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Sample records for platelet disorder qpd

  1. PREGNANCY WITH PLATELET FUNCTION DISORDER

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    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

  2. Investigation of platelet function and platelet disorders using flow cytometry.

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    Rubak, Peter; Nissen, Peter H; Kristensen, Steen D; Hvas, Anne-Mette

    2016-01-01

    Patients with thrombocytopenia or platelet disorders are at risk of severe bleeding. We report the development and validation of flow cytometry assays to diagnose platelet disorders and to assess platelet function independently of platelet count. The assays were developed to measure glycoprotein levels (panel 1) and platelet function (panel 2) in sodium citrated blood. Twenty healthy volunteers and five patients diagnosed with different platelet disorders were included. Glycoprotein expression levels of the receptors Ia, Ib, IIb, IIIa and IX were measured and normalised with forward scatter (FS) as a measurement of platelet size. Platelet function was assessed by CD63, P-selectin and bound fibrinogen in response to arachidonic acid, adenosine diphosphate (ADP), collagen-related peptide, ristocetin and thrombin receptor-activation peptide-6. All patients except one with suspected δ-granule defect showed aberrant levels of glycoproteins in panel 1. Glanzmann's thrombasthenia and genetically verified Bernard-Soulier syndrome could be diagnosed using panel 1. All patients showed reduced platelet function according to at least one agonist. Using panel 2 it was possible to diagnose Bernard-Soulier syndrome, δ-granule defect and GPVI disorder. By combining the two assays, we were able to diagnose different platelet disorders and investigate platelet function independent of platelet count.

  3. Inherited platelet disorders and oral health.

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    Valera, Marie-Cécile; Kemoun, Philippe; Cousty, Sarah; Sie, Pierre; Payrastre, Bernard

    2013-02-01

    Platelets play a key role in thrombosis and hemostasis. Accumulation of platelets at the site of vascular injury is the first step in the formation of hemostatic plugs, which play a pivotal role in preventing blood loss after injury. Platelet adhesion at sites of injury results in spreading, secretion, recruitment of additional platelets, and formation of platelet aggregates. Inherited platelet disorders are rare causes of bleeding syndromes, ranging from mild bruising to severe hemorrhage. The defects can reflect deficiency or dysfunction of platelet surface glycoproteins, granule contents, cytoskeletal proteins, platelet pro-coagulant function, and signaling pathways. For instance, Bernard-Soulier syndrome and Glanzmann thrombasthenia are attributed to deficiencies of glycoprotein Ib/IX/V and GPIIb/IIIa, respectively, and are rare but severe platelet disorders. Inherited defects that impair platelet secretion and/or signal transduction are among the most common forms of mild platelet disorders and include gray platelet syndrome, Hermansky-Pudlak syndrome, and Chediak-Higashi syndrome. When necessary, desmopressin, antifibrinolytic agents, and transfusion of platelets remain the most common treatment of inherited platelet disorders. Alternative therapies such as recombinant activated factor VII are also available for a limited number of situations. In this review, we will discuss the management of patients with inherited platelet disorders in various clinical situations related to dental cares, including surgical intervention. © 2012 John Wiley & Sons A/S.

  4. Platelet Disorders: MedlinePlus Health Topic

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    ... Article: Erythropoietin and thrombopoietin mimetics: Natural alternatives to erythrocyte and platelet... Article: Detection of CALR Mutation in Clonal and Nonclonal Hematologic Diseases... Platelet Disorders -- see more articles Thrombocytopenias -- see more ...

  5. Platelet Function Tests in Bleeding Disorders.

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    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

  6. Laboratory testing for platelet function disorders.

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    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.

  7. Desmopressin in inherited disorders of platelet function.

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    Coppola, A; Di Minno, G

    2008-01-01

    Following the first clinical use in haemophilia and von Willebrand disease in 1977, the synthetic analogue of vasopressin 1-deamino-8-D-arginine vasopressin (DDAVP, desmopressin) was successfully employed for the management of a series of bleeding disorders, including congenital and acquired defects of platelet function. In this setting, few haemostatic approaches are available and, in particular for severe bleeding and major invasive procedures, the transfusion of platelet concentrates is the first-choice treatment. Therefore, DDAVP was (and remains) an attractive therapeutic alternative, being well tolerated, cost-saving, administrable at home (by the intranasal or subcutaneous concentrated formulations) and, in particular, enabling the avoidance of blood product exposition and the related risks (allergic reactions, transfusion transmitted infections). Despite three decades of clinical use, cellular mechanisms of haemostatic effects of DDAVP in platelet defects remain poorly known and the excellent results reported in some case series have not been strengthened by rigorous clinical trials, hampered by the rarity and the heterogeneity of these disorders. However, clinical experience more than evidence-based medicine reserved an established place to DDAVP in the management of inherited platelet disorders. This review will focus the available clinical data and the open issues of DDAVP in this setting.

  8. 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 

  9. Erythrocyte and platelet proteomics in hematological disorders.

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    Chakrabarti, Abhijit; Halder, Suchismita; Karmakar, Shilpita

    2016-04-01

    Erythrocytes undergo ineffective erythropoesis, hemolysis, and premature eryptosis in sickle cell disease and thalassemia. Abnormal hemoglobin variants associated with hemoglobinopathy lead to vesiculation, membrane instability, and loss of membrane asymmetry with exposal of phosphatidylserine. This potentiates thrombin generation resulting in activation of the coagulation cascade responsible for subclinical phenotypes. Platelet activation also results in the release of microparticles, which express and transfer functional receptors from platelet membrane, playing key roles in vascular reactivity and activation of intracellular signaling pathways. Over the last decade, proteomics had proven to be an important field of research in studies of blood and blood diseases. Blood cells and its fluidic components have been proven to be easy systems for studying differential expressions of proteins in hematological diseases encompassing hemoglobinopathies, different types of anemias, myeloproliferative disorders, and coagulopathies. Proteomic studies of erythrocytes and platelets reported from several groups have highlighted various factors that intersect the signaling networks in these anucleate systems. In this review, we have elaborated on the current scenario of anucleate blood cell proteomes in normal and diseased individuals and the cross-talk between the two major constituent cell types of circulating blood.

  10. Inherited platelet disorders: Insight from platelet genomics using next-generation sequencing.

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    Maclachlan, Annabel; Watson, Steve P; Morgan, Neil V

    2017-01-01

    Inherited platelet disorders (IPDs) are a heterogeneous group of disorders associated with normal or reduced platelet counts and bleeding diatheses of varying severities. The identification of the underlying cause of IPDs is clinically challenging due to the absence of a gold-standard platelet test, and is often based on a clinical presentation and normal values in other hematology assays. As a consequence, a DNA-based approach has a potentially important role in the investigation of these patients. Next-generation sequencing (NGS) technologies are allowing the rapid analysis of genes that have been previously implicated in IPDs or that are known to have a key role in platelet regulation, as well as novel genes that have not been previously implicated in platelet dysfunction. The potential limitations of NGS arise with the interpretation of the sheer volume of genetic information obtained from whole exome sequencing (WES) or whole genome sequencing (WGS) in order to identify function-disrupting variants. Following on from bioinformatic analysis, a number of candidate genetic variants usually remain, therefore adding to the difficulty of phenotype-genotype segregation verification. Linking genetic changes to an underlying bleeding disorder is an ongoing challenge and may not always be feasible due to the multifactorial nature of IPDs. Nevertheless, NGS will play a key role in our understanding of the mechanisms of platelet function and the genetics involved.

  11. A Platelet Acquired Storage Pool Disorder Associated with Tamoxifen Therapy

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    Lalitha Nayak

    2012-01-01

    Full Text Available The antiestrogenic drug tamoxifen, used in patients with breast cancer, is associated with an increase in arterial and venous thrombotic events, the mechanism of which is not clearly understood. We report a case of a lady who presented with new bruising and prolonged bleeding following a tooth extraction 4–6 weeks after starting tamoxifen. Investigations were consistent with an acquired platelet storage pool disorder. Repeat platelet function analysis was normal, performed 3 months after discontinuation of tamoxifen. We present a previously clinically unreported effect of tamoxifen on platelet function.

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

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    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.

  13. A study of platelet disorders in pregnancy

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    Uma Pandey

    2016-07-01

    Conclusions: Mode of delivery was not influenced by platelet count, but for obstetric indications. Management of patients was as per the diagnosis. Single donor plasma is preferable to random donor plasma. PPH was the commonest complication and we should be wary of that. [Int J Reprod Contracept Obstet Gynecol 2016; 5(7.000: 2377-2379

  14. What’s new in using platelet research? To unravel thrombopathies and other human disorders

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    Freson, Kathleen; Labarque, Veerle; Thys, Chantal; Wittevrongel, Christine; Van Geet, Chris

    2007-01-01

    This review on platelet research focuses on defects of adhesion, cytoskeletal organisation, signal transduction and secretion. Platelet defects can be studied by different laboratory platelet functional assays and morphological studies. Easy bruising or a suspected platelet-based bleeding disorder is of course the most obvious reason to test the platelet function in a patient. However, nowadays platelet research also contributes to our understanding of human pathology in other disciplines suc...

  15. What's new in using platelet research? To unravel thrombopathies and other human disorders.

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    Freson, Kathleen; Labarque, Veerle; Thys, Chantal; Wittevrongel, Christine; Geet, Chris Van

    2007-12-01

    This review on platelet research focuses on defects of adhesion, cytoskeletal organisation, signal transduction and secretion. Platelet defects can be studied by different laboratory platelet functional assays and morphological studies. Easy bruising or a suspected platelet-based bleeding disorder is of course the most obvious reason to test the platelet function in a patient. However, nowadays platelet research also contributes to our understanding of human pathology in other disciplines such as neurology, nephrology, endocrinology and metabolic diseases. Apart from a discussion on classical thrombopathies, this review will also deal with the less commonly known relation between platelet research and disorders with a broader clinical phenotype. Classical thrombopathies involve disorders of platelet adhesion such as Glanzmann thrombastenia and Bernard-Soulier syndrome, defective G protein signalling diseases with impaired phospholipase C activation, and abnormal platelet granule secretion disorders such as gray platelet disorder and delta-storage pool disease. Other clinical symptoms besides a bleeding tendency have been described in MYH9-related disorders and Duchenne muscular dystrophy due to adhesion defects, and also in disorders of impaired Gs signalling, in Hermansky Pudlack disease and Chediak Higashi disease with abnormal secretion. Finally, platelet research can also be used to unravel novel mechanisms involved in many neurological disorders such as depression and autism with only a subclinical platelet defect.

  16. What’s new in using platelet research? To unravel thrombopathies and other human disorders

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    Labarque, Veerle; Thys, Chantal; Wittevrongel, Christine; Geet, Chris Van

    2007-01-01

    This review on platelet research focuses on defects of adhesion, cytoskeletal organisation, signal transduction and secretion. Platelet defects can be studied by different laboratory platelet functional assays and morphological studies. Easy bruising or a suspected platelet-based bleeding disorder is of course the most obvious reason to test the platelet function in a patient. However, nowadays platelet research also contributes to our understanding of human pathology in other disciplines such as neurology, nephrology, endocrinology and metabolic diseases. Apart from a discussion on classical thrombopathies, this review will also deal with the less commonly known relation between platelet research and disorders with a broader clinical phenotype. Classical thrombopathies involve disorders of platelet adhesion such as Glanzmann thrombastenia and Bernard-Soulier syndrome, defective G protein signalling diseases with impaired phospholipase C activation, and abnormal platelet granule secretion disorders such as gray platelet disorder and delta-storage pool disease. Other clinical symptoms besides a bleeding tendency have been described in MYH9-related disorders and Duchenne muscular dystrophy due to adhesion defects, and also in disorders of impaired Gs signalling, in Hermansky Pudlack disease and Chediak Higashi disease with abnormal secretion. Finally, platelet research can also be used to unravel novel mechanisms involved in many neurological disorders such as depression and autism with only a subclinical platelet defect. PMID:17619901

  17. Acquired platelet function defect

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    Acquired qualitative platelet disorders; Acquired disorders of platelet function ... blood clotting. Disorders that can cause problems in platelet function include: Idiopathic thrombocytopenic purpura Chronic myelogenous leukemia Multiple ...

  18. Mean platelet volume in children with attention deficit hyperactivity disorder.

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    Yorbik, Ozgur; Mutlu, Caner; Tanju, Ilhan Asya; Celik, Dincer; Ozcan, Omer

    2014-03-01

    The mean platelet volume (MPV), the accurate measure of platelet size, is considered a marker and determinant of platelet function. MPV can be a potentially useful prognostic biomarker in patients with cardiovascular disease. After reviewing literature, we hypothesized that attention deficit hyperactivity disorder (ADHD) in childhood may be a risk factor for coronary heart disease (CHD) in adulthood. The aim of this study was investigation of MPV and platelet count (PLT) in children with ADHD and healthy subjects. The MPV and the PLT were measured in 70 children with ADHD (aged 6-16 years), and compared with 41 healthy controls. The MPV was found to be significantly increased in ADHD group compared to control group (p=.006). There was no significant difference in the PLT between groups (p>.05). To our knowledge, this was the first study of investigating the levels of MPV and PLT in children with ADHD. Although significance and cause of increased MPV level in ADHD remain unclear in present study, further studies are warranted to investigate relationships among MPV, ADHD in childhood and CHD in adulthood.

  19. Platelets

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    ... tiny fraction of the blood volume. The principal function of platelets is to prevent bleeding. Red blood cells are ... forming a long string. This illustrates the basic function of platelets, to stick to any foreign surface and then ...

  20. External quality assessment of platelet disorder investigations: results of international surveys on diagnostic tests for dense granule deficiency and platelet aggregometry interpretation.

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    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.

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

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    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.

  2. The Inflammatory Role of Platelets: Translational Insights from Experimental Studies of Autoimmune Disorders

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    Susann Pankratz

    2016-10-01

    Full Text Available Beyond their indispensable role in hemostasis, platelets have shown to affect the development of inflammatory disorders, as they have been epidemiologically and mechanistically linked to diseases featuring an inflammatory reaction in inflammatory diseases like multiple sclerosis, rheumatoid arthritis and inflammatory bowel disorders. The identification of novel molecular mechanisms linking inflammation and to platelets has highlighted them as new targets for therapeutic interventions. In particular, genetic and pharmacological studies have identified an important role for platelets in neuroinflammation. This review summarizes the main molecular links between platelets and inflammation, focusing on immune regulatory factors, receptors, cellular targets and signaling pathways by which they can amplify inflammatory reactions and that make them potential therapeutic targets.

  3. Platelet serotonin concentration and suicidal behavior in combat related posttraumatic stress disorder.

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    Kovacic, Zrnka; Henigsberg, Neven; Pivac, Nela; Nedic, Gordana; Borovecki, Andrea

    2008-02-15

    Posttraumatic stress disorder (PTSD) is a serious and global problem, a psychiatric disorder that frequently occurs with different comorbidities, and is associated with a high suicide rate. Pathophysiologically, both PTSD and suicidal behavior are related to disturbances in the central serotonergic system. Serotonin (5-hydroxytryptamine, 5-HT) controls emotional behavior, anxiety, impulsivity and aggression, and nearly all known antidepressants and antianxiety drugs affect 5-HT transmission. Platelet 5-HT can be used as a limited peripheral marker of the central serotonergic synaptosomes, since it is related to particular basic psychopathological characteristics of several psychiatric disorders. Platelet 5-HT concentration has been reported to be similar in PTSD subjects and healthy controls, but suicidal patients across different psychiatric diagnoses have reduced platelet 5-HT concentration. This study examined platelet 5-HT concentration by the spectrofluorimetric method in male subjects: 73 suicidal and 47 non-suicidal veterans with current and chronic combat related PTSD, 45 suicidal and 30 non-suicidal comparative non-PTSD subjects and 147 healthy men. The presence of suicidal behavior (score=0, non-suicidal; scores > or =1, suicidal) was assessed with the Hamilton Depression Rating Scale-17 (HDRS). Platelet 5-HT concentration was significantly lower in suicidal PTSD and non-PTSD patients compared to non-suicidal patients or healthy controls. Since the majority of patients scored very low on item 3 of HDRS, no significant correlation between suicidal scores and platelet 5-HT concentration was found. These results show that reduced platelet 5-HT concentration is related to suicidal behavior in PTSD, and suggest that platelet 5-HT concentration might be used as a peripheral marker to predict suicidal behavior across psychiatric diagnoses.

  4. Congenital platelet function defects

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    ... storage pool disorder; Glanzmann's thrombasthenia; Bernard-Soulier syndrome; Platelet function defects - congenital ... Congenital platelet function defects are bleeding disorders that ... function, even though there are normal platelet numbers. Most ...

  5. Platelet (/sup 3/H)imipramine binding in affective disorders: trait versus state characteristics

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    Baron, M.; Barkai, A.; Gruen, R.; Peselow, E.; Fieve, R.R.; Quitkin, F.

    1986-06-01

    Platelet (3H)imipramine binding (Bmax) was determined in 67 patients with major affective illness (33 euthymic bipolar, 34 depressed unipolar) and 58 normal control subjects. Bipolar patients had significantly lower Bmax values than did control subjects. The mean Bmax in the unipolar patients was lower than in the control subjects, but the difference was not statistically significant. Dissociation constant (Kd) values did not distinguish patients in either category from control subjects. The significantly lower Bmax in euthymic bipolar patients and the apparent state independence of Bmax in some but not all unipolar patients suggest that platelet imipramine binding may be a trait marker in a subset of affective disorders.

  6. Psychobiology of borderline personality traits related to subtypes of eating disorders: a study of platelet MAO activity.

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    Díaz-Marsá, Marina; Carrasco, Jose L; de Anta, Laura; Molina, Rosa; Sáiz, Jerónimo; Cesar, Jesus; López-Ibor, Juan J

    2011-12-30

    Increased and decreased levers of platelet monoamine oxidase (MAO) activity have been reported in patients with eating disorders, indicating abnormalities of the serotonin turnover. However, whether these findings are related to eating disorders or are rather reflecting the pathophysiology of borderline personality traits in these patients is still unknown. Platelet MAO activity and comorbid personality disorders were investigated in 72 patients with different subtypes of eating disorders (ED) and in a group of 28 healthy controls. ED patients comprised the following subtypes: 25 anorexia nervosa (AN) restrictive, 14 AN binge eating-purging (AN b-p), 3 anorexia nervosa not otherwise specified (AN NOS) and 30 bulimia nervosa (BN). Personality disorders and traits were assessed with the Structured Interview for Personality Disorders (SCID-II), the Zanarini Rating Scale for Borderline Personality Disorder, and the Barrat Impulsiveness Scale. Platelet MAO activity was significantly lower in ED patients with comorbid borderline personality disorder (BPD) than in ED without Borderline personality disorder (BDP). Platelet MAO activity was significantly and inversely correlated with the number and severity of BPD clinical features. In the subsample of patients with binge eating-purging symptoms (AN b-p, AN NOS and BN), platelet MAO activity was significantly lower in binge-purge patients with comorbid BPD than in binge-purge patients without BPD. The whole group of eating disorders had a significantly reduced lever of platelet MAO activity compared with the control group. The results suggest that low platelet MAO activity might characterize eating disorders with comorbid borderline personality traits, reflecting greater serotonin dysfunction in these patients. The role of decreased platelet MAO as an endophenotype with specific clinical manifestations should be explored in future studies.

  7. Psychological traits and platelet monoamine oxidase activity in eating disorder patients: their relationship and stability.

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    Podar, Iris; Jaanisk, Maiken; Allik, Jüri; Harro, Jaanus

    2007-01-30

    Self-reported behavior and attitudes towards eating [Eating Disorder Inventory-2; Garner DM (1991). Eating Disorder Inventory-2: Professional Manual. Odessa, Fl.: Psychological Assessment Resources; Estonian version Podar I, Hannus A, Allik J (1999). Personality and Affectivity Characteristics Associated With Eating Disorders: a Comparison of Eating Disordered, Weight-Preoccupied, and Normal Samples. J Pers Assess; 73(1), 133-147] and the activity of platelet monoamine oxidase (MAO) was studied in 11 patients with anorexia nervosa (AN), 43 patients with bulimia nervosa (BN) and a healthy control group (n=138). Nineteen patients filled in the EDI-2 questionnaire and donated blood samples three times with three month intervals in order to determine platelet MAO activity. Eating disordered (ED) patients scored higher on all EDI-2 subscales and had lower MAO activity compared to the control group. They also scored higher than the control group on the Neuroticism domain but lower on the Extraversion, Openness, and Conscientiousness domains of the NEO-PI-R questionnaire. The average stability of MAO on different occasions (r=.56) was slightly smaller than the stability of the EDI-2 scores (r=.70). The lack of correlations between personality dispositions and MAO activity indicates that they have independent influence on eating disorders. A possible relationship between neurochemical mechanisms and psychological symptoms of eating disordered behavior is discussed.

  8. The multifunctionality of berries toward blood platelets and the role of berry phenolics in cardiovascular disorders.

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    Olas, Beata

    2016-10-25

    Diet and nutrition have an important influence on the prophylaxis and progression of cardiovascular disease; one example is the inhibition of blood platelet functions by specific components of fruits and vegetables. Garlic, onion, ginger, dark chocolate and polyunsaturated fatty acids all reduce blood platelet aggregation. A number of fruits contain a range of cardioprotective antioxidants and vitamins, together with a large number of non-nutrient phytochemicals such as phenolic compounds, which may possess both antioxidant properties and anti-platelet activity. Fresh berries and berry extracts possess high concentrations of phenolic compounds, i.e. phenolic acid, stilbenoids, flavonoids and lignans. The aim of this review article is to provide an overview of current knowledge of the anti-platelet activity of berries, which form an integral part of the human diet. It describes the effects of phenolic compounds present in a number of berries, i.e. black chokeberries - aronia berries (Aronia melanocarpa), blueberries (Vaccinium myrtillus), cranberries (Vaccinium sect. Oxycoccus), sea buckthorn berries (Hippophae rhamnoides) and grapes (Vitis), as well as various commercial products from berries (i.e. juices), on platelets and underlying mechanisms. Studies show that the effects of berries on platelet activity are dependent on not only the concentrations of the phenolic compounds in the berries or the class of phenolic compounds, but also the types of berry and the form (fresh berry, juice or medicinal product). Different results indicate that berries may play a role in the prevention of cardiovascular disorders, but the development of well-controlled clinical studies with berries is encouraged.

  9. Molecular phenotype and bleeding risks of an inherited platelet disorder in a family with a RUNX1 frameshift mutation.

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    Badin, M S; Iyer, J K; Chong, M; Graf, L; Rivard, G E; Waye, J S; Paterson, A D; Pare, G; Hayward, C P M

    2017-05-01

    Inherited defects in RUNX1 are important causes of platelet function disorders. Our goals were to evaluate RUNX1-related platelet disorders among individuals evaluated for uncharacterized, inherited platelet function disorders and test a proof of concept that bleeding risks could be quantitatively estimated for typical families with an inherited platelet function disorder. Index cases with an uncharacterized inherited platelet function disorder were subjected to exome sequencing with confirmation of RUNX1 mutations by Sanger sequencing. Laboratory findings were obtained from medical records and persistence of platelet non-muscle myosin heavy chain IIB (MYH10), a biomarker of RUNX1 defects, was assessed by Western blotting. Bleeding histories were assessed using standardized assessment tools. Bleeding risks were estimated as odds ratios (OR) using questionnaire data for affected individuals compared to controls. Among 12 index cases who had their exomes sequenced, one individual from a family with eight study participants had a c.583dup in RUNX1 that segregated with the disease and was predicted to cause a frameshift and RUNX1 haploinsufficiency. Unlike unaffected family members (n = 2), affected family members (n = 6) had increased bleeding scores and abnormal platelet aggregation and dense granule release responses to agonists but only some had thrombocytopenia and/or dense granule deficiency. This family's mutation was associated with persistence of MYH10 in platelets and increased risks (OR 11-440) for wound healing problems and mild bleeding symptoms, including bleeding interfering with lifestyle in women. Inherited platelet dysfunction due to a RUNX1 haploinsufficiency mutation significantly increases bleeding risks. © 2017 John Wiley & Sons Ltd.

  10. Mean platelet volume and red cell distribution width levels in initial evaluation of panic disorder

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    Asoglu M

    2016-09-01

    Full Text Available Mehmet Asoglu,1 Mehmet Aslan,2 Okan Imre,1 Yuksel Kivrak,3 Oznur Akil,1 Emin Savik,4 Hasan Buyukaslan,5 Ulker Fedai,1 Abdurrahman Altındag6 1Department of Psychiatry, Faculty of Medicine, Harran University, Sanliurfa, 2Department of Internal Medicine, Faculty of Medicine, Yuzuncu Yil University, Van, 3Department of Psychiatry, Faculty of Medicine, Kafkas University, Kars, 4Department of Clinical Biochemistry, Faculty of Medicine, Harran University, 5Department of Emergency Medicine, Faculty of Medicine, Harran University, Sanliurfa, 6Department of Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey Background: As the relationship between psychological stress and platelet activation has been widely studied in recent years, activated platelets lead to certain biochemical changes, which occur in the brain in patients with mental disorders. However, data relating to the mean platelet volume (MPV in patients with panic disorder (PD are both limited and controversial. Herein, we aimed to evaluate, for the first time, the red cell distribution width (RDW levels combined with MPV levels in patients with PD.Patients and methods: Between January 2012 and June 2015, data of 30 treatment-naïve patients (16 females, 14 males; mean age: 37±10 years; range: 18–59 years who were diagnosed with PD and 25 age- and sex-matched healthy volunteers (10 females, 15 males; mean age: 36±13 years; range: 18–59 years (control group were retrospectively analyzed. The white blood cell count (WBC, MPV, and RDW levels were measured in both groups.Results: The mean WBC, MPV, and RDW levels were 9,173.03±2,400.31/mm3, 8.19±1.13 fl, and 12.47±1.14%, respectively, in the PD group. These values were found to be 7,090.24±1,032.61, 6.85±0.67, and 11.63±0.85, respectively, in the healthy controls. The WBC, MPV, and RDW levels were significantly higher in the patients with PD compared to the healthy controls (P=0.001, P=0.001, and P=0

  11. Adenylate-cyclase activity in platelets of patients with obsessive-compulsive disorder

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    D Marazziti, S Baroni

    2009-07-01

    Full Text Available D Marazziti, S Baroni, L Palego, I Masala, G Consoli, M Catena Dell’Osso, G Giannaccini, A LucacchiniDipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, Pisa, ItalyAbstract: Although the main biological hypothesis on the pathophysiology of obsessive-compulsive disorder (OCD is centered on the serotonin system, indications are available that other neurotransmitters, and even second messengers, particularly the cyclic adenosine monophosphate (cAMP signaling, may be involved, though effective data are few. Therefore, the aim of the present study was to evaluate and compare the basal and isoprenaline (ISO-stimulated velocity of adenylate-cyclase (AC in human platelet membranes of patients with OCD and healthy control subjects. The results showed that the basal and ISO-stimulated AC activity, as well as the dose-response curves of ISO by using agonist concentrations ranging between 0.1 nM and 10 µM, were not different in the two groups. However, OCD patients showed lower EC50 and higher Emax values than healthy subjects. These findings suggest the presence of supersensitive β-adrenergic receptors in platelets of OCD patients.Keywords: obsessive-compulsive disorder, norepinephrine, second messengers, adenylate-cyclase, platelets, isoprenaline, β-adrenergic receptors

  12. RUNX1 deficiency (familial platelet disorder with predisposition to myeloid leukemia, FPDMM).

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    Schlegelberger, Brigitte; Heller, Paula G

    2017-04-01

    In this review, we discuss disease-causing alterations of RUNT-related transcription factor 1 (RUNX1), a master regulator of hematopoietic differentiation. Familial platelet disorder with predisposition to myeloid leukemia (FPDMM) typically presents with (1) mild to moderate thrombocytopenia with normal-sized platelets; (2) functional platelets defects leading to prolonged bleeding; and (3) an increased risk to develop myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), or T-cell acute lymphoblastic leukemia (T-ALL). Hematological neoplasms in carriers of a germline RUNX1 mutation need additional secondary mutations or chromosome aberrations to develop. If a disease-causing mutation is known in the family, it is important to prevent hematopoietic stem cell transplantation from a sibling or other relative carrying the familial mutation. First experiments introducing a wild-type copy of RUNX1 into induce pluripotent stem cells (iPSC) lines from patients with FPDMM appear to demonstrate that by gene correction reversal of the phenotype may be possible. Copyright © 2017. Published by Elsevier Inc.

  13. 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.

  14. Family platelet disorder with propensity to acute myeloid leukemia: new family with RUNX1 mutation

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    V. O. Bobrynina

    2014-07-01

    Full Text Available Familial platelet disorder with propensity to develop acute myeloid leukemia (FPD/AML is a rare autosomal dominant disorder caused by inherited mutation of RUNX1. To date only 35 families have been described. We report on a family in which number and function of platelet were impaired in members of 4 generations. Acute myeloid leukemia developed in 3 members of 2 generations. The age of leukemia development was 11, 19 и 76 years. In all 5 affected family members available for study novel heterozygous mutation in runt domain of RUNX1 (c2018 A > C, pT147P was detected by direct sequencing. This mutation is predicted to impair binding of CBF to core motif of DNA. Two affected patients died of leukemia; while in one complete remission was achieved with conventional and consolidated with allogeneic BMT from HLA-matched sister proved to be RUNX1 mutation negative.

  15. Family platelet disorder with propensity to acute myeloid leukemia: new family with RUNX1 mutation

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    V. O. Bobrynina

    2011-01-01

    Full Text Available Familial platelet disorder with propensity to develop acute myeloid leukemia (FPD/AML is a rare autosomal dominant disorder caused by inherited mutation of RUNX1. To date only 35 families have been described. We report on a family in which number and function of platelet were impaired in members of 4 generations. Acute myeloid leukemia developed in 3 members of 2 generations. The age of leukemia development was 11, 19 и 76 years. In all 5 affected family members available for study novel heterozygous mutation in runt domain of RUNX1 (c2018 A > C, pT147P was detected by direct sequencing. This mutation is predicted to impair binding of CBF to core motif of DNA. Two affected patients died of leukemia; while in one complete remission was achieved with conventional and consolidated with allogeneic BMT from HLA-matched sister proved to be RUNX1 mutation negative.

  16. Mean platelet volume in bipolar disorder: the search for an ideal biomarker

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    Mert DG

    2016-08-01

    Full Text Available Derya Guliz Mert,1 Hatice Terzi2 1Department of Psychiatry, 2Department of Hematology, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey Background: The pathophysiology of bipolar disorder (BD remains a mystery. In this context, interest in the role of the immune and inflammatory systems in BD has been increasing. We aimed to compare the routine hemogram values of BD patients with those of the participants in the healthy control group, to assess the inflammation levels of the two groups. Mean platelet volume (MPV can be obtained as routine hemogram parameters and may aid in the detection of systemic inflammation. Subjects and methods: This study was conducted with BD (manic episode inpatients (n=132 and healthy controls (n=135. Abnormally distributed variables (ie, neutrophil–lymphocyte ratio [NLR], platelet–lymphocyte ratio [PLR], neutrophils, lymphocytes, hemoglobin, hematocrit [HCT], mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], red cell distribution width [RDW], MPV, and plateletcrit [PCT] were compared using the Mann–Whitney U-test. Student’s t-test was used to compare the mean ages and white blood cell, red blood cell, and platelet counts of the patients with BD against those of the participants in the control group. Results: The comparisons revealed that while the mean WBC and the median NLR, PLR, neutrophil, lymphocyte, MPV, and PCT values were significantly higher in the patients with BD (P<0.05, the median hemoglobin, RBC, HCT, and MCHC values were significantly higher in the control group (P<0.05. Conclusion: Comparisons of hemogram values of patients with BD against those of the healthy control group revealed that inflammatory cells (absolute neutrophil count, platelet count, PCT, and MPV and ratios (NLR, PLR seem to be altered during manic episodes. These findings support the hypothesis that inflammatory activation occurs in BD during manic

  17. Ehlers-danlos syndrome with platelet aggregation defect-presenting as mysterious bleeding disorder

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    Sawhney M

    2003-01-01

    Full Text Available A 7-year-old girl presented with recurrent episodes of petechiae, purpura and ecchymoses since six months of age and recurrent episodes of mild to severe epistaxis since two years of age requiring repeated blood transfusions. In April '99 while being investigated for a massive epistaxis, she was found to have platelet function defect with abnormal aggregation of platelets to ADP, epinephrine, collagen as well as to ristocetin. Further investigations ruled out the possibility of Glanzmann's disorder and von-Willebrand's disease as to its cause. In May 2001 she was referred to the dermatologist for evaluation of subcutaneous tumours, which had developed since the last six months. On clinical evaluation, she was found to be having mild hyperextensibility of the skin, joint hypermobility, atrophic scars over knee, spontaneous bruises over right forearm and left thigh and nontender firm to hard subcutaneous nodules over both wrists, both shoulders, right index finger and dorsum of right foot consistent with a clinical picture of a mild form of Ehlers-Danlos syndrome (EDS. Histopathology of the nodule from left wrist was consistent with molluscoid tumour of EDS and skin histopathology and ultrastructure studies showed thick irregular collagen fibrils. Only other sibling, a five-year-old male also had history of repeated mild to moderate epistaxis and on examination was found to have a milder variant of EDS. Born out of I degree consanguineous marriage of normal parents with mildly affected other sibling, she was diagnosed to be suffering from EDS with autosomal recessive inheritance, most probably EDS type X due to the associated platelet aggregation defect. Only one such family with EDS type X has been reported so far.

  18. Ehlers-danlos syndrome with platelet aggregation defect-presenting as mysterious bleeding disorder

    Directory of Open Access Journals (Sweden)

    Sawhney M

    2003-03-01

    Full Text Available A 7-year-old girl presented with recurrent episodes of petechiae, purpura and ecchymoses since six months of age and recurrent episodes of mild to severe epistaxis since two years of age requiring repeated blood transfusions. In April '99 while being investigated for a massive epistaxis, she was found to have platelet function defect with abnormal aggregation of platelets to ADP, epinephrine, collagen as well as to ristocetin. Further investigations ruled out the possibility of Glanzmann's disorder and von-Willebrand's disease as to its cause. In May 2001 she was referred to the dermatologist for evaluation of subcutaneous tumours, which had developed since the last six months. On clinical evaluation, she was found to be having mild hyperextensibility of the skin, joint hypermobility, atrophic scars over knee, spontaneous bruises over right forearm and left thigh and nontender firm to hard subcutaneous nodules over both wrists, both shoulders, right index finger and dorsum of right foot consistent with a clinical picture of a mild form of Ehlers-Danlos syndrome (EDS. Histopathology of the nodule from left wrist was consistent with molluscoid tumour of EDS and skin histopathology and ultrastructure studies showed thick irregular collagen fibrils. Only other sibling, a five-year-old male also had history of repeated mild to moderate epistaxis and on examination was found to have a milder variant of EDS. Born out of I degree consanguineous marriage of normal parents with mildly affected other sibling, she was diagnosed to be suffering from EDS with autosomal recessive inheritance, most probably EDS type X due to the associated platelet aggregation defect. Only one such family with EDS type X has been reported so far.

  19. Clinical and laboratory characteristics of adolescents with platelet function disorders and heavy menstrual bleeding

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    Amesse Lawrence S

    2013-01-01

    Full Text Available Abstract Background Platelet function disorders (PFDs have emerged as an important etiology of heavy menstrual bleeding (HMB in adolescents. However, neither clinical nor laboratory data have been methodically analyzed in this population subset. The objective of this study was to evaluate these parameters in order to distinguish characteristics of the disorder that in turn will lead to earlier diagnosis and therapy initiation. Methods Retrospective review of medical records from postmenarcheal adolescents with documented PFDs referred to a hemophilia treatment center and university faculty practices for bleeding diatheses with their clinical and laboratory data evaluated. Results Of 63 teens with documented PFDs, HMB was the most common clinical manifestation of PFD (43; 68.3%. Of these, 37 (86% were diagnosed with PFD either at or after menarche with the diagnosis based on HMB symptoms alone. Only 6 (14% were diagnosed with a PFD prior to menarche, based on associated bleeding, i.e., epistaxis, ecchymosis, and all developed HMB after menstruation onset. Interestingly, 20 girls were diagnosed with a PFD prior to menarche and of these, only 6 (30% went on to develop HMB after pubertal transition, while the majority (14; 70% did not. The average age-at-PFD diagnosis was 14.5yrs, significantly differing from the 10.9yrs average age-at-PFD diagnosis in their counterparts that, after menarche, did not develop HMB (PP P Conclusions Adolescents with PFDs and HMB appear to be clinically distinct from their non-HMB counterparts. This group of girls is characterized by HMB the major bleeding symptom, significantly high incidences of blood group O and the δ-SPD with a PFD diagnosed well after menarche. High false negative standard platelet function study results indicate additional diagnostic strategies, particularly for δ-SPD, should be considered.

  20. Association of Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorders with Mean Platelet Volume and Vitamin D

    Science.gov (United States)

    Garipardic, Mesut; Doğan, Murat; Bala, Keziban Asli; Mutluer, Tuba; Kaba, Sultan; Aslan, Oktay; Üstyol, Lokman

    2017-01-01

    Background The purpose of this study was to assess the values of the mean platelet volume (MPV) in children with attention deficit hyperactivity disorder (ADHD) and with autism spectrum disorders (ASDs) to determine the risk of cardiovascular disease in these 2 disorder groups. Material/Methods The study included a total of 79 patients with ADHD or ASDs and controls in the Van region of Turkey. The control group included subjects of matching age and sex with no ADHD, ASDs, or chronic disease and taking no vitamins. The hematological parameters of the patients, including MPV, vitamin B12, and vitamin D, were assessed. Results The study included a total of 79 children and adolescents aged 2–18 years (32 females and 47 males). Of the patients, 36 were in the ADHD group, 18 in the ASDs group, and 25 in the control group. There was no statistically significant difference in hematological parameters between the groups, but there were significant differences in terms of vitamin D and vitamin B12. The patient groups showed lower levels of vitamin B12 and vitamin D. In the ADHD group, there was a negative correlation between both vitamins and MPV (pdisorders should be closely followed up. PMID:28319054

  1. The change and significance of platelet parameters and blood coagulation function index in patients with hypertensive disorder complicating pregnancy

    Institute of Scientific and Technical Information of China (English)

    Yu-Xia Shi; Yi-Xin Yang; Qian Xu; Yanhua Zhu

    2015-01-01

    Objective:To explore the change and significance of platelet parameters and blood coagulation function index in patients with hypertensive disorder complicating pregnancy.Methods: Chose 89 patients with HDCP, they were set as HDCP group, chose another 60 cases health late pregnancy women and 42 cases non pregnant female, they were set as late pregnant group and non-pregnant control group, detected the platelet parameters: the average blood platelet count (PLT), platelet volume (MPV), platelet distribution width (PDW) and blood coagulation indexes, plasma prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), D-dimer (D-D), activated partial blood coagulation time (APTT) live enzymes in three groups.Results: (1) Compared with the non-pregnant group and late pregnant group, PLT was significantly lower, while the MPV and PDW were significantly higher in HDCP group; PLT in late pregnant group was significantly lower than that in non-pregnant group, and there were no significantly difference of MPV and PDW in the two groups; (2) Compared with the non-pregnant group and late pregnant group, PT and APTT levels were significantly lower, while FIB and D-D were significantly higher in HDCP group; The level of PT and APTT in late pregnant group were significantly lower, and FIB and D-D levels were significantly higher than that in non-pregnant group, However, The level of TT were no statistical significance difference among the three groups.Conclusion: HDCP existence phenomenon of platelet activation and apparent high coagulation state, dynamic detection of HDCP patients platelet parameters and blood coagulation indexes to prevent related complications, improve obstetrics safety is of great significance.

  2. Clinical investigation of oral findings in inherited disorders of platelet function

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    Müjgan Güngör Hatipoğlu

    2011-12-01

    Full Text Available Objective: Bleeding disorders are a very important health problem due to the associated high risk of hemorrhage during dental procedures. The present study aimed to investigate oral manifestations of inherited disorders of platelet function (IDPF. Materials and Methods: The study included 20 IDPF patients (mean age: 31.90±10.71 years and 40 healthy controls (mean age: 31.63±9.07 years. Tooth brushing habits, level of education, and clinical index scores (Simplified Oral Hygiene Index [OHI-S], Decayed Missing Filled Teeth Index [DMFT] index, probing depth [PD] index, Gingival Bleeding Index [GBI], and Community Periodontal Index [CPI] were recorded. Results: There weren’t any significant differences between the 2 groups with respect to tooth brushing habit, level of education level, OHI-S, DMFT index, or CPI (p>0.05, whereas significant differences in PD index and GBI were observed between the groups (p<0.05.Conclusion: The present study’s findings show that IDPF has a negative effect on periodontal tissues.

  3. Epistaxis as a Common Presenting Symptom of Glanzmann’s Thrombasthenia, a Rare Qualitative Platelet Disorder: Illustrative Case Examples

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    Michael Recht

    2017-01-01

    Full Text Available Children often present to emergency departments (EDs with uncontrollable nose bleeding. Although usually due to benign etiologies, epistaxis may be the presenting symptom of an inherited bleeding disorder. Whereas most bleeding disorders are detected through standard hematologic assessments, diagnosing rare platelet function disorders may be challenging. Here we present two case reports and review diagnostic and management challenges of platelet function disorders with a focus on Glanzmann’s thrombasthenia (GT. Patient 1 was a 4-year-old boy with uncontrolled epistaxis. His medical history included frequent and easy bruising. Previous laboratory evaluation revealed only mild microcytic anemia. An otolaryngologist stopped the bleeding, and referral to a pediatric hematologist led to the definitive diagnosis of GT. Patient 2 was a 2.5-year-old girl with severe epistaxis and a history of milder recurrent epistaxis. She had a bruise on her abdomen with a palpable hematoma and many scattered petechiae. Previous assessments revealed no demonstrable hemostatic anomalies. Platelet aggregation studies were performed following referral to a pediatric hematologist, leading to the diagnosis of GT. As evidenced by these cases, the ED physician may often be the first to evaluate severe or recurrent epistaxis and should recognize indications for coagulation testing and hematology consultation/referral for advanced hematologic assessments.

  4. Evaluation of participants with suspected heritable platelet function disorders including recommendation and validation of a streamlined agonist panel.

    Science.gov (United States)

    Dawood, Ban B; Lowe, Gillian C; Lordkipanidzé, Marie; Bem, Danai; Daly, Martina E; Makris, Mike; Mumford, Andrew; Wilde, Jonathan T; Watson, Steve P

    2012-12-13

    Light transmission aggregometry (LTA) is used worldwide for the investigation of heritable platelet function disorders (PFDs), but interpretation of results is complicated by the feedback effects of ADP and thromboxane A(2) (TxA(2)) and by the overlap with the response of healthy volunteers. Over 5 years, we have performed lumi-aggregometry on 9 platelet agonists in 111 unrelated research participants with suspected PFDs and in 70 healthy volunteers. Abnormal LTA or ATP secretion test results were identified in 58% of participants. In 84% of these, the patterns of response were consistent with defects in Gi receptor signaling, the TxA(2) pathway, and dense granule secretion. Participants with defects in signaling to Gq-coupled receptor agonists and to collagen were also identified. Targeted genotyping identified 3 participants with function-disrupting mutations in the P2Y(12) ADP and TxA(2) receptors. The results of the present study illustrate that detailed phenotypic analysis using LTA and ATP secretion is a powerful tool for the diagnosis of PFDs. Our data also enable subdivision at the level of platelet-signaling pathways and in some cases to individual receptors. We further demonstrate that most PFDs can be reliably diagnosed using a streamlined panel of key platelet agonists and specified concentrations suitable for testing in most clinical diagnostic laboratories.

  5. A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders

    Science.gov (United States)

    Simeoni, Ilenia; Stephens, Jonathan C.; Hu, Fengyuan; Deevi, Sri V. V.; Megy, Karyn; Bariana, Tadbir K.; Lentaigne, Claire; Schulman, Sol; Sivapalaratnam, Suthesh; Vries, Minka J. A.; Westbury, Sarah K.; Greene, Daniel; Papadia, Sofia; Alessi, Marie-Christine; Attwood, Antony P.; Ballmaier, Matthias; Baynam, Gareth; Bermejo, Emilse; Bertoli, Marta; Bray, Paul F.; Bury, Loredana; Cattaneo, Marco; Collins, Peter; Daugherty, Louise C.; Favier, Rémi; French, Deborah L.; Furie, Bruce; Gattens, Michael; Germeshausen, Manuela; Ghevaert, Cedric; Goodeve, Anne C.; Guerrero, Jose A.; Hampshire, Daniel J.; Hart, Daniel P.; Heemskerk, Johan W. M.; Henskens, Yvonne M. C.; Hill, Marian; Hogg, Nancy; Jolley, Jennifer D.; Kahr, Walter H.; Kelly, Anne M.; Kerr, Ron; Kostadima, Myrto; Kunishima, Shinji; Lambert, Michele P.; Liesner, Ri; López, José A.; Mapeta, Rutendo P.; Mathias, Mary; Millar, Carolyn M.; Nathwani, Amit; Neerman-Arbez, Marguerite; Nurden, Alan T.; Nurden, Paquita; Othman, Maha; Peerlinck, Kathelijne; Perry, David J.; Poudel, Pawan; Reitsma, Pieter; Rondina, Matthew T.; Smethurst, Peter A.; Stevenson, William; Szkotak, Artur; Tuna, Salih; van Geet, Christel; Whitehorn, Deborah; Wilcox, David A.; Zhang, Bin; Revel-Vilk, Shoshana; Gresele, Paolo; Bellissimo, Daniel B.; Penkett, Christopher J.; Laffan, Michael A.; Mumford, Andrew D.; Rendon, Augusto; Freson, Kathleen; Ouwehand, Willem H.; Turro, Ernest

    2016-01-01

    Inherited bleeding, thrombotic, and platelet disorders (BPDs) are diseases that affect ∼300 individuals per million births. With the exception of hemophilia and von Willebrand disease patients, a molecular analysis for patients with a BPD is often unavailable. Many specialized tests are usually required to reach a putative diagnosis and they are typically performed in a step-wise manner to control costs. This approach causes delays and a conclusive molecular diagnosis is often never reached, which can compromise treatment and impede rapid identification of affected relatives. To address this unmet diagnostic need, we designed a high-throughput sequencing platform targeting 63 genes relevant for BPDs. The platform can call single nucleotide variants, short insertions/deletions, and large copy number variants (though not inversions) which are subjected to automated filtering for diagnostic prioritization, resulting in an average of 5.34 candidate variants per individual. We sequenced 159 and 137 samples, respectively, from cases with and without previously known causal variants. Among the latter group, 61 cases had clinical and laboratory phenotypes indicative of a particular molecular etiology, whereas the remainder had an a priori highly uncertain etiology. All previously detected variants were recapitulated and, when the etiology was suspected but unknown or uncertain, a molecular diagnosis was reached in 56 of 61 and only 8 of 76 cases, respectively. The latter category highlights the need for further research into novel causes of BPDs. The ThromboGenomics platform thus provides an affordable DNA-based test to diagnose patients suspected of having a known inherited BPD. PMID:27084890

  6. Higher proportion of inactive Gsk3β in platelets of elderly patients with bipolar disorder: an effect of treatment?

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    Rodolfo Braga Ladeira

    2013-09-01

    Full Text Available Objective: It has been postulated that mood stabilizers inhibit glycogen synthase kinase 3-beta (Gsk3β activity, mainly through its phosphorylation on serine-9 (Ser9. However, in vivo studies addressing Gsk3β activity in patients with bipolar disorder are scarce. Here, we compare Gsk3β inactivation (as indicated by Ser9-phosphorylation in platelets of elderly patients with bipolar disorder undergoing clinical treatment and healthy elderly adults not taking medication. Methods: Platelet samples were obtained from 37 elderly adults (bipolar disorder = 19, controls = 18. Relative changes in Gsk3β inactivation was estimated by comparing the ratios of phosphorylated Gsk3β to total Gsk3β (p-Gsk3β Ser9/Gsk3β between the disease and control groups. Results: Phosphorylated-Gsk3β (p < 0.001 and the p-Gsk3β Ser9/Gsk3β ratio (p = 0.006 were elevated in bipolar patients. In the bipolar disorder group, p-Gsk3β Ser9/Gsk3β was positively correlated with serum lithium levels (r = 0.478, p = 0.039. Conclusions: Gsk3β inactivation is higher in this group of elderly adults undergoing treatment for bipolar disorder. However, whether the treatment or the disease causes Gsk3β inactivation was confounded by the lack of an unmedicated, bipolar control group and the non-uniform treatment regimens of the bipolar disorder group. Thus, further studies should help distinguish whether Gsk3β inactivation is an effect of drug treatment or an intrinsic characteristic of bipolar disorder.

  7. Bone marrow pathologic abnormalities in familial platelet disorder with propensity for myeloid malignancy and germline RUNX1 mutation.

    Science.gov (United States)

    Kanagal-Shamanna, Rashmi; Loghavi, Sanam; DiNardo, Courtney D; Medeiros, L Jeffrey; Garcia-Manero, Guillermo; Jabbour, Elias; Routbort, Mark J; Luthra, Rajyalakshmi; Bueso-Ramos, Carlos E; Khoury, Joseph D

    2017-06-28

    A subset of patients with familial platelet disorder with propensity to myeloid malignancy and germline RUNX1 mutation develops hematological malignancies, often myelodysplastic syndrome/acute myeloid leukemia, currently recognized in the 2016 WHO classification. Patients who develop hematologic malignancies are typically young, respond poorly to conventional therapy, and need allogeneic stem cell transplant from non-familial donors. Understanding the spectrum of bone marrow morphologic and genetic findings in these patients is critical to ensure diagnostic accuracy and develop criteria to recognize the onset of hematologic malignancies, particularly myelodysplastic syndrome. However, bone marrow features remain poorly characterized. To address this knowledge gap, we analyzed the clinicopathologic and genetic findings of 11 patients from 7 pedigrees. Of these, 6 patients did not develop hematologic malignancies over a 22-month follow-up period; 5 patients developed hematologic malignancies (3 acute myeloid leukemia; 2 myelodysplastic syndrome). All patients had thrombocytopenia at initial presentation. All 6 patients who did not develop hematologic malignancies showed baseline bone marrow abnormalities: low-for-age cellularity (n=4), dysmegakaryopoiesis (n=5), megakaryocytic hypoplasia/hyperplasia (n=5), and eosinophilia (n=4). Two patients had multiple immunophenotypic alterations in CD34-positive myeloblasts; 1 patient had clonal hematopoiesis. In contrast, patients who developed hematologic malignancies had additional cytopenia(s) (n=4), abnormal platelet granulation (n=5), bone marrow hypercellularity (n=4), dysplasia in ≥2 lineages including megakaryocytes (n=3) and acquired clonal genetic aberrations (n=5). In conclusion, our study demonstrated that specific bone marrow abnormalities and acquired genetic alterations may be harbingers of progression to hematological malignancies in patients with familial platelet disorder with germline RUNX1 mutation

  8. Childhood trauma and platelet brain-derived neurotrophic factor (BDNF) after a three month follow-up in patients with major depressive disorder.

    Science.gov (United States)

    Jeon, Hong Jin; Kang, Eun-Suk; Lee, Eun Ho; Jeong, Eu-Gene; Jeon, Ju-Ri; Mischoulon, David; Lee, Dongsoo

    2012-07-01

    A large amount of brain-derived neurotrophic factor (BDNF) is stored in the human platelets and only small amounts of it circulate in the plasma. However, a few studies have focused on platelet BDNF in patients with major depressive disorder (MDD) and childhood trauma. Our study population consisted of 105 MDD patients and 50 healthy controls. We used the mini-international neuropsychiatric interview (M.I.N.I.), the early trauma inventory self report-short form (ETISR-SF), as well as measured serum, plasma, and platelet BDNF at baseline, 1 month, and 3 month periods. There was a significant association between childhood trauma and platelet BDNF at baseline, 1 month, and 3 months, after adjusting for age, gender, education, body mass index, severity of depression, anxiety, alcohol consumption, and current stress. Conversely, plasma and serum BDNF did not have a significant association with childhood trauma. MDD patients revealed significantly higher levels of platelet BDNF in those with childhood trauma than in those without (t = 2.4, p = 0.018), and platelet BDNF was significantly higher in cases with sexual abuse on post-hoc analysis (p = 0.042). However, no significant differences were found in healthy controls, according to whether or not they had experienced childhood trauma. Platelet BDNF showed a significant correlation with severity of childhood trauma at baseline (r = 0.25, p = 0.012) and at 3 months (r = 0.38, p = 0.003) in MDD. In conclusion, platelet BDNF was significantly higher in MDD patients with childhood trauma than in those without, and it was correlated with severity of trauma.

  9. Lithium increases platelet serine-9 phosphorylated GSK-3β levels in drug-free bipolar disorder during depressive episodes.

    Science.gov (United States)

    de Sousa, Rafael T; Zanetti, Marcus V; Talib, Leda L; Serpa, Mauricio H; Chaim, Tiffany M; Carvalho, Andre F; Brunoni, Andre R; Busatto, Geraldo F; Gattaz, Wagner F; Machado-Vieira, Rodrigo

    2015-03-01

    Glycogen synthase kinase-3 β (GSK3β) is an intracellular enzyme directly implicated in several neural processes relevant to bipolar disorder (BD) pathophysiology. GSK3β is also an important target for lithium and antidepressants. When phosphorylated at serine-9, GSK3β becomes inactive. Few studies evaluated serine-9 phosphorylated GSK3β (phospho-GSK3β) levels in BD subjects in vivo and no study has assessed it specifically in bipolar depression. Also, the effect of lithium monotherapy on GSK3β has never been studied in humans. In 27 patients with bipolar depression, total GSK3β and phospho-GSK3β were assessed in platelets by enzyme immunometric assay. Subjects were evaluated before and after 6 weeks of lithium treatment at therapeutic levels. Healthy subjects (n = 22) were used as a control group. No differences in phospho-GSK3β or total GSK3β were observed when comparing drug-free BD subjects in depression and healthy controls. Baseline HAM-D scores were not correlated with phospho-GSK3β and total GSK3β levels. From baseline to endpoint, lithium treatment inactivated GSK3β by significantly increasing phospho-GSK3β levels (p = 0.010). Clinical improvement (baseline HAM-D - endpoint HAM-D) negatively correlated with the increase in phospho-GSK3β (p = 0.03). The present results show that lithium inactivates platelet GSK3β in BD during mood episodes. No direct association with pathophysiology of BD was observed. Further studies are needed to clarify the role of GSK3β as a key biomarker in BD and its association with treatment response as well as the relevance of GSK3β in other neuropsychiatric disorders and as a new therapeutic target per se. Published by Elsevier Ltd.

  10. Overview of platelet physiology and laboratory evaluation of platelet function.

    Science.gov (United States)

    Rodgers, G M

    1999-06-01

    Appropriate laboratory testing for the platelet-type bleeding disorders hinges on an adequate assessment in the history and physical examination. Patients with histories and screening laboratory results consistent with coagulation disorders (hemophilia, disseminated intravascular coagulation) are not appropriate candidates for platelet function testing. In contrast, patients with a lifelong history of platelet-type bleeding symptoms and perhaps a positive family history of bleeding would be appropriate for testing. Figure 6 depicts one strategy to evaluate these patients. Platelet morphology can easily be evaluated to screen for two uncommon qualitative platelet disorders: Bernard-Soulier syndrome (associated with giant platelets) and gray platelet syndrome, a subtype of storage pool disorder in which platelet granulation is morphologically abnormal by light microscopy. If the bleeding disorder occurred later in life (no bleeding with surgery or trauma early in life), the focus should be on acquired disorders of platelet function. For those patients thought to have an inherited disorder, testing for vWD should be done initially because approximately 1% of the population has vWD. The complete vWD panel (factor VIII coagulant activity, vWf antigen, ristocetin cofactor activity) should be performed because many patients will have abnormalities of only one particular panel component. Patients diagnosed with vWD should be classified using multimeric analysis to identify the type 1 vWD patients likely to respond to DDAVP. If vWD studies are normal, platelet aggregation testing should be performed, ensuring that no antiplatelet medications have been ingested at least 1 week before testing. If platelet aggregation tests are normal and if suspicion for an inherited disorder remains high, vWD testing should be repeated. The evaluation of thrombocytopenia may require bone marrow examination to exclude primary hematologic disorders. If future studies with thrombopoietin assays

  11. Platelet mimicry

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moein; Hunter, Alan Christy; Peer, Dan

    2016-01-01

    Here we critically examine whether coating of nanoparticles with platelet membranes can truly disguise them against recognition by elements of the innate immune system. We further assess whether the "cloaking technology" can sufficiently equip nanoparticles with platelet-mimicking functionalities...

  12. Platelet Count

    Science.gov (United States)

    ... their spleen removed surgically Use of birth control pills (oral contraceptives) Some conditions may cause a temporary (transitory) increased ... increased platelet counts include estrogen and birth control pills (oral contraceptives). Mildly decreased platelet counts may be seen in ...

  13. Erythropoietin and thrombopoietin mimetics: Natural alternatives to erythrocyte and platelet disorders.

    Science.gov (United States)

    Gutti, Usha; Pasupuleti, Satya Ratan; Sahu, Itishri; Kotipalli, Aneesh; Undi, Ram Babu; Kandi, Ravinder; Venakata Saladi, Raja Gopal; Gutti, Ravi Kumar

    2016-12-01

    Erythropoietin (EPO) and thrombopoietin (TPO) plays a major role in the regulation of hematopoietic development. Though, blood transfusion was the most widely used method to treat low blood count, over the years with advancements in recombinant technology and drug designing, the EPO and TPO mimetics are dominating the therapeutics industry. On the other hand, the recombinant human EPO and TPO are associated either with reduced half-life or immune reactions. The restoration of alternate medicine in recent years has the hope to overcome limitations associated with recombinant technology, to treat various disorder including blood diseases, with low to no side effects. The work in recent years on plant derived mimetics suggests a paradigm shift in the way diseases are treated. Here, we are providing a comprehensive review on the EPO and TPO recombinant counterparts and synthetic mimetics studied till date with a focus on the need for more natural alternatives.

  14. Kinetics of 3H-serotonin uptake by platelets in infantile autism and developmental language disorder (including five pairs of twins)

    Energy Technology Data Exchange (ETDEWEB)

    Katsui, T.; Okuda, M.; Usuda, S.; Koizumi, T.

    1986-03-01

    The kinetics of 5-HT uptake by platelets was studied in cases of infantile autism and developmental language disorder (DLD) and normal subjects. Two patients of the autism group were twins, and the seven patients of the DLD group were members of four pairs of twins. The Vmax values (means +/- SD) for autism and DLD were 6.46 +/- .90 pmol 5-HT/10(7) cells/min and 4.85 +/- 1.50 pmol 5-HT/10(7) cells/min, respectively. These values were both significantly higher than that of 2.25 +/- .97 pmole 5-HT/10(7) cells/min for normal children. The Km values of the three groups were not significantly different. Data on the five pairs of twins examined suggested that the elevated Vmax of 5-HT uptake by platelets was determined genetically.

  15. Treatment of Anxiety Disorders and Comorbid Alcohol Abuse with Buspirone in a Patient with Antidepressant-Induced Platelet Dysfunction: A Case Report

    Directory of Open Access Journals (Sweden)

    Mir Mazhar

    2013-01-01

    Full Text Available The risk of abnormal bleeding with serotonin reuptake inhibitors has been known, but there is insufficient evidence base to guide pharmacological treatment of anxiety in patients with underlying haematological conditions. The following case report is about a 50-year-old female with generalized anxiety disorder, social phobia, obsessive compulsive disorder, and alcohol abuse where pharmacological treatment of anxiety symptoms has been difficult as it would lead to bruising due to the patient’s underlying qualitative platelet dysfunction. Treatment with venlafaxine, citalopram, escitalopram, and clomipramine resulted in improvement and anxiety symptoms, as well as reduction in alcohol use, but pharmacological treatment has to be discontinued because of bruising and hematomas. In view of an active substance use disorder, benzodiazepines were avoided as a treatment option. The patient’s anxiety symptoms and comorbid alcohol abuse responded well to pharmacological treatment with buspirone which gradually titrated up to a dose of 30 mg BID. Patient was followed for around a six-month period while she was on buspirone before being discharged to family doctor’s care. Buspirone is unlikely to have a significant effect on platelet serotonin transponder and could be an effective alternative for pharmacological treatment of anxiety in patients with a bleeding diathesis.

  16. 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.

  17. 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.

  18. Blood Platelet Disorder and Laboratory Examination%血小板疾病及实验室检查

    Institute of Scientific and Technical Information of China (English)

    台虹

    2006-01-01

    血小板是一个多功能的细胞,它的主要生理功能是参与止血与血栓的形成。血小板疾病依据血小板质和量异常被分为血小板功能异常性疾病(Platelet Function Disorder)和血小板数量异常性疾病(Platelet Quantity Disorder)。血小板数量异常包括血小板减少症(Thrombocytopenia)和血小板增多症(Throbocythemia)。

  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. Platelet Donation

    Science.gov (United States)

    ... of gratitude that washed over me when I saw those platelets going into my husband’s body. I ... Needles LGBTQ+ Donors Blood Donor Community SleevesUp Games Facebook Avatars and Badges Banners eCards Red Cross Information ...

  1. Platelet function tests: a comparative review

    Directory of Open Access Journals (Sweden)

    Paniccia R

    2015-02-01

    Full Text Available Rita Paniccia,1,2 Raffaella Priora,1,2 Agatina Alessandrello Liotta,2 Rosanna Abbate1,2 1Department of Experimental and Clinical Medicine, Thrombosis Center, University of Florence, Florence, Italy; 2Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Abstract: In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or quantitative platelet defects promote bleeding, whereas the high residual reactivity of platelets in patients on antiplatelet therapies moves forward thromboembolic complications. The biochemical mechanisms of the different phases of platelet activation – adhesion, shape change, release reaction, and aggregation – have been well delineated, whereas their complete translation into laboratory assays has not been so fulfilled. Laboratory tests of platelet function, such as bleeding time, light transmission platelet aggregation, lumiaggregometry, impedance aggregometry on whole blood, and platelet activation investigated by flow cytometry, are traditionally utilized for diagnosing hemostatic disorders and managing patients with platelet and hemostatic defects, but their use is still limited to specialized laboratories. To date, a point-of-care testing (POCT dedicated to platelet function, using pertinent devices much simpler to use, has now become available (ie, PFA-100, VerifyNow System, Multiplate Electrode Aggregometry [MEA]. POCT includes new methodologies which may be used in critical clinical settings and also in general laboratories because they are rapid and easy to use, employing whole blood without the necessity of sample processing. Actually, these different platelet methodologies for the evaluation of inherited and acquired bleeding disorders and/or for monitoring antiplatelet therapies are spreading and the study of platelet function is strengthening. In this review, well

  2. 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.

  3. Effect of Jin-3-Needling Therapy on Plasma Corticosteroid, Adrenocorticotrophic Hormone and Platelet 5-HT Levels in Patients with Generalized Anxiety Disorder

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To observe the therapeutic efficacy of Jin-3-needling therapy(J3N)on generalized anxiety disorder(GAD)through clinical global impression scale(CGI),and to explore the mechanism by measuring the plasma levels of corticosteroid(CS),adrenocorticotrophic hormone (ACTH),and platelet 5-hydroxytryptamine(5-HT)before and after treatment.Methods:Eightysix GAD patients with the diagnosis agreeing with the inclusion criteria were assigned,according to the sequence of visiting time,to three groups.The 29 patients in the Western medicine group were treated mainly with fluoxetine or paroxetine,Alprazolam might be given additionally in severe conditions if necessary;the 29 patients in the needling group received J3N therapy with Sishenzhen,Dingshenzhen,Neiguan(PC6),Shenmen(HT7)and Sanyinjiao(SP6)as the chief acupoints selected;and the 28 patients in the combined treatment group were treated with both drugs and needling in the same way as applied in the above two groups.The therapeutic course for all was 6weeks.Conditions of patients were evaluated before and after treatment with CGI,and levels of CS,ACTH as well as 5-HT were measured by high performance liquid chromatography-electrochemistry.Results:By CGI scoring,the scores of severity index and the general index were not different significantly in the three groups,but the efficacy index proved to be the highest in the needling group,the second in the combined trentment group,and the lowest in the drug group.Plasma level of ACTH and platelet content of 5-HT were lowered in all the three groups after treatment,showing statistical significance(P<0.05),but no significant change was found in CS level(P>0.05).Conclusion:The therapeutic efficacy of J3N in treating GAD is equivalent to,but with the efficacy index significantly higher than,that of conventional treatment.Moreover,when combined with drugs,needling might effectively prevent the side effect of the routinely used Western drugs.The regulatory action of needling

  4. Role of platelets in neuroinflammation: a wide-angle perspective

    Directory of Open Access Journals (Sweden)

    Etemadifar Masoud

    2010-02-01

    Full Text Available Abstract Objectives This review summarizes recent developments in platelet biology relevant to neuroinflammatory disorders. Multiple sclerosis (MS is taken as the "Poster Child" of these disorders but the implications are wide. The role of platelets in inflammation is well appreciated in the cardiovascular and cancer research communities but appears to be relatively neglected in neurological research. Organization After a brief introduction to platelets, topics covered include the matrix metalloproteinases, platelet chemokines, cytokines and growth factors, the recent finding of platelet PPAR receptors and Toll-like receptors, complement, bioactive lipids, and other agents/functions likely to be relevant in neuroinflammatory diseases. Each section cites literature linking the topic to areas of active research in MS or other disorders, including especially Alzheimer's disease. Conclusion The final section summarizes evidence of platelet involvement in MS. The general conclusion is that platelets may be key players in MS and related disorders, and warrant more attention in neurological research.

  5. 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.

  6. Ultrastructural studies of the gray platelet syndrome.

    Science.gov (United States)

    White, J G

    1979-05-01

    The gray platelet syndrome (GPS) is a rare inherited disorder in which peripheral blood platelets are relatively large, vacuolated, and almost devoid of cytoplasmic granulation. In the present study we have evaluated the ultrastructure and cytochemistry of platelets from 2 patients with the GPS to determine precisely which organelles are missing from their cells. The findings indicate that gray platelets contain normal numbers of mitochondria, dense bodies, peroxisomes, and lysosomes but specifically lack alpha-granules. Preliminary studies of megakaryocytes from 1 of the 2 patients suggest that the defect in granule formation may lie at the level of the Golgi zone.

  7. The use of platelet-rich plasma to augment conservative and surgical treatment of hip and pelvic disorders

    Science.gov (United States)

    Kraeutler, Matthew J.; Garabekyan, Tigran; Mei-Dan, Omer

    2016-01-01

    Summary Background In recent years, platelet-rich plasma (PRP) has gained popularity within the orthopaedic community as a treatment modality to enhance tissue healing. Purpose This review aims to concisely present the current indications for PRP injections in the treatment of hip and pelvic pathologies and to describe some novel applications for PRP which have not yet been reported in the literature. Methods We reviewed the literature on the non-operative and operative indications for PRP in the treatment of hip and pelvic pathologies. Conclusions With regard to hip and pelvic pathologies, PRP injections are used most commonly as a non-operative intervention, and have been described in the literature to treat osteoarthritis of the hip joint as well as tendinopathy of the hamstrings, adductor longus, and gluteus medius. In contrast, most of the surgical applications of PRP for the hip are novel, with few reported studies in the literature. Because of the increasing awareness of PRP’s beneficial effects on musculoskeletal healing and thus the growing number of indications for its use, this review also describes some novel applications for PRP, including osteitis pubis, post-microfracture of the hip, tears of the rectus femoris, and avulsion of the sartorius muscle. Level of evidence V. PMID:28066748

  8. Platelet Function Tests

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Platelet Function Tests Share this page: Was this page helpful? ... their patients by ordering one or more platelet function tests. Platelet function testing may include one or more of ...

  9. Hereditary sideroblastic anemia with associated platelet abnormalities.

    Science.gov (United States)

    Soslau, G; Brodsky, I

    1989-12-01

    A 62 year old male (R.H.) presented with a mild anemia (Hb 11-12 gm%) and a history of multiple hemorrhagic episodes. The marrow had 40-50% sideroblasts. Marrow chromosomes were normal. His wife was hematologically normal, while one daughter, age 30 years, had a sideroblastic anemia (Hb 11-12 gm%) with 40-50% sideroblasts in the marrow. Her anemia was first noted at age 15 years. Administration of vitamin B6 did not correct the anemia in either the father or daughter. Platelet abnormalities inherited jointly with this disorder are described for the first time. Both R.H. and his daughter had prolonged bleeding times, with normal PTT, PT times, fVIII:C, fVIII:Ag levels, and vWF multimers, which may rule out a von Willebrand's disease. They have normal platelet numbers but abnormally low platelet adhesiveness and greatly depressed ADP, collagen, and epinephrine responsiveness. Response to ristocetin was in the low normal range, and aggregation with thrombin was normal. While desmopressin completely normalized R.H.'s bleeding time, none of these platelet parameters were improved. No differences in the SDS PAGE protein patterns of RH platelets could be detected in comparison to normal samples. His platelets took up and released serotonin (5HT) normally, and electron micrographs defined no morphological abnormalities. However, no ATP was released from platelets activated with collagen, and when followed by thrombin about fourfold greater ATP was released by control platelets as compared to RH platelets. The dense granule fraction derived from RH platelets contained about 20% the level of ATP, 40% the level of ADP, and 50% the level of 5HT detected in a normal sample. The results indicate that the bleeding disorder is related to a non-classical heritable storage pool defect. The connection between the inherited sideroblastic anemia and platelet defects is obscure.

  10. Roll, adhere, spread and contract: structural mechanics of platelet function.

    Science.gov (United States)

    Sorrentino, Simona; Studt, Jan-Dirk; Medalia, Ohad; Tanuj Sapra, K

    2015-01-01

    Platelets are involved in life-sustaining processes such as hemostasis, wound healing, atherothrombosis and angiogenesis. Mechanical trauma to blood vessels causes platelet activation resulting in their adherence and clot formation at the damaged site, culminating in clot retraction and tissue repair. Two of the major players underlying this process are the cytoskeleton, i.e., actin and microtubules, and the membrane integrin receptors. Rare congenital bleeding disorders such as Glanzmann thrombasthenia and Bernard-Soulier syndrome are associated with genetic alterations of platelet surface receptors, also affecting the platelet cytoskeletal structure. In this review, we summarize the current knowledge about platelet structure and adhesion, and delve into the mechanical aspects of platelet function. Platelets lack a nucleus, and can thus provide a minimal model of a biological cell. New biophysical tools may help to scrutinize platelets anew and to extend the existing knowledge on cell biology.

  11. Platelet mitochondrial function and dysfunction: physiological consequences

    Energy Technology Data Exchange (ETDEWEB)

    Popov, D.

    2015-07-01

    There is a general trend in revisiting mitochondria using the up-to-date technologies that uncovered novel attributes of this organelle, such as the intracellular displacement to locations where an energy supply is needed, the dynamic shape changes and turnover, the initiation of signaling to the rest of the cell, and the ability to crosstalk with other cellular organelles. The in-depth scrutiny of platelet mitochondria role in health and pathology is included within this ongoing revisiting trend. The current article puts into a nutshell the most recent data on platelet mitochondria function and disease-related ion, focusing on generation of stress- and apoptosis-related signaling molecules, overproduction of reactive oxygen species during activation and disease, on the biomarker potential of platelets mitochondria, and their prospective exploitation in translational applications. These novel findings complete the physiological profile of platelets and could have potential therapeutic effectiveness in platelet-associated disorders.

  12. Platelet matching for alloimmunized patients

    Institute of Scientific and Technical Information of China (English)

    S H.Hsu

    2010-01-01

    @@ Platelets play an essential role in blood coagulation,hemostasis and maintenance of vascular integrity.Platelets are utilized primarily to prevent or treat bleeding in thrombocytopenic patients and patients with impaired platelet production in the bone marrow and/or with dysfunctional platelets.In current practice,platelet transfusion begins with randomly selected platelet products:either pooled platelets prepared from whole blood derived platelets; or single donor platelets prepared by apheresis procedures.

  13. Single-platelet nanomechanics measured by high-throughput cytometry

    Science.gov (United States)

    Myers, David R.; Qiu, Yongzhi; Fay, Meredith E.; Tennenbaum, Michael; Chester, Daniel; Cuadrado, Jonas; Sakurai, Yumiko; Baek, Jong; Tran, Reginald; Ciciliano, Jordan C.; Ahn, Byungwook; Mannino, Robert G.; Bunting, Silvia T.; Bennett, Carolyn; Briones, Michael; Fernandez-Nieves, Alberto; Smith, Michael L.; Brown, Ashley C.; Sulchek, Todd; Lam, Wilbur A.

    2016-10-01

    Haemostasis occurs at sites of vascular injury, where flowing blood forms a clot, a dynamic and heterogeneous fibrin-based biomaterial. Paramount in the clot's capability to stem haemorrhage are its changing mechanical properties, the major drivers of which are the contractile forces exerted by platelets against the fibrin scaffold. However, how platelets transduce microenvironmental cues to mediate contraction and alter clot mechanics is unknown. This is clinically relevant, as overly softened and stiffened clots are associated with bleeding and thrombotic disorders. Here, we report a high-throughput hydrogel-based platelet-contraction cytometer that quantifies single-platelet contraction forces in different clot microenvironments. We also show that platelets, via the Rho/ROCK pathway, synergistically couple mechanical and biochemical inputs to mediate contraction. Moreover, highly contractile platelet subpopulations present in healthy controls are conspicuously absent in a subset of patients with undiagnosed bleeding disorders, and therefore may function as a clinical diagnostic biophysical biomarker.

  14. Platelet function in bleeding disorders

    NARCIS (Netherlands)

    van Bladel, E.R.

    2013-01-01

    The first bleeding diathesis we studied was hemophilia A. Since FVIII activity level does not always correlate with the bleeding tendency in individual patients, bleeding tendency must also be influenced by other factors. Earlier studies excluded the remaining clotting factors and FVIII genotype as

  15. 儿童血液病血小板无效输注的机制和治疗%The treatment and mechanism of platelet transfusion refractoriness in pediatric hematological disorders

    Institute of Scientific and Technical Information of China (English)

    洪丹; 郑德菲; 卢俊; 肖佩芳; 孙伊娜; 吕慧; 翟宗; 翟钦; 杜智卓

    2015-01-01

    Objective To explore the treatment and mechanism of platelet transfusion refractoriness in pediatric hema-tological disorders.Methods Retrospective analyses were performed from 4 children diagnosed with platelet transfusion refractoriness between 2013 and 2014 in Children's Hospital of Soochow University. Clinical manifestation, laboratory tests, and the effect of plasma exchange were evaluated on pediatric platelet refractoriness.Results Two males and two females with age ranged from 2 years to 11 years and 9 months met the criteria of platelet refractoriness. Three cases were diagnosed as AML-M5 (M5), and one case was diagnosed as severe aplastic anemia (SAA). Platelet refractoriness occurred in one case of M5 after induction chemotherapy, and two cases in the stage of hematopoietic stem cell transplantation (HSCT). The SAA patient showed platelet refractoriness on her admission. The screening for HLA antibodies with the method of Immune Luminex beads streaming technology (Luminex) revealed that HLA-I antibody reaction were positive in three patients. All four patients showed a good response to the treatment of plasma exchange.Conclusions HLA-I class antibodies are closely associated with platelet refracto-riness, the plasma exchange treatment is effective and safe for platelet refractoriness in children.%目的 探讨儿童血液肿瘤患者血小板无效输注的分子学机制及治疗.方法回顾性分析2013年至2014年收治的4例血小板无效输注患儿的临床特征及实验室检查资料,评估血浆置换对儿童血小板无效输注的疗效.结果 4例患儿中男2例、女2例,年龄2岁~11岁9个月,其中3例为急性单核细胞白血病(M5),1例为重型再生障碍性贫血(SAA).1例M5患儿首次化疗后、2例M5患儿造血干细胞移植后发生血小板无效输注,1例SAA患儿入院时即表现为血小板无效输注.免疫磁珠流式液相芯片技术(Luminex)检测,3例患儿HLA-I类抗体阳性,1例患者HLA-I类阴性.

  16. Clinical application of radiolabelled platelets

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, C. (Medical Univ. Lubeck, Lubeck (DE))

    1990-01-01

    This book presents papers on the clinical applications of radiolabelled platelets. The papers are grouped into six sections on platelet labelling techniques, radiolabelled platelets in cardiology, monitoring of antiplatelet therapy, platelet scintigraphy in stroke patients, platelet scintigraphy in angiology, and platelet scintigraphy in hematology and other clinical applications, including renal transplant rejection.

  17. 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.

  18. Enhanced platelet adhesion in essential thrombocythemia after in vitro activation

    Directory of Open Access Journals (Sweden)

    Andreas C. Eriksson

    2010-06-01

    Full Text Available Objective: Essential thrombocythemia (ET is a chronic myeloproliferative disorder characterized by elevated platelet counts and increased risk of thrombosis. Ex vivo data suggest increased platelet reactivity in agreement with the increased thrombosis risk, while in vitro tests often detect decreased platelet activity. The present study aimed to investigate adhesion of ET-platelets in vitro, which is an aspect of platelet function that has been addressed in only a few studies on ET patients. Material and Methods: The study included 30 ET patients and 14 healthy controls. Platelet adhesion was measured with a static platelet adhesion assay. Results: The main finding was that ET-platelets were more readily activated by adhesion-inducing stimuli in vitro than control platelets. This was particularly evident in elderly patients and when using multiple stimuli, such as surfaces of collagen or fibrinogen combined with addition of adenosine 5’-diphosphate or ristocetin. Such multiple stimuli resulted in adhesion above the control mean +2 standard deviations for approximately 50% of the patients.Conclusion: The results are in accordance with the concept of increased platelet activity in ET, but opposite to most other in vitro studies. We suggest that the conditions in the adhesion assay might mimic the in vivo situation regarding the presence of chronic platelet activation.

  19. A new ibuprofen derivative inhibits platelet aggregation and ROS mediated platelet apoptosis.

    Directory of Open Access Journals (Sweden)

    Kodagahalli S Rakesh

    Full Text Available Thrombocytopenia is a serious issue connected with the pathogenesis of several human diseases including chronic inflammation, arthritis, Alzheimer's disease, cardiovascular diseases (CVDs and other oxidative stress-associated pathologies. The indiscriminate use of antibiotics and other biological drugs are reported to result in thrombocytopenia, which is often neglected during the treatment regime. In addition, augmented oxidative stress induced by drugs and pathological conditions has also been shown to induce thrombocytopenia, which seems to be the most obvious consequence of elevated rate of platelet apoptosis. Thus, blocking oxidative stress-induced platelet apoptosis would be of prime importance in order to negotiate thrombocytopenia and associated human pathologies. The current study presents the synthesis and platelet protective nature of novel ibuprofen derivatives. The potent anti-oxidant ibuprofen derivative 4f was selected for the study and the platelet protective efficacy and platelet aggregation inhibitory property has been demonstrated. The compound 4f dose dependently mitigates the oxidative stress-induced platelet apoptosis in both platelet rich plasma and washed platelets. The platelet protective nature of compound 4f was determined by assessing various apoptotic markers such as ROS generation, cytosolic Ca2+ levels, PS externalization, cytochrome C translocation, Caspase activation, mitochondrial membrane depolarization, cytotoxicity, LDH leakage and tyrosine phosphorylation of cytosolic proteins. Furthermore, compound 4f dose dependently ameliorated agonist induced platelet aggregation. Therefore, compound 4f can be estimated as a potential candidate in the treatment regime of pathological disorders associated with platelet activation and apoptosis. In addition, compound 4f can be used as an auxiliary therapeutic agent in pathologies associated with thrombocytopenia.

  20. 21 CFR 864.7695 - Platelet factor 4 radioimmunoassay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Platelet factor 4 radioimmunoassay. 864.7695 Section 864.7695 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES.... This device measures platelet activiation, which may indicate a coagulation disorder, such as...

  1. Platelets and hemostasis

    Directory of Open Access Journals (Sweden)

    M. A. Panteleev

    2014-09-01

    Full Text Available Platelets are anuclear cell fragments playing important role in hemostasis, termination of bleeding after damage, as well as in pathological thrombus formation. The main action of platelets is the formation of aggregates, overlapping the injury. They obtained the ability to aggregate by the transition process called activation. Despite the relatively simple and definite function platelet structure is very difficult: they have almost a full set of organelles, including the endoplasmic reticulum, mitochondria and other entities. When activated platelets secrete various granules interact with plasma proteins and red blood cells and other tissues. Their activation is controlled by multiple receptors and complex signaling cascades. In this review platelet structure, mechanisms of its functioning in health and disease, diagnostic methods of platelet function and approaches to their correction were considered. Particular attention will be given to those areas of the science of platelets, which still lay hidden mysteries.

  2. 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.

  3. 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.

  4. The functional role of platelets in the regulation of angiogenesis.

    Science.gov (United States)

    Walsh, Tony G; Metharom, Pat; Berndt, Michael C

    2015-01-01

    Functionally, platelets are primarily recognized as key regulators of thrombosis and hemostasis. Upon vessel injury, the typically quiescent platelet interacts with subendothelial matrix to regulate platelet adhesion, activation and aggregation, with subsequent induction of the coagulation cascade forming a thrombus. Recently, however, newly described roles for platelets in the regulation of angiogenesis have emerged. Platelets possess an armory of pro- and anti-angiogenic proteins, which are actively sequestered and highly organized in α-granule populations. Platelet activation facilitates their release, eliciting potent angiogenic responses through mechanisms that appear to be tightly regulated. In conjunction, the release of platelet-derived phospholipids and microparticles has also earned merit as synergistic regulators of angiogenesis. Consequently, platelets have been functionally implicated in a range of angiogenesis-dependent processes, including physiological roles in wound healing, vascular development and blood/lymphatic vessel separation, whilst facilitating aberrant angiogenesis in a range of diseases including cancer, atherosclerosis and diabetic retinopathy. Whilst the underlying mechanisms are only starting to be elucidated, significant insights have been established, suggesting that platelets represent a promising therapeutic strategy in diseases requiring angiogenic modulation. Moreover, anti-platelet therapies targeting thrombotic complications also exert protective effects in disorders characterized by persistent angiogenesis.

  5. Detection of Platelet-Monocyte Aggregates by the ADAM® Image Cytometer

    OpenAIRE

    Jung, Bo Kyeung; Cho, Chi Hyun; Moon, Kyung Chul; sung Hur, Dae; YOON, Jeong-Ah; Yoon, Soo-Young

    2014-01-01

    Background: Inappropriate platelet activation is known to be associated with various thrombotic disorders. Platelet-monocyte aggregates (PMAs), whose formation is mediated by platelet surface P-selectin (CD62P), can be used as a reliable marker to detect platelet activation. Previous studies have generally detected PMAs through flow cytometry-based approaches. Recently, the ADAM® image cytometer (Nanoentek Inc., Seoul, Korea) was developed for image-based cellular analysis. In this study, we ...

  6. The role of platelets in hemostasis and the effects of snake venom toxins on platelet function.

    Science.gov (United States)

    de Queiroz, Mayara Ribeiro; de Sousa, Bruna Barbosa; da Cunha Pereira, Déborah Fernanda; Mamede, Carla Cristine Neves; Matias, Mariana Santos; de Morais, Nadia Cristina Gomes; de Oliveira Costa, Júnia; de Oliveira, Fábio

    2017-07-01

    The human body has a set of physiological processes, known as hemostasis, which keeps the blood fluid and free of clots in normal vessels; in the case of vascular injury, this process induces the local formation of a hemostatic plug, preventing hemorrhage. The hemostatic system in humans presents complex physiological interactions that involve platelets, plasma proteins, endothelial and subendothelial structures. Disequilibrium in the regulatory mechanisms that control the growth and the size of the thrombus is one of the factors that favors the development of diseases related to vascular disorders such as myocardial infarction and stroke, which are among the leading causes of death in the western world. Interfering with platelet function is a strategy for the treatment of thrombotic diseases. Antiplatelet drugs are used mainly in cases related to arterial thrombosis and interfere in the formation of the platelet plug by different mechanisms. Aspirin (acetylsalicylic acid) is the oldest and most widely used antithrombotic drug. Although highly effective in most cases, aspirin has limitations compared to other drugs used in the treatment of homeostatic disorders. For this reason, research related to molecules that interfere with platelet aggregation are of great relevance. In this regard, snake venoms are known to contain a number of molecules that interfere with hemostasis, including platelet function. The mechanisms by which snake venom components inhibit or activate platelet aggregation are varied and can be used as tools for the diagnosis and the treatment of several hemostatic disorders. The aim of this review is to present the role of platelets in hemostasis and the mechanisms by which snake venom toxins interfere with platelet function. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. 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.).

  8. 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.

  9. 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.

  10. 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.

  11. Effects of clomipramine treatment on cerebrospinal fluid monoamine metabolites and platelet sup 3 H-imipramine binding and serotonin uptake and concentration in major depressive disorder

    Energy Technology Data Exchange (ETDEWEB)

    Maartensson, B.; Waegner, A.; Aasberg, M. (Department of Psychiatry and Psychology, Karolinska Hospital, Stockholm (Sweden)); Beck, O.; Brodin, K. (Department of Clinical Pharmacology, Karolinska Hospital, Stockholm (Sweden)); Monterio, D. (Department of Clinical Pharmacology, Huddinge Hospital, Karolinska Institute, Stockholm (Sweden))

    1991-01-01

    In an open study of 12 inpatients who met the DSM-III criteria for a major depressive episode, the effects of clomipramine (CI) on the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) in cerebrospinal fluid (CSF) were measured simultaneously with the effects on {sup 3}H-imipramine binding, serotonin (5-HT) uptake and 5-HT concentration in platelets after 3 and 6 weeks of treatment. Drug (CI and desmethylclomipramine) plasma concentrations were determined. The concentrations of 5-HIAA and HMPG decreased substantially, and the concentration of HVA remained unchanged. There was also a large and significant reduction of the number of imipramine binding sites (B{sub max}) and of the platelet 5-HT concentration. The 5-HT uptake was not measurable aftet 3 weeks of treatment. None of the parameters changed significantly between weeks 3 and 6. There were no significant correlations between antidepressant effect (measured by the Montgomery-Aasberg Depression Rating Scale) and plasma drug concentrations, although a tendency to a significant correlation between antidepressant effect and CI was observed at 3 weeks. There were no significant intercorrelations between the different 5-HT parameters and no other significant correlations between the biochemical measures and clinical outcome. (author).

  12. 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 patient...

  13. Flavanols and Platelet Reactivity

    Directory of Open Access Journals (Sweden)

    Debra A. Pearson

    2005-01-01

    Full Text Available Platelet activity and platelet-endothelial cell interactions are important in the acute development of thrombosis, as well as in the pathogenesis of cardiovascular disease. An increasing number of foods have been reported to have platelet-inhibitory actions, and research with a number of flavanol-rich foods, including, grape juice, cocoa and chocolate, suggests that these foods may provide some protection against thrombosis. In the present report, we review a series of in vivo studies on the effects of flavanol-rich cocoa and chocolate on platelet activation and platelet-dependent primary hemostasis. Consumption of flavanol-rich cocoa inhibited several measures of platelet activity including, epinephrine- and ADP-induced glycoprotein (GP IIb/IIIa and P-Selectin expression, platelet microparticle formation, and epinephrine-collagen and ADP-collagen induced primary hemostasis. The epinephrine-induced inhibitory effects on GP IIb/IIIa and primary hemostasis were similar to, though less robust than those associated with the use of low dose (81 mg aspirin. These data, coupled with information from other studies, support the concept that flavanols present in cocoa and chocolate can modulate platelet function through a multitude of pathways.

  14. 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...

  15. 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.

  16. Regulation of the genetic code in megakaryocytes and platelets.

    Science.gov (United States)

    Rondina, M T; Weyrich, A S

    2015-06-01

    Platelets are generated from nucleated precursors referred to as megakaryocytes. The formation of platelets is one of the most elegant and unique developmental processes in eukaryotes. Because they enter the circulation without nuclei, platelets are often considered simple, non-complex cells that have limited functions beyond halting blood flow. However, emerging evidence over the past decade demonstrates that platelets are more sophisticated than previously considered. Platelets carry a rich repertoire of messenger RNAs (mRNAs), microRNAs (miRNAs), and proteins that contribute to primary (adhesion, aggregation, secretion) and alternative (immune regulation, RNA transfer, translation) functions. It is also becoming increasingly clear that the 'genetic code' of platelets changes with race, genetic disorders, or disease. Changes in the 'genetic code' can occur at multiple points including megakaryocyte development, platelet formation, or in circulating platelets. This review focuses on regulation of the 'genetic code' in megakaryocytes and platelets and its potential contribution to health and disease. © 2015 International Society on Thrombosis and Haemostasis.

  17. Alloimmune refractoriness to platelet transfusions.

    Science.gov (United States)

    Sandler, S G

    1997-11-01

    Patients who are transfused on multiple occasions with red cells or platelets may develop platelet-reactive alloantibodies and experience decreased clinical responsiveness to platelet transfusion. This situation, conventionally described as "refractoriness to platelet transfusions," is defined by an unsatisfactory low post-transfusion platelet count increment. If antibodies to HLAs are detected, improved clinical outcomes may result from transfusions of HLA-matched or donor-recipient cross-matched platelets. Because refractoriness is an expected, frequently occurring phenomenon, prevention of HLA alloimmunization is an important management strategy. Prevention strategies include efforts to decrease the number of transfusions, filtration of cellular components to reduce the number of HLA-bearing leukocytes, or pretransfusion ultraviolet B irradiation of cellular components to decrease their immunogenicity. Other investigational approaches include reducing the expression of HLAs on transfused platelets, inducing a transient reticuloendothelial system blockade by infusions of specialized immunoglobulin products, or transfusing semisynthetic platelet substitutes (thromboerythrocytes, thrombospheres) or modified platelets (infusible platelet membranes, lyophilized platelets).

  18. Platelet function in dogs

    DEFF Research Database (Denmark)

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

    2007-01-01

    Cairn Terriers, 10 Boxers, and 11 Labrador Retrievers) were included in the study. Platelet function was assessed by whole-blood aggregation with ADP (1, 5, 10, and 20 µM) as agonist and by PFA-100 using collagen and epinephrine (Col + Epi) and Cpæ + ADP as agonists. Plasma thromboxane B2 concentration......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...

  19. Cisplatin triggers platelet activation.

    Science.gov (United States)

    Togna, G I; Togna, A R; Franconi, M; Caprino, L

    2000-09-01

    Clinical observations suggest that anticancer drugs could contribute to the thrombotic complications of malignancy in treated patients. Thrombotic microangiopathy, myocardial infarction, and cerebrovascular thrombotic events have been reported for cisplatin, a drug widely used in the treatment of many solid tumours. The aim of this study is to explore in vitro cisplatin effect on human platelet reactivity in order to define the potentially active role of platelets in the pathogenesis of cisplatin-induced thrombotic complications. Our results demonstrate that cisplatin increases human platelet reactivity (onset of platelet aggregation wave and thromboxane production) to non-aggregating concentrations of the agonists involving arachidonic acid metabolism. Direct or indirect activation of platelet phospholipase A(2) appears to be implicated. This finding contributes to a better understanding of the pathogenesis of thrombotic complications occurring during cisplatin-based chemotherapy.

  20. 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....

  1. Continuation of medically necessary platelet aggregation inhibitors - acetylsalicylic acid and clopidogrel - during surgery for spinal degenerative disorders: Results in 100 patients

    Directory of Open Access Journals (Sweden)

    Reza Akhavan-Sigari

    2014-01-01

    Full Text Available Background: Patients undergoing spinal surgery while under anticoagulation therapy are at risk of developing bleeding complications, even though lower incidences have been reported for joint arthroplasty surgery. There is a gap in the medical literature examining the incidence of postoperative spinal bleeding in patients who were under anticoagulation medication at the time of surgery. Methods: We prospectively followed a consecutive cohort of 100 patients (58 male, 42 female undergoing spinal surgery. The average patient age was 48.7 years and the minimum follow up time was 12 months. Diagnosis was lumbar spinal stenosis in 20, herniated lumbar discs in 63, degenerative cervical disc disease in 3, and cervical disc herniation in 14 cases. In our study, platelet aggregation inhibitors (clopidogrel and/or acetylsalicylic acid were given for the treatment of cardiovascular and cerebrovascular thrombotic events, to reduce risk of stroke in patients who have had transient ischemia of the brain or acute coronary syndrome, and as secondary prevention of atherosclerotic events (fatal or nonfatal myocardial infarction (MI. A cessation of anticoagulants (acetylsalicylic acid or clopidogrel in our patients in the peri- and postoperative period was contraindicated. Results: Sixty-three patients were on both clopidogrel and acetylsalicylic acid and 37 on acetylsalicylic acid only. None of the patients suffered any postoperative bleeding complication. Three patients suffered postoperative wound dehiscence and one patient had an infection that required reoperation. Conclusion: The question of whether preoperative platelet aggregation inhibitors must be stopped before elective spinal surgery has never been answered in the literature. In our prospective series, we have found no increase in the risk of postoperative spinal bleeding with the use of clopidogrel or acetylsalicylic acid. This finding suggests that spine surgery can be done without stopping

  2. Study of Platelet Serotonin in Adolescents with Internet Addiction Disorder%青少年网络成瘾患者血小板5-羟色胺水平分析

    Institute of Scientific and Technical Information of China (English)

    罗江洪; 吴汉荣; 蒙衡; 杜亚松; 林治光

    2011-01-01

    Objective To explore the role of serotonin ( 5 - HT) in internet addiction disorder ( IAD), and to provide evidence for the behavioral intervention and medical treatment. Methods Thirty-three adolescents with lAD and 44 normal ones as control were included in the study.Platelet serotonin level was determined with high performance liquid chromatography. Emotional status was investigated with Self-rating Depression Scale ( SDS) and Self-rating Anxiety Scale (SAS). A t-test and correlation analysis were used by SPSS 14. 0. Results Platelet serotonin level of lAD was significantly lower than that of controls ( t = - 2. 135 ,P < 0.05 ). SDS and SAS scores of lAD group were significantly higher than that of control group ( P < 0. 05 ). Correlation analysis showed platelet serotonin level was related with the degree of lAD, SDS and SAS ( P < 0.05 ). Conclusion IAD is perhaps related to neurons' maladjustment.%目的 探索5-羟色胺(5-HT)在青少年网络成瘾发生中的作用,为心理疏导、行为干预和药物治疗提供依据.方法 应用高效液相色谱法,测定33例网络成瘾患者青少年和44例正常对照的血小板5-HT含量;采用抑郁自评量表(SDS)、焦虑自评量表(SAS),测评情绪状态.应用SPSS 14.0进行t检验和相关分析.结果 网络成瘾组血小板5-HT水平低于正常对照组,差异有统计学意义(t=-2.135,P<0.05);网络成瘾组抑郁评分高于对照组,差异有统计学意义(t=3.310,P<0.01);网络成瘾组焦虑评分高于对照组,差异有统计学意义(t=3.110,P<0.01).相关分析显示,血小板5-HT水平与网络成瘾、抑郁、焦虑程度均呈负相关(P值均<0.05).结论 网络成瘾发病可能与神经元功能失调有关.

  3. Measurement of platelet aggregation, independently of patient platelet count

    DEFF Research Database (Denmark)

    Vinholt, P. J.; Frederiksen, H.; Hvas, A.M.

    2017-01-01

    platelet aggregation ruled out bleeding tendency in thrombocytopenic patients. Summary: Background: Methods for testing platelet aggregation in thrombocytopenia are lacking. Objective: To establish a flow-cytometric test of in vitro platelet aggregation independently of the patient's platelet count......, and examine the association of aggregation with a bleeding history in thrombocytopenic patients. Patients/methods: We established a flow-cytometric assay of platelet aggregation, and measured samples from healthy individuals preincubated with antiplatelet drugs, and samples from two patients with inherited...... platelets at platelet counts of > 10 × 109 L-1; otherwise, platelet isolation was required. The platelet aggregation percentage decreased with increasing antiplatelet drug concentration. Platelet aggregation in patients was reduced as compared with healthy individuals: 42% (interquartile range [IQR] 27...

  4. Platelet-collagen adhesion enhances platelet aggregation induced by binding of VWF to platelets

    Energy Technology Data Exchange (ETDEWEB)

    Laduca, F.M.; Bell, W.R.; Bettigole, R.E. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA) State Univ. of New York, Buffalo (USA))

    1987-11-01

    Ristocetin-induced platelet aggregation (RIPA) was evaluated in the presence of platelet-collagen adhesion. RIPA of normal donor platelet-rich plasma (PRP) demonstrated a primary wave of aggregation mediated by the binding of von Willebrand factor (VWF) to platelets and a secondary aggregation wave, due to a platelet-release reaction, initiated by VWF-platelet binding and inhibitable by acetylsalicylic acid (ASA). An enhanced RIPA was observed in PRP samples to which collagen had been previously added. These subthreshold concentrations of collagen, which by themselves were insufficient to induce aggregation, caused measurable platelet-collagen adhesion. Subthreshold collagen did not cause microplatelet aggregation, platelet release of ({sup 3}H)serotonin, or alter the dose-responsive binding of {sup 125}I-labeled VWF to platelets, which occurred with increasing ristocetin concentrations. However, ASA inhibition of the platelet release reaction prevented collagen-enhanced RIPA. These results demonstrate that platelet-collagen adhesion altered the platelet-release reaction induced by the binding of VWF to platelets causing a platelet-release reaction at a level of VWF-platelet binding not normally initiating a secondary aggregation. These findings suggest that platelet-collagen adhesion enhances platelet function mediated by VWF.

  5. 血液病患者单采血小板输注无效的原因及对策%Reasons for apheresis platelet transfusion refractory on patients with blood disorder and its countermeasures

    Institute of Scientific and Technical Information of China (English)

    沈胜建; 赵明峰; 张宇辰

    2014-01-01

    目的:探讨血液病患者单采血小板输注无效( PTR)发生率及其影响因素,为临床正确应用血小板制剂提供指导。方法回顾性分析单采血小板输注的70例患者318例次输注资料,通过计算血小板计数增加指数和血小板恢复百分率结合患者出血状况有无改善,判断血小板输注有效性,并讨论其影响因素及处理措施。结果急性白血病、再生障碍性贫血、骨髓异常综合征和特发性血小板减少性紫癜患者PTR发生率分别为22.1%、25.5%、38.3%和51.2%,四种类型的血液病患者血小板PTR发生率差别有统计学意义(P均<0.05);同种疾病无并发症患者PTR发生率低于有并发症者(P<0.05);无并发症患者PTR发生率随着输注次数的增加而上升(P<0.05)。未过滤白细胞与过滤白细胞患者PTR发生率比较差异有统计学意义( P<0.05)。结论疾病类型、有无并发症等因素影响血液病患者血小板输注的治疗效果,减少并发症、过滤白细胞可提高血小板的输注效果。%Objective To explore incidence rate and influence factor of apheresis platelet transfusion refractory ( PTR) on patients with blood disorder .Methods The data of 318 infusions for 70 patients subject to apheresis platelet infusion were retrospectively analyzed , by calculating corrected Count increment ( CCI ) and percent platelet recovery ( PPR) and combining hemorrhage improvement condition in patients , the effect of platelet transfusion were determined and influence factors and treatment measures were discussed .Results ①The PTR occurrence rate of acute leukemia (AL), aplastic anemia (AA), bone marrow abnormalities syndrome (MDS) and idiopathic thrombocytopenic purpura (ITP) in patients hit 22.1%, 25.5%, 38.3%and 22.1%respectively, the difference in platelet PTR rate in four types of blood diseases was statistically significant (P<0.05).②The difference

  6. Defining Platelet Function During Polytrauma

    Science.gov (United States)

    2013-02-01

    using calibrated automated thrombography ( CAT ). 3. Platelet-induced clot contraction and using viscoelastic measures such as TEG with Platelet Mapping...using calibrated automated thrombography ( CAT ) in platelet-rich plasma. 3. Platelet-induced clot contraction and effect on clot structure by platelet...if injury with stable vital signs on initial evaluation.  Pregnancy (confirmed with urine pregnancy testing)  Documented do not resuscitate order

  7. 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.

  8. Clinical application of radiolabelled platelets

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, C. (Medical University Luebeck (Federal Republic of Germany). Department of Neurology); Hardeman, M.R. (Amsterdam Univ. (Netherlands). Academisch Ziekenhuis); Henningsen, H. (Heidelberg Univ. (Germany, F.R.). Neurologische Klinik); Petrovici, J.-N. (Cologne-Merheim Hospital (Federal Republic of Germany). Department of Neurology) (eds.)

    1990-01-01

    The increasing number of therapeutic modalities available for the management of patients with thromboembolic complications, such as fibrinolytic treatment or vascular surgery, require the development of new imaging techniques to provide more information on the xtent, age and activity of the thromboembolic material causing clinical symptoms. Since the introduction of radiolabelling of platelets with indium-111, platelet scintigraphy (PSC) has been used as a tool in the diagnosis of various thromboembolic diseases. During the International Symposium on Radiolabelled Platelets scientists from a variety of medical backgrounds presented their results on the clinical applictions of radiolabelled platelets. The papers presented there have been updated to take account of the latest results before publication in this volume. The papers are grouped into six sections on platelet labelling techniques, radiolabelled platelets in cardiology, monitoring of antiplatelet therapy, platelet scintigraphy in stroke patients, platelet scintigraphy in angiology, and platelet scintigraphy in hematology and other clinical applications, including renal transplant rejection. refs.; figs.; tabs.

  9. 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.

  10. 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.

  11. 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.

  12. Platelet reactive alloantibodies responsible for immune thrombocytopenia in Malay population

    Directory of Open Access Journals (Sweden)

    Mohd I. Armawai

    2014-10-01

    Full Text Available Background: Alloantibodies against human platelet alloantigens (HPAs are responsible for the development of platelet transfusion refractoriness (PTR in patients receiving random platelets and bleeding disorder in babies with fetal neonatal alloimmune thrombocytopenia (FNAIT. Recently, our results based on the analysis of the allelic distribution of HPAs indicated that immunization may occur among Malay. In this study, we sought to analyze the frequencies of platelet reactive alloantibodies responsible for FNAIT and PTR in Malaysia.Methods: Sera from suspected FNAIT (n = 295 and PTR (n = 74 were collected in five years period (2008-2013 and tested for the presence of platelet reactive antibodies by the use of antigen capture assay.Results: In 5/74 (5.41% platelet specific antibodies against HPA-2b (n = 1, HPA-5a (n = 1, HPA-5b (n = 1, HPA-15b (n = 2 could be identified in our PTR cohort. In FNAIT cohort, platelet specific alloantibodies could be detected in 18 sera (6.10% consisting anti-HPA-1a (n = 1, anti-HPA-3a (n = 3, anti-HPA-5a (n = 6, anti-HPA-5b (n = 6, anti-HPA-15a (n = 1, and anti-HPA-15b (n = 1.Conclusion: Our study indicates that anti-HPA-3, -HPA-5 and -HPA-15 antibodies seems to be the most platelet specific antibodies involved in FNAIT and PTR cases in Malaysian population. Since similar HPA allelic distribution among Malaysian and Indonesian populations have been observed, immunization against these three HPA systems are expected to be the most potential risk of alloimmune mediated platelet disorders in Indonesia.

  13. 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.

  14. Platelet Activation in Human Immunodeficiency Virus Type-1 Patients Is Not Altered with Cocaine Abuse.

    Directory of Open Access Journals (Sweden)

    Michelle Kiebala

    Full Text Available Recent work has indicated that platelets, which are anucleate blood cells, significantly contribute to inflammatory disorders. Importantly, platelets also likely contribute to various inflammatory secondary disorders that are increasingly associated with Human Immunodeficiency Virus Type-1 (HIV infection including neurological impairments and cardiovascular complications. Indeed, HIV infection is often associated with increased levels of platelet activators. Additionally, cocaine, a drug commonly abused by HIV-infected individuals, leads to increased platelet activation in humans. Considering that orchestrated signaling mechanisms are essential for platelet activation, and that nuclear factor-kappa B (NF-κB inhibitors can alter platelet function, the role of NF-κB signaling in platelet activation during HIV infection warrants further investigation. Here we tested the hypothesis that inhibitory kappa B kinase complex (IKK activation would be central for platelet activation induced by HIV and cocaine. Whole blood from HIV-positive and HIV-negative individuals, with or without cocaine abuse was used to assess platelet activation via flow cytometry whereas IKK activation was analyzed by performing immunoblotting and in vitro kinase assays. We demonstrate that increased platelet activation in HIV patients, as measured by CD62P expression, is not altered with reported cocaine use. Furthermore, cocaine and HIV do not activate platelets in whole blood when treated ex vivo. Finally, HIV-induced platelet activation does not involve the NF-κB signaling intermediate, IKKβ. Platelet activation in HIV patients is not altered with cocaine abuse. These results support the notion that non-IKK targeting approaches will be better suited for the treatment of HIV-associated inflammatory disorders.

  15. SIGNIFICANCE OF PLATELET COUNT AND PLATELET INDICES IN PATIENTS WITH SOME THROMBOCYTOPENIC CONDITIONS

    Directory of Open Access Journals (Sweden)

    Omer Noureldaim Abdalla

    2016-01-01

    Full Text Available Background: Thrombocytopenia is one of the most frequent causes for hematologic consultation in the practice of medicine and can result from a wide variety of conditions. Objective: The study was conducted on behave of platelets count in tie with platelet volume indices to measure their consistency. Methods: The study was “prospective cross-sectional hospital based design” and conducted at Khartoum hospitals (A.Gasim, Jafar I A, and R.ICK. Studied populations texture has stipulated concurred diagnosis of heart disorders (HD, lymphoid neoplasms (LN, hypoplastic bone marrow (HPB, renal transplantation (RT, patients under chemotherapy (CT, and fully checked healthy Sudanese population (HSP. Platelet (PLT count and platelet volume index (PVI were measured using automated method of Sysmex KX-21N and the data was analyzed using SPSS. Results: does established (24 mean and standard for the study population among which (HSP was platelet distribution width (PDW (11.4±1.5 fl, mean platelet volume (MPV (9.3±0.8 fl, platelet large cell ratio (P- LCR (20.6±6.7% and PLT count (245±45 X109/L, and established correlations between PLT count and PVI in thrombocytopenic conditions. Conclusion: we conclude that, PVI has the ability to change from normal to higher or lower than (HSP in thrombocytopenic conditions and Sudanese has PVI mean lower than the mean of reference range, and there are inverse and reverse correlations between PLT count and PVI but not in (HSP and reverse correlation in between PVI except between PDW and P-LCR in (HPB

  16. The Platelet and Platelet Function Testing in Liver Disease

    NARCIS (Netherlands)

    Hugenholtz, Greg G. C.; Porte, Robert J.; Lisman, Ton

    2009-01-01

    Patients who have liver disease commonly present with alterations in platelet number and function. Recent data have questioned the contribution of these changes to bleeding complications in these patients. Modern tests of platelet function revealed compensatory mechanisms for the decreased platelet

  17. Reproducibility of Manual Platelet Estimation Following Automated Low Platelet Counts

    Directory of Open Access Journals (Sweden)

    Zainab S Al-Hosni

    2016-11-01

    Full Text Available Objectives: Manual platelet estimation is one of the methods used when automated platelet estimates are very low. However, the reproducibility of manual platelet estimation has not been adequately studied. We sought to assess the reproducibility of manual platelet estimation following automated low platelet counts and to evaluate the impact of the level of experience of the person counting on the reproducibility of manual platelet estimates. Methods: In this cross-sectional study, peripheral blood films of patients with platelet counts less than 100 × 109/L were retrieved and given to four raters to perform manual platelet estimation independently using a predefined method (average of platelet counts in 10 fields using 100× objective multiplied by 20. Data were analyzed using intraclass correlation coefficient (ICC as a method of reproducibility assessment. Results: The ICC across the four raters was 0.840, indicating excellent agreement. The median difference of the two most experienced raters was 0 (range: -64 to 78. The level of platelet estimate by the least-experienced rater predicted the disagreement (p = 0.037. When assessing the difference between pairs of raters, there was no significant difference in the ICC (p = 0.420. Conclusions: The agreement between different raters using manual platelet estimation was excellent. Further confirmation is necessary, with a prospective study using a gold standard method of platelet counts.

  18. Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice

    OpenAIRE

    Deppermann, Carsten; Cherpokova, Deya; Nurden, Paquita; Schulz, Jan-Niklas; Thielmann, Ina; Kraft, Peter; Vögtle, Timo; Kleinschnitz, Christoph; Dütting, Sebastian; Krohne, Georg; Eming, Sabine A.; Nurden, Alan T; Eckes, Beate; Stoll, Guido; Stegner, David

    2013-01-01

    Platelets are anuclear organelle-rich cell fragments derived from bone marrow megakaryocytes (MKs) that safeguard vascular integrity. The major platelet organelles, α-granules, release proteins that participate in thrombus formation and hemostasis. Proteins stored in α-granules are also thought to play a role in inflammation and wound healing, but their functional significance in vivo is unknown. Mutations in NBEAL2 have been linked to gray platelet syndrome (GPS), a rare bleeding disorder ch...

  19. 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.

  20. 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.

  1. 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.

  2. Mean platelet volume levels in children with adenoid hypertrophy.

    Science.gov (United States)

    Kucur, Cuneyt; Kulekci, Semra; Zorlu, Aylin; Savran, Bircan; Oghan, Fatih; Yildirim, Nadir

    2014-01-01

    Adenoid hypertrophy (AH) is a common disorder in children, resulting in chronic nasal congestion. This chronic congestion should be evaluated carefully because it can lead to chronic upper airway obstruction. Many authors have suggested that increased nasal resistance to respiration may cause disturbances in the pulmonary ventilation and carry the risk of cardiopulmonary diseases. Mean platelet volume (MPV) is a marker of platelet function and is positively associated with indicators of platelet activity. Mean platelet volume is an indicator of larger and more reactive platelets and has been shown to be increased in patients with vascular disease, including peripheral, pulmonary, and coronary artery disease. Recently, MPV levels have also been shown to be increased in patients with severe obstructive sleep apnea, and marked nasal septal deviation. Moreover, increased MPV has also been shown to have a prognostic role in cardiovascular disease. We investigated whether MPV is higher in patients with AH and whether higher MPV levels can be reduced by adenoidectomy. To the best of our knowledge, this is the first study to investigate MPV in patients with AH. Our results suggest that MPV, a determinant of platelet activation, is elevated in patients with AH and adenoidectomy is an effective therapeutic measure in such patients. Increased platelet activation may be related to an increase of cardiopulmonary risk in patients with AH.

  3. Mean platelet volume and mean platelet volume/platelet count ratio ...

    African Journals Online (AJOL)

    Amira M. Elsayed

    2016-03-30

    Mar 30, 2016 ... Abstract The mean platelet volume (MPV) is a laboratory marker associated with platelet func- tion and activity. .... the first 24 h of presentation to the emergency department. Severity of ..... J Neurol Neurosurg Psychiatry.

  4. Mean platelet volume in children with Reye-like syndrome.

    Science.gov (United States)

    Sert, Ahmet; Kilicaslan, Cengizhan; Solak, Ece Selma; Arslan, Sukru

    2015-01-01

    Reye-like syndrome (RLS) is considered to be a systemic disorder in which the cytokine storm plays a major role. Mean platelet volume (MPV), which is commonly used as a measure of platelet size, indicates the rate of platelet production and platelet activation. We aimed to study MPV in children with RLS. The study population consisted of 30 children with RLS and 30 healthy control subjects. White blood cell (WBC) count, aspartate transaminase (AST) and alanine transaminase (ALT) values were significantly higher and MPV values were significantly lower in patients with RLS at an early stage of illness when compared to controls. Erythrocyte sedimentation rate (ESR), C-reactive protein, AST and ALT values were significantly decreased in patients with RLS after the treatment when compared to baseline whereas MPV values were increased. MPV values were negatively correlated with ESR and WBC. In conclusion, at an early stage of RLS MPV values were lower when compared to controls.

  5. Prophylactic platelets in dengue

    DEFF Research Database (Denmark)

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

    2012-01-01

    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. Rho GTPases in platelet function.

    Science.gov (United States)

    Aslan, J E; McCarty, O J T

    2013-01-01

    The Rho family of GTP binding proteins, also commonly referred to as the Rho GTPases, are master regulators of the platelet cytoskeleton and platelet function. These low-molecular-weight or 'small' GTPases act as signaling switches in the spatial and temporal transduction, and amplification of signals from platelet cell surface receptors to the intracellular signaling pathways that drive platelet function. The Rho GTPase family members RhoA, Cdc42 and Rac1 have emerged as key regulators in the dynamics of the actin cytoskeleton in platelets and play key roles in platelet aggregation, secretion, spreading and thrombus formation. Rho GTPase regulators, including GEFs and GAPs and downstream effectors, such as the WASPs, formins and PAKs, may also regulate platelet activation and function. In this review, we provide an overview of Rho GTPase signaling in platelet physiology. Previous studies of Rho GTPases and platelets have had a shared history, as platelets have served as an ideal, non-transformed cellular model to characterize Rho function. Likewise, recent studies of the cell biology of Rho GTPase family members have helped to build an understanding of the molecular regulation of platelet function and will continue to do so through the further characterization of Rho GTPases as well as Rho GAPs, GEFs, RhoGDIs and Rho effectors in actin reorganization and other Rho-driven cellular processes. © 2012 International Society on Thrombosis and Haemostasis.

  7. Platelet microvesicles in health and disease.

    Science.gov (United States)

    Melki, Imene; Tessandier, Nicolas; Zufferey, Anne; Boilard, Eric

    2017-05-01

    Interest in cell-derived extracellular vesicles and their physiological and pathological implications is constantly growing. Microvesicles, also known as microparticles, are small extracellular vesicles released by cells in response to activation or apoptosis. Among the different microvesicles present in the blood of healthy individuals, platelet-derived microvesicles (PMVs) are the most abundant. Their characterization has revealed a heterogeneous cargo that includes a set of adhesion molecules. Similarly to platelets, PMVs are also involved in thrombosis through support of the coagulation cascade. The levels of circulatory PMVs are altered during several disease manifestations such as coagulation disorders, rheumatoid arthritis, systemic lupus erythematosus, cancers, cardiovascular diseases, and infections, pointing to their potential contribution to disease and their development as a biomarker. This review highlights recent findings in the field of PMV research and addresses their contribution to both healthy and diseased states.

  8. Platelets possess functional TGF-beta receptors and Smad2 protein.

    Science.gov (United States)

    Lev, P R; Salim, J P; Marta, R F; Osorio, M J Mela; Goette, N P; Molinas, F C

    2007-02-01

    TGF-beta1 plays a main role in tissue repair by regulating extracellular matrix production and tissue granulation. Platelets are one of the main sources of this cytokine in the circulation. The aim of this study was to evaluate the presence of the TGF-beta receptors on platelets, the effect of TGF-beta1 on platelet aggregation and the underlying intracellular mechanisms. TGF-beta receptors on platelets were studied by flow cytometry and their mRNA by PCR. Platelet aggregation was assessed by turbidimetric methods and intracellular pathways by Western blot. TGF-beta receptor type II and mRNA codifying for TbetaRI and TbetaRII were found in platelets. We demonstrated that TGF-beta1 did not trigger platelet aggregation by itself but had a modulating effect on ADP-induced platelet aggregation. Either inhibition or increase in platelet aggregation, depending on the exposure time to TGF-beta1 and the ADP concentration used, were shown. We found that platelets possess Smad2 protein and that its phosphorylation state is increased after exposure to TGF-beta1. Besides, TGF-beta1 modified the pattern of ADP-induced tyrosine phosphorylation. Increased phosphorylation levels of 64-, 80- and 125-kDa proteins during short time incubation with TGF-beta1 and increased phosphorylation of 64- and 125-kDa proteins after longer incubation were observed. The modulating effect of TGF-beta1 on platelet aggregation could play a role during pathological states in which circulating TGF-beta1 levels are increased and intravascular platelet activation is present, such as myeloproliferative disorders. In vascular injury, in which platelet activation followed by granule release generates high local ADP concentrations, it could function as a physiological mechanism of platelet activation control.

  9. Unusual hematologic disease affecting Caucasian children traveling to Southeast Asia: acquired platelet dysfunction with eosinophilia

    Directory of Open Access Journals (Sweden)

    Anselm Chi-Wai Lee

    2012-02-01

    Full Text Available An 11-year-old American boy was staying with his family in Indonesia. He presented with a 5-month history of recurrent bruises and ecchymosis. A clinical diagnosis of acquired platelet dysfunction with eosinophilia was made when his full blood counts showed hypereosinophilia (7.4×10 9/L with normal platelet count and gray platelets under the microscope. The diagnosis was supported by abnormal platelet aggregation tests consistent with a storage pool disorder. The bleeding symptoms and eosinophilia resolved a month later with a full course of antihelminthic therapy. Hematologists should be aware of this unusual disease in travelers returning from the Southeast Asia.

  10. Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan

    OpenAIRE

    Liu, Zhi-Jian; Hoffmeister, Karin M.; Hu, Zhongbo; Mager, Donald E.; Ait-Oudhia, Sihem; Debrincat, Marlyse A.; Pleines, Irina; Josefsson, Emma C.; Benjamin T Kile; Italiano, Joseph; Ramsey, Haley; Grozovsky, Renata; Veng-Pedersen, Peter; Chavda, Chaitanya; Sola-Visner, Martha

    2014-01-01

    Rapid growth and rising platelet counts result in a significant expansion of platelet mass during neonatal life.The rise in platelet counts is mediated by a prolongation in the neonatal platelet lifespan.

  11. Platelet-type von Willebrand disease: new insights into the molecular pathophysiology of a unique platelet defect.

    Science.gov (United States)

    Othman, Maha; Kaur, Harmanpreet; Emsley, Jonas

    2013-09-01

    Compared with coagulation factor defects, little attention is given to defects of platelet function as causes of rare bleeding disorders. Platelet-type von Willebrand disease (PT-VWD) is an autosomal dominant bleeding disorder and is unique among platelet disorders because it is characterized by platelet hyperresponsiveness rather than decreased function. The disease is caused by gain-of-function mutations in the platelet GP1BA gene, which codes for the platelet von Willebrand factor (VWF) receptor, GPIbα. Only five mutations (four missense and one deletion) have so far been reported. Affected patients suffer from mild to moderate mucocutaneous bleeding, low VWF activity compared with antigen, decreased high-molecular-weight VWF multimers, variable degree of thrombocytopenia and typically platelet aggregation in response to low concentrations of ristocetin. All reported PT-VWD missense mutations occur within the R-loop of GPIbα and it was speculated that the introduction of short branched chain mutations such as Val in PT-VWD stabilized the extended β-hairpin. Examination of this theory by surveying all the available GPIbα structures showed that a distinct conformation predominates for the R-loop when GPIbα is not bound to VWF-A1 and this provides the framework of a new hypothesis for the molecular basis of PT-VWD. Worldwide efforts to improve diagnosis of PT-VWD continue, and international systematic studies are required to further our understanding of the phenotype and the influence of the hyperresponsive GPIbα beyond hemostasis.

  12. Detection and identification of platelet antibodies and antigens in the clinical laboratory.

    Science.gov (United States)

    Curtis, B R; McFarland, J G

    2009-01-01

    As a result of the unique functional properties of platelets, more-robust methods were required for detection of antibodies raised against them. Immunofluorescence detection by flow cytometry, solid-phase red cell adherence, and antigen capture ELISAs are some of the current tests that have been developed to meet the challenges of platelet antibody detection and identification and antigen phenotyping. Recently developed protein liquid bead arrays are becoming the next-generation platelet antibody tests. Fueled by development of PCR and determination of the molecular basis of the PlA1 human platelet antigen (HPA), serologic platelet typing has now been replaced by genotyping of DNA. Allele-specific PCR, melting curve analysis, and 5'-nuclease assays are now evolving into more high-throughput molecular tests. Laboratory testing for the diagnosis of immune platelet disorders has advanced considerably from its humble beginnings.

  13. Role of Platelet Parameters on Sudden Sensorineural Hearing Loss: A Case-Control Study in Iran

    Science.gov (United States)

    2016-01-01

    Sudden sensorineural hearing loss (SSNHL) is a common otological disorder characterized by a hearing loss greater than 30 dB over three consecutive frequencies, in less than 72 hours. It has been established that platelet parameters, such as mean platelet volume, are associated with ischemic heart events, whose clinical manifestations are similar to those of SSNHL. Hence, we aimed to determine if the platelet count, mean platelet volume and platelet distribution width are related to the occurrence and severity of sudden sensorineural hearing loss. A case-control prospective study was conducted in a teaching hospital in Iran. One hundred-eight patients with SSNHL and an equal number of healthy, age- and sex-matched controls were enrolled in the study. Peripheral venous blood samples were collected from the subjects, and the platelet count, mean platelet volume and platelet distribution width were measured with an automated blood cell counter. Analysis of the audiometry and hematological test results using SPSS22 software showed no statistical correlation between the platelet parameters and the occurrence of SSNHL, but correlation coefficients showed a significant correlation between PDW and hearing loss severity in patients group. However, further investigation is required to unequivocally establish the absence of correlation between the platelet parameters and occurrence of SSNHL. PMID:26829393

  14. Role of Platelet Parameters on Sudden Sensorineural Hearing Loss: A Case-Control Study in Iran.

    Science.gov (United States)

    Mirvakili, Abbas; Dadgarnia, Mohammad Hossein; Baradaranfar, Mohammad Hossein; Atighechi, Saeid; Zand, Vahid; Ansari, Abdollah

    2016-01-01

    Sudden sensorineural hearing loss (SSNHL) is a common otological disorder characterized by a hearing loss greater than 30 dB over three consecutive frequencies, in less than 72 hours. It has been established that platelet parameters, such as mean platelet volume, are associated with ischemic heart events, whose clinical manifestations are similar to those of SSNHL. Hence, we aimed to determine if the platelet count, mean platelet volume and platelet distribution width are related to the occurrence and severity of sudden sensorineural hearing loss. A case-control prospective study was conducted in a teaching hospital in Iran. One hundred-eight patients with SSNHL and an equal number of healthy, age- and sex-matched controls were enrolled in the study. Peripheral venous blood samples were collected from the subjects, and the platelet count, mean platelet volume and platelet distribution width were measured with an automated blood cell counter. Analysis of the audiometry and hematological test results using SPSS22 software showed no statistical correlation between the platelet parameters and the occurrence of SSNHL, but correlation coefficients showed a significant correlation between PDW and hearing loss severity in patients group. However, further investigation is required to unequivocally establish the absence of correlation between the platelet parameters and occurrence of SSNHL.

  15. Role of Platelet Parameters on Sudden Sensorineural Hearing Loss: A Case-Control Study in Iran.

    Directory of Open Access Journals (Sweden)

    Abbas Mirvakili

    Full Text Available Sudden sensorineural hearing loss (SSNHL is a common otological disorder characterized by a hearing loss greater than 30 dB over three consecutive frequencies, in less than 72 hours. It has been established that platelet parameters, such as mean platelet volume, are associated with ischemic heart events, whose clinical manifestations are similar to those of SSNHL. Hence, we aimed to determine if the platelet count, mean platelet volume and platelet distribution width are related to the occurrence and severity of sudden sensorineural hearing loss. A case-control prospective study was conducted in a teaching hospital in Iran. One hundred-eight patients with SSNHL and an equal number of healthy, age- and sex-matched controls were enrolled in the study. Peripheral venous blood samples were collected from the subjects, and the platelet count, mean platelet volume and platelet distribution width were measured with an automated blood cell counter. Analysis of the audiometry and hematological test results using SPSS22 software showed no statistical correlation between the platelet parameters and the occurrence of SSNHL, but correlation coefficients showed a significant correlation between PDW and hearing loss severity in patients group. However, further investigation is required to unequivocally establish the absence of correlation between the platelet parameters and occurrence of SSNHL.

  16. Effects of hormones on platelet aggregation.

    Science.gov (United States)

    Farré, Antonio López; Modrego, Javier; Zamorano-León, José J

    2014-04-01

    Platelets and their activation/inhibition mechanisms play a central role in haemostasis. It is well known agonists and antagonists of platelet activation; however, during the last years novel evidences of hormone effects on platelet activation have been reported. Platelet functionality may be modulated by the interaction between different hormones and their platelet receptors, contributing to sex differences in platelet function and even in platelet-mediated vascular damage. It has suggested aspects that apparently are well established should be reviewed. Hormones effects on platelet activity are included among them. This article tries to review knowledge about the involvement of hormones in platelet biology and activity.

  17. Gambaran Mean Platelet Volume Pada Pasien Diabetes Melitus Tipe 2 Yang Rawat Inap Di RSUP. Haji Adam Malik Medan Tahun 2014

    OpenAIRE

    Simanjuntak, Fitri

    2016-01-01

    Introduction :Epidemiological studies in various parts of the world showed an inclination of increased incidence and prevalence of Diabetes Mellitus Type 2. Diabetes Mellitus Type 2 is a degenerative disease that requires proper and serious handling because it can cause complications, one of the complications is platelet disorder. Mean Platelet Volume(MPV) is a picture and the average size of platelets in circulation which can be used to assess the activity of platelets. Obj...

  18. 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...

  19. Identification of the platelet ADP receptor targeted by antithrombotic drugs.

    Science.gov (United States)

    Hollopeter, G; Jantzen, H M; Vincent, D; Li, G; England, L; Ramakrishnan, V; Yang, R B; Nurden, P; Nurden, A; Julius, D; Conley, P B

    2001-01-11

    Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation. The second ADP receptor required for aggregation (variously called P2Y(ADP), P2Y(AC), P2Ycyc or P2T(AC)) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases.

  20. Morphological evaluation of canine platelets on Giemsa- and PAS-stained blood smears.

    Science.gov (United States)

    Halmay, Dóra; Sótonyi, P; Vajdovich, P; Gaál, T

    2005-01-01

    The morphology of canine platelets (changes in size, shape, staining characteristics, degree of activation and clump formation, distribution of granules, appearance of vacuoles on Giemsa-stained smears) was investigated in 20 healthy control and 181 diseased dogs. In the group of the sick dogs 84 animals suffered from disorders affecting directly the haematological parameters or the haematopoietic organs such as bleeding, thymic haemorrhage, haemolytic disorders, lymphoma, immune-mediated thrombocytopenia, and other 97 dogs were affected by other diseases (hepatopathy, nephropathy, hepatic, splenic or intestinal neoplasm, skin diseases, diabetes mellitus, Cushing's syndrome, sepsis). The alterations found in platelet morphology were not specific for any disorder. The most common platelet abnormalities were polychromasia and the presence of giant platelets. These changes occurred in a high number in disorders accompanied by bleeding or haemolysis. Anisocytosis was the most frequent finding in hepatic, splenic or intestinal neoplasms and in certain endocrinopathies. Microcytosis was observed in immune-mediated thrombocytopenia, hepatic neoplasms and endocrine disorders. Extreme platelet activation was common in haemolysis, hepatopathies, neoplastic diseases and sepsis. Vacuolisation was present in thymic haemorrhage, pancreatitis, diabetes mellitus and Cushing's syndrome. A new morphologic phenomenon, i.e. a ring-like formation of granules, was described in the cytoplasm of the platelets both in healthy and diseased animals. In addition, two forms of pathologic granulation were also described for the first time in Giemsa-stained blood smears: the pseudonuclear and the spot-like formation of granules, which were observed especially in disorders affecting the blood cells. The granulation and morphological characteristics of platelets on smears stained by periodic acid-Schiff reaction (PAS) were also studied. Three localisations of granulation were observed, such as

  1. Platelets in inflammation and immunity.

    Science.gov (United States)

    Herter, J M; Rossaint, J; Zarbock, A

    2014-11-01

    The paradigm of platelets as mere mediators of hemostasis has long since been replaced by a dual role: hemostasis and inflammation. Now recognized as key players in innate and adaptive immune responses, platelets have the capacity to interact with almost all known immune cells. These platelet-immune cell interactions represent a hallmark of immunity, as they can potently enhance immune cell functions and, in some cases, even constitute a prerequisite for host defense mechanisms such as NETosis. In addition, recent studies have revealed a new role for platelets in immunity: They are ubiquitous sentinels and rapid first-line immune responders, as platelet-pathogen interactions within the vasculature appear to precede all other host defense mechanisms. Here, we discuss recent advances in our understanding of platelets as inflammatory cells, and provide an exemplary review of their role in acute inflammation.

  2. Estrogen, inflammation, and platelet phenotype.

    Science.gov (United States)

    Miller, Virginia M; Jayachandran, Muthuvel; Hashimoto, Kazumori; Heit, John A; Owen, Whyte G

    2008-01-01

    Although exogenous estrogenic therapies increase the risk of thrombosis, the effects of estrogen on formed elements of blood are uncertain. This article examines the genomic and nongenomic actions of estrogen on platelet phenotype that may contribute to increased thrombotic risk. To determine aggregation, secretion, protein expression, and thrombin generation, platelets were collected from experimental animals of varying hormonal status and from women enrolled in the Kronos Early Estrogen Prevention Study. Estrogen receptor beta predominates in circulating platelets. Estrogenic treatment in ovariectomized animals decreased platelet aggregation and adenosine triphosphate (ATP) secretion. However, acute exposure to 17beta-estradiol did not reverse decreases in platelet ATP secretion invoked by lipopolysaccharide. Thrombin generation was positively correlated to the number of circulating microvesicles expressing phosphatidylserine. Assessing the effect of estrogen treatments on blood platelets may lead to new ways of identifying women at risk for adverse thrombotic events with such therapies.

  3. Complement Activation Alters Platelet Function

    Science.gov (United States)

    2015-12-01

    Award Number: W81XWH-12-1-0523 TITLE: Complement Activation Alters Platelet Function PRINCIPAL INVESTIGATOR: George Tsokos, M.D. CONTRACTING...Activation Alters Platelet Function 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0523 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) George Tsokos, M.D...a decreased level of disease. Further studies will expand upon these observations better outlining the function of platelets in the injury associated

  4. Burro aortic collagen: composition and characteristics of interaction with platelets

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, M.D. (Comparative Animal Research Lab., Oak Ridge, TN); Huang, W.O.W.; Cross, F.H.; Lin, K.T.D.

    1979-03-01

    A collagenous protein(s) from the aortas of three aged burros (Equus asinus) was isolated, using an acid (83.5 mM glacial acetic acid) extraction technique and subsequent pepsin digestion of the extracts with extensive dialysis. This protein(s) was then precipitated by adding solid NaCl (w/v, 9.45 g/100 ml) to the dialyzed aortic tissue extracts. The precipitate was collected by ultracentrifugation, concentrated by dissolving in one-fourth the original volume of acetic acid, and again extensively dialyzed. Values for amino acids in residues/1,000 indicated that the extractable aortic material(s) contained substantial amounts of proline, hydroxyproline, lysine, hydroxylysine, cysteine, and all other amino acid residues usually found in collagen. Examination by electrophoresis in sodium dodecyl sulfate polyacrylamide-gel indicated the presence of 5 major polypeptide subunits of the molecular weight range of 116,000 to 300,000. A powerful inducer of platelet aggregation was found in the acid solubilized, pepsin-digested aortic extracts. Human platelets were sensitive to the agent(s) down to 0.1 to 0.2 ..mu..g of aortic solids added to 0.45 ml of platelet-rich plasma. Platelets from goats and sheep were sensitive down to additions of 0.2 ..mu..g of solids, burro platelets to 0.5 to 1 ..mu..g, bovine platelets to 1 to 2 ..mu..g, and swine platelets to 2 to 3 ..mu..g. Thus, this powerful burro aortic collagen-containing material(s) may help to distinguish minor modifications in functional characteristics of platelets from persons or animals suffering from hemostatic or thrombotic disorders.

  5. Platelet effects on ovarian cancer

    Science.gov (United States)

    Davis, Ashley; Afshar-Kharghan, Vahid; Sood, Anil K.

    2014-01-01

    Growing understanding of the role of thrombocytosis, high platelet turnover, and the presence of activated platelets in the circulation in cancer progression and metastasis has brought megakaryocytes into focus. Platelet biology is essential to hemostasis, vascular integrity, angiogenesis, inflammation, innate immunity, wound healing, and cancer biology. However, before megakaryocyte/platelet-directed therapies can be considered for clinical use, understanding of the mechanism and biology of paraneoplastic thrombocytosis in malignancy is required. Here, we provide an overview of the clinical implications, biological significance, and mechanisms of paraneoplastic thrombocytosis in the context of ovarian cancer. PMID:25023353

  6. 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.

  7. Differential proteomic analysis of platelets suggested possible signal cascades network in platelets treated with salvianolic acid B.

    Directory of Open Access Journals (Sweden)

    Chao Ma

    Full Text Available BACKGROUND: Salvianolic acid B (SB is an active component isolated from Danshen, a traditional Chinese medicine widely used for the treatment of cardiovascular disorders. Previous study suggested that SB might inhibit adhesion as well as aggregation of platelets by a mechanism involving the integrin α2β1. But, the signal cascades in platelets after SB binding are still not clear. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, a differential proteomic analysis (two-dimensional electrophoresis was conducted to check the protein expression profiles of rat platelets with or without treatment of SB. Proteins altered in level after SB exposure were identified by MALDI-TOF MS/MS. Treatment of SB caused regulation of 20 proteins such as heat shock-related 70 kDa protein 2 (hsp70, LIM domain protein CLP-36, copine I, peroxiredoxin-2, coronin-1 B and cytoplasmic dynein intermediate chain 2C. The regulation of SB on protein levels was confirmed by Western blotting. The signal cascades network induced by SB after its binding with integrin α2β1 was predicted. To certify the predicted network, binding affinity of SB to integrin α2β1 was checked in vitro and ex vivo in platelets. Furthermore, the effects of SB on protein levels of hsp70, coronin-1B and intracellular levels of Ca²+ and reactive oxygen species (ROS were checked with or without pre-treatment of platelets using antibody against integrin α2β1. Electron microscopy study confirmed that SB affected cytoskeleton structure of platelets. CONCLUSIONS/SIGNIFICANCE: Integrin α2β1 might be one of the direct target proteins of SB in platelets. The signal cascades network of SB after binding with integrin α2β1 might include regulation of intracellular Ca²+ level, cytoskeleton-related proteins such as coronin-1B and cytoskeleton structure of platelets.

  8. Differential Proteomic Analysis of Platelets Suggested Possible Signal Cascades Network in Platelets Treated with Salvianolic Acid B

    Science.gov (United States)

    Ma, Chao; Yao, Yan; Yue, Qing-Xi; Zhou, Xin-Wen; Yang, Peng-Yuan; Wu, Wan-Ying; Guan, Shu-Hong; Jiang, Bao-Hong; Yang, Min; Liu, Xuan; Guo, De-An

    2011-01-01

    Background Salvianolic acid B (SB) is an active component isolated from Danshen, a traditional Chinese medicine widely used for the treatment of cardiovascular disorders. Previous study suggested that SB might inhibit adhesion as well as aggregation of platelets by a mechanism involving the integrin α2β1. But, the signal cascades in platelets after SB binding are still not clear. Methodology/Principal Findings In the present study, a differential proteomic analysis (two-dimensional electrophoresis) was conducted to check the protein expression profiles of rat platelets with or without treatment of SB. Proteins altered in level after SB exposure were identified by MALDI-TOF MS/MS. Treatment of SB caused regulation of 20 proteins such as heat shock-related 70 kDa protein 2 (hsp70), LIM domain protein CLP-36, copine I, peroxiredoxin-2, coronin-1 B and cytoplasmic dynein intermediate chain 2C. The regulation of SB on protein levels was confirmed by Western blotting. The signal cascades network induced by SB after its binding with integrin α2β1 was predicted. To certify the predicted network, binding affinity of SB to integrin α2β1 was checked in vitro and ex vivo in platelets. Furthermore, the effects of SB on protein levels of hsp70, coronin-1B and intracellular levels of Ca(2+) and reactive oxygen species (ROS) were checked with or without pre-treatment of platelets using antibody against integrin α2β1. Electron microscopy study confirmed that SB affected cytoskeleton structure of platelets. Conclusions/Significance Integrin α2β1 might be one of the direct target proteins of SB in platelets. The signal cascades network of SB after binding with integrin α2β1 might include regulation of intracellular Ca(2+) level, cytoskeleton-related proteins such as coronin-1B and cytoskeleton structure of platelets. PMID:21379382

  9. Platelet Concentrates: Past, Present and Future

    OpenAIRE

    2011-01-01

    Platelets play a crucial role in hemostasis and wound healing, platelet growth factors are well known source of healing cytokines. Numerous techniques of autologous platelet concentrates have been developed and applied in oral and maxillofacial surgery. This review describes the evolution of the first and second generation of platelet concentrates (platelet rich plasma and platelet rich fibrin respectively) from their fore runner-fibrin sealants.

  10. Studies on megakaryopoiesis and platelet function

    OpenAIRE

    Meinders, M.

    2015-01-01

    Platelets are blood circulating specialized subcellular fragments, which are produced by megakaryocytes. Platelets are essential for hemostasis and wound healing but also play a role in non-hemostatic processes such as the immune response or cancer metastasis. Considering the immediate precursors of platelets, normal megakaryocyte development is essential for normal platelet function. Although much is known about platelet development, some aspects of platelet production remain poorly understo...

  11. 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

  12. [STRUCTURAL CHARACTERIZATION OF PLATELETS AND PLATELET-DERIVED MICROVESICLES].

    Science.gov (United States)

    Ponomareva, A A; Nevzorova, T A; Mordakhanova, E R; Andrianova, I A; Litvinov, R I

    2016-01-01

    Platelets are the anucleated blood cells, wich together with the fibrin stop bleeding (hemostasis). Cellular microvesicles are membrane-surrounded microparticles released into extracellular space upon activation and/or apoptosis of various cells. Platelet-derived macrovesicles from the major population of circulating blood microparticles that play an important role in hemostasis and thrombosis. Despite numerous studies on the pathophysiology of platelet-derived macrovesicles, mechanisms of their formation and structural details remain poorly understood. Here we investigated the ultrastructure of parental platelets and platelet-derived microvesicles formed in vitro by quiescent cells as well as by cells stimulated with one of the following activators: arachidonic acid, ADP, thrombin, calcium ionophore A23187. Using transmission electron microscopy of human platelets and isolated microvesicles, we analyzed the intracellular origin, steps of formation, structural diversity, and size distributions of the subcellular particles. We have revealed that thrombin, unlike other stimuli, not only induced vesiculation of the plasma membrane but also caused break-up of the cells followed by formation of microparticles that are comparable with microvesicles by size. A fraction of these microparticles contained cellular organelles surrounded by a thin membrane. The size of platelet-derived macrovesicles varied from 30 nm to 500 nm, however, the size distributions depended on the nature of a cell-activating stimulus. The results obtained provide new information about the formation of platelet-derived macrovesicles and their structural diversity, wich is important to understand their multiple functions in normal and disease states.

  13. 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.

  14. Involvement of Ca2+ Activated Cl- Channel Ano6 in Platelet Activation and Apoptosis

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    Guoxing Liu

    2015-11-01

    Full Text Available Background/Aims: The ubiquitously expressed Ca2+ Activated Cl- Channel Ano6 participates in the stimulation of cell membrane scrambling. Defective Ano6 underlies the Scott syndrome, an inherited bleeding disorder with impaired scrambling of plasma membrane phospholipids. At least in theory, the bleeding disorder of Scott syndrome may result from impaired platelet function. Activators of platelets include thrombin and collagen related peptide (CRP, which trigger increase of cytosolic Ca2+-activity ([Ca2+]i, production of reactive oxygen species (ROS, degranulation, integrin activation, as well as cell shrinkage and phospholipid scrambling of the cell membrane. The present study thus explored whether Ano6 modifies activation-induced alterations of cytosolic Ca2+-activity ([Ca2+]i, degranulation (P-selectin exposure, integrin activation, phosphatidylserine exposure on the platelet surface and platelet volume. Methods: Platelets from mice lacking Ano6 (ano6-/- were compared to platelets from corresponding wild-type mice (ano6+/+. [Ca2+]i was estimated from Fluo-3 fluorescence, ROS from DCFDA fluorescence, degranulation from P-selectin abundance, integrin activation from αIIbβ3-integrin abundance, phosphatidylserine abundance from annexin-V-binding, and cell volume from forward scatter. Results: Platelet number in blood was slightly higher in ano6-/- mice than in ano6+/+ mice. Without activation [Ca2+]i and volume were similar in ano6-/- and ano6+/+ platelets as well as ROS abundance, P-selectin abundance, αIIbβ3 integrin activation, and phosphatidylserine exposure were negligible in both genotypes. Thrombin (0.01 U/ml and CRP (2 or 5 µg/ml increased [Ca2+]i, ROS abundance, platelet degranulation, αIIbβ3 integrin activation, and triggered annexin-V-binding as well as cell shrinkage, all effects less pronounced in ano6-/- than in ano6+/+ platelets. Conclusions: Genetic knockout of Ano6 blunts thrombin- and CRP-induced activation and apoptosis

  15. 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.

  16. The influence of conjugates isolated from Matricaria chamomilla L. on platelets activity and cytotoxicity.

    Science.gov (United States)

    Bijak, Michał; Saluk, Joanna; Tsirigotis-Maniecka, Marta; Komorowska, Halina; Wachowicz, Barbara; Zaczyńska, Ewa; Czarny, Anna; Czechowski, Franciszek; Nowak, Paweł; Pawlaczyk, Izabela

    2013-10-01

    Cardiovascular diseases (CVD) remain the principal cause of death in both advanced and developing countries of the world. Blood platelets are involved in the pathogenesis of atherosclerosis and thrombosis. Platelet adhesion and aggregation are critical events that occur in unstable coronary syndromes. The current research is focused on the role of polysaccharide-polyphenolic conjugates isolated from chamomile (Matricaria chamomilla L.) at concentrations of 10, 25, 50 and 100 μg/mL on blood platelets (obtained from healthy donors and from patients received combined anti-platelet therapy complex with clopidogrel and acetylsalicylic acid) aggregation and experimentally induced cell toxicity. The treatment of PRP obtained from healthy donors with polyphenolic-polysaccharide conjugates from M. chamomilla (L.) (MC) resulted in a dose-dependent, decrease of platelet aggregation induced by multiple agonists (ADP, collagen and arachidonic acid). In this study we also observed that the MC reduced platelet aggregation in PRP obtained from patients with cardiovascular disorders. The result of testing the MC on human blood platelets, mouse fibroblast cultures L929 and human lung cells A549 did not show any cytotoxicity effects. Compounds obtained from M. chamomilla L. are potential composite to the development of a new anti-platelet agent, which could be an alternative to the currently used anti-platelet drugs.

  17. Doxorubicin-loaded platelets as a smart drug delivery system: An improved therapy for lymphoma

    Science.gov (United States)

    Xu, Peipei; Zuo, Huaqin; Chen, Bing; Wang, Ruju; Ahmed, Arsalan; Hu, Yong; Ouyang, Jian

    2017-01-01

    Chemotherapy is majorly used for the treatment of many cancers, including lymphoma. However, cytotoxic drugs, utilized in chemotherapy, can induce various side effects on normal tissues because of their non-specific distribution in the body. Natural platelets are used as drug carriers because of their biocompatibility and specific targeting to vascular disorders, such as cancer, inflammation, and thrombosis. In this work, doxorubicin (DOX) was loaded in natural platelets for treatment of lymphoma. Results showed that DOX was loaded into platelets with high drug loading and encapsulation efficiency. DOX did not significantly induce morphological and functional changes in platelets. DOX-platelet facilitated intracellular drug accumulation through “tumor cell-induced platelet aggregation” and released DOX into the medium in a pH-controlled manner. This phenomenon reduced the adverse effects and enhanced the therapeutic efficacy. The growth inhibition of lymphoma Raji cells was enhanced, and the cardiotoxicity of DOX was reduced when DOX was loaded in platelets. DOX-platelet improved the anti-tumor activity of DOX by regulating the expression of apoptosis-related genes. Thus, platelets can serve as potential drug carriers to deliver DOX for clinical treatment of lymphoma. PMID:28198453

  18. Analyzing the platelet proteome.

    Science.gov (United States)

    García, Angel; Zitzmann, Nicole; Watson, Steve P

    2004-08-01

    During the last 10 years, mass spectrometry (MS) has become a key tool for protein analysis and has underpinned the emerging field of proteomics. Using high-throughput tandem MS/MS following protein separation, it is potentially possible to analyze hundreds to thousands of proteins in a sample at a time. This technology can be used to analyze the protein content (i.e., the proteome) of any cell or tissue and complements the powerful field of genomics. The technology is particularly suitable for platelets because of the absence of a nucleus. Cellular proteins can be separated by either gel-based methods such as two-dimensional gel electrophoresis or one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by liquid chromatography (LC) -MS/MS or by multidimensional LC-MS/MS. Prefractionation techniques, such as subcellular fractionations or immunoprecipitations, can be used to improve the analysis. Each method has particular advantages and disadvantages. Proteomics can be used to compare the proteome of basal and diseased platelets, helping to reveal information on the molecular basis of the disease.

  19. 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.

  20. 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.

  1. [Murine models of platelet diseases].

    Science.gov (United States)

    Lanza, F

    2007-05-01

    Platelet-related diseases correspond to functional defects or abnormal production (thrombopoiesis) of hereditary and immunological origins. Recent progress in the manipulation of the mouse genome (transgenesis, gene inactivation or insertion) has resulted in the generation of numerous strains exhibiting defective platelet function or production. Some strains reproduce known hereditary diseases affecting haemostasis (Glanzmann thrombasthenia, Bernard-Soulier syndrome (BSS) or thrombopoiesis (Wiscott-Aldrich or May-Hegglin syndrome). More often the mutated strains have no human equivalent and represent useful models to study: (i) the role of adhesive or signalling receptors or of signalling proteins in platelet-dependent haemostasis and thrombosis or; (ii) to study the poorly characterized mechanisms of thrombopoiesis, which implicate transcription factors (GATA, Fli1), growth factors and receptors (TPO, cMPL), and cytoskeletal or contractile proteins (tubulin, myosin). Additional mouse strains result from the selection of spontaneous mutants many of which affect intracellular platelet granules, representing models of storage pool diseases (SPD) such as the Gray platelet syndrome (alphaSPD) or Hermansky-Pudlack syndrome (deltaSPD). More recently, a systematic chemical mutagenesis approach has also identified genes involved in thrombopoiesis and platelet survival. Finally, mouse models of auto- or allo-immune thrombocytopenia have been developed to study the mechanisms of platelet destruction or removal.

  2. Platelet scintigraphy in atherothrombotic disease

    Energy Technology Data Exchange (ETDEWEB)

    Isaka, Yoshinari (Osaka National Hospital (Japan))

    1993-01-01

    Indium-111 platelet scintigraphy for the measurement of in vivo thrombogenicity is a useful noninvasive technique with a number of applications. From 1982 to 1989, we explored clinical relevance of this method for 576 consecutive patients with atherothrombotic disease. There was a disease-related difference in the percentage of positive platelet accumulation; 85% in patients with Dacron bifurcation graft, 75% in abdominal or thoracic aneurysm, 40% in intra-cardiac thrombi, 33% in arteriosclerosis obliterans and 25% in ischemic cerebrovascular disease. Labelled platelets accumulated frequently in the lesion with severe arteriographic abnormality. Aspirin clearly inhibited platelet accumulation on carotid atheroma but the effect of ticlopidine has been less conclusive. Short-term orally active PGI[sub 2] analogue had inhibitory effects on platelet accumulation in carotid atheroma and platelet aggregability, but did not cause significant reduction in plaque size. The results suggest the usefulness of platelet scintigraphy for monitoring the thrombogenicity in various atherothrombotic diseases. It will be necessary, however, to simplify the labelling procedures and to develop a new [sup 99m]Tc-labelled thrombus imaging agent, if thrombus imaging is to be considered for more generall use for patients with atherosclerosis. (author).

  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. Inflammasome in Platelets: Allying Coagulation and Inflammation in Infectious and Sterile Diseases?

    Directory of Open Access Journals (Sweden)

    Eugenio D. Hottz

    2015-01-01

    Full Text Available Platelets are crucial effector cells in hemostasis. In addition, platelets are increasingly recognized as major inflammatory cells with key roles in innate and adaptive immune responses. Activated platelets have key thromboinflammatory activities linking coagulation to inflammatory response in a variety of coagulation disorders and vasculopathies. Recently identified inflammatory activities of platelets include the synthesis of IL-1β from spliced pre-RNA, as well as the presence and assembly of inflammasome which intermediate IL-1β secretion. Here we review the mechanisms by which platelets activate translation machinery and inflammasome assembly to synthesize and release IL-1β. The contributions of these processes to protective and pathogenic responses during infectious and inflammatory diseases are discussed.

  5. Amarogentin, a Secoiridoid Glycoside, Abrogates Platelet Activation through PLCγ2-PKC and MAPK Pathways

    Directory of Open Access Journals (Sweden)

    Ting-Lin Yen

    2014-01-01

    Full Text Available Amarogentin, an active principle of Gentiana lutea, possess antitumorigenic, antidiabetic, and antioxidative properties. Activation of platelets is associated with intravascular thrombosis and cardiovascular diseases. The present study examined the effects of amarogentin on platelet activation. Amarogentin treatment (15~60 μM inhibited platelet aggregation induced by collagen, but not thrombin, arachidonic acid, and U46619. Amarogentin inhibited collagen-induced phosphorylation of phospholipase C (PLCγ2, protein kinase C (PKC, and mitogen-activated protein kinases (MAPKs. It also inhibits in vivo thrombus formation in mice. In addition, neither the guanylate cyclase inhibitor ODQ nor the adenylate cyclase inhibitor SQ22536 affected the amarogentin-mediated inhibition of platelet aggregation, which suggests that amarogentin does not regulate the levels of cyclic AMP and cyclic GMP. In conclusion, amarogentin prevents platelet activation through the inhibition of PLCγ2-PKC cascade and MAPK pathway. Our findings suggest that amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders.

  6. Molecular typing of human platelet and neutrophil antigens (HPA and HNA).

    Science.gov (United States)

    Veldhuisen, Barbera; Porcelijn, Leendert; Ellen van der Schoot, C; de Haas, Masja

    2014-04-01

    Genotyping is an important tool in the diagnosis of disorders involving allo-immunisation to antigens present on the membranes of platelets and neutrophils. To date 28 human platelet antigens (HPAs) have been indentified on six polymorphic glycoproteins on the surface of platelets. Antibodies against HPAs play a role in foetal and neonatal alloimmune thrombocytopenia (FNAIT), post-transfusion purpura (PTP) and refractoriness to donor platelets. The 11 human neutrophil antigens (HNAs) described to date have been indentified on five polymorphic proteins on the surface of granulocytes. Antibodies to HNAs are implicated with foetal and neonatal alloimmune neutropenia (FNAIN), autoimmune neutropenia (AIN) and transfusion related acute lung injury (TRALI). In this report, we will review the molecular basis and techniques currently available for the genotyping of human platelet and neutrophil antigens.

  7. Inflammasome in Platelets: Allying Coagulation and Inflammation in Infectious and Sterile Diseases?

    Science.gov (United States)

    Hottz, Eugenio D.; Monteiro, Ana Paula T.; Bozza, Fernando A.; Bozza, Patrícia T.

    2015-01-01

    Platelets are crucial effector cells in hemostasis. In addition, platelets are increasingly recognized as major inflammatory cells with key roles in innate and adaptive immune responses. Activated platelets have key thromboinflammatory activities linking coagulation to inflammatory response in a variety of coagulation disorders and vasculopathies. Recently identified inflammatory activities of platelets include the synthesis of IL-1β from spliced pre-RNA, as well as the presence and assembly of inflammasome which intermediate IL-1β secretion. Here we review the mechanisms by which platelets activate translation machinery and inflammasome assembly to synthesize and release IL-1β. The contributions of these processes to protective and pathogenic responses during infectious and inflammatory diseases are discussed. PMID:25814789

  8. Platelet enzyme abnormalities in leukemias

    Directory of Open Access Journals (Sweden)

    S Sharma

    2011-01-01

    Full Text Available Aim of the Study: The aim of this study was to evaluate platelet enzyme activity in cases of leukemia. Materials and Methods: Platelet enzymes glucose-6-phosphate dehydrogenase (G6PD, pyruvate kinase (PK and hexokinase (HK were studied in 47 patients of acute and chronic leukemia patients, 16 patients with acute myeloid leukemia (AML(13 relapse, three in remission, 12 patients with acute lymphocytic leukemia (ALL (five in relapse, seven in remission, 19 patients with chronic myeloid leukemia (CML. Results: The platelet G6PD activity was significantly low in cases of AML, ALL and also in CML. G6PD activity was normalized during AML remission. G6PD activity, although persistently low during ALL remission, increased significantly to near-normal during remission (P < 0.05 as compared with relapse (P < 0.01. Platelet PK activity was high during AML relapse (P < 0.05, which was normalized during remission. Platelet HK however was found to be decreased during all remission (P < 0.05. There was a significant positive correlation between G6PD and PK in cases of AML (P < 0.001 but not in ALL and CML. G6PD activity did not correlate with HK activity in any of the leukemic groups. A significant positive correlation was however seen between PK and HK activity in cases of ALL remission (P < 0.01 and CML (P < 0.05. Conclusions: Both red cell and platelet enzymes were studied in 36 leukemic patients and there was no statistically significant correlation between red cell and platelet enzymes. Platelet enzyme defect in leukemias suggests the inherent abnormality in megakaryopoiesis and would explain the functional platelet defects in leukemias.

  9. Platelet surface glutathione reductase-like activity.

    Science.gov (United States)

    Essex, David W; Li, Mengru; Feinman, Richard D; Miller, Anna

    2004-09-01

    We previously found that reduced glutathione (GSH) or a mixture of GSH/glutathione disulfide (GSSG) potentiated platelet aggregation. We here report that GSSG, when added to platelets alone, also potentiates platelet aggregation. Most of the GSSG was converted to GSH by a flavoprotein-dependent platelet surface mechanism. This provided an appropriate redox potential for platelet activation. The addition of GSSG to platelets generated sulfhydryls in the beta subunit of the alpha(IIb)beta(3) fibrinogen receptor, suggesting a mechanism for facilitation of agonist-induced platelet activation.

  10. Mechanisms of platelet-mediated liver regeneration.

    Science.gov (United States)

    Lisman, Ton; Porte, Robert J

    2016-08-04

    Platelets have multiple functions beyond their roles in thrombosis and hemostasis. Platelets support liver regeneration, which is required after partial hepatectomy and acute or chronic liver injury. Although it is widely assumed that platelets stimulate liver regeneration by local excretion of mitogens stored within platelet granules, definitive evidence for this is lacking, and alternative mechanisms deserve consideration. In-depth knowledge of mechanisms of platelet-mediated liver regeneration may lead to new therapeutic strategies to treat patients with failing regenerative responses.

  11. Platelets as delivery systems for disease treatments

    OpenAIRE

    Shi, Qizhen; Montgomery, Robert R.

    2010-01-01

    Platelets are small, anucleate, discoid shaped blood cells that play a fundamental role in hemostasis. Platelets contain a large number of biologically active molecules within cytoplasmic granules that are critical to normal platelet function. Because platelets circulate in blood through out the body, release biological molecules and mediators on demand, and participate in hemostasis as well as many other pathophysiologic processes, targeting expression of proteins of interest to platelets an...

  12. [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.

  13. 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.

  14. Platelets in the paediatric population: the influence of age and the limitations of automation.

    Science.gov (United States)

    Felle, P; McMahon, C; Rooney, S; Donnelly, P; Ni Chonchubhair, F

    2005-08-01

    Accurate and precise platelet counting is important for the clinical management of children with platelet disorders. Current automated technologies are often unable to discriminate platelets from non-platelet particles particularly in circumstances where platelet anisocytosis is common. This study compares manual methodology and the automated technologies; impedance, optical density and CD61 immunoplatelet method (available on the Cell Dyn 4000) with the reference method of flow cytometric analysis in a paediatric population. A total of 141 samples were analysed and divided into specific age related groups and groups with thrombocytopenia and thrombocytosis. Data analysis showed that the CD61 method compared best with the reference method and this was evident in all the specified groups. The mean platelet count obtained by optical and manual methods were lower, suggesting that these methods are less reliable. The impedance count method was accurate despite its limitations. Strong correlations were observed in the 2-14 year age group but there was greater variation in the platelet characteristics in neonates. The CD61 method is the automated method of choice and would be particularly useful in the problem groups (platelet counts <50 x 10(9)/l and neonates <1 month old).

  15. Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice.

    Science.gov (United States)

    Deppermann, Carsten; Cherpokova, Deya; Nurden, Paquita; Schulz, Jan-Niklas; Thielmann, Ina; Kraft, Peter; Vögtle, Timo; Kleinschnitz, Christoph; Dütting, Sebastian; Krohne, Georg; Eming, Sabine A; Nurden, Alan T; Eckes, Beate; Stoll, Guido; Stegner, David; Nieswandt, Bernhard

    2013-07-01

    Platelets are anuclear organelle-rich cell fragments derived from bone marrow megakaryocytes (MKs) that safeguard vascular integrity. The major platelet organelles, α-granules, release proteins that participate in thrombus formation and hemostasis. Proteins stored in α-granules are also thought to play a role in inflammation and wound healing, but their functional significance in vivo is unknown. Mutations in NBEAL2 have been linked to gray platelet syndrome (GPS), a rare bleeding disorder characterized by macrothrombocytopenia, with platelets lacking α-granules. Here we show that Nbeal2-knockout mice display the characteristics of human GPS, with defective α-granule biogenesis in MKs and their absence from platelets. Nbeal2 deficiency did not affect MK differentiation and proplatelet formation in vitro or platelet life span in vivo. Nbeal2-deficient platelets displayed impaired adhesion, aggregation, and coagulant activity ex vivo that translated into defective arterial thrombus formation and protection from thrombo-inflammatory brain infarction following focal cerebral ischemia. In a model of excisional skin wound repair, Nbeal2-deficient mice exhibited impaired development of functional granulation tissue due to severely reduced differentiation of myofibroblasts in the absence of α-granule secretion. This study demonstrates that platelet α-granule constituents are critically required not only for hemostasis but also thrombosis, acute thrombo-inflammatory disease states, and tissue reconstitution after injury.

  16. Platelet-containing tantalum powders

    Energy Technology Data Exchange (ETDEWEB)

    Schiele, E.K.

    1988-04-26

    A method of forming platelet tantalum powders is described comprising the steps of: (a) providing an ingot-derived precursor tantalum powder, and (b) ball-milling the precursor powder for a time sufficient to form a platelet powder having an average FSSS of less than about 2 micrometers, a Scott density not greater than about 30 g/in/sup 3/ and a BET surface area of at least about 0.7 in/sup 2//g.

  17. Blood mean platelet volume and platelet lymphocyte ratio as new predictors of hip osteoarthritis severity.

    Science.gov (United States)

    Taşoğlu, Özlem; Şahin, Ali; Karataş, Gülşah; Koyuncu, Engin; Taşoğlu, İrfan; Tecimel, Osman; Özgirgin, Neşe

    2017-02-01

    Osteoarthritis (OA) is a low grade systemic inflammatory disease in which many inflammatory mediators are known to be elevated in the peripheric blood. Blood platelet lymphocyte ratio (PLR) and mean platelet volume (MPV) are accepted as novel markers in many of the systemic inflammatory disorders, but have not been investigated in synovitis-free radiographic OA yet.The aim of this study was to evaluate the levels of blood PLR and MPV in radiographic hip OA. A total of 880 patients were evaluated retrospectively and after certain exclusion criteria, 237 of them who have primary hip OA were included. Age, sex, height, weight, body mass index, neutrophil, lymphocyte and platelet counts, erythrocyte sedimentation rate (ESR), PLR, and MPV levels were recorded, Kellgren-Lawrence (KL) grading of the hip joints were performed. Patients were then divided into 2 groups as KL grades 1 to 2 (mild-moderate) and KL grades 3 to 4 (severe) hip OA.Mean age, mean neutrophil, lymphocyte and platelet counts, mean MPV, mean PLR, and mean ESR were statistically significantly different between mild/moderate hip OA group and severe hip OA group. In univariate analysis, older age and higher MPV, PLR, and ESR were severely associated with severe hip OA. In multiple logistic regression analysis, MPV, PLR, and ESR emerged as independent predictors of severe hip OA.The results of the present study, for the first time in the literature, suggest blood PLR and MPV as novel inflammatory markers predicting the radiographic severity of hip OA in the daily practice.

  18. 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.

  19. 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.

  20. Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover.

    Science.gov (United States)

    Stratz, Christian; Nührenberg, Thomas; Amann, Michael; Cederqvist, Marco; Kleiner, Pascal; Valina, Christian M; Trenk, Dietmar; Neumann, Franz-Josef; Hochholzer, Willibald

    2016-10-28

    Reticulated platelets are associated with impaired antiplatelet response to thienopyridines. It is uncertain whether this interaction is caused by a decreased drug exposure due to high platelet turnover reflected by elevated levels of reticulated platelets or by intrinsic properties of reticulated platelets. This study sought to investigate if the impact of reticulated platelets on early antiplatelet response to thienopyridines is mainly caused by platelet turnover as previously suggested. Elective patients undergoing coronary intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60 mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and at day 1 after loading. Immature platelet count was assessed as marker of reticulated platelets by flow cytometry. Platelet reactivity increased with rising levels of immature platelet count in both groups. This effect was more distinctive in patients on clopidogrel as compared to patients on prasugrel. Overall, immature platelet count correlated well with on-treatment platelet reactivity at all time-points (p < 0.001). These correlations did not change over time in the entire cohort as well as in patients treated with clopidogrel or prasugrel indicating an effect independent of platelet turnover (comparison of correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of immature platelet count with impaired antiplatelet response to thienopyridines is similar early and late after loading. This finding suggests as main underlying mechanism another effect of reticulated platelets on thienopyridines than platelet turnover.

  1. Platelet satellitism in infectious disease?

    Science.gov (United States)

    Laskaj, Renata; Sikiric, Dubravka; Skerk, Visnja

    2015-01-01

    Background Platelet satellitism is a phenomenon of unknown etiology of aggregating platelets around polymorphonuclear neutrophils and other blood cells which causes pseudothrombocytopenia, visible by microscopic examination of blood smears. It has been observed so far in about a hundred cases in the world. Case subject and methods Our case involves a 73-year-old female patient with a urinary infection. Biochemical serum analysis (CRP, glucose, AST, ALT, ALP, GGT, bilirubin, sodium, potassium, chloride, urea, creatinine) and blood cell count were performed with standard methods on autoanalyzers. Serum protein fractions were examined by electrophoresis and urinalysis with standard methods on autoanalyzer together with microscopic examination of urine sediment. Erythrocyte sedimentation rate, blood culture and urine culture tests were performed with standard methods. Results Due to typical pathological values for bacterial urinary infection, the patient was admitted to the hospital. Blood smear examination revealed phenomenon, which has persisted for three weeks after the disease has been cured. Blood smears with EDTA as an anticoagulant had platelet satellitism whereas the phenomenon was not observed in tubes with different anticoagulants (Na, Li-heparin) and capillary blood. Discussion We hypothesize that satellitism was induced by some immunological mechanism through formation of antibodies which have mediated platelets binding to neutrophil membranes and vice versa. Unfortunately we were unable to determine the putative trigger for this phenomenon. To our knowledge this is the second case of platelet satellitism ever described in Croatia. PMID:26110042

  2. Evaluation of platelet aggregation in platelet concentrates: storage implications

    Directory of Open Access Journals (Sweden)

    Neiva Teresinha J.C.

    2003-01-01

    Full Text Available The use of hemo-derivatives is nowadays a fundamentally important therapeutic modality in the exercise of medicine. Among the various hemo-components employed, we have the platelet concentrate (PC, indicated in cases of hemorrhagic disturbances. We previously showed that platelet function in blood donors is reduced in their screening phase and after the separation process of PCs. Currently, we are providing evidence for the existence of biochemical and functional changes in PC preparations stored for three days at temperatures of 20 ± 2 ºC. Platelet concentrates from 40 healthy donors, collected in CPD anticoagulant and PL-146 polyvinylchloride containers, were examined in order to determine the pH value, pCO2 ,pO2 and lactate concentrations. In addition, the aggregation of platelets with thrombin and collagen were examined to evaluate platelet function. A pH increase from 7.07 ± 0.04 to 7.36 ± 0.07 (p < 0.01 was observed. The pCO2 concentration decreased progressively from 69.2 ± 7.7 mmHg to 28.8 ± 6.2 mmHg (p < 0.001 during the storage period. In contrast, pO2 value increase from 103.4 ± 30.6 to 152.3 ± 24.6 mmHg (p < 0.001 was evidenced during the 48 hours of storage. The lactate concentration increased from 17.97 ± 5.2 to 57.21 ± 5.7 mg/dl (p < 0.001. Platelet aggregation using 0.25 U/ml-thrombin and 2.0 µg/ml-collagen showed significant hypofunction from 61.8 ± 2.7% to 24.8 ± 9.8% and 62.7±5.0 to 33.4± 6.2 (p < 0.001, respectively. We concluded that the evaluated biochemical parameters and the platelet function changed significantly when the platelets were kept under routine storage conditions.

  3. 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

  4. 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...

  5. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2013-01-01

    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  6. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2014-07-01

    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  7. Effect of photodynamic therapy on mouse platelets

    Science.gov (United States)

    Zhou, Chuannong; Chi, Shunji; Deng, Jinsheng; Zhang, Hua; Liang, Junlin; Ha, Xian-wen

    1993-06-01

    Normal mice received hematoporphyrin derivative (HpD) i.v. prior to red light irradiation and the platelet-rich plasma was prepared and irradiated by red light. The platelets were processed for EM examination and stereological analysis. It was shown the 16 hrs after irradiation almost all platelets were necrotized; 8 hours after irradiation about one fourth of the platelets were necrotized and the remaining were considerably damaged. Immediately after irradiation a small number of platelets became necrotic and most other platelets were swollen and deformated, showing significantly increased mean area, perimeter and short axis, and mean cell volume and cell surface area. The findings indicate that platelets are highly sensitive to PDT action and can be directly and rapidly damaged by PDT even in the absence of vascular endothelial cells. The early platelet photoactivation may play an important role in the initiation of early vascular damage and microcirculatory alterations induced by PDT in vivo.

  8. 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.

  9. [Interaction effect of serotonin transporter gene and brain-derived neurotrophic factor on the platelet serotonin content in stroke patients].

    Science.gov (United States)

    Golimbet, V E; Brusov, O S; Factor, M I; Zlobina, G P; Lezheĭko, T V; Lavrushina, O M; Petrova, E A; Savina, M A; Skvortsova, V I

    2010-01-01

    Platelet serotonin content in patients in the acute period of stroke is an important index of clinical changes during the post stroke period as well as a predictor of development of mental disorders. We studied the association between two polymorphisms (5-HTTLPR and Val66Met BDNF) and the platelet serotonin content in 47 patients with stroke. We also investigated the moderating effect of genetic variants on the association between platelet serotonin content and development of affective and anxiety disorders in stroke patients in the acute period of stroke. The interaction effect of two polymorphisms on levels of platelet serotonin was found. The lowest level was observed in patients with the diplotype LL*ValVal, the highest level--in the group of patients with the LL genotype and genotypes containing at least one copy of a Met allele. No moderating effect of genetic variants on the relationship between serotonin content and affective or anxiety disorder was found.

  10. Effect of platelet age on adhesiveness to collagen and platelet surface charge

    Energy Technology Data Exchange (ETDEWEB)

    Castellan, R.M.; Steiner, M.

    1976-11-30

    Adhesion to collagen was investigated as a function of platelet age in rat platelets. Platelet adherence was measured using EDTA-containing platelet- rich plasma which was added to preparations of collagen fibers clamped between magnetic stirrers by recording changes in light transmission. The plot of light transmission versus logarithm of time was linear and allowed calculation of a slope factor which related to the rate of adherence. Neither the amount of collagen nor the platelet count were limiting in the test. Young platelet populations (less than or equal to 1 day old) were obtained during the recovery phase from immune induced thrombocytopenia. Old platelet populations were prepared by blocking thrombopoiesis with cyclophosphamide. Young platelets did not differ significantly from randomly aged platelets in this function. The electrophoretic mobility of platelets was not affected by their age.

  11. 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.

  12. 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.

  13. Platelets Inhibit Migration of Canine Osteosarcoma Cells.

    Science.gov (United States)

    Bulla, S C; Badial, P R; Silva, R C; Lunsford, K; Bulla, C

    2017-01-01

    The interaction between platelets and tumour cells is important for tumour growth and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on cancer metastasis, demonstrating potentially important roles for platelets in tumour progression. To our knowledge, there is no information regarding the role of platelets in cancer progression in dogs. This study was designed to test whether canine platelets affected the migratory behaviour of three canine osteosarcoma cell lines and to give insights of molecular mechanisms. Intact platelets, platelet lysate and platelet releasate inhibited the migration of canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet samples did not alter the inhibitory effect on migration. Platelet treatment also significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes. The interaction between canine platelets or molecules released during platelet activation and these tumour cell lines inhibits their migration, which suggests that canine platelets might antagonize metastasis of canine osteosarcoma. This effect is probably due to, at least in part, downregulation of genes related to epithelial-mesenchymal transition. Copyright © 2016. Published by Elsevier Ltd.

  14. Platelet regulating properties of insulin revisited

    NARCIS (Netherlands)

    Andrade Ferreira, I. (Irlando)

    2005-01-01

    Disturbances in platelet responsiveness in diabetes mellitus (DM) lead to platelet-dependent complications in the vasculature. Our studies showed that insulin inhibits platelet activation by inhibiting ADP- and thrombin-induced Ca2+ levels. Ca2+ is under control of cAMP that is a potent endogenous p

  15. 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.

  16. Platelets and platelet alloantigens: Lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia

    Science.gov (United States)

    Vadasz, Brian; Chen, Pingguo; Yougbaré, Issaka; Zdravic, Darko; Li, June; Li, Conglei; Carrim, Naadiya; Ni, Heyu

    2017-01-01

    Platelets play critical roles in hemostasis and thrombosis. Emerging evidence indicates that they are versatile cells and also involved in many other physiological processes and disease states. Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life threatening bleeding disorder caused by fetal platelet destruction by maternal alloantibodies developed during pregnancy. Gene polymorphisms cause platelet surface protein incompatibilities between mother and fetus, and ultimately lead to maternal alloimmunization. FNAIT is the most common cause of intracranial hemorrhage in full-term infants and can also lead to intrauterine growth retardation and miscarriage. Proper diagnosis, prevention and treatment of FNAIT is challenging due to insufficient knowledge of the disease and a lack of routine screening as well as its frequent occurrence in first pregnancies. Given the ethical difficulties in performing basic research on human fetuses and neonates, animal models are essential to improve our understanding of the pathogenesis and treatment of FNAIT. The aim of this review is to provide an overview on platelets, hemostasis and thrombocytopenia with a focus on the advancements made in FNAIT by utilizing animal models.

  17. Human platelet antigen genotyping of platelet donors in southern Brazil.

    Science.gov (United States)

    Merzoni, J; Fagundes, I S; Lunardi, L W; Lindenau, J D-R; Gil, B C; Jobim, M; Dias, V G; Merzoni, L; Sekine, L; Onsten, T G H; Jobim, L F

    2015-10-01

    Human platelet antigens (HPA) are immunogenic structures that result from single nucleotide polymorphisms (SNPs) leading to single amino acid substitutions. This study sought to determine the allele and genotype frequencies of HPA-1, HPA-2, HPA-3, HPA-4, HPA-5 and HPA-15 in platelet donors from the state of Rio Grande do Sul (RS), Brazil, and compare their allele frequencies to those observed in other populations. HPA genotyping was performed by PCR-SSP method. The study sample comprised 201 platelet donors (167 Caucasians and 34 non-Caucasians). Allele 'a' was that most commonly found for HPA-1 to 5 in both groups. The HPA-15ab genotype predominated over homozygous genotypes of this system. Fisher's exact test revealed statistically significant differences for the HPA-5 system, with a greater prevalence of the HPA-5b allele in non-Caucasians. The neighbour-joining method and principal components analysis revealed genetic proximity between our Caucasian group and European populations. We conclude that the allele frequencies of HPA-1 to 5 and HPA-15 found in our Caucasian sample are similar to those reported for European populations. These findings corroborate the ethnic makeup of the population of RS. The higher frequency of the HPA-5b allele found in the non-Caucasian group of our sample suggests the possibility of allosensitization in patients who receive platelet transfusions from genetically incompatible donors.

  18. Platelet count and platelet indices in women with preeclampsia

    Directory of Open Access Journals (Sweden)

    AlSheeha MA

    2016-11-01

    Full Text Available Muneera A AlSheeha,1 Rafi S Alaboudi,1 Mohammad A Alghasham,1 Javed Iqbal,2 Ishag Adam1 1Department of Obstetrics and Gynaecology, College of Medicine, Qassim University, Buriadah, 2Department of Obstetrics and Gynecology, Maternity and Children’s Hospital, Qassim, Kingdom of Saudi Arabia Background: Although the exact pathophysiology of preeclampsia is not completely understood, the utility of different platelets indices can be utilized to predict preeclampsia.Objective: To compare platelet indices, namely platelet count (PC, mean platelet volume (MPV, platelet distribution width (PDW, and PC to MPV ratio in women with preeclampsia compared with healthy controls.Setting: Qassim Hospital, Kingdom of Saudi Arabia.Design: A case–control study. Sixty preeclamptic women were the cases and an equal number of healthy pregnant women were the controls.Results: There was no significant difference in age, parity, and body mass index between the study groups. Sixteen and 44 of the cases were severe and mild preeclampsia, respectively. There was no significant difference in PDW and MPV between the preeclamptic and control women. Both PC and PC to MPV ratios were significantly lower in the women with preeclampsia compared with the controls. There was no significant difference in the PC, PDW, MPV, and PC to MPV ratio when women with mild and severe preeclampsia were compared. Using receiver operating characteristic (ROC curves, the PC cutoff was 248.0×103/µL for diagnosis of preeclampsia (P=0.019; the area under the ROC curve was 62.4%. Binary regression suggests that women with PC <248.010×103/µL were at higher risk of preeclampsia (odds ratio =2.2, 95% confidence interval =1.08–4.6, P=0.03. The PC/MPV cutoff was 31.2 for diagnosis of preeclampsia (P=0.035, the area under the ROC curve was 62.2%.Conclusion: PC <248.010×103/µL and PC to MPV ratio 31.2 are valid predictors of preeclampsia. Keywords: preeclampsia, platelets, PDW, mean platelet

  19. Platelet count and platelet indices in women with preeclampsia.

    Science.gov (United States)

    AlSheeha, Muneera A; Alaboudi, Rafi S; Alghasham, Mohammad A; Iqbal, Javed; Adam, Ishag

    2016-01-01

    Although the exact pathophysiology of preeclampsia is not completely understood, the utility of different platelets indices can be utilized to predict preeclampsia. To compare platelet indices, namely platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), and PC to MPV ratio in women with preeclampsia compared with healthy controls. Qassim Hospital, Kingdom of Saudi Arabia. A case-control study. Sixty preeclamptic women were the cases and an equal number of healthy pregnant women were the controls. There was no significant difference in age, parity, and body mass index between the study groups. Sixteen and 44 of the cases were severe and mild preeclampsia, respectively. There was no significant difference in PDW and MPV between the preeclamptic and control women. Both PC and PC to MPV ratios were significantly lower in the women with preeclampsia compared with the controls. There was no significant difference in the PC, PDW, MPV, and PC to MPV ratio when women with mild and severe preeclampsia were compared. Using receiver operating characteristic (ROC) curves, the PC cutoff was 248.0×10(3)/µL for diagnosis of pre-eclampsia (P=0.019; the area under the ROC curve was 62.4%). Binary regression suggests that women with PC preeclampsia (odds ratio =2.2, 95% confidence interval =1.08-4.6, P=0.03). The PC/MPV cutoff was 31.2 for diagnosis of preeclampsia (P=0.035, the area under the ROC curve was 62.2%). PC preeclampsia.

  20. 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.

  1. Effect of ionizing radiation on platelet function in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kalovidouris, A.E.; Papayannis, A.G. (Evangelismos Hospital, Athens (Greece))

    1981-01-01

    The effect of ionizing radiation on platelet function was investigated in vitro. Platelet-rich plasma (300x10/sup 9//l) was irradiated with doses of 1, 4, 10, 20 and 50 Gy. Platelet function tests were performed on both irradiated and control (non-irradiated) platelet samples. The platelet function tests were (1) platelet aggregation by ADP (1, 2, 4 ..mu..mol final concentration), adrenaline and collagen, (2) ADP-release from platelets, (3) clot retraction and (4) platelet factor-3 availability. It was found that roentgen irradiation of platelets in vitro did not affect these platelet function tests.

  2. 颅脑创伤后强迫症患者血小板5-羟色胺水平的对照研究%A comparative study of platelet serotonin in patients after traumatic brain injury with obsessive compulsive disorder

    Institute of Scientific and Technical Information of China (English)

    杨永林; 庄须伟; 王兴强; 王善仕; 尹红霞

    2010-01-01

    目的 探讨颅脑创伤后强迫症患者血小板5-羟色胺(5-HT)水平.方法 测定符合诊断标准的27例颅脑创伤后强迫症患者(强迫症组)和27名颅脑创伤后非强迫症患者(对照组)的血小板5-HT水平.结果 颅脑创伤后强迫症组血小板5-HT水平[(139±172)μg/L]低于正常人组[(248±215)μg/L],差异具有显著性(P<0.05).结论 强迫症患者症状与5-HT浓度变化有相关性;单纯强迫思维者的5-HT浓度与单纯强迫动作患者的差异有显著性.%Objective To explore the role of serotonin(5-HT) in obsessive compulsive disorder(OCD) and the difference in platelet 5-HT content between OCD and healthy controls, the obsession and the compulsion subgroup. Methods The concentration of serotonin (5-HT) in twenty-seven patients with OCD and twenty-seven patients without OCD were detected in the study. Results Platelet serotonin level in patients with OCD ( ( 139 ±172 ) μg/L) was lower than that in patients without OCD ( ( 248 ± 215 ) μg/L), and the differences were significant (P<0.05). Conclusion The present results support the hypothesis that 5-HT hypofunctionality contribute to OCD. And the differences between the obsession and the compulsion subgroup in the role of 5-HT are significant.

  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.

    Science.gov (United States)

    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. 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.

  6. Dual role of IL-21 in megakaryopoiesis and platelet homeostasis.

    Science.gov (United States)

    Benbarche, Salima; Strassel, Catherine; Angénieux, Catherine; Mallo, Léa; Freund, Monique; Gachet, Christian; Lanza, François; de la Salle, Henri

    2017-01-05

    Gene profiling studies have indicated that in vitro differentiated human megakaryocytes express the receptor for IL-21 (IL-21R), an immunostimulatory cytokine associated with inflammatory disorders and currently under evaluation in cancer therapy. The aim of this study was to investigate whether IL-21 modulates megakaryopoiesis. We first checked the expression of IL-21 receptor on human bone marrow and in vitro differentiated megakaryocytes. Then, we investigated the effect of IL-21 on the in vitro differentiation of human blood CD34+ progenitors into megakaryocytes. Finally, we analyzed the consequences of hydrodynamic transfection-mediated transient expression of IL-21, on megakaryopoieisis and thrombopoiesis in mice. The IL-21Rα chain was expressed in human bone marrow megakaryocytes and was progressively induced during in vitro differentiation of human peripheral CD34+ progenitors, while the signal transducing γ chain was down-regulated. Consistently, the STAT3 phosphorylation induced by IL-21 diminished during the later stages of megakaryocytic differentiation. In vitro, IL-21 increased the number of CFU-MKs generated from CD34+ cells and the number of megakaryocyte differentiated from CD34+ progenitors in a JAK3- and STAT3-dependent manner. Forced expression of IL-21 in mice increased the density of bi-potent MK progenitors and bone marrow megakaryocytes, and the platelet generation, but increased platelet clearance and consequently resulting in reduced blood platelet counts. Our work suggests that IL-21 regulates megakaryocyte development and platelet homeostasis. Thus IL-21 may link immune responses to physiological or pathological platelet-dependent processes.

  7. Platelet activation by extracellular matrix proteins in haemostasis and thrombosis.

    Science.gov (United States)

    Watson, Steve P

    2009-01-01

    The prevention of excessive blood loss to avoid fatal haemorrhage is a pivotal process for all organisms possessing a circulatory system. Increased circulating blood volume and pressure, as required in larger animals, make this process all the more important and challenging. It is essential to have a powerful and rapid system to detect damage and generate an effective seal, and which is also exquisitely regulated to prevent unwanted, excessive or systemic activation so as to avoid blockage of vessels. Thus, a highly specialised and efficient haemostatic system has evolved that consists of cellular (platelets) and protein (coagulation factors) components. Importantly, this is able to support haemostasis in both the low shear environment of the venous system and the high shear environment of the arterial system. Endothelial cells, lining the entire circulation system, play a crucial role in the delicate balance between activation and inhibition of the haemostatic system. An intact and healthy endothelium supports blood flow by preventing attachment of cells and proteins which is required for initiation of coagulation and platelet activation. Endothelial cells produce and release the two powerful soluble inhibitors of platelet activation, nitric oxide and prostacyclin, and express high levels of CD39 which rapidly metabolises the major platelet feedback agonist, ADP. This antithrombotic environment however can rapidly change following activation or removal of endothelial cells through injury or rupture of atherosclerotic plaques. Loss of endothelial cells exposes the subendothelial extracellular matrix which creates strong signals for activation of the haemostatic system including powerful platelet adhesion and activation. Quantitative and qualitative changes in the composition of the subendothelial extracellular matrix influence these prothrombotic characteristics with life threatening thrombotic and bleeding complications, as illustrated by formation of

  8. Adjusting MtDNA Quantification in Whole Blood for Peripheral Blood Platelet and Leukocyte Counts.

    Science.gov (United States)

    Hurtado-Roca, Yamilee; Ledesma, Marta; Gonzalez-Lazaro, Monica; Moreno-Loshuertos, Raquel; Fernandez-Silva, Patricio; Enriquez, Jose Antonio; Laclaustra, Martin

    2016-01-01

    Alterations of mitochondrial DNA copy number (mtDNAcn) in the blood (mitochondrial to nuclear DNA ratio) appear associated with several systemic diseases, including primary mitochondrial disorders, carcinogenesis, and hematologic diseases. Measuring mtDNAcn in DNA extracted from whole blood (WB) instead of from peripheral blood mononuclear cells or buffy coat may yield different results due to mitochondrial DNA present in platelets. The aim of this work is to quantify the contribution of platelets to mtDNAcn in whole blood [mtDNAcn(WB)] and to propose a correction formula to estimate leukocytes' mtDNAcn [mtDNAcn(L)] from mtDNAcn(WB). Blood samples from 10 healthy adults were combined with platelet-enriched plasma and saline solution to produce artificial blood preparations. Aliquots of each sample were combined with five different platelet concentrations. In 46 of these blood preparations, mtDNAcn was measured by qPCR. MtDNAcn(WB) increased 1.07 (95%CI 0.86, 1.29; p<0.001) per 1000 platelets present in the preparation. We proved that leukocyte count should also be taken into account as mtDNAcn(WB) was inversely associated with leukocyte count; it increased 1.10 (95%CI 0.95, 1.25, p<0.001) per unit increase of the ratio between platelet and leukocyte counts. If hematological measurements are available, subtracting 1.10 the platelets/leukocyte ratio from mtDNAcn(WB) may serve as an estimation for mtDNAcn(L). Both platelet and leukocyte counts in the sample are important sources of variation if comparing mtDNAcn among groups of patients when mtDNAcn is measured in DNA extracted from whole blood. Not taking the platelet/leukocyte ratio into account in whole blood measurements, may lead to overestimation and misclassification if interpreted as leukocytes' mtDNAcn.

  9. Adjusting MtDNA Quantification in Whole Blood for Peripheral Blood Platelet and Leukocyte Counts

    Science.gov (United States)

    Gonzalez-Lazaro, Monica; Moreno-Loshuertos, Raquel; Fernandez-Silva, Patricio; Enriquez, Jose Antonio; Laclaustra, Martin

    2016-01-01

    Alterations of mitochondrial DNA copy number (mtDNAcn) in the blood (mitochondrial to nuclear DNA ratio) appear associated with several systemic diseases, including primary mitochondrial disorders, carcinogenesis, and hematologic diseases. Measuring mtDNAcn in DNA extracted from whole blood (WB) instead of from peripheral blood mononuclear cells or buffy coat may yield different results due to mitochondrial DNA present in platelets. The aim of this work is to quantify the contribution of platelets to mtDNAcn in whole blood [mtDNAcn(WB)] and to propose a correction formula to estimate leukocytes' mtDNAcn [mtDNAcn(L)] from mtDNAcn(WB). Blood samples from 10 healthy adults were combined with platelet-enriched plasma and saline solution to produce artificial blood preparations. Aliquots of each sample were combined with five different platelet concentrations. In 46 of these blood preparations, mtDNAcn was measured by qPCR. MtDNAcn(WB) increased 1.07 (95%CI 0.86, 1.29; p<0.001) per 1000 platelets present in the preparation. We proved that leukocyte count should also be taken into account as mtDNAcn(WB) was inversely associated with leukocyte count; it increased 1.10 (95%CI 0.95, 1.25, p<0.001) per unit increase of the ratio between platelet and leukocyte counts. If hematological measurements are available, subtracting 1.10 the platelets/leukocyte ratio from mtDNAcn(WB) may serve as an estimation for mtDNAcn(L). Both platelet and leukocyte counts in the sample are important sources of variation if comparing mtDNAcn among groups of patients when mtDNAcn is measured in DNA extracted from whole blood. Not taking the platelet/leukocyte ratio into account in whole blood measurements, may lead to overestimation and misclassification if interpreted as leukocytes' mtDNAcn. PMID:27736919

  10. 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.

  11. 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.

  12. Molecular defects in the ABCA1 pathway affect platelet function.

    Science.gov (United States)

    Schmitz, Gerd; Schambeck, Christian M

    2006-01-01

    Platelet function is sensitive to alterations in cholesterol metabolism, and hypercholesterolemia is associated with enhanced platelet reagibility. Atherogenic low-density lipoproteins (LDL), in particular oxidized LDL, activate src-kinase-family-dependent signalling. In contrast, antiatherogenic high-density lipoproteins(HDL) inhibit platelet aggregation and target the phosphatidylinositol phospholipase C (PI-PLC) pathway. Sphingosine 1-phosphate is a major HDL component and may be crucial for downstream reactions of collagen-induced glycoprotein VI signalling and phosphoinositide 3-kinase. The ATP-binding cassette transporter A1 (ABCA1) regulates cell membrane phospholipid and cholesterol homeostasis and their release to lipid-poor apolipoprotein AI to generate prebeta-HDL precursor particles. ABCA1 also interacts with modulators of vesicular trafficking and number and impaired release of dense bodies from platelets. The ABCA1-NH2-terminus-associated Syntaxin-13, a SNARE complex protein, interacts with syntaxin 13-interacting protein (pallidin) whose deficiency leads to impaired platelet granule release from the dense granule Adapter Protein-3 (AP-3)-related pathway. Interestingly, the cholesterol transporter ABCG1 in addition to ABCA1 is another constituent of the AP-3 pathway, and disorders of lysosome-related organelles such as the Hermansky-Pudlack syndrome complex, Chediak-Higashi syndrome and the ceroid lipofuscinoses provide new opportunities to understand AP-3 pathway-related disorders and the irrelation to membrane phospholipid processing. ABCA1 mutations are involved in dysregulated vesicular trafficking from the trans golgi compartment to the plasma membrane, and ABCA1 R1925Q was shown to contribute to Scott syndrome, a phospholipid-processing disorder of missing surface exposure of phosphatidlyserine. The P2Y12 receptor triggers dense granule secretion by downstream effectors including the G-protein-coupled inward rectifier K+ channel-4 (GIRK-4), and

  13. Platelet-mediated cytotoxicity and its enhancement by platelet activating factor.

    Science.gov (United States)

    Bykovskaya, S N; Bolvacheva, A V; Kiselevsky, M V; Khaylenko, V A; Bykovsky, A F

    1991-01-01

    Platelet cytotoxicity was assessed in 70 cancer patients with various tumor localizations and in 30 normal donors. The data presented reveal that the ACL cell line displays the highest sensitivity to platelet cytotoxicity. Using the ACL cells, we discovered that platelets from oncological patients and normal donors display comparable cytotoxicity. The level of platelet lytic activity is irrelevant to tumor localisation; however, it appears to be dependent on the stage of tumor growth. Incubation of platelets, both from donors and patients, with PAF (concentration range 10 pM to 10 nM) results in a significant rise of the killing activity of platelets. PAF induces greater cytotoxicity enhancement for platelets with lower initial activity, this pattern appearing to be the specific feature of the PAF mediated effect. Hence, platelets can be considered as effector cells relevant to antitumor immunity; PAF-mediated enhancement of platelet cytotoxicity can appear to be useful in the search for new immunotherapeutic drugs.

  14. 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.

  15. 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.

  16. Kinetics and sites of destruction of /sup 111/In-oxine-labeled platelets in idiopathic thrombocytopenic purpura: a quantitative study

    Energy Technology Data Exchange (ETDEWEB)

    Heyns, A.D.; Loetter, M.G.; Badenhorst, P.N.; de Kock, F.; Pieters, H.; Herbst, C.; van Reenen, O.R.; Kotze, H.; Minnaar, P.C.

    1982-04-01

    Kinetics and quantification of the sites of destruction of /sup 111/In-oxine-labeled autologous platelets were investigated in eight patients with idiopathic thrombocytopenic purpura. The mean platelet count was 17 +/- 9 X 10(9)/liter; platelets were separated by differential centrifugation and labeled with 5.6 +/- 2.5 MBq /sup 111/In. Whole body and organ /sup 111/In-platelet distribution was quantitated with a scintillation camera and a computer-assisted imaging system acquisition matrix. Areas of interest were selected with the computer and organ /sup 111/In-radioactivity expressed as a percentage of whole body activity. Mean platelet survival was 49.5 +/- 29.6 hr and the survival curves were exponential. Equilibrium percentage organ /sup 111/In-radioactivity was (normal values in parentheses): spleen 33.7 +/- 8.8 (31.1 +/- 10.2); liver 16.1 +/- 9.5 (13.1 +/- 1.3); thorax 22.8 +/- 3.7 (28.2 +/- 5.6). Percentage organ /sup 111/In-activity at the time when labeled platelets had disappeared from the circulation was: spleen 44.5 +/- 16.4 (40 +/- 16); liver 16.0 +/- 11.5 (32.4 +/- 7.2); thorax 19.7 +/- 6.0 (17.7 +/- 10.3). Thorax activity corresponds to bone marrow radioactivity. Three patterns of platelet sequestration were evident. Three patients had mainly splenic sequestration, two mainly hepatic sequestration, and three diffuse reticuloendothelial system sequestration with a major component of platelets destroyed in the bone marrow. Splenectomy was performed in two patients. The pattern of /sup 111/In-platelet sequestration was not predictive of response of glucocorticoid therapy or indicative of the necessity for splenectomy. Quantitative /sup 111/In-labeled autologous platelet kinetic studies provide a new tool for the investigation of platelet disorders.U

  17. Platelet count and platelet indices in women with preeclampsia

    OpenAIRE

    AlSheeha MA; Alaboudi RS; Alghasham MA; Iqbal J; Adam I

    2016-01-01

    Muneera A AlSheeha,1 Rafi S Alaboudi,1 Mohammad A Alghasham,1 Javed Iqbal,2 Ishag Adam1 1Department of Obstetrics and Gynaecology, College of Medicine, Qassim University, Buriadah, 2Department of Obstetrics and Gynecology, Maternity and Children’s Hospital, Qassim, Kingdom of Saudi Arabia Background: Although the exact pathophysiology of preeclampsia is not completely understood, the utility of different platelets indices can be utilized to predict preeclampsia.Obj...

  18. Pathogen-Reduced, Platelet Additive Solution, Extended Stored Platelets (PREPS)

    Science.gov (United States)

    2015-10-01

    associated sepsis remains the principal lethal risk associated with platelet transfusion. Cold storage (4°C) is known to reduce post transfusion...and no residual radiation is detectable . *P-selectin samples will be prepped on end of storage day and batch tested. **Bacterial Culture sample...temperature controlled room until such time as they have no detectable residual radiation. This is generally about 3-4 months. At that point they are

  19. Detection of microbial contamination in platelets

    Science.gov (United States)

    Berg, Tracy L.; Leparc, German; Huffman, Debra E.; Gennaccaro, Angela L.; Garcia-Lopez, Alicia; Klungness, Greta; Stephans, Christie; Garcia-Rubio, Luis H.

    2005-03-01

    In the United States, approximately 100 patients develop fatal sepsis associated with platelet transfusions every year. Current culture methods take 24-48 hours to acquire results, which in turn decrease the shelf life of platelets. Many of the microorganisms that contaminate platelets can replicate easily at room temperature, which is the necessary storage temperature to keep platelets functional. Therefore, there is a need for in-situ quality control assessment of the platelet quality. For this purpose, a real time spectrophotometric technique has been developed. The Spectral Acquisition Processing Detection (SAPD) method, comprised of a UV-vis spectrophotometer and modeling algorithms, is a rapid method that can be performed prior to platelet transfusion to decrease the risk of bacterial infection to patients. The SAPD method has been used to determine changes in cell suspensions, based on size, shape, chemical composition and internal structure. Changes in these cell characteristics can in turn be used to determine microbial contamination, platelet aging and other physiologic changes. Detection limits of this method for platelet suspensions seeded with bacterial contaminants were identified to be less than 100 cfu/ml of sample. Bacterial counts below 1000 cfu/ml are not considered clinically significant. The SAPD method can provide real-time identification of bacterial contamination of platelets affording patients an increased level of safety without causing undue strain on laboratory budgets or personnel while increasing the time frame that platelets can be used by dramatically shortening contaminant detection time.

  20. Influence of Oxidative Stress on Stored Platelets

    Directory of Open Access Journals (Sweden)

    K. Manasa

    2016-01-01

    Full Text Available Platelet storage and its availability for transfusion are limited to 5-6 days. Oxidative stress (OS is one of the causes for reduced efficacy and shelf-life of platelets. The studies on platelet storage have focused on improving the storage conditions by altering platelet storage solutions, temperature, and materials. Nevertheless, the role of OS on platelet survival during storage is still unclear. Hence, this study was conducted to investigate the influence of storage on platelets. Platelets were stored for 12 days at 22°C. OS markers such as aggregation, superoxides, reactive oxygen species, glucose, pH, lipid peroxidation, protein oxidation, and antioxidant enzymes were assessed. OS increased during storage as indicated by increments in aggregation, superoxides, pH, conjugate dienes, and superoxide dismutase and decrements in glucose and catalase. Thus, platelets could endure OS till 6 days during storage, due to the antioxidant defense system. An evident increase in OS was observed from day 8 of storage, which can diminish the platelet efficacy. The present study provides an insight into the gradual changes occurring during platelet storage. This lays the foundation towards new possibilities of employing various antioxidants as additives in storage solutions.

  1. 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.

  2. Trehalose lyophilized platelets for wound healing.

    Science.gov (United States)

    Pietramaggiori, Giorgio; Kaipainen, Arja; Ho, David; Orser, Cindy; Pebley, Walter; Rudolph, Alan; Orgill, Dennis P

    2007-01-01

    Fresh platelet preparations are utilized to treat a wide variety of wounds, although storage limitations and mixed results have hampered their clinical use. We hypothesized that concentrated lyophilized and reconstituted platelet preparations, preserved with trehalose, maintain and possibly enhance fresh platelets' ability to improve wound healing. We studied the ability of a single dose of trehalose lyophilized and reconstituted platelets to enhance wound healing when topically applied on full-thickness wounds in the genetically diabetic mouse. We compared these results with the application of multiple doses of fresh platelet preparations and trehalose lyophilized and reconstituted platelets as well as multiple doses of vascular endothelial growth factor (VEGF) and wounds left untreated. Trehalose lyophilized and reconstituted platelets, in single and multiple applications, multiple applications of fresh platelets and multiple applications of VEGF increased granulation tissue deposition, vascularity, and proliferation when compared with untreated wounds, as assessed by histology and immunohistochemistry. Wounds treated with multiple doses of VEGF and a single dose of freeze-dried platelets reached 90% closure faster than wounds left untreated. A single administration of trehalose lyophilized and reconstituted platelet preparations enhanced diabetic wound healing, therefore representing a promising strategy for the treatment of nonhealing wounds.

  3. Small RNAs as potential platelet therapeutics.

    Science.gov (United States)

    Edelstein, Leonard C; Bray, Paul F

    2012-01-01

    MicroRNAs (miRNAs) are 21-23 nucleotide RNAs that regulate more than 60% of mammalian protein coding genes. miRNAs play critical roles in hematopoiesis and megakaryocyte function and development. Platelets, in addition to possessing functional miRNA processing machinery, have miRNA levels that have been correlated with platelet reactivity, and these miRNAs have been shown to target mRNAs that encode proteins that alter platelet function. There are potential uses of platelet miRNA as biomarkers and therapeutic agents. Due to the ability of platelets to release miRNA-containing microparticles at sites of activation, including angiogenic regions, tumors, and atherosclerotic plaques, there is the possibility of engineering platelets to deliver miRNA-based therapies to these sites. Cellpreferential expression of miRNAs could be exploited to restrict transgene expression in hematopoietic stem cell gene therapy to the desired lineage, including megakaryocytes and platelets. Finally, manipulation of gene expression in stored platelets may allow more effective platelet storage. Although much work remains to be done, there is great potential in miRNA-based platelet therapies.

  4. Understanding platelet function through signal transduction.

    Science.gov (United States)

    Lazarus, Alan H; Song, Seng; Crow, Andrew R

    2003-01-01

    Platelets are activated by a number of stimuli resulting in the expression and/or activation of surface receptors, secretion of vasoactive substances, adhesion, aggregation, and finally thrombus formation. These events are propagated by a process known as transmembrane signaling, which relays the activating signal from the platelet membrane (eg, von Willebrand Factor binding to glycoprotein Ib) to the inside of the platelet which then serves to activate the platelet via a cascade of biochemical interactions. Inhibition of these transmembrane signaling molecules with a variety of available inhibitors or antagonists can in many cases prevent the platelet from becoming activated. An awareness of the mechanisms involved in platelet transmembrane signaling and the recent availability of new reagents to inhibit signaling may provide us with additional means to prevent platelet activation and perhaps even ameliorate the platelet storage lesion. This review will provide an introduction to the field of platelet transmembrane signaling and give an overview of some of the platelet signaling mechanisms that are relevant to transfusion medicine. Copyright 2003, Elsevier Science (USA). All rights reserved.

  5. Platelet destruction in autoimmune thrombocytopenic purpura: kinetics and clearance of indium-111-labeled autologous platelets

    Energy Technology Data Exchange (ETDEWEB)

    Stratton, J.R.; Ballem, P.J.; Gernsheimer, T.; Cerqueira, M.; Slichter, S.J.

    1989-05-01

    Using autologous /sup 111/In-labeled platelets, platelet kinetics and the sites of platelet destruction were assessed in 16 normal subjects (13 with and three without spleens), in 17 studies of patients with primary autoimmune thrombocytopenic purpura (AITP), in six studies of patients with secondary AITP, in ten studies of patients with AITP following splenectomy, and in five thrombocytopenic patients with myelodysplastic syndromes. In normal subjects, the spleen accounted for 24 +/- 4% of platelet destruction and the liver for 15 +/- 2%. Untreated patients with primary AITP had increased splenic destruction (40 +/- 14%, p less than 0.001) but not hepatic destruction (13 +/- 5%). Compared with untreated patients, prednisone treated patients did not have significantly different spleen and liver platelet sequestration. Patients with secondary AITP had similar platelet counts, platelet survivals, and increases in splenic destruction of platelets as did patients with primary AITP. In contrast, patients with myelodysplastic syndromes had a normal pattern of platelet destruction. In AITP patients following splenectomy, the five nonresponders all had a marked increase (greater than 45%) in liver destruction compared to five responders (all less than 40%). Among all patients with primary or secondary AITP, there was an inverse relationship between the percent of platelets destroyed in the liver plus spleen and both the platelet count (r = 0.75, p less than 0.001) and the platelet survival (r = 0.86, p less than 0.001). In a stepwise multiple linear regression analysis, total liver plus spleen platelet destruction, the platelet survival and the platelet turnover were all significant independent predictors of the platelet count. Thus platelet destruction is shifted to the spleen in primary and secondary AITP. Failure of splenectomy is associated with a marked elevation in liver destruction.

  6. Platelet activation patterns in platelet size sub-populations: differential responses to aspirin in vitro.

    Science.gov (United States)

    Mangalpally, Kiran Kumar R; Siqueiros-Garcia, Alan; Vaduganathan, Muthiah; Dong, Jing-Fei; Kleiman, Neal S; Guthikonda, Sasidhar

    2010-10-01

    Circulating platelets are heterogeneous in size and structure. Whether this translates into differences in platelet function and efficacy of antiplatelet therapy is unclear. Hence, we decided to investigate the activation patterns among different platelet populations differentiated by size, and to compare the inhibitory effects of aspirin in these populations. Circulating platelets from 9 healthy volunteers were separated by size and stratified into the largest and smallest quintiles. Platelets were stimulated with 75 μM arachidonic acid (AA), 10 μM ADP or 25 μM TRAP. Alpha-granule protein secretion and expression (P-selectin, VWF, fibrinogen), surface-protein activation (activated integrin αIIbβ3) were assessed. Platelet thromboxane B(2) (TxB(2)) synthesis following AA stimulation was measured in vitro before and after incubation with 265 μM aspirin. Reticulated (juvenile) platelets were assessed using thiazole orange staining. A greater number of large platelets in the largest quintile were reticulated compared with the smallest quintile (6.1 ± 2.8% vs. 1.2 ± 1.5% respectively, p aspirin (1029 ± 190 pg/mL vs. 851 ± 159 pg/mL, respectively, p = 0.03). After stimulation with each agonist, a greater proportion of large platelets bound fibrinogen, VWF, P-selectin and activated integrin αIIbβ3 than small platelets both in the presence and in the absence of in vitro aspirin. In an in vitro setting, large platelets appear to be more active than small platelets and continue to be more active even after in vitro aspirin. Platelets exhibit heterogeneity in size and structure. Whether this translates into platelet function and efficacy of antiplatelet therapy is unclear. We evaluated platelet functional properties and the effects of aspirin on separated platelet subpopulations in an in vitro setting. Platelets were sorted into the largest and smallest size quintiles using flow cytometry forward scatter. Alpha-granule protein release, dense granule content

  7. Caffeic acid treatment alters the extracellular adenine nucleotide hydrolysis in platelets and lymphocytes of adult rats.

    Science.gov (United States)

    Anwar, Javed; Spanevello, Roselia Maria; Pimentel, Victor Camera; Gutierres, Jessié; Thomé, Gustavo; Cardoso, Andreia; Zanini, Daniela; Martins, Caroline; Palma, Heloisa Einloft; Bagatini, Margarete Dulce; Baldissarelli, Jucimara; Schmatz, Roberta; Leal, Cláudio Alberto Martins; da Costa, Pauline; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

    2013-06-01

    This study evaluated the effects of caffeic acid on ectonucleotidase activities such as NTPDase (nucleoside triphosphate diphosphohydrolase), Ecto-NPP (nucleotide pyrophosphatase/phosphodiesterase), 5'-nucleotidase and adenosine deaminase (ADA) in platelets and lymphocytes of rats, as well as in the profile of platelet aggregation. Animals were divided into five groups: I (control); II (oil); III (caffeic acid 10 mg/kg); IV (caffeic acid 50 mg/kg); and V (caffeic acid 100 mg/kg). Animals were treated with caffeic acid diluted in oil for 30 days. In platelets, caffeic acid decreased the ATP hydrolysis and increased ADP hydrolysis in groups III, IV and V when compared to control (P<0.05). The 5'-nucleotidase activity was decreased, while E-NPP and ADA activities were increased in platelets of rats of groups III, IV and V (P<0.05). Caffeic acid reduced significantly the platelet aggregation in the animals of groups III, IV and V in relation to group I (P<0.05). In lymphocytes, the NTPDase and ADA activities were increased in all groups treated with caffeic acid when compared to control (P<0.05). These findings demonstrated that the enzymes were altered in tissues by caffeic acid and this compound decreased the platelet aggregation suggesting that caffeic acid should be considered a potentially therapeutic agent in disorders related to the purinergic system.

  8. STABILIZATION OF STANDARD PLATELET CONCENTRATES AND MINIMIZATION OF THE PLATELET STORAGE LESION BY A PROSTACYCLIN ANALOG

    NARCIS (Netherlands)

    ELIAS, M; HEETHUIS, A; BOM, [No Value; BLOM, N; MCSHINE, RL; HALIE, MR; SIBINGA, CTS

    Platelet concentrates were pretreated with a stable synthetic prostacyclin analogue (Iloprost) at two different concentrations before the second centrifugation step (pelleting step) of preparation. This resulted in loss. of platelet sensitivity to aggregating agents. To mimic the situation after

  9. Mean platelet volume in acute rheumatic fever.

    Science.gov (United States)

    Sert, Ahmet; Aypar, Ebru; Odabas, Dursun

    2013-01-01

    Acute rheumatic fever (ARF) is still an endemic disease, especially among school-aged children in developing countries. Mean platelet volume (MPV), which is commonly used as a measure of platelet size, indicates the rate of platelet production and platelet activation. We aimed to investigate MPV in children with ARF. The study population consisted of 40 children with ARF (32 patients with carditis and 8 patients without carditis) and 40 healthy control subjects. White blood cell (WBC) and platelet counts were significantly higher and MPV values were significantly lower in patients with ARF during the acute stage when compared to controls. Erythrocyte sedimentation rate (ESR) and C-reactive protein values significantly decreased in patients with ARF after the treatment when compared to baseline, whereas MPV values increased. MPV values were negatively correlated with ESR and WBC, and platelet counts. In conclusion, during the acute stage of ARF, MPV values were lower when compared to controls.

  10. Therapeutic platelet reduction: Use in postsplenectomy thrombocytosis

    Directory of Open Access Journals (Sweden)

    Gita Negi

    2015-01-01

    Full Text Available Therapeutic platelet reduction is an effective modality for the reduction of platelet count in patients with treatment of extreme thrombocytosis resulting from a variety of primary and secondary causes of thrombocytosis, which may be associated with thrombotic or hemorrhagic complications of varying degrees. These cases when symptomatic fall into the ASFA Category II indication for therapeutic platelet apheresis procedure. Here, we report a case of postsplenectomy secondary thrombocytosis presenting with extremely high platelet counts and subsequent thrombosis in the shunt and successful treatment after therapeutic platelet reduction. The case is being presented to bring forth the fact that therapeutic platelet reduction is an easy procedure that gives quick and good results and also to bring to the attention of transfusion specialists an associated but as yet unreported procedural finding.

  11. Differential effects of platelets and platelet inhibition by ticagrelor on TLR2- and TLR4-mediated inflammatory responses

    NARCIS (Netherlands)

    Tunjungputri, R.N.; Ven, A.J.A.M. van der; Riksen, N.P.; Rongen, G.A.P.J.M.; Tacke, S.; Berg, T.N.A. van den; Fijnheer, R.; Gomes, M.E.; Dinarello, C.A.; Veerdonk, F.L. van de; Gasem, M.H.; Netea, M.G.; Joosten, L.A.B.; Groot, P.G. de; Mast, Q. de

    2015-01-01

    Platelets and platelet-monocyte interaction play an important role in inflammation. Both pro- and anti-inflammatory effects of platelet inhibition have been reported in animal models. This study aimed to investigate the effect of platelets and platelet inhibition by the new P2Y12 receptor antagonist

  12. LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism.

    Science.gov (United States)

    Carnevale, Roberto; Bartimoccia, Simona; Nocella, Cristina; Di Santo, Serena; Loffredo, Lorenzo; Illuminati, Giulio; Lombardi, Elisabetta; Boz, Valentina; Del Ben, Maria; De Marco, Luigi; Pignatelli, Pasquale; Violi, Francesco

    2014-11-01

    Platelets generate oxidized LDL (ox-LDL) via NOX2-derived oxidative stress. We investigated if once generated by activated platelets ox-LDL can propagate platelet activation. Experiments were performed in platelets from healthy subjects (HS), hyper-cholesterolemic patients and patients with NOX2 hereditary deficiency. Agonist-stimulated platelets from HS added with LDL were associated with a dose-dependent increase of reactive oxidant species and ox-LDL. Agonist-stimulated platelets from HS added with a fixed dose of LDL (57.14 μmol/L) or added with homogenized human atherosclerotic plaque showed enhanced ox-LDL formation (approximately +50% and +30% respectively), which was lowered by a NOX2 inhibitor (approximately -35% and -25% respectively). Compared to HS, ox-LDL production was more pronounced in agonist-stimulated platelet rich plasma (PRP) from hyper-cholesterolemic patients but was almost absent in PRP from NOX2-deficient patients. Platelet aggregation and 8-iso-PGF2α-ΙΙΙ formation increased in LDL-treated washed platelets (+42% and +53% respectively) and PRP (+31% and +53% respectively). Also, LDL enhanced platelet-dependent thrombosis at arterial shear rate (+33%) but did not affect platelet activation in NOX2-deficient patients. Platelet activation by LDL was significantly inhibited by CD36 or LOX1 blocking peptides, two ox-LDL receptor antagonists, or by a NOX2 inhibitor. LDL-added platelets showed increased p38MAPK (+59%) and PKC (+51%) phosphorylation, p47(phox) translocation to platelet membrane (+34%) and NOX2 activation (+30%), which were inhibited by ox-LDL receptor antagonists. Platelets oxidize LDL, which in turn amplify platelet activation via specific ox-LDL receptors; both effects are mediated by NOX2 activation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Quercetin changes purinergic enzyme activities and oxidative profile in platelets of rats with hypothyroidism.

    Science.gov (United States)

    Baldissarelli, Jucimara; Santi, Adriana; Schmatz, Roberta; Zanini, Daniela; Cardoso, Andréia M; Abadalla, Fátima H; Thomé, Gustavo R; Murussi, Camila; Polachini, Carla R N; Delenogare, Diéssica P; Loro, Vania L; Morsch, Vera M; Schetinger, Maria R C

    2016-12-01

    Diseases related to thyroid hormones have been extensively studied because affect a large number of individuals, and these hormones participate in the regulation of the whole organism homeostasis. However, little is known about the involvement of purinergic signaling related to oxidative stress in hypothyroidism and possible therapeutic adjuncts for treatment of this disorder. Thus, the present study investigates the effects of quercetin on NTPDase, 5'-nucleotidase and adenosine deaminase activities, platelet aggregation and oxidative profile in platelets of rats with methimazole (MMI)-induced hypothyroidism. Methimazole at a concentration of 20mg/100mL was administered for 90days. From the second month the animals received quercetin 10 or 25mg/kg for 60days. Results showed that: Ecto-5'-nucleotidase activity decreased in methimazole/water group and the treatment with quercetin 25mg/kg decreased NTPDase, 5'-nucleotidase and adenosine deaminase activities. Moreover, platelet aggregation increased in methimazole/water group. Lipid peroxidation increased while superoxide dismutase and catalase activities decreased, but, interestingly, the treatment with quercetin reversed these changes. These results demonstrated that quercetin modulates adenine nucleotide hydrolysis decreasing the ADP formation and adenosine deamination. At the same time quercetin improves the oxidative profile, as well as reduces platelet aggregation, which together with the modulation in the nucleotides levels can contribute to the prevention of platelet disorders.

  14. Marked reduction in the number of platelet-tritiated imipramine binding sites in geriatric depression

    Energy Technology Data Exchange (ETDEWEB)

    Nemeroff, C.B.; Knight, D.L.; Krishnan, R.R.; Slotkin, T.A.; Bissette, G.; Melville, M.L.; Blazer, D.G.

    1988-10-01

    The number (Bmax) and affinity (Kd) of platelet-tritiated imipramine binding sites was determined in young and middle-aged controls 50 years of age and younger (n = 25), elderly normal controls over 60 years of age (n = 18), patients who fulfilled DSM-III criteria for major depression who were under 50 years of age (n = 29), patients who fulfilled DSM-III criteria for major depression who were 60 years of age and older (n = 19), and patients who fulfilled both DSM-III criteria for primary degenerative dementia and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer's disease (n = 13). Both groups of depressed patients (under 50 and over 60 years of age) exhibited significant reductions (decreases 42%) in the number of platelet-tritiated imipramine binding sites with no change in affinity, when compared with their age-matched controls. There was little overlap in Bmax values between the elderly depressed patients and their controls. The patients with probable Alzheimer's disease showed no alteration in platelet-tritiated imipramine binding. There was no statistically significant relationship between postdexamethasone plasma cortisol concentrations and tritiated imipramine binding. These results indicate that platelet-tritiated imipramine binding may have potential utility as a diagnostic adjunct in geriatric depression, and moreover that the reduction in the number of platelet-tritiated imipramine binding sites is not due to hypercortisolemia.

  15. 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.

  16. 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.

  17. Identification of platelet refractoriness in oncohematologic patients

    Directory of Open Access Journals (Sweden)

    Aline Aparecida Ferreira

    2011-01-01

    Full Text Available OBJECTIVES: To identify the occurrence and the causes of platelet refractoriness in oncohematologic patients. INTRODUCTION: Platelet refractoriness (unsatisfactory post-transfusion platelet increment is a severe problem that impairs the treatment of oncohematologic patients and is not routinely investigated in most Brazilian services. METHODS: Forty-four episodes of platelet concentrate transfusion were evaluated in 16 patients according to the following parameters: corrected count increment, clinical conditions and detection of anti-platelet antibodies by the platelet immunofluorescence test (PIFT and panel reactive antibodies against human leukocyte antigen class I (PRA-HLA. RESULTS: Of the 16 patients evaluated (median age: 53 years, nine (56% were women, seven of them with a history of pregnancy. An unsatisfactory increment was observed in 43% of the transfusion events, being more frequent in transfusions of random platelet concentrates (54%. Platelet refractoriness was confirmed in three patients (19%, who presented immunologic and non-immunologic causes. Alloantibodies were identified in eight patients (50% by the PIFT and in three (19% by the PRA-HLA. Among alloimmunized patients, nine (64% had a history of transfusion, and three as a result of pregnancy (43%. Of the former, two were refractory (29%. No significant differences were observed, probably as a result of the small sample size. CONCLUSION: The high rate of unsatisfactory platelet increment, refractoriness and alloimmunization observed support the need to set up protocols for the investigation of this complication in all chronically transfused patients, a fundamental requirement for the guarantee of adequate management.

  18. Does bipolar pacemaker current activate blood platelets?

    DEFF Research Database (Denmark)

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

    2009-01-01

    OBJECTIVE: The aim of this study was to investigate whether bipolar pacemaker current lead can activate blood platelets. The null hypothesis was that 1 minute of electrical stimulation of platelets would not influence their subsequent reactivity to adenosine diphosphate (ADP). BACKGROUND: Both...... 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...

  19. 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.

  20. 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

  1. Involvement of nuclear factor {kappa}B in platelet CD40 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Hachem, Ahmed [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Yacoub, Daniel [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Zaid, Younes [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Mourad, Walid [Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Merhi, Yahye, E-mail: yahye.merhi@icm-mhi.org [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer sCD40L induces TRAF2 association to CD40 and NF-{kappa}B activation in platelets. Black-Right-Pointing-Pointer I{kappa}B{alpha} phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. Black-Right-Pointing-Pointer I{kappa}B{alpha} is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-{kappa}B). Given that platelets contain NF-{kappa}B, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of I{kappa}B{alpha}, which are abolished by CD40L blockade. Inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced I{kappa}B{alpha} phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on I{kappa}B{alpha} phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-{kappa}B activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against thrombo

  2. Storage pool diseases illuminate platelet dense granule biogenesis.

    Science.gov (United States)

    Ambrosio, Andrea L; Di Pietro, Santiago M

    2016-11-16

    Platelet dense granules (DGs) are membrane bound compartments that store polyphosphate and small molecules such as ADP, ATP, Ca(2+), and serotonin. The release of DG contents plays a central role in platelet aggregation to form a hemostatic plug. Accordingly, congenital deficiencies in the biogenesis of platelet DGs underlie human genetic disorders that cause storage pool disease and manifest with prolonged bleeding. DGs belong to a family of lysosome-related organelles, which also includes melanosomes, the compartments where the melanin pigments are synthesized. These organelles share several characteristics including an acidic lumen and, at least in part, the molecular machinery involved in their biogenesis. As a result, many genes affect both DG and melanosome biogenesis and the corresponding patients present not only with bleeding but also with oculocutaneous albinism. The identification and characterization of such genes has been instrumental in dissecting the pathways responsible for organelle biogenesis. Because the study of melanosome biogenesis has advanced more rapidly, this knowledge has been extrapolated to explain how DGs are produced. However, some progress has recently been made in studying platelet DG biogenesis directly in megakaryocytes and megakaryocytoid cells. DGs originate from an endosomal intermediate compartment, the multivesicular body. Maturation and differentiation into a DG begins when newly synthesized DG-specific proteins are delivered from early/recycling endosomal compartments. The machinery that orchestrates this vesicular trafficking is composed of a combination of both ubiquitous and cell type-specific proteins. Here, we review the current knowledge on DG biogenesis. In particular, we focus on the individual human and murine genes encoding the molecular machinery involved in this process and how their deficiencies result in disease.

  3. Platelet-rich plasma preparation using three devices : Implications for platelet activation and platelet growth factor release

    NARCIS (Netherlands)

    Everts, Peter A. M.; Mahoney, Christine Brown; Hoffmann, Johannes J. M. L.; Schonberger, Jacques P. A. M.; Box, Henk A. M.; Van Zundert, Andre; Knape, Johannes T. A.

    2006-01-01

    Background: In this study, three commercial systems for the preparation of platelet-rich plasma (PRP) were compared and platelet growth factors release was measured. Methods: Ten healthy volunteers donated whole blood that was fractionated by a blood cell separator, and a table-top centrifuge to pre

  4. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets

    DEFF Research Database (Denmark)

    Pleines, Irina; Eckly, Anita; Elvers, Margitta;

    2010-01-01

    formation and exocytosis in various cell types, but its exact function in platelets is not established. Here, we show that the megakaryocyte/platelet-specific loss of Cdc42 leads to mild thrombocytopenia and a small increase in platelet size in mice. Unexpectedly, Cdc42-deficient platelets were able to form...... reduced, suggesting increased clearing of the cells under physiologic conditions. These data point to novel multiple functions of Cdc42 in the regulation of platelet activation, granule organization, degranulation, and a specific role in GPIb signaling....

  5. 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.

  6. Human platelets antigens influence the viral load of platelets after the interaction of the platelets with HCV and HIV in vitro

    Directory of Open Access Journals (Sweden)

    Rejane Maria Tommasini Grotto

    Full Text Available Abstract: INTRODUCTION: In this study, we evaluated hepatitis C virus (HCV and human immunodeficiency virus (HIV - platelet interactions in vitro as well as human platelets antigen (HPA polymorphisms. METHODS: Platelets were obtained from 100 healthy HPA-genotyped volunteer donors and incubated with HIV or HCV. The viral load after in vitro exposure was detected. RESULTS: The viral load in the platelets after exposure to the virus was higher in the HIV exposure than in the HCV exposure. CONCLUSIONS: HIV-platelet ligation could be more efficient than HCV-platelet interaction. Further, the HPA-1b allele seems to influence the interaction of platelets with HCV.

  7. Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan.

    Science.gov (United States)

    Liu, Zhi-Jian; Hoffmeister, Karin M; Hu, Zhongbo; Mager, Donald E; Ait-Oudhia, Sihem; Debrincat, Marlyse A; Pleines, Irina; Josefsson, Emma C; Kile, Benjamin T; Italiano, Joseph; Ramsey, Haley; Grozovsky, Renata; Veng-Pedersen, Peter; Chavda, Chaitanya; Sola-Visner, Martha

    2014-05-29

    The fetal/neonatal hematopoietic system must generate enough blood cells to meet the demands of rapid growth. This unique challenge might underlie the high incidence of thrombocytopenia among preterm neonates. In this study, neonatal platelet production and turnover were investigated in newborn mice. Based on a combination of blood volume expansion and increasing platelet counts, the platelet mass increased sevenfold during the first 2 weeks of murine life, a time during which thrombopoiesis shifted from liver to bone marrow. Studies applying in vivo biotinylation and mathematical modeling showed that newborn and adult mice had similar platelet production rates, but neonatal platelets survived 1 day longer in circulation. This prolonged lifespan fully accounted for the rise in platelet counts observed during the second week of murine postnatal life. A study of pro-apoptotic and anti-apoptotic Bcl-2 family proteins showed that neonatal platelets had higher levels of the anti-apoptotic protein Bcl-2 and were more resistant to apoptosis induced by the Bcl-2/Bcl-xL inhibitor ABT-737 than adult platelets. However, genetic ablation or pharmacologic inhibition of Bcl-2 alone did not shorten neonatal platelet survival or reduce platelet counts in newborn mice, indicating the existence of redundant or alternative mechanisms mediating the prolonged lifespan of neonatal platelets. © 2014 by The American Society of Hematology.

  8. [Platelet allo-antibodies identification strategies for preventing and managing platelet refractoriness].

    Science.gov (United States)

    Basire, A; Picard, C

    2014-11-01

    Platelet refractoriness is a serious complication for patients receiving recurrent platelet transfusions, which can be explained by non-immune and immune causes. Human Leukocyte Antigens (HLA) allo-immunization, especially against HLA class I, is the major cause for immune platelet refractoriness. To a lesser extent, allo-antibodies against specific Human Platelet Antigen (HPA) are also involved. Pregnancy, transplantation and previous transfusions can lead to allo-immune reaction against platelet antigens. After transfusion, platelet count is decreased by accelerated platelet destruction related to antibodies fixation on incompatible platelet antigens. New laboratory tests for allo-antibodies identification were developed to improve sensibility and specificity, especially with the LUMINEX(®) technology. The good use and interpretation of these antibodies assays can improve strategies for platelet refractoriness prevention and management with a patient adapted response. Compatible platelets units can be selected according to their identity with recipient typing or immune compatibility regarding HLA or HPA antibodies or HLA epitope compatibility. Prospective studies are needed to further confirm the clinical benefit of new allo-antibodies identification methods and consensus strategies for immune platelet refractoriness management.

  9. Platelet antibodies, activated platelets and serum leptin in childhood immune thrombocytopenic purpura.

    Science.gov (United States)

    Badrawy, Hosny; Elsayh, Khalid I; Zahran, Asmaa M; El-Ghazali, Mohamad Hamdy

    2013-01-01

    The aim of this study was to evaluate the levels of platelet-associated antibodies (PAIgG and PAIgM), activated platelets and serum leptin in children with acute immune thrombocytopenic purpura (ITP). The study included 40 patients with ITP and 40 healthy age- and sex-matched controls. PAIgG, PAIgM and activated platelet levels were estimated by flow cytometry, and serum leptin levels were estimated by ELISA. Activated platelets and serum leptin were significantly higher in the ITP patients than in the controls. The percentage and mean fluorescence intensity of PAIgG and PAIgM staining were significantly higher in the patients than in the controls. Serum leptin and activated platelet levels in patients with thrombocytopenia of brief duration were significantly lower than those in patients with thrombocytopenia of prolonged duration. The levels of activated platelets, serum leptin and PAIgG were positively correlated, and the levels of serum leptin, activated platelets and platelet counts were negatively correlated. The increased levels of activated platelets, serum leptin and platelet-associated antibodies in children with acute ITP suggest that these factors could play a role in ITP pathogenesis. Additionally, activated platelets and serum leptin could have prognostic significance in paediatric acute ITP. Copyright © 2013 S. Karger AG, Basel.

  10. Diversity and impact of rare variants in genes encoding the platelet G protein-coupled receptors

    OpenAIRE

    Jones, M.L.; Norman, J E; Morgan, N. V.; Mundell, S J; Lordkipanidze, M.; Lowe, G. C.; Daly, M E; Simpson, M.A.; Drake, S.; Watson, S P; Mumford, A D; UKGAPPS,

    2016-01-01

    Platelet responses to activating agonists are influenced by common\\ud population variants within or near G protein-coupled receptor (GPCR)\\ud genes that affect receptor activity. However, the impact of rare GPCR\\ud gene variants is unknown. We describe the rare single nucleotide variants\\ud (SNVs) in the coding and splice regions of 18 GPCR genes in\\ud 7,595 exomes from the 1,000-genomes and Exome Sequencing\\ud Project databases and in 31 cases with inherited platelet function disorders\\ud (I...

  11. Bulk fluid phase behaviour of colloidal platelet-sphere and platelet-polymer mixtures.

    Science.gov (United States)

    de las Heras, Daniel; Schmidt, Matthias

    2013-04-13

    Using a geometry-based fundamental measure density functional theory, we calculate bulk fluid phase diagrams of colloidal mixtures of vanishingly thin hard circular platelets and hard spheres. We find isotropic-nematic phase separation, with strong broadening of the biphasic region, upon increasing the pressure. In mixtures with large size ratio of platelet and sphere diameters, there is also demixing between two nematic phases with differing platelet concentrations. We formulate a fundamental measure density functional for mixtures of colloidal platelets and freely overlapping spheres, which represent ideal polymers, and use it to obtain phase diagrams. We find that, for low platelet-polymer size ratio, in addition to isotropic-nematic and nematic-nematic phase coexistence, platelet-polymer mixtures also display isotropic-isotropic demixing. By contrast, we do not find isotropic-isotropic demixing in hard-core platelet-sphere mixtures for the size ratios considered.

  12. IgG platelet antibodies in EDTA-dependent pseudothrombocytopenia bind to platelet membrane glycoprotein IIb.

    Science.gov (United States)

    Fiorin, F; Steffan, A; Pradella, P; Bizzaro, N; Potenza, R; De Angelis, V

    1998-08-01

    EDTA-dependent pseudothrombocytopenia (PTCP) consists of an inappropriate low platelet count caused by autoantibodies present in the serum samples reacting with platelets only in EDTA-anticoagulated blood. By using immunoprecipitation and Western blot techniques, we studied the immunochemical specificity of platelet agglutinating autoantibodies in the serum samples of 10 patients with PTCP. Furthermore, to evaluate a possible role of PTCP-associated IgG autoantibodies in increased platelet turnover, we assayed the plasma glycocalicin (GC) level and calculated the GC index for every patient. Our results provide direct evidence that an epitope located on platelet membrane glycoprotein IIb is recognized by PTCP-associated IgG antibodies; moreover GC levels in patients with EDTA-dependent PTCP were similar to control levels, thus excluding an increased platelet turnover. We conclude that antiplatelet antibodies directed against platelet cryptantigens are unlikely to have a major role in the increased removal of cells from circulation.

  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. Clinica use of platelet additive solutions.

    Science.gov (United States)

    van Rhenen, Dick J

    2007-12-01

    Randomised clinical trial (RCT) to study the clinical efficacy and safety of new platelet products using platelet additive solutions are scarce. In this paper a number of recent RCT's is discussed. It can be the start of a development where new transfusion products enter a RCT before the product is applied in clinical practice.

  15. Platelets in liver transplantation : Friend or foe?

    NARCIS (Netherlands)

    Pereboom, Ilona T. A.; Lisman, Ton; Porte, Robert J.

    2008-01-01

    Apart from the well-known role of blood platelets in hemostasis, there is emerging evidence that platelets have various nonhemostatic properties that play a critical role in inflammation, angiogenesis, tissue repair and regeneration, and ischemia/reperfusion (I/R) injury. All these processes may be

  16. Studies on megakaryopoiesis and platelet function

    NARCIS (Netherlands)

    Meinders, M.

    2015-01-01

    Platelets are blood circulating specialized subcellular fragments, which are produced by megakaryocytes. Platelets are essential for hemostasis and wound healing but also play a role in non-hemostatic processes such as the immune response or cancer metastasis. Considering the immediate precursors of

  17. Erythrocyte-platelet interaction in uncomplicated pregnancy.

    Science.gov (United States)

    Swanepoel, Albe C; Pretorius, Etheresia

    2014-12-01

    Maternal and fetal requirements during uncomplicated pregnancy are associated with changes in the hematopoietic system. Platelets and erythrocytes [red blood cells (RBCs)], and especially their membranes, are involved in coagulation, and their interactions may provide reasons for the changed hematopoietic system during uncomplicated pregnancy. We review literature regarding RBC and platelet membrane structure and interactions during hypercoagulability and hormonal changes. We then study interactions between RBCs and platelets in uncomplicated pregnancy, as their interactions may be one of the reasons for increased hypercoagulability during uncomplicated pregnancy. Scanning electron microscopy was used to study whole blood smears from 90 pregnant females in different phases of pregnancy. Pregnancy-specific interaction was seen between RBCs and platelets. Typically, one or more platelets interacted through platelet spreading and pseudopodia formation with a single RBC. However, multiple interactions with RBCs were also shown for a single platelet. Specific RBC-platelet interaction seen during uncomplicated pregnancy may be caused by increased estrogen and/or increased fibrinogen concentrations. This interaction may contribute to the hypercoagulable state associated with healthy and uncomplicated pregnancy and may also play a fundamental role in gestational thrombocytopenia.

  18. BETA-ADRENOBLOCKERS AND PLATELET AGGREGATION. CARVEDILOL

    Directory of Open Access Journals (Sweden)

    A. N. Zakirova

    2008-01-01

    Full Text Available Approaches evolution to studying of beta-blockers influence on platelet aggregation is reviewed. The current view on of beta-blocker antiplatelet effects is presented on the basis of physical and chemical drug properties (water repellency, dipole moment, molecular mass. Trail results on carvedilol influence on platelet aggregation are focused.

  19. 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.

  20. 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),

  1. Platelet affinity for burro aorta collagen

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, M.D.

    1977-10-01

    Despite ingenious concepts, there are no unequivocal clues as to what, when, and how some undefined biochemical factor(s) or constituent(s) that localizes in the arterial wall can precipitate a thromboatheromatous lesion or arterial disease. The present study focused on the extraction, partial purification, and characterization of a collagen-active platelet stimulator from the aortas of aged burros. The aggregator moiety in the aorta extracts invariably had a higher affinity for platelets in citrated platelet-rich plasma of human beings than for platelets of homologous burros. The platelet-aggregating factor(s) in the aorta extract was retained by incubation with ..cap alpha..-chymotrypsin. Platelet-aggregating activity was rapidly abolished after incubation with collagenase, as determined by platelet-aggregometry tests. Evidence based on light microscope and polysaccharide histochemical reactions indicates a probability that the intracellular amorphous matrix (PAS-positive) and filamentous components (PTAH-positive) expelled from smooth muscle cells disrupted during homogenization of the aorta may be a principal source of a precursor collagen species which is a potent inducer of platelet aggregation.

  2. 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...

  3. Function of eltrombopag-induced platelets compared to platelets from control patients with immune thrombocytopenia.

    Science.gov (United States)

    Haselboeck, Johanna; Kaider, Alexandra; Pabinger, Ingrid; Panzer, Simon

    2013-04-01

    Data on the in vivo function of platelets induced by the thrombopoietin receptor agonist eltrombopag are scarce. To assess a possible influence of eltrombopag we compared platelet function of eltrombopag-treated immune thrombocytopenia (ITP) patients (group 1; n=10) after treatment response to that from control ITP patients (group 2; n=12). We further analysed platelet function at baseline and after one, three, and four weeks of eltrombopag treatment and estimated daily changes of platelet function during the eltrombopag-induced platelet rise. The formation of platelet-monocyte aggregates (PMA), P-selectin expression [MFI], and platelet adhesion under high shear conditions (surface coverage, SC) in vivo and after in vitro addition of agonists (ADP, TRAP-6, Collagen) were similar between both groups after response to eltrombopag treatment. Only TRAP-6 induced a lower SC in the eltrombopag group (p=0.03). All platelet function parameters except for Collagen-induced P-selectin expression changed significantly during treatment with eltrombopag. PMA, naïve and after addition of ADP or TRAP-6 increased with increasing platelet counts. P-selectin expression decreased, when measured without and upon addition of ADP, increased in the presence of TRAP-6, and remained unchanged after addition of Collagen. SC increased during the eltrombopag-induced platelet rise. All significant changes of platelet function correlated to changes in platelet counts. Two patients developed venous thromboses during eltrombopag treatment, but no association with any distinct single platelet function parameter or combinations thereof was identifiable. Thus, eltrombopag-induced platelets function similar to those from control ITP patients without discernible increased hyper-reactivity.

  4. A platelet monoclonal antibody inhibition assay for detection of glycoprotein IIb/IIIa-related platelet alloantibodies.

    Science.gov (United States)

    Reiner, A P; Teramura, G; Nelson, K A; Slichter, S J

    1995-08-18

    Post-transfusion purpura (PTP) and neonatal alloimmune thrombocytopenia (NAT) result from formation of alloantibodies to platelet membrane glycoprotein-associated antigens. The detection and identification of platelet-specific alloantibodies in patient sera is often complicated by the presence of co-existing HLA antibodies and/or more than one platelet specificity in the same serum. We describe a solid phase assay that specifically detects antibodies to platelet membrane associated alloantigens by measuring the ability of patient antisera to inhibit the binding of glycoprotein GPIIb or GPIIIa monoclonal antibodies to intact platelets. When tested in the GPIIIa assay against a panel of random platelet donors, the reactivities of two known PLAI antisera that also contained different HLA antibodies were highly correlated (r = 0.99) and allowed PLA phenotyping of the population. A standard direct binding platelet ELISA, on the other hand, was unable to accurately PLA phenotype the same population. The reactivities of two known Baka antisera (one containing additional anti-PLA2 and the other anti-Brb specificities) were highly correlated (r = 0.95) in the GPIIb assay, and Bak phenotype determination was similarly accomplished for a random platelet panel. Furthermore, a comparison of platelet phenotype results (using the monoclonal inhibition assay) and genotype results (using DNA analysis) for the PLA and Bak systems showed a concordance of 98% for 146 alleles tested. In conclusion, the platelet monoclonal antibody inhibition assay: (1) allows determination of platelet-specific alloantibodies in the presence of contaminating HLA antibodies and/or in sera containing multiple platelet alloantibodies; (2) allows accurate platelet phenotyping for the GPIIIa-associated PLA and GPIIb-associated Bak antigen systems; and (3) may be applicable to the detection of other known or even novel platelet glycoprotein-associated antigens.

  5. Platelet Activation and Thrombus Formation over IgG Immune Complexes Requires Integrin αIIbβ3 and Lyn Kinase.

    Science.gov (United States)

    Zhi, Huiying; Dai, Jing; Liu, Junling; Zhu, Jieqing; Newman, Debra K; Gao, Cunji; Newman, Peter J

    2015-01-01

    IgG immune complexes contribute to the etiology and pathogenesis of numerous autoimmune disorders, including heparin-induced thrombocytopenia, systemic lupus erythematosus, rheumatoid- and collagen-induced arthritis, and chronic glomerulonephritis. Patients suffering from immune complex-related disorders are known to be susceptible to platelet-mediated thrombotic events. Though the role of the Fc receptor, FcγRIIa, in initiating platelet activation is well understood, the role of the major platelet adhesion receptor, integrin αIIbβ3, in amplifying platelet activation and mediating adhesion and aggregation downstream of encountering IgG immune complexes is poorly understood. The goal of this investigation was to gain a better understanding of the relative roles of these two receptor systems in immune complex-mediated thrombotic complications. Human platelets, and mouse platelets genetically engineered to differentially express FcγRIIa and αIIbβ3, were allowed to interact with IgG-coated surfaces under both static and flow conditions, and their ability to spread and form thrombi evaluated in the presence and absence of clinically-used fibrinogen receptor antagonists. Although binding of IgG immune complexes to FcγRIIa was sufficient for platelet adhesion and initial signal transduction events, platelet spreading and thrombus formation over IgG-coated surfaces showed an absolute requirement for αIIbβ3 and its ligands. Tyrosine kinases Lyn and Syk were found to play key roles in IgG-induced platelet activation events. Taken together, our data suggest a complex functional interplay between FcγRIIa, Lyn, and αIIbβ3 in immune complex-induced platelet activation. Future studies may be warranted to determine whether patients suffering from immune complex disorders might benefit from treatment with anti-αIIbβ3-directed therapeutics.

  6. Platelet Activation and Thrombus Formation over IgG Immune Complexes Requires Integrin αIIbβ3 and Lyn Kinase.

    Directory of Open Access Journals (Sweden)

    Huiying Zhi

    Full Text Available IgG immune complexes contribute to the etiology and pathogenesis of numerous autoimmune disorders, including heparin-induced thrombocytopenia, systemic lupus erythematosus, rheumatoid- and collagen-induced arthritis, and chronic glomerulonephritis. Patients suffering from immune complex-related disorders are known to be susceptible to platelet-mediated thrombotic events. Though the role of the Fc receptor, FcγRIIa, in initiating platelet activation is well understood, the role of the major platelet adhesion receptor, integrin αIIbβ3, in amplifying platelet activation and mediating adhesion and aggregation downstream of encountering IgG immune complexes is poorly understood. The goal of this investigation was to gain a better understanding of the relative roles of these two receptor systems in immune complex-mediated thrombotic complications. Human platelets, and mouse platelets genetically engineered to differentially express FcγRIIa and αIIbβ3, were allowed to interact with IgG-coated surfaces under both static and flow conditions, and their ability to spread and form thrombi evaluated in the presence and absence of clinically-used fibrinogen receptor antagonists. Although binding of IgG immune complexes to FcγRIIa was sufficient for platelet adhesion and initial signal transduction events, platelet spreading and thrombus formation over IgG-coated surfaces showed an absolute requirement for αIIbβ3 and its ligands. Tyrosine kinases Lyn and Syk were found to play key roles in IgG-induced platelet activation events. Taken together, our data suggest a complex functional interplay between FcγRIIa, Lyn, and αIIbβ3 in immune complex-induced platelet activation. Future studies may be warranted to determine whether patients suffering from immune complex disorders might benefit from treatment with anti-αIIbβ3-directed therapeutics.

  7. Modulatory effect of coffee on platelet function.

    Science.gov (United States)

    Bhaskar, Shobha; Rauf, Arun A

    2010-01-01

    Blood platelets play a major role in cardiovascular disease (CVD) and thrombosis. Conflicting information exists regarding the effect of coffee consumption on the cardiovascular system. We have investigated whether the consumption of moderate amount of coffee affect platelet functions and primary hemostasis in vivo in normal and high fat diet fed rats. Coffee fed group showed significant (P production from membrane arachidonic acid and it was decreased in coffee treated group. Platelet aggregation studies with ADP, collagen, arachidonic acid and epinephrine showed significant (P coffee fed group. Scanning electron microscopic studies revealed that platelet aggregation tendency increased in HFD group and was reduced in coffee fed group. These results indicate that coffee is active in inhibiting platelet aggregation, a critical step involved in thrombosis.

  8. 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.

  9. Platelet bioreactor-on-a-chip

    Science.gov (United States)

    Mazutis, Linas; Wu, Stephen; Sylman, Joanna L.; Ehrlicher, Allen; Machlus, Kellie R.; Feng, Qiang; Lu, Shijiang; Lanza, Robert; Neeves, Keith B.; Weitz, David A.; Italiano, Joseph E.

    2014-01-01

    Platelet transfusions total >2.17 million apheresis-equivalent units per year in the United States and are derived entirely from human donors, despite clinically significant immunogenicity, associated risk of sepsis, and inventory shortages due to high demand and 5-day shelf life. To take advantage of known physiological drivers of thrombopoiesis, we have developed a microfluidic human platelet bioreactor that recapitulates bone marrow stiffness, extracellular matrix composition, micro-channel size, hemodynamic vascular shear stress, and endothelial cell contacts, and it supports high-resolution live-cell microscopy and quantification of platelet production. Physiological shear stresses triggered proplatelet initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platelets. Modeling human bone marrow composition and hemodynamics in vitro obviates risks associated with platelet procurement and storage to help meet growing transfusion needs. PMID:25606631

  10. Platelet-rich plasma in otolaryngology.

    Science.gov (United States)

    Stavrakas, M; Karkos, P D; Markou, K; Grigoriadis, N

    2016-12-01

    Platelet-rich plasma is a novel material that is being used more frequently in many surgical specialties. A literature review on the current and potential uses of platelet-rich plasma in otolaryngology was performed. There is limited evidence on the use of platelet-rich plasma in otolaryngology compared with other specialties: only 11 studies on various subspecialties (otology, rhinology and laryngology) were included in the final review. Based on the limited number of studies, we cannot draw safe conclusions about the value of platelet-rich plasma in otolaryngology. Nevertheless, the available literature suggests that platelet-rich plasma holds promise for future research and may have a number of clinical applications.

  11. Protective Mechanisms of Guanosine from Solanum lycopersicum on Agonist-Induced Platelet Activation: Role of sCD40L

    Directory of Open Access Journals (Sweden)

    Iván Palomo

    2013-07-01

    Full Text Available In the past 30 years, only three natural products have been sources of new drugs with antiplatelet activity. In this study, we have demonstrated for the first time that guanosine from Solanum lycopersicum possesses antiplatelet (secretion, spreading, adhesion and aggregation activity in vitro and inhibition of platelet inflammatory mediator of atherosclerosis (sCD40L. According to ADP-induced platelet aggregation inhibiting, the total extract residue was fractionated by liquid chromatography/phase separation, affording an aqueous fraction. This fraction was subjected to repeated permeation over Sephadex LH-20 and semi-preparative TLC. The isolated compound finally obtained was identified as guanosine on the basis of its UV-spectra, HPLC and 1H-NMR data. Guanosine concentration dose-dependently (1 to 4 mmol/L inhibited platelet secretion and aggregation induced by ADP and collagen. Spread of human platelets on collagen in the presence of guanosine was fully inhibited. After incubation of whole blood with guanosine, the platelet adhesion and aggregation under flow conditions was inhibited concentration dependently (0.2 to 2 mmol/L. At the same concentrations that guanosine inhibits platelet aggregation, levels of sCD40L were significantly decreased. Guanosine is thus likely to exert significant protective effects in thromboembolic-related disorders by inhibiting platelet aggregation.

  12. The canonical transient receptor potential 6 (TRPC6) channel is sensitive to extracellular pH in mouse platelets.

    Science.gov (United States)

    Berna-Erro, Alejandro; Albarran, Letizia; Dionisio, Natalia; Redondo, Pedro C; Alonso, Nieves; Gomez, Luis J; Salido, Gines M; Rosado, Juan A

    2014-01-01

    The canonical transient receptor potential-6 (TRPC6) is a receptor-activated non-selective Ca(2+) channel regulated by a variety of modulators such as diacylglycerol, Ca(2+)/calmodulin or phosphorylation. The present study is aimed to investigate whether different situations, such as acidic pH, exposure to reactive oxygen species (ROS) or hypoxic-like conditions modulate TRPC6 channel function. Here we show normal aggregation and Ca(2+) mobilization stimulated by thrombin in TRPC6 KO platelets; however, OAG (1-oleoyl-2-acetyl-sn-glycerol)-evoked Ca(2+) entry was attenuated in the absence of TRPC6. Exposure of mouse platelets to acidic pH resulted in abolishment of thrombin-evoked aggregation and attenuated platelet aggregation induced by thapsigargin (TG) or OAG. Both OAG-induced Ca(2+) entry and platelet aggregation were greatly attenuated in cells expressing TRPC6 channels. Exposure of platelets to H2O2 or deferoxamine did not clearly alter thrombin, TG or OAG-induced platelet aggregation. Our results indicate that TRPC6 is sensitive to acidic pH but not to exposure to ROS or hypoxic-like conditions, which might be involved in the pathogenesis of the altered platelet responsiveness to DAG-generating agonists in disorders associated to acidic pH.

  13. Venous levels of shear support neutrophil-platelet adhesion and neutrophil aggregation in blood via P-selectin and beta2-integrin

    Science.gov (United States)

    Konstantopoulos, K.; Neelamegham, S.; Burns, A. R.; Hentzen, E.; Kansas, G. S.; Snapp, K. R.; Berg, E. L.; Hellums, J. D.; Smith, C. W.; McIntire, L. V.; Simon, S. I.

    1998-01-01

    BACKGROUND: After activation, platelets adhere to neutrophils via P-selectin and beta2-integrin. The molecular mechanisms and adhesion events in whole blood exposed to venous levels of hydrodynamic shear in the absence of exogenous activation remain unknown. METHODS AND RESULTS: Whole blood was sheared at approximately 100 s(-1). The kinetics of neutrophil-platelet adhesion and neutrophil aggregation were measured in real time by flow cytometry. P-selectin was upregulated to the platelet surface in response to shear and was the primary factor mediating neutrophil-platelet adhesion. The extent of neutrophil aggregation increased linearly with platelet adhesion to neutrophils. Blocking either P-selectin, its glycoprotein ligand PSGL-1, or both simultaneously by preincubation with a monoclonal antibody resulted in equivalent inhibition of neutrophil-platelet adhesion (approximately 30%) and neutrophil aggregation (approximately 70%). The residual amount of neutrophil adhesion was blocked with anti-CD11b/CD18. Treatment of blood with prostacyclin analogue ZK36374, which raises cAMP levels in platelets, blocked P-selectin upregulation and neutrophil aggregation to baseline. Complete abrogation of platelet-neutrophil adhesion required both ZK36374 and anti-CD18. Electron microscopic observations of fixed blood specimens revealed that platelets augmented neutrophil aggregation both by forming bridges between neutrophils and through contact-mediated activation. CONCLUSIONS: The results are consistent with a model in which venous levels of shear support platelet adherence to neutrophils via P-selectin binding PSGL-1. This interaction alone is sufficient to mediate neutrophil aggregation. Abrogation of platelet adhesion and aggregation requires blocking Mac-1 in addition to PSGL-1 or P-selectin. The described mechanisms are likely of key importance in the pathogenesis and progression of thrombotic disorders that are exacerbated by leukocyte-platelet aggregation.

  14. Platelet derivatives in regenerative medicine: an update.

    Science.gov (United States)

    De Pascale, Maria Rosaria; Sommese, Linda; Casamassimi, Amelia; Napoli, Claudio

    2015-01-01

    Prior preclinical and clinical studies support the use of platelet-derived products for the treatment of soft and hard tissue lesions. These regenerative effects are controlled by autocrine and paracrine biomolecules including growth factors and cytokines contained in platelet alpha granules. Each growth factor is involved in a phase of the healing process, such as inflammation, collagen synthesis, tissue granulation, and angiogenesis collectively promoting tissue restitution. Platelet derivatives have been prepared as platelet-rich plasma, platelet gel, platelet-rich fibrin, and platelet eye drops. These products vary in their structure, growth factors, composition, and cytokine concentrations. Here, we review the current use of platelet-derived biological products focusing on the rationale for their use and the main requirements for their preparation. Variation in the apparent therapeutic efficacy may have resulted from a lack of reproducible, standardized protocols for preparation. Despite several individual studies showing favorable treatment effects, some randomized controlled trials as well as meta-analyses have found no constant clinical benefit from the application of platelet-derived products for prevention of tissue lesions. Recently, 3 published studies in dentistry showed an improvement in bone density. Seven published studies showed positive results in joint regeneration. Five published studies demonstrated an improvement in the wound healing, and an improvement of eye epithelial healing was observed in 2 reports. Currently, at least 14 ongoing clinical trials in phase 3 or 4 have been designed with large groups of treated patients (n > 100). Because the rationale of the therapy with platelet-derived compounds is still debated, a definitive insight can be acquired only when these large randomized trials will be completed.

  15. Flow cytometry-based platelet function testing is predictive of symptom burden in a cohort of bleeders.

    Science.gov (United States)

    Boknäs, Niklas; Ramström, Sofia; Faxälv, Lars; Lindahl, Tomas L

    2017-09-12

    Platelet function disorders (PFDs) are common in patients with mild bleeding disorders (MBDs), yet the significance of laboratory findings suggestive of a PFD remain unclear due to the lack of evidence for a clinical correlation between the test results and the patient phenotype. Herein, we present the results from a study evaluating the potential utility of platelet function testing using whole-blood flow cytometry in a cohort of 105 patients undergoing investigation for MBD. Subjects were evaluated with a test panel comprising two different activation markers (fibrinogen binding and P-selectin exposure) and four physiologically relevant platelet agonists (ADP, PAR1-AP, PAR4-AP, and CRP-XL). Abnormal test results were identified by comparison with reference ranges constructed from 24 healthy controls or with the fifth percentile of the entire patient cohort. We found that the abnormal test results are predictive of bleeding symptom severity, and that the greatest predictive strength was achieved using a subset of the panel, comparing measurements of fibrinogen binding after activation with all four agonists with the fifth percentile of the patient cohort (p = 0.00008, hazard ratio 8.7; 95% CI 2.5-40). Our results suggest that whole-blood flow cytometry-based platelet function testing could become a feasible alternative for the investigation of MBDs. We also show that platelet function testing using whole-blood flow cytometry could provide a clinically relevant quantitative assessment of platelet-related hemostasis.

  16. The Role of Platelet-Activating Factor in Chronic Inflammation, Immune Activation, and Comorbidities Associated with HIV Infection

    Science.gov (United States)

    Kelesidis, Theodoros; Papakonstantinou, Vasiliki; Detopoulou, Paraskevi; Fragopoulou, Elizabeth; Chini, Maria; Lazanas, Marios C.; Antonopoulou, Smaragdi

    2016-01-01

    With the advent of highly effective antiretroviral therapy, cardiovascular disease has become an important cause of morbidity and mortality among people with treated HIV-1, but the pathogenesis is unclear. Platelet-activating factor is a potent lipid mediator of inflammation that has immunomodulatory effects and a pivotal role in the pathogenesis of inflammatory disorders and cardiovascular disease. Limited scientific evidence suggests that the platelet-activating factor pathway may be a mechanistic link between HIV-1 infection, systemic inflammation, and immune activation that contribute to pathogenesis of chronic HIV-related comorbidities, including cardiovascular disease and HIV-associated neurocognitive disorders. In this review, we examine the mechanisms by which the cross-talk between HIV-1, immune dysregulation, inflammation, and perturbations in the platelet-activating factor pathway may directly affect HIV-1 immunopathogenesis. Understanding the role of platelet-activating factor in HIV-1 infection may pave the way for further studies to explore therapeutic interventions, such as diet, that can modify platelet-activating factor activity and use of platelet-activating factor inhibitors that might improve the prognosis of HIV-1 infected patients. PMID:26616844

  17. Enu mutagenesis identifies a novel platelet phenotype in a loss-of-function Jak2 allele.

    Directory of Open Access Journals (Sweden)

    Nicole M Anderson

    Full Text Available Utilizing ENU mutagenesis, we identified a mutant mouse with elevated platelets. Genetic mapping localized the mutation to an interval on chromosome 19 that encodes the Jak2 tyrosine kinase. We identified a A3056T mutation resulting in a premature stop codon within exon 19 of Jak2 (Jak2(K915X, resulting in a protein truncation and functionally inactive enzyme. This novel platelet phenotype was also observed in mice bearing a hemizygous targeted disruption of the Jak2 locus (Jak2(+/-. Timed pregnancy experiments revealed that Jak2(K915X/K915X and Jak2(-/- displayed embryonic lethality; however, Jak2(K915X/K915X embryos were viable an additional two days compared to Jak2(-/- embryos. Our data suggest that perturbing JAK2 activation may have unexpected consequences in elevation of platelet number and correspondingly, important implications for treatment of hematological disorders with constitutive Jak2 activity.

  18. Development of North American consensus guidelines for medical laboratories that perform and interpret platelet function testing using light transmission aggregometry.

    Science.gov (United States)

    Hayward, Catherine P M; Moffat, Karen A; Raby, Anne; Israels, Sara; Plumhoff, Elizabeth; Flynn, Greg; Zehnder, James L

    2010-12-01

    Platelet function testing is important for the diagnostic evaluation of common and rare bleeding disorders. Our study goals were to promote best practices and reduce unnecessary testing variances by developing North American guidelines on platelet function testing. Guidelines were developed by consensus for expert recommendations (minimum level for approval, 70%) that included recommendations on the evaluation and interpretation of light transmission platelet aggregometry (LTA). To assess consensus, medical opinions on recommendations were gathered from diagnostic laboratories that perform LTA, in collaboration with the Quality Management Program-Laboratory Services (QMP-LS) in Ontario, Canada (10 laboratories), and the North American Specialized Coagulation Laboratory Association (NASCOLA; 47 laboratories, 5 overlapping the QMP-LS group). Adequate consensus was achieved for all and 89% of recommendations for the QMP-LS and NASCOLA groups, respectively. The recommendations adopted provide North American laboratories with additional guidance on platelet function testing, including how to interpret LTA abnormalities.

  19. Wiskott-Aldrich Syndrome With Normal-Sized Platelets in an Eighteen-Month-Old Boy: A Rare Mutation

    Directory of Open Access Journals (Sweden)

    Jayitri Mazumdar

    2015-07-01

    Full Text Available Introduction: Wiskott-Aldrich syndrome (WAS is an X-linked recessive disorder characterized by thrombocytopenia, eczema, and recurrent infections. The disease is usually associated with small defective platelets. Case Presentation: We described an 18-month-old boy who presented with lower gastrointestinal bleeding, eczema, and recurrent infections. There was pancytopenia with normal-sized platelets. In addition, the CD4 count was significantly low and serum IgA and IgE levels were increased. The diagnosis of WAS was confirmed by detecting a mutation of WAS gene, which was due to a deletion mutation resulting in frameshift (c.177DelT. Conclusions: Usually microplatelets with mean platelet volume of 4-5 fL are seen in WAS, but in this case, the patient had normal-sized platelets with a rare mutation of WAS gene. Therefore, high index of clinical suspicion is needed to diagnose WAS.

  20. Decreased TGF-β1 and VEGF Release in Cystic Fibrosis Platelets: Further Evidence for Platelet Defects in Cystic Fibrosis

    Science.gov (United States)

    Maloney, James P.; Narasimhan, Jayashree; Biller, Julie

    2016-01-01

    Purpose Cystic fibrosis (CF) patients suffer from chronic lung inflammation. This inflammation may activate platelets. There are limited data on the role of platelet-secreted cytokines in CF. Platelet cytokines with inflammatory effects include vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). As levels of these cytokines are tenfold greater in serum than plasma due to platelet release, serum levels may be one index of platelet content; but a more specific index is release during the aggregation of isolated platelets. We postulated that altered release of these platelet cytokines occurs in CF. Methods We obtained sera and plasma from CF outpatients (n=21) and from healthy controls (n=20), measured VEGF and TGF-β1, assessed for correlations with platelet number, analyzed cytokine release during platelet aggregation to collagen, and analyzed differences in maximal platelet aggregation. Results Platelet number and maximal aggregation levels were higher in CF. Plasma and serum levels of TGF-β1 and VEGF were higher in CF, but these levels were similar after adjusting for platelet number (serum cytokines correlated with platelet count). The release of VEGF and TGF-β1 during aggregation was decreased in CF platelets (by 52% and 29%, respectively). Conclusion Platelet release is not a source of the elevated blood proinflammatory cytokines TGF-β1 and VEGF in CF, as platelets from CF patients actually release less of these cytokines. These data provide further evidence for platelet defects in CF. PMID:27423781

  1. Pseudo (Platelet-type von Willebrand disease in pregnancy: a case report

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    Grover Neetu

    2013-01-01

    Full Text Available Abstract Background Pseudo (platelet-type-von Willebrand disease is a rare autosomal dominant bleeding disorder caused by an abnormal function of the glycoprotein lb protein; the receptor for von Willebrand factor. This leads to an increased removal of VWF multimers from the circulation as well as platelets and this results in a bleeding diathesis. Worldwide, less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD. Case presentation We describe the management of platelet type von Willebrand disease in pregnancy of a 26 year old Caucasian primigravida. The initial diagnosis was made earlier following a significant haemorrhage post tonsillectomy several years prior to pregnancy. The patient was managed under a multidisciplinary team which included obstetricians, haematologists, anaesthetists and neonatologists. Care plans were made for the ante- natal, intra-partum and post-partum periods in partnership with the patient. The patient’s platelet count levels dropped significantly during the antenatal period. This necessitated the active exclusion of other causes of thrombocytopenia in pregnancy. A vaginal delivery was desired and plans were made for induction of labour at 38 weeks of gestation with platelet cover in view of the progressive fall of the platelet count. The patient however went into spontaneous labour on the day of induction. She was transfused two units of platelets before delivery. She had an unassisted vaginal delivery of a healthy baby. The successful antenatal counselling has encouraged the diagnosis of the same condition in her mother and sister. We found this to be a particularly interesting case as well as challenging to manage due to its rarity. Psuedo von Willebrand disease in pregnancy can be confused with a number of other differential diagnoses, such as gestational thrombocutopenia, idiopathatic thrombocytopenia, thrombotic thrombocytopenic purpura and pre-eclampsia; all need consideration

  2. A critical role for the transient receptor potential channel type 6 in human platelet activation.

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    Hari Priya Vemana

    Full Text Available While calcium signaling is known to play vital roles in platelet function, the mechanisms underlying its receptor-operated calcium entry component (ROCE remain poorly understood. It has been proposed, but never proven in platelets, that the canonical transient receptor potential channel-6 (TRPC6 mediates ROCE. Nonetheless, we have previously shown that the mouse TRPC6 regulates hemostasis, thrombogenesis by regulating platelet aggregation. In the present studies, we used a pharmacological approach to characterize the role of TRPC6 in human platelet biology. Thus, interestingly, we observed that a TRPC6 inhibitor exerted significant inhibitory effects on human platelet aggregation in a thromboxane receptor (TPR-selective manner; no additional inhibition was observed in the presence of the calcium chelator BAPTA. This inhibitor also significantly inhibited human platelet secretion (dense and alpha granules, integrin IIb-IIIa, Akt and ERK phosphorylation, again, in a TPR-selective manner; no effects were observed in response to ADP receptor stimulation. Furthermore, there was a causal relationship between these inhibitory effects, and the capacity of the TRPC6 inhibitor to abrogate elevation in intracellular calcium, that was again found to be TPR-specific. This effect was not found to be due to antagonism of TPR, as the TRPC6 inhibitor did not displace the radiolabeled antagonist [3H]SQ29,548 from its binding sites. Finally, our studies also revealed that TRPC6 regulates human clot retraction, as well as physiological hemostasis and thrombus formation, in mice. Taken together, our findings demonstrate, for the first time, that TRPC6 directly regulates TPR-dependent ROCE and platelet function. Moreover, these data highlight TRPC6 as a novel promising therapeutic strategy for managing thrombotic disorders.

  3. Investigation of the relationship between mean platelet volume and obstructive sleep apnea syndrome

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    Ersin Şükrü Erden

    2013-12-01

    Full Text Available Objective: Obstructive sleep apnea syndrome (OSAS is characterized by recurrent upper airway obstruction and intermittent hypoxia during sleep. Intermittent hypoxia and increased inflammatory activity plays a role in increased risk of cardiovascular disease in the OSAS. OSAS is an important cause of morbidity and mortality and cardiovascular disorders are the most important complications of OSAS. Mean platelet volume (MPV is a marker of platelet activation and function, and increased platelet volume is associated with increased platelet activity. Different diseases related with inflammation, hypoxia, vascular injury, thrombosis and atherosclerosis were found to be associated with MPV. In this study, we aimed to investigate the relationship between OSAS and MPV. Methods: In this retrospective study, data of sex and age matched 33 patients with moderate OSAS, 34 patients with severe OSAS and 30 healthy subjects were evaluated. Results: The mean MPV was found in control, moderate OSAS and severe OSAS groups as 7.83±1.00, 8.26±1.40 and 8.94±1.20 (fL respectively. The mean MPV value was significantly higher in severe OSAS group than control subjects (p=0.001. In correlation analysis, there were positive correlation between MPV with apnea-hypopnea index and total sleep time, and negative correlation between MPV with platelet count and minimum oxygen saturation (Respectively, p=0.003 / R=0.295, p=0.030 / R=0.221, p=0.011 / R= -0.257, p=0.019 / R= -0.238. Conclusion: In this study, the increased MPV was associated with severe OSAS and the results of this study suggest that the platelet activation is increased in OSAS. Hypoxia caused by OSAS, due to the activated platelets, may play a role in the development of cardiovascular diseases which is an important cause of morbidity and mortality in OSAS. J Clin Exp Invest 2013; 4 (4: 492-496

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

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    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

  5. Platelet lysates produced from expired platelet concentrates support growth and osteogenic differentiation of mesenchymal stem cells.

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    Sandra Mjoll Jonsdottir-Buch

    Full Text Available BACKGROUND: Mesenchymal stem cells are promising candidates in regenerative cell therapy. Conventional culture methods involve the use of animal substances, specifically fetal bovine serum as growth supplement. Since the use of animal-derived products is undesirable for human applications, platelet lysates produced from human platelets are an attractive alternative. This is especially true if platelet lysates from already approved transfusion units at blood banks can be utilized. The purpose of this study was to produce human platelet lysates from expired, blood bank-approved platelet concentrates and evaluate their use as growth supplement in the culture of mesenchymal stem cells. METHODOLOGY/PRINCIPAL FINDINGS: In this study, bone marrow-derived mesenchymal stem cells were cultured with one of three culture supplements; fetal bovine serum, lysates from freshly prepared human platelet concentrates, or lysates from expired human platelet concentrates. The effects of these platelet-derived culture supplements on basic mesenchymal stem cell characteristics were evaluated. All cultures maintained the typical mesenchymal stem cell surface marker expression, trilineage differentiation potential, and the ability to suppress in vitro immune responses. However, mesenchymal stem cells supplemented with platelet lysates proliferated faster than traditionally cultured cells and increased the expression of the osteogenic marker gene RUNX-2; yet no difference between the use of fresh and expired platelet concentrates was observed. CONCLUSION/SIGNIFICANCE: Our findings suggest that human platelet lysates produced from expired platelet concentrates can be used as an alternative to fetal bovine serum for mesenchymal stem cell culture to the same extent as lysates from fresh platelets.

  6. Study on the relationship between mean platelet volume and platelet distribution width with coronary artery lesion in children with Kawasaki disease.

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    Liu, Ruixi; Gao, Fang; Huo, Junming; Yi, Qijian

    2012-01-01

    Mean platelet volume (MPV) and platelet distribution width (PDW) are correlated with platelet function and may be a more sensitive index than platelet number as a marker of clinical interest in various disorders. Therefore, this study was designed to answer the following questions: do MPV and PDW levels change in Kawasaki disease (KD), is there any relation between CAL in children with MPV and PDW and whether MPV and PDW might support a diagnosis of incomplete KD. A total of 309 KD patients and 160 sex-age matched healthy subjects were enrolled into the study. For all subjects following tests were performed: MPV, PDW, platelet count, white blood cells counts (WBC), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Patients with CALs were assigned to three groups depending on the extent of CALs which were visualized by echocardiography: dilatation and/or ectasia, aneurysm and giant aneurysms. We compared patients with fever and four or five of the principal criteria (complete KD, cKD) to the other patients (iKD). Compared with healthy controls a significant decrease in MPV and PDW (p platelet count, CRP and ESR (p all children with KD. There were no statistically differences in MPV and PDW between KD with CALs and KD without CALs (p > 0.05). However, MPV and PDW were significantly lower in patients with iKD than in group with cKD (p = 0.003, p = 0.014, respectively). It was first shown that patients with KD have lower MPV and PDW than control subjects. The diagnosis of iKD is challenging but can be supported by the presence of lower MPV and PDW.

  7. Role of Helicobacter pylori Eradication Therapy on Platelet Recovery in Chronic Immune Thrombocytopenic Purpura

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    Khan Sheema

    2017-01-01

    Full Text Available Background. Idiopathic thrombocytopenic purpura (ITP is a bleeding disorder in which the immune system destroys native platelets. In this condition an autoantibody is generated against a platelet antigen. ITP affects women more often than men and is more common in children than adults. Objective. To assess the effect of Helicobacter pylori eradication therapy (HPET on platelet count in Helicobacter pylori associated chronic immune thrombocytopenic purpura (chronic ITP in adult. Materials and Methods. It is an interventional prospective study conducted at Liaquat University of Medical and Health Sciences, Jamshoro, from 2014 to 2015. A set of 85 patients diagnosed with chronic ITP were included in the study via convenient sampling. Patients with platelets count 3 months were selected. They were posed to first-line investigations which comprised complete blood count (CBC and peripheral blood smear examination followed by second-line tests including bone marrow examination and Helicobacter pylori stool specific antigen (HpSA-EIA. Standard H. pylori eradication therapy was offered and the patients were assessed at regular intervals for 6 months. Results. Of the 85 study patients, 32 (37.6% were male and 53 (62.3% were female. Mean ages of H. pylori positive and negative subjects were 43.89 ± 7.06 and 44.75 ± 7.91 years, respectively. Bone marrow examination confirmed the diagnosis and excluded other related BM disorders. H. pylori stool antigen (HpSA was detected in 34 (40% patients and hence regarded as H. pylori positive; the rest were negative. Treatment with eradication therapy significantly improved the mean platelet counts from 48.56±21.7 × 109/l to 94.2±26.8 × 109/l. Conclusion. We concluded that the anti-H. pylori eradication therapy improves blood platelet counts in chronic immune thrombocytopenia.

  8. Role of Helicobacter pylori Eradication Therapy on Platelet Recovery in Chronic Immune Thrombocytopenic Purpura

    Science.gov (United States)

    Sheema, Khan; Arshi, Naz; Farah, Naz; Imran, Sheikh

    2017-01-01

    Background. Idiopathic thrombocytopenic purpura (ITP) is a bleeding disorder in which the immune system destroys native platelets. In this condition an autoantibody is generated against a platelet antigen. ITP affects women more often than men and is more common in children than adults. Objective. To assess the effect of Helicobacter pylori eradication therapy (HPET) on platelet count in Helicobacter pylori associated chronic immune thrombocytopenic purpura (chronic ITP) in adult. Materials and Methods. It is an interventional prospective study conducted at Liaquat University of Medical and Health Sciences, Jamshoro, from 2014 to 2015. A set of 85 patients diagnosed with chronic ITP were included in the study via convenient sampling. Patients with platelets count 3 months were selected. They were posed to first-line investigations which comprised complete blood count (CBC) and peripheral blood smear examination followed by second-line tests including bone marrow examination and Helicobacter pylori stool specific antigen (HpSA-EIA). Standard H. pylori eradication therapy was offered and the patients were assessed at regular intervals for 6 months. Results. Of the 85 study patients, 32 (37.6%) were male and 53 (62.3%) were female. Mean ages of H. pylori positive and negative subjects were 43.89 ± 7.06 and 44.75 ± 7.91 years, respectively. Bone marrow examination confirmed the diagnosis and excluded other related BM disorders. H. pylori stool antigen (HpSA) was detected in 34 (40%) patients and hence regarded as H. pylori positive; the rest were negative. Treatment with eradication therapy significantly improved the mean platelet counts from 48.56 ± 21.7 × 109/l to 94.2 ± 26.8 × 109/l. Conclusion. We concluded that the anti-H. pylori eradication therapy improves blood platelet counts in chronic immune thrombocytopenia.

  9. 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.

  10. Blood platelets in the progression of Alzheimer's disease.

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    Nina S Gowert

    Full Text Available Alzheimer's disease (AD is characterized by neurotoxic amyloid-ß plaque formation in brain parenchyma and cerebral blood vessels known as cerebral amyloid angiopathy (CAA. Besides CAA, AD is strongly related to vascular diseases such as stroke and atherosclerosis. Cerebrovascular dysfunction occurs in AD patients leading to alterations in blood flow that might play an important role in AD pathology with neuronal loss and memory deficits. Platelets are the major players in hemostasis and thrombosis, but are also involved in neuroinflammatory diseases like AD. For many years, platelets were accepted as peripheral model to study the pathophysiology of AD because platelets display the enzymatic activities to generate amyloid-ß (Aß peptides. In addition, platelets are considered to be a biomarker for early diagnosis of AD. Effects of Aß peptides on platelets and the impact of platelets in the progression of AD remained, however, ill-defined. The present study explored the cellular mechanisms triggered by Aß in platelets. Treatment of platelets with Aß led to platelet activation and enhanced generation of reactive oxygen species (ROS and membrane scrambling, suggesting enhanced platelet apoptosis. More important, platelets modulate soluble Aß into fibrillar structures that were absorbed by apoptotic but not vital platelets. This together with enhanced platelet adhesion under flow ex vivo and in vivo and platelet accumulation at amyloid deposits of cerebral vessels of AD transgenic mice suggested that platelets are major contributors of CAA inducing platelet thrombus formation at vascular amyloid plaques leading to vessel occlusion critical for cerebrovascular events like stroke.

  11. Brief Report: Platelet-Poor Plasma Serotonin in Autism

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    Anderson, George M.; Hertzig, Margaret E.; McBride, P. A.

    2012-01-01

    Possible explanations for the well-replicated platelet hyperserotonemia of autism include an alteration in the platelet's handling of serotonin (5-hydroxyserotonin, 5-HT) or an increased exposure of the platelet to 5-HT. Measurement of platelet-poor plasma (PPP) levels of 5-HT appears to provide the best available index of in vivo exposure of the…

  12. 21 CFR 864.5700 - Automated platelet aggregation system.

    Science.gov (United States)

    2010-04-01

    ... addition of an aggregating reagent to a platelet-rich plasma. (b) Classification. Class II (performance... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated platelet aggregation system. 864.5700... § 864.5700 Automated platelet aggregation system. (a) Identification. An automated platelet...

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

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    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

  14. Determination of serum aluminum, platelet aggregation and lipid peroxidation in hemodialyzed patients

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    T.J.C. Neiva

    2002-03-01

    Full Text Available Aluminum (Al3+ overload is frequently associated with lipid peroxidation and neurological disorders. Aluminum accumulation is also reported to be related to renal impairment, anemia and other clinical complications in hemodialysis patients. The aim of the present study was to determine the degree of lipid peroxidation, platelet aggregation and serum aluminum in patients receiving regular hemodialytic treatment. The level of plasma lipid peroxidation was evaluated on the basis of thiobarbituric acid reactive substances (TBARS. Mean platelet peroxidation in patients undergoing hemodialysis was significantly higher than in normal controls (2.7 ± 0.03 vs 1.8 ± 0.06 nmol/l, P<0.05. Platelet aggregation and serum aluminum levels were determined by a turbidimetric method and atomic absorption spectrophotometry, respectively. Serum aluminum was significantly higher in patients than in normal controls (44.5 ± 29 vs 10.8 ± 2.5 µg/l, P<0.05. Human blood platelets were stimulated with collagen (2.2 µg/ml, adenosine diphosphate (6 µM and epinephrine (6 µM and showed reduced function with the three agonists utilized. No correlation between aluminum levels and platelet aggregation or between aluminum and peroxidation was observed in hemodialyzed patients.

  15. Platelet thrombosis in cardiac-valve prostheses

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    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.

  16. Changes in platelet parameters in leukocytosis.

    Science.gov (United States)

    Ozturk, Nurinnisa; Baygutalp, Nurcan Kilic; Bakan, Ebubekir; Altas, Gulsum Feyza; Polat, Harun; Dorman, Emrullah

    2016-01-01

    In recent years, platelets are known to have a large variety of functions in many pathophysiological processes and their interaction with endothelial cells and leukocytes is known to play an important role in the pathophysiology of vascular inflammation. The aim of this study was to investigate the relationship between white blood cell count in conditions resulting in leukocytosis and platelet count and platelet parameters including mean platelet volume, platelet distribution width, and plateletcrit. White blood cell counts count and all platelet parameters were evaluated in 341 results of normal complete blood count (of which the white blood cell counts were within reference range, group 1) and 327 results of elevated white blood cell counts count (group 2). There was a significant difference between these two groups in PLT counts and PCT values, being higher in Group 2. However, there was no statistically significant difference between two groups in MPV and PDW values. On the other hand, there were statistically significant, but weak, correlations between the WBC and platelet counts in both groups (p<0.01, r=0.235 for group 1, p<0.05, r=0.116 for group 2). As a conclusion PLT count and PCT values increase in infectious conditions. This study and previous studies show that PLTs are employed in infectious conditions but the exact mechanism and the exact clinical importance of this response remains to be cleared by further studies.

  17. 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.

  18. Evaluation of platelet function using multiple electrode platelet aggregometry in dogs with septic peritonitis.

    Science.gov (United States)

    Li, Ronald H L; Chan, Daniel L

    2016-09-01

    To assess platelet function via multiple electrode platelet aggregometry (MEPA) in dogs with septic peritonitis and in healthy dogs. The secondary aim was to determine if there is prognostic significance to changes in platelet function observed in septic dogs. Prospective, observational cohort study conducted from January 2012 to March 2014. University teaching hospital. Twenty dogs with septic peritonitis and 23 healthy dogs. None. MEPA using arachidonic acid, adenosine diphosphate, and collagen (COL) as agonists was measured within 24 hours of diagnosis of sepsis. Compared to healthy dogs, platelet aggregation was reduced in dogs with septic peritonitis for all agonists (P peritonitis. Circulating platelets from dogs with septic peritonitis have diminished aggregation in response to multiple platelet agonists. MEPA may serve as an assessment tool for illness severity in this patient population. © Veterinary Emergency and Critical Care Society 2016.

  19. [Glycoproteins, inherited diseases of platelets, and the role of platelets in wound healing].

    Science.gov (United States)

    Nurden, Alan T; Nurden, Paquita

    2013-02-01

    Recognition that platelets have a glycocalyx rich in membrane glycoproteins prompted the discovery in France that inherited bleeding syndromes due to defects of platelet adhesion and aggregation were caused by deficiencies in major receptors at the platelet surface. Identification of the alpha IIb beta3 integrin prompted the development of powerful anti-thrombotic drugs that have gained worldwide use. Since these discoveries, the genetic causes of many other defects of platelet function and production have been elucidated, with the identification of an ADP receptor, P2 Y12, another widespread target for anti-thrombotic drugs. Discovery of the molecular basis of a rare disease of storage of biologically active proteins in platelet alpha-granules has been accompanied by the recognition of the roles of platelets in inflammation, the innate immune system and tissue repair, opening new avenues for therapeutic advances.

  20. Decrease in platelet activating factor stimulated phosphoinositide turnover during storage of human platelets in plasma

    Energy Technology Data Exchange (ETDEWEB)

    Carter, M.G.; Shukla, S.D. (Univ. of Missouri School of Medicine, Columbia (USA))

    1987-05-01

    Human platelet concentrate from the American Red Cross Blood Center was stored at 24{degree}C in a shaker and aliquots were taken out at time intervals aseptically. Platelet activating factor (PAF) stimulated turnover of phosphoinositide (PPI) was monitored by assaying {sup 32}P incorporation into phosphoinositides using platelet rich plasma (PRP). Platelets in PRP were incubated with 1 {times} 10{sup {minus}7} M PAF at 37{degree}C with gentle shaking and after 5 min their lipids were extracted and analysed by TLC for {sup 32}P-phosphoinositides. The percent stimulation of {sup 32}P incorporation by PAF (over control) into PPI was approximately 250, 100, 60, 25 and 20 on days 1, 2, 3, 5 and 6, respectively. This indicated a dramatic decrease in PAF responsive turnover of platelet PPI during storage. These findings have important implications in relation to PAF receptor activity and viability of platelets at different periods of storage.

  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. Transcellular lipoxygenase metabolism between monocytes and platelets

    Energy Technology Data Exchange (ETDEWEB)

    Bigby, T.D.; Meslier, N. (Univ. of California, San Francisco (USA))

    1989-09-15

    We have examined the effects of co-culture and in vitro co-stimulation on lipoxygenase metabolism in monocytes and platelets. Monocytes were obtained from the peripheral blood of normal volunteers by discontinuous gradient centrifugation and adherence to tissue culture plastic. Platelets were obtained from the platelet-rich plasma of the same donor. When 10(9) platelets and 2.5 x 10(6) monocytes were co-stimulated with 1 microM A23187, these preparations released greater quantities of 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid, 5(S),12-(S)dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acid, and leukotriene C4, 5(S)-hydroxy-6(R)-S-glutathionyl-7,9-trans-11,14-cis-eicosatetraenoic (LTC4) when compared with monocytes alone. Release of arachidonic acid, 5-HETE, delta 6-trans-LTB4, and delta 6-trans-12-epi-LTB4 from monocytes was decreased in the presence of platelets. A dose-response curve was constructed and revealed that the above changes became evident when the platelet number exceeded 10(7). Dual radiolabeling experiments with 3H- and 14C-arachidonic acid revealed that monocytes provided arachidonic acid, 5-HETE, and LTA4 for further metabolism by the platelet. Monocytes did not metabolize platelet intermediates detectably. In addition, as much as 1.2 microM 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid and 12(S)-hydroperoxy-10-trans-5,8,14-cis-eicosatetraenoic acid had no effect on monocyte lipoxygenase metabolism. Platelets were capable of converting LTA4 to LTC4, but conversion of LTA4 to LTB4 was not detected. We conclude that the monocyte and platelet lipoxygenase pathways undergo a transcellular lipoxygenase interaction that differs from the interaction of the neutrophil and platelet lipoxygenase pathways. In this interaction monocytes provide intermediate substrates for further metabolic conversion by platelets in an unidirectional manner.

  3. Flow cytometric assessment of activation of peripheral blood platelets in dogs with normal platelet count and asymptomatic thrombocytopenia.

    Science.gov (United States)

    Żmigrodzka, M; Guzera, M; Winnicka, A

    2016-01-01

    Platelets play a crucial role in hemostasis. Their activation has not yet been evaluated in healthy dogs with a normal and low platelet count. The aim of this study was to determine the influence of activators on platelet activation in dogs with a normal platelet count and asymptomatic thrombocytopenia. 72 clinically healthy dogs were enrolled. Patients were allocated into three groups. Group 1 consisted of 30 dogs with a normal platelet count, group 2 included 22 dogs with a platelet count between 100 and 200×109/l and group 3 consisted of 20 dogs with a platelet count lower than 100×109/l. Platelet rich-plasma (PRP) was obtained from peripheral blood samples using tripotassium ethylenediaminetetraacetic acid (K3-EDTA) as anticoagulant. Next, platelets were stimulated using phorbol-12-myristate-13-acetate or thrombin, stabilized using procaine or left unstimulated. The expression of CD51 and CD41/CD61 was evaluated. Co-expression of CD41/CD61 and Annexin V served as a marker of platelet activation. The expression of CD41/CD61 and CD51 did not differ between the 3 groups. Thrombin-stimulated platelets had a significantly higher activity in dogs with a normal platelet count than in dogs with asymptomatic thrombocytopenia. Procaine inhibited platelet activity in all groups. In conclusion, activation of platelets of healthy dogs in vitro varied depending on the platelet count and platelet activator.

  4. Pathogen-Reduced, Extended Platelet Storage in Platelet Additive Solution (PAS)

    Science.gov (United States)

    2016-10-01

    concentrations will be performed to ensure the desired concentration was achieved. Platelet Additive Solutions are isotonic solutions used to replace a...Sherrill J. Slichter, MD CONTRACTING ORGANIZATION: Bloodworks Northwest Seattle, WA 98104 REPORT DATE: October 2016 TYPE OF REPORT: Annual...TITLE AND SUBTITLE Pathogen-Reduced, Extended Platelet Storage in Platelet Additive Solution (PAS) 5a. CONTRACT NUMBER W81XWH-12-1-0441 5b. GRANT

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

    OpenAIRE

    Ye-Ming Lee; Kuo-Hsien Hsieh; Wan-Jung Lu; Hsiu-Chu Chou; Duen-Suey Chou; Li-Ming Lien; Joen-Rong Sheu; Kuan-Hung Lin

    2012-01-01

    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...

  6. Platelet Lysates Produced from Expired Platelet Concentrates Support Growth and Osteogenic Differentiation of Mesenchymal Stem Cells

    OpenAIRE

    Sandra Mjoll Jonsdottir-Buch; Ramona Lieder; Olafur Eysteinn Sigurjonsson

    2013-01-01

    BACKGROUND: Mesenchymal stem cells are promising candidates in regenerative cell therapy. Conventional culture methods involve the use of animal substances, specifically fetal bovine serum as growth supplement. Since the use of animal-derived products is undesirable for human applications, platelet lysates produced from human platelets are an attractive alternative. This is especially true if platelet lysates from already approved transfusion units at blood banks can be utilized. The purpose ...

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

    OpenAIRE

    Neelam Mittal; Isha Narang

    2012-01-01

    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 ...

  8. Platelet lipidomics: a modern day perspective on lipid discovery and characterization in platelets

    OpenAIRE

    O’Donnell, Valerie B.; Murphy, Robert C.; Watson, Steve P.

    2014-01-01

    Lipids are diverse families of biomolecules that perform essential structural and signaling roles in platelets. Their formation and metabolism is tightly controlled by enzymes and signal transduction pathways, and their dysregulation leads to significant defects in platelet function and disease. Platelet activation is associated with significant changes to membrane lipids, and formation of diverse bioactive lipids that play essential roles in hemostasis. In recent years, new generation mass s...

  9. 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.

  10. Platelet interaction with bacterial toxins and secreted products.

    Science.gov (United States)

    Shannon, Oonagh

    2015-01-01

    Bacteria that enter the bloodstream will encounter components of the cellular and soluble immune response. Platelets contribute to this response and have emerged as an important target for bacterial pathogens. Bacteria produce diverse extracellular proteins and toxins that have been reported to modulate platelet function. These interactions can result in complete or incomplete platelet activation or inhibition of platelet activation, depending on the bacteria and bacterial product. The nature of the platelet response may be highly relevant to disease pathogenesis.

  11. 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.

  12. Single-step separation of platelets from whole blood coupled with digital quantification by interfacial platelet cytometry (iPC).

    Science.gov (United States)

    Basabe-Desmonts, L; Ramstrom, S; Meade, G; O'Neill, S; Riaz, A; Lee, L P; Ricco, A J; Kenny, D

    2010-09-21

    We report the efficient single-step separation of individual platelets from unprocessed whole blood, enabling digital quantification of platelet function using interfacial platelet cytometry (iPC) on a chip. iPC is accomplished by the precision micropatterning of platelet-specific protein surfaces on solid substrates. By separating platelets from whole blood using specific binding to protein spots of a defined size, iPC implements a simple incubate-and-rinse approach, without sample preparation, that enables (1) the study of platelets in the physiological situation of interaction with a protein surface, (2) the choice of the number of platelets bound on each protein spot, from one to many, (3) control of the platelet-platelet distance, including the possibility to study noninteracting single platelets, (4) digital quantification (counting) of platelet adhesion to selected protein matrices, enabling statistical characterization of platelet subpopulations from meaningfully large numbers of single platelets, (5) the study of platelet receptor expression and spatial distribution, and (6) a detailed study of the morphology of isolated single platelets at activation levels that can be manipulated. To date, we have demonstrated 1-4 of the above list. Platelets were separated from whole blood using iPC with fibrinogen, von Willebrand factor (VWF), and anti-CD42b antibody printed "spots" ranging from a fraction of one to several platelet diameters (2-24 μm). The number of platelets captured per spot depends strongly on the protein matrix and the surface area of the spot, together with the platelet volume, morphology, and activation state. Blood samples from healthy donors, a May-Hegglin-anomaly patient, and a Glanzmann's Thrombasthenia patient were analyzed via iPC to confirm the specificity of the interaction between protein matrices and platelets. For example, the results indicate that platelets interact with fibrinogen spots only through the fibrinogen receptor (

  13. Thrombopoietin induces p-selectin expression on platelets and subsequent platelet/leukocyte interactions.

    Science.gov (United States)

    Tibbles, Heather E; Navara, Christopher S; Hupke, Michael A; Vassilev, Alexei O; Uckun, Fatih M

    2002-04-12

    Ligation of thrombopoietin (TPO) to the platelet c-Mpl receptor induces numerous biochemical pathways in the absence of aggregation. Two forms of recombinant TPO are currently in clinical trials for the treatment of thrombocytopenia. This study focuses on the effects of the full-length recombinant human TPO (rhTPO) on platelets in a whole blood system. Platelet-leukocyte associations (PLAs) were visualized following rhTPO stimulation as CD42b/CD 45 double positive clusters by FACS analysis. Treatment of washed platelets with rhTPO induced granule release and expression of the leukocyte adhesion receptor P-selectin (CD 62P) in the absence of aggregation and calcium mobilization. RhTPO also induced platelet-leukocyte interactions in whole blood. Following stimulation, leukocytes were recruited by platelets through P-selectin in a calcium-dependent manner. rhTPO stimulates platelet-leukocyte associations in whole blood through expression of platelet P-selectin. To our knowledge, this is the first report that identifies TPO as a promoter of platelet-leukocyte interactions.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Propranolol modifies platelet serotonergic mechanisms in rats.

    Science.gov (United States)

    Zółtowski, R; Pawlak, R; Matys, T; Pietraszek, M; Buczko, W

    2002-06-01

    Though the mechanisms for the vascular actions of vasodilatory beta-blockers are mostly determined, some of their interactions with monoaminergic systems are not elucidated. Because there are evidences supporting a possible involvement of serotonin (5-HT) in the actions of beta-blockers, we studied the effect of propranolol on peripheral serotonergic mechanisms in normotensive and Goldblatt two-kidney - one clip (2K1C) hypertensive rats. In both groups of animals propranolol decreased systolic blood pressure, significantly increased whole blood serotonin concentration and at the same time it decreased platelet serotonin level. The uptake of the amine by platelets from hypertensive animals was lower than that of normotensive animals and it was decreased by propranolol only in the latter. In both groups propranolol inhibited potentiation of ADP-induced platelet aggregation by serotonin. In conclusion, this study provides evidence that propranolol modifies platelet serotonergic mechanisms in normotensive and renal hypertensive rats.

  20. Activation of human platelets by misfolded proteins

    NARCIS (Netherlands)

    Herczenik, E.; Bouma, B.; Korporaal, J.A.; Strangi, R.; Zeng, Q.; Gros, P.; van Eck, M.; van Berkel, T.J.C.; Gebbink, M.F.B.G.; Akkerman, J.W.N.

    2007-01-01

    Objective: Protein misfolding diseases result from the deposition of insoluble protein aggregates that often contain fibrils called amyloid. Amyloids are found in Alzheimer disease, atherosclerosis, diabetes mellitus, and systemic amyloidosis,which are diseases where platelet activation might be

  1. Mapuche herbal medicine inhibits blood platelet aggregation.

    Science.gov (United States)

    Falkenberg, Susan Skanderup; Tarnow, Inge; Guzman, Alfonso; Mølgaard, Per; Simonsen, Henrik Toft

    2012-01-01

    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 (H(2)O), 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 (H(2)O) were substantial and confirmed by inhibition of platelet surface activation markers.

  2. 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.

  3. Relationship between platelet parameters and sudden ...

    African Journals Online (AJOL)

    Relationship between platelet parameters and sudden sensorineural hearing loss: a ... Data source: A PubMed, Science Direct, Scopus, OVID, EMBASE and ... relationship of PDW and SSNHL but due to the limited studies on this subject more ...

  4. Effects of drugs on platelet function.

    Science.gov (United States)

    Morse, E E

    1977-01-01

    Numerous drugs and chemicals affect the function of human blood platelets. The mechanism of action of some medications is partly understood. Aspirin is the most frequently involved drug. It appears to interfere with the platelet release reaction by acetylation of a platelet membrane protein which may be involved in the synthesis of prostaglandins. Other anti-inflammatory drugs, including indomethacin, phenylbutazone, ibuprophen (Motrin) and clonixin, also interfere with the release reaction but have a shorter acting course than aspirin. Some drugs stimulate adenylcyclase (gliclazide) or block phosphodiesterase, (dipyridamole, caffeine) both of which actions lead to an increase in adenosine cyclic 3':5' monophosphate (cAMP) and decrease aggregation by adenosine diphosphate (ADP). These interactions should be known to clinical scientists since patients using these medicaments may manifest abnormal platelet function tests in the laboratory and mild hemorrhagic syndromes in the clinic.

  5. 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.

  6. Evaluation of polyphenolic fraction isolated from aerial parts of Tribulus pterocarpus on biological properties of blood platelets in vitro.

    Science.gov (United States)

    Olas, Beata; Morel, Agnieszka; Hamed, Arafa I; Oleszek, Wieslaw; Stochmal, Anna

    2013-01-01

    The antiplatelet and antioxidative activity of polyphenolic fraction isolated from aerial parts of Tribulus pterocarpus in blood platelets stimulated by thrombin was studied. Thrombin as a strong physiological agonist induces the enzymatic peroxidation of endogenous arachidonic acid, the formation of different reactive oxygen species, including superoxide anion radicals ([Formula: see text](·)) and the platelet aggregation. Therefore, the aim of our study was to assess if the polyphenolic fraction from aerial parts of T. pterocarpus may change the biological properties of blood platelets activated by thrombin. We used cytochrome c reduction method to test the ability of this fraction to change [Formula: see text](·) generation in platelets. Arachidonic acid metabolism was measured by the level of thiobarbituric acid reactive substances (TBARS) and by the production of 8-epi-prostaglandin (8-EPI) F(2). Moreover, we determined the effects of the fraction on blood platelet aggregation induced by thrombin. We observed that the polyphenolic fraction from T. pterocarpus reduced [Formula: see text](·), 8-EPI and TBARS production in these cells. The ability of the fraction to decrease the [Formula: see text](·) generation in blood platelets supports the importance of free radicals in platelet functions, including aggregation process. This study may suggest that the tested plant fraction might be a good candidate for protecting blood platelets against changes of their biological functions, which may be associated with the pathogenesis of different cardiovascular disorders.

  7. Platelet Glycoprotein lb-1X and Malignancy

    Science.gov (United States)

    2011-09-01

    patient with systemic lupus erythematosus . Am J Hematol 2001; 67:262-67. 20. Arthur JF, Dunkley S and Andrews RK. Platelet glycoprotein VI-related...Moroi M. Antibody against platelet membrane glyco- protein VI in a patient with systemic lupus erythematosus . Am J Hematol 2001; 67: 262–7. 9 Arthur JF...Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the

  8. 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.

  9. Platelet dynamics in three-dimensional simulation of whole blood.

    Science.gov (United States)

    Vahidkhah, Koohyar; Diamond, Scott L; Bagchi, Prosenjit

    2014-06-03

    A high-fidelity computational model using a 3D immersed boundary method is used to study platelet dynamics in whole blood. We focus on the 3D effects of the platelet-red blood cell (RBC) interaction on platelet margination and near-wall dynamics in a shear flow. We find that the RBC distribution in whole blood becomes naturally anisotropic and creates local clusters and cavities. A platelet can enter a cavity and use it as an express lane for a fast margination toward the wall. Once near the wall, the 3D nature of the platelet-RBC interaction results in a significant platelet movement in the transverse (vorticity) direction and leads to anisotropic platelet diffusion within the RBC-depleted zone or cell-free layer (CFL). We find that the anisotropy in platelet motion further leads to the formation of platelet clusters, even in the absence of any platelet-platelet adhesion. The transverse motion, and the size and number of the platelet clusters are observed to increase with decreasing CFL thickness. The 3D nature of the platelet-RBC collision also induces fluctuations in off-shear plane orientation and, hence, a rotational diffusion of the platelets. Although most marginated platelets are observed to tumble just outside the RBC-rich zone, platelets further inside the CFL are observed to flow with an intermittent dynamics that alters between sliding and tumbling, as a result of the off-shear plane rotational diffusion, bringing them even closer to the wall. To our knowledge, these new findings are based on the fundamentally 3D nature of the platelet-RBC interaction, and they underscore the importance of using cellular-scale 3D models of whole blood to understand platelet margination and near-wall platelet dynamics.

  10. [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.

  11. Effects of irradiation on platelet function

    Energy Technology Data Exchange (ETDEWEB)

    Rock, G.; Adams, G.A.; Labow, R.S.

    1988-09-01

    Current medical practice involves the irradiation of blood components, including platelet concentrates, before their administration to patients with severe immunosuppression. The authors studied the effect of irradiation on in vitro platelet function and the leaching of plasticizers from the bag, both immediately and after 5 days of storage. The platelet count, white cell count, pH, glucose, lactate, platelet aggregation and release reaction, and serotonin uptake were not altered by the irradiation of random-donor or apheresis units with 2000 rads carried out at 0 and 24 hours and 5 days after collection. The leaching of di(2-ethylhexyl)phthalate from the plastic bags followed by the conversion to mono(2-ethylhexyl)phthalate was not increased by irradiation. Therefore, it is possible to irradiate platelet concentrates on the day of collection and subsequently store them for at least 5 days while maintaining in vitro function. This procedure could have considerable benefit for blood banks involved in the provision of many platelet products.

  12. Lymphocyte-platelet crosstalk in Graves' disease.

    Science.gov (United States)

    Kuznik, Boris I; Vitkovsky, Yuri A; Gvozdeva, Olga V; Solpov, Alexey V; Magen, Eli

    2014-03-01

    Platelets can modulate lymphocytes' role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves' disease (GD). One hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation. The group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3, HLA-DR+ lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10 cells/µL) than TMG group (251 ± 97 × 10 cells/µL; P < 0.05) and control group (262 ± 95 × 10 cells/µL; P < 0.05). In GD group, more platelet-bound lymphocytes (332 ± 91 /µL) were found than that in TMG group (116 ± 67/µL, P < 0.005) and control group (104 ± 58 /µL; P < 0.001). GD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Studies on platelet function in bronchial asthma Part 2. Production of 12-hydroxyeicosatetraenoic acid from platelets and the platelet-lymphocyte interaction in bronchial asthmatics

    OpenAIRE

    角南, 宏二

    1992-01-01

    To clarify the role of platelets in the pathogenesis of bronchial asthma, the production of 12-hydroxyeicosatetraenoic acid(12HETE) from platelets of asthmatics was examined by high performance liquid chromatography(HPLC). The effect of platelets on lymphocyte function was also studied by lymphocyte blastogenesis. The results were as follows : 1) The production of 12HETE from platelets of asthmatics were significantly higher than that of normal subjects(p

  15. 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.

  16. Effect of Antrodia camphorata on Inflammatory Arterial Thrombosis-Mediated Platelet Activation: The Pivotal Role of Protein Kinase C

    Directory of Open Access Journals (Sweden)

    Wan-Jung Lu

    2014-01-01

    Full Text Available Antrodia camphorata is a rare Taiwanese medicinal mushroom. Antrodia camphorata extract has been reported to exhibit antioxidant, anti-inflammation, antimetastasis, and anticancer activities and plays a role in liver fibrosis, vasorelaxation, and immunomodulation. Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Platelet activation plays a crucial role in intravascular thrombosis, which is involved in a wide variety of cardiovascular diseases. However, the effect of Antrodia camphorata on platelet activation remains unclear. We examined the effects of Antrodia camphorata on platelet activation. In the present study, Antrodia camphorata treatment (56–224 μg/mL inhibited platelet aggregation induced by collagen, but not U46619, an analogue of thromboxane A2, thrombin, and arachidonic acid. Antrodia camphorata inhibited collagen-induced calcium (Ca2+ mobilization and phosphorylation of protein kinase C (PKC and Akt. In addition, Antrodia camphorata significantly reduced the aggregation and phosphorylation of PKC in phorbol-12, 13-dibutyrate (PDBu activated platelets. In conclusion, Antrodia camphorata may inhibit platelet activation by inhibiting of Ca2+ and PKC cascade and the Akt pathway. Our study suggests that Antrodia camphorata may be a potential therapeutic agent for preventing or treating thromboembolic disorders.

  17. 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.

  18. 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.

  19. 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.

  20. Platelet production in hypoxic and RBC-transfused mice

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, T.P.

    1978-01-01

    Platelet production rates were studied in hypoxic, red blood cell (RBC) transfused, and normal mice. In addition, platelet depletion was induced in some of the mice by injection of rabbit anti-mouse platelet serum (RAMPS) to stimulate platelet production. Hypoxia alone caused an increase in haematocrit and platelet count at 1 to 3 d, followed by a decrease in platelet counts to below normal values at 6 to 7 d. On the other hand, RBC transfusion caused increased haematocrit and decreased platelet count of mice at 1 to 4 d, with a return of platelet counts to normal by 5 to 6 d. Normal mice and mice transfused with RBC responded to platelet depletion with rebound-thrombocytosis with maximum platelet production 3 to 5 d later and elevated platelet counts on day 5 to 6. However, platelet production in platelet-depleted mice exposed to hypoxia was less marked, and platelet counts did not reach normal levels. The data are consistent with the hypothesis that hypoxia causes thrombocytopenia by stem cell competition between erythroid and megakaryocytic cell lines and/or inhibition of thrombopoietin production.

  1. Platelet activation determines the severity of thrombocytopenia in dengue infection

    Science.gov (United States)

    Ojha, Amrita; Nandi, Dipika; Batra, Harish; Singhal, Rashi; Annarapu, Gowtham K.; Bhattacharyya, Sankar; Seth, Tulika; Dar, Lalit; Medigeshi, Guruprasad R.; Vrati, Sudhanshu; Vikram, Naval K.; Guchhait, Prasenjit

    2017-01-01

    Thrombocytopenia is common in patients with dengue virus (DENV) infections. With a focus on understanding the possible mechanism of thrombocytopenia in DENV infections we described a direct correlation between activation and depletion of platelets in patients. Our data showed a sharp decrease in platelet counts at day 4 of fever in patients. The high DENV genome copies in platelets correlated directly with the elevated platelet activation along with increased binding of complement factor C3 and IgG on their surface at day 4. Recovery in platelet count was observed on day 10 through day 6 and 8 with simultaneous decrease in platelet activation markers. Further, our in vitro data supported the above observations describing a concentration-dependent increase in platelet activation by DENV serotype-2. The high copy number of DENV2 genome in the platelet pellet correlated directly with platelet activation, microparticle generation and clot formation. Furthermore the DENV2-activated platelets were phagocytosed in large numbers by the monocytes. The DENV2-mediated lysis and clearance of platelets were abrogated in presence of platelet activation inhibitor, prostacyclin. These observations collectively suggest that platelet activation status is an important determinant of thrombocytopenia in dengue infections. A careful strategy of inactivation of platelets may rescue them from rapid destruction during DENV infections. PMID:28139770

  2. Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

    Directory of Open Access Journals (Sweden)

    Mărginean Alina

    2016-01-01

    Full Text Available It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low- or nonresponders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.

  3. Pharmacological Characterization of Inositol 1,4,5-tris Phosphate Receptors in Human Platelet Membranes

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    Yogesh Dwivedi

    2009-01-01

    Full Text Available The phosphatidylinositol (PI hydrolysis signaling system has been shown to be altered in platelets of depressed and schizophrenic subjects. Inositol (1,4,5 trisphosphate (Ins(1,4,5P3, an integral component of the PI signaling system, mobilizes Ca2+ by activating Ins(1,4,5P3 receptors. To eventually investigate the role of Ins(1,4,5P3 receptors in depression and other mental disorders, we characterized [H3]Ins(1,4,5P3 binding sites in crude platelet membranes prepared from small amounts of blood obtained from healthy human control subjects. We found a single, saturable binding site for [H3]Ins(1,4,5P3 to crude platelet membranes, which is time dependent and modulated by pH, inositol phosphates, and heparin. Since cyclic adenosine monophosphate (cAMP and Ca2+ have been shown to be important modulators in Ins(1,4,5P3 receptors, in the present study we also determined the effects of various concentrations of CaCI2 and forskolin on Ins(1,4,5P3 binding to platelet membranes. CaCI2 modulated [3H]Ins(1,4,5P3 binding sites in a biphasic manner: at lower concentrations it inhibited [3H]Ins(1,4,5P3 binding, whereas at higher concentrations, it stimulated [3H]Ins(1,4,5P3 binding. On the other hand, forskolin inhibited [3H]Ins(1,4,5P3 binding. Our results thus suggest that the pharmacological characteristics of [3H]Ins(1,4,5P3 binding to crude platelet membranes are similar to that of Ins(1,4,5P3 receptors; and that both Ca2+ and cAMP modulate [3H]Ins(1,4,5P3 binding in crude platelet membranes.

  4. Experimental evaluation of analgesic, anti-inflammatory and anti-platelet potential of Dashamoola

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    Reshma R Parekar

    2015-01-01

    Full Text Available Background: Dashamoola, in the form of arishta and kwath, is a commonly used classical Ayurvedic multi-ingredient formulation for management of pain, arthritis and inflammatory disorders. Objective: To study analgesic, anti-inflammatory and anti-platelet activity of Dashamoola and its combination with aspirin. Materials and Methods: Wistar albino rats (180-200 g and Swiss albino mice (20-25 g of either sex were divided randomly into five groups: Distilled water, aspirin (500mg/kg in rats; 722.2 mg/kg in mice, Dashamoolarishta (1.8 mL/kg in rats; 2.5 mL/kg in mice and Dashamoolarishta with aspirin. Anti-inflammatory activity was measured by change in paw volume in carrageenan-induced inflammation, protein content in model of peritonitis and granuloma weight in cotton pellet granuloma. Analgesic effect was evaluated by counting number of writhes in writhing model. Maximum platelet aggregation and percentage inhibition of ADP and collagen-induced platelet aggregation were estimated in vitro. Statistical analysis was done using one way ANOVA (post hoc Tukey′s test and P < 0.05 was considered significant. Results: Dashamoolarishta and its combination with aspirin showed significantly (P < 0.01 less number of writhes. It showed significant (P < 0.001 anti-inflammatory activity by paw edema reduction in rats, decrease in proteins in peritoneal fluid (P < 0.001 and decrease in granuloma weight (P < 0.05 as compared to respective vehicle control groups. Dashamoola kwath alone and in combination with aspirin inhibited maximum platelet aggregation and percent inhibition of platelets as compared to vehicle (P < 0.001. Conclusion: Dashamoola formulation alone and its combination with aspirin showed comparable anti-inflammatory, analgesic and anti-platelet effects to aspirin.

  5. Effects of cesarean section on mean platelet volume.

    Science.gov (United States)

    Usluoğullari, Betül; Kaygusuz, Ikbal; Simavli, Serap; Eser, Ayla; Inegol Gumus, İknur

    2015-01-01

    Mean platelet volume (MPV) is a risk factor for cardiovascular complications, cerebrovascular disorders, and low-grade inflammatory conditions prone to arterial and venous thromboses. Cesarean delivery is the most important risk factor for pulmonary embolism, stroke, and intracranial venous thrombosis. The hypothesis is that increase in the prevalence of cesarean section and high MPV may be associated with cardiovascular complications such as stroke along with intracranial complications in addition to known systemic and surgical complications. In this study, platelet counts and MPV for postpartum women who delivered by cesarean section and normal vaginal parturition are compared. The subjects were divided in two groups, one was study group consisting of 118 patients giving birth by cesarean section and the other was the control group consisting 94 patients giving birth by normal vaginal parturition. Peripheral venous blood samples in EDTA tubes were collected from all the subjects 1 week before and after the delivery for their prenatal and postpartum periods, respectively. The values were compared between the groups and also before and after the delivery. In the cesarean group, while the MPV level was 8.60 (1.64) fl in the prenatal period, it increased to 9.10 (2.00) fl in the postnatal period (p cesarean section.

  6. 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

    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...... to 0.5 or 20 microM ADP) was higher in nephropathy patients compared with normoalbuminuric patients (P = 0.027), and non-diabetic controls (P = 0.0057). NPAs were higher in nephropathy patients compared to normoalbuminuric patients (P = 0.0088). MPAs were higher in nephropathy patients compared to non-diabetic...

  7. 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.

  8. Calcium-binding proteins from human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Gogstad, G.O.; Krutnes, M.B.; Solum, N.O.

    1983-06-01

    Calcium-binding platelet proteins were examined by crossed immunoelectrophoresis of solubilized platelets against antibodies to whole platelets followed by incubation of the immunoplates with /sup 45/Ca/sup 2 +/ and autoradiography. When the immunoplates had been pretreated with EDTA at pH 9.0 in order to remove divalent cations, three immunoprecipitates were markedly labelled with /sup 45/Ca/sup 2 +/. These corresponded to the glycoprotein IIb-IIIa complex, glycoprotein Ia and a presently unidentified antigen termed G18. These antigens were membrane-bound and surface-oriented. When an excess of EDTA was introduced in the incubation media the results revealed that the glycoprotein IIb-IIIa complex and antigen G18, but not glycoprotein Ia, contained sites with a stronger affinity for calcium than has EDTA at pH 7.4. Immunoprecipitates of the separate glycoproteins IIb and IIIa both bound calcium in the same manner as the glycoprotein IIb-IIIa complex. As another approach, platelet-rich plasma was incubated with /sup 45/Ca/sup 2 +/ prior to crossed immunoelectrophoresis of the solubilized platelets. A single immunoprecipitate was weakly labelled. This did not correspond to any of the immunoprecipitates which were visible after staining with Coomassie blue. The labelling of this antigen was markedly increased when the platelet-rich plasma had been preincubated with EDTA and in this case a weak labelling of the glycoprotein IIB-IIIa precipitate also became apparent. No increased incorporation of calcium occured in any of these immunoprecipitates when the platelets were aggregated with ADP in the presence of /sup 45/Ca/sup 2 +/.

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

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    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.

  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. 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

    2011-01-01

    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 PlA1/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 PlA1/A1 genotype had increased in vivo platelet activation (P = 0.001). Furthermore, neither GPIIIa PlA1/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. PMID:21044892

  12. [Four cases of pseudothrombocytopenia due to platelet cold agglutinins].

    Science.gov (United States)

    Kurata, Yoshiyuki; Hayashi, Satoru; Jouzaki, Kiyoshi; Konishi, Ichirou; Kashiwagi, Hirokazu; Tomiyama, Yoshiaki

    2006-08-01

    We report 4 cases of pseudothrombocytopenia due to platelet cold agglutinins. Case 1 was a 57 y.o. female whose platelet count was 97 x 10(3)/microl. Case 2 was a 37 y.o. male with a platelet count of 96 x 10(3)/microl. Case 3 was a 74 y.o. male with a platelet count of 28 x 10(3)/microl. Case 4 was a 62 y.o. female whose platelet count was 34 x 10(3)/microl. The platelet counts in these 4 cases were decreased and blood smears showed platelet clumping in blood drawn in a tube without anticoagulant just after withdrawal, as well as in blood drawn in a tube with anticoagulant. The platelets from these patients agglutinated at a temperature below 10 degrees C (case 1 and 4) and 24 degrees C (case 2). The immunoglobulin class of the platelet cold agglutinins in cases 1, 2 and 4 was IgM. Agglutinated platelets showed no activation marker, such as CD62P, CD63 or CD40L, on the surface of the platelets. The target antigen of cold agglutinins was GPIIb-IIIa in cases 1 and 2. We considered that the detection of platelet agglutination in blood without anticoagulant is important to diagnose pseudothrombocytopenia due to platelet cold agglutinins. Although this disease is considered to be very rare, we suspect that this disease may be misdiagnosed as pseudothrombocytopenia due to the presence of an anticoagulant, and overlooked.

  13. 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

  14. Mean platelet volume in hepatitis A.

    Science.gov (United States)

    Almiş, H; Bucak, I H; Çelik, V; Tekin, M; Karakoç, F; Konca, Ç; Turgut, M

    2016-06-01

    Hepatitis A virus (HAV) still continues to be a serious public health problem worldwide. Mean platelet volume (MPV) is a marker of platelet function and activation. This study aimed to evaluate the relationship between MPV in acute hepatitis A patients as compared to the control group and to assess MPV as an acute phase reactant in acute hepatitis A. Seventy-six patients were enrolled in this study. The control group consisted of 41 healthy age- and sex-matched individuals. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, prothrombin time (PT), platelet count (PC), serum albumin (ALB), and mean platelet volume (MPV) levels were recorded. The diagnosis of HAV infection was based on anti-HAV Ig M positivity. The mean levels of MPV in the study group were significantly statistically lower than in the control group (p 0.05), but the MPV levels correlated with the platelet counts (p hepatitis A. MPV levels were significantly lower in the patients with acute hepatitis A as compared to the healthy control group. This study demonstrated that MPV may be a negative acute phase reactant for acute hepatitis A. Further studies will explain the role that MPV plays in inflammation and other viral infections.

  15. Functional platelet defects in children with severe chronic ITP as tested with 2 novel assays applicable for low platelet counts.

    Science.gov (United States)

    van Bladel, Esther R; Laarhoven, Annemieke G; van der Heijden, Laila B; Heitink-Pollé, Katja M; Porcelijn, Leendert; van der Schoot, C Ellen; de Haas, Masja; Roest, Mark; Vidarsson, Gestur; de Groot, Philip G; Bruin, Marrie C A

    2014-03-06

    Immune thrombocytopenia (ITP) is an autoimmune disease with a complex heterogeneous pathogenesis and a bleeding phenotype that is not necessarily correlated to platelet count. In this study, the platelet function was assessed in a well-defined cohort of 33 pediatric chronic ITP patients. Because regular platelet function test cannot be performed in patients with low platelet counts, 2 new assays were developed to determine platelet function: first, the microaggregation test, measuring in platelets isolated from 10 mL of whole blood the platelet potential to form microaggregates in response to an agonist; second, the platelet reactivity assay, measuring platelet reactivity to adenosine diphosphate (ADP), convulxin (CVX), and thrombin receptor activator peptide in only 150 μL of unprocessed whole blood. Patients with a severe bleeding phenotype demonstrated a decreased aggregation potential upon phorbol myristate acetate stimulation, decreased platelet degranulation following ADP stimulation, and a higher concentration of ADP and CVX needed to activate the glycoprotein IIbIIIa complex compared with patients with a mild bleeding phenotype. In conclusion, here we have established 2 functional tests that allow for evaluation of platelet function in patients with extremely low platelet counts (platelet function is related to bleeding phenotype in chronic ITP.

  16. 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.

  17. 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.

  18. 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.

  19. The Role of Platelets in Cardiovascular Disease: Molecular Mechanisms.

    Science.gov (United States)

    Papapanagiotou, Angeliki; Daskalakis, Georgios; Siasos, Gerasimos; Gargalionis, Antonios; Papavassiliou, Athanasios G

    2016-01-01

    The role of platelets in atherosclerotic process and subsequently in the pathophysiology of cardiovascular disease is essential as platelets in addition to their contribution to thrombosis and hemostasis modulating inflammatory reactions and immune response. Platelets after adhesion on the injured vascular endothelium and activation release a wide range of molecules stored in platelets granules such as chemokines, proinflammatory molecules and other biological response modulators accelerating interaction among platelets, endothelial cells and leukocytes. These interactions establish a localized inflammatory response that promotes the atherosclerotic process. Moreover, activated platelets give rise to microparticles another active participant within the blood stream. The purpose of this review is to present the role of platelets in the above mechanisms giving an emphasis on the nature of the platelet derived- molecules and their contribution to the atherosclerotic process.

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

    Science.gov (United States)

    Lee, Ye-Ming; Hsieh, Kuo-Hsien; Lu, Wan-Jung; Chou, Hsiu-Chu; Chou, Duen-Suey; Lien, Li-Ming; Sheu, Joen-Rong; Lin, Kuan-Hung

    2012-01-01

    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 [Ca(2+)](i) mobilization, thromboxane A(2) formation, hydroxyl radical (OH(●)) formation, and phospholipase C (PLC)γ2, 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 A(2) formation, thereby leading to inhibition of [Ca(2+)](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.

  1. 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.

  2. Increased intracellular free calcium and sensitivity to angiotensin II in platelets of preeclamptic women.

    Science.gov (United States)

    Haller, H; Oeney, T; Hauck, U; Distler, A; Philipp, T

    1989-04-01

    Preeclampsia is characterized by a generalized vasoconstriction and increased vascular sensitivity to angiotensin II. Intracellular free calcium, implicated in vascular smooth muscle contraction, has been found to be elevated in platelets of other hypertensive disorders. We therefore measured intracellular free calcium concentrations by using the fluorescent probe quin-2 in platelets of six patients with preeclampsia and compared them to measurements in ten normotensive pregnant women and ten age-matched nonpregnant women. Intracellular free calcium was also determined in the preeclamptic women after delivery. We found that intracellular free calcium was slightly elevated in normal pregnancy (102 +/- 13 nmol/L v 87 +/- 17 nmol/L) but was markedly increased in preeclampsia (138 +/- 13 nmol/L, P less than .05). This increase disappeared six weeks after delivery (84 + 10 nmol/L, P less than .01). To investigate whether the increased intracellular free calcium was related to angiotensin II, the platelets were exposed to thrombin and angiotensin II in vitro. Exposure to thrombin and angiotensin II caused a dose-dependent increase in intracellular free calcium. The intracellular response to thrombin was not significantly different in the three groups. However, stimulation with angiotensin II revealed an increased response in intracellular free calcium in preeclampsia (P less than .05) that disappeared after delivery. Our findings show a sustained increase in platelet intracellular free calcium in preeclampsia and suggest a functional alteration of the angiotensin II receptor in this disease.

  3. Sertraline reduces glutamate uptake in human platelets.

    Science.gov (United States)

    Rodrigues, Débora Olmedo; Bristot, Ivi Juliana; Klamt, Fábio; Frizzo, Marcos Emílio

    2015-12-01

    Mitochondrial damage and declines in ATP levels have been recently attributed to sertraline. The effects of sertraline on different parameters were investigated in washed platelets from 18 healthy male volunteers, after 24h of drug exposure. Sertraline toxicity was observed only at the highest concentrations, 30 and 100 μM, which significantly reduced platelet viability to 76 ± 3% and 20 ± 2%, respectively. The same concentrations significantly decreased total ATP to 73 ± 3% and 13 ± 2%, respectively. Basal values of glycogen were not significantly affected by sertraline treatment. Glutamate uptake was significantly reduced after treatment with 3, 30 and 100 μM, by 28 ± 6%, 32 ± 5% and 54 ± 4%, respectively. Our data showed that sertraline at therapeutic concentrations does not compromise platelet viability and ATP levels, but they suggest that in a situation where extracellular glutamate levels are potentially increased, sertraline might aggravate an excitotoxic condition.

  4. 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.

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

    Science.gov (United States)

    Suchetha, A.; Lakshmi, P.; Bhat, Divya; Mundinamane, Darshan B.; Soorya, K. V.; Bharwani, G. Ashit

    2015-01-01

    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. PMID:26681857

  6. The synthesis of proteins in unnucleated blood platelets

    OpenAIRE

    Michał Bijak; Joanna Saluk; Michał Błażej Ponczek Ponczek; Paweł Nowak; Barbara Wachowicz

    2013-01-01

    Platelets are the smallest, unnucleated blood cells that play a key role in maintaining normal hemostasis. In the human body about 1x1011 platelets are formed every day, as a the result of complex processes of differentiation, maturation and fragmentation of megakaryocytes. Studies done over 4 decades ago demonstrated that circulating in blood mature platelets can synthesize proteins. Recent discoveries confirm protein synthesis by unnucleated platelets in response to activation. Moreover, pr...

  7. IVBT-documented platelet function correlates with flow cytometric data.

    Science.gov (United States)

    Hoffmann, J; Bonacker, G; Kretschmer, V; Schulzki, T; Heimanns, J

    1996-12-01

    Thrombocytopenic patients with identical platelet counts often show different bleeding tendencies owing to significant differences in the platelet function. This could be demonstrated by the in vitro bleeding test (IVBT). Using flow cytometry, we tried to find characteristics of platelet antigen expression in order to explain these differences in function. Thirty patients with bone marrow hypoplasia receiving 65 platelet transfusions (mainly from a cell separator) were observed for 3 to 29 days. Size, granulation and fluorescence of platelet-rich plasma (n = 522 samples) were evaluated using monoclonal antibodies against GP IIIb (collagen receptor), GP IIb/IIIa (fibrinogen receptor) and GP Ib (thrombin receptor). We defined separate gates for each antibody using the results from 50 normals and by laying an orthograde cross over the gate to divide the gate into four equal quadrants. The platelet populations were divided into four different groups according to the occlusion time (OT) of the IVBT and the Simplate time (ST). The thrombocytes with the most impaired function (OT > or = 485 s/ST > 30 min) had significantly less platelet fluorescence when marked with antibodies against GP IIIb and GP Ib than those with short OT and ST (OT platelet fluorescence when marked with anti-GP IIIb and anti-GP Ib than thrombocytopenic patients, who had a spontaneous platelet rise beyond 30,000 platelets/microliters a few days later. One day after platelet transfusion, significantly more platelets with high GP IIIb and Ib expression could be found. We were also able to document better transfusion efficacy of platelet concentrates with high GP IIIb and Ib expression. Finally, patients with high bleeding scores showed less GP Ib expression on the platelets than patients with low bleeding scores. In summary, the IVBT-documented platelet function clearly corresponded to an increased expression of the collagen receptor and the thrombin receptor of platelets.

  8. Stimulation of Platelet Death by Vancomycin

    Directory of Open Access Journals (Sweden)

    Syeda T. Towhid

    2013-01-01

    Full Text Available Background/Aims: Side effects of vancomycin, a widely used antibiotic, include thrombocytopenia. The vancomycin-induced thrombocytopenia has been attributed to immune reactions. At least in theory, thrombocytopenia could result in part from the triggering of apoptosis, which results in cell shrinkage and cell membrane scrambling with subsequent phosphatidylserine exposure at the cell surface. The cell membrane scrambling could be initiated by a signaling involving increase of cytosolic Ca2+ activity, ceramide formation, mitochondrial depolarization and/or caspase activation. Vancomycin has indeed been shown to trigger neutrophil apoptosis. An effect of vancomycin on platelet apoptosis has, however, never been tested. The present study thus explored the effect of vancomycin on platelet activation and apoptosis. Methods: Human blood platelets were exposed to vancomycin and forward scatter was utilized to estimate cell volume, annexin V-binding to quantify phosphatidylserine (PS exposure, Fluo-3 AM fluorescence to estimate cytosolic Ca2+ activity ([Ca2+]i, antibodies to quantify ceramide formation and immunofluorescence to quantify protein abundance of active caspase-3. Results: A 30 minutes exposure to vancomycin (≥1 µg/ ml decreased cell volume, triggered annexin V-binding, increased [Ca2+]i, activated caspase 3, stimulated ceramide formation, triggered release of thromboxane B2, and upregulated surface expression of CD62P (P-selectin as well as activated integrin αllbβ3. Annexin V-binding and upregulation of CD62P (P-selectin and integrin αllbβ3 was significantly blunted by removal of extracellular Ca2+. Annexin V-binding was not significantly blunted by pan-caspase inhibitor zVAD-FMK (1 µM. In conclusion, vancomycin results in platelet activation and suicidal platelet death with increase of [Ca2+]i, caspase-3 activation, cell membrane scrambling and cell shrinkage. Activation and cell membrane scrambling required the presence of Ca2

  9. 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...... and methods We included 121 healthy individuals to establish reference intervals and six healthy individuals for evaluation of the day-to-day variation. Platelet aggregation was evaluated on hirudin whole blood employing Multiplate® induced by arachidonic acid, ADP, collagen and ristocetin (RISTOlow...... reference interval is presented as 95% confidence interval suitable for any age and both sex. Day-to-day variation was

  10. Thrombopoietin the primary regulator of platelet production.

    Science.gov (United States)

    Kaushansky, K

    1997-03-01

    Although the term thrombopoietin was first used nearly 40 years ago to describe the humoral regulator of platelet production, doubts surrounding its existence remained until the molecule was cloned 3 years ago. Using the recombinant protein, several investigators have shown that thrombopoietin influences all aspects of megakaryocyte development, from the hematopoietic stem cell to the mature platelet. The present review focuses on the discovery and characterization of this hormone, the initial stages of its clinical development, and some important yet unanswered questions of its molecular and cellular physiology. (Trends Endocrinol Metab 1997;8:45-50). (c) 1997, Elsevier Science Inc.

  11. Platelet Function in Basset Hound Hereditary Thrombopathy.

    Science.gov (United States)

    1986-01-01

    Hematol, 17(4),242-258, 1980. 5. CHARO, I.F., FEINMAN , R.D., DETWILER, T.C. Interrelation of platelet aggregation and secretion. J. Clin. Invest...of dogs affected with Basset Hound Hereditary Thrombopathy. Thromb Au, 3, 61-71, 1985. 4. DETWILER, T.C., CHARO, I.F., AND FEINMAN , R.D. Evidence...glycoproteins. Surv Synth Path Res 1:274, 1983. Charo IF, Feinman RD, and Detwiler TC. Interrelation of platelet aggregation and secretion. J Clin Invest 60

  12. 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...

  13. Platelet satellitism in a trauma patient

    Science.gov (United States)

    Kopcinovic, Lara Milevoj; Pavic, Marina

    2012-01-01

    Platelet satellitism (PS) is a rare phenomenon observed in blood smears obtained from blood anticoagulated with EDTA. It is characterised by platelet rosetting around polymorphonuclear neutrophils and in rare cases around other blood cells. PS is a rare cause of pseudothrombocytopenia. References about the phenomenon of PS in medical literature are few. In this report we describe a case of PS fortunately noticed in one trauma patient. Furthermore, we discuss the possible pathophysiological mechanisms of PS proposed in the literature. To our knowledge this is the first case of PS reported in Croatia. PMID:22384529

  14. MEAN PLATELET VOLUME AND RISK OF THROMBOTIC STROKE

    Directory of Open Access Journals (Sweden)

    Prasantha Kumar Thankappan

    2017-07-01

    Full Text Available BACKGROUND Stroke is a major cause of long term morbidity and mortality. Several factors are known to increase the liability to stroke. Platelets play a crucial role in the pathogenesis of atherosclerotic complications, contributing to thrombus formation. Platelet size (mean platelet volume, MPV is a marker and possible determinant of platelet function, large platelets being potentially more reactive. Hence an attempt has-been made to study the association if any between mean platelet volume and thrombotic stroke. The aim of this study was to determine whether an association exists between Mean Platelet Volume (MPV and thrombotic stroke. MATERIALS AND METHODS The study is a case control study and data was collected at Government Medical College Hospital, Kottayam, Kerala a tertiary care referral centre. The study was carried out among fifty patients diagnosed with thrombotic stroke and presenting to the hospital within forty eight hours of onset of symptoms. Fifty age group and sex matched controls were also recruited. Mean platelet volume was obtained using a SYSMEX automated analyser. RESULTS This study has shown a statistically significant relation between mean platelet volume and risk of thrombotic stroke but no statistically significant correlation between clinical severity of stroke and mean platelet volume. CONCLUSION This study has shown an elevation of MPV in acute phase of thrombotic stroke. Platelet mass was found to be more or less a constant. This study did not find a statistically significant correlation between clinical severity of stroke and mean platelet volume.

  15. 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.

  16. Ultra-pure platelet isolation from canine whole blood.

    Science.gov (United States)

    Trichler, Shauna A; Bulla, Sandra C; Thomason, John; Lunsford, Kari V; Bulla, Camilo

    2013-07-17

    Several research applications involving platelets, such as proteomic and transcriptomic analysis, require samples with very low numbers of contaminating leukocytes, which have considerably higher RNA and protein content than platelets. We sought to develop a platelet purification protocol that would minimize contamination, involve minimal centrifugation steps, and yield highly pure platelet samples derived from low volume whole blood samples from healthy dogs. Using an optimized OptiPrep density gradient technique, platelet recovery was 51.56% with 99.99% platelet purity and leukocyte contamination of 100 leukocytes per 108 platelets, on average. Platelet samples were subjected to additional purification with CD45-labeled Dynabeads after density barrier centrifugation resulting in a 95-fold depletion of residual leukocytes. Platelets purified using these methods remained inactivated as assessed by Annexin V and P-selectin labeling with flow cytometry. The use of OptiPrep density gradient is a quick method for obtaining highly purified platelet samples from low volumes of canine whole blood with minimal contamination. Additional depletion of residual leukocytes can be achieved using CD45-labeled beads. These platelet samples can then be used for many downstream applications that require ultra-pure platelet samples such as RNA and protein analysis.

  17. [The synthesis of proteins in unnucleated blood platelets].

    Science.gov (United States)

    Bijak, Michał; Saluk, Joanna; Ponczek, Michał Błażej Ponczek; Nowak, Paweł; Wachowicz, Barbara

    2013-07-23

    Platelets are the smallest, unnucleated blood cells that play a key role in maintaining normal hemostasis. In the human body about 1x1011 platelets are formed every day, as a the result of complex processes of differentiation, maturation and fragmentation of megakaryocytes. Studies done over 4 decades ago demonstrated that circulating in blood mature platelets can synthesize proteins. Recent discoveries confirm protein synthesis by unnucleated platelets in response to activation. Moreover, protein synthesis alters the phenotype and function of platelets. Platelets synthesize several proteins involved in hemostasis (COX, αIIbβ3, TF PAI-1, Factor XI, protein C inhibitor) and in inflammatory process (IL-1β, CCL5/RANTES). In spite of lack of transcription platelets have a stable mRNA transcripts with a long life correlated with platelet life span. Platelets also show expression of two important key regulators of translation eIF4E and EIF-2α and have a variety of miRNA molecules responsible for translational regulation. This article describes the historical overview of research on protein synthesis by platelets and presents the molecular mechanisms of protein synthesis in activated platelets (and synthesis of the most important platelet proteins).

  18. Glycoprotein Ibalpha signalling in platelet apoptosis and clearance

    NARCIS (Netherlands)

    van der Wal, E.

    2010-01-01

    Storage of platelets at low temperature reduces bacterial growth and might better preserve the haemostatic function of platelets than current procedures. Incubation at 0C is known to expose ?-N-acetyl-D-glucosamine-residues on glycoprotein (GP)Ibalpha inducing receptor-clustering and platelet destru

  19. Ultrastructure of platelets in Bernard-Soulier syndrome.

    Science.gov (United States)

    Maldonado, J E; Gilchrist, G S; Brigden, L P; Bowie, E J

    1975-07-01

    The platelets of a patient with the Bernard-Soulier syndrome were studied by electron microscopy. The main abnormalities were the presence of giant and often round platelets, hypertrophic and frequently widely dilated open canalicular system, disorganized microtubules, and platelets with sparse or absent granulation. Although well defined, these ultrastructural morphologic aberrations are not considered diagnostic or pathognomonic of the syndrome.

  20. 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)

  1. 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)

  2. 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.

  3. 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.

  4. Horizontal RNA transfer mediates platelet-induced hepatocyte proliferation

    NARCIS (Netherlands)

    Kirschbaum, Marc; Karimian, Golnar; Adelmeijer, Jelle; Giepmans, Ben N. G.; Porte, Robert J.; Lisman, Ton

    2015-01-01

    Liver regeneration is stimulated by blood platelets, but the molecular mechanisms involved are largely unexplored. Although platelets are anucleate, they do contain coding or regulatory RNAs that can be functional within the platelet or, after transfer, in other cell types. Here, we show that

  5. The Role of Inflammation in Regulating Platelet Production and Function: Toll-like Receptors in Platelets and Megakaryocytes

    OpenAIRE

    Beaulieu, Lea M.; Freedman, Jane E.

    2009-01-01

    Platelets have been extensively studied as hemostatic regulators, stopping uncontrolled flow of blood from an injured vessel and allowing for repair. However, multiple studies have shown that platelets can interact with bacterial proteins, particularly seen during sepsis and inflammation. Immune cells recognize pathogens through Toll-like Receptors (TLRs). These same receptors allow platelets to recognize bacterial proteins and regulate platelet immunity and function. This review examines the...

  6. Comparison of Platelet Transfusion as Fresh Whole Blood Versus Apheresis Platelets for Massively Transfused Combat Trauma patients

    Science.gov (United States)

    2011-02-01

    T R A N S F U S I O N P R A C T I C E Comparison of platelet transfusion as fresh whole blood versus apheresis platelets for massively transfused...is able to provide blood products to include apheresis platelets (aPLT), but also has extensive experience using fresh whole blood (FWB). In massively...bleeding, resuscitation with blood products is an ABBREVIATIONS: AIS(s) = Abbreviated Injury Scale(s); aPLT = apheresis platelets; ARDS = adult

  7. 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

  8. 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)

  9. Simple platelet markers: Mean platelet volume and congestive heart failure coexistent with periodontal disease. Pilot studies.

    Science.gov (United States)

    Czerniuk, Maciej R; Bartoszewicz, Zbigniew; Dudzik-Niewiadomska, Iwona; Pilecki, Tomasz; Górska, Renata; Filipiak, Krzysztof J

    2017-07-17

    Conducted pilot study concerning mean platelet volume parameter among patients suffering from congestive heart failure and periodontal disease. Examination of dynamic changes of platelet and periodontal markers in group of 50 patients before and an average of 6 months subsequent to professional periodontal treatment. Both platelet and periodontal parameters decreased after periodontal treatment, what is more, the decrease of mean platelet volume (MPV) value due to periodontal disease/mm improvement was shown to be statistically significant (p = 0.05). Improvement of periodontal status may influence decrease of MPV value andincrease of congestive heart failure treatment efficacy and effect patient comfort. It is a new, not frequently used pattern of chronic disease treatment optimalization.

  10. 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

    Platelet alignment in Al2O3pl - TZ3YS composites formed by injection moulding, slip casting, and tape casting, has been examined. Mechanical properties have been determined in terms of flexural strength and fracture toughness, with respect to materials formed by different techniques......, and to the platelet orientation. Materials produced by injection moulding exhibited fewer and smaller internal defects, compared to the slip casting and tape casting, thus giving rise to the maximum average strength. The fracture toughness showed more increase for samples with stronger textures, ie. platelet...... 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...

  11. Platelets and Platelet-Derived Microvesicles as Immune Effectors in Type 2 Diabetes.

    Science.gov (United States)

    Cortez-Espinosa, Nancy; Mayoral, Laura Perez-Campos; Perez-Campos, Eduardo; Cabrera Fuentes, Hector Alejandro; Mayoral, Eduardo Perez-Campos; Martínez-Cruz, Ruth; Canseco, Socorro Pina; Andrade, Gabriel Mayoral; Cruz, Margarito Martinez; Velasco, Itandehui Gallegos; Cruz, Pedro Hernandez

    2017-01-01

    The association between type 2 diabetes mellitus (T2DM) and systemic inflammation may increase platelet reactivity and the accelerated development of vascular disease. Platelets are able to modulate the function of immune cells via the direct release of growth factors and pro-inflammatory chemokines through the production of microvesicles. The microvesicles trigger a transcellular delivery system of bioactive molecules to other cells acting as vectors in the exchange of biological information. Here, we consider the influence of platelets and platelet-derived microvesicles on cells of the immune system and the implications in the pathogenesis of T2DM. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Namibia's transition from whole blood-derived pooled platelets to single-donor apheresis platelet collections

    NARCIS (Netherlands)

    Pitman, John P.; Basavaraju, Sridhar V.; Shiraishi, Ray W.; Wilkinson, Robert; von Finckenstein, Bjorn; Lowrance, David W.; Marfin, Anthony A.; Postma, Maarten; Mataranyika, Mary; Smit Sibinga, Cees Th.

    2015-01-01

    BACKGROUNDFew African countries separate blood donations into components; however, demand for platelets (PLTs) is increasing as regional capacity to treat causes of thrombocytopenia, including chemotherapy, increases. Namibia introduced single-donor apheresis PLT collections in 2007 to increase PLT

  13. Anxiety Disorders and Cardiovascular Disease.

    Science.gov (United States)

    Celano, Christopher M; Daunis, Daniel J; Lokko, Hermioni N; Campbell, Kirsti A; Huffman, Jeff C

    2016-11-01

    Anxiety and its associated disorders are common in patients with cardiovascular disease and may significantly influence cardiac health. Anxiety disorders are associated with the onset and progression of cardiac disease, and in many instances have been linked to adverse cardiovascular outcomes, including mortality. Both physiologic (autonomic dysfunction, inflammation, endothelial dysfunction, changes in platelet aggregation) and health behavior mechanisms may help to explain the relationships between anxiety disorders and cardiovascular disease. Given the associations between anxiety disorders and poor cardiac health, the timely and accurate identification and treatment of these conditions is of the utmost importance. Fortunately, pharmacologic and psychotherapeutic interventions for the management of anxiety disorders are generally safe and effective. Further study is needed to determine whether interventions to treat anxiety disorders ultimately impact both psychiatric and cardiovascular health.

  14. 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.

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

    OpenAIRE

    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 cou...

  16. Lipid profile of platelets and platelet-derived microparticles in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Qianghua Hu

    2016-12-01

    General significance: As far as we are aware, our study is the first study on platelet lipidomics in ovarian cancer. The importance of our findings for the future studies are: 1 a similar change in lipid profile of platelets and PMP may be responsible for hypercoagulability in other cancers, and 2 plasma level of high-risk lipids for venous thrombosis may be useful biomarkers.

  17. Radiation-induced volatile hydrocarbon production in platelets

    Energy Technology Data Exchange (ETDEWEB)

    Radha, E.; Vaishnav, Y.N.; Kumar, K.S.; Weiss, J.F.

    1989-01-01

    Generation of volatile hydrocarbons (ethane, pentane) as a measure of lipid peroxidation was followed in preparations from platelet-rich plasma irradiated in vitro. The hydrocarbons in the headspace of sealed vials containing irradiated and nonirradiated washed platelets, platelet-rich plasma, or platelet-poor plasma increased with time. The major hydrocarbon, pentane, increased linearly and significantly with increasing log radiation dose, suggesting that reactive oxygen species induced by ionizing radiation result in lipid peroxidation. Measurements of lipid peroxidation products may give an indication of suboptimal quality of stored and/or irradiated platelets.

  18. 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.

  19. [The influence of erythrocyte-derived microvesicles on aggregation of platelets in burn injury].

    Science.gov (United States)

    Levin, G Ya; Sukhareva, E G

    2015-01-01

    Burn Injury is accompanied by a significant homeostasis disorder, including the disorder of primary homeostasis, associated with aggregation of platelets. The role of erythrocyte-derived microvesicles in this process has not undergone thorough research. Microvesicles were isolated from washed erythrocytes after one day of storage by ultracentrifugation at 100000 g. The number of MVs was determined by flow cytometry and was standardized in the samples. Heparin-dependent and heparin-independent antithrombin activity in erythrocyte microvesicles was studied by coagulation method. We studied platelet aggregation induced and not induced by ADP under the conditions of artificial shear flow. It was shown that at the early stage of bum injury the number of erythrocyte-derived microvesicles in blood demonstrated a 4.2-fold ncrease. We determined that microvesicles, derived from the erythrocytes of burn patients displayed a significantly less aggregation activity than the microvesicles from donors. The main reason is a considerably lower antithrombin activity in the erythrocyte microvesicles of bum patients. Thus, we can conclude that the decrease of antiaggregation and antithrombin activity of erythrocyte microvesicles associated with the increase in their concentration in blood contributes to thrombophilia of bum patients. Keywords: erythrocytes, microvesicles, bum injury, platelet aggregation, antithrombin activity

  20. Platelet-rich fibrin: the benefits.

    Science.gov (United States)

    Kumar, Yuvika Raj; Mohanty, Sujata; Verma, Mahesh; Kaur, Raunaq Reet; Bhatia, Priyanka; Kumar, Varun Raj; Chaudhary, Zainab

    2016-01-01

    Current published data presents confusing results about the effects of platelet-rich fibrin on bone, and there is a need for studies that throw light on its effect. Our main objective therefore was to evaluate (by fractal analysis) osseous regeneration in extraction sockets with and without platelet-rich fibrin in a study with a substantial sample and a reliable technique to calibrate its effects on bone cells. We also assessed the soft tissue response. Thirty-four patients had their bilaterally impacted third molars (68 surgical sites) extracted in this split-mouth study, following which platelet-rich fibrin was placed in one of the sockets. Patients were followed up clinically and radiographically, and a pain score and fractal analysis were used to evaluate healing of soft tissue and bone, respectively. We conclude that platelet-rich fibrin improves healing of both soft and hard tissues. Although osseous healing did not differ significantly between the groups, healing of soft tissue as judged by the pain score was significantly better in the experimental group.

  1. Platelets in leucocyte recruitment and function.

    Science.gov (United States)

    Rossaint, Jan; Zarbock, Alexander

    2015-08-01

    Platelets have a longstanding recognition as an essential cellular component of the coagulation system. However, substantial research over the last decade has added another important aspect to platelet function in that they are also an integral part of the innate immune system. Complex organisms are facing a constant threat of infections by invading pathogens, and they have developed a sophisticated and elegant measure to combat this threat, namely the immune system. Leucocyte recruitment to sites of infections is an essential step at the forefront of the immune response. Platelets have been shown to be involved in several steps of this process and they are an integrated connecting element among haemostasis, host defence, and additional immunological functions (e.g. neutrophil extracellular traps formation). However, the immune system also requires a tight regulation, as an overshooting immune response carries the risk of harming the host itself. This review aims at highlighting the unique features and molecular mechanisms that allow for the interactions of platelets and leucocytes and the regulation of this process. Furthermore, this article identifies the functional relevance of these events for the immune response.

  2. 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.

  3. Platelet-rich plasma in clinical practice

    African Journals Online (AJOL)

    bone healing in orthopaedics, maxillofacial surgery and dental implants, PRP treatment for ... and the red blood cells removed, leaving a high concentration of platelets and ... therapy in the proportion of bones united at one year. However, this benefit .... recurring alopecia areata of at least two years' duration were randomly ...

  4. Platelet pool inventory management: theory meets practice

    NARCIS (Netherlands)

    Kort, de Wim; Janssen, Michiel; Kortbeek, Nikky; Jansen, Naud; Wal, van der Jan; Dijk, van Nico

    2011-01-01

    BACKGROUND: The shelf life of platelet concentrates (PCs) is a matter of days. Simultaneously, the demand is highly variable, shortages are not allowed, and producing too many results in outdating. Concurrently, younger PCs, implying an extended time till outdating (TTO), are preferred. Common PC in

  5. 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.

  6. Platelet-derived microparticles and platelet function profile in children with congenital heart disease.

    Science.gov (United States)

    Ismail, Eman Abdel Rahman; Youssef, Omneya Ibrahim

    2013-01-01

    Platelet microparticles (PMPs) and function profile in children with congenital heart disease (CHD) have not been widely explored. We investigated platelet aggregation, flow cytometric platelet surface receptors (P-selectin and glycoprotein (GP) IIb/IIIa) and PMPs in 23 children with cyanotic CHD (CCHD), 30 children with acyanotic CHD (ACHD) and 30 healthy controls correlating these variables to hematological and coagulation parameters including von Willebrand factor antigen (vWF Ag) as a marker of endothelial dysfunction. Hemoglobin, hematocrit (HCT), D-dimer, and vWF Ag were significantly higher in CCHD than ACHD group. Platelet MPs and P-selectin expression were increased in patients than controls, particularly in CCHD and positively correlated to HCT, D-dimer, and vWF Ag while platelet count, aggregation, and GP IIb/IIIa expression were decreased in CCHD compared with ACHD group and negatively correlated to HCT. The overproduction of PMPs and platelet activation with suppressed aggregation may be implicated in the pathogenesis of coagulation/hemostatic abnormalities in children with CCHD.

  7. The Signaling Role of CD40 Ligand in Platelet Biology and in Platelet Component Transfusion

    Directory of Open Access Journals (Sweden)

    Chaker Aoui

    2014-12-01

    Full Text Available The CD40 ligand (CD40L is a transmembrane molecule of crucial interest in cell signaling in innate and adaptive immunity. It is expressed by a variety of cells, but mainly by activated T-lymphocytes and platelets. CD40L may be cleaved into a soluble form (sCD40L that has a cytokine-like activity. Both forms bind to several receptors, including CD40. This interaction is necessary for the antigen specific immune response. Furthermore, CD40L and sCD40L are involved in inflammation and a panoply of immune related and vascular pathologies. Soluble CD40L is primarily produced by platelets after activation, degranulation and cleavage, which may present a problem for transfusion. Soluble CD40L is involved in adverse transfusion events including transfusion related acute lung injury (TRALI. Although platelet storage designed for transfusion occurs in sterile conditions, platelets are activated and release sCD40L without known agonists. Recently, proteomic studies identified signaling pathways activated in platelet concentrates. Soluble CD40L is a good candidate for platelet activation in an auto-amplification loop. In this review, we describe the immunomodulatory role of CD40L in physiological and pathological conditions. We will focus on the main signaling pathways activated by CD40L after binding to its different receptors.

  8. Detection of platelet deposition at the site of peripheral balloon angioplasty using indium-111 platelet scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Pope, C.F.; Ezekowitz, M.D.; Smith, E.O.; Rapoport, S.; Glickman, M.; Sostman, H.D.; Zaret, B.L.

    1985-02-01

    Restenosis after balloon angioplasty may be mediated through platelet deposition at the site of arterial dilatation. The purpose of this study was to determine whether platelet deposition at the site of dilatation could be detected using indium-111 platelet scintigraphy. Fifteen patients, aged 60 +/- 9 years, with iliac or femoral (n . 12), renal artery (n . 2) or distal aortic (n . 1) stenoses were studied. All patients received intravenous heparin at the time of dilatation. Labeled platelets containing 471 +/- 65 muCi indium-111 were injected 0.25 to 4 hours after dilatation and 1 to 24 hours after imaging. In 11 of 12 patients with iliac and femoral dilatations, focal uptake was demonstrated at the angioplasty site. In 4 patients (2 patients with renal, 1 patient with iliofemoral, and 1 with distal aortic stenoses), uptake at the dilatation sites was not detected. This preliminary study indicates that despite intravenous heparin, platelets accumulate at sites of balloon dilatation. Platelet scintigraphy may be useful in predicting sites of future narrowing after angioplasty and may be used to test the efficacy of antiplatelet therapy in retarding restenosis.

  9. Platelet aggregation secondary to coronary obstruction.

    Science.gov (United States)

    Moore, S

    1976-03-01

    From many observations made at autopsy it is apparent that thrombosis in a coronary artery is usually, if not always, associated with rupture of an atheromatous plaque. The sequelae of such rupture include hemorrhage into the plaque with further narrowing of the lumen, formation of an occlusive thrombus or of a non-occlusive thrombus. A developing thrombus in an artery undergoes fragmentation with showering of the distal microcirculation by aggregates of platelets possibly with some admixture of fibrin. In many cases of sudden cardiac death associated with severe atherosclerotic stenosis of the coronary vessels, an occlusive thrombus is not found and the myocardium shows no morphological lesion or else focal patchy early damage in the subendocardial region. One possible mechanism that might explain these findings is microembolism from mural nonobstructing coronary thrombus. Such a mechanism is well established in transient ischemia of the brain and retina related to ulcerated atheroma of the internal carotid artery. Experimental observations indicate that platelet aggregates in the myocardial circulation cause arrhythmias, sudden death, vasculitis, and myocardial ischemic damage. Induction of an occlusive coronary artery thrombus is associated with development of an infarct involving the full thickness of the myocardium. A nonocclusive thrombus is associated with either no myocardial damage or focal subendocardial ischemic injury. It is possible that further aggregation of platelets may facilitate the extension of infarction subsequent to an occlusive event, although there is little evidence on this point. A number of clinical studies show increased platelet reactivity to agents causing aggregation, such as norepinephrine or collagen, in subjects experiencing thromboembolic episodes. It seems unlikely, however, that in vitro tests of platelet function can identify or predict clinical arterial thrombotic disease, although studies of platelet survival and turnover

  10. Analysis of Platelet-Rich Plasma Extraction

    Science.gov (United States)

    Fitzpatrick, Jane; Bulsara, Max K.; McCrory, Paul Robert; Richardson, Martin D.; Zheng, Ming Hao

    2017-01-01

    Background: Platelet-rich plasma (PRP) has been extensively used as a treatment in tissue healing in tendinopathy, muscle injury, and osteoarthritis. However, there is variation in methods of extraction, and this produces different types of PRP. Purpose: To determine the composition of PRP obtained from 4 commercial separation kits, which would allow assessment of current classification systems used in cross-study comparisons. Study Design: Controlled laboratory study. Methods: Three normal adults each donated 181 mL of whole blood, some of which served as a control and the remainder of which was processed through 4 PRP separation kits: GPS III (Biomet Biologics), Smart-Prep2 (Harvest Terumo), Magellan (Arteriocyte Medical Systems), and ACP (Device Technologies). The resultant PRP was tested for platelet count, red blood cell count, and white blood cell count, including differential in a commercial pathology laboratory. Glucose and pH measurements were obtained from a blood gas autoanalyzer machine. Results: Three kits taking samples from the “buffy coat layer” were found to have greater concentrations of platelets (3-6 times baseline), while 1 kit taking samples from plasma was found to have platelet concentrations of only 1.5 times baseline. The same 3 kits produced an increased concentration of white blood cells (3-6 times baseline); these consisted of neutrophils, leukocytes, and monocytes. This represents high concentrations of platelets and white blood cells. A small drop in pH was thought to relate to the citrate used in the sample preparation. Interestingly, an unexpected increase in glucose concentrations, with 3 to 6 times greater than baseline levels, was found in all samples. Conclusion: This study reveals the variation of blood components, including platelets, red blood cells, leukocytes, pH, and glucose in PRP extractions. The high concentrations of cells are important, as the white blood cell count in PRP samples has frequently been ignored

  11. CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes.

    Science.gov (United States)

    Zhang, Nanyan; Zhi, Huiying; Curtis, Brian R; Rao, Sridhar; Jobaliya, Chintan; Poncz, Mortimer; French, Deborah L; Newman, Peter J

    2016-02-11

    Human platelet alloantigens (HPAs) reside on functionally important platelet membrane glycoproteins and are caused by single nucleotide polymorphisms in the genes that encode them. Antibodies that form against HPAs are responsible for several clinically important alloimmune bleeding disorders, including fetal and neonatal alloimmune thrombocytopenia and posttransfusion purpura. The HPA-1a/HPA-1b alloantigen system, also known as the Pl(A1)/Pl(A2) polymorphism, is the most frequently implicated HPA among whites, and a single Leu33Pro amino acid polymorphism within the integrin β3 subunit is responsible for generating the HPA-1a/HPA-1b alloantigenic epitopes. HPA-1b/b platelets, like those bearing other low-frequency platelet-specific alloantigens, are relatively rare in the population and difficult to obtain for purposes of transfusion therapy and diagnostic testing. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) gene-editing technology to transform Leu33 (+) megakaryocytelike DAMI cells and induced pluripotent stem cells (iPSCs) to the Pro33 allotype. CD41(+) megakaryocyte progenitors derived from these cells expressed the HPA-1b (Pl(A2)) alloantigenic epitope, as reported by diagnostic NciI restriction enzyme digestion, DNA sequencing, and western blot analysis using HPA-1b-specific human maternal alloantisera. Application of CRISPR/Cas9 technology to genetically edit this and other clinically-important HPAs holds great potential for production of designer platelets for diagnostic, investigative, and, ultimately, therapeutic use. © 2016 by The American Society of Hematology.

  12. 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.

  13. Modeling HIV-1 Induced Neuroinflammation in Mice: Role of Platelets in Mediating Blood-Brain Barrier Dysfunction.

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    Letitia D Jones

    Full Text Available The number of HIV-1 positive individuals developing some form of HIV-associated neurocognitive disorder (HAND is increasing. In these individuals, the integrity of the blood-brain barrier (BBB is compromised due to an increase in exposure to pro-inflammatory mediators, viral proteins, and virus released from infected cells. It has been shown that soluble CD40L (sCD40L is released upon platelet activation and is an important mediator of the pathogenesis of HAND but the underlying mechanisms are unclear, emphasizing the need of an effective animal model. Here, we have utilized a novel animal model in which wild-type (WT mice were infected with EcoHIV; a derivative of HIV-1 that contains a substitution of envelope protein gp120 with that of gp80 derived from murine leukemia virus-1 (MuLV-1. As early as two-weeks post-infection, EcoHIV led to increased permeability of the BBB associated with decreased expression of tight junction protein claudin-5, in CD40L and platelet activation-dependent manner. Treatment with an antiplatelet drug, eptifibatide, in EcoHIV-infected mice normalized BBB function, sCD40L release and platelet activity, thus implicating platelet activation and platelet-derived CD40L in virally induced BBB dysfunction. Our results also validate and underscore the importance of EcoHIV infection mouse model as a tool to explore therapeutic targets for HAND.

  14. Modeling HIV-1 Induced Neuroinflammation in Mice: Role of Platelets in Mediating Blood-Brain Barrier Dysfunction.

    Science.gov (United States)

    Jones, Letitia D; Jackson, Joseph W; Maggirwar, Sanjay B

    2016-01-01

    The number of HIV-1 positive individuals developing some form of HIV-associated neurocognitive disorder (HAND) is increasing. In these individuals, the integrity of the blood-brain barrier (BBB) is compromised due to an increase in exposure to pro-inflammatory mediators, viral proteins, and virus released from infected cells. It has been shown that soluble CD40L (sCD40L) is released upon platelet activation and is an important mediator of the pathogenesis of HAND but the underlying mechanisms are unclear, emphasizing the need of an effective animal model. Here, we have utilized a novel animal model in which wild-type (WT) mice were infected with EcoHIV; a derivative of HIV-1 that contains a substitution of envelope protein gp120 with that of gp80 derived from murine leukemia virus-1 (MuLV-1). As early as two-weeks post-infection, EcoHIV led to increased permeability of the BBB associated with decreased expression of tight junction protein claudin-5, in CD40L and platelet activation-dependent manner. Treatment with an antiplatelet drug, eptifibatide, in EcoHIV-infected mice normalized BBB function, sCD40L release and platelet activity, thus implicating platelet activation and platelet-derived CD40L in virally induced BBB dysfunction. Our results also validate and underscore the importance of EcoHIV infection mouse model as a tool to explore therapeutic targets for HAND.

  15. Purification and Characterization of BmooAi: A New Toxin from Bothrops moojeni Snake Venom That Inhibits Platelet Aggregation

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    Mayara Ribeiro de Queiroz

    2014-01-01

    Full Text Available In this paper, we describe the purification/characterization of BmooAi, a new toxin from Bothrops moojeni that inhibits platelet aggregation. The purification of BmooAi was carried out through three chromatographic steps (ion-exchange on a DEAE-Sephacel column, molecular exclusion on a Sephadex G-75 column, and reverse-phase HPLC chromatography on a C2/C18 column. BmooAi was homogeneous by SDS-PAGE and shown to be a single-chain protein of 15,000 Da. BmooAi was analysed by MALDI-TOF Spectrometry and revealed two major components with molecular masses 7824.4 and 7409.2 as well as a trace of protein with a molecular mass of 15,237.4 Da. Sequencing of BmooAi by Edman degradation showed two amino acid sequences: IRDFDPLTNAPENTA and ETEEGAEEGTQ, which revealed no homology to any known toxin from snake venom. BmooAi showed a rather specific inhibitory effect on platelet aggregation induced by collagen, adenosine diphosphate, or epinephrine in human platelet-rich plasma in a dose-dependent manner, whereas it had little or no effect on platelet aggregation induced by ristocetin. The effect on platelet aggregation induced by BmooAi remained active even when heated to 100°C. BmooAi could be of medical interest as a new tool for the development of novel therapeutic agents for the prevention and treatment of thrombotic disorders.

  16. 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

  17. Platelet antibody detection by flow cytometry: an effective method to evaluate and give transfusional support in platelet refractoriness

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    Carolina Bonet Bub

    2013-01-01

    Full Text Available BACKGROUND: Immune platelet refractoriness is mainly caused by human leukocyte antigen antibodies (80-90% of cases and, to a lesser extent, by human platelet antigen antibodies. Refractoriness can be diagnosed by laboratory tests and patients should receive compatible platelet transfusions. A fast, effective and low cost antibody-screening method which detects platelet human leukocyte/platelet antigen antibodies is essential in the management of immune platelet refractoriness. OBJECTIVE: The aim of this study was to evaluate the efficiency of the flow cytometry platelet immunofluorescence test to screen for immune platelet refractoriness. METHODS: A group of prospective hematologic patients with clinically suspected platelet refractoriness treated in a referral center in Campinas, SP during July 2006 and July 2011 was enrolled in this study. Platelet antibodies were screened using the flow cytometry platelet immunofluorescence test. Anti-human leukocyte antigen antibodies were detected by commercially available methods. The sensitivity, specificity and predictive values of the immunofluorescence test were determined taking into account that the majority of antiplatelet antibodies presented human leukocyte antigen specificity. RESULTS: Seventy-six samples from 32 female and 38 male patients with a median age of 43.5 years (range: 5-84 years were analyzed. The sensitivity of the test was 86.11% and specificity 75.00% with a positive predictive value of 75.61% and a negative predictive value of 85.71%. The accuracy of the method was 80.26%. CONCLUSION: This study shows that the flow cytometry platelet immunofluorescence test has a high correlation with the anti-human leukocyte antigen antibodies. Despite a few limitations, the method seems to be efficient, fast and feasible as the initial screening for platelet antibody detection and a useful tool to crossmatch platelets for the transfusional support of patients with immune platelet refractoriness.

  18. Co-stimulation with LPS or Poly I:C markedly enhances the anti-platelet immune response and severity of fetal and neonatal alloimmune thrombocytopenia.

    Science.gov (United States)

    Li, Conglei; Chen, Pingguo; Vadasz, Brian; Ma, Li; Zhou, Hui; Lang, Sean; Freedman, John; Ni, Heyu

    2013-12-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal antibodies against fetal/neonatal platelets. FNAIT is also linked with miscarriages, although the incidence and mechanisms of fetal death have not been well studied. IntegrinαIIbβ3 (GPIIbIIIa) and the GPIbα complex are major glycoproteins expressed on platelets and are also major antigens targeted in autoimmune thrombocytopenia (ITP), but reported cases of anti-GPIb-mediated FNAIT are rare. Bacterial and viral infections have been causally linked with the pathogenesis of immune-mediated thrombocytopenia (ITP); however, it is unknown whether these infections contribute to the severity of FNAIT. Here, immune responses against platelet antigens were examined by transfusing wild-type (WT) mouse platelets into β3-/- or GPIbα-/- mice. To mimic bacterial or viral infections, lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (Poly I:C) were injected intraperitoneally following platelet transfusions. The FNAIT model was established by breeding the immunised female mice with WT male mice. We demonstrated for the first time that the platelet GPIbα has lower immunogenicity compared to β3 integrin. Interestingly, co-stimulation with LPS or Poly I:C markedly enhanced the immune response against platelet GPIbα and caused severe pathology of FNAIT (i.e. miscarriages). LPS or Poly I:C also enhanced the immune response against platelet β3 integrin. Our data suggest that bacterial and viral infections facilitate the anti-platelet GPIbα response, which may lead to a severe non-classical FNAIT (i.e. miscarriage but not neonatal bleeding) that has not been adequately reported in humans.

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

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    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.

  20. 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.

  1. 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.

  2. Modified expression of surface glyconjugates in stored human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Dhar, A.; Ganguly, P.

    1987-05-01

    Platelets are anucleated cells which play an important part in blood coagulation and thrombosis. These cells may be stored in the blood bank for only 4/5 days. In order to improve the storage of platelets, it is essential to first understand the changes in these cells due to storage. In this work, human platelets were stored in autologous plasma at 4/sup 0/ or 22/sup 0/ and their surface changes were monitored with three lectins - wheat germ afflutinin (WGA), concanavalin A (Con A) and lentil lectin (LL). Blood was drawn from healthy donors and platelet rich plasma (PRP) was collected by slow speed centrifugation. Platelets stored at either temperature for different times showed increased sensitivity to agglutination by WGA after 34-48 hrs. Lectins, Con A and LL, which were not agglutinating to fresh platelets readily caused agglutination after 48-72 hrs. The platelets stored for 25 hrs or longer period were insensitive to thrombin but showed enhanced aggregation with WGA. Labelling of surface glycoconjugates of stored platelets with /sup 3/H-boro-hydride revealed progressive loss of a glycoprotein of Mr 150,000 (GPIb infinity) together with the appearance of components of Mr 69,000; Mr 60,000; Mr 25,000. New high molecular weight glycoproteins were also detected only in stored platelets. The author studies clearly indicate that modification or altered expression of platelets surface glycoproteins may be one factor of storage related dysfunction of platelets.

  3. 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.

  4. 2-Arachidonoylglycerol enhances platelet formation from human megakaryoblasts.

    Science.gov (United States)

    Gasperi, Valeria; Avigliano, Luciana; Evangelista, Daniela; Oddi, Sergio; Chiurchiù, Valerio; Lanuti, Mirko; Maccarrone, Mauro; Valeria Catani, Maria

    2014-01-01

    Platelets modulate vascular system integrity, and their loss is critical in haematological pathologies and after chemotherapy. Therefore, identification of molecules enhancing platelet production would be useful to counteract thrombocytopenia. We have previously shown that 2-arachidonoylglycerol (2-AG) acts as a true agonist of platelets, as well as it commits erythroid precursors toward the megakaryocytic lineage. Against this background, we sought to further interrogate the role of 2-AG in megakaryocyte/platelet physiology by investigating terminal differentiation, and subsequent thrombopoiesis. To this end, we used MEG-01 cells, a human megakaryoblastic cell line able to produce in vitro platelet-like particles. 2-AG increased the number of cells showing ruffled surface and enhanced surface expression of specific megakaryocyte/platelet surface antigens, typical hallmarks of terminal megakaryocytic differentiation and platelet production. Changes in cytoskeleton modeling also occurred in differentiated megakaryocytes and blebbing platelets. 2-AG acted by binding to CB1 and CB2 receptors, because specific antagonists reverted its effect. Platelets were split off from megakaryocytes and were functional: they contained the platelet-specific surface markers CD61 and CD49, whose levels increased following stimulation with a natural agonist like collagen. Given the importance of 2-AG for driving megakaryopoiesis and thrombopoiesis, not surprisingly we found that its hydrolytic enzymes were tightly controlled by classical inducers of megakaryocyte differentiation. In conclusion 2-AG, by triggering megakaryocyte maturation and platelet release, may have clinical efficacy to counteract thrombocytopenia-related diseases.

  5. [Mechanism of cooked blanched garlic leaves against platelet aggregation].

    Science.gov (United States)

    Wang, Xin-Hua; Di, Yan-Hui

    2014-06-01

    This study was purposed to explore the mechanism of cooked blanched garlic leave juice against platelet aggregation. The juice of blanched garlic leaves was mixed with platelet rich plasma (PRP), the human platelet aggregation, the activation of human platelets induced by adenosine diphosphate (ADP) and collagen were observed; the expression levels of the activated platelets (Fib-R) and P-selectin (CD62P), and the amount of platelet fibrinogen binding were detected by flow cytometry; 10 rabbits were randomly divided into two groups, in addition to the normal diet, they were fed with physiologic saline and cooked blanched garlic leave juice respectively. After 1, 3, 5 , 8 weeks, the maximum ratio of rabbit platelet aggregation induced by ADP and collagen were observed . The results showed that the cooked blanched garlic leave juice could significantly inhibit human platelet aggregation induced by ADP and collagen (P 0.05), but was able to inhibit platelet fibrinogen binding capacity (P garlic leave juice was significantly lower than that in control group (P garlic leave juice can inhibit platelet aggregation in vitro and in vivo, the inhibition of aggregation pathway mainly is blocking the combination of fibrinogen with Fib-R, which finally results in the inhibition of platelet aggregation. Therefore, regular consumption of cooked blanched garlic leaves may prevent cardiovascular thrombotic diseases.

  6. 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.

  7. Fractal analysis of circulating platelets in type 2 diabetic patients.

    Science.gov (United States)

    Bianciardi, G; Tanganelli, I

    2015-01-01

    This paper investigates the use of computerized fractal analysis for objective characterization by means of transmission electron microscopy of the complexity of circulating platelets collected from healthy individuals and from type 2 diabetic patients, a pathologic condition in which platelet hyperreactivity has been described. Platelet boundaries were extracted by means of automatically image analysis. Local fractal dimension by box counting (measure of geometric complexity) was automatically calculated. The results showed that the platelet boundary observed by electron microscopy is fractal and that the shape of the circulating platelets is significantly more complex in the diabetic patients in comparison to healthy subjects (p fractal analysis of platelet shape by transmission electron microscopy can provide accurate, quantitative, data to study platelet activation in diabetes mellitus.

  8. 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.

  9. Heparanase expression upregulates platelet adhesion activity and thrombogenicity

    Science.gov (United States)

    Österholm, Cecilia; Zhang, Xiao; Hedin, Ulf; Vlodavsky, Israel; Li, Jin-Ping

    2016-01-01

    Heparanase is an endo-glucuronidase that specifically cleaves heparan sulfate (HS) and heparin polysaccharides. The enzyme is expressed at low levels in normal tissues, but is often upregulated under pathological conditions such as cancer and inflammation. Normal human platelets express exceptionally high levels of heparanase, but the functional consequences of this feature remain unknown. We investigated functional roles of heparanase by comparing the properties of platelets expressing high (Hpa-tg) or low (Ctr) levels of heparanase. Upon activation, Hpa-tg platelets exhibited a much stronger adhesion activity as compared to Ctr platelets, likely contributing to a higher thrombotic activity in a carotid thrombosis model. Furthermore, we found concomitant upregulated expression of both heparanase and CD62P (P-selectin) upon activation of mouse and human platelets. As platelets play important roles in tumor metastasis, these findings indicate contribution of the platelet heparanase to hyper-thrombotic conditions often seen in patients with metastatic cancer. PMID:27129145

  10. Platelet gel for healing cutaneous chronic wounds.

    Science.gov (United States)

    Crovetti, Giovanni; Martinelli, Giovanna; Issi, Marwan; Barone, Marilde; Guizzardi, Marco; Campanati, Barbara; Moroni, Marco; Carabelli, Angelo

    2004-04-01

    Wound healing is a specific host immune response for restoration of tissue integrity. Experimental studies demonstrated an alteration of growth factors activity due to their reduced synthesis, increased degradation and inactivation. In wound healing platelets play an essential role since they are rich of alpha-granules growth factors (platelet derived growth factor--PDGF; transforming growth factor-beta--TGF-beta; vascular endothelial growth factor--VEGF). Topical use of platelet gel (PG), hemocomponent obtained from mix of activated platelets and cryoprecipitate, gives the exogenous and in situ adding of growth factors (GF). The hemocomponents are of autologous or homologous origin. We performed a technique based on: multicomponent apheretic procedure to obtain plasma rich platelet and cryoprecipitate; manual processing in an open system, in sterile environment, for gel activation. Every step of the gel synthesis was checked by a quality control programme. The therapeutic protocol consists of the once-weekly application of PG. Progressive reduction of the wound size, granulation tissue forming, wound bed detersion, regression and absence of infective processes were considered for evaluating clinical response to hemotherapy. 24 patients were enrolled. They had single or multiple cutaneous ulcers with different ethiopathogenesis. Only 3 patients could perform autologous withdrawal; in the others homologous hemocomponent were used, always considering suitability and traceability criteria for transfusional use of blood. Complete response was observed in 9 patients, 2 were subjected to cutaneous graft, 4 stopped treatment, 9 had partial response and are still receiving the treatment. In each case granulation tissue forming increased following to the first PG applications, while complete re-epithelization was obtained later. Pain was reduced in every treated patient. Topical haemotherapy with PG may be considered as an adjuvant treatment of a multidisciplinary process

  11. Diversity and Impact of Rare Variants in Genes Encoding the Platelet G Protein-Coupled Receptors

    Science.gov (United States)

    Jones, Matthew L.; Norman, Jane E.; Morgan, Neil V.; Mundell, Stuart J.; Lordkipanidzé, Marie; Lowe, Gillian C.; Daly, Martina E.; Simpson, Michael A.; Drake, Sian; Watson, Steve P.

    2015-01-01

    Summary Platelet responses to activating agonists are influenced by common population variants within or near G protein-coupled receptor (GPCR) genes that affect receptor activity. However, the impact of rare GPCR gene variants is unknown. We describe the rare single nucleotide variants (SNVs) in the coding and splice regions of 18 GPCR genes in 7,595 exomes from the 1,000-genomes and Exome Sequencing Project databases and in 31 cases with inherited platelet function disorders (IPFDs). In the population databases, the GPCR gene target regions contained 740 SNVs (318 synonymous, 410 missense, 7 stop gain and 6 splice region) of which 70% had global minor allele frequency (MAF) low individual frequencies, but are collectively abundant in the population. Potentially damaging variants are also present in pedigrees with IPFDs and may contribute to complex laboratory phenotypes. PMID:25567036

  12. Diversity and impact of rare variants in genes encoding the platelet G protein-coupled receptors.

    Science.gov (United States)

    Jones, Matthew L; Norman, Jane E; Morgan, Neil V; Mundell, Stuart J; Lordkipanidzé, Marie; Lowe, Gillian C; Daly, Martina E; Simpson, Michael A; Drake, Sian; Watson, Steve P; Mumford, Andrew D

    2015-04-01

    Platelet responses to activating agonists are influenced by common population variants within or near G protein-coupled receptor (GPCR) genes that affect receptor activity. However, the impact of rare GPCR gene variants is unknown. We describe the rare single nucleotide variants (SNVs) in the coding and splice regions of 18 GPCR genes in 7,595 exomes from the 1,000-genomes and Exome Sequencing Project databases and in 31 cases with inherited platelet function disorders (IPFDs). In the population databases, the GPCR gene target regions contained 740 SNVs (318 synonymous, 410 missense, 7 stop gain and 6 splice region) of which 70 % had global minor allele frequency (MAF) low individual frequencies, but are collectively abundant in the population. Potentially damaging variants are also present in pedigrees with IPFDs and may contribute to complex laboratory phenotypes.

  13. STUDY OF SIGNIFICANCE OF PLATELET COUNT IN FEVER CASES

    Directory of Open Access Journals (Sweden)

    Vasavilatha

    2015-01-01

    diagnosis difficult. This highlights the importance of thrombocytopenia in various febrile disorder s. Hence, there is a need for study to know the importance of platelet count estimation in all types of fever as a basic investigation to establish correct diagnosis and prevent fatal outcome

  14. Low density and high affinity of platelet [3H]paroxetine binding in women with bulimia nervosa.

    Science.gov (United States)

    Ekman, Agneta; Sundblad-Elverfors, Charlotta; Landén, Mikael; Eriksson, Tomas; Eriksson, Elias

    2006-06-15

    Impaired serotonin transmission has been suggested to be implicated in the pathophysiology of bulimia nervosa. As an indirect measure of brain serotonergic activity, the binding of tritiated ligands to platelet serotonin transporters has been studied in bulimia nervosa as well as in other putatively serotonin-related psychiatric disorders. In this study, the density and affinity of platelet serotonin transporters were assessed in 20 women meeting the DSM-IV criteria for bulimia nervosa and in 14 controls without previous or ongoing eating disorder using [(3)H]paroxetine as a ligand. In comparison to controls, women with bulimia nervosa had a significantly reduced number of platelet binding sites (B(max) = 721 +/- 313 vs. 1145 +/- 293 fmol/mg protein) and an increase in the affinity for the ligand demonstrated by a lower dissociaton constant (K(d) = 33 +/- 10 vs. 44 +/- 10 pM). A significant correlation between B(max) and K(d) values was found in patients but not in controls. Our results support the notion that bulimia nervosa is associated with a reduction in platelet serotonin transporter density. In addition, our study is the first to report that this reduced transporter density in women with bulimia nervosa is accompanied by an increase in the affinity of the transporter for the ligand.

  15. Mechanisms of Alloimmunization and Subsequent Bone Marrow Transplantation Rejection Induced by Platelet Transfusion in a Murine Model

    Science.gov (United States)

    Patel, Seema R; Smith, Nicole H; Kapp, Linda; Zimring, James C

    2015-01-01

    For many non-malignant hematological disorders, HLA-matched bone marrow transplantation (BMT) is curative. However, due to lack of neoplasia, the toxicity of stringent conditioning regimens is difficult to justify, and reduced-intensity conditioning is used. Unfortunately, current reduced-intensity regimens have high rates of BMT rejection. We have recently reported in a murine model that mHAs on transfused platelet products induce subsequent BMT rejection. Most non-malignant hematological disorders require transfusion support prior to BMT and the rate of BMT rejection in humans correlates to the number of transfusions given. Herein, we perform a mechanistic analysis of platelet transfusion induced BMT rejection and report that unlike exposure to alloantigens during transplantation, platelet transfusion primes alloimmunity but does not stimulate full effector function. Subsequent BMT is itself an additional and distinct immunizing event, which does not induce rejection without antecedent priming from transfusion. Both CD4+ and CD8+ T cells are required for priming during platelet transfusion, but only CD8+ T cells are required for BMT rejection. In neither case are antibodies required for rejection to occur. PMID:22300526

  16. Thrombocytopenia, bleeding, and use of platelet transfusions in sick neonates.

    Science.gov (United States)

    Stanworth, Simon J

    2012-01-01

    Survival rates for infants born prematurely have improved significantly, in part due to better supportive care such as RBC transfusion. The role of platelet transfusions in neonates is more controversial. Neonatal thrombocytopenia is common in premature infants. The primary causal factors are intrauterine growth restriction/maternal hypertension, in which the infant presents with thrombocytopenia soon after birth, and sepsis/necrotizing enterocolitis, which are the common morbidities associated with thrombocytopenia in neonates > 72 hours of age. There is no evidence of a relationship between platelet count and occurrence of major hemorrhage, and cardiorespiratory problems are considered the main etiological factors in the development of intraventricular and periventricular hemorrhage in the neonatal period. Platelet transfusions are used commonly as prophylaxis in premature neonates with thrombocytopenia. However, there is widespread variation in the pretransfusion thresholds for platelet count and evidence of marked disparities in platelet transfusion practice between hospitals and countries. Platelet transfusions are biological agents and as such are associated with risks. Unlike other patient groups, specifically patients with hematological malignancies, there have been no recent clinical trials undertaken comparing different thresholds for platelet transfusion in premature neonates. Therefore, there is no evidence base with which to inform safe and effective practice for prophylactic platelet transfusions. There is a need for randomized controlled trials to define the optimal use of platelet transfusions in premature neonates, who at present are transfused heavily with platelets.

  17. Transporters in human platelets: physiologic function and impact for pharmacotherapy.

    Science.gov (United States)

    Jedlitschky, Gabriele; Greinacher, Andreas; Kroemer, Heyo K

    2012-04-12

    Platelets store signaling molecules (eg, serotonin and ADP) within their granules. Transporters mediate accumulation of these molecules in platelet granules and, on platelet activation, their translocation across the plasma membrane. The balance between transporter-mediated uptake and elimination of signaling molecules and drugs in platelets determines their intracellular concentrations and effects. Several members of the 2 major transporter families, ATP-binding cassette (ABC) transporters and solute carriers (SLCs), have been identified in platelets. An example of an ABC transporter is MRP4 (ABCC4), which facilitates ADP accumulation in dense granules. MRP4 is a versatile transporter, and various additional functions have been proposed, notably lipid mediator release and a role in aspirin resistance. Several other ABC proteins have been detected in platelets with functions in glutathione and lipid homeostasis. The serotonin transporter (SERT, SLC6A4) in the platelet plasma membrane represents a well-characterized example of the SLC family. Moreover, recent experiments indicate expression of OATP2B1 (SLCO2B1), a high affinity transporter for certain statins, in platelets. Changes in transporter localization and expression can affect platelet function and drug sensitivity. This review summarizes available data on the physiologic and pharmacologic role of transporters in platelets.

  18. Determinants of ABH expression on human blood platelets.

    Science.gov (United States)

    Cooling, Laura L W; Kelly, Kathleen; Barton, James; Hwang, Debbie; Koerner, Theodore A W; Olson, John D

    2005-04-15

    Platelets express ABH antigens, which can adversely effect platelet transfusion recovery and survival in ABH-incompatible recipients. To date, there has been no large, comprehensive study comparing specific donor factors with ABH expression on platelet membranes and glycoconjugates. We studied ABH expression in 166 group A apheresis platelet donors by flow cytometry, Western blotting, and thin layer chromatography relative to donor age, sex, A1/A2 subgroup, and Lewis phenotype. Overall, A antigen on platelet membranes, glycoproteins, and glycosphingolipids was linked to an A1 red blood cell (RBC) phenotype. Among A1 donors, platelet ABH varied significantly between donors (0%-87%). Intradonor variability, however, was minimal, suggesting that platelet ABH expression is a stable, donor-specific characteristic, with 5% of A1 donors typing as either ABH high- or low-expressers. Group A2 donors, in contrast, possessed a Bombay-like phenotype, lacking both A and H antigens. Unlike RBCs, ABH expression on platelets may be determined primarily by H-glycosyltransferase (FUT1) activity. Identification of A2 and A1 low expressers may increase the availability and selection of crossmatched and HLA-matched platelets. Platelets from group A2 may also be a superior product for patients undergoing A/O major mismatch allogeneic progenitor cell transplantation.

  19. Morphometric analysis of density subpopulations of normal human platelets.

    Science.gov (United States)

    Chamberlain, K G; Froebel, M; Macpherson, J; Penington, D G

    1988-08-30

    Platelets from seven normal subjects were fractionated on continuous Percoll density gradients and low density (LD), intermediate, and high density (HD) platelets were prepared for transmission electron microscopy followed by computerised morphometric analysis. Normal ultrastructural appearance and discoid shape were preserved by incubation of the platelets in nutrient medium at 37 degrees C immediately before fixation. HD platelet sections had a larger mean cross-sectional area but a lower ratio of the major to the minor axis compared to LD platelet sections. HD platelets contained more alpha granules, dense granules and mitochondria per square micron of section area than LD platelets. The percentage of section area occupied by open canalicular system was greater in the LD platelets while the percentage area occupied by glycogen fields was over ten-fold higher in the HD platelets. The mean cross-sectional areas of individual alpha granules and dense granules increased with density while the opposite trend was found for mitochondria. It is suggested that these ultrastructural differences mainly arise during thrombopoiesis and may indicate some functional specialization among platelets.

  20. Platelet reactions to modified surfaces under dynamic conditions.

    Science.gov (United States)

    Rhodes, N P; Shortland, A P; Rattray, A; Williams, D F

    1998-12-01

    The influence of surfaces on the reactions of platelets in whole blood under laminar flow was investigated in a cone and plate viscometer. Citrated whole blood was exposed to steel, PMMA and PMMA modified with PEO at low (500 s(-1)) and high (4000 s(-1)) wall shear rates at room temperature for a period of 100 s. Treated blood samples were fixed with paraformaldehyde, stained with a monoclonal antibody for CD41 (platelet GPIIb/IIIa) conjugated with phycoerythrin and analyzed by flow cytometry. The reactions of platelets (microparticle generation and formation of platelet-platelet, platelet-red blood cell and red blood cell-microparticle aggregates) to these environments were quantified. Additionally, the size of platelet-platelet aggregates was assessed. The percentage platelet aggregation and numbers of microparticles generated were independent of surface type at any shear rate. The composition of the aggregates formed was influenced by the surface: at low and high shear rates PMMA caused the generation of platelet-platelet aggregates of the greatest size. The numbers of red blood cell-platelet and red blood cell-microparticle aggregates also varied depending on the surface. Fewer red blood cell-platelet aggregates were formed at higher shear rates, whereas the reverse was true for red blood cell-microparticle aggregates. It is concluded that these variations may help to explain the differential effects of surfaces to the induction of distant thrombotic events: microparticles may be protected from loss from the blood stream by their association with red blood cells at high shear rates.

  1. A novel inflammatory role for platelets in sickle cell disease.

    Science.gov (United States)

    Davila, Jennifer; Manwani, Deepa; Vasovic, Ljiljana; Avanzi, Mauro; Uehlinger, Joan; Ireland, Karen; Mitchell, W Beau

    2015-01-01

    The severe pain, ischemia and organ damage that characterizes sickle cell disease (SCD) is caused by vaso-occlusion, which is the blockage of blood vessels by heterotypic aggregates of sickled erythrocytes and other cells. Vaso-occlusion is also a vasculopathy involving endothelial cell dysfunction, leukocyte activation, platelet activation and chronic inflammation resulting in the multiple adhesive interactions between cellular elements. Since platelets mediate inflammation as well as thrombosis via release of pro- and anti-inflammatory molecules, we hypothesized that platelets may play an active inflammatory role in SCD by secreting increased amounts of cytokines. Since platelets have been shown to contain mRNA and actively produce proteins, we also hypothesized that SCD platelets may contain increased cytokine mRNA. In this cross-sectional study, we sought to compare both the quantity of cytokines secreted and the cytokine mRNA content, between SCD and control platelets. We measured the secretion of Th1, Th2, and Th17-related cytokines from platelets in a cohort of SCD patients. We simultaneously measured platelet mRNA levels of those cytokines. Platelets from SCD patients secreted increased quantities of IL-1β, sCD40L, and IL-6 compared to controls. Secretion was increased in patients with alloantibodies. Additionally, mRNA of those cytokines was increased in SCD platelets. Platelets from sickle cell patients secrete increased amounts of inflammatory cytokines, and contain increased cytokine mRNA. These findings suggest a novel immunological role for platelets in SCD vasculopathy, in addition to their thrombotic role, and strengthen the rationale for the use of anti-platelet therapy in SCD.

  2. Megakaryocytes and platelets express nicotinic acetylcholine receptors but nicotine does not affect megakaryopoiesis or platelet function.

    Science.gov (United States)

    Schedel, Angelika; Kaiser, Kerstin; Uhlig, Stefanie; Lorenz, Florian; Sarin, Anip; Starigk, Julian; Hassmann, Dennis; Bieback, Karen; Bugert, Peter

    2016-01-01

    In our previous investigations we have shown that platelets and their precursors express nicotinic α7 acetylcholine receptors (nAChRα7) that are involved in platelet function and in vitro differentiation of the megakaryoblastic cell line MEG-01. In this study, we were interested in the expression analysis of additional nAChR and the effects of nicotine in an ex vivo model using megakaryocytic cells differentiated from cord blood derived CD34(+) cells (CBMK) and an in vivo model using blood samples from smokers. CBMK were differentiated with thrombopoietin (TPO) for up to 17 days. Quantitative real-time PCR (QRT-PCR), Western blot analysis and flow cytometry were used to investigate nAChR expression (nAChRα7, nAChRα4, nAChRβ2) and nicotine effects. In blood samples of 15 nonsmokers and 16 smokers platelet parameters (count, mean platelet volume--MPV and platelet distribution width--PDW) were determined as indicators for changes of in vivo megakaryopoiesis. Platelet function was determined by the use of whole blood aggregometry and flow cytometry. The functional role of nAChR was evaluated using specific antagonists in aggregometry. CHRNA7, CHRNA4 and CHRNB2 gene transcripts and the corresponding proteins could be identified in CBMK during all stages of differentiation. Platelets contain nAChRα7 and nAChRβ2 but not nAChRα4. Nicotine had no effect on TPO-induced differentiation of CBMK. There was no significant difference in all platelet parameters of the smokers compared to the nonsmokers. In line with this, cholinergic gene transcripts as well as the encoded proteins were equally expressed in both the study groups. Despite our observation of nAChR expression in megakaryopoiesis and platelets, we were not able to detect effects of nicotine in our ex vivo and in vivo models. Thus, the functional role of the nAChR in these cells remains open.

  3. A Novel Platelet Concentrate: Titanium-Prepared Platelet-Rich Fibrin

    Directory of Open Access Journals (Sweden)

    Mustafa Tunalı

    2014-01-01

    Full Text Available We developed a new product called titanium-prepared platelet-rich fibrin (T-PRF. The T-PRF method is based on the hypothesis that titanium may be more effective in activating platelets than the silica activators used with glass tubes in Chouckroun’s leukocyte- and platelet-rich fibrin (L-PRF method. In this study, we aimed to define the structural characteristics of T-PRF and compare it with L-PRF. Blood samples were collected from 10 healthy male volunteers. The blood samples were drawn using a syringe. Nine milliliters was transferred to a dry glass tube, and 9 mL was transferred to a titanium tube. Half of each clot (i.e., the blood that was clotted using T-PRF or L-PRF was processed with a scanning electron microscope (SEM. The other half of each clot was processed for fluorescence microscopy analysis and light microscopy analysis. The T-PRF samples seemed to have a highly organized network with continuous integrity compared to the other L-PRF samples. Histomorphometric analysis showed that T-PRF fibrin network covers larger area than L-PRF fibrin network; also fibrin seemed thicker in the T-PRF samples. This is the first human study to define T-PRF as an autogenous leukocyte- and platelet-rich fibrin product. The platelet activation by titanium seems to offer some high characteristics to T-PRF.

  4. A novel platelet concentrate: titanium-prepared platelet-rich fibrin.

    Science.gov (United States)

    Tunalı, Mustafa; Özdemir, Hakan; Küçükodacı, Zafer; Akman, Serhan; Yaprak, Emre; Toker, Hülya; Fıratlı, Erhan

    2014-01-01

    We developed a new product called titanium-prepared platelet-rich fibrin (T-PRF). The T-PRF method is based on the hypothesis that titanium may be more effective in activating platelets than the silica activators used with glass tubes in Chouckroun's leukocyte- and platelet-rich fibrin (L-PRF) method. In this study, we aimed to define the structural characteristics of T-PRF and compare it with L-PRF. Blood samples were collected from 10 healthy male volunteers. The blood samples were drawn using a syringe. Nine milliliters was transferred to a dry glass tube, and 9 mL was transferred to a titanium tube. Half of each clot (i.e., the blood that was clotted using T-PRF or L-PRF) was processed with a scanning electron microscope (SEM). The other half of each clot was processed for fluorescence microscopy analysis and light microscopy analysis. The T-PRF samples seemed to have a highly organized network with continuous integrity compared to the other L-PRF samples. Histomorphometric analysis showed that T-PRF fibrin network covers larger area than L-PRF fibrin network; also fibrin seemed thicker in the T-PRF samples. This is the first human study to define T-PRF as an autogenous leukocyte- and platelet-rich fibrin product. The platelet activation by titanium seems to offer some high characteristics to T-PRF.

  5. Characterization of human platelet glutathione reductase.

    Science.gov (United States)

    Moroff, G; Kosow, D P

    1978-12-08

    Glutathione reductase (NAD(P)h:oxidized glutathione oxidoreductase, EC 1.6.4.2) has been purified 1000-fold from the cytoplasmic fraction of human platelets. Salts, including the heretofore unreported effect of sodium citrate, activate the NADPH-dependent reduction of oxidized glutathione. Sodium citrate and monovalent salt activation appears to involve multiple sites having different binding affinities. At sub-saturating sodium phosphate, non-linear double reciprocal plots indicative of substrate activation by oxidized glutathione were observed. Initial velocity double reciprocal plots at sub-saturating and saturating concentrations of phosphate generate a family of converging lines. NADP+ is a partial inhibitor, indicating that the reduction of oxidized glutathione can proceed by more than one pathway. FMN, FAD, and riboflavin inhibit platelet glutathione reductase by influencing only the V while nitrofurantoin inhibition is associated with an increase Koxidized glutathione and a decreased V.

  6. Platelet Parameters in Hepatic Hydatid Cysts

    Directory of Open Access Journals (Sweden)

    Mustafa Sit

    2013-01-01

    Full Text Available Background. Hepatic hydatid cyst infection is caused by microorganisms named Echinococcus which belong to family Taeniidae. Platelets are considered as a mediator in inflammation and infectious diseases because of the various proinflammatory substances that they contain. Design and Methods. Thirty-three patients who were admitted to Doğubayazıt State Hospital’s General Surgery Clinic with a diagnosis of hepatic cyst hydatid were enrolled in this retrospective study. Laboratory data of the patients in pre- and postoperative periods were obtained from computerized medical records database of the hospital. Results. Preoperative mean platelet volume (MPV of the patients was significantly increased compared to postoperative MPV values. Conclusion. We claim that MPV is a useful follow-up marker after surgery in patients with hydatid cyst.

  7. Platelet Rich Plasma and Knee Surgery

    Directory of Open Access Journals (Sweden)

    Mikel Sánchez

    2014-01-01

    Full Text Available In orthopaedic surgery and sports medicine, the knee joint has traditionally been considered the workhorse. The reconstruction of every damaged element in this joint is crucial in achieving the surgeon’s goal to restore the knee function and prevent degeneration towards osteoarthritis. In the last fifteen years, the field of regenerative medicine is witnessing a boost of autologous blood-derived platelet rich plasma products (PRPs application to effectively mimic and accelerate the tissue healing process. The scientific rationale behind PRPs is the delivery of growth factors, cytokines, and adhesive proteins present in platelets and plasma, as well as other biologically active proteins conveyed by the plasma such as fibrinogen, prothrombin, and fibronectin; with this biological engineering approach, new perspectives in knee surgery were opened. This work describes the use of PRP to construct and repair every single anatomical structure involved in knee surgery, detailing the process conducted in ligament, meniscal, and chondral surgery.

  8. Platelet factor XIII increases the fibrinolytic resistance of platelet-rich clots by accelerating the crosslinking of alpha 2-antiplasmin to fibrin

    Science.gov (United States)

    Reed, G. L.; Matsueda, G. R.; Haber, E.

    1992-01-01

    Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha 2-antiplasmin (alpha 2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha 2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha 2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha 2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha 2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis.

  9. Role of nitric oxide synthase in collagen-platelet interaction: involvement of platelet nonintegrin collagen receptor nitrotyrosylation.

    Science.gov (United States)

    Chiang, T M; Cole, F; Woo-Rasberry, V; Kang, E S

    2001-05-15

    Platelets possess the endothelial isoform of nitric oxide synthase (eNOS), which plays an important role in platelet function. Other laboratories, including ours, have reported that nitric oxide (NO) is released upon exposure of platelets to collagen, but the mechanism of the interaction is not yet established. The objective of this study is to examine the possible role of nonintegrin receptor nitrotyrosylation on collagen-induced platelet aggregation. Results of the study show that two platelet proteins with M(r) of 65- and 23-kDa proteins are nitrotyrosylated in a time-dependent manner after the addition of type I collagen. The M(r) 65-kDa protein is identified as the platelet receptor for type I collagen. The recombinant protein of the platelet receptor for type I collagen can also be nitrotyrosylated. The nitrotyrosylated recombinant protein loses its ability to inhibit type I collagen-induced platelet aggregation. In addition, the polyclonal anti-65 kDa immunoprecipitates eNOS suggesting that the platelet nonintegrin receptor for type I collagen is closely linked to the eNOS. These results demonstrate that the inhibitory effect of NO on collagen-induced platelet aggregation may be mediated by the nitrotyrosylation of the 65-kDa receptor.

  10. 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.

  11. The relationship between fractional flow reserve, platelet reactivity and platelet leukocyte complexes in stable coronary artery disease.

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    Jan-Willem E M Sels

    Full Text Available BACKGROUND: The presence of stenoses that significantly impair blood flow and cause myocardial ischemia negatively affects prognosis of patients with stable coronary artery disease. Altered platelet reactivity has been associated with impaired prognosis of stable coronary artery disease. Platelets are activated and form complexes with leukocytes in response to microshear gradients caused by friction forces on the arterial wall or flow separation. We hypothesized that the presence of significantly flow-limiting stenoses is associated with altered platelet reactivity and formation of platelet-leukocyte complexes. METHODS: One hundred patients with stable angina were studied. Hemodynamic significance of all coronary stenoses was assessed with Fractional Flow Reserve (FFR. Patients were classified FFR-positive (at least one lesion with FFR≤0.75 or FFR-negative (all lesions FFR>0.80. Whole blood samples were stimulated with increasing concentrations of ADP, TRAP, CRP and Iloprost with substimulatory ADP. Expression of P-selectin as platelet activation marker and platelet-leukocyte complexes were measured by flowcytometry. Patients were stratified on clopidogrel use. FFR positive and negative patient groups were compared on platelet reactivity and platelet-leukocyte complexes. RESULTS: Platelet reactivity between FFR-positive patients and FFR-negative patients did not differ. A significantly lower percentage of circulating platelet-neutrophil complexes in FFR-positive patients and a similar non-significant decrease in percentage of circulating platelet-monocyte complexes in FFR-positive patients was observed. CONCLUSION: The presence of hemodynamically significant coronary stenoses does not alter platelet reactivity but is associated with reduced platelet-neutrophil complexes in peripheral blood of patients with stable coronary artery disease.

  12. Kaempferol inhibits thrombosis and platelet activation.

    Science.gov (United States)

    Choi, Jun-Hui; Park, Se-Eun; Kim, Sung-Jun; Kim, Seung

    2015-08-01

    The objectives of the present study were to investigate whether kaempferol affects pro-coagulant proteinase activity, fibrin clot formation, blood clot and thrombin (or collagen/epinephrine)-stimulated platelet activation, thrombosis, and coagulation in ICR (Imprinting Control Region) mice and SD (Sprague-Dawley) rats. Kaempferol significantly inhibited the enzymatic activities of thrombin and FXa by 68 ± 1.6% and 52 ± 2.4%, respectively. Kaempferol also inhibited fibrin polymer formation in turbidity. Microscopic analysis was performed using a fluorescent conjugate. Kaempferol completely attenuated phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and phosphoinositide 3-kinase (PI3K)/PKB (AKT) in thrombin-stimulated platelets and delayed aggregation time (clotting) by 34.6% in an assay of collagen/epinephrine-stimulated platelet activation. Moreover, kaempferol protected against thrombosis development in 3 animal models, including collagen/epinephrine- and thrombin-induced acute thromboembolism models and an FeCl3-induced carotid arterial thrombus model. The ex vivo anticoagulant effect of kaempferol was further confirmed in ICR mice. This study demonstrated that kaempferol may be clinically useful due to its ability to reduce or prevent thrombotic challenge.

  13. [Indications and surveillance of platelet transfusions in surgery].

    Science.gov (United States)

    Coffe, C; Bardiaux, L; Couteret, Y; Devillers, M; Leroy, M; Morel, P; Pouthier-Stein, F; Hervé, P

    1995-01-01

    Surgery, after hematology, is the biggest consumer of homologous platelet concentrates. Platelet transfusion is indicated to prevent or control bleeding associated with deficiencies in platelet number or function. In surgery, general patterns (in function of pre-surgery platelet count) can be adopted in most of the indications for platelets. In emergency situations, and in some particular cases (related to the patient, the type of operation, etc.), the transfusion procedure depends on the team's experience, the results of the available clinical and biological tests, and the drugs. Strict monitoring is required during the transfusion procedure. The efficacy of the transfusion must be controlled 1 h and 24 hours after the transfusion, and a number of factors must be assessed, namely the immunological impact of the transfusion (on red blood cells, leukocytes and platelets) and the occurrence of infectious diseases transmitted via transfusion. In addition, for a possible future transfusion, a strategy must be proposed.

  14. Monitoring aspirin therapy with the Platelet Function Analyzer-100

    DEFF Research Database (Denmark)

    Mortensen, Jette; Poulsen, Tina Svenstrup; Grove, Erik Lerkevang;

    2008-01-01

    OBJECTIVE: Low platelet response to aspirin has been reported to be associated with a high incidence of vascular events. The reported prevalence of aspirin low-responsiveness varies, which may be explained by poor reproducibility of the methods used to evaluate aspirin response and low compliance....... The Platelet Function Analyzer-100 (PFA-100) is a commonly used platelet function test. We aimed to assess the reproducibility of the PFA-100 and the agreement with optical platelet aggregometry (OPA) in healthy volunteers and in patients with coronary artery disease (CAD) treated with low-dose aspirin....... MATERIAL AND METHODS: Twenty-one healthy volunteers and 43 patients with CAD took part in the study. During treatment with aspirin 75 mg daily, all participants had platelet function assessed in duplicate with the PFA-100 and OPA on 4 consecutive days. Additionally, platelet function was assessed before...

  15. 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.

  16. 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.

  17. 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.

  18. Platelet subpopulation bearing leukocyte specific antigen and tissue factor.

    Science.gov (United States)

    Gabbasov, Z A; Saburova, O S; Antonova, O A; Golubeva, N V; Khaspekova, S G; Shustova, O N; Zyuryaev, I T; Ruda, M Ya; Mazurov, A V

    2016-11-01

    Platelets bearing leukocyte antigen CD45 were identified in the blood of patients with myocardial infarction (MI) and healthy donors by flow cytofluorimetry. Part of these platelets contained tissue factor (TF)-primary initiator of blood clotting. The number of CD45(+) and CD45(+)/TF(+) platelets in MI patients at the first day was comparable with their level in healthy donors, but was increased at 8-12 days after MI onset. At that time in some patients the amount of CD45(+) and CD45(+)/TF(+) platelets reached 5-6 and 2-3% of their total number. It is assumed that CD45(+)/TF(+) platelets could be formed as a result of platelet interaction with leukocytes or leukocyte produced membrane microparticles.

  19. Heparin platelet factor 4 antibody positivity in pseudothrombocytopenia.

    Science.gov (United States)

    Balcik, Ozlem Sahin; Akdeniz, Derya; Cipil, Handan; Uysal, Sema; Isik, Ayse; Kosar, Ali

    2012-01-01

    Pseudothrombocytopenia (PTCP) is a laboratory event of platelet clustering related to drugs used for anticoagulation. This condition is engendered by autoantibodies against platelets in usually EDTA-anticoagulated blood. Pseudothrombocytopenia has no clinical significance but when evaluated as true thrombocytopenia, this misconception may lead to unnecessary diagnostic procedures. Heparin-induced thrombocytopenia with thrombosis (HITT) is a complication of heparin treatment caused by heparin platelet factor 4 (HPF-4) antibodies, leading to platelet activation and hypercoagulability. In our study, 48 patients with PTCP and 36 healthy volunteers were included. Heparin platelet factor 4 antibody positivity was detected in 12 patients from PTCP group; nobody from control group had. Citrated serum samples and peripheral blood smears showed normal platelet count. Of the 4 patients using heparin derivative, 1 (2.1%) had antibody positivity but without any bleeding symptoms. In conclusion, HPF-4 antibody positivity might be a risk factor for PTCP. Clinicians should be aware of this kind of condition.

  20. [A case of pseudothrombocytopenia due to platelet cold agglutinins].

    Science.gov (United States)

    Hayashi, Satoru; Nishiyama, Miho; Jouzaki, Kiyoshi; Tomiyama, Yoshiaki; Kurata, Yoshiyuki

    2005-08-01

    We report a case of pseudothrombocytopenia due to platelet cold agglutinins. Platelet counts were decreased in blood drawn in a tube without anti-coagulant just after withdrawal as well as in blood drawn in a tube with anti-coagulant, such as EDTA-2K, MgSO4, citrate or heparin. In our case, platelet aggregates were noted on blood-smear made from blood samples obtained with and without anti-coagulant. RBC and WBC counts were within the normal range. Platelet aggregates mainly consisted of 2-5 platelets. Patient plasma agglutinated normal platelets at a temperature below 10 degrees C. Immunoglobulin class was determined as IgM by flow cytometry.

  1. Preoperative elevated platelet count and thrombocytosis in gynecologic malignancies.

    Science.gov (United States)

    Menczer, Joseph

    2017-01-01

    Platelets have multiple functions and they also play an important role in malignancies. Elevated platelet count and thrombocytosis at the time of diagnosis in patients with many solid tumors correlates with prognosis and is associated with poor survival. The aim of the following report is to review the literature concerning elevated platelet count and thrombocytosis in gynecologic malignancies. A PubMed search of all English literature peer-reviewed publications was performed containing the terms elevated platelet count or thrombocytosis and vulvar cancer, cervical cancer, endometrial cancer, and ovarian cancer. All studies published until December 31, 2015, were included in the following review. A pretreatment elevated platelet count and thrombocytosis have been shown to be associated with a poor prognosis in many studies of gynecologic malignancies with the exception of vulvar carcinoma. Since elevated platelet count and thrombocytosis may be prevented by blocking thrombopoietic cytokines, their assessment may, in the future, be of therapeutic significance.

  2. Successful treatment of de Quervain tenosynovitis with ultrasound-guided percutaneous needle tenotomy and platelet-rich plasma injection: a case presentation.

    Science.gov (United States)

    Peck, Evan; Ely, Erin

    2013-05-01

    De Quervain tenosynovitis is a disorder of the tendons of the first dorsal compartment of the wrist that causes pain and functional disability, which may be refractory to conservative treatments. We present a case of ultrasound-guided percutaneous needle tenotomy and platelet-rich plasma injection for the successful treatment of de Quervain tenosynovitis.

  3. /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.

  4. Increased platelet aggregability following an atherogenic diet in rabbits

    OpenAIRE

    Velkovski Saško D.; Mazić Sanja; Nešić Dejan M.; Igrački Iva; Milošević Verica L.; Starčević Vesna P.

    2002-01-01

    In atherosclerosis researches different animal models are used but the most common is the rabbit, because of the easy development of atherosclerotic lesions. Atherosclerosis is a multicellular process and platelets play an important role in atherogenesis. Excessive plasma lipids stimulate platelet aggregability and thus atherosclerosis development. The effects of an atherogenic diet on lipid status, abdominal aorta wall structure, and platelet aggregability were studied in rabbits. Adult male...

  5. Plasma functionalization of titanium surface for repulsion of blood platelets

    OpenAIRE

    Cvelbar, Uros; Modic, Martina; Kovac, J.; Lazovic, S; Filipic, G; Vujosevic, D; Junkar, Ita; Elersic, Kristina; Brühl, S.P.; Canal Barnils, Cristina; Belmonte, Thierry; Mozetic, Miran

    2012-01-01

    Thrombosis and restenosis are the most common problems during insertion of biocompatible implants like titanium stents into human blood, due to aggregation of platelets on their surfaces. Because of this reason, we studied the response of blood platelets to a plasma treated titanium surface. The aim was to design a functionalized surface which would repel blood platelets or prevent their adhesion. Therefore, we functionalized surfaces with low-temperature inductively coupled oxygen plasma tre...

  6. Role of platelets in the pathogenesis of antiphospholipid syndrome

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    NK Singh

    2013-07-01

    Full Text Available AimTo delineate the role of platelets in thrombotic process in APS patients.BackgroundPathogenesis of APS is an ongoing area of research and studying the role of platelets will be helpful in developing newer diagnostic and therapeutic strategies.Materials and methodsForty patients with APS, diagnosed as per modified 2006 Sapporo’s Criteria and who were not on aspirin or any other antiplatelet drug, were included. The same number of age- and sex-matched healthy controls was also recruited for comparison. The following platelet function studies were performed using the blood samples collected from APS patients as well as healthy controls: platelet aggregation studies, platelet secretion of dense granules (a. total degranulation b. platelet secretion of granules in relation to time c. visualization of platelet degranulation, clot retraction studies, and western blot studies on clot retracted samples for demonstration of activated proteomes.ResultsA significant increase (P < 0.001 in the platelet aggregation in APS patients as compared to healthy controls was noted. The subjects also showed a significant increase (P < 0.05 in the platelet granule release as well as more degranulation (P < 0.001 in relation to time at stored condition, which were well-visualized under phase-contrast microscope. Sixty-five percent of APS patients showed lesser as well as delayed clot retraction as compared to healthy controls, signifying that the platelet clots are less retractile in APS patients.ConclusionThe study clearly demonstrates the hyperactivity of platelets in APS patients in each step of their activation as compared to the controls. This indicates the major role played by platelets in APS pathogenesis.

  7. 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.

  8. Morphological and functional platelet abnormalities in Berkeley sickle cell mice.

    Science.gov (United States)

    Shet, Arun S; Hoffmann, Thomas J; Jirouskova, Marketa; Janczak, Christin A; Stevens, Jacqueline R M; Adamson, Adewole; Mohandas, Narla; Manci, Elizabeth A; Cynober, Therese; Coller, Barry S

    2008-01-01

    Berkeley sickle cell mice are used as animal models of human sickle cell disease but there are no reports of platelet studies in this model. Since humans with sickle cell disease have platelet abnormalities, we studied platelet morphology and function in Berkeley mice (SS). We observed elevated mean platelet forward angle light scatter (FSC) values (an indirect measure of platelet volume) in SS compared to wild type (WT) (37+/-3.2 vs. 27+/-1.4, mean+/-SD; p<0.001), in association with moderate thrombocytopenia (505+/-49 x 10(3)/microl vs. 1151+/-162 x 10(3)/microl; p<0.001). Despite having marked splenomegaly, SS mice had elevated levels of Howell-Jolly bodies and "pocked" erythrocytes (p<0.001 for both) suggesting splenic dysfunction. SS mice also had elevated numbers of thiazole orange positive platelets (5+/-1% vs. 1+/-1%; p<0.001), normal to low plasma thrombopoietin levels, normal plasma glycocalicin levels, normal levels of platelet recovery, and near normal platelet life spans. Platelets from SS mice bound more fibrinogen and antibody to P-selectin following activation with a threshold concentration of a protease activated receptor (PAR)-4 peptide compared to WT mice. Enlarged platelets are associated with a predisposition to arterial thrombosis in humans and some humans with SCD have been reported to have large platelets. Thus, additional studies are needed to assess whether large platelets contribute either to pulmonary hypertension or the large vessel arterial occlusion that produces stroke in some children with sickle cell disease.

  9. 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.

  10. Tongue Disorders

    Science.gov (United States)

    ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ...

  11. Mental Disorders

    Science.gov (United States)

    Mental disorders include a wide range of problems, including Anxiety disorders, including panic disorder, obsessive-compulsive disorder, post- ... disorders, including schizophrenia There are many causes of mental disorders. Your genes and family history may play a ...

  12. [Erythrocytes infected by Plasmodium falciparum activate human platelets].

    Science.gov (United States)

    Polack, B; Peyron, F; Sheick Zadiuddin, I; Kolodié, L; Ambroise-Thomas, P

    1990-01-01

    Blood platelets are involved in Plasmodium falciparum malaria pathology as shown by thrombocytopenia and increased plasma level of two alpha granule proteins: beta thromboglobulin (beta TG) and platelet factor 4 (PF4). In this study we demonstrate that Plasmodium falciparum parasitized erythrocytes activate directly the secretion of beta TG and PF4 by human platelets. This secretion is related to parasitemia and occurs immediately after contact. Treatment of parasited erythrocytes by trypsin and diffusion chamber experiments suggest that platelet activation is triggered by parasitic substances shed on erythrocyte membrane and released in the culture medium.

  13. In vitro model of platelet aggregation in stenotic arteries

    Energy Technology Data Exchange (ETDEWEB)

    Morley, D.; Santamore, W.P.

    1988-07-01

    Clinical and experimental evidence suggest a strong relationship between arterial stenosis, platelet aggregation, and subsequent thrombus formation. To facilitate the study of platelet accumulation in stenotic arteries, we developed an in vitro preparation. Arterial segments were perfused with whole citrated blood. A stenosis was created by applying an external plastic constrictor to the artery. Platelet accumulation within the stenosis was assessed by scanning electron microscopy and by radioactive counts from Indium-111 labeled platelets. Utilizing this preparation, 30 carotid arterial segments from 10 mongrel dogs were perfused at 100 mmHg for 15 min. In 10 arteries without a stenosis, scanning electron microscopy and radioactive counts demonstrated little platelet accumulation. In contrast, extensive platelet aggregation was observed in 10 arteries with stenoses. Moreover, in 10 stenotic arteries exposed to the thromboxane mimetic, U46619 (Upjohn Diagnostic Group), scanning electron microscopy and radioactive counts demonstrated a significant increase in platelet deposition. Conversely, we demonstrated a dimunition of platelet accumulation in stenosed arterial segments exposed to the prostacyclin analogue platelet inhibitor, Iloprost. The in vitro preparation allows precise control of hemodynamic variables and makes it possible to perform multiple tests on segments of the same vessel from the same animal.

  14. Platelets protect lung from injury induced by systemic inflammatory response

    Science.gov (United States)

    Luo, Shuhua; Wang, Yabo; An, Qi; Chen, Hao; Zhao, Junfei; Zhang, Jie; Meng, Wentong; Du, Lei

    2017-01-01

    Systemic inflammatory responses can severely injure lungs, prompting efforts to explore how to attenuate such injury. Here we explored whether platelets can help attenuate lung injury in mice resulting from extracorporeal circulation (ECC)-induced systemic inflammatory responses. Mice were subjected to ECC for 30 min, then treated with phosphate-buffered saline, platelets, the GPIIb/IIIa inhibitor Tirofiban, or the combination of platelets and Tirofiban. Blood and lung tissues were harvested 60 min later, and lung injury and inflammatory status were assessed. As expected, ECC caused systemic inflammation and pulmonary dysfunction, and platelet transfusion resulted in significantly milder lung injury and higher lung function. It also led to greater numbers of circulating platelet-leukocyte aggregates and greater platelet accumulation in the lung. Platelet transfusion was associated with higher production of transforming growth factor-β and as well as lower levels of tumour necrosis factor-α and neutrophil elastase in plasma and lung. None of these platelet effects was observed in the presence of Tirofiban. Our results suggest that, at least under certain conditions, platelets can protect lung from injury induced by systemic inflammatory responses. PMID:28155889

  15. 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.

  16. 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.

  17. The detection of platelet isoantibodies by membrane immunofluorescence.

    Science.gov (United States)

    van der Schans, G S; Veenhoven, W A; Snijder, J A; Nieweg, H O

    1977-07-01

    A membrane ummunofluorescence test for the detection of platelet isoantibodies is described. Gel filtration of the incubation mixture was incorporated in the procedure and proved effective for the removal of serum proteins from the platelet suspension. With this technique isoantibodies were found in the serum of 13 out of a group of 16 patients who had received multiple transfusions. The results were checked by measuring the uptake of 125I-labeled anti-IgG fraction by gel-filtered platelets. Subsequently the membrane immunofluorescence method was also compared with established techniques described for the detection of isoantibodies such as the microtest for lymphocytotoxicity and a complement-fixation method and the procedures based on the release of labeled serotonin, the phagocytosis of chromium-tagged platelets, the increase of platelet factor 3 activity, and on platelet aggregation. We had the opportunity to investigate the serum of one patient for the presence of isoantibodies against platelets from HLA identical siblings both before and after the administration of their platelets. On the basis of this experience it is concluded that the membrane immunofluorescence test for platelet isoantibodies is a relatively simple method with a high degree of specificity and adequate sensitivity.

  18. Enhancement by platelets of oxygen radical responses of human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    McCulloch, K.K.; Powell, J.; Johnson, K.J.; Ward, P.A.

    1986-03-01

    When human blood neutrophils were incubated with immune complexes (consisting of IgG antibody) in the presence of platelets, there was a 2 to 10 fold enhancement in the generation of O-/sub 2/ and H/sub 2/O/sub 2/. This enhancement phenomenon was proportional to the dose of immune complex added and the number of platelets present. The response was not agonist specific since similar enhancement also occurred with the following agonists: phorbol myristate acetate, opsonized zymosan particles and the chemotactic peptide N-formyl-met-leu-phe. The platelet related phenomenon of enhanced O-/sub 2/ generation could not be reproduced by the addition of serotonin, histamine or platelet-derived growth factor and was not affected by prior treatment of platelets with cyclooxygenase inhibitors (indomethacin, piroxicam) or lipoxygenase inhibitors (nafazatrom, BW755C or nordihydroguaiaretic acid). However, activation of platelets by thrombin caused release into the platelet supernatant fluid of a factor that, only in the presence of immune complexes, caused enhanced O-/sub 2/ responses to neutrophils. These data indicate that platelets potentiate oxygen radical responses of human neutrophils and suggest a mechanisms by which platelets may participate in tissue injury which is mediated by oxygen radical products from activated neutrophils.

  19. Clinical use of platelet scintigraphy with 111-In-oxine

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, C.; Reuther, R.; Berentelg, J.; Kimmig, B.

    1983-01-01

    Platelet scintigraphy was performed on 62 patients with cerebral ischaemia. Pathological scintigraphic images were obtained in 29 of the 62 patients. In 79.3% of these 29 patients the scan was abnormal in the vessel clinically affected. Platelet scintigraphy was abnormal in 21 of 34 patients with normal angiogram or only slight atherosclerosis. In patients undergoing antiplatelet therapy, platelet scintigraphy was less often positive than in untreated patients. It is suggested that platelet scintigraphy could be an appropriate technique for detecting small mural thrombi of the carotid artery, which are the source of arterio-arterial emboli, and for controlling the efficiency of antiplatelet therapy.

  20. Platelet Dynamics in Three-Dimensional Simulation of Whole Blood

    OpenAIRE

    Vahidkhah, Koohyar; Diamond, Scott L.; Bagchi, Prosenjit

    2014-01-01

    A high-fidelity computational model using a 3D immersed boundary method is used to study platelet dynamics in whole blood. We focus on the 3D effects of the platelet-red blood cell (RBC) interaction on platelet margination and near-wall dynamics in a shear flow. We find that the RBC distribution in whole blood becomes naturally anisotropic and creates local clusters and cavities. A platelet can enter a cavity and use it as an express lane for a fast margination toward the wall. Once near the ...