increase in Sgk1 mRNA levels paralleled that of Slc26a4 mRNA levels in platelets of sgk1+/+ mice. In addition, DOCA treatment further increased Slc26a4 protein abundance in platelets isolated from sgk1+/+ mice. Conclusions: Pendrin is expressed in platelets and is presumably regulated by SGK1 and mineralocorticoids.

  8. Platelet Counts, MPV and PDW in Culture Proven and Probable Neonatal Sepsis and Association of Platelet Counts with Mortality Rate

    International Nuclear Information System (INIS)

    Objective: To determine frequency of thrombocytopenia and thrombocytosis, the MPV (mean platelet volume) and PDW (platelet distribution width) in patients with probable and culture proven neonatal sepsis and determine any association between platelet counts and mortality rate. Study Design: Descriptive analytical study. Place and Duration of Study: NICU, Fazle Omar Hospital, from January 2011 to December 2012. Methodology: Cases of culture proven and probable neonatal sepsis, admitted in Fazle Omar Hospital, Rabwah, were included in the study. Platelet counts, MPV and PDW of the cases were recorded. Mortality was documented. Frequencies of thrombocytopenia ( 450000/mm3) were ascertained. Mortality rates in different groups according to platelet counts were calculated and compared by chi-square test to check association. Results: Four hundred and sixty nine patients were included; 68 (14.5%) of them died. One hundred and thirty six (29%) had culture proven sepsis, and 333 (71%) were categorized as probable sepsis. Thrombocytopenia was present in 116 (24.7%), and thrombocytosis was present in 36 (7.7%) cases. Median platelet count was 213.0/mm3. Twenty eight (27.7%) patients with thrombocytopenia, and 40 (12.1%) cases with normal or raised platelet counts died (p < 0.001). Median MPV was 9.30, and median PDW was 12.30. MPV and PDW of the patients who died and who were discharged were not significantly different from each other. Conclusion: Thrombocytopenia is a common complication of neonatal sepsis. Those with thrombocytopenia have higher mortality rate. No significant difference was present between PDW and MPV of the cases who survived and died. (author)

  9. Platelet rich fibrin: a new paradigm in periodontal regeneration.

    Science.gov (United States)

    Kumar, R Vinaya; Shubhashini, N

    2013-09-01

    Among the great challenges facing clinical research is the development of bioactive surgical additives regulating inflammation and increasing healing. Although the use of fibrin adhesives and platelet-rich plasma (PRP) is well documented, they have their own limitations. Hence, reconstructive dental surgeons are looking for an "edge" that jump starts the healing process to maximize predictability as well as the volume of regenerated bone. Overcoming the restrictions related to the reimplantation of blood-derived products, a new family of platelet concentrate, which is neither a fibrin glue nor a classical platelet concentrate, was developed in France. This second generation platelet concentrate called platelet-rich fibrin (PRF), has been widely used to accelerate soft and hard tissue healing. Its advantages over the better known PRP include ease of preparation/application, minimal expense, and lack of biochemical modification (no bovine thrombin or anticoagulant is required). This article serves as an introduction to the PRF "concept" and its potential clinical applications with emphasis on periodontal regeneration.

  10. Platelet granule exocytosis: A comparison with chromaffin cells

    Directory of Open Access Journals (Sweden)

    Jennifer eFitch-Tewfik

    2013-06-01

    Full Text Available The rapid secretion of bioactive amines from chromaffin cells constitutes an important component of the fight or flight response of mammals to stress. Platelets respond to stresses within the vasculature by rapidly secreting cargo at sites of injury, inflammation, or infection. Although chromaffin cells derive from the neural crest and platelets from bone marrow megakaryocytes, both have evolved a heterogeneous assemblage of granule types and a mechanism for efficient release. This article will provide an overview of granule formation and exocytosis in platelets with an emphasis on areas in which the study of chromaffin cells has influenced that of platelets and on similarities between the two secretory systems. Commonalities include the use of transporters to concentrate bioactive amines and other cargos into granules, the role of cytoskeletal remodeling in granule exocytosis, and the use of granules to provide membrane for cytoplasmic projections. The SNAREs and SNARE accessory proteins used by each cell type will also be considered. Finally, we will discuss the newly appreciated role of dynamin family proteins in regulated fusion pore formation. This evaluation of the comparative cell biology of regulated exocytosis in platelets and chromaffin cells demonstrates a convergence of mechanisms between two disparate cell types both tasked with responding rapidly to physiological stimuli.

  11. Modification of Platelet Margination Rate via Reduction of Viscosity Ratio

    Science.gov (United States)

    Reasor, Daniel; Mehrabadi, Marmar; Ku, David; Aidun, Cyrus

    2011-11-01

    Experimental investigations of platelet margination have primarily been limited to effects of hematocrit (Ht.) and shear rate. The suspending fluids used commonly have viscosities greater than plasma which can modify the transition in dynamical regimes from tumbling to tank-treading for isolated RBCs. This work focuses on the effects of λ, the ratio of internal to suspending fluid viscosity of RBCs, on the rate of platelet margination in a rigid 41.3 μm diameter vessel. Simulations are performed with a lattice-Boltzmann fluid solver using the standard bounce-back boundary condition coupled with a coarse-grained spectrin-link RBC membrane model and a Newtonian dynamics solver for rigid platelets. Our results are consistent with observations that an increase in Ht. increases the rate of platelet margination for Ht.=20-40%, but we focus on the modification of λ at Ht.=20%. Our results show that rigid RBCs inhibit margination, but modifying λ with deformable RBCs show significant increases in margination rate. Our observations demonstrate an increase in platelet wall-normal velocity fluctuations, enhanced margination rate, and an increase in the wall-normal diffusivity as λ is reduced from the physiological value of five. NSF TeraGrid Grant: TG-CTS100012.

  12. Effect of taurine on platelets and the plasma coagulation system.

    Science.gov (United States)

    Miglis, Mitchell; Wilder, Donna; Reid, Thomas; Bakaltcheva, Irina

    2002-02-01

    It is not yet clear what exact mechanisms are at work in hibernating animals that prevent clot formation and maintain tissue perfusion under conditions of very slow blood flow and increased blood viscosity brought about by the low temperatures. It has been shown that the total amino acid pool increases more then two fold in hibernating animals with taurine accounting for about 50% of this increase [Storey et al., Proc Natl Acad Sci USA 1988; 85(21): 8350-4]. This work investigates the effect of taurine on platelets and the plasma coagulation system. Taurine was added at different concentrations in the range between 5 and 25 mM to donor plasma. Using STA/STA Compact coagulation analyzer the following tests were performed: prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). At the highest concentration tested (25 mM) taurine prolonged TT by 9%. The prolongation was statistically significant but not clinically significant retaining TT within normal limits (16.7-20.7 s). PT and APTT remained unchanged by taurine. The effect of taurine on platelets was assessed by platelet aggregation by thrombin, extent of platelet shape change (ESC) induced by ADP, and thrombelastography. Taurine at 5 mM final concentration inhibited platelet aggregation by 10%. Increasing taurine concentration to 25 mM did not result in a further augmentation of the inhibitory effect. ESC was unaffected by taurine. Clot strength determined by thrombelastography also remained unchanged by taurine. PMID:11918831

  13. Alzheimer disease and platelets: how’s that relevant

    Directory of Open Access Journals (Sweden)

    Catricala Silvia

    2012-09-01

    Full Text Available Abstract Alzheimer Disease (AD is the most common neurodegenerative disorder worldwide, and account for 60% to 70% of all cases of progressive cognitive impairment in elderly patients. At the microscopic level distinctive features of AD are neurons and synapses degeneration, together with extensive amounts of senile plaques and neurofibrillars tangles. The degenerative process probably starts 20–30 years before the clinical onset of the disease. Senile plaques are composed of a central core of amyloid β peptide, Aβ, derived from the metabolism of the larger amyloid precursor protein, APP, which is expressed not only in the brain, but even in non neuronal tissues. More than 30 years ago, some studies reported that human platelets express APP and all the enzymatic activities necessary to process this protein through the same pathways described in the brain. Since then a large number of evidence has been accumulated to suggest that platelets may be a good peripheral model to study the metabolism of APP, and the pathophysiology of the onset of AD. In this review, we will summarize the current knowledge on the involvement of platelets in Alzheimer Disease. Although platelets are generally accepted as a suitable model for AD, the current scientific interest on this model is very high, because many concepts still remain debated and controversial. At the same time, however, these still unsolved divergences mirror a difficulty to establish constant parameters to better defined the role of platelets in AD.

  14. Antiplatelet Agents Inhibit the Generation of Platelet-Derived Microparticles

    Science.gov (United States)

    Giacomazzi, Alice; Degan, Maurizio; Calabria, Stefano; Meneguzzi, Alessandra; Minuz, Pietro

    2016-01-01

    Platelet microparticles (PMPs) contribute to thrombogenesis but the effects of antiplatelet drugs on PMPs generation is undefined. The present study investigated the cellular events regulating PMPs shedding, testing in vitro platelet agonists and inhibitors. Platelet-rich plasma from healthy subjects was stimulated with arachidonic acid (AA), U46619, collagen type-I (10 and 1.5 μg/mL), epinephrine, ADP or TRAP-6 and pre-incubated with acetylsalicylic acid (ASA, 100 and 10 μmol/L), SQ-29,548, apyrase, PSB-0739, or eptifibatide. PMPs were detected by flow-cytometry using CD61 and annexin-V as fluorescent markers. Platelet agonists induced annexin V-positive PMPs shedding. The strongest response was to high concentration collagen. ADP-triggered PMPs shedding was dose-independent. ASA reduced PMPs induced by AA- (645, 347–2946 vs. 3061, 446–4901 PMPs/μL; median ad range, n = 9, P PMP shedding. The crucial role of the fibrinogen receptor and the collagen receptor in PMPs generation, independently of platelet aggregation, was identified. PMID:27695417

  15. Influence of caffeine on blood pressure and platelet aggregation

    Directory of Open Access Journals (Sweden)

    José Wilson S. Cavalcante

    2000-08-01

    Full Text Available OBJECTIVE: Studies have demonstrated that methylxanthines, such as caffeine, are A1 and A2 adenosine receptor antagonists found in the brain, heart, lungs, peripheral vessels, and platelets. Considering the high consumption of products with caffeine in their composition, in Brazil and throughout the rest of the world, the authors proposed to observe the effects of this substance on blood pressure and platelet aggregation. METHODS: Thirteen young adults, ranging from 21 to 27 years of age, participated in this study. Each individual took 750mg/day of caffeine (250mg tid, over a period of seven days. The effects on blood pressure were analyzed through the pressor test with handgrip, and platelet aggregation was analyzed using adenosine diphosphate, collagen, and adrenaline. RESULTS: Diastolic pressure showed a significant increase 24 hours after the first intake (p<0.05. This effect, however, disappeared in the subsequent days. The platelet aggregation tests did not reveal statistically significant alterations, at any time during the study. CONCLUSION: The data suggest that caffeine increases diastolic blood pressure at the beginning of caffeine intake. This hypertensive effect disappears with chronic use. The absence of alterations in platelet aggregation indicates the need for larger randomized studies.

  16. Ultraviolet irradiation of platelet concentrates: Feasibility in transfusion practice

    Energy Technology Data Exchange (ETDEWEB)

    Andreu, G.; Boccaccio, C.; Lecrubier, C.; Fretault, J.; Coursaget, J.; LeGuen, J.P.; Oleggini, M.; Fournel, J.J.; Samama, M. (Secteur d' Hemobiologie Transfusion, Paris (France))

    1990-06-01

    Ultraviolet (UV)-B irradiation abolishes lymphocyte functions (the ability to respond and to stimulate) in mixed lymphocyte culture (MLC). This effect may have practical application in the prevention or reduction of transfusion-induced alloimmunization against HLA class I antigens. To study this, platelet concentrates (PCs) were obtained with a cell separator, suspended in autologous plasma in a final volume of 400 mL, and transferred into a large (22 X 30 cm) cell culture bag. This plastic showed a good transmittance of UV-B rays at 310 nm (54%). PCs were placed between two quartz plates (surface of irradiation = 25 X 37 cm), and the two sides were irradiated simultaneously. Energy delivered to the surface of the plastic bag was automatically monitored. The ability to respond (in MLC and to phytohemagglutinin) and to stimulate allogeneic lymphocytes was completely abolished with energy of 0.75 J per cm2 (irradiation time less than 3 min). The temperature increase during irradiation was negligible. Platelet aggregation (collagen, adrenalin, ADP, arachidonic acid, ristocetin) was not impaired if UV-B energy was below 3 J per cm2. Recovery and survival of autologous 111In-labeled platelets were studied in four volunteers; no differences were found between UV-B-treated (1.5 J/cm2) platelets and untreated platelets. These results show that a large-scale clinical trial using UV-B-irradiated PCs to prevent HLA alloimmunization is feasible.

  17. Changing common sense: Anti-platelet/coagulation therapyagainst cirrhosis

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Until recently, anti-platelet/coagulation therapy hadnot been recommended for patients with cirrhosis.Although venous thrombosis is one of the representativecomplications of cirrhosis and ischemic disordersassociated with atherosclerosis are not infrequent incirrhotic patients, many clinicians have tended to hesitateto introduce anti-platelet/coagulation therapy to theirpatients. Undoubtedly, this is due to the increased riskof hemorrhagic diathesis in cirrhotic patients. However,accumulating evidence has revealed the benefits ofanti-platelet/coagulation therapy for cirrhotic patients.In addition to the safety of the therapy carried outagainst cardiovascular diseases in cirrhotic patients,some clinical data have indicated its preventive effecton venous thrombosis. Moreover, the efficacy of antiplatelet/coagulation therapy against cirrhosis itself hasbeen demonstrated both clinically and experimentally.The conceptual basis for application of anti-platelet/coagulation therapy against cirrhosis was constructedthrough two pathologic studies on intrahepatic thrombosisin cirrhotic livers. It may be better to use thrombopoietinreceptoragonists, which have been tested as a treatmentfor cirrhosis-related thrombocytopenia, in combinationwith anti-platelet drugs to reduce the risk of venousthrombosis. During the last decade, the World Journalof Gastroenterology , a sister journal of World Journal ofHepatology , has been one of the main platforms of activediscussion of this theme.

  18. Platelet cold agglutinins and thrombocytopenia: A diagnostic dilemma in the intensive care unit

    Directory of Open Access Journals (Sweden)

    TV Bharath Kumar

    2014-01-01

    Full Text Available We report a case of pseudo-thrombocytopenia due to cold agglutinins against platelets. These cold agglutinins were the cause for diagnostic confusion and resulted in extensive workup and unnecessary therapeutic precautions. A thirty two year old female with Guillain-Barre syndrome was admitted in the ICU and serial work-up showed markedly low levels of platelets. The patient had no symptoms of bleeding and patient was investigated extensively for deciphering the etiology of low platelet count. In-vitro clumping of platelets was suspected and in-vitro studies showed marked clumping of platelets with ethylene-diamine-tetra-acetic acid, citrate and heparinized samples. The manual platelet count was found to be within normal limits. Thrombocytopenia as a result of platelet cold agglutinins is a rare cause of in-vitro low platelet counts. No clinical problems have been reported due to the same.

  19. The effect of centrifugation speed and time on pre-analytical platelet activation

    DEFF Research Database (Denmark)

    Söderström, Anna C; Nybo, Mads; Nielsen, Christian;

    2016-01-01

    BACKGROUND: The results of laboratory analyses are affected by pre-analytical variables, and in particular can platelets be activated by shear handling stress and secrete granular substances. We therefore evaluated the effect of centrifugation speed and time on pre-analytical platelet activation....... METHODS: Citrate- and EDTA-anticoagulated blood from healthy volunteers were centrifuged at 80-10,000 g for 5-15 min to prepare plasma and platelet-rich plasma. Pre-analytical platelet activation was assessed by flow cytometric measurement of platelet P-selectin (CD62p) expression. Blood cell counts, mean...... of platelets expressing P-selectin in citrate- and EDTA-plasma centrifuged at 2000 g for 10 min were 43% [interquartile range (IQR), 38%-53%] and 56% (IQR, 31%-78%), respectively (p=0.82). Platelet-rich plasma prepared at 100-250 g for 10 min had significantly lower platelet P-selectin expression (11%-15%), p...

  20. The PPAR-Platelet Connection: Modulators of Inflammation and Potential Cardiovascular Effects

    Directory of Open Access Journals (Sweden)

    S. L. Spinelli

    2008-01-01

    Full Text Available Historically, platelets were viewed as simple anucleate cells responsible for initiating thrombosis and maintaining hemostasis, but clearly they are also key mediators of inflammation and immune cell activation. An emerging body of evidence links platelet function and thrombosis to vascular inflammation. peroxisome proliferator-activated receptors (PPARs play a major role in modulating inflammation and, interestingly, PPARs (PPARβ/δ and PPARγ were recently identified in platelets. Additionally, PPAR agonists attenuate platelet activation; an important discovery for two reasons. First, activated platelets are formidable antagonists that initiate and prolong a cascade of events that contribute to cardiovascular disease (CVD progression. Dampening platelet release of proinflammatory mediators, including CD40 ligand (CD40L, CD154, is essential to hinder this cascade. Second, understanding the biologic importance of platelet PPARs and the mechanism(s by which PPARs regulate platelet activation will be imperative in designing therapeutic strategies lacking the deleterious or unwanted side effects of current treatment options.

  1. Activated platelets enhance IL-10 secretion and reduce TNF-α secretion by monocytes

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Hasselbalch, Hans C; Nielsen, Claus H

    2013-01-01

    Activated platelets are known to modulate immune responses by secreting or shedding a range of immunomodulatory substances. We examined the influence of activated platelets on cytokine production by normal human mononuclear cells, induced by tetanus toxoid (TT), human thyroglobulin (TG), Escheric......Activated platelets are known to modulate immune responses by secreting or shedding a range of immunomodulatory substances. We examined the influence of activated platelets on cytokine production by normal human mononuclear cells, induced by tetanus toxoid (TT), human thyroglobulin (TG...... production. Moreover, Ab-mediated blockade of CD40L counteracted the effect of platelets and platelet supernatants on TNF-α production. Monocytes separated into two populations with respect to IL-10 production induced by TG; the high-secreting fraction increased from 0.8 to 2.1% (p ... of activated platelets. Adherence of platelets increased TG- and TT-induced IL-10 secretion by monocytes (p

  2. Epinephrine enhances platelet-neutrophil adhesion in whole blood in vitro.

    NARCIS (Netherlands)

    Horn, N.A.; Anastase, D.M.; Hecker, K.E.; Baumert, J.H.; Robitzsch, T.; Rossaint, R.

    2005-01-01

    Previous studies showed that alpha- or beta-adrenoceptor stimulation by catecholamines influenced neutrophil function, cytokine liberation, and platelet aggregability. We investigated whether adrenergic stimulation with epinephrine also alters platelet-neutrophil adhesion. This might be of specific

  3. Platelet function in patients with a history of unexplained recurrent miscarriage who subsequently miscarry again.

    LENUS (Irish Health Repository)

    Dempsey, Mark Anthony

    2015-05-01

    This study was designed to evaluate platelet aggregation in pregnant women with a history of unexplained recurrent miscarriage (RM) and to compare platelet function in such patients who go on to have either another subsequent miscarriage or a successful pregnancy.

  4. The PPAR-Platelet Connection: Modulators of Inflammation and Potential Cardiovascular Effects.

    Science.gov (United States)

    Spinelli, S L; O'Brien, J J; Bancos, S; Lehmann, G M; Springer, D L; Blumberg, N; Francis, C W; Taubman, M B; Phipps, R P

    2008-01-01

    Historically, platelets were viewed as simple anucleate cells responsible for initiating thrombosis and maintaining hemostasis, but clearly they are also key mediators of inflammation and immune cell activation. An emerging body of evidence links platelet function and thrombosis to vascular inflammation. peroxisome proliferator-activated receptors (PPARs) play a major role in modulating inflammation and, interestingly, PPARs (PPARbeta/delta and PPARgamma) were recently identified in platelets. Additionally, PPAR agonists attenuate platelet activation; an important discovery for two reasons. First, activated platelets are formidable antagonists that initiate and prolong a cascade of events that contribute to cardiovascular disease (CVD) progression. Dampening platelet release of proinflammatory mediators, including CD40 ligand (CD40L, CD154), is essential to hinder this cascade. Second, understanding the biologic importance of platelet PPARs and the mechanism(s) by which PPARs regulate platelet activation will be imperative in designing therapeutic strategies lacking the deleterious or unwanted side effects of current treatment options.

  5. The effects of ropivacaine hydrochloride on platelet function: an assessment using the platelet function analyser (PFA-100).

    LENUS (Irish Health Repository)

    Porter, J

    2012-02-03

    Amide local anaesthetics impair blood clotting in a concentration-dependent manner by inhibition of platelet function and enhanced fibrinolysis. We hypothesised that the presence of ropivacaine in the epidural space could decrease the efficacy of an epidural blood patch, as this technique requires that the injected blood can clot in order to be effective. Ropivacaine is an aminoamide local anaesthetic used increasingly for epidural analgesia during labour. The concentration of local anaesthetic in blood achieved in the epidural space during the performance of an epidural blood patch is likely to be the greatest which occurs (intentionally) in any clinical setting. This study was undertaken to investigate whether concentrations of ropivacaine in blood, which could occur: (i) clinically in the epidural space and (ii) in plasma during an epidural infusion of ropivacaine, alter platelet function. A platelet function analyser (Dade PFA-100, Miami) was employed to assess the effects of ropivacaine-treated blood on platelet function. The greater concentrations of ropivacaine studied (3.75 and 1.88 mg x ml(-1)), which correspond to those which could occur in the epidural space, produced significant inhibition of platelet aggregation. We conclude that the presence of ropivacaine in the epidural space may decrease the efficacy of an early or prophylactic epidural blood patch.

  6. Small-size platelet microparticles trigger platelet and monocyte functionality and modulate thrombogenesis via P-selectin.

    Science.gov (United States)

    Montoro-García, Silvia; Shantsila, Eduard; Hernández-Romero, Diana; Jover, Eva; Valdés, Mariano; Marín, Francisco; Lip, Gregory Y H

    2014-08-01

    This study aimed to examine the mechanisms of cellular activation by small-size platelet microparticles (sPMP) and to present the performance of high-resolution flow cytometry for the analysis of subcellular entities from different origins. Plasma counts of sPMP were analysed in coronary artery disease patients (n = 40) and healthy controls (n = 40). The effect of sPMP and platelet debris (PD) in pathophysiologically relevant doses on platelet and monocyte activation parameters and thrombogenesis was investigated via flow cytometry and thromboelastometry. New generation flow cytometry identifies differences in size, levels and surface molecules of sPMP derived in the absence of stimulus, thrombin activation and platelet disruption. Addition of sPMP resulted in platelet degranulation and P-selectin redistribution to the membrane (P = 0·019) in a dose and time-dependent manner. Blood clotting time decreased after addition of sPMP (P = 0·005), but was not affected by PD. Blocking P-selectin (CD62P) in sPMP markedly reverted the effect on thrombus kinetics (P = 0·035). Exposure to sPMP stimulated monocyte expression of intercellular adhesion molecule-1 (P P-selectin expression.

  7. Platelet-rich-fibrin: A novel root coverage approach

    Directory of Open Access Journals (Sweden)

    Anilkumar K

    2009-01-01

    Full Text Available Treatment of gingival recession has become an important therapeutic issue due to increasing cosmetic demand. Multiple surgical procedures have been developed to obtain predictable esthetic root coverage. More specifically, after periodontal regenerative surgery, the aim is to achieve complete wound healing and regeneration of the periodontal unit. A recent innovation in dentistry is the preparation and use of platelet-rich plasma (PRP, a concentrated suspension of the growth factors, found in platelets. These growth factors are involved in wound healing and postulated as promoters of tissue regeneration. This paper reports the use of PRF membrane for root coverage on the labial surfaces of the mandibular anterior teeth. This was accomplished using laterally displaced flap technique with platelet rich fibrin (PRF membrane at the recipient site.

  8. Macroscopic domain formation in the platelet plasma membrane

    DEFF Research Database (Denmark)

    Bali, Rachna; Savino, Laura; Ramirez, Diego A.;

    2009-01-01

    There has been ample debate on whether cell membranes can present macroscopic lipid domains as predicted by three-component phase diagrams obtained by fluorescence microscopy. Several groups have argued that membrane proteins and interactions with the cytoskeleton inhibit the formation of large...... phase behavior of the platelet plasma membrane by FTIR, and compare it to a POPC/Sphingomyelin/Cholesterol model representing the outer leaflet composition. We find that this model closely reflects the platelet phase behavior. Previous work has shown that the platelet plasma membrane presents...... domains. In contrast, some polarizable cells do show large regions with qualitative differences in lipid fluidity. It is important to ask more precisely, based on the current phase diagrams, under what conditions would large domains be expected to form in cells. In this work we study the thermotropic...

  9. Clinical Applications of Platelet-Rich Plasma in Patellar Tendinopathy

    Directory of Open Access Journals (Sweden)

    D. U. Jeong

    2014-01-01

    Full Text Available Platelet-rich plasma (PRP, a blood derivative with high concentrations of platelets, has been found to have high levels of autologous growth factors (GFs, such as transforming growth factor-β (TGF-β, platelet-derived growth factor (PDGF, fibroblastic growth factor (FGF, vascular endothelial growth factor (VEGF, and epidermal growth factor (EGF. These GFs and other biological active proteins of PRP can promote tissue healing through the regulation of fibrosis and angiogenesis. Moreover, PRP is considered to be safe due to its autologous nature and long-term usage without any reported major complications. Therefore, PRP therapy could be an option in treating overused tendon damage such as chronic tendinopathy. Here, we present a systematic review highlighting the clinical effectiveness of PRP injection therapy in patellar tendinopathy, which is a major cause of athletes to retire from their respective careers.

  10. Clinical applications of platelet-rich plasma in patellar tendinopathy.

    Science.gov (United States)

    Jeong, D U; Lee, C-R; Lee, J H; Pak, J; Kang, L-W; Jeong, B C; Lee, S H

    2014-01-01

    Platelet-rich plasma (PRP), a blood derivative with high concentrations of platelets, has been found to have high levels of autologous growth factors (GFs), such as transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), fibroblastic growth factor (FGF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). These GFs and other biological active proteins of PRP can promote tissue healing through the regulation of fibrosis and angiogenesis. Moreover, PRP is considered to be safe due to its autologous nature and long-term usage without any reported major complications. Therefore, PRP therapy could be an option in treating overused tendon damage such as chronic tendinopathy. Here, we present a systematic review highlighting the clinical effectiveness of PRP injection therapy in patellar tendinopathy, which is a major cause of athletes to retire from their respective careers. PMID:25136568

  11. The role of platelets in the pathogenesis of systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Giuseppe A. eRamirez

    2012-06-01

    Full Text Available Systemic sclerosis (SSc is an inflammatory disease of unknown etiology characterized by widespread organ dysfunction due to fibrosis and ischemia. Its nebulous pathogenic background and the consequent absence of an etiological therapy prevent the adoption of satisfying treatment strategies, able to improve patients' quality of life and survival and stimulate researchers to identify a unifying pathogenic target. Platelets show a unique biological behavior, lying at the crossroads between vascular function, innate and adaptive immunity and regulation of cell proliferation. Consequently they are also emerging players in the pathogenesis of many inflammatory diseases, including systemic sclerosis. In the setting of SSc platelets are detectable in a persistent activated state, which is intimately linked to the concomitant presence of an injured endothelium and to the widespread activation of the innate and adaptive immune system. As a consistent circulating source of bioactive compounds platelets contribute to the development of many characteristic phenomena of SSc, such as fibrosis and impaired vascular tone.

  12. A physical description of the adhesion and aggregation of platelets

    CERN Document Server

    Chopard, Bastien; Latt, Jonas; Dubois, Frank; Yourassowsky, Catherine; Van Antwerpen, Pierre; Eker, Omer; Vanhamme, Luc; Perez-Morga, David; Courbebaisse, Guy; Boudjeltia, Karim Zouaoui

    2015-01-01

    The early stages of clot formation in blood vessels involve platelets adhesion-aggregation. Although these mechanisms have been extensively studied, gaps in their understanding still persist. We have performed detailed in-vitro experiments and developed a numerical model to better describe and understand this phenomenon. Unlike previous studies, we took into account both activated and non-activated platelets, as well as the 3D nature of the aggregation process. Our investigation reveals that blood albumin is a major parameter limiting platelet adhesion and aggregation. Our results also show that the well accepted Zydney-Colton shear-induced diffusivity is much too low to explain the observed deposition rate. Simulations are in very good agreement with observations and provide quantitative estimates of the adhesion and aggregation rates that are hard to measure experimentally.

  13. Pulmonary platelet trapping induced by bleomycin: correlation with fibrosis and involvement of the beta 2 integrins.

    OpenAIRE

    Piguet, P F; Vesin, C

    1994-01-01

    Platelet trapping was explored during the course of bleomycin induced pulmonary fibrosis by the injection of indium-111 labelled platelets and by light and electron microscopy (EM) of the alveolar capillaries. An i.v. injection of bleomycin markedly increased the localization of labelled platelets in the lung (but not in other organs) for about 3 weeks. On day 7 after bleomycin injection, a significant increase in the number of platelets in contact with the alveolar endothelium was seen with ...

  14. Protein Kinase C ε Expression in Platelets from Patients with Acute Myocardial Infarction

    OpenAIRE

    Cecilia Carubbi; Prisco Mirandola; Maria Mattioli; Daniela Galli; Nicola Marziliano; Piera Angelica Merlini; Daniela Lina; Francesca Notarangelo; Maria Rita Cozzi; Marco Gesi; Diego Ardissino; Luigi De Marco; Marco Vitale; Giuliana Gobbi

    2012-01-01

    OBJECTIVE: Platelets play crucial roles in the pathophysiology of thrombosis and myocardial infarction. Protein kinase C ε (PKCε) is virtually absent in human platelets and its expression is precisely regulated during human megakaryocytic differentiation. On the basis of what is known on the role of platelet PKCε in other species, we hypothesized that platelets from myocardial infarction patients might ectopically express PKCε with a pathophysiological role in the disease. METHODS AND RESULTS...

  15. Presence of intratumoral platelets is associated with tumor vessel structure and metastasis

    OpenAIRE

    Li, Rong; Ren, Meiping; Chen, Ni; Luo, Mao; Deng, Xin; Xia, Jiyi; Yu, Guang; Liu, Jinbo; HE Bing; Zhang, Xu; Zhang, Zhuo; Zhang, Xiao; Ran, Bing; Wu, Jianbo

    2014-01-01

    Background Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in hematogenous dissemination of tumor cells. Abundant platelets were detected in the tumor microenvironment outside of the blood vessel, thus, platelet -tumor cell interaction outside of the bloodstream may play a role in regulating primary tumor growth and metastasis initiation. However, it is unclear that platelet depletion affects tumor vessel structure and dynamics. Methods Using thr...

  16. Platelet Activation Determines Angiopoietin-1 and VEGF Levels in Malaria: Implications for Their Use as Biomarkers

    OpenAIRE

    Judith Brouwers; Rintis Noviyanti; Rob Fijnheer; de Groot, Philip G.; Leily Trianty; Siti Mudaliana; Mark Roest; Din Syafruddin; Andre van der Ven; Quirijn de Mast

    2013-01-01

    INTRODUCTION: The angiogenic proteins angiopoietin (Ang)-1, Ang-2 and vascular endothelial growth factor (VEGF) are regulators of endothelial inflammation and integrity. Since platelets store large amounts of Ang-1 and VEGF, measurement of circulation levels of these proteins is sensitive to platelet number, in vivo platelet activation and inadvertent platelet activation during blood processing. We studied plasma Ang-1, Ang-2 and VEGF levels in malaria patients, taking the necessary precautio...

  17. Platelets As Initiators and Mediators of Inflammation at the Vessel Wall

    OpenAIRE

    Shi, Guanfang; Morrell, Craig N.

    2010-01-01

    Platelets are dynamic cells with activities that extend beyond thrombosis including an important role in initiating and sustaining vascular inflammation. A role for platelets has been described in many physiologic and pathophysiologic processes such as atherosclerosis, stem cell trafficking, tumor metastasis, and arthritis. Platelet activation at sites of an intact inflamed endothelium contributes to vascular inflammation and vascular wall remodeling. Platelets secrete a wide array of preform...

  18. Platelet activation and dysfunction in a large-animal model of traumatic brain injury and hemorrhage

    DEFF Research Database (Denmark)

    Sillesen, Martin; Johansson, Pär I; Rasmussen, Lars S;

    2013-01-01

    Traumatic brain injury (TBI) and hemorrhage are the leading causes of trauma-related mortality. Both TBI and hemorrhage are associated with coagulation disturbances, including platelet dysfunction. We hypothesized that platelet dysfunction could be detected early after injury, and that this dysfu......Traumatic brain injury (TBI) and hemorrhage are the leading causes of trauma-related mortality. Both TBI and hemorrhage are associated with coagulation disturbances, including platelet dysfunction. We hypothesized that platelet dysfunction could be detected early after injury...

  19. Platelets Roll on Stimulated Endothelium in vivo: An Interaction Mediated by Endothelial P-Selectin

    Science.gov (United States)

    Frenette, Paul S.; Johnson, Robert C.; Hynes, Richard O.; Wagner, Denisa D.

    1995-08-01

    P-selectin, found in storage granules of platelets and endothelial cells, can be rapidly expressed upon stimulation. Mice lacking this membrane receptor exhibit a severe impairment of leukocyte rolling. We observed that, in addition to leukocytes, platelets were rolling in mesenteric venules of wild-type mice. To investigate the role of P-selectin in this process, resting or activated platelets from wild-type or P-selectin-deficient mice were fluorescently labeled and transfused into recipients of either genotype. Platelet-endothelial interactions were monitored by intravital microscopy. We observed rolling of either wild-type or P-selectin-deficient resting platelets on wild-type endothelium. Endothelial stimulation with the calcium ionophore A23187 increased the number of platelets rolling 4-fold. Activated P-selectin-deficient platelets behaved similarly, whereas activated wild-type platelets bound to leukocytes and were seen rolling together. Platelets of either genotype, resting or activated, interacted minimally with mutant endothelium even after A23187 treatment. The velocity of platelet rolling was 6- to 9-fold greater than that of leukocytes. Our results demonstrate that (i) platelets roll on endothelium in vivo, (ii) this interaction requires endothelial but not platelet P-selectin, and (iii) platelet rolling appears to be independent of platelet activation, indicating constitutive expression of a P-selectin ligand(s) on platelets. We have therefore observed an interesting parallel between platelets and leukocytes in that both of these blood cell types roll on stimulated vessel wall and that this process is dependent on the expression of endothelial P-selectin.

  20. Slow Coronary Flow Phenomenon and Increased Platelet Volume Indices

    Science.gov (United States)

    Seyyed-Mohammadzad, Mir Hossein; Kerachian, Abdollah; Eskandari, Ramin; Rezaei, Yousef

    2014-01-01

    Background and Objectives We sought to determine the relationship between mean platelet volume (MPV), platelet distribution width (PDW), and platelet larger cell ratio (P-LCR) with slow coronary flow (SCF). Subjects and Methods Eighty participants who underwent coronary angiography were divided into two groups, 50 participants with SCF as case group, and 30 with normal coronary flow (NCF) as control group. Baseline characteristics and laboratory data were collected before angiography. Results Platelet volume indices MPV (10.8±1.2 fL), PDW (14.5±2.2 fL), and P-LCR (30.5±8.1%) in the SCF group were significantly (p<0.05) higher than those (10.1±0.9 fL, 13.2±1.8 fL, and 26.8±6.8%, respectively) in the NCF group. The patients with three SCF arteries had significantly higher platelet volume indices compared to those with NCF arteries; however, the patients with one SCF artery did not. Based on linear regression model, MPV, PDW, and P-LCR were independent predictors of mean infarction frame counting (TFC). In multivariate analysis, MPV {odds ratio (OR)=32.393, 95% confidence interval (CI)=1.189-882.606, p=0.039} and P-LCR (OR=0.566, 95% CI=0.330-0.937, p=0.028) were independent predictors of SCF. Conclusion Platelet volume indices MPV, PDW, and P-LCR were associated with both the presence and extent of SCF. PMID:25469142

  1. Phorbol ester stimulates calcium sequestration in saponized human platelets

    International Nuclear Information System (INIS)

    When platelets are activated by agonists, calcium (Ca2+) is released from an intracellular storage site. Recent studies using fura-2 show that, after thrombin stimulation, the rise in free calcium is transient and returns to base-line levels in 2-3 min, while the transient following ADP stimulation lasts only 15-20 s. We reported previously that the phorbol ester 12,13-phorbol myristate acetate (PMA), added at nanomolar levels after thrombin, immediately accelerated the rate of return of calcium to the base line severalfold. In the present study, we used both intact and saponized platelets to determine whether this is due to stimulation of calcium sequestration. Using fura-2 and intact platelets, we found 1) that PMA stimulated the restoration of free Ca2+ levels after ADP as well as after thrombin, and 2) that H-7, an inhibitor of protein kinase C (Ca2+/phospholipid-dependent enzyme), slowed the return of Ca2+ to baseline levels. Using saponized platelets, we also found 3) that pretreatment of platelets with PMA before saponin treatment increased the ATP-dependent 45Ca2+ uptake 2-fold, with a half-maximal effect at 5 nm; 4) that most of the Ca2+ released by ionomycin or by myoinositol 1,4,5-trisphosphate; and 5) that a GTP-binding protein inhibitor, guanosine 5'-O-(2-thiodiphosphate), decreased basal or PMA-stimulated 45Ca2+ uptake in saponin-treated platelets. Our data suggest that activation of protein kinase C stimulates the sequestration of Ca2+ independently of cAMP or myoinositol 1,4,5-trisphosphate

  2. STUDY ON PLATELET INDICES IN PREGNANCY INDUCED HYPERTENSION

    Directory of Open Access Journals (Sweden)

    Rabi a Parveen

    2015-10-01

    Full Text Available INTRODUCTION : Pregnancy induced hypertension includes gestational hypertension, preeclampsia, and eclampsia. In PIH, lower the platelet count, greater are maternal and fetal morbidity and mortality. Recent studies suggest that platele t parameters like platelet indices are most simple and cost effective method for prediction of PIH, way before the appearance of derangements in PT, APTT, TT values so we undertook this study with an aim to see an association between platelet indices and pregnancy induced hypertension. MATERIAL AND METHOD : This was prospective analytical case control study. Study included 125 cases, who were diagnosed as PIH with B.P. > 140/90 mmHg, detected after 20 weeks of pregnancy. Under all aseptic precautions samples were collected randomly in EDTA vials . Samples were analysed for platelet indices . RESULT : Maximum number of cases of Preeclampsia (88.57% & Eclampsia (87.5% were fo und in age group of 21 to 25 . Controls were of same age group i.e. 21 to 25 years. It was observed that platelet count showed gradual decrease in eclampsia (1.44580± 36,210 & pre - e clampsia patients (1.97850± 39,010 as compared to normotensive subjects (2.42620± 40,412. MPV showed gradual increase in eclampsia ( 10.49 ±1.12 & pre - eclampsia ( 9.14 ±0.612 patients as compared to normotensive subjects ( 8.422 ±0.743. PDW value also shows gradual increase in eclampsia ( 18.39 ±2.62 & pre - eclampsia ( 16.29 ±2.34 p atients as compared to normotensive subjects ( 12.09 ±2.53. CONCLUSION : Study showed that platelet indices were important, simple, effortless and cost effective investigations which can be used for early recognition of preventable eclampsia complications.

  3. gamma. -hexachlorocyclohexane (. gamma. -HCH) activates washed rabbit platelets

    Energy Technology Data Exchange (ETDEWEB)

    Lalau-Keraly, C.; Delautier, D.; Benveniste, J.; Puiseux-Dao, S.

    1986-03-01

    In guinea-pig macrophages, ..gamma..-HCH triggers activation of the phosphatidylinositol cycle and Ca/sup 2 +/ mobilization. Since these two biochemical events are also involved in platelet activation, the authors examined the effects of ..gamma..-HCH on washed rabbit platelets. Release of /sup 14/C-serotonin (/sup 14/C-5HT) and ATP from platelets prelabelled with /sup 14/C-5HT was measured simultaneously with aggregation. ..gamma..-HCH induced shape-change, aggregation and release reaction of platelets. Maximal aggregation (89 arbitrary units, AU), was observed using 170 ..mu..M ..gamma..-HCH, and was associated with 38.1 +/- 6.9% and 161 +/- 48 nM for /sup 14/C-5HT and ATP release respectively (mean +/- 1 SD, n=3). Using 80 ..mu..M ..gamma..-HCH yielded 18 AU, 12.8 +/- 1.0% and 27 +/- 14 nM for aggregation, C-5HT and ATP release respectively (n=3). No effect was observed with 40 ..mu.. M ..gamma..-HCH. Aspirin (ASA), a cyclooxygenase blocker, did not affect ..gamma..-HCH-induced platelet activation. Apyrase (APY), an ADP scavenger, inhibited by 90% aggregation induced by 170 ..mu..M ..gamma..-HCH and slightly inhibited (15%) the /sup 14/C-5HT release. In the presence of both ASA and APY, 96% inhibition of aggregation and 48% inhibition of /sup 14/C-5HT release were observed. Thus, ..gamma..-HCH induced platelet activation in a dose-dependent manner ADP, but not cyclooxygenase-dependent arachidonate metabolites, is involved in ..gamma..-HCH-induced aggregation, whereas, both appear to play a role in ..gamma..-HCH-induced release reaction.

  4. Factors Associated with Early Platelet Activation in Obese Children

    Science.gov (United States)

    García, Anel Gómez; Núñez, Guillermina García; Sandoval, Martha Eva Viveros; Castellanos, Sergio Gutierrez; Aguilar, Cleto Alvarez

    2014-01-01

    Objective To investigate the factors associated with platelet activation in obese children. Design Cross-sectional study. Setting Department of Pediatrics of Regional Hospital N∘ 1 of Mexican Institute of Social Security in Morelia, Michoacán, Mexico. Participants 79 obese and 64 non-obese children between the ages of 5 and 10 years. Main Outcomes Measures Obese children (body mass index [BMI] >85 in growth curves for Centers for Disease Control/National Center for Health Statistics), and the control group of 64 non-obese children (percentile <85), % body fat, platelet activation was assessed by sP-selectin. Other measures were leptin, uric acid (UA), von Willebrand Factor (vWF), plasminogen activator inhibitor (PAI-1), lipid profile, and glucose. Results Obese children displayed higher plasma sP-selectin, leptin, PAI-1, and vWF than non-obese children. In the univariate logistic regression analysis, leptin, vWF, UA, and high density lipoprotein (HDL), but not with PAI-1, were factors associated with platelet activation. By stepwise linear regression analysis adjusted by sex and age, the best predictor variables for platelet activation were leptin (β:0.381; t:4.665; P=0.0001), vWF (β:0.211; t:2.926; P=0.004), UA (β:0.166; t:2.146; P=0.034), and HDL (β:−0.215; t:−2.819; P=0.006). Conclusions Obese children have a higher risk of developing early platelet activation. Factors associated with platelet activation were Leptin, vWF, UA, and HDL. Further studies involving larger numbers of patients over a longer duration are needed to understand the possible molecular mechanism underlying the association between leptin, vWF, and UA and endothelial activation and/or endothelial damage/dysfunction in obese children and its influence in cardiovascular disease in adults. PMID:24415745

  5. Isolation and characterization of platelet-derived extracellular vesicles

    Directory of Open Access Journals (Sweden)

    Maria T. Aatonen

    2014-08-01

    Full Text Available Background: Platelet-derived extracellular vesicles (EVs participate, for example, in haemostasis, immunity and development. Most studies of platelet EVs have targeted microparticles, whereas exosomes and EV characterization under various conditions have been less analyzed. Studies have been hampered by the difficulty in obtaining EVs free from contaminating cells and platelet remnants. Therefore, we optimized an EV isolation protocol and compared the quantity and protein content of EVs induced by different agonists. Methods: Platelets isolated with iodixanol gradient were activated by thrombin and collagen, lipopolysaccharide (LPS or Ca2+ ionophore. Microparticles and exosomes were isolated by differential centrifugations. EVs were quantitated by nanoparticle tracking analysis (NTA and total protein. Size distributions were determined by NTA and electron microscopy. Proteomics was used to characterize the differentially induced EVs. Results: The main EV populations were 100–250 nm and over 90% were <500 nm irrespective of the activation. However, activation pathways differentially regulated the quantity and the quality of EVs, which also formed constitutively. Thrombogenic activation was the most potent physiological EV-generator. LPS was a weak inducer of EVs, which had a selective protein content from the thrombogenic EVs. Ca2+ ionophore generated a large population of protein-poor and unselectively packed EVs. By proteomic analysis, EVs were highly heterogeneous after the different activations and between the vesicle subpopulations. Conclusions: Although platelets constitutively release EVs, vesiculation can be increased, and the activation pathway determines the number and the cargo of the formed EVs. These activation-dependent variations render the use of protein content in sample normalization invalid. Since most platelet EVs are 100–250 nm, only a fraction has been analyzed by previously used methods, for example, flow cytometry. As

  6. Elevated Lipoprotein(A Impairs Platelet Radiolabeling Yield

    Directory of Open Access Journals (Sweden)

    Susanne Granegger

    2015-02-01

    Full Text Available Objectives: Platelet radiolabeling in clinical routine usually results in labeling efficiencies (LE above 80%. A variety of risk factors and clinical conditions are known to impair platelet labeling yield, among them elevated triglycerides and low-density lipoproteins. The potential influence of lipoprotein(a (Lp(a, an atherogenic lipoprotein particle containing a kringle subunit, which is widely found in the proteins of fibrinolysis pathway, has never been studied. Normal Lp(a levels range below 30 mg/ dl. The exact prevalence of elevated Lp(a is unknown, most likely ranging below 10%. Even more rare is an isolated elevation despite an otherwise normal lipoprotein profile. Methods: We examined the role of isolated elevated Lp(a (> 50 mg/dl, ranging up to 440 mg/dl compared to patients with normal lipid profile. Platelets were radiolabeled with in-111-oxine at 37 °C for 5 minutes using ISORBE-consensus methodology. Results: The findings indicate that already at levels below 100 mg/dl Lp(a decreases LE. LE assessment after cross-incubation of hyper-Lp(a platelets with normal Lp(a plasma and vice versa reveals that platelets rather than the plasmatic environment are responsible for the deterioration of labeling yield. This behavior already has been reported for elevated low-density lipoproteins. Apparently, the quantitative influence of LDL and Lp(a/mg is comparable. Plotting the sum of LDL and Lp(a versus LE reveals a clear significant negative correlation. Conclusion: As extremely elevated Lp(a, particularly above 150 mg/dl, may significantly impair labeling results. We therefore recommend to include extremely elevated Lp(a into the list of parameters, which should be known before performing radiolabeling of human platelets.

  7. Phorbol ester stimulates calcium sequestration in saponized human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, K.; Nachmias, V.T.

    1987-11-25

    When platelets are activated by agonists, calcium (Ca2+) is released from an intracellular storage site. Recent studies using fura-2 show that, after thrombin stimulation, the rise in free calcium is transient and returns to base-line levels in 2-3 min, while the transient following ADP stimulation lasts only 15-20 s. We reported previously that the phorbol ester 12,13-phorbol myristate acetate (PMA), added at nanomolar levels after thrombin, immediately accelerated the rate of return of calcium to the base line severalfold. In the present study, we used both intact and saponized platelets to determine whether this is due to stimulation of calcium sequestration. Using fura-2 and intact platelets, we found 1) that PMA stimulated the restoration of free Ca2+ levels after ADP as well as after thrombin, and 2) that H-7, an inhibitor of protein kinase C (Ca2+/phospholipid-dependent enzyme), slowed the return of Ca2+ to baseline levels. Using saponized platelets, we also found 3) that pretreatment of platelets with PMA before saponin treatment increased the ATP-dependent /sup 45/Ca2+ uptake 2-fold, with a half-maximal effect at 5 nm; 4) that most of the Ca2+ released by ionomycin or by myoinositol 1,4,5-trisphosphate; and 5) that a GTP-binding protein inhibitor, guanosine 5'-O-(2-thiodiphosphate), decreased basal or PMA-stimulated /sup 45/Ca2+ uptake in saponin-treated platelets. Our data suggest that activation of protein kinase C stimulates the sequestration of Ca2+ independently of cAMP or myoinositol 1,4,5-trisphosphate.

  8. Increased platelet expression of FcGammaRIIa and its potential impact on platelet reactivity in patients with end stage renal disease

    Directory of Open Access Journals (Sweden)

    Sobel Burton E

    2007-06-01

    Full Text Available Abstract Background Increased platelet reactivity has been implicated in cardiovascular disease – the major cause of death in patients with end stage renal disease (ESRD. FcGammaRIIA is a component of glycoprotein VI and Ib-IX-V that mediate activation of platelets by collagen and von Willebrand factor. To determine whether expression of FcGammaRIIA impacts platelet reactivity we quantified its expression and platelet reactivity in 33 patients with ESRD who were undergoing hemodialysis. Methods Blood samples were obtained from patients immediately before hemodialysis and before administration of heparin. Platelet expression of FcGammaRIIA and the activation of platelets in response to low concentrations of convulxin (1 ng/ml, selected to mimic effects of collagen, thrombin (1 nM, adenosine diphosphate (ADP, 0.2 uM, or platelet activating factor (PAF, 1 nM were determined with the use of flow cytometry in samples of whole blood anticoagulated with corn trypsin inhibitor (a specific inhibitor of Factor XIIa. Results Patients were stratified with respect to the median expression of FcGammaRIIA. Patients with high platelet expression of FcGammaRIIA exhibited 3-fold greater platelet reactivity compared with that in those with low expression in response to convulxin (p Conclusion Increased platelet reactivity in response to low concentrations of diverse agonists is associated with high expression of FcGammaRIIA and may contribute to an increased risk of thrombosis in patients with ESRD.

  9. Roles of thrombin and platelet membrane glycoprotein IIb/IIIa in platelet-subendothelial deposition after angioplasty in an ex vivo whole artery model

    International Nuclear Information System (INIS)

    Platelet deposition at the site of injury caused by balloon angioplasty is associated with acute closure and restenosis. In a new ex vivo whole artery angioplasty model, the authors examined the roles of thrombin inhibition with D-Phe-Pro-ArgCH2Cl (PPACK) and inhibition of the platelet membrane fibrinogen receptor glycoprotein IIb/IIIa (GPIIb/IIIa) with monoclonal antibody 7E3 on platelet deposition at the site of balloon injury. Fresh rabbit aortas were mounted in a perfusion chamber. One half of the mounted arterial segment was dilated with a standard angioplasty balloon catheter and the uninjured half served as the control segment. The vessels were perfused with human blood at physiological pressure and shear rates of 180-250 second-1 for 30 minutes. Platelet deposition was measured using 111In-labeled platelets and scanning electron microscopy. With heparin (2 units/ml) anticoagulation, 8.2 ± 2.2 x 10(6) platelets/cm2 were deposited at the site of balloon injury compared with 0.7 ± 0.2 x 10(6) platelets/cm2 on uninjured segments (p less than 0.02, n = 7). PPACK was tested at a concentration (10 microM) that totally inhibited platelet aggregation in response to thrombin. 7E3 was tested at a concentration (10 micrograms/ml) that totally inhibited platelet aggregation. Platelet deposition at the site of balloon injury was reduced 47% by PPACK and 70% by 7E3 compared with heparin. At shear rates seen in nonstenotic coronary arteries, PPACK and 7E3 are more effective than heparin in reducing platelet deposition at the site of balloon injury. The significant inhibition of platelet deposition by PPACK demonstrates the importance of heparin-resistant thrombin in platelet thrombus formation

  10. Effect of supine exercise on platelet aggregation and fibrinolytic activity

    DEFF Research Database (Denmark)

    Dag, B; Fornitz, Gitte Gleerup; Bak, A M;

    1994-01-01

    In 12 healthy young men, strenuous cycling exercise in the supine position, caused platelet aggregability to decrease and the ADP threshold to rise from 7.0 microM resting, to 9.5 exercising (P ... from 178 to 68 min, PAI-1 fell from 8.91 to 5.16 IU ml-1, and t-PA rose from 0.56 to 3.95 IU ml-1, all three values were significant to P exercise, it did not increase platelet activity as expected, but caused a modest increase...... of fibrinolytic activity. These results suggest that supine exercise will not affect the haemostatic system adversely....

  11. Activation of the Small GTPase Ral in Platelets

    OpenAIRE

    Wolthuis, Rob M. F.; Franke, Barbara; van Triest, Miranda; Bauer, Bettina; Cool, Robbert H.; Camonis, Jacques H.; Akkerman, Jan-Willem N.; Bos, Johannes L.

    1998-01-01

    Ral is a ubiquitously expressed Ras-like small GTPase which is abundantly present in human platelets. The biological function of Ral and the signaling pathway in which Ral is involved are largely unknown. Here we describe a novel method to measure Ral activation utilizing the Ral binding domain of the putative Ral effector RLIP76 as an activation-specific probe. With this assay we investigated the signaling pathway that leads to Ral activation in human platelets. We found that Ral is rapidly ...

  12. Bacterial contamination of platelet concentrates: pathogen detection and inactivation methods

    Directory of Open Access Journals (Sweden)

    Dana Védy

    2009-04-01

    Full Text Available Whereas the reduction of transfusion related viral transmission has been a priority during the last decade, bacterial infection transmitted by transfusion still remains associated to a high morbidity and mortality, and constitutes the most frequent infectious risk of transfusion. This problem especially concerns platelet concentrates because of their favorable bacterial growth conditions. This review gives an overview of platelet transfusion-related bacterial contamination as well as on the different strategies to reduce this problem by using either bacterial detection or inactivation methods.

  13. Stacking fault induced tunnel barrier in platelet graphite nanofiber

    Energy Technology Data Exchange (ETDEWEB)

    Lan, Yann-Wen, E-mail: chiidong@phys.sinica.edu.tw, E-mail: ywlan@phys.sinica.edu.tw; Chang, Yuan-Chih; Chang, Chia-Seng; Chen, Chii-Dong, E-mail: chiidong@phys.sinica.edu.tw, E-mail: ywlan@phys.sinica.edu.tw [Institute of Physics, Academia Sinica, Taipei 115, Taiwan (China); Chang, Wen-Hao [Institute of Physics, Academia Sinica, Taipei 115, Taiwan (China); Graduate Institute of Opto-Mechatronics, National Chung Cheng University, Chia-Yi 62102, Taiwan (China); Li, Yuan-Yao [Graduate Institute of Opto-Mechatronics, National Chung Cheng University, Chia-Yi 62102, Taiwan (China)

    2014-09-08

    A correlation study using image inspection and electrical characterization of platelet graphite nanofiber devices is conducted. Close transmission electron microscopy and diffraction pattern inspection reveal layers with inflection angles appearing in otherwise perfectly stacked graphene platelets, separating nanofibers into two domains. Electrical measurement gives a stability diagram consisting of alternating small-large Coulomb blockade diamonds, suggesting that there are two charging islands coupled together through a tunnel junction. Based on these two findings, we propose that a stacking fault can behave as a tunnel barrier for conducting electrons and is responsible for the observed double-island single electron transistor characteristics.

  14. Complement and platelets: Mutual interference in the immune network.

    Science.gov (United States)

    Speth, Cornelia; Rambach, Günter; Würzner, Reinhard; Lass-Flörl, Cornelia; Kozarcanin, Huda; Hamad, Osama A; Nilsson, Bo; Ekdahl, Kristina N

    2015-09-01

    In recent years, the view of platelets has changed from mere elements of hemostasis to immunological multitaskers. They are connected in manifold ways to other cellular and humoral components of the immune network, one of which is the complement system, a potent player in soluble innate immunity. Our article reviews the crucial and complex interplay between platelets and complement, focusing on mutual regulation of these two interaction partners by their respective molecular mechanisms. Furthermore, the putative relevance of these processes to infectious diseases, inflammatory conditions, and autoimmune disorders, as well as the treatment of patients with biomaterials is highlighted.

  15. Balneotherapy and platelet glutathione metabolism in type II diabetic patients

    Science.gov (United States)

    Ohtsuka, Yoshinori; Yabunaka, Noriyuki; Watanabe, Ichiro; Noro, Hiroshi; Agishi, Yuko

    1996-09-01

    Effects of balneotherapy on platelet glutathione metabolism were investigated in 12 type II (non-insulin-dependent) diabetic patients. Levels of the reduced form of glutathione (GSH) on admission were well correlated with those of fasting plasma glucose (FPG; r=0.692, P150 mg/dl), the value decreased ( Pmetabolism was partially improved by 4 weeks balneotherapy, an effect thought to be dependent on the control status of plasma glucose levels. It is suggested that balneotherapy is beneficial for patients whose platelet antioxidative defense system is damaged, such as those with diabetes mellitus and coronary heart disease.

  16. The Influence of Low Platelet Count on Whole Blood Aggregometry Assessed by Multiplate

    DEFF Research Database (Denmark)

    Stissing, Trine; Dridi, Nadia P; Ostrowski, Sisse R;

    2011-01-01

    The Multiplate, a whole blood (WB) platelet function test, has shown promising results identifying patients on antiplatelet therapy at increased risk of rethrombosis. In the present study, the influence of low platelet count on platelet aggregation was analyzed and compared with aggregation resul...

  17. Interindividual variation in platelets and the cardiovascular response to haemorrhage in the pig

    DEFF Research Database (Denmark)

    Zaar, Morten; Secher, Niels H; Gam, Christiane Marie Bourgin;

    2011-01-01

    The platelet count varies two-fold among healthy individuals. Considering the haemostatic role of platelets, this study evaluated the relation between cardiovascular and metabolic responses to uncontrolled haemorrhage and the pretrauma platelet count in pigs. A laceration liver injury was inflict...

  18. Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen

    DEFF Research Database (Denmark)

    Nieswandt, B; Brakebusch, C; Bergmeier, W;

    2001-01-01

    subsequent interactions with the activating platelet collagen receptor, glycoprotein VI (GPVI). Here we show that Cre/loxP-mediated loss of beta1 integrin on platelets has no significant effect on the bleeding time in mice. Aggregation of beta1-null platelets to native fibrillar collagen is delayed...

  19. Metabolic energy is required in human platelets at any stage during optical aggregation and secretion

    NARCIS (Netherlands)

    Akkerman, Jan Willem N.; Verhoeven, A.J.M.; Mommersteeg, M.E.

    1984-01-01

    The relationship between metabolic energy and platelet aggregation and secretion was investigated by sudden exhaustion of the cell energy content after these platelet responses had been initiated. In normal platelets, optical aggregation was at any stage susceptible to energy exhaustion, whereas sin

  20. PPARγ ligands decrease hydrostatic pressure-induced platelet aggregation and proinflammatory activity.

    Directory of Open Access Journals (Sweden)

    Fang Rao

    Full Text Available Hypertension is known to be associated with platelet overactivity, but the direct effects of hydrostatic pressure on platelet function remain unclear. The present study sought to investigate whether elevated hydrostatic pressure is responsible for platelet activation and to address the potential role of peroxisome proliferator-activated receptor-γ (PPARγ. We observed that hypertensive patients had significantly higher platelet volume and rate of ADP-induced platelets aggregation compared to the controls. In vitro, Primary human platelets were cultured under standard (0 mmHg or increased (120, 180, 240 mmHg hydrostatic pressure for 18 h. Exposure to elevated pressure was associated with morphological changes in platelets. Platelet aggregation and PAC-1 (the active confirmation of GPIIb/IIIa binding were increased, CD40L was translocated from cytoplasm to the surface of platelet and soluble CD40L (sCD40L was released into the medium in response to elevated hydrostatic pressure (180 and 240 mmHg. The PPARγ activity was up-regulated as the pressure was increased from 120 mmHg to 180 mmHg. Pressure-induced platelet aggregation, PAC-1 binding, and translocation and release of CD40L were all attenuated by the PPARγ agonist Thiazolidinediones (TZDs. These results demonstrate that platelet activation and aggregation are increased by exposure to elevated pressure and that PPARγ may modulate platelet activation induced by high hydrostatic pressure.

  1. Cost-effectiveness of pathogen inactivation for platelet transfusions in the Netherlands

    NARCIS (Netherlands)

    Postma, MJ; van Hulst, M; De Wolf, JTM; Botteman, M; Staginnus, U

    2005-01-01

    The objective of this study is to estimate cost-effectiveness of pathogen inactivation for platelet transfusions in the Netherlands. We used decision tree analysis to evaluate the cost-effectiveness of the addition of pathogen inactivation of pooled platelets to standard procedures for platelet tran

  2. Human platelet calmodulin-binding proteins: identification and Ca/sup 2 +/-dependent proteolysis upon platelet activation

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, R.W.; Tallant, E.A.; McManus, M.C.

    1987-05-19

    Calmodulin-binding proteins have been identified in human platelets by using Western blotting techniques and /sup 125/I-calmodulin. Ten distinct proteins of 245, 225, 175, 150, 90, 82 (2), 60, and 41 (2) kilodaltons (kDa) bound /sup 125/I-calmodulin in a Ca/sup 2 +/-dependent manner; the binding was blocked by ethylene glycol bis(..beta..-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), trifluoperazine, and nonradiolabeled calmodulin. Proteins of 225 and 90 kDa were labeled by antisera against myosin light chain kinase; 60- and 82-kDa proteins were labeled by antisera against the calmodulin-dependent phosphatase and caldesmon, respectively. The remaining calmodulin-binding proteins have not been identified. Calmodulin-binding proteins were degraded upon addition of Ca/sup 2 +/ to a platelet homogenate; the degradation could be blocked by either EGTA, leupeptin, or N-ethylmaleimide which suggests that the degradation was due to a Ca/sup 2 +/-dependent protease. Activation of intact platelets by thrombin, adenosine 5'-diphosphate, and collagen under conditions which promote platelet aggregation also resulted in limited proteolysis of calmodulin-binding proteins including those labeled with antisera against myosin light chain kinase and the calmodulin-dependent phosphatase. Activation by the Ca/sup 2 +/ ionophores A23187 and ionomycin also promoted degradation of the calmodulin-binding proteins in the presence of extracellular Ca/sup 2 +/. The data indicate that limited proteolysis of Ca/sup 2 +//calmodulin-regulated enzymes also occurs in the intact platelet and suggest that the proteolysis is triggered by an influx of extracellular Ca/sup 2 +/ associated with platelet aggregation.

  3. Increased platelet activation in early symptomatic versus asymptomatic carotid stenosis and relationship with microembolic status: Results from the Platelets And Carotid Stenosis (PACS) Study.

    LENUS (Irish Health Repository)

    Kinsella, Ja

    2013-04-26

    BACKGROUND: Cerebral microembolic signals (MES) may predict increased stroke risk in carotid stenosis. However, the relationship between platelet counts or platelet activation status and MES in symptomatic versus asymptomatic carotid stenosis has not been comprehensively assessed. SETTING: University teaching hospitals. METHODS: This prospective, pilot observational study assessed platelet counts and platelet activation status, and the relationship between platelet activation and MES in asymptomatic versus early (≤4 weeks after TIA\\/stroke) and late phase (≥3 months) symptomatic moderate or severe (≥50%) carotid stenosis patients. Full blood count measurements were performed, and whole blood flow cytometry was used to quantify platelet surface activation marker expression (CD62P and CD63) and circulating leucocyte-platelet complexes. Bilateral simultaneous transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed for 1 hour to classify patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic patients were compared with 46 symptomatic patients in the early phase, and 35 of these patients followed up to the late phase after symptom onset. The median platelet count (211 vs. 200 x 10(9) \\/L; p=0.03) and the median% lymphocyte-platelet complexes were higher in early symptomatic than asymptomatic patients (2.8 vs. 2.4%, p=0.001). The% lymphocyte-platelet complexes was higher in early symptomatic than asymptomatic patients with ≥70% carotid stenosis (p=0.0005), and in symptomatic patients recruited within 7 days of symptom onset (p=0.028). Complete TCD data were available in 25 asymptomatic and 31 early phase symptomatic, and 27 late phase symptomatic patients. 12% of asymptomatic versus 32% of early phase symptomatic (p=0.02) and 19% of late phase symptomatic patients (p=0.2) were MES-positive. Early symptomatic MES-negative patients had a higher% lymphocyte-platelet complexes than asymptomatic MES

  4. Mechanobiology of Platelets: Techniques to Study the Role of Fluid Flow and Platelet Retraction Forces at the Micro- and Nano-Scale

    Directory of Open Access Journals (Sweden)

    Nathan J. Sniadecki

    2011-12-01

    Full Text Available Coagulation involves a complex set of events that are important in maintaining hemostasis. Biochemical interactions are classically known to regulate the hemostatic process, but recent evidence has revealed that mechanical interactions between platelets and their surroundings can also play a substantial role. Investigations into platelet mechanobiology have been challenging however, due to the small dimensions of platelets and their glycoprotein receptors. Platelet researchers have recently turned to microfabricated devices to control these physical, nanometer-scale interactions with a higher degree of precision. These approaches have enabled exciting, new insights into the molecular and biomechanical factors that affect platelets in clot formation. In this review, we highlight the new tools used to understand platelet mechanobiology and the roles of adhesion, shear flow, and retraction forces in clot formation.

  5. External quality assessment of platelet disorder investigations: results of international surveys on diagnostic tests for dense granule deficiency and platelet aggregometry interpretation.

    Science.gov (United States)

    Hayward, Catherine P M; Moffat, Karen A; Plumhoff, Elizabeth; Timleck, Marnie; Hoffman, Suzanne; Spitzer, Ernie; Van Cott, Elizabeth M; Meijer, Piet

    2012-09-01

    The quality of platelet aggregation and dense granule deficiency testing is important for diagnosing platelet function disorders. After a successful pilot exercise on diagnosing platelet dense granule deficiency by electron microscopy (EM), the North American Specialized Coagulation Laboratory Association (NASCOLA) has launched regular external quality assurance (EQA) for dense granule EM, as well as for the interpretation of platelet aggregation findings. EQA records were analyzed to assess performance. For EM EQA, between 2009 and 2011, there was excellent performance in distinguishing normal from dense granule-deficient samples and good (>70%) agreement on classifying most electron dense structures in platelets. For aggregation EQA, some normal variants were misclassified and overall case interpretations were more acceptable for rare disorders than for common findings. NASCOLA experiences with these EQAs indicate that there is a need to improve the quality of platelet disorder evaluations. For aggregometry interpretations, deficits in performance could be addressed by translating guideline recommendations into practice.

  6. Sources of variability in platelet accumulation on type 1 fibrillar collagen in microfluidic flow assays.

    Directory of Open Access Journals (Sweden)

    Keith B Neeves

    Full Text Available Microfluidic flow assays (MFA that measure shear dependent platelet function have potential clinical applications in the diagnosis and treatment of bleeding and thrombotic disorders. As a step towards clinical application, the objective of this study was to measure how phenotypic and genetic factors, as well as experimental conditions, affect the variability of platelet accumulation on type 1 collagen within a MFA. Whole blood was perfused over type 1 fibrillar collagen at wall shear rates of 150, 300, 750 and 1500 s⁻¹ through four independent channels with a height of 50 µm and a width of 500 µm. The accumulation of platelets was characterized by the lag time to 1% platelet surface coverage (Lag(T, the rate of platelet accumulation (V(PLT, and platelet surface coverage (SC. A cohort of normal donors was tested and the results were correlated to plasma von Willebrand factor (VWF levels, platelet count, hematocrit, sex, and collagen receptors genotypes. VWF levels were the strongest determinant of platelet accumulation. VWF levels were positively correlated to V(PLT and SC at all wall shear rates. A longer Lag(T for platelet accumulation at arterial shear rates compared to venous shear rates was attributed to the time required for plasma proteins to adsorb to collagen. There was no association between platelet accumulation and hematocrit or platelet count. Individuals with the AG genotype of the GP6 gene had lower platelet accumulation than individuals with the AA genotype at 150 s⁻¹ and 300 s⁻¹. Recalcified blood collected into sodium citrate and corn trypsin inhibitor (CTI resulted in diminished platelet accumulation compared to CTI alone, suggesting that citrate irreversibly diminishes platelet function. This study the largest association study of MFA in healthy donors (n = 104 and will likely set up the basis for the determination of the normal range of platelet responses in this type of assay.

  7. Role of platelet plasma membrane Ca2+-ATPase in health and disease

    Institute of Scientific and Technical Information of China (English)

    William; L; Dean

    2010-01-01

    Platelets have essential roles in both health and disease. Normal platelet function is required for hemostasis.Inhibition of platelet function in disease or by pharmacological treatment results in bleeding disorders.On the other hand,hyperactive platelets lead to heart attack and stroke.Calcium is a major second messenger in platelet activation,and elevated intracellular calcium leads to hyperactive platelets.Elevated platelet calcium has been documented in hypertension and diabetes;both conditions increase the likelihood of heart attack and stroke. Thus,proper regulation of calcium metabolism in the platelet is extremely important.Plasma membrane Ca2+-ATPase(PMCA)is a major player in platelet calcium metabolism since it provides the only significant route for calcium efflux.In keeping with the important role of calcium in platelet function,PMCA is a highly regulated transporter.In human platelets,PMCA is activated by Ca2+/calmodulin,by cAMP-dependent phosphorylation and by calpain-dependent removal of the inhibitory peptide.It is inhibited by tyrosine phosphorylation and calpain-dependent proteolysis.In addition,the cellular location of PMCA is regulated by a PDZ-domain-dependent interaction with the cytoskeleton during platelet activation.Rapid regulation by phosphorylation results in changes in the rate of platelet activation,whereas calpain-dependent proteolysis and interaction with the cytoskeleton appears to regulate later events such as clot retraction.In hypertension and diabetes,PMCA expression is upregulated while activity is decreased, presumably due to tyrosine phosphorylation.Clearly,a more complete understanding of PMCA function in human platelets could result in the identification of new ways to control platelet function in disease states.

  8. Crocin prevents sesamol-induced oxidative stress and apoptosis in human platelets.

    Science.gov (United States)

    Thushara, Ram M; Hemshekhar, Mahadevappa; Paul, Manoj; Shanmuga Sundaram, Mahalingam; Shankar, Rohith L; Kemparaju, Kempaiah; Girish, Kesturu S

    2014-10-01

    Recent studies have reported the platelet proapoptotic propensity of plant-derived molecules such as, resveratrol, thymoquinone, andrographolide and gossypol. Meanwhile, there were also reports of phytochemicals such as cinnamtannin B1, which shows antiapoptotic effect towards platelets. Platelets are mainly involved in hemostasis, thrombosis and wound healing. However, altered platelet functions can have serious pathological outcomes that include cardiovascular diseases. Platelets are sensitive to external and internal stimuli including therapeutic and dietary components. The anuclear platelets do undergo apoptosis via mitochondrial pathway. However, exaggerated rate of platelet apoptosis could lead to thrombocytopenia and other bleeding disorders. The present study deals with ameliorative efficacy of crocin on sesamol-induced platelet apoptosis. The antiapoptotic property of crocin and the proapoptotic tendency of sesamol in platelets were previously demonstrated. Therefore, it was interesting to see how these two compounds would interact and wield their effects on human platelets. Crocin effectively inhibited sesamol-induced oxidative stress on platelets, which was evidenced by the measurement of endogenously generated reactive oxygen species, particularly hydrogen peroxide, and changes in thiol levels. Further, crocin abrogated sesamol-induced biochemical events of apoptosis in platelets, which include intracellular calcium mobilization, changes in mitochondrial membrane integrity, cytochrome c release, caspase activity and phosphatidylserine externalization. Even though sesamol has proapoptotic effects on platelets, its anti-platelet activity cannot be neglected. Thus, the study proposes that sesamol could be supplemented with crocin, an approach that could not only abolish the toxic effects of sesamol on platelets, but also enhance the quality of treatment due to their synergistic action.

  9. L-carnitine effectively improves the metabolism and quality of platelet concentrates during storage.

    Science.gov (United States)

    Deyhim, Mohammad Reza; Mesbah-Namin, Seyed Alireza; Yari, Fatemeh; Taghikhani, Mohammad; Amirizadeh, Naser

    2015-04-01

    Human platelets undergo structural and biochemical alternations during storage which are collectively called platelet storage lesion (PSL). PSL is characterized as metabolic and functionally changes. It causes decrease in platelet recovery and survival. Here, we evaluated the effect of L-carnitine (LC) on the metabolism, function, and mitochondrial metabolic activity of platelet during storage. Platelet-rich plasma was used to prepare platelet concentrate (PC) in Iranian Blood Transfusion Organization. For this purpose, ten PC bags from healthy donors were stored at 22 °C with gentle agitation in the presence or absence of LC. The effects of LC (15 mM) on the platelet quality were assessed by analyzing the levels of glucose, lactate, ATP, and lactate dehydrogenase (LDH) activity. Platelet aggregations induced by arachidonate and ristocetin were analyzed by aggregometer. Platelet mitochondrial melablolic activity was measured by tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay; platelet count and mean platelet volume were also determined by a hematology analyzer during 5 days of PC storage. The results indicated that LC could significantly decrease lactate concentration and glucose consumption accompanied with the increased oxygen consumption in stored PC. LDH activity also less significantly increased in LC-treated PC on days 2 and 5 of storage. Platelet aggregation in response to the ristocetin and arachidonate was significantly higher in LC-treated PC than that in untreated PC on day 5 of storage. Finally, platelet mitochondrial metabolic activity less significantly decreased in LC-treated PC compared to the control group on days 2 and 5 of storage. It seems that LC would be a good additive to reduce PSL and improve the platelet metabolism and quality of the stored PC for platelet transfusion therapy.

  10. Time-dependent inhibitory effects of cGMP-analogues on thrombin-induced platelet-derived microparticles formation, platelet aggregation, and P-selectin expression.

    Science.gov (United States)

    Nygaard, Gyrid; Herfindal, Lars; Kopperud, Reidun; Aragay, Anna M; Holmsen, Holm; Døskeland, Stein Ove; Kleppe, Rune; Selheim, Frode

    2014-07-01

    In platelets, nitric oxide (NO) activates cGMP/PKG signalling, whereas prostaglandins and adenosine signal through cAMP/PKA. Cyclic nucleotide signalling has been considered to play an inhibitory role in platelets. However, an early stimulatory effect of NO and cGMP-PKG signalling in low dose agonist-induced platelet activation have recently been suggested. Here, we investigated whether different experimental conditions could explain some of the discrepancy reported for platelet cGMP-PKG-signalling. We treated gel-filtered human platelets with cGMP and cAMP analogues, and used flow cytometric assays to detect low dose thrombin-induced formation of small platelet aggregates, single platelet disappearance (SPD), platelet-derived microparticles (PMP) and thrombin receptor agonist peptide (TRAP)-induced P-selectin expression. All four agonist-induced platelet activation phases were blocked when platelets were costimulated with the PKG activators 8-Br-PET-cGMP or 8-pCPT-cGMP and low-doses of thrombin or TRAP. However, extended incubation with 8-Br-PET-cGMP decreased its inhibition of TRAP-induced P-selectin expression in a time-dependent manner. This effect did not involve desensitisation of PKG or PKA activity, measured as site-specific VASP phosphorylation. Moreover, PKG activators in combination with the PKA activator Sp-5,6-DCL-cBIMPS revealed additive inhibitory effect on TRAP-induced P-selectin expression. Taken together, we found no evidence for a stimulatory role of cGMP/PKG in platelets activation and conclude rather that cGMP/PKG signalling has an important inhibitory function in human platelet activation.

  11. Effect of Composite Salvia Injection on Platelet Parameters in Children with Anaphylactoid Purpura

    Institute of Scientific and Technical Information of China (English)

    谢雪兰; 寇素茹; 许月红; 李朝英

    2009-01-01

    Objective:To explore the effect of composite salvia injection(CSI) on platelet parameters in children with anaphylactoid purpura(AP) and its clinical significance.Methods:One hundred and fifty children with AP were assigned to two groups,80 in Group A and 70 in Group B.They were treated,respectively,with conventional therapy only or conventional therapy combined with CSI.Their platelet parameters,including blood platelet count(BPC),mean platelet volume(MPV),platelet distribution width(PDW) and plateletcr...

  12. Prediction of bleeding and prophylactic platelet transfusions in cancer patients with thrombocytopenia

    DEFF Research Database (Denmark)

    Vinholt, Pernille J; Alnor, Anne; Nybo, Mads;

    2016-01-01

    platelet transfusion within 30 days were registered. Of 197 patients enrolled, 56 (28%) experienced bleeding. In multivariate analyses, predictors of bleeding were infection (adjusted odds ratio (OR) = 2.65 and 95% confidence interval (95% CI) 1.04-6.74); treatment with platelet inhibitors, heparin...... platelet transfusion but not bleeding. Bleeding risk factors were previous haematuria or gastrointestinal bleeding, infection, antiplatelet or anticoagulant treatment, high urea nitrogen, low haemoglobin or high creatinine.......Studies on markers for bleeding risk among thrombocytopenic cancer patients are lacking. This prospective observational cohort study investigated whether platelet parameters and a standardised bleeding questionnaire predicted bleeding or prophylactic platelet transfusions in patients with cancer...

  13. ROLE OF PLATELET TRANSFUSIONS IN DENGUE HEMORRHAGIC FEVER- 6 MONTHS REPORT

    Directory of Open Access Journals (Sweden)

    Geeta

    2012-08-01

    Full Text Available ABSTRACT: BACKGROUND: Allogenic platelet transfusion plays a major role in the management of thrombocytopenia. The study includes details of pla telet transfusion over a period of 6 months from January-2011 to June-2011 at blood bank of Gan dhi Hospital. Total number of patients who received were 487 and proportionate use of total un its of RDP (Random Donor Platelets issued from blood bank were as follows; dengue hemorrhagic fever (38% and remaining for acute leukemia (12%, Aplastic anemia (10%, sepsis (10% , DIC (Disseminated Intravascular Coagulation (10%, cardiac surgery (10%. In dengu e hemorrhagic fever, correlation of platelet count with platelet transfusion and platelet increm ent have been evaluated.

  14. Blood Platelet Production: Optimization by Dynamic Programming and Simulation

    NARCIS (Netherlands)

    Haijema, R.; Wal, van der J.; Dijk, van N.M.

    2007-01-01

    Blood platelets are precious, as voluntarily supplied by donors, and highly perishable, with limited lifetimes of 5¿7 days. Demand is highly variable and uncertain. A practical production and inventory rule is strived for that minimizes shortages and spill. The demand and production are periodic, as

  15. SPECIFIC ASPECTS OF INTERACTION OF PLATELETS WITH THE HEPARINIZED MATERIALS

    Directory of Open Access Journals (Sweden)

    E.A. Nemets

    2012-01-01

    Full Text Available Comparative analysis of anticoagulant nature on medical materials testing was done. It was found that change of citrate by heparin is accompanied by significant changes in platelet adhesion and activation. This results allowed us to arrive at a conclusion about reasonability of heparin usage as anticoagulant in in vitro testing. 

  16. Platelets--an important element of the immune system.

    Science.gov (United States)

    Trzeciak-Ryczek, A; Tokarz-Deptuła, B; Deptuła, W

    2013-01-01

    Platelets are anucleate cells derived from the megakaryocyte series, and have long been considered only as cells responsible for coagulation and the fibrinolysis process. However, recently more data shows that they are also effector cells in the inflammatory response and important elements of the immunological response. Platelets store and release many biologically active substances, including growth factors, cytokines and chemokines (tab. 1), which actively affect i.a. elements of the immune system, and thus become regulators of immunity and mediators of inflammatory response. Their impact on the immune system cells is also associated with the induction of leucocytes and progenitor cells to the site of pathogen permeation or vascular injury inflow, as well as endothelial cells. Interacting with neutrophils, monocytes and lymphocytes, they not only activate them, but also form platelet-leukocyte aggregates that immobilise pathogens and prevent their spreading. Furthermore, platelets are capable of absorbing pathogens, affecting anti-infection immunity of the system. It is also assumed that the presence of receptors on their surface, such as Toll-like receptors (TLRs), affects their initiation and activity of the immunological response.

  17. Cystic fibrosis heterozygotes do not have increased platelet activation

    DEFF Research Database (Denmark)

    Tarnow, Inge; Michelson, Alan D.; Frelinger III, Andrew L.;

    2007-01-01

    Introduction: We have previously demonstrated platelet hyperreactivity in cystic fibrosis (CF) patients. Carriers of one CF m utation (heterozygotes) have been shown to have abnormalities related to the presence of only one-half the normal amount of CF transmembrane conductance regulator protein...

  18. The effects of osmotic stress on human platelets.

    Science.gov (United States)

    Armitage, W J; Parmar, N; Hunt, C J

    1985-05-01

    The effect of osmotic stress on human platelets was investigated at 0, 25, and 37 degrees C. The osmolality of the suspending plasma was decreased by adding water or increased by adding sodium chloride or sucrose. After 5 min, isotonicity was restored by dilution with an excess of isotonic phosphate-buffered saline. After centrifugation, the platelets were resuspended in autologous plasma and then incubated for 1 hr at 37 degrees C before assaying the active transport of 5-hydroxytryptamine (5-HT) and the hypotonic stress response. Anisosmotic conditions had a greater effect on the extent of volume reversal in the hypotonic stress test than on 5-HT uptake. At 25 degrees C, only moderate degrees of hypotonicity (0.25 osmol/kg) or hypertonicity (0.59 osmol/kg) were sufficient to depress the hypotonic stress response. In general, platelets tolerated departures from isotonic conditions better at 0 degree C than at the higher temperatures. Furthermore, at 0 and 25 degrees C approximately equiosmolal concentrations of sucrose and sodium chloride depressed the hypotonic stress response to similar extents, but at 37 degrees C high osmolalities (greater than 2 osmol/kg) were tolerated better when the additive was sucrose than when it was sodium chloride. Platelets shrank when subjected to hyperosmotic conditions, but their discoid shape and the peripheral band of microtubules were maintained. PMID:3980588

  19. Devitrification of the glassy state in suspensions of charged platelets

    NARCIS (Netherlands)

    Mourad, M.C.D.; Verhoeff, A.A.; Belov, D.V.; Petukhov, A.V.; Lekkerkerker, H.N.W.

    2009-01-01

    Colloidal suspensions of charged gibbsite platelets at salt concentrations of 10−2 M and below and with a sufficiently high particle concentration form a kinetically arrested, glassy state. We study the evolution of the glassy state in suspensions of three different gibbsite systems. Despite differe

  20. Platelet-Rich Plasma for Frozen Shoulder: A Case Report

    Directory of Open Access Journals (Sweden)

    Hamidreza Aslani

    2016-01-01

    Full Text Available Frozen shoulder is a glenohumeral joint disorder that perturbs movement because of adhesion and the existence of fibrosis in the shoulder capsule. Platelet-rich plasma can produce collagen and growth factors, which increases stem cells and consequently enhances the healing. To date, there is no evidence regarding the effectiveness of platelet-rich plasma in frozen shoulder. A 45-year-old man with shoulder adhesive capsulitis volunteered for this treatment. He underwent two consecutive platelet-rich plasma injections at the seventh and eighth month after initiation of symptoms. We measured pain, function, and ROM by the visual analogue scale (VAS, and scores from the Disabilities of the Arm, Shoulder and Hand (DASH questionnaire and goniometer; respectively. After the first injection, the patient reported 60% improvement regarding diurnal shoulder pain, and no night pains. Also, two-fold improvement for ROM and more than 70% improvement for function were reported. This study suggests the use of platelet-rich plasma in frozen shoulder to be tested in randomized trials.

  1. Antithrombotic activity of Vitis labrusca extract on rat platelet aggregation.

    Science.gov (United States)

    Kwon, Se-Uk; Lee, Hoon-Yeon; Xin, Mingjie; Ji, Su-Jeong; Cho, Hyoung-Kwon; Kim, Dae-Sung; Kim, Dae-Ki; Lee, Young-Mi

    2016-03-01

    Vitis labrusca is a grapevine that has antioxidant, neuroprotective, hepatoprotective, and anticarcinogenic activity. However, the antithrombotic effect of Vitis labrusca leaves on platelets is yet to be ascertained. We investigated the inhibitory effect of V. labrusca leaf extract (VLE) on platelet aggregation in vitro and ex vivo. The thromboxane B2 (TXB2) and serotonin concentrations were measured by ELISA. The flavonoids content was measured by ultraperformance liquid chromatography (UPLC). The antithrombotic activity of VLE was evaluated using various agonists in vitro. VLE strongly inhibited adenosine diphosphate (ADP)-induced platelet aggregation. In rats, VLE treatment (100 mg/kg) reduced ADP-stimulated platelet aggregation, without affecting tail bleeding and coagulation time. Moreover, VLE significantly suppressed TXB2 and serotonin secretion. UPLC analysis indicated that VLE contains quercetin, isorhamnetin, and rutin. Our results indicate that VLE possesses antiplatelet activity via the suppression of TXB2 and serotonin, without affecting bleeding. Further, we identified the flavonoids present in VLE. Thus, VLE may be a potential agent for the prevention of cardiovascular diseases. PMID:26340455

  2. Platelet count kinetics following interruption of antiretroviral treatment

    DEFF Research Database (Denmark)

    Zetterberg, Eva; Neuhaus, Jacqueline; Baker, Jason V;

    2013-01-01

    To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow-up an......-up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART....

  3. Hemostatic resuscitation with plasma and platelets in trauma

    DEFF Research Database (Denmark)

    Johansson, Pär I; Oliveri, Roberto S; Ostrowski, Sisse R

    2012-01-01

    in an immediate and sustained manner as part of an early massive transfusion protocol has been introduced. The aim of the present review was to investigate the potential effect on survival of proactive administration of plasma and/or platelets (PLT) in trauma patients with massive bleeding....

  4. Platelets from Asthmatic Individuals Show Less Reliance on Glycolysis.

    Science.gov (United States)

    Xu, Weiling; Cardenes, Nayra; Corey, Catherine; Erzurum, Serpil C; Shiva, Sruti

    2015-01-01

    Asthma, a chronic inflammatory airway disease, is typified by high levels of TH2-cytokines and excessive generation of reactive nitrogen and oxygen species, which contribute to bronchial epithelial injury and airway remodeling. While immune function plays a major role in the pathogenesis of the disease, accumulating evidence suggests that altered cellular metabolism is a key determinant in the predisposition and disease progression of asthma. Further, several studies demonstrate altered mitochondrial function in asthmatic airways and suggest that these changes may be systemic. However, it is unknown whether systemic metabolic changes can be detected in circulating cells in asthmatic patients. Platelets are easily accessible blood cells that are known to propagate airway inflammation in asthma. Here we perform a bioenergetic screen of platelets from asthmatic and healthy individuals and demonstrate that asthmatic platelets show a decreased reliance on glycolytic processes and have increased tricarboxylic acid cycle activity. These data demonstrate a systemic alteration in asthma and are consistent with prior reports suggesting that oxidative phosphorylation is more efficient asthmatic individuals. The implications for this potential metabolic shift will be discussed in the context of increased oxidative stress and hypoxic adaptation of asthmatic patients. Further, these data suggest that platelets are potentially a good model for the monitoring of bioenergetic changes in asthma. PMID:26147848

  5. Platelets from Asthmatic Individuals Show Less Reliance on Glycolysis.

    Directory of Open Access Journals (Sweden)

    Weiling Xu

    Full Text Available Asthma, a chronic inflammatory airway disease, is typified by high levels of TH2-cytokines and excessive generation of reactive nitrogen and oxygen species, which contribute to bronchial epithelial injury and airway remodeling. While immune function plays a major role in the pathogenesis of the disease, accumulating evidence suggests that altered cellular metabolism is a key determinant in the predisposition and disease progression of asthma. Further, several studies demonstrate altered mitochondrial function in asthmatic airways and suggest that these changes may be systemic. However, it is unknown whether systemic metabolic changes can be detected in circulating cells in asthmatic patients. Platelets are easily accessible blood cells that are known to propagate airway inflammation in asthma. Here we perform a bioenergetic screen of platelets from asthmatic and healthy individuals and demonstrate that asthmatic platelets show a decreased reliance on glycolytic processes and have increased tricarboxylic acid cycle activity. These data demonstrate a systemic alteration in asthma and are consistent with prior reports suggesting that oxidative phosphorylation is more efficient asthmatic individuals. The implications for this potential metabolic shift will be discussed in the context of increased oxidative stress and hypoxic adaptation of asthmatic patients. Further, these data suggest that platelets are potentially a good model for the monitoring of bioenergetic changes in asthma.

  6. Platelet P2 receptors: from curiosity to clinical targets.

    Science.gov (United States)

    Cusack, N J; Hourani, S M

    2000-07-01

    Adenosine 5'-diphosphate (ADP) is a paracrine mediator that activates human blood platelets, causing them to become adhesive and thereby contributing to their role in hemostasis. The actions of ADP were initially thought to be mediated by a unique ADP receptor termed P2(T) found only on platelets and antagonized by ATP, but it appears that at least two P2Y receptor subtypes are involved, a P2Y(1) receptor linked in some way to control of intracellular-free calcium levels and another P2Y receptor linked via an inhibitory G protein to adenylate cyclase. In addition, the presence of excitatory P2X(1) receptors that mediate the influx of monovalent and divalent cations in response to both ADP and ATP has been demonstrated. The precise contribution that each of these P2 receptors make to the overall phenomena associated with platelet aggregation, adhesion and hemostasis is yet to be defined. Antithrombotic agents that interfere with the actions of ADP are marketed, and P2 receptor antagonists are entering clinical trials for acute treatments of thrombosis. This review seeks to summarize the present state of knowledge of platelet P2 receptor pharmacology and therapeutics.

  7. Role of dystrophins and utrophins in platelet adhesion process.

    Science.gov (United States)

    Cerecedo, Doris; Mondragón, Ricardo; Cisneros, Bulmaro; Martínez-Pérez, Francisco; Martínez-Rojas, Dalila; Rendón, Alvaro

    2006-07-01

    Platelets are crucial at the site of vascular injury, adhering to the sub-endothelial matrix through receptors on their surface, leading to cell activation and aggregation to form a haemostatic plug. Platelets display focal adhesions as well as stress fibres to contract and facilitate expulsion of growth and pro-coagulant factors contained in the granules and to constrict the clot. The interaction of F-actin with different actin-binding proteins determines the properties and composition of the focal adhesions. Recently, we demonstrated the presence of dystrophin-associated protein complex corresponding to short dystrophin isoforms (Dp71d and Dp71) and the uthophin gene family (Up400 and Up71), which promote shape change, adhesion, aggregation, and granule centralisation. To elucidate participation of both complexes during the platelet adhesion process, their potential association with integrin beta-1 fraction and the focal adhesion system (alpha-actinin, vinculin and talin) was evaluated by immunofluorescence and immunoprecipitation assays. It was shown that the short dystrophin-associated protein complex participated in stress fibre assembly and in centralisation of cytoplasmic granules, while the utrophin-associated protein complex assembled and regulated focal adhesions. The simultaneous presence of dystrophin and utrophin complexes indicates complementary structural and signalling mechanisms to the actin network, improving the platelet haemostatic role.

  8. Phase behavior of hard colloidal platelets using free energy calculations

    NARCIS (Netherlands)

    Marechal, M.A.T.; Cuetos, A.; Martínez-Haya, B.; Dijkstra, M.

    2011-01-01

    We investigate the phase behavior of a model for colloidal hard platelets and rigid discotic molecules: oblate hard spherocylinders (OHSC). We perform free energy calculations using Monte Carlo simulations to map out the phase diagram as a function of the aspect ratio L/D of the particles. The phase

  9. Reticulated platelets interfere with flow cytometric reticulocyte counts.

    Science.gov (United States)

    Ivory, K; Sarria, B; Fairweather-Tait, S J; Hughes, D A

    2007-10-01

    As part of an iron absorption study, we needed to accurately count reticulocytes in the peripheral blood of healthy human volunteers before measuring their enrichment with stable iron isotopes given in an oral dose. Recent studies have suggested the usefulness of reticulocyte counting by flow cytometry, through a combination of differential light scatter and measurement of the stoichiometric binding of thiazole orange (TO) to RNA within the maturing erythrocyte. Using this method we set out to improve the precision of our quantitative analysis by counting more cells, as reticulocytes normally comprise <2% of the red cell population. To ensure exclusion of other cell types, we identified WBCs and platelets with CD16+CD45- allophycocyanin and CD61- phycoerythrin, respectively. After removal of CD16(+) CD45(+) TO(+) WBCs and CD61(+) TO(-) platelets from analysis, the remaining cells were a combination of CD61(-) TO(-) erythrocytes, CD61(-) TO(+) reticulocytes and CD61(+) TO(+) reticulated platelets. Reticulocyte counts were lower after exclusion of CD61(+) TO(+) cells from analysis. They were similarly lower when erythrocyte precursors were positively identified through their glycophorin A expression and TO uptake. We conclude that it is necessary to exclude reticulated platelets from flow cytometric reticulocyte analysis. PMID:17824916

  10. New gene functions in megakaryopoiesis and platelet formation

    NARCIS (Netherlands)

    Gieger, Christian; Radhakrishnan, Aparna; Cvejic, Ana; Tang, Weihong; Porcu, Eleonora; Pistis, Giorgio; Serbanovic-Canic, Jovana; Elling, Ulrich; Goodall, Alison H.; Labrune, Yann; Lopez, Lorna M.; Maegi, Reedik; Meacham, Stuart; Okada, Yukinori; Pirastu, Nicola; Sorice, Rossella; Teumer, Alexander; Voss, Katrin; Zhang, Weihua; Ramirez-Solis, Ramiro; Bis, Joshua C.; Ellinghaus, David; Goegele, Martin; Hottenga, Jouke-Jan; Langenberg, Claudia; Kovacs, Peter; O'Reilly, Paul F.; Shin, So-Youn; Esko, Toenu; Hartiala, Jaana; Kanoni, Stavroula; Murgia, Federico; Parsa, Afshin; Stephens, Jonathan; van der Harst, Pim; van der Schoot, C. Ellen; Allayee, Hooman; Attwood, Antony; Balkau, Beverley; Bastardot, Francois; Basu, Saonli; Baumeister, Sebastian E.; Biino, Ginevra; Bomba, Lorenzo; Bonnefond, Amelie; Cambien, Francois; Chambers, John C.; Cucca, Francesco; D'Adamo, Pio; Davies, Gail; de Boer, Rudolf A.; de Geus, Eco J. C.; Doering, Angela; Elliott, Paul; Erdmann, Jeanette; Evans, David M.; Falchi, Mario; Feng, Wei; Folsom, Aaron R.; Frazer, Ian H.; Gibson, Quince D.; Glazer, Nicole L.; Hammond, Chris; Hartikainen, Anna-Liisa; Heckbert, Susan R.; Hengstenberg, Christian; Hersch, Micha; Illig, Thomas; Loos, Ruth J. F.; Jolley, Jennifer; Khaw, Kay Tee; Kuehnel, Brigitte; Kyrtsonis, Marie-Christine; Lagou, Vasiliki; Lloyd-Jones, Heather; Lumley, Thomas; Mangino, Massimo; Maschio, Andrea; Mateo Leach, Irene; McKnight, Barbara; Memari, Yasin; Mitchell, Braxton D.; Montgomery, Grant W.; Nakamura, Yusuke; Nauck, Matthias; Navis, Gerjan; Noethlings, Ute; Nolte, Ilja M.; Porteous, David J.; Pouta, Anneli; Pramstaller, Peter P.; Pullat, Janne; Ring, Susan M.; Rotter, Jerome I.; Ruggiero, Daniela; Ruokonen, Aimo; Sala, Cinzia; Samani, Nilesh J.; Sambrook, Jennifer; Schlessinger, David; Schreiber, Stefan; Schunkert, Heribert; Scott, James; Smith, Nicholas L.; Snieder, Harold; Starr, John M.; Stumvoll, Michael; Takahashi, Atsushi; Tang, W. H. Wilson; Taylor, Kent; Tenesa, Albert; Thein, Swee Lay; Toenjes, Anke; Uda, Manuela; Ulivi, Sheila; van Veldhuisen, Dirk J.; Visscher, Peter M.; Voelker, Uwe; Wichmann, H-Erich; Wiggins, Kerri L.; Willemsen, Gonneke; Yang, Tsun-Po; Zhao, Jing Hua; Zitting, Paavo; Bradley, John R.; Dedoussis, George V.; Gasparini, Paolo; Hazen, Stanley L.; Metspalu, Andres; Pirastu, Mario; Shuldiner, Alan R.; van Pelt, L. Joost; Zwaginga, Jaap-Jan; Boomsma, Dorret I.; Deary, Ian J.; Franke, Andre; Froguel, Philippe; Ganesh, Santhi K.; Jarvelin, Marjo-Riitta; Martin, Nicholas G.; Meisinger, Christa; Psaty, Bruce M.; Spector, Timothy D.; Wareham, Nicholas J.; Akkerman, Jan-Willem N.; Ciullo, Marina; Deloukas, Panos; Greinacher, Andreas; Jupe, Steve; Kamatani, Naoyuki; Khadake, Jyoti; Kooner, Jaspal S.; Penninger, Josef; Prokopenko, Inga; Stemple, Derek; Toniolo, Daniela; Wernisch, Lorenz; Sanna, Serena; Hicks, Andrew A.; Rendon, Augusto; Ferreira, Manuel A.; Ouwehand, Willem H.; Soranzo, Nicole

    2011-01-01

    Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a

  11. Prolactin does not affect human platelet aggregation or secretion

    NARCIS (Netherlands)

    A.Q. Reuwer; R. Nieuwland; I. Fernandez; V. Goffin; C.M. van Tiel; M.C.L. Schaap; R.J. Berckmans; J.J.P. Kastelein; M.T.B. Twickler

    2009-01-01

    Platelets play an important role in the development of plaque formation and in the events after rupture of the atherosclerotic plaque, leading to atherothrombosis. Multiple hormones, either in excess or when deficient, are involved in the development of atherothrombotic disease, but, to which extent

  12. Clay platelet partition within polymer blend nanocomposite films by EFTEM.

    Science.gov (United States)

    Linares, Elisângela M; Rippel, Márcia M; Galembeck, Fernando

    2010-12-01

    Transmission electron microscopy (TEM) is the main technique used to investigate the spatial distribution of clay platelets in polymer nanocomposites, but it has not often been successfully used in polymer blend nanocomposites because the high contrast between polymer phases impairs the observation of clay platelets. This work shows that electron spectral imaging in energy-filtered TEM (EFTEM) in the low-energy-loss spectral crossover region allows the observation of platelets on a clear background. Separate polymer domains are discerned by imaging at different energy losses, above and below the crossover energy, revealing the material morphology. Three blends (natural rubber [NR]/poly(styrene-butyl acrylate) [P(S-BA)], P(S-BA)/poly(vinyl chloride) [PVC], and NR/starch) were studied in this work, showing low contrast between the polymer phases in the 40-60 eV range. In the NR/P(S-BA) and P(S-BA)/PVC blend nanocomposites, the clay platelets accumulate in the P(S-BA) phase, while in the P(S-BA)/PVC nanocomposites, clay is also found at the interfaces. In the NR/starch blend, clay concentrates at the interface, but it also penetrates the two polymer phases. These observations reveal that nanostructured soft materials can display complex morphochemical patterns that are discerned thanks to the ability of EFTEM to produce many contrast patterns for the same sample. PMID:21117636

  13. Correlation between increased platelet ADP aggregability and silent brain infarcts

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate the correlation between platelet aggregability and silent brain infarcts. The study subjects were 445 people (264 men, 181 women; mean age, 53±14 years) with no neurologic signs, history of brain tumor, trauma, cerebrovascular disease, or antiplatelet medications. Adenosine diphosphate (ADP)-induced platelet aggregation was measured by the aggregation-size analytic method. Platelet aggregability was classified into 9 classes. The presence of headache/vertigo, hypertension, diabetes mellitus, hyperlipidemia, or smoking was elicited by questioning or blood sampling. A head MRI scan was performed, and if marked atherosclerosis or obvious stenosis in the intracranial vessels was detected, it was defined as a positive MR angiography (MRA) finding. Silent brain infarcts were detected in 26.3% of subjects. Hyperaggregability defined as that above class 6, 7, and 8 was present in 43.8%, 30.8%, and 15.7% of subjects, respectively. The risk factors for silent brain infarcts by multiple logistic regression analysis were aging, hypertension, positive MRA findings, and hyperaggregability. Platelet ADP hyperaggregability might be a risk factor for silent brain infarcts. (author)

  14. Effects of the breed, sex and age on cellular content and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel

    OpenAIRE

    Giraldo Carlos E; López Catalina; Álvarez María E; Samudio Ismael J; Prades Marta; Carmona Jorge U

    2013-01-01

    Abstract Background There is no information on the effects of the breed, gender and age on the cellular content and growth factor (GF) release from equine pure-platelet rich plasma (P-PRP) and pure-platelet rich gel (P-PRG). The objectives of this study were: 1) to compare the cellular composition of P-PRP with whole blood and platelet poor plasma (PPP); 2) to compare the concentration of transforming GF beta 1 (TGF-β1) and platelet derived GF isoform BB (PDGF-BB) between P-PRP treated with n...

  15. Patients with previous definite stent thrombosis have a larger fraction of immature platelets and a reduced antiplatelet effect of aspirin

    DEFF Research Database (Denmark)

    Würtz, Morten; Grove, Erik; Wulff, Lise Nielsen;

    turnover. Key Words: aspirin; immature platelets; platelet aggregation; platelet function tests; stent thrombosis Abbreviations: ARU, aspirin reaction units; AU, aggregation units; BMS, bare-metal stent(s); DES, drug-eluting stent(s); IPF, immature platelet fraction; MEA, multiple electrode aggregometry...

  16. RhoA is essential for maintaining normal megakaryocyte ploidy and platelet generation.

    Directory of Open Access Journals (Sweden)

    Aae Suzuki

    Full Text Available RhoA plays a multifaceted role in platelet biology. During platelet development, RhoA has been proposed to regulate endomitosis, proplatelet formation, and platelet release, in addition to having a role in platelet activation. These processes were previously studied using pharmacological inhibitors in vitro, which have potential drawbacks, such as non-specific inhibition or incomplete disruption of the intended target proteins. Therefore, we developed a conditional knockout mouse model utilizing the CRE-LOX strategy to ablate RhoA, specifically in megakaryocytes and in platelets to determine its role in platelet development. We demonstrated that deleting RhoA in megakaryocytes in vivo resulted in significant macrothrombocytopenia. RhoA-null megakaryocytes were larger, had higher mean ploidy, and exhibited stiff membranes with micropipette aspiration. However, in contrast to the results observed in experiments relying upon pharmacologic inhibitors, we did not observe any defects in proplatelet formation in megakaryocytes lacking RhoA. Infused RhoA-null megakaryocytes rapidly released platelets, but platelet levels rapidly plummeted within several hours. Our evidence supports the hypothesis that changes in membrane rheology caused infused RhoA-null megakaryocytes to prematurely release aberrant platelets that were unstable. These platelets were cleared quickly from circulation, which led to the macrothrombocytopenia. These observations demonstrate that RhoA is critical for maintaining normal megakaryocyte development and the production of normal platelets.

  17. Omic approaches to quality biomarkers for stored platelets: are we there yet?

    Science.gov (United States)

    Kulkarni, Sandhya; Kannan, Meganathan; Atreya, Chintamani D

    2010-07-01

    At present, there is no single biomarker that serves as the "gold standard" predictive of the quality of stored platelets used for transfusion. Some of the measurable features of platelets such as morphology, biochemical status, physiologic response to osmotic stress and agonist-induced changes, and measurement of process-associated activation indicators of platelets are considered useful in assessing the in vitro quality of stored platelets. Such in vitro measurements combined with in vivo survival estimations using radiolabeled platelets in healthy volunteers provide reasonable estimates of in vivo platelet function after transfusion. Thus, the current practice of estimating the quality and functional aspects of ex vivo stored platelets involves utilization of a battery of tests that dates back to pre-omic era. On the other hand, during the last decade, seminal discoveries have been made in platelet molecular and cell biology by using "omic"-based approaches such as proteomics, genomics, and transcriptomics. Can we mobilize some of these discoveries toward developing reliable quality biomarkers for stored platelets? To address this topic, we briefly review current practices and provide insights into some of the omic approaches that could be helpful in identifying quality storage biomarkers of platelets in the near future. We also briefly discuss here some of the challenges in using proteomic approaches and advantages of using one of the transcriptomics approaches toward platelet biomarker development.

  18. Effect of Mirasol pathogen reduction technology system on in vitro quality of MCS+ apheresis platelets.

    Science.gov (United States)

    Mastroianni, Maria Adele; Llohn, Abid Hussain; Akkök, Çiğdem Akalın; Skogheim, Ruby; Ødegaard, Elna Rathe; Nybruket, Monica Jenssen; Flesland, Annika; Mousavi, Seyed Ali

    2013-10-01

    Reducing the risk of pathogen transmission to transfusion recipients is one of the great concerns in transfusion medicine. Important among the measures suggested to minimise pathogen transmission is pathogen reduction technology (PRT) systems. The present study examined the effects of Mirasol PRT system on MCS+ apheresis platelets in vitro quality measures during a seven-day storage period at 22°C. Statistical analysis indicated no significant difference in platelet concentrations between the control and treated platelet concentrates (PCs) during the storage period. Glucose and lactate levels were measured to determine metabolic activities of control and treated platelets. In both control and treated platelets, the amount of glucose consumed and lactate produced increased significantly with storage time, but glucose consumption and lactate production rates were significantly higher in treated platelets compared with control platelets. The mean pH of treated PCs was decreased at all time points relative to control PCs but remained within acceptable limits. The expression of P-selectin was also higher in Mirasol PRT treated platelets throughout the storage period, but differences were not statistically significant on Days 1 and 4. Finally, visual inspection of swirling indicated that Mirasol PRT treatment of platelets is associated with platelet shape change. Overall, our results show that MCS+ apheresis platelets treated with Mirasol PRT can preserve adequate in vitro properties for at least 5 days of storage.

  19. Altered glycosylation of platelet-derived von Willebrand factor confers resistance to ADAMTS13 proteolysis.

    Science.gov (United States)

    McGrath, Rachel T; van den Biggelaar, Maartje; Byrne, Barry; O'Sullivan, Jamie M; Rawley, Orla; O'Kennedy, Richard; Voorberg, Jan; Preston, Roger J S; O'Donnell, James S

    2013-12-12

    Platelet-von Willebrand factor (VWF) is stored within α-granules and accounts for ∼20% of total VWF in platelet-rich plasma. This platelet-VWF pool is distinct from plasma-VWF and is enriched in high molecular weight multimers (HMWM). Previous studies have described significant functional discrepancies between platelet-VWF and plasma-VWF; however, the molecular basis of these differences is not well understood. We have characterized terminal glycan expression on platelet-VWF. Our findings demonstrate that platelet-VWF exists as a distinct natural glycoform. In particular, N-linked sialylation is markedly reduced (>50%) compared with plasma-VWF. Moreover, unlike plasma-VWF, platelet-VWF does not express AB blood group determinants, although precursor H antigen expression is similar to that on plasma-VWF. Because of this differential glycosylation, platelet-VWF exhibits specific resistance to ADAMTS13 proteolysis. Thus platelet activation at sites of vascular injury results in the release of high local concentrations of HMWM platelet-VWF that is more resistant to ADAMTS13, thereby facilitating platelet-plug formation. PMID:24106205

  20. Granule stores from cellubrevin/VAMP-3 null mouse platelets exhibit normal stimulus-induced release.

    Science.gov (United States)

    Schraw, Todd D; Rutledge, Tara W; Crawford, Garland L; Bernstein, Audrey M; Kalen, Amanda L; Pessin, Jeffery E; Whiteheart, Sidney W

    2003-09-01

    It is widely accepted that the platelet release reaction is mediated by heterotrimeric complexes of integral membrane proteins known as SNAREs (SNAP receptors). In an effort to define the precise molecular machinery required for platelet exocytosis, we have analyzed platelets from cellubrevin/VAMP-3 knockout mice. Cellubrevin/VAMP-3 has been proposed to be a critical v-SNARE for human platelet exocytosis; however, data reported here suggest that it is not required for platelet function. Upon stimulation with increasing concentrations of thrombin, collagen, or with thrombin for increasing time there were no differences in secretion of [3H]-5HT (dense core granules), platelet factor IV (alpha granules), or hexosaminidase (lysosomes) between null and wild-type platelets. There were no gross differences in bleeding times nor in agonist-induced aggregation measured in platelet-rich plasma or with washed platelets. Western blotting of wild-type, heterozygous, and null platelets confirmed the lack of cellubrevin/VAMP-3 in nulls and showed that most elements of the secretion machinery are expressed at similar levels. While the secretory machinery in mice was similar to humans, mice did express apparently higher levels of synaptobrevin/VAMP-2. These data show that the v-SNARE, cellubrevin/VAMP-3 is not a requirement for the platelet release reaction in mice.