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  1. Diagnostic Value of Measuring Platelet Von Willebrand Factor in Von Willebrand Disease

    PubMed Central

    Casonato, Alessandra; Cattini, Maria Grazia; Daidone, Viviana; Pontara, Elena; Bertomoro, Antonella; Prandoni, Paolo

    2016-01-01

    Von Willebrand disease (VWD) may be caused by an impaired von Willebrand factor (VWF) synthesis, its increased clearance or abnormal function, or combinations of these factors. It may be difficult to recognize the different contributions of these anomalies. Here we demonstrate that VWD diagnostics gains from measuring platelet VWF, which can reveal a defective VWF synthesis. Measuring platelet VWF revealed that: severe type 1 VWD always coincided with significantly lower platelet and plasma VWF levels, whereas mild forms revealed low plasma VWF levels associated with low or normal platelet VWF levels, and the latter were associated with a slightly shorter VWF survival; type Vicenza (the archetype VWD caused by a reduced VWF survival) featured normal platelet VWF levels despite significantly reduced plasma VWF levels; type 2B patients could have either normal platelet VWF levels associated with abnormal multimer patterns, or reduced platelet VWF levels associated with normal multimer patterns; type 2A patients could have reduced or normal platelet VWF levels, the former associated mainly with type 2A-I, the latter with type 2A-II; plasma and platelet VWF levels were normal in type 2N, except when the defect was associated with a quantitative VWF mutation. Our findings show that measuring platelet VWF helps to characterize VWD, especially the ambiguous phenotypes, shedding light on the mechanisms underlying the disorder. PMID:27532107

  2. Terminal platelet production is regulated by von Willebrand factor.

    PubMed

    Poirault-Chassac, Sonia; Nguyen, Kim Anh; Pietrzyk, Audrey; Casari, Caterina; Veyradier, Agnes; Denis, Cecile V; Baruch, Dominique

    2013-01-01

    It is established that proplatelets are formed from mature megakaryocytes (MK) as intermediates before platelet production. Recently, the presence of proplatelets was described in blood incubated in static conditions. We have previously demonstrated that platelet and proplatelet formation is upregulated by MK exposure to high shear rates (1800 s(-1)) on immobilized von Willebrand factor (VWF). The purpose of the present study was to investigate whether VWF is involved in the regulation of terminal platelet production in blood. To this end, Vwf (-/-) mice, a model of severe von Willebrand disease, were used to create a situation in which blood cells circulate in a vascular tree that is completely devoid of VWF. Murine platelets were isolated from Vwf (-/-) and Vwf (+/+) blood, exposed to VWF at 1800 s(-1) in a microfluidic platform, and examined by means of videomicroscopy, as well as fluorescence and activation studies. Proplatelets became visible within 5 minutes, representing 38% of all platelets after 12 minutes and 46% after 28 min. The proportion of proplatelets was 1.8-fold higher in blood from Vwf(-/-) mice than from Vwf(+/+) mice, suggesting a role of VWF in vivo. Fragmentation of these proplatelets into smaller discoid platelets was also observed in real-time. Platelets remained fully activatable by thrombin. Compensation of plasmatic VWF following hydrodynamic gene transfer in Vwf(-/-) mice reduced the percentage of proplatelets to wild-type levels. A thrombocytopenic mouse model was studied in the flow system, 7 days after a single 5-FU injection. Compared to untreated mouse blood, a 2-fold increase in the percentage of proplatelets was detected following exposure to 1800 s(-1) on VWF of samples from mice treated with 5-FU. In conclusion, VWF and shear stress together appear to upregulate proplatelet reorganization and platelet formation. This suggests a new function for VWF in vivo as regulator of bloodstream thrombopoiesis.

  3. Interaction of the von Willebrand factor with platelets and thrombosis.

    PubMed

    Perutelli, P; Mori, P G

    1997-11-01

    The human von Willebrand factor (vWf) is a multimeric glycoprotein present in plasma, platelets, endothelial cells and subendothelium and synthesized in endothelial cells and megakaryocytes. vWf plays a pivotal role in the mechanisms of blood clotting and platelet thrombus formation; quantitative and qualitative abnormalities of vWf cause the most common congenital bleeding disorder in man, the von Willebrand disease. vWf stabilizes factor VIII and interacts with subendothelial components and with platelet membrane receptors. The multimeric structure of vWf provides an array of binding sites which allows multivalent interactions with its ligands, thus supporting the formation of stable platelet aggregates at the site of vascular injury, particularly under flow conditions characterized by high shear stress. In the last years, remarkable progress has been made toward understanding the structure of vWf protein and gene, and the elucidation of many structure-function relationships, which may result in improved therapeutic intervention for vWD patients, and in the development of effective strategies for antithrombotic therapy.

  4. Gray platelet syndrome: immunoelectron microscopic localization of fibrinogen and von Willebrand factor in platelets and megakaryocytes.

    PubMed

    Cramer, E M; Vainchenker, W; Vinci, G; Guichard, J; Breton-Gorius, J

    1985-12-01

    An immunogold method was used for investigating the subcellular localization of von Willebrand factor (vWF) and fibrinogen (Fg) in platelets and cultured megakaryocytes from normal subjects and from three patients with the gray platelet syndrome (GPS), a rare congenital disorder characterized by the absence of alpha-granules. In normal platelets at rest, vWF was detected exclusively in alpha-granules, with a characteristic distribution: gold particles were localized at one pole of each labeled granule, outlining the inner face of its membrane. vWF was distributed similarly in the alpha-granules of megakaryocytes at day 12 of culture, where it was also found in small vesicles near the Golgi complex. In contrast, Fg was observed in the whole matrix of all platelet alpha-granules but not in the nucleoids. In platelets from three patients with GPS, vWF and Fg were distributed homogeneously in the rare normal alpha-granules, which could be recognized by their size, and also in small granules identified as abnormal alpha-granules, which were similar in size to the small, possibly immature granules present in normal megakaryocytes. In addition, in some unstimulated platelets, Fg labeling was associated with dense material in the lumen of the surface-connected canalicular system (SCCS). At day 12 of culture, megakaryocytes from the patients with GPS contained some small alpha-granules labeled for Fg and vWF identical to those found in mature platelets. The majority of alpha-granules of normal size appeared partially or completely empty. Thus, we conclude that vWF is distributed differently from Fg in normal alpha-granules, and that unstimulated platelets from patients with GPS contain Fg and vWF in a population of small granules identifiable as abnormal alpha-granules only by immunoelectron microscopy. In addition, the presence of Fg in the SCCS of gray platelets suggests a spontaneous release of the alpha-granule content.

  5. A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of artificial platelet nanoconstructs without interfering with VWF-adhesion of natural platelets

    NASA Astrophysics Data System (ADS)

    Haji-Valizadeh, Hassan; Modery-Pawlowski, Christa L.; Sen Gupta, Anirban

    2014-04-01

    There is substantial clinical interest in synthetic platelet analogs for potential application in transfusion medicine. To this end, our research is focused on self-assembled peptide-lipid nanoconstructs that can undergo injury site-selective adhesion and subsequently promote site-directed active platelet aggregation, thus mimicking platelet's primary hemostatic actions. For injury site-selective adhesion, we have utilized a coagulation factor FVIII-derived VWF-binding peptide (VBP). FVIII binds to VWF's D'-D3 domain while natural platelet GPIbα binds to VWF's A1 domain. Therefore, we hypothesized that the VBP-decorated nanoconstructs will adhere to VWF without mutual competition with natural platelets. We further hypothesized that the adherent VBP-decorated constructs can enhance platelet aggregation when co-decorated with a fibrinogen-mimetic peptide (FMP). To test these hypotheses, we used glycocalicin to selectively block VWF's A1 domain and, using fluorescence microscopy, studied the binding of fluorescently labeled VBP-decorated nanoconstructs versus platelets to ristocetin-treated VWF. Subsequently, we co-decorated the nanoconstructs with VBP and FMP and incubated them with human platelets to study construct-mediated enhancement of platelet aggregation. Decoration with VBP resulted in substantial construct adhesion to ristocetin-treated VWF even if the A1-domain was blocked by glycocalicin. In comparison, such A1-blocking resulted in significant reduction of platelet adhesion. Without A1-blocking, the VBP-decorated constructs and natural platelets could adhere to VWF concomitantly. Furthermore, the constructs co-decorated with VBP and FMP enhanced active platelet aggregation. The results indicate significant promise in utilizing the FVIII-derived VBP in developing synthetic platelet analogs that do not interfere with VWF-binding of natural platelets but allow site-directed enhancement of platelet aggregation when combined with FMP.There is substantial

  6. Structure of von Willebrand factor and its function in platelet adhesion and thrombus formation.

    PubMed

    Ruggeri, Z M

    2001-06-01

    The adhesive protein von Willebrand factor mediates the initiation and progression of thrombus formation at sites of vascular injury. von Willebrand factor is synthesized in endothelial cells and megakaryocytes as a very large polymer composed of identical subunits. In the plasma, it appears as a series of multimers of regularly decreasing molecular mass, from several thousand to 500 kDa. The size of circulating von Willebrand factor multimers is controlled by proteolytic cleavage carried out by a specific protease. The biological functions of von Willebrand factor are exerted through specific domains that interact with extracellular matrix components and cell membrane receptors to promote the initial tethering and adhesion of platelets to subendothelial surfaces, as well as platelet aggregation. Moreover, von Willebrand factor binds the procoagulant co-enzyme, factor VIII, contributing to its stability and, indirectly, to its function in the generation of fibrin. This chapter presents a review of current knowledge on the structure, biosynthesis and functions of von Willebrand factor.

  7. Visualizing the von Willebrand factor/glycoprotein Ib-IX axis with a platelet-type von Willebrand disease mutation.

    PubMed

    Guerrero, Jose A; Kyei, Mark; Russell, Susan; Liu, Junling; Gartner, T Kent; Storrie, Brian; Ware, Jerry

    2009-12-24

    Platelet-type von Willebrand disease (PT-VWD) is a bleeding disorder of the platelet glycoprotein Ib-IX/von Willebrand factor (VWF) axis caused by mutations in the glycoprotein Ib-IX receptor that lead to an increased affinity with VWF. In this report, platelets from a mouse expressing a mutation associated with PT-VWD have been visualized using state-of-the art image collection and processing. Confocal analysis revealed that VWF bound to the surface of single platelets and bridging micro-aggregates of platelets. Surface-bound VWF appears as a large, linear structure on the surface of 50% of the PT-VWD platelets. In vivo thrombus formation after chemical injury to the carotid artery revealed a severe impairment to occlusion as a consequence of the PT-VWD mutation. In vitro stimulation of PT-VWD platelets with adenosine diphosphate or thrombin demonstrates a significant block in their ability to bind fibrinogen. The impairment of in vivo thrombus formation and in vitro fibrinogen binding are more significant than might be expected from the observed platelet binding to VWF polymers over a small portion of the plasma membrane. Visualization of the receptor/ligand interaction and characterization of a severe antithrombotic phenotype provide a new understanding on the molecular basis of bleeding associated with the PT-VWD phenotype.

  8. Platelet dysfunction and a high bone mass phenotype in a murine model of platelet-type von Willebrand disease.

    PubMed

    Suva, Larry J; Hartman, Eric; Dilley, Joshua D; Russell, Susan; Akel, Nisreen S; Skinner, Robert A; Hogue, William R; Budde, Ulrich; Varughese, Kottayil I; Kanaji, Taisuke; Ware, Jerry

    2008-02-01

    The platelet glycoprotein Ib-IX receptor binds surface-bound von Willebrand factor and supports platelet adhesion to damaged vascular surfaces. A limited number of mutations within the glycoprotein Ib-IX complex have been described that permit a structurally altered receptor to interact with soluble von Willebrand factor, and this is the molecular basis of platelet-type von Willebrand disease. We have developed and characterized a mouse model of platelet-type von Willebrand disease (G233V) and have confirmed a platelet phenotype mimicking the human disorder. The mice have a dramatic increase in splenic megakaryocytes and splenomegaly. Recent studies have demonstrated that hematopoetic cells can influence the differentiation of osteogenic cells. Thus, we examined the skeletal phenotype of mice expressing the G233V variant complex. At 6 months of age, G233V mice exhibit a high bone mass phenotype with an approximate doubling of trabecular bone volume in both the tibia and femur. Serum measures of bone resorption were significantly decreased in G233V animals. With decreased bone resorption, cortical thickness was increased, medullary area decreased, and consequently, the mechanical strength of the femur was significantly increased. Using ex vivo bone marrow cultures, osteoclast-specific staining in the G233V mutant marrow was diminished, whereas osteoblastogenesis was unaffected. These studies provide new insights into the relationship between the regulation of megakaryocytopoiesis and bone mass.

  9. Mimicking adhesive functionalities of blood platelets using ligand-decorated liposomes.

    PubMed

    Ravikumar, Madhumitha; Modery, Christa L; Wong, Timothy L; Dzuricky, Michael; Sen Gupta, Anirban

    2012-06-20

    Platelet transfusion is used for treating a variety of bleeding complications. Natural platelet-based transfusion products have very short storage life (3-7 days) and high risks of biological contamination and side effects. Consequently, there is significant clinical interest in synthetic platelet-mimetic constructs that can promote hemostasis, while allowing convenient large-scale production, easy portability, long storage life, and minimal biological risks. To this end, research efforts are being directed toward particles that can amplify aggregation of activated platelets or can mimic platelet's ability to undergo adhesion to various vascular matrix proteins. Here, we report on a synthetic construct design that combines the mimicry of platelet's shear-dependent adhesion to vWF and shear-independent adhesion to collagen under flow, on a single particle. For this, we have used 150-nm-diameter liposomes as model particles and have decorated their surface simultaneously with vWF-binding and collagen-binding recombinant protein fragments or synthetic peptide motifs. We demonstrate in vitro that these surface-modified liposomes are able to adhere onto vWF surfaces in a shear-dependent fashion and onto collagen surfaces in a shear-independent fashion under flow. Moreover, when the vWF-binding and the collagen-binding were integrated on a single liposomal platform, the resultant heteromultivalent liposomes showed significantly enhanced adhesion to a vWF/collagen mixed surface compared to liposomes bearing vWF-binding or collagen-binding ligands only, as long as the ligand motifs did not spatially interfere with each other. Altogether, our results establish the feasibility of efficiently mimicking platelet's dual adhesion mechanisms on synthetic particles.

  10. Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions.

    PubMed

    Levade, Marie; David, Elodie; Garcia, Cédric; Laurent, Pierre-Alexandre; Cadot, Sarah; Michallet, Anne-Sophie; Bordet, Jean-Claude; Tam, Constantine; Sié, Pierre; Ysebaert, Loïc; Payrastre, Bernard

    2014-12-18

    The oral Bruton's tyrosine kinase inhibitor, ibrutinib, has recently demonstrated high efficiency in patients with relapsed B-cell malignancies. Occurrence of bleeding events has been reported in a subgroup of ibrutinib-treated patients. We demonstrate that ibrutinib selectively inhibits platelet signaling and functions downstream of the collagen receptor glycoprotein VI and strongly affects firm platelet adhesion on von Willebrand factor (VWF) under arterial flow. A longitudinal study of 14 patients indicated a correlation between occurrence of bleeding events and decreased platelet aggregation in response to collagen in platelet-rich plasma and firm adhesion on VWF under arterial flow. The addition of 50% untreated platelets was sufficient to efficiently reverse the effects of ibrutinib, and platelet functions recovered after treatment interruption as physiological platelet renewal occurred. These data have important clinical implications and provide a basis for hemostasis management during ibrutinib treatment.

  11. Interaction of Platelet Membrane Receptors with von Willebrand Factor, Ristocetin, and the Fc Region of Immunoglobulin G

    PubMed Central

    Moore, Anne; Ross, Gordon D.; Nachman, Ralph L.

    1978-01-01

    The agglutination of human platelets by ristocetin and von Willebrand factor was inhibited by aggregated immunoglobulin (Ig)G and by Fc fragments of IgG, but not by Fab, F(ab′)2 or pFc fragments of IgG. Because this inhibition occurred with formalin-fixed platelets as well as with normal platelets, a generalized aggregation of fluid membrane components by Fc fragments was not responsible for this inhibition of ristocetin and von Willebrand factor-induced agglutination. Reciprocal inhibition of platelet Fc receptors was produced by prior incubation of platelets with von Willebrand factor and ristocetin. Sucrose density gradient ultracentrifugation studies demonstrated that aggregated IgG did not form fluid-phase complexes with von Willebrand factor and ristocetin. Furthermore, passage of von Willebrand factor and ristocetin through a column of immobilized heat-aggregated IgG did not alter platelet agglutinating activity which indicates that aggregated IgG did not inactivate von Willebrand factor or ristocetin. Thus, it was likely that the IgG-mediated interference with platelet agglutination by ristocetin and von Willebrand factor did not occur in the fluid phase but at the platelet surface. These studies suggest that the platelet membrane Fc receptor may be either a part of, or sterically related to, the membrane glycoprotein I complex that interacts with von Willebrand factor, and that occupation of one of these surface components blocks the availability of the other. PMID:309473

  12. Type 2B von Willebrand disease associated with the release of platelet agglutinates from megakaryocytes in the bone marrow.

    PubMed

    Slayton, William B; Patel, Milin; Sola-Visner, Martha; Harris, Neil; Rivers, Angela; Montgomery, Robert R; Friedman, Kenneth D

    2008-09-01

    We report a child with thrombocytopenia since birth, circulating platelet agglutinates, and a tendency to bleed. A bone marrow aspirate revealed large platelet clumps within the bone marrow and megakaryocyte nuclei surrounded by halos of clumped platelets. Laboratory evaluation revealed type 2B von Willebrand disease. Gene sequencing revealed a G to C mutation at base 3923 of the VWF gene. This mutation was previously described in a family with circulating platelet clumps and abnormal megakaryopoiesis with release of clumped platelets in culture. This same mutation was previously described in a family with circulating platelet aggregates and abnormalities of platelet release from megakaryocytes in vitro. Presence of megakaryocytes with halos of clumped platelets in our patient suggests that platelet agglutinate occurs in the bone marrow in some type 2B von Willebrand disease patients.

  13. Platelet-independent adhesion of calcium-loaded erythrocytes to von Willebrand factor

    PubMed Central

    Bierings, Ruben; Meems, Henriet; Mul, Frederik P. J.; Geerts, Dirk; Vlaar, Alexander P. J.; Voorberg, Jan; Hordijk, Peter L.

    2017-01-01

    Adhesion of erythrocytes to endothelial cells lining the vascular wall can cause vaso-occlusive events that impair blood flow which in turn may result in ischemia and tissue damage. Adhesion of erythrocytes to vascular endothelial cells has been described in multiple hemolytic disorders, especially in sickle cell disease, but the adhesion of normal erythrocytes to endothelial cells has hardly been described. It was shown that calcium-loaded erythrocytes can adhere to endothelial cells. Because sickle erythrocyte adhesion to ECs can be enhanced by ultra-large von Willebrand factor multimers, we investigated whether calcium loading of erythrocytes could promote binding to endothelial cells via ultra-large von Willebrand factor multimers. We used (immunofluorescent) live-cell imaging of washed erythrocytes perfused over primary endothelial cells at venular flow rate. Using this approach, we show that calcium-loaded erythrocytes strongly adhere to histamine-stimulated primary human endothelial cells. This adhesion is mediated by ultra-large von Willebrand factor multimers. Von Willebrand factor knockdown or ADAMTS13 cleavage abolished the binding of erythrocytes to activated endothelial cells under flow. Platelet depletion did not interfere with erythrocyte binding to von Willebrand factor. Our results reveal platelet-independent adhesion of calcium-loaded erythrocytes to endothelium-derived von Willebrand factor. Erythrocyte adhesion to von Willebrand factor may be particularly relevant for venous thrombosis, which is characterized by the formation of erythrocyte-rich thrombi. PMID:28249049

  14. Synthesis by guinea pig megakaryocytes of platelet glycoprotein receptors for fibrinogen and von Willebrand factor.

    PubMed

    Kupinski, J M; Miller, J L

    1986-08-01

    In the preceding paper, we described two monoclonal antibodies, PG-1 and PG-2, that selectively blocked the binding of von Willebrand factor (PG-1) or of fibrinogen (PG-2) to guinea pig platelets. In this study we examine the structures and site of synthesis of these receptors. NP-40 lysates of radiolabeled guinea pig platelets were immunoprecipitated with monoclonal antibodies PG-1 or PG-2, and the precipitates analyzed by SDS-PAGE. PG-1 recognized a single polypeptide with reduced Mr of 143,000 daltons, while PG-2 precipitated two chains with reduced Mr of 121,000 and 93,000 daltons. Periodate-[3H]borohydride labeling of platelets, in conjunction with two-dimensional SDS-PAGE, showed that all three of the polypeptides are glycoproteins and that the 143,000 and 121,000 dalton chains are linked by disulfide bond(s) to smaller, approximately 25,000 dalton polypeptides. Guinea pig megakaryocytes synthesized polypeptides immunoprecipitable by PG-1 and PG-2, with molecular weights similar to polypeptides found associated with platelet membranes. These studies demonstrate that guinea pig platelets have functional receptors for fibrinogen and von Willebrand factor that are structurally homologous to human platelet glycoproteins Ib, IIb and IIIa, and that these glycoproteins are synthesized by megakaryocytes.

  15. Type 2B von Willebrand Disease: A Matter of Plasma Plus Platelet Abnormality.

    PubMed

    Castaman, Giancarlo; Federici, Augusto B

    2016-07-01

    Type 2B von Willebrand disease (VWD2B) is a rare, autosomal-dominant inherited bleeding disorder, characterized by an enhanced ristocetin-induced platelet aggregation in platelet-rich plasma and often with variable degree of thrombocytopenia and loss of high-molecular-weight multimers von Willebrand factor (VWF). All these phenomena are caused by a mutant VWF, normally synthesized and assembled by endothelial cells, but with heightened affinity binding to the platelet receptor glycoprotein Ib-α (GpIb-α). When this abnormal VWF is released into the circulation and under specific clinical circumstances, in vivo platelet clumping is observed. Mutations, invariably clustered in exon 28 of the VWF gene encoding for the VWF A1 domain involved in VWF binding to GpIb-α, are responsible for VWD2B phenotype. Clinical and laboratory phenotype appears strongly related to the type of VWF-causative mutations. However, recent evidences suggest that a true platelet defect is also present in this type, with several morphological and functional abnormalities being detected in a subset of VWD2B patients.

  16. The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress.

    PubMed Central

    Ikeda, Y; Handa, M; Kawano, K; Kamata, T; Murata, M; Araki, Y; Anbo, H; Kawai, Y; Watanabe, K; Itagaki, I

    1991-01-01

    Exposure of platelets to shear stress leads to aggregation in the absence of exogenous agonists. We have now found that different adhesive proteins and platelet membrane glycoproteins are involved in aggregation depending on the shear stress conditions and the concentration of divalent cations in the medium. When blood is collected with trisodium citrate as anticoagulant, which causes a decrease in the levels of external ionized calcium ([Ca2+]o), platelet aggregation can be induced under low shear force (12 dyn/cm2) and is mediated by fibrinogen binding to the glycoprotein IIb-IIIa complex. Aggregates formed under these conditions are not stable, and when shear force is increased to 68 dyn/cm2, disaggregation results. By contrast, platelets from blood collected with hirudin as anticoagulant, wherein [Ca2+]o is within normal plasma levels, do not undergo low shear-induced aggregation; however, after exposure to a shear force above 80 dyn/cm2, aggregation is observed but only when von Willebrand factor is present and can interact with both its platelet binding sites, glycoprotein Ib-IX and glycoprotein IIb-IIIa. Fibrinogen is not involved in high shear-induced aggregation which, in fact, occurs normally in patients with severe afibrinogenemia. Thus, von Willebrand factor in the absence of exogenous agonists can mediate platelet aggregation in experimental conditions that may mimic the hemorheological situation of partially occluded arteries. This pathway of platelet aggregation involving only one adhesive ligand and two membrane adhesion receptors may play a relevant role in thrombogenesis. PMID:2010539

  17. Interaction of blood platelets with a microfibrillar extract from adult bovine aorta: requirement for von Willebrand factor.

    PubMed Central

    Fauvel, F; Grant, M E; Legrand, Y J; Souchon, H; Tobelem, G; Jackson, D S; Caen, J P

    1983-01-01

    Adult bovine aortic tissue was treated with 6 M guanidinium chloride in the presence of proteinase inhibitors to obtain an extract that was essentially devoid of collagenous components and appeared homogeneous by electron microscopy. When this extract was dispersed by sonication it was found to be a very potent inducer of human platelet aggregation. This interaction required the presence of von Willebrand factor and of its receptor (glycoprotein Ib) on platelet membrane. This was demonstrated by the fact that the aggregation of normal blood platelets resuspended in plasmas deficient in von Willebrand factor was significantly diminished as compared to aggregation in control plasma. Moreover, this aggregation was inhibited by a monoclonal antibody, IgG AN51, to platelet glycoprotein Ib. These studies provide direct biochemical evidence for the existence of a thrombogenic constituent of the vessel wall that is noncollagenous and von Willebrand factor-dependent. Images PMID:6601274

  18. Abnormal VWF modifies megakaryocytopoiesis: studies of platelets and megakaryocyte cultures from patients with von Willebrand disease type 2B.

    PubMed

    Nurden, Paquita; Gobbi, Giuliana; Nurden, Alan; Enouf, Jocelyne; Youlyouz-Marfak, Ibtissam; Carubbi, Cecilia; La Marca, Silvia; Punzo, Margherita; Baronciani, Luciano; De Marco, Luigi; Vitale, Marco; Federici, Augusto B

    2010-04-01

    von Willebrand factor (VWF) is an essential mediator of platelet adhesion to the vessel wall, but little is known about its role in megakaryocytopoiesis. VWF and its platelet receptor, glycoprotein Ibalpha (GPIbalpha), are both expressed during megakaryocyte (MK) maturation. This study was designed to evaluate whether the enhanced VWF-GPIbalpha interactions typical of patients with von Willebrand disease type 2B (VWD2B) modify platelet production. Platelets from 9 patients with VWD2B with 7 different gain-of-function mutations were examined by electron microscopy (EM) and immunofluorescence labeling. For the patients with VWD2B, EM characteristically showed variable numbers of structurally abnormal giant platelets, sometimes in agglutinates. Cultures of MKs from controls performed with or without purified VWF confirmed a positive influence of VWF on platelet production with specific inhibition by an antibody blocking VWF binding to GPIbalpha. VWD2B MK cultures examined by EM showed a disorganized demarcation membrane system and abnormal granule distribution. They produced platelets with structural abnormalities typical of VWD2B. Confocal examination of MK revealed limited extension of pseudopods with few large proplatelets. These results confirm that megakaryocytopoiesis is modified by the enhanced VWF-GPIbalpha interactions. These data obtained for controls and patients with VWD2B suggest a novel regulatory role of VWF-GPIbalpha interactions in platelet production.

  19. Functional self-association of von Willebrand factor during platelet adhesion under flow

    NASA Astrophysics Data System (ADS)

    Savage, Brian; Sixma, Jan J.; Ruggeri, Zaverio M.

    2002-01-01

    We have used recombinant wild-type human von Willebrand factor (VWF) and deletion mutants lacking the A1 and A3 domains, as well as specific function-blocking monoclonal antibodies, to demonstrate a functionally relevant self-association at the interface of soluble and surface-bound VWF. Platelets perfused at the wall shear rate of 1,500 s1 over immobilized VWF lacking A1 domain function failed to become tethered to the surface when they were in a plasma-free suspension with erythrocytes, but adhered promptly if soluble VWF with functional A1 domain was added to the cells. The same results were observed when VWF was immobilized onto collagen through its A3 domain and soluble VWF with deleted A3 domain was added to the cells. Thus, VWF bound to glass or collagen sustains a process of homotypic self-association with soluble VWF multimers that, as a result, can mediate platelet adhesion. The latter finding demonstrates that direct immobilization on a substrate is not a strict requirement for VWF binding to platelet glycoprotein Ib. The dynamic and reversible interaction of surface-bound and soluble VWF appears to be specifically homotypic, because immobilized BSA, human fibrinogen, and fibronectin cannot substitute for VWF in the process. Our findings highlight a newly recognized role of circulating VWF in the initiation of platelet adhesion. The self-assembly of VWF multimers on an injured vascular surface may provide a relevant contribution to the arrest of flowing platelets opposing hemodynamic forces, thus facilitating subsequent thrombus growth.

  20. O-linked carbohydrate of recombinant von Willebrand factor influences ristocetin-induced binding to platelet glycoprotein 1b.

    PubMed Central

    Carew, J A; Quinn, S M; Stoddart, J H; Lynch, D C

    1992-01-01

    By transfecting the full-length cDNA for human von Willebrand factor (vWf) into a line of Chinese hamster ovary cells with a defect in carbohydrate metabolism, we have prepared recombinant vWf specifically lacking O-linked carbohydrates. We have compared this under-glycosylated protein to fully glycosylated recombinant vWf with respect to several structural and binding properties. vWf deficient in O-linked glycans was synthesized, assembled into multimers, and secreted in an apparently normal manner and was not prone to degradation in the extracellular milieu. It did not differ from fully glycosylated vWf in ability to bind to heparin or to collagen type I but did interact less well with glycoprotein 1b on formalin-fixed platelets. This decreased interaction was evidenced in both a lessened overall binding to platelets and in diminished capacity to promote platelet agglutination, in the presence of ristocetin. In contrast, no difference was seen in platelet binding in the presence of botrocetin. These data indicate a possible role for O-linked carbohydrates in the vWf-glycoprotein 1b interaction promoted by ristocetin and suggest that abnormalities in carbohydrate modification might contribute to the altered ristocetin-dependent reactivity between vWf and platelets described for some variant forms of von Willebrand disease. Images PMID:1469086

  1. Expression of the phenotypic abnormality of platelet-type von Willebrand disease in a recombinant glycoprotein Ib alpha fragment.

    PubMed Central

    Murata, M; Russell, S R; Ruggeri, Z M; Ware, J

    1993-01-01

    The platelet GP Ib-IX receptor supports platelet adhesion and activation by binding to vWf in the exposed subendothelial matrix. An abnormal GP Ib-IX complex exists in platelet-type or pseudo-von Willebrand disease and has a characteristic increased affinity for soluble vWf resulting in impaired hemostatic function due to the removal of larger vWf multimers from the circulation. Genetic studies within an afflicted family have demonstrated that the disease is linked to a Gly233-->Val amino acid substitution within the alpha-subunit of the oligomeric GP Ib-IX complex (Miller, J.L., D. Cunningham, V.A. Lyle, and C. L. Finch. 1991. Proc. Natl. Acad. Sci. USA. 88:4761-4765). To evaluate the functional consequences of this mutation, we constructed a recombinant analogue of the alpha-subunit of GP Ib containing Val233. Experiments comparing molecules with either Gly233 or Val233 revealed that the Val substitution generates a molecule with increased affinity for vWf. The recombinant fragment reproduces the functional abnormality of the GP Ib-IX complex in platelet-type von Willebrand disease, thus establishing the molecular basis of the bleeding disorder within this family. Moreover, it becomes apparent that structural elements responsible for the regulation of hemostasis through modulation of vWf affinity for platelets reside within the alpha-subunit of the GP Ib-IX complex. Images PMID:8486780

  2. Molecular Imaging of Platelet-Endothelial Interactions and Endothelial Von Willebrand Factor In Early and Mid-Stage Atherosclerosis

    PubMed Central

    Shim, Chi Young; Liu, Ya Ni; Atkinson, Tamara; Xie, Aris; Foster, Ted; Davidson, Brian P.; Treible, Mackenzie; Qi, Yue; López, José A.; Munday, Adam; Ruggeri, Zaverio; Lindner, Jonathan R.

    2015-01-01

    Background Non-thrombotic platelet-endothelial interactions may contribute to atherosclerotic plaque development, although in vivo studies examining mechanism without platelet pre-activation are lacking. Using in vivo molecular imaging at various stages of atherosclerosis, we quantified platelet-endothelial interactions and evaluated the contribution of major adhesion pathways. Methods and Results Mice deficient for the LDL-receptor and Apobec-1 were studied as an age-dependent model of atherosclerosis at 10, 20, 30, and 40 wks of age, which provided progressive increase in stage from very early fatty streak (10 wks) to large complex plaques without rupture (40 wks). Platelet-targeted contrast ultrasound molecular imaging of the thoracic aorta performed with microbubbles targeted to GPIbα demonstrated selective signal enhancement as early as 10 weeks of age. This signal increased progressively with age (almost 8-fold increase from 10 to 40 weeks, ANOVA p<0.001). Specificity for platelet targeting was confirmed by the reduction in platelet-targeted signal commensurate with the decrease in platelet count after immunodepletion with anti-GPIb or anti-CD41 antibody. Inhibition of P-selectin in 20 and 40 wk atherosclerotic mice resulted in a small (15-30%) reduction in platelet signal. Molecular imaging with microbubbles targeted to the A1 domain of von Willebrand factor (VWF) demonstrated selective signal enhancement at all time points which did not significantly increase with age. Treatment of 20 and 40 week mice with recombinant ADAMTS13 eliminated platelet and VWF molecular imaging signal. Conclusions Platelet-endothelial interactions occur in early atherosclerosis. These interactions are in part due to endothelial VWF large multimers which can be reversed with exogenous ADAMTS13. PMID:26156014

  3. Use of monoclonal antibody and colloidal gold in E.M. localization of von Willebrand factor in megakaryocytes and platelets.

    PubMed

    Jeanneau, C; Avner, P; Sultan, Y

    1984-10-01

    The subcellular localization of Factor VIII/von Willebrand protein (VIII R:Ag) is studied with monoclonal antibody and gold immunocytochemical technique. Monoclonal antibody against purified VIII R:Ag is brightly fluorescent on megakaryocytes and platelets. In E.M., gold immunolabeling is performed on thin cell sections of human megakaryocytes and platelets. Different embedding materials are used to preserve the antigenicity : Epon embedded megakaryocytes show a high concentration of VIII R:Ag in alpha-granules using 4F9 monoclonal antibody. In comparison, lowicryl K4M embedded material does not improve the same specificity, only a few platelets granules were stained. This subcellular localization, in full agreement with biochemical results appears visualized for the first time in E.M.

  4. Trigramin: Primary structure and its inhibition of von Willebrand factor binding to glycoprotein IIb/IIIa complex on human platelets

    SciTech Connect

    Huang, Turfu; Holt, J.C.; Kirby, E.P.; Niewiarowski, S.

    1989-01-24

    Trigramin, a naturally occurring peptide purified from Trimeresurus gramineus snake venom, inhibits platelet aggregation and the binding of {sup 125}I-fibrinogen to ADP-stimulated platelets without affecting the platelet-release reaction. {sup 125}I-trigramin binds to ADP-stimulated and to chymotrypsin-treated normal platelets but not to thrombasthenic platelets. {sup 125}I-trigramin binding to platelets is blocked by monoclonal antibodies directed against the glycoprotein IIb/IIIa complex and by Arg-Gly-Asp-Ser (RGDS). The authors determined the primary structure of trigramin, which is composed of a single polypeptide chain of 72 amino acid residues and six disulfide bridges. The molecular weight of trigramin calculated on the basis of amino acid sequence was 7500, and the average pI was 5.61. An RGD sequence appeared in the carboxy-terminal domain of trigramin. An amino-terminal fragment (7-33) of trigramin showed 39% homology with a region (1555-1581) of von Willebrand factor (vWF). Trigramin also showed 36% identity in a 42 amino acid overlap and 53% identity in a 15 amino acid overlap when compared with two adhesive proteins, collagen {alpha}{sub 1} (I) and laminin B{sub 1}, respectively. Trigramin blocked binding of human vWF to the glycoprotein IIb/IIIa complex in thrombin-activated platelets in a dose-dependent manner. In conclusion, the data suggest that the biological activity of trigramin may depend upon the presence of an RGD sequence, the secondary structure of the molecule, and perhaps some other sequences that it shares with adhesive proteins.

  5. Enzymes that hydrolyze adenine nucleotides in platelets and polymorphisms in the alpha2 gene of integrin alpha2beta1 in patients with von Willebrand disease.

    PubMed

    Santos, Karen Freitas; Battisti, Vanessa; Corrêa, Maísa de Carvalho; Mann, Thaís Rapachi; Pereira, Renata da Silva; Araújo, Maria do Carmo; Brülê, Alice Odete; Schetinger, Maria Rosa Chitolina; Morsch, Vera Maria

    2010-07-01

    Von Willebrand disease (VWD) is one of the most common inherited bleeding diseases caused by a qualitative or quantitative deficiency of the von Willebrand factor (FvW). FvW is a multimeric glycoprotein synthesized by megakaryocytes and endothelial cells and it is present in the subendothelial matrix, blood plasma, platelets, and endothelium. This glycoprotein plays an important role in thrombus formation by initiating platelet adhesion to sites of injury as well as platelet aggregation. The aim of this study was to evaluate the activities of enzymes that hydrolyze adenine nucleotides in platelets, ristocetin-induced platelet aggregation (RIPA), and polymorphisms of the alpha2 gene of alpha2beta1 integrin from VWD patients. Platelet nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase, and ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP) activities were verified in 14 VWD patients. For RIPA determination, a final concentration of 1.25 mg/ml of ristocetin was used. Polymorphisms of the alpha2 gene were analyzed through PCR. Platelet NTPDase and E-NPP were decreased in VWD patients. 5'-Nucleotidase activity was not statistically significant between controls and VWD patients. RIPA was significantly reduced, with an allelic frequency of 78.57% for 807C in VWD patients. Our results indicated reduced platelet NTPDase and E-NPP activities which might be related to the low platelet adhesiveness. The prevalence of the 807C allele might account for the variability in bleeding in VWD.

  6. Abnormal platelet von Willebrand factor (vWF) as a marker of abnormal function in megakaryocytic dysplasia.

    PubMed

    de Cataldo, F; Baudo, F; Redaelli, R; Corno, A R

    1995-03-01

    The myelodysplastic syndromes (MDS) are neoplastic disorders of the hemopoietic system; multilineage involvement is also evidenced by specific cellular dysfunctions. The von Willebrand factor (vWF), synthesized and processed in the megakaryocytes (MK), is stored in the alpha granules of the platelets. The platelet vWF multimeric pattern was studied in 18 patients with MDS, and in 4 with pernicious anemia (PA), to investigate whether the processing of vWF is abnormal in the megakaryocytic dysplasia. An abnormal multimeric pattern was observed in 10/18 MDS and 4/4 PA patients. The abnormality of this specific protein is the discrete expression of the basic disorder, and is reversible when hemopoiesis is normalized. Although the data do not allow any conclusion, abnormal synthesis is the likely explantation of the abnormality.

  7. Increased von Willebrand factor levels in patients with systemic lupus erythematosus reflect inflammation rather than increased propensity for platelet activation

    PubMed Central

    Raymond, Warren D; Eilertsen, Gro Østli

    2016-01-01

    Background von Willebrand factor (VWF) is involved in platelet plug formation and protein transport. Increased VWF levels in systemic lupus erythematous (SLE) are considered risk factors for vascular events. VWF protein levels, however, do not accurately reflect its platelet-aggregating function, which has not been examined in SLE. Methods Cross-sectional study with clinical and laboratory data obtained in patients with SLE (n=92) from a regional lupus registry. VWF function was determined by ristocetin-induced platelet aggregation (VWF ristocetin cofactor, VWF:RCo) and VWF levels by turbidimetric assay (VWF antigen, VWF:Ag). The platelet-aggregating activity per VWF unit was estimated by the VWF RCo/Ag ratio. Healthy controls served as comparators and associations were evaluated by non-parametric methods. Results VWF:Ag (142% vs 107%, p=0.001) and VWF:RCo levels (123% vs 78%, p<0.041) were increased in patients with SLE, but VWF RCo/Ag ratio was similar as in controls (0.83 vs 0.82, p=0.8). VWF:Ag levels were higher in patients experiencing serositis but unrelated to other manifestations, thrombotic disease, Systemic Lupus Erythematous Disease Activity Index 2000 or Systemic Lupus International Collaborative Clinics-Damage Index. VWF:Ag levels correlated significantly with VWF:RCo levels (Rs 0.8, p<0.001), erythrocyte sedimentation rate (ESR) (Rs 0.32, p<0.01), anti-dsDNA Ab (Rs 0.27, p<0.01), total IgG (Rs 0.33 p<0.01), fibrinogen (Rs 0.28, p<0.01) and ceruloplasmin (Rs 0.367, p<0.01) levels. VWF:RCo levels were not related to clinical findings but were correlated with ESR, anti-dsDNA and transferrin levels. No serological associations existed for VWF RCo/Ag ratio (all p>0.2). Conclusions In this SLE cohort, VWF:Ag behaved similarly to acute-phase reactants, but VWF:Ag increases were not matched by increases in functional activity per unit of VWF. Thus, more VWF did not increase the propensity for platelet aggregation in SLE. PMID:27651919

  8. Modification of the platelet binding domain of von Willebrand Factor (vWF)

    SciTech Connect

    Silverman, C.; Mascelli, M.A.; Karl, D.W.; Kirby, E.P.

    1986-05-01

    Bovine vWF has been modified with /sup 125/I-Bolton Hunter reagent (I/sup */-BHR) with a concomittant loss of its platelet agglutinating activity and a reduction in its ability to bind to platelets. BHR labels free alpha and epsilon amino groups. The I/sup */-BHR-vWF migrated as a single band of M/sub r/ = 210kD on reduced SDS polyacrylamide gels. Its multimeric composition on SDS agarose gels was identical to unlabeled vWF. Incorporation of an average of 1.2 moles of I/sup */-BHR/subunit vWF at pH 8.5 caused a 50% loss of platelet agglutinating activity. This represents less than 2% of the 118 lysine residues in each subunit vWF. No I/sup */-BHR was released after treatment with 1M hydroxylamine which would cleave O-acylated tyrosines. Digestion of both unlabeled and I/sup */-BHR-vWF with Protease 1, a metalloprotease from the venom of western diamondback rattlesnake, produces two fragments which have an M/sub r/ of 250kD and 200kD. The 250kD fragment contains the platelet binding site and is composed of 3 peptide chains with M/sub r/ 125kD, 78kD and 45kD. Gels of the 250kD fragment from I/sup */-BHR-vWF revealed radioactivity predominantly in the 125kD fragment, suggesting that the platelet binding site resides on the 125kD fragment.

  9. von Willebrand Factor-Rich Platelet Thrombi in the Liver Cause Sinusoidal Obstruction Syndrome following Oxaliplatin-Based Chemotherapy

    PubMed Central

    Nishigori, Naoto; Matsumoto, Masanori; Koyama, Fumikazu; Hayakawa, Masaki; Hatakeyayama, Kinta; Ko, Saiho; Fujimura, Yoshihiro; Nakajima, Yoshiyuki

    2015-01-01

    Oxaliplatin-based chemotherapy is widely used to treat advanced colorectal cancer (CRC). Sinusoidal obstruction syndrome (SOS) due to oxaliplatin is a serious type of chemotherapy-associated liver injury (CALI) in CRC patients. SOS is thought to be caused by the sinusoidal endothelial cell damage, which results in the release of unusually-large von Willebrand factor multimers (UL-VWFMs) from endothelial cells. To investigate the pathophysiology of CALI after oxaliplatin-based chemotherapy, we analyzed plasma concentration of von Willebrand factor (VWF) and the distribution of VWFMs in CRC patients. Twenty-three patients with advanced CRC who received oxaliplatin-based chemotherapy with (n = 6) and without (n = 17) bevacizumab were analyzed. CALI (n = 6) and splenomegaly (n = 9) were found only in patients who did not treated with bevacizumab. Plasma VWF antigen (VWF:Ag) and serum aspartate aminotransferase (AST) levels increased after chemotherapy only in patients without bevacizumab. VWFM analysis in patients who did not receive bevacizumab showed the presence of UL-VWFMs and absence of high molecular weight VWFMs during chemotherapy, especially in those with CALI. In addition, plasma VWF:Ag and AST levels increased after chemotherapy in patients with splenomegaly (n = 9), but not in patients without splenomegaly (n = 14). Histological findings in the liver tissue of patients who did not receive bevacizumab included sinusoidal dilatation and microthrombi in the sinusoids. Many microthrombi were positive for both anti-IIb/IIIa and anti-VWF antibodies. Plasma UL-VWFM levels might be increased by damage to endothelial cells as a result of oxaliplatin-based chemotherapy. Bevacizumab could prevent CALI and splenomegaly through inhibition of VWF-rich platelet thrombus formation. PMID:26580395

  10. Von Willebrand disease

    MedlinePlus

    ... done to diagnose this disease include: Bleeding time Blood typing Factor VIII level Platelet function analysis Platelet count Ristocetin cofactor test Von Willebrand factor specific tests ... invasive procedure. Blood plasma or certain factor VIII preparations may also ...

  11. von Willebrand factor fibers promote cancer-associated platelet aggregation in malignant melanoma of mice and humans

    PubMed Central

    Bauer, Alexander T.; Suckau, Jan; Frank, Kathrin; Desch, Anna; Goertz, Lukas; Wagner, Andreas H.; Hecker, Markus; Goerge, Tobias; Umansky, Ludmila; Beckhove, Philipp; Utikal, Jochen; Gorzelanny, Christian; Diaz-Valdes, Nancy; Umansky, Viktor

    2015-01-01

    Tumor-mediated procoagulatory activity leads to venous thromboembolism and supports metastasis in cancer patients. A prerequisite for metastasis formation is the interaction of cancer cells with endothelial cells (ECs) followed by their extravasation. Although it is known that activation of ECs and the release of the procoagulatory protein von Willebrand factor (VWF) is essential for malignancy, the underlying mechanisms remain poorly understood. We hypothesized that VWF fibers in tumor vessels promote tumor-associated thromboembolism and metastasis. Using in vitro settings, mouse models, and human tumor samples, we showed that melanoma cells activate ECs followed by the luminal release of VWF fibers and platelet aggregation in tumor microvessels. Analysis of human blood samples and tumor tissue revealed that a promoted VWF release combined with a local inhibition of proteolytic activity and protein expression of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type I repeats 13) accounts for this procoagulatory milieu. Blocking endothelial cell activation by the low-molecular-weight heparin tinzaparin was accompanied by a lack of VWF networks and inhibited tumor progression in a transgenic mouse model. Our findings implicate a mechanism wherein tumor-derived vascular endothelial growth factor-A (VEGF-A) promotes tumor progression and angiogenesis. Thus, targeting EC activation envisions new therapeutic strategies attenuating tumor-related angiogenesis and coagulation. PMID:25977583

  12. Platelet aggregation test

    MedlinePlus

    ... disorders Uremia (a result of kidney failure ) Von Willebrand disease (a bleeding disorder) Risks There is very little ... vasculitis Platelet count Polycythemia vera Prerenal azotemia Von Willebrand disease Review Date 1/27/2015 Updated by: Yi- ...

  13. A novel platelet-type von Willebrand disease mutation (GP1BA p.Met255Ile) associated with type 2B "Malmö/New York" von Willebrand disease.

    PubMed

    Lavenu-Bombled, Cécile; Guitton, Corinne; Dupuis, Arnaud; Baas, Marie-Jeanne; Desconclois, Céline; Dreyfus, Marie; Li, Renhao; Caron, Claudine; Gachet, Christian; Fressinaud, Edith; Lanza, François

    2016-11-30

    Interaction between von Willebrand factor (VWF) and platelet GPIbα is required for primary haemostasis. Lack or loss-of-function in the ligand-receptor pair results in bleeding complications. Paradoxically, gain-of-function mutations in VWF or GPIbα also result in bleeding complications as observed in type 2B von Willebrand disease (VWD) and platelet-type- (PT-) VWD, respectively. A similar phenotype is observed with increased ristocetin-induced platelet agglutination and disappearance of the highest molecular weight multimers of VWF. We evaluated a patient with a bleeding disorder and a biological presentation compatible with type 2B VWD. VWF and platelet functional assays, sequencing of the VWF and GP1BA genes, and expression studies in HEK cells were performed. Sequencing of the VWF gene in the propositus revealed a heterozygous p.Pro1266Leu mutation previously found in type 2B VWD Malmö/New York. These variants are characterised by a mild phenotype and a normal VWF multimer composition suggesting the presence of a second mutation in our propositus. Sequencing of the GP1BA gene revealed a heterozygous c.765G>A substitution changing Met at position 255 of GPIbα to Ile. This new mutation is located in the β-switch domain where five other gain-of-function mutations have been reported in PT-VWD. Expression of GPIbα Ile255 in HEK GPIb-IX cells resulted in enhanced VWF binding compared to wild-type, similar to known PT-VWD mutations (p.Val249, p.Ser249 and p.Val255) indicating that it contributes to the propositus defects. This first report associating PT- with type 2B VWD illustrates the importance of combining biological assays with genetic testing to better understand the clinical phenotype.

  14. Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR) Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.

    PubMed

    Stockley, Jacqueline; Nisar, Shaista P; Leo, Vincenzo C; Sabi, Essa; Cunningham, Margaret R; Eikenboom, Jeroen C; Lethagen, Stefan; Schneppenheim, Reinhard; Goodeve, Anne C; Watson, Steve P; Mundell, Stuart J; Daly, Martina E

    2015-01-01

    The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12) could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =), both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N) was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =). Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder.

  15. THE PAPWORTH PLUG - successful use of high dose fibrinogen concentrate and platelet concentrate in potential life-threatening complication after cardiopulmonary bypass surgery in a patient with Type 2M Vicenza von Willebrand Disease.

    PubMed

    Amerikanou, R; MacDonald, S; Lawrence, K; Large, S; Besser, M W

    2012-07-01

    Anecdotally, fibrinogen concentrate (FC) has been used as a "universal" haemostatic agent in complex post-cardiopulmonary bypass (CPB) coagulopathy. We present a case where FC and two pools of platelets prevented life-threatening bleeding in a patient with moderate von Willebrand Disease (vWD) immediately post CPB.

  16. Tetraglyme Coatings Reduce Fibrinogen and von Willebrand Factor Adsorption and Platelet Adhesion under Both Static and Flow Conditions

    PubMed Central

    Zhang, Min; Horbett, Thomas A.

    2013-01-01

    Previous studies have showed that radio-frequency plasma deposited tetraglyme coatings greatly reduced fibrinogen adsorption (ΓFg) from highly diluted plasmas (0.1% and 1%) and subsequent platelet adhesion under static conditions. In this study, the protein resistant properties of tetraglyme were re-examined with high-concentration plasma, and subsequent platelet adhesion was measured under both static and flow conditions. The resistance of tetraglyme to vWf adsorption (ΓvWf) and the role of vWf in platelet adhesion under flow were also investigated. ΓFg and ΓvWf were measured with 125I radiolabeled proteins. Flow studies were done at shear rates of 50 or 500 s−1 by passing a platelet/red cell suspension through a GlycoTech flow chamber. When adsorbed from a series of increasing plasma concentrations, the adsorption of both proteins to tetraglyme increased steadily, and did not show a peak at intermediate dilutions, i.e. there was no Vroman effect. When plasma concentration was less than 10%, the tetraglyme surface was highly non-fouling, exhibiting ultralow ΓFg (less than 5 ng/ cm2) and extremely low platelet adhesion under both static and flow conditions. However, when the adsorption was done from 100% plasma, ΓFg was much higher (~ 85 ng/cm2), indicating that tetraglyme surface may not be sufficiently protein-resistant in the physiological environment. To correlate platelet adhesion under flow with ΓFg and ΓvWf, a series of tetraglyme surfaces varying in ether content and protein adsorption was created by varying deposition power. On these surfaces, platelet adhesion at low shear rate depended only on the amount of ΓFg, but under high shear, both ΓFg and ΓvWf affected platelet adhesion. In particular, it was found that ΓvWf must be reduced to less than 0.4 ng/cm2 to achieve ultra low platelet adhesion under high shear. PMID:18496865

  17. Simplagrin, a Platelet Aggregation Inhibitor from Simulium nigrimanum Salivary Glands Specifically Binds to the Von Willebrand Factor Receptor in Collagen and Inhibits Carotid Thrombus Formation In Vivo

    PubMed Central

    Chagas, Andrezza C.; McPhie, Peter; San, Hong; Narum, David; Reiter, Karine; Tokomasu, Fuyuki; Brayner, Fabio A.; Alves, Luiz C.; Ribeiro, José M. C.; Calvo, Eric

    2014-01-01

    Background Among the several challenges faced by bloodsucking arthropods, the vertebrate hemostatic response against blood loss represents an important barrier to efficient blood feeding. Here we report the first inhibitor of collagen-induced platelet aggregation derived from the salivary glands of a black fly (Simulium nigrimanum), named Simplagrin. Methods and Findings Simplagrin was expressed in mammalian cells and purified by affinity-and size-exclusion chromatography. Light-scattering studies showed that Simplagrin has an elongated monomeric form with a hydrodynamic radius of 5.6 nm. Simplagrin binds to collagen (type I-VI) with high affinity (2–15 nM), and this interaction does not involve any significant conformational change as determined by circular dichroism spectroscopy. Simplagrin-collagen interaction is both entropically and enthalpically driven with a large negative ΔG, indicating that this interaction is favorable and occurs spontaneously. Simplagrin specifically inhibits von Willebrand factor interaction with collagen type III and completely blocks platelet adhesion to collagen under flow conditions at high shear rates; however, Simplagrin failed to block glycoprotein VI and Iα2β1 interaction to collagen. Simplagrin binds to RGQOGVMGF peptide with an affinity (KD 11 nM) similar to that of Simplagrin for collagen. Furthermore, Simplagrin prevents laser-induced carotid thrombus formation in vivo without significant bleeding in mice and could be useful as an antithrombotic agent in thrombosis related disease. Conclusion Our results support the orthology of the Aegyptin clade in bloodsucking Nematocera and the hypothesis of a faster evolutionary rate of salivary function of proteins from blood feeding arthropods. PMID:24921659

  18. Lyophilized Platelets: Challenges and Opportunities

    DTIC Science & Technology

    2011-05-01

    and protozoan infections; alloimmunization resulting in refracto- riness to future platelet transfusions; and graft-versus-host disease . The...for preparation of lyophilized platelets has recently been described.7 Freeze-dried platelets retain native von Willebrand factor-mediated adhesion

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

    SciTech Connect

    Laduca, F.M.; Bell, W.R.; Bettigole, R.E. State Univ. of New York, Buffalo )

    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.

  20. Platelet activation risk index as a prognostic thrombosis indicator

    PubMed Central

    Zlobina, K. E.; Guria, G. Th.

    2016-01-01

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

  1. Collection Development "Budget Decorating": Decorating Cents

    ERIC Educational Resources Information Center

    Kumaran, Maha

    2008-01-01

    Home decorating is a popular idea these days as seen in the rise of cable television channels like TLC and HGTV (Home & Garden Television) and TV shows like "Trading Spaces, Take This House and Sell It, Design on a Dime, Decorating Cents," and many others. Throughout history, humans have always expressed the desire to personalize and beautify…

  2. Human Platelet Senescence Study.

    DTIC Science & Technology

    1980-03-01

    ability to measure certain enzymes to their oxidation-reduc other enzymes which can be measured by o phosphatase , acid phosphatase , chymotryp...alkaline sin, trypsin, esterases (17)); M use of n A or wheat germ agglutinin in the second etect specific carbohydrate constituents. We have...Von Willebrand factor. Nurden and Caen also demonstrated that GPI was rich in sialic acid (5) and probably responsible for the platelets’ surface

  3. Platelet Glycoprotein lb-1X and Malignancy

    DTIC Science & Technology

    2010-09-01

    of mouse models of platelet dysfunction in the progression of cancer to metastatic disease . During the next year we propose to examine the relevance...spread of metastatic disease represents a fundamental change in significantly shortening the life span of patients with breast cancer. Thus...von Willebrand factor (vWF) and thrombin, illustrating platelet GP Ib-IX as a major initiator of platelet thrombus formation in the arterial

  4. Platelet Glycoprotein Ib-IX and Malignancy

    DTIC Science & Technology

    2010-09-01

    cancer to metastatic disease . During the next year we propose to examine the relevance of platelet receptors in models of spontaneous metastasis. A...the prognosis for recovery from breast cancer cannot be under emphasized. Indeed, the spread of metastatic disease represents a fundamental change in...IX have been identified, including von Willebrand factor (vWF) and thrombin, illustrating platelet GP Ib-IX as a major initiator of platelet thrombus

  5. [Activation and inhibitory mechanisms of blood platelets].

    PubMed

    Suzuki-Inoue, Katsue

    2014-07-01

    Exposure of platelets to subendothelial matrices initiates physiological hemostasis and pathological thrombosis. Under high shear stress, von Willebrand factor bridges newly exposed collagen to glycoprotein (GP) Ib on platelets. This initial tethering facilitates association between the collagen receptor GPVI and collagen, which generates tyrosine kinase-dependent activation signals, followed by release of secondary mediators and integrin activation. Activated integrin can bind to their ligands including fibrinogen. The released secondary mediators, ADP and thromboxane A2, activate integrin of flowing platelets, which enables formation of platelet thrombi by binding of activated flowing platelets and adhered platelets to collagen via binding between activated aIIbbeta3 integrin and fibrinogen. Platelets also have inhibitory mechanisms, which help to prevent unwanted platelet activation in vivo.

  6. von Willebrand factor and von Willebrand disease.

    PubMed

    Matsui, Taei; Hamako, Jiharu

    von Willebrand factor (VWF) has two major roles in hemostasis, as a form of molecular glue which functions in platelet plug formation and as a protective transporter for coagulation factor VIII (FVIII). VWF shows a multimeric chain structure composed of 270 kDa subunits containing binding domains for FVIII, platelet and collagens. Biosynthesis, storage, secretion of VWF and the cleavage process by ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 repeats 13) regulating VWF activity have been elucidated. von Willebrand disease (VWD) is an autosomal bleeding disorder, first documented in 1926, caused by quantitative or qualitative deficiency of VWF. The classification and molecular pathogenesis of VWD have been developed during a 90-year period based on clinical laboratory analysis of VWF, and structure-function analysis of mutant VWF with amino acid substitutions (genetic changes). VWF is a unique and very large multifunctional plasma protein, the hemostatic activity of which is dynamically regulated by physiological shear stress in the blood stream.

  7. Two novel anti-von Willebrand factor monoclonal antibodies.

    PubMed

    Spadafora-Ferreira, M; Lopes, A A; Coelho, V; Guilherme, L; Kalil, J

    2000-01-15

    Von Willebrand Factor is a multimer produced by endothelial cells and megakaryocytes, being stored in intracellular organelles, such as the Weibel-Palade bodies and alpha-granules in endothelial cells and platelets, respectively. This molecule acts as a carrier protein for factor VIIIc, involved in the intrinsic pathway of blood coagulation maintaining its stability in circulation. Von Willebrand Factor also plays an important role in platelet aggregation and adhesion to injured vessel wall. It interacts with platelets through two distinct glycoproteins, GPIb and GPIIb/IIIa. We raised two monoclonal antibodies, ECA-3 and ECA-4, against human umbilical vascular endothelial cells that recognize and immunoprecipitate von Willebrand Factor. Interestingly, ECA-4 monoclonal antibody is able to completely inhibit platelet agglutination induced by ristocetin, suggesting that it binds to von Willebrand Factor close to platelet GPIb binding site. The use of monoclonal antibodies to identify von Willebrand Factor binding regions to factor VIII or platelets has been reported by others. In pulmonary hypertension, abnormalities have been detected on the multimeric structure of the molecule as well as on its proteolytic fragments, by using monoclonal antibodies. Moreover, monoclonal antibodies raised against specific regions of von Willebrand Factor molecule may allow studies of functional abnormalities of this protein in inherited and acquired disorders like subtypes of von Willebrand's disease.

  8. Activity of platelet hemostasis in children with spinal deformities.

    PubMed

    Medvedev, I N; Lapshina, E V; Zavalishina, S Yu

    2010-10-01

    An increase of adhesion and aggregation functions of platelets in vivo and in vitro was detected in 5-6-year-old children with scoliosis. These disorders were caused by hyperproduction of von Willebrand's factor in the vascular wall and intensification of thromboxane production in blood platelets. Activation of thromboxane formation is the main cause of platelet hyperactivity in children with scoliosis. Correction of platelet hemostasis may include pathogenetically substantiated complex of therapeutic exercises, swimming, and massage.

  9. Basic Cake Decorating Workbook.

    ERIC Educational Resources Information Center

    Bogdany, Mel

    Included in this student workbook for basic cake decorating are the following: (1) Drawings of steps in a basic way to ice a layer cake, how to make a paper cone, various sizes of flower nails, various sizes and types of tin pastry tubes, and special rose tubes; (2) recipes for basic decorating icings (buttercream, rose paste, and royal icing);…

  10. Multiscale model of platelet translocation and collision

    NASA Astrophysics Data System (ADS)

    Wang, Weiwei; Mody, Nipa A.; King, Michael R.

    2013-07-01

    The tethering of platelets on the injured vessel surface mediated by glycoprotein Ibα (GPIbα) - Von Willebrand factor (vWF) bonds, as well as the interaction between flowing platelets and adherent platelets, are two key events that take place immediately following blood vessel injury. This early-stage platelet deposition and accumulation triggers the initiation of hemostasis, a self-defensive mechanism to prevent the body from excessive blood loss. To understand and predict this complex process, one must integrate experimentally determined information on the mechanics and biochemical kinetics of participating receptors over very small time frames (1-1000 μs) and length scales (10-100 nm), to collective phenomena occurring over seconds and tens of microns. In the present study, a unique three dimensional multiscale computational model, Platelet Adhesive Dynamics (PAD), was applied to elucidate the unique physics of (i) a non-spherical, disk-shaped platelet interacting and tethering onto the damaged vessel wall followed by (ii) collisional interactions between a flowing platelet with a downstream adherent platelet. By analyzing numerous simulations under different physiological conditions, we conclude that the platelet's unique spheroid-shape provides heterogeneous, orientation-dependent translocation (rolling) behavior which enhances cell-wall interactions. We also conclude that platelet-platelet near field interactions are critical for cell-cell communication during the initiation of microthrombi. The PAD model described here helps to identify the physical factors that control the initial stages of platelet capture during this process.

  11. Platelet Donation

    MedlinePlus

    ... donating platelets, can I still donate blood? What blood types should donate platelets? Can I donate plasma at ... Community Learn About Blood Blood Facts and Statistics Blood Types Blood Components What Happens to Donated Blood Blood ...

  12. Platelet transport in microchannels

    NASA Astrophysics Data System (ADS)

    Reyssat, Mathilde; Le Goff, Anne; Blin, Antoine; Pujos, Justine; Magniez, Aurélie; Baruch, Dominique

    2013-11-01

    Blood platelets are small enucleated cells responsible for the arrest of bleeding. These cells have the ability to tether and translocate on injured vascular endothelium, thanks to a specific interaction between a receptor of their membrane and a protein expressed by the cells composing the inner wall of the vessel, the von Willebrand factor (VWF). Others cells have such abilities of rolling. Leucocytes, for example, translocate on surface due to a specific interaction between selectin molecules and their respective glycoprotein ligands. These kinds of cells present two modes of transport: they can either be advected by the flux, or translocate on surfaces due to specific ligand-receptor interactions. Our work consists first in studying experimentally the transport of platelets along a microchannel and then in modeling this particular cell transport. Due to these two modes of transport along a channel, platelets adhering to the surface are not equally distributed along the channel axis. We describe the evolution of the density of platelets with time and distance.

  13. [Biology of von Willebrand factor].

    PubMed

    Girma, Jean-Pierre

    2006-01-01

    Von Willebrand factor (VWF) is a multimeric glycoprotein synthesized by megakaryocytes and endothelial cells. It is stored in platelets and endothelial cells and secreted towards subendothelium and plasma. VWF multimers consist of linear arrangements of identical subunits with a molecular weight of 270 kDa. The longest multimers reach more than 20 x 10(6) Da in storage granules. In the circulation, the multimer size is limited by the specific protease ADAMTS13. In primary hemostasis, VWF plays a key role as a molecular bridge in adhesion between platelets and subendothelium and between platelets during their aggregation. These functions, which involve the interaction with platelet glycoprotein lb, are mainly enhanced by VWF immobilization onto hydrophobic surfaces (collagen, cell membrane) and by high shear rates found in microcirculation and stenosed arteries. In these functions, the higher molecular weight forms are the most efficient. Under such hemodynamic conditions, proteolytic activity of ADAMTS13 is also optimal and limits the multimer size to about 15 x 10(6) Da as soon as their secretion. Thus ADAMTS13 appears as a key physiologic regulator of the VWF platelet functions. In the microcirculation, the lack of ADAMTS13 activity can result in the formation of VWF-rich platelet aggregates responsible for thrombotic thrombocytopenic purpura.

  14. Signaling during platelet adhesion and activation

    PubMed Central

    Li, Zhenyu; Delaney, M. Keegan; O’Brien, Kelly A.; Du, Xiaoping

    2011-01-01

    Upon vascular injury, platelets are activated by adhesion to adhesive proteins like von Willebrand factor and collagen, or by soluble platelet agonists like ADP, thrombin, and thromboxane A2. These adhesive proteins and soluble agonists induce signal transduction via their respective receptors. The various receptor-specific platelet activation signaling pathways converge into common signaling events, which stimulate platelet shape change, granule secretion, and ultimately induce the “inside-out” signaling process leading to activation of the ligand binding function of integrin αIIbβ3. Ligand binding to integrin αIIbβ3 mediates platelet adhesion and aggregation and triggers “outside-in” signaling, resulting in platelet spreading, additional granule secretion, stabilization of platelet adhesion and aggregation, and clot retraction. It has become increasingly evident that agonist-induced platelet activation signals also crosstalk with integrin “outside-in” signals to regulate platelet responses. Platelet activation involves a series of rapid positive feedback loops that greatly amplify initial activation signals, and enable robust platelet recruitment and thrombus stabilization. Recent studies have provided novel insight into the molecular mechanisms of these processes. PMID:21071698

  15. Desmopressin (DDAVP) improves recruitment of activated platelets to collagen but simultaneously increases platelet endothelial interactions in vitro.

    PubMed

    Calmer, Simone; Ferkau, Annika; Larmann, Jan; Johanning, Kai; Czaja, Eliana; Hagl, Christian; Echtermeyer, Frank; Goudeva, Lilia; Heuft, Hans-Gert; Theilmeier, Gregor

    2014-01-01

    Platelet dysfunction can cause clinically relevant bleeding. Treatment with DDAVP is advocated for this condition. DDAVP increases von Willebrand factor (VWF) on endothelial cells (ECs) and in plasma. VWF could facilitate platelet deposition on subendothelial collagen. VWF also facilitates platelet/EC interactions. Therefore DDAVP could precipitate thromboembolic events. We used a flow chamber model to study in vitro and ex vivo if DDAVP alters recruitment of platelets to EC and collagen. Resting or TRAP-activated platelets and EC were treated individually or simultaneously with 0.4 ng/ml DDAVP. Fluorophor-labeled platelets (10(6)/ml) were resuspended in reconstituted blood and superfused across EC and collagen in an in vitro flow chamber model at arterial shear (320 s(-1)). Adhesion of platelets to the respective surface was recorded fluorescence microscopically and platelet covered area was assessed. TRAP significantly induced adhesiveness of platelets for collagen and EC. DDAVP pretreatment of platelets did not affect adhesiveness of resting or TRAP-activated platelets for collagen or EC. Adhesiveness of resting but not TRAP-activated platelets was induced on DDAVP-treated EC. DDAVP-conditioned EC supernatant contained vWF and significantly increased platelet deposition on collagen. Platelets from patients with clinically suspected platelet dysfunction undergoing aortic valve replacement exhibited decreased platelet deposition on collagen surfaces. In summary, our data confirm that DDAVP can induce release of platelet adhesion promoting factors from EC, which is most likely vWF. DDAVP has no direct effect on platelets. Blood samples from DDAVP-treated patients do not exhibit significantly augmented platelet deposition on collagen ex vivo. This influence of released promoting factors might cause an increase of undesirable interactions of platelets with EC.

  16. Altered megakaryocytopoiesis in von Willebrand type 2B disease.

    PubMed

    Nurden, A T; Federici, A B; Nurden, P

    2009-07-01

    Type 2B von Willebrand disease (VWD2B) is caused by gain-of-function amino acid substitutions in the von Willebrand factor (VWF) A1 domain. These allow facilitated binding of mutated VWF to platelet GPIbalpha with prolonged lifetimes of VWF bonds and enhanced ADAMTS-13 cleavage of large VWF multimers. A bleeding rather than prothrombotic syndrome is due to: (i) decreased large VWF multimers in plasma; (ii) limited thrombus formation; and (iii) thrombocytopenia affecting some but not all patients. Accumulating evidence points to an altered megakaryocytopoiesis in VWD2B with the production of enlarged or giant platelets showing an abnormal ultrastructure and, in a cohort of patients, the presence of circulating platelet agglutinates. In fact, evidence from in vitro cultures and marrow aspirates suggests that the upregulated VWF function can lead to abnormal VWF trafficking in megakaryocytes, a modified platelet production with interacting proplatelets, and the presence or even release of platelet agglutinates in the bone marrow.

  17. An update on type 2B von Willebrand disease.

    PubMed

    Mikhail, Sameh; Aldin, Ehab Saad; Streiff, Michael; Zeidan, Amer

    2014-04-01

    Type 2B von Willebrand disease (VWD) accounts for fewer than 5% of all VWD patients. In this disease, mutations in the A1 domain result in increased von Willebrand factor (VWF) binding to platelet GPIbα receptors, causing increased platelet clearance and preferential loss of high molecular weight VWF multimers. Diagnosis is complicated because of significant clinical variations even among patients with identical mutations. Platelet transfusion often provides suboptimal results since transfused platelets may be aggregated by the patients' abnormal VWF. Desmopressin may cause a transient decrease in platelet count that could lead to an increased risk of bleeding. Replacement therapy with factor VIII/VWF concentrates is the most effective approach to prevention and treatment of bleeding in type 2B VWD.

  18. Biosynthesis, processing and secretion of von Willebrand factor: biological implications.

    PubMed

    de Wit, T R; van Mourik, J A

    2001-06-01

    von Willebrand factor is a multimeric plasma glycoprotein that is required for normal haemostasis. von Willebrand factor is synthesized by endothelial cells and megakaryocytes, and originates from its precursor pro-von Willebrand factor. The endoproteolytic processing of pro-von Willebrand factor results in mature von Willebrand factor and von Willebrand factor propeptide (also known as von Willebrand Ag II). In endothelial cells, the propeptide controls the polymerization and subsequent targeting of von Willebrand factor to the storage vesicles, the so-called Weibel-Palade bodies. Upon stimulation of the endothelial cells, the Weibel-Palade bodies are translocated to the plasma membrane of the cell, and mature von Willebrand factor and its propeptide are co-secreted. After release, these polypeptides have divergent fates and serve different biological functions. Mature von Willebrand factor both controls platelet adhesion and aggregation at sites of vascular injury and acts as a chaperone protein for coagulation factor VIII. The von Willebrand factor propeptide may serve a role in modulating inflammatory processes. This still growing body of information indicates that the biological function of the von Willebrand factor gene product is more diverse than was previously thought.

  19. Qualitative disorders of platelets and megakaryocytes.

    PubMed

    Nurden, A T

    2005-08-01

    Qualitative disorders of platelet function and production form a large group of rare diseases which cover a multitude of genetic defects that by and large have as a common symptom, excessive mucocutaneous bleeding. Glanzmann thrombasthenia, is enabling us to learn much about the pathophysiology of integrins and of how alphaIIb beta3 functions. Bernard-Soulier syndrome, an example of macrothrombocytopenia, combines the production of large platelets with a deficit or non-functioning of the major adhesion receptor of platelets, the GPIb-IX-V complex. Amino acid substitutions in GPIb alpha, may lead to up-regulation and spontaneous binding of von Willebrand factor as in Platelet-type von Willebrand disease. In disorders with defects in the MYH9 gene, macrothrombocytopenias are linked to modifications in kidney, eye or ear, whereas other inherited thrombocytopenias variously link a low platelet count with a propensity to leukemia, skeletal defects, learning impairment, and abnormal red cells. Defects of secretion from platelets include an abnormal alpha-granule formation as in the gray platelet syndrome (with marrow myelofibrosis), and of organelle biogenesis in the Hermansky-Pudlak and Chediak-Higashi syndromes where platelet dense body defects are linked to abnormalities of other lysosomal-like organelles including melanosomes. Finally, defects involving surface receptors (P2Y(12), TPalpha) for activating stimuli, of proteins essential for signaling pathways (including Wiskott-Aldrich syndrome), and of platelet-derived procoagulant activity (Scott syndrome) show how studies on platelet disorders are helping unravel the pathways of primary hemostasis.

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

    PubMed

    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 (

  1. Thrombospondin-1 in von Willebrand factor function.

    PubMed

    Bonnefoy, Arnaud; Hoylaerts, Marc F

    2008-10-01

    Thrombospondin-1 (TSP1), expressed in many cells and tissues is abundantly present in platelet alpha-granules, from where it is released upon platelet activation. Murine Tsp1(-/-) platelet studies have revealed that TSP1 is redundant for platelet aggregation, but that it reinforces platelet aggregate stabilization, especially in a shear field. von Willebrand factor (VWF), synthesized by megakaryocytes and endothelial cells is stored both in platelet alpha-granules and in endothelial Weibel-Palade bodies as ultralarge multimers. When released from endothelial cells, these multimers are temporarily retained on the endothelium, to be cleaved by the plasma protease ADAMTS13 into smaller and hemostatically less reactive multimers, released in plasma. This protease shows partial sequence identity with the type 1 (TSR1) and type 2 (TSR2) repeats of TSP1 and contains 1 TSR1 and 6 TSR2 repeats. TSP1, locally released by platelets, competes with ADAMTS13 during VWF proteolysis and controls the degree of VWF multimer processing. In addition, TSP1 and VWF both interact with the platelet GPIb/V/IX membrane complex, primarily in flow. These interactions control the recruitment of platelets to (sub) endothelial VWF and TSP1, exposed to the circulation, as a consequence of vascular inflammation and endothelial injury. TSP1-VWF interactions do not strictly enhance platelet recruitment and secreted TSP1 even weakly competes with the dynamic platelet rolling and adhesion onto VWF. Hence, TSP1 and VWF show partially related hemostatic functions, the most important one being the TSP1 role in the ADAMTS13 operated VWF multimer processing, in pro-inflammatory and thrombogenic conditions.

  2. Reversible Hypothermia-Induced Inhibition of Human Platelet Activation in Whole Blood in Vitro and in Vivo

    DTIC Science & Technology

    2007-11-02

    IX complex (the von Willebrand factor receptor) (12), thromboxane Bj generation (the stable metabolite of thromboxane A2) (13), platelet aggregate...6D1 (provided by Dr. Barry S. Coller, SUNY, Stony Brook) is directed against the von Willebrand factor receptor on the glycocalicin portion of the a...Fig 1, panel A) and, after a delay of approximately 20 seconds, downregulation of the platelet surface expression of GPIb (the von Willebrand factor

  3. Antibody decoration of neurofilaments

    PubMed Central

    1981-01-01

    We have decorated neurofilaments with antibodies against three polypeptides (designated here as H [mol wt = 195,000], 45[mol wt = 145,000], and 46[mol wt = 73,000]) in an effort to understand the arrangement of these polypeptides within neurofilaments. The three polypeptides were purified and antibodies were raised against each. The cross-reactivity of the antibodies suggested that each polypeptide contains both shared and unique antigenic determinants. The differential reactivities of each antibody preparation were enhanced by adsorption with the two heterologous polypeptides, and the resulting preparations were used to decorate purified neurofilaments, which were then negatively stained and examined in an electron microscope. The appearance of the antibody-decorated structures led to the following conclusions: All three polypeptides are physically associated with the same neurofilament. However, the disposition of H and 46 within a filament is different; 46 antigens appear to be associated with a "central core" of the filament, whereas H antigens compose a structure more loosely and peripherally attached to the central core and periodically arranged along its axis. The antibody-decorated H- containing structure assumes variable configurations; in some cases it appears asa bridge connecting two filaments; in other cases it appears as a helix wrapping the central core with a period of approximately 1,000 A and an apparent unit length of approximately 1.5 periods. These configurations suggest several functional implications, including the possibility that H is a component of the cross-bridges observed between filaments in situ. We also note that the central core-helix relationship could be used in the design of an intracellular transport motor. PMID:6788775

  4. Human blood platelets lack nitric oxide synthase activity.

    PubMed

    Böhmer, Anke; Gambaryan, Stepan; Tsikas, Dimitrios

    2015-01-01

    Reports on expression and functionality of nitric oxide synthase (NOS) activity in human blood platelets and erythrocytes are contradictory. We used a specific gas chromatography-mass spectrometry (GC-MS) method to detect NOS activity in human platelets. The method measures simultaneously [(15)N]nitrite and [(15)N]nitrate formed from oxidized (15)N-labeled nitric oxide ((15)NO) upon its NOS-catalyzed formation from the substrate l-[guanidino-(15)N2]-arginine. Using this GC-MS assay, we did not detect functional NOS in non-stimulated platelets and in intact platelets activated by various agonists (adenosine diphosphate, collagen, thrombin, or von Willebrand factor) or lysed platelets. l-[guanidino-nitro]-Arginine-inhibitable NOS activity was measured after addition of recombinant human endothelial NOS to lysed platelets. Previous and recent studies from our group challenge expression and functionality of NOS in human platelets and erythrocytes.

  5. 7. WEST PORTAL. NOTE DECORATIVE ELEMENTS, INCLUDING DECORATIVE CAPS COVERING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. WEST PORTAL. NOTE DECORATIVE ELEMENTS, INCLUDING DECORATIVE CAPS COVERING COMPRESSION BLOCKS. NAME OF THE BRIDGE COMPANY WITH HERALDIC CARTOUCHE BEARING NAMES OF THREE COUNTY COMMISSIONERS BELOW, AND OPEN SCROLL WORK IN WROUGHT IRON. - Peevy Road Bridge, Peevy Road spanning Perkiomen Creek in Upper Hanover Township, East Greenville, Montgomery County, PA

  6. The role of von Willebrand factor in thrombus formation.

    PubMed

    Ruggeri, Zaverio M

    2007-01-01

    Von Willebrand factor (VWF) is a large multimeric glycoprotein produced in endothelial cells and megakaryocytes and present in subendothelial matrix, blood plasma and platelets. VWF mediates adhesion and aggregation of platelets at sites of vascular injury, processes that are critical for both haemostasis and thrombosis. Thrombus formation involves complex events that are influenced by different environmental conditions. Progress in understanding the structure and function of VWF and the mechanisms that underlie its interactions with platelets has led to important insight into the differentiation between normal haemostasis and pathological arterial thrombosis. The conventional view of signalling-induced platelet aggregation has recently been extended to include activation-independent aggregation. A novel mechanism has been demonstrated for initiating thrombus formation under high haemodynamic forces that involves alpha(IIb)beta(3)-independent platelet aggregation at the interface between immobilised and soluble VWF. This VWF-mediated process may be a key determinant of platelet accumulation in stenotic arteries leading to acute thrombotic occlusion.

  7. von Willebrand Disease

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Von Willebrand Disease? Von Willebrand disease (VWD) is a bleeding disorder. ... while hemophilia mainly affects males. Types of von Willebrand Disease The three major types of VWD are called ...

  8. Hereditary sideroblastic anemia with associated platelet abnormalities.

    PubMed

    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.

  9. Platelet-mimetic strategies for modulating the wound environment and inflammatory responses

    PubMed Central

    Nandi, Seema

    2016-01-01

    Platelets closely interface with the immune system to fight pathogens, target wound sites, and regulate tissue repair. Natural platelet levels within the body can be depleted for a variety of reasons, including excessive bleeding following traumatic injury, or diseases such as cancer and bacterial or viral infections. Platelet transfusions are commonly used to improve platelet count and hemostatic function in these cases, but transfusions can be complicated by the contamination risks and short storage life of donated platelets. Lyophilized platelets that can be freeze-dried and stored for longer periods of time and synthetic platelet-mimetic technologies that can enhance or replace the functions of natural platelets, while minimizing adverse immune responses have been explored as alternatives to transfusion. Synthetic platelets typically comprise nanoparticles surface-decorated with peptides or ligands to recreate specific biological characteristics of platelets, including targeting of wound and disease sites and facilitating platelet aggregation. Recent efforts in synthetic platelet design have additionally focused on matching platelet shape and mechanics to recreate the marginalization and clot contraction capabilities of natural platelets. The ability to specifically tune the properties of synthetic platelet-mimetic materials has shown utility in a variety of applications including hemostasis, drug delivery, and targeted delivery of cancer therapeutics. PMID:27190260

  10. Complications of decorative tattoo.

    PubMed

    Shinohara, Michi M

    2016-01-01

    Decorative tattoo is a popular practice that is generally safe when performed in the professional setting but can be associated with a variety of inflammatory, infectious, and neoplastic complications, risks that may be increased with current trends in home tattooing. Modern tattoo inks contain azo dyes and are often of unknown composition and not currently regulated for content or purity. Biopsy of most (if not all) tattoo reactions presenting to the dermatologist is recommended, given recent clusters of nontuberculous mycobacterial infections occurring within tattoo, as well as associations between tattoo reactions and systemic diseases such as sarcoidosis.

  11. [Molecular biology of von Willebrand disease].

    PubMed

    Melo-Nava, Brenda; Peñaloza, Rosenda

    2007-01-01

    Von Willebrand Factor (VWF) is a large multimeric glycoprotein expressed in the megakaryocytes and endothelial cells of all vertebrates. It participates fundamentally in the primary and secondary hemostasis because it induces the adhesion of platelets to vascular subendothelium and promotes aggregation of platelets when blood vessels and capillaries are damaged. In addition, VWF links to factor VIII which avoids its proteolysis. The deficiency or the inadequate synthesis of the VWF causes von Willebrand disease (VWD), which is the most common hereditary bleeding disorder in humans principally from mucous and cutaneous sites. VWD is difficult to detect with accuracy due to interrelation among VWF with different components of hemostasis, although it is performed by different tests of haemostatic system, and the basic mechanisms in VWD are herein emphasized. The diagnosis of VWD is difficult due to the heterogeneous manifestation of the disease, which also complicates its classification. This article focuses on the molecular aspects of the disease and discusses their possible clinical implications.

  12. Nanostructured carbon materials decorated with organophosphorus moieties: synthesis and application

    PubMed Central

    Biagiotti, Giacomo; Langè, Vittoria; Ligi, Cristina; Caporali, Stefano; Muniz-Miranda, Maurizio; Flis, Anna; Pietrusiewicz, K Michał; Ghini, Giacomo; Brandi, Alberto

    2017-01-01

    A new synthetic approach for the production of carbon nanomaterials (CNM) decorated with organophosphorus moieties is presented. Three different triphenylphosphine oxide (TPPO) derivatives were used to decorate oxidized multiwalled carbon nanotubes (ox-MWCNTs) and graphene platelets (GPs). The TPPOs chosen bear functional groups able to react with the CNMs by Tour reaction (an amino group), nitrene cycloaddition (an azido group) or CuAAC reaction (one terminal C–C triple bond). All the adducts were characterized by FTIR, Raman spectroscopy, TEM, XPS, elemental analysis and ICP-AES. The cycloaddition of nitrene provided the higher loading on ox-MWCNTs and GPs as well, while the Tour approach gave best results with nanotubes (CNTs). Finally, we investigated the possibility to reduce the TPPO functionalized CNMs to the corresponding phosphine derivatives and applied one of the materials produced as heterogeneous organocatalyst in a Staudinger ligation reaction. PMID:28326239

  13. Management of Type 2B von Willebrand Disease during Pregnancy.

    PubMed

    McLaughlin, David; Kerr, Ron

    2017-01-01

    Type 2B von Willebrand disease is a rare bleeding condition resulting in thrombocytopenia and a reduction in large VWF multimers. It usually has an autosomal dominant pattern of inheritance. We report the management of a patient with type 2B von Willebrand disease, whose diagnosis was confirmed by demonstration of a R1306W mutation, through her first pregnancy. The patient's von Willebrand factor (VWF) antigen and VWF ristocetin cofactor levels rose throughout pregnancy, with an associated drop in the platelet count. The patient was successfully managed through labour to a surgical delivery with VWF concentrate, platelet transfusions and tranexamic acid. The patient delivered a male baby who was found to have inherited type 2B von Willebrand disease and had a significant cephalhaematoma at delivery. The baby was managed with VWF concentrate and platelet transfusions and made a full recovery. There is a lack of evidence to guide the best management of pregnant patients with type 2B von Willebrand disease. We adopted a pragmatic management plan, in keeping with other published case reports. To the best of our knowledge, this is the first case report in which the child was found to have inherited type 2B von Willebrand disease and encountered bleeding problems, making this case unique amongst the published literature.

  14. Alloantibody induced platelet responses in transplants: potent mediators in small packages.

    PubMed

    Kuo, Hsiao-Hsuan; Morrell, Craig N; Baldwin, William M

    2012-12-01

    The early histological studies of organ allografts noted platelets attached to vascular endothelium. Platelets adhere to vessels before any morphological evidence of endothelial injury. Subsequently, in vitro and in vivo experiments have demonstrated that alloantibodies can induce exocytosis of von Willebrand factor and P-selectin from endothelial cells and attachment of platelets within minutes. Platelets also adhere to and stimulate leukocytes. These interactions are increased by complement activation. After attachment platelets degranulate, releasing preformed mediators. Some chemokines stored together in platelet granules can form heteromers with synergistic functions. Heteromers containing platelet factor 4 (PF4; CXCL4) are specific to platelets and provide insights to unique platelet functions and opportunities for therapeutic intervention.

  15. Abnormal megakaryocyte development and platelet function in Nbeal2(-/-) mice.

    PubMed

    Kahr, Walter H A; Lo, Richard W; Li, Ling; Pluthero, Fred G; Christensen, Hilary; Ni, Ran; Vaezzadeh, Nima; Hawkins, Cynthia E; Weyrich, Andrew S; Di Paola, Jorge; Landolt-Marticorena, Carolina; Gross, Peter L

    2013-11-07

    Gray platelet syndrome (GPS) is an inherited bleeding disorder associated with macrothrombocytopenia and α-granule-deficient platelets. GPS has been linked to loss of function mutations in NEABL2 (neurobeachin-like 2), and we describe here a murine GPS model, the Nbeal2(-/-) mouse. As in GPS, Nbeal2(-/-) mice exhibit splenomegaly, macrothrombocytopenia, and a deficiency of platelet α-granules and their cargo, including von Willebrand factor (VWF), thrombospondin-1, and platelet factor 4. The platelet α-granule membrane protein P-selectin is expressed at 48% of wild-type levels and externalized upon platelet activation. The presence of P-selectin and normal levels of VPS33B and VPS16B in Nbeal2(-/-) platelets suggests that NBEAL2 acts independently of VPS33B/VPS16B at a later stage of α-granule biogenesis. Impaired Nbeal2(-/-) platelet function was shown by flow cytometry, platelet aggregometry, bleeding assays, and intravital imaging of laser-induced arterial thrombus formation. Microscopic analysis detected marked abnormalities in Nbeal2(-/-) bone marrow megakaryocytes, which when cultured showed delayed maturation, decreased survival, decreased ploidy, and developmental abnormalities, including abnormal extracellular distribution of VWF. Our results confirm that α-granule secretion plays a significant role in platelet function, and they also indicate that abnormal α-granule formation in Nbeal2(-/-) mice has deleterious effects on megakaryocyte survival, development, and platelet production.

  16. Von Willebrand factor processing.

    PubMed

    Brehm, Maria A

    2017-01-31

    Von Willebrand factor (VWF) is a multimeric glycoprotein essential for primary haemostasis that is produced only in endothelial cells and megakaryocytes. Key to VWF's function in recruitment of platelets to the site of vascular injury is its multimeric structure. The individual steps of VWF multimer biosynthesis rely on distinct posttranslational modifications at specific pH conditions, which are realized by spatial separation of the involved processes to different cell organelles. Production of multimers starts with translocation and modification of the VWF prepropolypeptide in the endoplasmic reticulum to produce dimers primed for glycosylation. In the Golgi apparatus they are further processed to multimers that carry more than 300 complex glycan structures functionalized by sialylation, sulfation and blood group determinants. Of special importance is the sequential formation of disulfide bonds with different functions in structural support of VWF multimers, which are packaged, stored and further processed after secretion. Here, all these processes are being reviewed in detail including background information on the occurring biochemical reactions.

  17. Fire-Retardant, Decorative Inks

    NASA Technical Reports Server (NTRS)

    Kourtides, D.; Nir, Z.; Mikroyannidis, J.

    1987-01-01

    Effectiveness of fire-retardant additives evaluated. Fire retardance of decorative acrylic printing inks for aircraft interiors enhanced by certain commercial and experimental fire-retardant additives, according to study.

  18. Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor

    PubMed Central

    Deng, Wei; Xu, Yan; Chen, Wenchun; Paul, David S.; Syed, Anum K.; Dragovich, Matthew A.; Liang, Xin; Zakas, Philip; Berndt, Michael C.; Di Paola, Jorge; Ware, Jerry; Lanza, Francois; Doering, Christopher B.; Bergmeier, Wolfgang; Zhang, X. Frank; Li, Renhao

    2016-01-01

    Mechanisms by which blood cells sense shear stress are poorly characterized. In platelets, glycoprotein (GP)Ib–IX receptor complex has been long suggested to be a shear sensor and receptor. Recently, a relatively unstable and mechanosensitive domain in the GPIbα subunit of GPIb–IX was identified. Here we show that binding of its ligand, von Willebrand factor, under physiological shear stress induces unfolding of this mechanosensory domain (MSD) on the platelet surface. The unfolded MSD, particularly the juxtamembrane ‘Trigger' sequence therein, leads to intracellular signalling and rapid platelet clearance. These results illustrate the initial molecular event underlying platelet shear sensing and provide a mechanism linking GPIb–IX to platelet clearance. Our results have implications on the mechanism of platelet activation, and on the pathophysiology of von Willebrand disease and related thrombocytopenic disorders. The mechanosensation via receptor unfolding may be applicable for many other cell adhesion receptors. PMID:27670775

  19. Analysis of aggregation of platelets in thrombosis

    NASA Astrophysics Data System (ADS)

    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.

  20. Platelets in Early Antibody-Mediated Rejection of Renal Transplants

    PubMed Central

    Kuo, Hsiao-Hsuan; Fan, Ran; Dvorina, Nina; Chiesa-Vottero, Andres

    2015-01-01

    Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses. PMID:25145937

  1. Platelet associated antibodies

    MedlinePlus

    ... medlineplus.gov/ency/article/003552.htm Platelet-associated antibodies blood test To use the sharing features on ... JavaScript. This blood test shows if you have antibodies against platelets in your blood. Platelets are a ...

  2. Platelet-like Nanoparticles: Mimicking Shape, Flexibility, and Surface Biology of Platelets To Target Vascular Injuries

    PubMed Central

    2015-01-01

    Targeted delivery of therapeutic and imaging agents in the vascular compartment represents a significant hurdle in using nanomedicine for treating hemorrhage, thrombosis, and atherosclerosis. While several types of nanoparticles have been developed to meet this goal, their utility is limited by poor circulation, limited margination, and minimal targeting. Platelets have an innate ability to marginate to the vascular wall and specifically interact with vascular injury sites. These platelet functions are mediated by their shape, flexibility, and complex surface interactions. Inspired by this, we report the design and evaluation of nanoparticles that exhibit platelet-like functions including vascular injury site-directed margination, site-specific adhesion, and amplification of injury site-specific aggregation. Our nanoparticles mimic four key attributes of platelets, (i) discoidal morphology, (ii) mechanical flexibility, (iii) biophysically and biochemically mediated aggregation, and (iv) heteromultivalent presentation of ligands that mediate adhesion to both von Willebrand Factor and collagen, as well as specific clustering to activated platelets. Platelet-like nanoparticles (PLNs) exhibit enhanced surface-binding compared to spherical and rigid discoidal counterparts and site-selective adhesive and platelet-aggregatory properties under physiological flow conditions in vitro. In vivo studies in a mouse model demonstrated that PLNs accumulate at the wound site and induce ∼65% reduction in bleeding time, effectively mimicking and improving the hemostatic functions of natural platelets. We show that both the biochemical and biophysical design parameters of PLNs are essential in mimicking platelets and their hemostatic functions. PLNs offer a nanoscale technology that integrates platelet-mimetic biophysical and biochemical properties for potential applications in injectable synthetic hemostats and vascularly targeted payload delivery. PMID:25318048

  3. Blood platelet kinetics and platelet transfusion.

    PubMed

    Aster, Richard H

    2013-11-01

    The discovery of citrate anticoagulant in the 1920s and the development of plastic packs for blood collection in the 1960s laid the groundwork for platelet transfusion therapy on a scale not previously possible. A major limitation, however, was the finding that platelet concentrates prepared from blood anticoagulated with citrate were unsuitable for transfusion because of platelet clumping. We found that this could be prevented by simply reducing the pH of platelet-rich plasma to about 6.5 prior to centrifugation. We used this approach to characterize platelet kinetics and sites of platelet sequestration in normal and pathologic states and to define the influence of variables such as anticoagulant and ABO incompatibility on post-transfusion platelet recovery. The "acidification" approach enabled much wider use of platelet transfusion therapy until alternative means of producing concentrates suitable for transfusion became available.

  4. Tunable superconductivity in decorated graphene

    NASA Astrophysics Data System (ADS)

    Han, Zheng; Allain, Adrien; Marty, Laetitia; Bendiab, Nedjma; Toulemonde, Pierre; Strobel, Pierre; Coraux, Johann; Bouchiat, Vincent

    2013-03-01

    Graphene offers an exposed bidimensional gas of high mobility charge carriers with gate tunable density. Its chemical inertness offers an outstanding platform to explore exotic 2D superconductivity. Superconductivity can be induced in graphene by means of proximity effect (by depositing a set of superconducting metal clusters such as lead or tin nanoparticles). The influence of decoration material, density or particles and disorder of graphene will be discussed. In the case of disordered graphene, Tin decoration leads to a gate-tunable superconducting-to-insulator quantum phase transition. Superconductivity in graphene is also expected to occur under strong charge doping (induced either by gating or under chemical decoration, in analogy with graphite intercalated compounds). I will also show preliminary results showing the influence of Calcium intercalation of few layer graphene and progress toward the demonstration of intrinsic superconductivity in such systems. Work supported by EU GRANT FP7-NMP GRENADA.

  5. von Willebrand Disease

    MedlinePlus

    ... take aspirin and ibuprofen because they interfere with platelet function and can increase the risk of bleeding. It's ... or fever, since it has no effect on platelet function. Medicines for vWD Some people with more serious ...

  6. Reversible translocation of glycoprotein Ib in plasmin-treated platelets: consequences for platelet function.

    PubMed

    Lu, H; Soria, C; Soria, J; De Romeuf, C; Perrot, J Y; Tenza, D; Garcia, I; Caen, J P; Cramer, E M

    1993-12-01

    Understanding the effect of fibrinolysis on platelet function is of clinical importance. Plasmin is recognized to affect platelet adhesive function by reducing the interaction of platelet glycoprotein (GP) Ib with von Willebrand factor (vWF) bound to the subendothelium. This platelet function is commonly explored in vitro by the ristocetin-induced agglutination test. Our previous study demonstrated a plasmin-induced redistribution of GP Ib molecules from the platelet surface to the linings of the surface-connected canalicular system (SCCS), a critical mechanism for understanding plasmin-induced GP Ib dysfunction. Here, we demonstrate that neutralization of plasmin by its inhibitors, aprotinin or tripeptide Val-Phe-Lys-CH2Cl, permits a time dependent recovery (within 30 min) of ristocetin-induced agglutination in the platelets which were stimulated by plasmin at < 1 CU ml-1. This functional recovery was accompanied with a restoration of a normal amount of GP Ib on the platelet surface, as measured by the binding of both monoclonal anti-GP Ib antibody SZ 2 and 125I-labelled vWF to the platelets. Cytochalasin D did not inhibit this recovery, suggesting that this process may be due to passive actin depolymerization. These findings were further confirmed by immunoelectron microscopic study. Utilizing the platelets pre-labelled with anti-GP Ib antibody prior to plasmin stimulation, it was demonstrated that the observed recovery is due to a reverse translocation from the SCCS to the plasma membrane of the same GP Ib molecules which were present initially at the cell surface.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. FlnA-null megakaryocytes prematurely release large and fragile platelets that circulate poorly.

    PubMed

    Jurak Begonja, Antonija; Hoffmeister, Karin M; Hartwig, John H; Falet, Hervé

    2011-08-25

    Filamin A (FlnA) is a large cytoplasmic protein that crosslinks actin filaments and anchors membrane receptors and signaling intermediates. FlnA(loxP) PF4-Cre mice that lack FlnA in the megakaryocyte (MK) lineage have a severe macrothrombocytopenia because of accelerated platelet clearance. Macrophage ablation by injection of clodronate-encapsulated liposomes increases blood platelet counts in FlnA(loxP) PF4-Cre mice and reveals the desintegration of FlnA-null platelets into microvesicles, a process that occurs spontaneously during storage. FlnA(loxP) PF4-Cre bone marrows and spleens have a 2.5- to 5-fold increase in MK numbers, indicating increased thrombopoiesis in vivo. Analysis of platelet production in vitro reveals that FlnA-null MKs prematurely convert their cytoplasm into large CD61(+) platelet-sized particles, reminiscent of the large platelets observed in vivo. FlnA stabilizes the platelet von Willebrand factor receptor, as surface expression of von Willebrand factor receptor components is normal on FlnA-null MKs but decreased on FlnA-null platelets. Further, FlnA-null platelets contain multiple GPIbα degradation products and have increased expression of the ADAM17 and MMP9 metalloproteinases. Together, the findings indicate that FlnA-null MKs prematurely release large and fragile platelets that are removed rapidly from the circulation by macrophages.

  8. [In vitro platelet production].

    PubMed

    Dunois-Lardé, C; Baruch, D

    2011-04-01

    This review aims at presenting a state of the art on platelet functions, not only in well-characterized hemostasis and thrombosis, but also in various domains such as inflammation, immunity, angiogenesis, source of growth factors, metastasis and vascular remodelling. This multivalent phenotype of platelets suggests new potential applications of platelets. The second objective is to present new advances in platelet formation from megakaryocytes and direct platelet release, as initially shown by our group and more recently by others.

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

    PubMed

    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.

  10. Platelet concentrates transfusion in cardiac surgery in relation to preoperative point-of-care assessment of platelet adhesion and aggregation.

    PubMed

    Solomon, Cristina; Hartmann, Jennifer; Osthaus, Alexander; Schöchl, Herbert; Raymondos, Kostas; Koppert, Wolfgang; Rahe-Meyer, Niels

    2010-01-01

    Platelet dysfunction is an important cause of bleeding early after cardiac surgery. Whole-blood multiple electrode aggregometry (MEA), investigating the adhesion and aggregation of activated platelets onto metal electrodes, has shown correlations with platelet concentrates transfusion in this setting. Platelet activity in vivo is dependent on shear stress, an aspect that cannot be investigated with MEA, but with the cone and plate(let) analyzer (CPA) Impact-R that measures the interaction of platelets and von Willebrand factor (vWF) in whole blood under shear. We hypothesized that preoperative CPA may show better correlation with platelet concentrates transfusion post-cardiac surgery than MEA, since it is dependent on both platelet activity and platelet interaction with vWF multimers. Blood was obtained preoperatively from 30 patients undergoing aorto-coronary bypass (ACB) and 20 patients with aortic valve (AV) surgery. MEA was performed in hirudin-anticoagulated blood. The Impact-R analyses were performed in blood anticoagulated with hirudin, heparin or the standard anticoagulant citrate. For the light microscopy images obtained, the parameter surface coverage (SC) was calculated. Preoperative Impact-R results were abnormally decreased in AV patients and significantly lower than in ACB patients. For the Impact-R analysis performed in citrated blood, no correlation with platelet concentrates transfusion was observed. In contrast, MEA was comparable between the groups and correlated significantly with intraoperative platelet concentrates transfusion in both groups (rho between -0.47 and -0.62, p < 0.05). Multiple electrode aggregometry appeared more useful and easier to apply than CPA for preoperatively identifying patients with platelet concentrates transfusion in cardiac surgery.

  11. The evolutionary ecology of decorating behaviour

    PubMed Central

    Ruxton, Graeme D.; Stevens, Martin

    2015-01-01

    Many animals decorate themselves through the accumulation of environmental material on their exterior. Decoration has been studied across a range of different taxa, but there are substantial limits to current understanding. Decoration in non-humans appears to function predominantly in defence against predators and parasites, although an adaptive function is often assumed rather than comprehensively demonstrated. It seems predominantly an aquatic phenomenon—presumably because buoyancy helps reduce energetic costs associated with carrying the decorative material. In terrestrial examples, decorating is relatively common in the larval stages of insects. Insects are small and thus able to generate the power to carry a greater mass of material relative to their own body weight. In adult forms, the need to be lightweight for flight probably rules out decoration. We emphasize that both benefits and costs to decoration are rarely quantified, and that costs should include those associated with collecting as well as carrying the material. PMID:26041868

  12. Biosynthesis of von Willebrand protein by human megakaryocytes.

    PubMed

    Sporn, L A; Chavin, S I; Marder, V J; Wagner, D D

    1985-09-01

    Immunofluorescence staining of buffy coat smears from a patient with chronic myelogenous leukemia in accelerated phase showed that approximately 13% of all nucleated cells contained von Willebrand protein and, therefore, appeared to be of megakaryocytic origin. This was confirmed by positive staining with antisera against platelet factor 4 and platelet glycoproteins. Short-term cultures of the buffy coat, which lacked endothelial cells, were metabolically labeled with [35S]methionine, and von Willebrand protein was immunopurified from cell lysates and culture medium. Cultures from this patient synthesized and secreted von Willebrand protein, in contrast with cultures from other patients with leukemia, who lacked circulating megakaryocytes, and from normal volunteers. The subunit composition of the megakaryocytic von Willebrand protein was very similar to that of human umbilical vein endothelial cells. The size of the processed subunit (220 kD) and of the cellular (260 kD) and secreted (275 kD) precursors from the two cell types were indistinguishable by gel electrophoresis. Furthermore, the ratio of precursor to processed subunit and the pattern of cellular and secreted nonreduced multimers were very similar. It appears, therefore, that the processing steps in biosynthesis of von Willebrand protein used by the megakaryocytes are very similar to those of umbilical vein endothelial cells.

  13. Platelet membrane glycoproteins and their function: an overview.

    PubMed

    Kunicki, T J

    1989-07-01

    The membrane glycoproteins (GP) of human platelets act as receptors that mediate two important functions, adhesion to the subendothelial matrix and platelet-platelet cohesion, or aggregation. Many of these glycoprotein receptors exist as noncovalently linked heterodimers, including those that belong to the supergene family of adhesion receptors called the integrins. Human platelets contain at least five members of this integrin family, including a collagen receptor (GP Ia-IIa; alpha 2, beta 1), a fibronectin receptor (GP Ic-IIa; alpha 5, beta 1), a laminin receptor (GP Ic'-IIa; alpha 6, beta 1), a vitronectin receptor (VnR; alpha v, beta 3), and a promiscuous, activation-dependent receptor that is thought to be the receptor most responsible for fibrinogen-dependent, platelet-platelet cohesion (GP IIb-IIIa; alpha IIb, beta 3). Some, but not all, of the integrins bind to a tripeptide sequence, arginine-glycine-aspartic acid (RGD), on the adhesive proteins. In addition to the integrins, platelets contain other membrane glyco-proteins: GP Ib-IX, a receptor for von Willebrand factor, which is thought to be the receptor most responsible for platelet adhesion to the subendothelial matrix in a flowing system; GP V, which may be associated with GP Ib-IX and whose function remains unknown; and GP IV (GP IIIb), which functions as a receptor for thrombospondin and collagen.

  14. Weibel-Palade bodies: a window to von Willebrand disease.

    PubMed

    Valentijn, K M; Eikenboom, J

    2013-04-01

    Weibel-Palade bodies (WPBs) are the storage organelles for von Willebrand factor (VWF) in endothelial cells. VWF forms multimers that assemble into tubular structures in WPBs. Upon demand, VWF is secreted into the blood circulation, where it unfolds into strings that capture platelets during the onset of primary hemostasis. Numerous mutations affecting VWF lead to the bleeding disorder von Willebrand disease. This review reports the recent findings on the effects of VWF mutations on the biosynthetic pathway of VWF and its storage in WPBs. These new findings have deepened our understanding of VWF synthesis, storage, secretion, and function.

  15. Normal platelets and megakaryocytes are produced in vivo in the absence of thrombopoietin.

    PubMed

    Bunting, S; Widmer, R; Lipari, T; Rangell, L; Steinmetz, H; Carver-Moore, K; Moore, M W; Keller, G A; de Sauvage, F J

    1997-11-01

    Thrombopoietin (TPO) has been established as the major regulator of megakaryocyte and platelet production. In vitro and in vivo studies have demonstrated that TPO affects both megakaryocyte proliferation and maturation. In vitro, TPO has been reported to be essential for full development of megakaryocytes and platelets. These studies are in contrast to results observed in vivo in mice deficient in the TPO or c-mpl gene (TPO-/- and c-mpl-/-). Both TPO-/- and c-mpl-/- mice exhibit a 90% reduction in megakaryocyte and platelet levels. But even with this small number of circulating platelets, these mice do not have any excessive bleeding. Ultrastructural analysis indicates that platelets and megakaryocytes present in the knockout mice are morphologically normal. Characterization of platelet function shows that platelets from knockout mice are functionally identical to the wild-type platelets as measured by upregulation of 125I-fibrinogen binding to platelets in response to adenosine diphosphate (ADP) stimulation and by platelet attachment to the immobilized extracellular matrix proteins, collagen and von Willebrand factor (vWF). These results demonstrate that in vivo, TPO is required for the control of megakaryocyte and platelet number but not for their maturation. Other factors with megakaryocytopoietic activity may be able to compensate for the maturational role of TPO and lead to the formation of normal megakaryocytes and platelets in TPO-/- and c-mpl-/- mice.

  16. Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice.

    PubMed

    Jansen, A J Gerard; Josefsson, Emma C; Rumjantseva, Viktoria; Liu, Qiyong Peter; Falet, Hervé; Bergmeier, Wolfgang; Cifuni, Stephen M; Sackstein, Robert; von Andrian, Ulrich H; Wagner, Denisa D; Hartwig, John H; Hoffmeister, Karin M

    2012-02-02

    When refrigerated platelets are rewarmed, they secrete active sialidases, including the lysosomal sialidase Neu1, and express surface Neu3 that remove sialic acid from platelet von Willebrand factor receptor (VWFR), specifically the GPIbα subunit. The recovery and circulation of refrigerated platelets is greatly improved by storage in the presence of inhibitors of sialidases. Desialylated VWFR is also a target for metalloproteinases (MPs), because GPIbα and GPV are cleaved from the surface of refrigerated platelets. Receptor shedding is inhibited by the MP inhibitor GM6001 and does not occur in Adam17(ΔZn/ΔZn) platelets expressing inactive ADAM17. Critically, desialylation in the absence of MP-mediated receptor shedding is sufficient to cause the rapid clearance of platelets from circulation. Desialylation of platelet VWFR therefore triggers platelet clearance and primes GPIbα and GPV for MP-dependent cleavage.

  17. Theodore von Karman

    NASA Technical Reports Server (NTRS)

    1926-01-01

    Theodore von Karman. NACA: In the eyes of most aeronautical experts, the overall record of Max Munk in aerodynamic research falls short of that achieved by fellow immigrant Theodore von Karman (the short man in the double breasted coat in the middle), shown here visiting Langley in December 1926. People in the photo include Max Munk, aerodynamic researcher; Theodore von Karman; George Lewis, director of research; Henry Reid, engineer in charge; Fred Weick, PRT head; Paul Hemke; Elliott Reid, future Stanford University Professor.

  18. Platelets and Infections – Complex Interactions with Bacteria

    PubMed Central

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

    2015-01-01

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

  19. Living with von Willebrand Disease

    MedlinePlus

    ... from the NHLBI on Twitter. Living With von Willebrand Disease If you have von Willebrand disease (VWD), you ... that they get tested too. Pregnancy and von Willebrand Disease Pregnancy can be a challenge for women who ...

  20. Clinical application of radiolabelled platelets

    SciTech Connect

    Kessler, C. )

    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.

  1. Surface decorated platinum carbonyl clusters

    NASA Astrophysics Data System (ADS)

    Ciabatti, Iacopo; Femoni, Cristina; Iapalucci, Maria Carmela; Longoni, Giuliano; Zacchini, Stefano; Zarra, Salvatore

    2012-06-01

    Four molecular Pt-carbonyl clusters decorated by Cd-Br fragments, i.e., [Pt13(CO)12{Cd5(μ-Br)5Br2(dmf)3}2]2- (1), [Pt19(CO)17{Cd5(μ-Br)5Br3(Me2CO)2}{Cd5(μ-Br)5Br(Me2CO)4}]2- (2), [H2Pt26(CO)20(CdBr)12]8- (3) and [H4Pt26(CO)20(CdBr)12(PtBr)x]6- (4) (x = 0-2), have been obtained from the reactions between [Pt3n(CO)6n]2- (n = 2-6) and CdBr2.H2O in dmf at 120 °C. The structures of these molecular clusters with diameters of 1.5-2 nm have been determined by X-ray crystallography. Both 1 and 2 are composed of icosahedral or bis-icosahedral Pt-CO cores decorated on the surface by Cd-Br motifs, whereas 3 and 4 display a cubic close packed Pt26Cd12 metal frame decorated by CO and Br ligands. An oversimplified and unifying approach to interpret the electron count of these surface decorated platinum carbonyl clusters is suggested, and extended to other low-valent organometallic clusters and Au-thiolate nanoclusters.Four molecular Pt-carbonyl clusters decorated by Cd-Br fragments, i.e., [Pt13(CO)12{Cd5(μ-Br)5Br2(dmf)3}2]2- (1), [Pt19(CO)17{Cd5(μ-Br)5Br3(Me2CO)2}{Cd5(μ-Br)5Br(Me2CO)4}]2- (2), [H2Pt26(CO)20(CdBr)12]8- (3) and [H4Pt26(CO)20(CdBr)12(PtBr)x]6- (4) (x = 0-2), have been obtained from the reactions between [Pt3n(CO)6n]2- (n = 2-6) and CdBr2.H2O in dmf at 120 °C. The structures of these molecular clusters with diameters of 1.5-2 nm have been determined by X-ray crystallography. Both 1 and 2 are composed of icosahedral or bis-icosahedral Pt-CO cores decorated on the surface by Cd-Br motifs, whereas 3 and 4 display a cubic close packed Pt26Cd12 metal frame decorated by CO and Br ligands. An oversimplified and unifying approach to interpret the electron count of these surface decorated platinum carbonyl clusters is suggested, and extended to other low-valent organometallic clusters and Au-thiolate nanoclusters. CCDC 867747 and 867748. For crystallographic data in CIF or other electronic format see DOI: 10.1039/c2nr30400g

  2. Principles of care for the diagnosis and treatment of von Willebrand disease.

    PubMed

    Castaman, Giancarlo; Goodeve, Anne; Eikenboom, Jeroen

    2013-05-01

    Von Willebrand disease is a common autosomal inherited bleeding disorder caused by quantitative or qualitative defects of von Willebrand factor, a multi-adhesive protein that binds platelets to exposed subendothelium and carries factor VIII in circulation. As a result of von Willebrand factor deficiency or abnormality, levels of factor VIII, the protein deficient in hemophilia A, may be variably reduced. Clinical manifestations are mainly represented by mucous membrane and of soft tissue bleeding. Their severity is variable depending on the degree of von Willebrand factor and factor VIII reduction. While a clear-cut diagnosis is easy in severe von Willebrand factor reductions, the advantage of pursuing a definite diagnosis in mild or dubious cases should be weighed against the risk of over-medicalization. The aim of treatment is to correct the dual defect of hemostasis caused by the abnormal/reduced von Willebrand factor and the concomitant deficiency of factor VIII. Desmopressin is the treatment of choice for type 1 von Willebrand disease patients with factor VIII and von Willebrand factor levels of 10 U/dL or over who have proved responsive to a test-infusion with the compound. Von Willebrand factor/factor VIII concentrates are needed when desmopressin is ineffective (mainly type 2 and 3 von Willebrand disease).

  3. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Wernher Von Braun (left) and Fred W. Kelley examine a ST-100 Stellar Instrument Platform in the astrionics lab. Dr. Von Braun, then deputy associate administrator for planning, NASA, was visiting on the anniversary of the establishment of the Marshall Space Flight Center.

  4. Megakaryocytes and platelets in alpha-granule disorders.

    PubMed

    Smith, M P; Cramer, E M; Savidge, G F

    1997-02-01

    This chapter summarizes research data contributing to current understanding of disorders affecting alpha-granules of megakaryocytes and platelets. Diagnostic features of the gray platelet syndrome are well defined. Combined evidence suggests a defect, specific to the megakaryocyte cell lineage, causing a cytoskeletal abnormality and defective targeting of endogenously synthesized proteins to the alpha-granule. The abnormalities linked by signal transduction pathways. von Willebrand disease and afibrinogenaemia are disorders which highlight the functional importance of platelet storage pools of von Willebrand factor and fibrinogen, essential ligands in the process of adhesion and aggregation. The abnormality in the factor V Quebec disorder leads to a degradation of most proteins contained within the alpha-granule. The familial platelet disorder Paris-Trousseau thrombocytopenia is the only alpha-granule disorder associated with a cytogenetic abnormality, and it presents a useful model for exploring the genetic influence on regulation of thrombopoiesis. Study of these syndromes has elucidated aspects of the physiology of normal megakaryocyte maturation and platelet formation, including storage organelle biosynthesis.

  5. Dr. Wernher von Braun

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Dr. von Braun is looking out from a 10th floor window of building 4200 at the Marshall Space Flight Center (MSFC). He was the first Center Director and served as the Director from July 1960 through February 1970. Following World War II, Dr. von Braun and his German colleagues arrived in the United States under the Project Paperclip (American acquisition of German rocket experts) to continue their rocket development work. In 1950, von Braun and his German Rocket Team (also called the Peenemuende Team) were transferred from Ft. Bliss, Texas to Huntsville, Alabama to work for the Army's rocket program at Redstone Arsenal and later, NASA's Marshall Space Flight Center (MSFC). Under Dr. von Braun's leadership, MSFC developed the Saturn V launch vehicle, which placed the first men, two American astronauts, on the Moon. Wernher von Braun's life was dedicated to expanding man's knowledge through the exploration of space.

  6. Low-power laser irradiation of blood inhibits platelet function: role of cyclic GMP

    NASA Astrophysics Data System (ADS)

    Brill, Alexander G.; Brill, Gregory E.; Shenkman, Boris; Tamarin, Ilya; Dardik, Rima; Varon, David; Savion, Naphtali

    1998-12-01

    The aim of the present work was to investigate effect of low power laser irradiation (LPLI) on platelet function in vitro. He-Ne laser (Optronix, USA; (lambda) - 632.8 nm, output power - 7 mW) was employed. Platelet adhesion and aggregation in whole blood (WB) under defined shear conditions were assayed by a Cone and Plate(let) Analyzer. Platelet activation was evaluated by flow cytometry. Level of platelet cGMP was estimated by immunoenzyme assay. Experiments performed showed that LPLI of WB resulted in decrease of platelet deposition on extracellular matrix at high shear rate (1300 s-1). Similar results were obtained using surfaces precoated with either collagen type I or von Willebrand factor. LPLI inhibited fibrinogen binding as well as P-selectin expression on the platelet membrane, induced by thrombin analogue. It was found out that primary acceptor of laser energy responsible for the effect on platelets was located in platelets themselves and not in blood plasma or in other blood cells. LPLI of gel- filtered platelets resulted in increase of intracellular level of cGMP both in the absence and in presence of izobutylmethylxantine (phosphodiesterase inhibitor) suggesting stimulation of synthesis rather than destruction of cGMP under the influence of LPLI. It is suggested that guanylate cyclase and/or NO-synthase might serve as primary acceptors of He-Ne laser light in platelets.

  7. Echicetin coated polystyrene beads: a novel tool to investigate GPIb-specific platelet activation and aggregation.

    PubMed

    Navdaev, Alexey; Subramanian, Hariharan; Petunin, Alexey; Clemetson, Kenneth J; Gambaryan, Stepan; Walter, Ulrich

    2014-01-01

    von Willebrand factor/ristocetin (vWF/R) induces GPIb-dependent platelet agglutination and activation of αIIbβ3 integrin, which also binds vWF. These conditions make it difficult to investigate GPIb-specific signaling pathways in washed platelets. Here, we investigated the specific mechanisms of GPIb signaling using echicetin-coated polystyrene beads, which specifically activate GPIb. We compared platelet activation induced by echicetin beads to vWF/R. Human platelets were stimulated with polystyrene beads coated with increasing amounts of echicetin and platelet activation by echicetin beads was then investigated to reveal GPIb specific signaling. Echicetin beads induced αIIbβ3-dependent aggregation of washed platelets, while under the same conditions vWF/R treatment led only to αIIbβ3-independent platelet agglutination. The average distance between the echicetin molecules on the polystyrene beads must be less than 7 nm for full platelet activation, while the total amount of echicetin used for activation is not critical. Echicetin beads induced strong phosphorylation of several proteins including p38, ERK and PKB. Synergistic signaling via P2Y12 and thromboxane receptor through secreted ADP and TxA2, respectively, were important for echicetin bead triggered platelet activation. Activation of PKG by the NO/sGC/cGMP pathway inhibited echicetin bead-induced platelet aggregation. Echicetin-coated beads are powerful and reliable tools to study signaling in human platelets activated solely via GPIb and GPIb-triggered pathways.

  8. The omnipotent platelet.

    PubMed

    Steinberg, L A

    1996-03-01

    This information was derived from the increase in platelets of patients following fractures and/or bone surgery and in conjunction with a vast amount of published literature. The increase in numbers of platelets reflects the extent of bone involvement, especially noted in the hip, knee, post-coronary artery bypass graft, and multiple fractures. The role of the platelet in any and all tissues, i.e. soft tissue or bone, whether beneficial or detrimental, is multifunctional. The platelet responds to all physiologic and pathologic states and, if tissue involved is sufficient, the role of the platelet becomes obvious.

  9. Rhesus monkey platelets

    SciTech Connect

    Harbury, C.B.

    1986-03-01

    The purpose of this abstract is to describe the adenine nucleotide metabolism of Rhesus monkey platelets. Nucleotides are labelled with /sup 14/C-adenine and extracted with EDTA-ethanol (EE) and perchlorate (P). Total platelet ATP and ADP (TATP, TADP) is measured in the Holmsen Luciferase assay, and expressed in nanomoles/10/sup 8/ platelets. TR=TATP/TADP. Human platelets release 70% of their TADP, with a ratio of released ATP/ADP of 0.7. Rhesus platelets release 82% of their TADP, with a ratio of released ATP/ADP of 0.33. Thus, monkey platelets contain more ADP than human platelets. Thin layer chromatography of EE gives a metabolic ratio of 11 in human platelets and 10.5 in monkey platelets. Perchlorate extracts metabolic and actin bound ADP. The human and monkey platelets ratios were 5, indicating they contain the same proportion of actin. Thus, the extra ADP contained in monkey platelets is located in the secretory granules.

  10. The Platelet Proteome

    PubMed Central

    Senzel, Lisa; Gnatenko, Dmitri V.; Bahou, Wadie F.

    2010-01-01

    Purpose of review The proteome is the pool of proteins expressed at a given time and circumstance. The word “proteomics” summarizes several technologies for visualization, quantitation and identification of these proteins. Recent advances in these techniques are helping to elucidate platelet processes which are relevant to bleeding and clotting disorders, transfusion medicine and regulation of angiogenesis. Recent findings Over 1100 platelet proteins have been identified using proteomic techniques. Various subproteomes have been characterized, including platelet releasates (the “secretome”), alpha and dense granules, membrane and cytoskeletal proteins, platelet-derived microparticles, and the platelet “phosphoproteome”. Proteomic data about platelets have become increasingly available in integrated databases. Summary Proteomic experiments in resting and activated platelets have identified novel signaling pathways and secreted proteins which may represent therapeutic targets, as well as potential cancer biomarkers. PMID:19550320

  11. Functional property of von Willebrand factor under flowing blood.

    PubMed

    Sugimoto, Mitsuhiko; Miyata, Shigeki

    2002-01-01

    von Willebrand factor (vWF) is produced in megakaryocytes and endothelial cells, is stored in the alpha-granule of platelets and in the Weibel-Palade body of endothelial cells, and is present in plasma and vascular subendothelium. This huge protein with a unique multimeric structure plays a pivotal role in both hemostasis and pathological intravascular thrombosis, in which vWF contributes to both platelet adhesion/aggregation and blood coagulation through its multiple adhesive functions for the platelet membrane receptors, glycoprotein Ib-IX-V complex, integrin alphaIIbbeta3, heparin, various types of collagen, and coagulation factor VIII. Among various functions, the most characteristic feature of vWF is its determinant role on platelet thrombus formation under high-shear-rate conditions. Indeed, at in vivo rheological situations where platelets are flowing with high speed in the bloodstream, the only reaction that can initiate mural thrombogenesis is the interaction of vWF with platelet glycoprotein Ibalpha. The recent x-ray analysis of the crystal structure of various functional domains and functional studies of this protein under experimental flow conditions have rapidly advanced and revised our knowledge of the structure-function relationships of vWF, a key protein for hemostasis and arterial thrombosis.

  12. Reversibility of thrombin-induced decrease in platelet glycoprotein Ib function.

    PubMed

    Lu, H; Menashi, S; Garcia, I; Cramer, E M; Li, H; Tenza, D; De Romeuf, C; Soria, J; Soria, C

    1993-09-01

    Thrombin induces a redistribution of glycoprotein (GP) Ib/GP IX complex from the platelet surface into the surface connected canalicular system (SCCS). This redistribution results in a reduced interaction of platelet GP Ib with von Willebrand factor (vWF) bound to subendothelium leading to impaired platelet adhesion. In this study we show that the platelet aggregation and degranulation require concentrations of thrombin above 0.05 U/ml, while the decrease in GP Ib function (about 50% of control value), as determined by ristocetin induced platelet agglutination, can be induced by lower concentrations (0.01-0.04 U/ml). Moreover, we show that when adding thrombin inhibitors to the platelets preincubated with < 0.04 U/ml thrombin for 5 min, their agglutinability by ristocetin was gradually recovered within 30 min, indicating that in these conditions the decrease in platelet adhesiveness is reversible. Immuno-electromicroscopic study showed that this restoration of platelet GP Ib function was associated with a reversed translocation of GP Ib from the SCCS to the plasma membrane. The data obtained from counting gold particles showed that the ratio of GP Ib immunolabelling on the external membrane versus that on the SCCS was 3.31 +/- 0.90 for resting platelets, down-regulated to 0.84 +/- 0.13 (P < 0.05 versus resting platelets) for the platelets treated with 0.04 U/ml thrombin and returned to 2.63 +/- 2.21 (P > 0.05 versus resting platelets) after incubation for 30 min with hirudin. However, the translocation of GP Ib was poorly reversed by thrombin inhibitors when higher concentrations of thrombin were used which induced platelet aggregation and large extent of degranulation. We conclude that thrombin affects platelets in a dose dependent manner, and that at low concentrations the decrease in platelet GP Ib related function is a reversible phenomenon.

  13. The Role of Decorative Pictures in Learning

    ERIC Educational Resources Information Center

    Lenzner, Alwine; Schnotz, Wolfgang; Müller, Andreas

    2013-01-01

    Three experiments with students from 7th and 8th grade were performed to investigate the effects of decorative pictures in learning as compared to instructional pictures. Pictures were considered as instructional, when they were primarily informative, and as decorative, when they were primarily aesthetically appealing. The experiments…

  14. Painter and Decorator. Occupational Analyses Series.

    ERIC Educational Resources Information Center

    Chapman, Mike; MacCallum, Marilyn; Maddocks, Christopher

    This analysis covers tasks performed by a painter and decorator, an occupational title some provinces and territories of Canada have also identified as painter and painter and decorator--commercial and residential. A guide to analysis discusses development, structure, and validation method; scope of the occupation; trends; and safety. To…

  15. von Willebrand Disease.

    PubMed

    Swami, Arjun; Kaur, Varinder

    2016-01-01

    von Willebrand disease (vWD) is the most common inherited disorder of hemostasis and comprises a spectrum of heterogeneous subtypes. Significant advances have been made in understanding von Willebrand factor ( vWF) gene mutations, resultant physiologic deficits in the vWF peptide, and their correlation to clinical presentation. Diagnostic tests for this disorder are complex, and interpretation requires a thorough understanding of the underlying pathophysiology by the practicing physician. The objective of this review is to summarize our current understanding of pathophysiology, laboratory investigations, and evolving treatment paradigm of vWD with the availability of recombinant von Willebrand factor.

  16. Platelets: handle with care.

    PubMed

    Thomas, S

    2016-10-01

    Platelets are delicate cells that require careful handling between collection, preparation and transfusion. This review addresses practical questions relating to platelet concentration, resting time after collection, total time and number of periods without agitation and temperature. The bags in which platelets are stored are made from gas-permeable plastic to allow sufficient oxygen for the platelets to maintain aerobic respiration. Manufacturers have assigned limits for platelet content and concentration, and these must not be exceeded. There is no strong evidence for or against the resting of platelets post-collection and pre-agitation, but platelets should not be over-wrapped during this period as this compromises gas exchange; a short rest period of up to 1 h may allow the separation of minor aggregates. It is necessary to transport platelet concentrates (e.g. from manufacturing site to hospital), but these periods without gas exchange must be limited to avoid excessive damage to the platelets. Current data support a total of 24 h of transportation per component but with no individual period lasting more than 8 h. Platelets need to be stored at 20-24 °C based on evidence that colder storage leads to irreversible changes on the platelet membrane, resulting in phagocytosis of the platelets following transfusion. Storage at warmer temperatures may lead to an increase in bacterial risk. On the basis of this review, the UK Guidelines for Blood Transfusion Services have been updated to ensure that platelets are handled in the most appropriate way to ensure that efficacious components are provided for patients.

  17. Misfolding of vWF to Pathologically Disordered Conformations Impacts the Severity of von Willebrand Disease

    PubMed Central

    Tischer, Alexander; Madde, Pranathi; Moon-Tasson, Laurie; Auton, Matthew

    2014-01-01

    The primary hemostatic von Willebrand factor (vWF) functions to sequester platelets from rheological blood flow and mediates their adhesion to damaged subendothelium at sites of vascular injury. We have surveyed the effect of 16 disease-causing mutations identified in patients diagnosed with the bleeding diathesis disorder, von Willebrand disease (vWD), on the structure and rheology of vWF A1 domain adhesiveness to the platelet GPIbα receptor. These mutations have a dynamic phenotypical range of bleeding from lack of platelet adhesion to severe thrombocytopenia. Using new rheological tools in combination with classical thermodynamic, biophysical, and spectroscopic metrics, we establish a high propensity of the A1 domain to misfold to pathological molten globule conformations that differentially alter the strength of platelet adhesion under shear flow. Rheodynamic analysis establishes a quantitative rank order between shear-rate-dependent platelet-translocation pause times that linearly correlate with clinically reported measures of patient platelet counts and the severity of thrombocytopenia. These results suggest that specific secondary structure elements remaining in these pathological conformations of the A1 domain regulate GPIbα binding and the strength of vWF-platelet interactions, which affects the vWD functional phenotype and the severity of thrombocytopenia. PMID:25185554

  18. Decoration Increases the Conspicuousness of Raptor Nests.

    PubMed

    Canal, David; Mulero-Pázmány, Margarita; Negro, Juan José; Sergio, Fabrizio

    2016-01-01

    Avian nests are frequently concealed or camouflaged, but a number of species builds noticeable nests or use conspicuous materials for nest decoration. In most cases, nest decoration has a role in mate choice or provides thermoregulatory or antiparasitic benefits. In territorial species however, decorations may serve additional or complementary functions, such as extended phenotypic signaling of nest-site occupancy and social status to potential intruders. The latter may benefit both signaler and receiver by minimizing the risk of aggressive interactions, especially in organisms with dangerous weaponry. Support for this hypothesis was recently found in a population of black kites (Milvus migrans), a territorial raptor that decorates its nest with white artificial materials. However, the crucial assumption that nest decorations increased nest-site visibility to conspecifics was not assessed, a key aspect given that black kite nests may be well concealed within the canopy. Here, we used an unmanned aircraft system to take pictures of black kite nests, with and without an experimentally placed decoration, from different altitudes and distances simulating the perspective of a flying and approaching, prospecting intruder. The pictures were shown to human volunteers through a standardized routine to determine whether detection rates varied according the nest decoration status and distance. Decorated nests consistently showed a higher detection frequency and a lower detection-latency, compared to undecorated versions of the same nests. Our results confirm that nest decoration in this species may act as a signaling medium that enhances nest visibility for aerial receivers, even at large distances. This finding complements previous work on this communication system, which showed that nest decoration was a threat informing trespassing conspecifics on the social dominance, territory quality and fighting capabilities of the signaler.

  19. Decoration Increases the Conspicuousness of Raptor Nests

    PubMed Central

    Canal, David; Mulero-Pázmány, Margarita; Negro, Juan José; Sergio, Fabrizio

    2016-01-01

    Avian nests are frequently concealed or camouflaged, but a number of species builds noticeable nests or use conspicuous materials for nest decoration. In most cases, nest decoration has a role in mate choice or provides thermoregulatory or antiparasitic benefits. In territorial species however, decorations may serve additional or complementary functions, such as extended phenotypic signaling of nest-site occupancy and social status to potential intruders. The latter may benefit both signaler and receiver by minimizing the risk of aggressive interactions, especially in organisms with dangerous weaponry. Support for this hypothesis was recently found in a population of black kites (Milvus migrans), a territorial raptor that decorates its nest with white artificial materials. However, the crucial assumption that nest decorations increased nest-site visibility to conspecifics was not assessed, a key aspect given that black kite nests may be well concealed within the canopy. Here, we used an unmanned aircraft system to take pictures of black kite nests, with and without an experimentally placed decoration, from different altitudes and distances simulating the perspective of a flying and approaching, prospecting intruder. The pictures were shown to human volunteers through a standardized routine to determine whether detection rates varied according the nest decoration status and distance. Decorated nests consistently showed a higher detection frequency and a lower detection-latency, compared to undecorated versions of the same nests. Our results confirm that nest decoration in this species may act as a signaling medium that enhances nest visibility for aerial receivers, even at large distances. This finding complements previous work on this communication system, which showed that nest decoration was a threat informing trespassing conspecifics on the social dominance, territory quality and fighting capabilities of the signaler. PMID:27455066

  20. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Wernher Von Braun (right), Deputy Associate Administrator for planning, National Aeronautics and Space Administration, inspects the mockup of the Saturn Workshop during a visit marking the 10th anniversary of the Marshall Center. Shown with Dr. Von Braun, from left to right, are Karl Heimburg, Director of the astronautics lab; Herman K. Weidner, Director of Science and Engineering, and George Hardy of the Astronautics lab.

  1. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Wernher Von Braun (right), Deputy Associate Administrator for Planning, National Aeronautics and Space Administration, inspects the mockup of the Saturn Workshop during a visit marking the 10th anniversary of the Marshall Center. Shown with Dr. Von Braun, from left to right, are Karl Heimburg, Director of the Astronautics Lab; Herman K. Weidner, Director of Science and Engineering, and George Hardy of the Astronautics Lab.

  2. Responses to aggregating agents after cleavage of GPIb of human platelets by the O-sialoglycoprotein endoprotease from Pasteurella haemolytica- potential surrogates for Bernard-Soulier platelets?

    PubMed

    Kinlough-Rathbone, R L; Perry, D W; Rand, M L; Packham, M A

    2000-07-15

    Most proteolytic enzymes that cleave glycoprotein lb (GPlb) also cleave other glycoproteins or receptors on the surface of platelets. We have used an O-sialoglycoprotein endoprotease from Pasteurella haemolytica that selectively cleaves the heavily O-glycosylated GPlb, but does not cleave N-linked glycoproteins or unglycosylated proteins. Isolated, [14C]serotonin-labeled platelets in Tyrode-albumin solution were incubated with 10 microg/mL endoprotease for 60 minutes at 37 degrees C. These platelets did not release [14C]serotonin, had no detectable GPIb, and were unresponsive to ristocetin/von Willebrand factor. Compared with control platelets, aggregation and release of [14C]serotonin by the endoprotease-pretreated platelets were inhibited in response to low concentrations of thrombin, SFLLRN (the PAR-1-activating peptide), collagen, and U46619 (a thromboxane A(2) mimetic); aggregates were smaller in size. The presence of fibrinogen overcame the inhibition of responses induced by SFLLRN, collagen, and U46619. With fibrinogen, primary ADP-induced aggregation was scarcely affected by pretreatment with the endoprotease. Thus, the PAR-1 receptor for thrombin, and receptors for collagen, thromboxane A(2), fibrinogen (GPIIb/IIIa), and ADP appear to function normally on the endoprotease-pretreated platelets. Since only GPIb is cleaved by the endoprotease, these platelets seem to provide potential surrogates for Bernard-Soulier syndrome platelets for further studies of platelet functions in this condition.

  3. Exposure of human megakaryocytes to high shear rates accelerates platelet production.

    PubMed

    Dunois-Lardé, Claire; Capron, Claude; Fichelson, Serge; Bauer, Thomas; Cramer-Bordé, Elisabeth; Baruch, Dominique

    2009-08-27

    Platelets originate from megakaryocytes (MKs) by cytoplasmic elongation into proplatelets. Direct platelet release is not seen in bone marrow hematopoietic islands. It was suggested that proplatelet fragmentation into platelets can occur intravascularly, yet evidence of its dependence on hydrodynamic forces is missing. Therefore, we investigated whether platelet production from MKs could be up-regulated by circulatory forces. Human mature MKs were perfused at a high shear rate on von Willebrand factor. Cells were observed in real time by videomicroscopy, and by confocal and electron microscopy after fixation. Dramatic cellular modifications followed exposure to high shear rates: 30% to 45% adherent MKs were converted into proplatelets and released platelets within 20 minutes, contrary to static conditions that required several hours, often without platelet release. Tubulin was present in elongated proplatelets and platelets, thus ruling out membrane tethers. By using inhibitors, we demonstrated the fundamental roles of microtubule assembly and MK receptor GPIb. Secretory granules were present along the proplatelet shafts and in shed platelets, as shown by P-selectin labeling. Platelets generated in vitro were functional since they responded to thrombin by P-selectin expression and cytoskeletal reorganization. In conclusion, MK exposure to high shear rates promotes platelet production via GPIb, depending on microtubule assembly and elongation.

  4. Multimeric analysis of von Willebrand factor in megakaryocytes.

    PubMed

    Kupinski, J M; Miller, J L

    1985-06-15

    Von Willebrand factor (vWF) is a glycoprotein that appears to play a major role in subserving the adhesion of platelets to subendothelium during hemostasis. Endothelial cells have been shown capable of synthesizing and releasing this large, multimeric glycoprotein that normally circulates in the plasma in association with the factor VIII coagulant molecule. Megakaryocytes, the precursor cells of blood platelets, also appear to possess vWF biosynthetic capacity, since cultured guinea pig megakaryocytes have been shown to produce a polypeptide precipitable by antibody to vWF. We now report a study of the multimeric structure of vWF in the megakaryocyte, as well as a quantitative comparison of megakaryocyte vWF with that of platelets and plasma in the guinea pig. Multimeric analysis on SDS agarose gels employing 125I-emu anti-human vWF revealed striking homology between human and guinea pig vWF. Platelets and megakaryocytes from the same guinea pigs contained vWF of highly comparable multimeric composition. Moreover, megakaryocytes and platelets both contained a subset of very high molecular weight multimers not present in plasma. Quantitation of vWF in megakaryocytes and platelets was achieved with a radioimmunoassay performed on detergent (NP-40) lysates of washed cells. These measurements showed that megakaryocytes and platelets contain 0.079 and 0.069 U of vWF per mg protein, respectively. The results of these studies suggest that megakaryocytes represent the primary, if in fact not sole, source of platelet vWF.

  5. Endotoxin Interactions with Platelets

    DTIC Science & Technology

    1985-01-01

    irreversible aggregation of human platelets (Hamberg and Sainuelsson 1974; Hlamberg et al 1975). Acetylsalicylic acid , an inhibitor of cyclooxygenase aud...exposure to endotoxin (100 ttg/nil). To simulate the lipopolysac- charide of endotoxin, several different fatty acids were added individually to platelet...platelet lytic capability. Similarity, iflegaradt doses of ganima radiation 6wCo destroy fatty acid groups on lipid A (L. Bertok, personal communication

  6. Functional fractionation of platelets.

    PubMed

    Haver, V M; Gear, A R

    1981-02-01

    Studies of platelet populations suggest that they are heterogeneous in size, age, and metabolic parameters. In an attempt to correlate these parameters with efficiency of aggregation, a new technique, functional fractionation, was developed. Platelet populations are separated by their differential reactivity to aggregating agents. For example, low doses of ADP (0.1 to 0.7 microM) are added to stirred PRP, after which gentle centrifugation is used to remove aggregates from single unreacted platelets. The loose aggregates can be readily dispersed for comparison of the physical or biochemical properties of the reacted versus unreacted platelets. It was found that reactive platelets were larger (6.5 micrometer3) than unreacted platelets (5.51 micrometer3). No significant difference in density existed between the two populations, and no release of [14C]serotonin from prelabeled platelets occurred during functional fractionation. Scanning and transmission electron microscopy confirmed the size difference and revealed that in both populations platelets were structurally intact with a normal discoid shape and no significant difference in organelle content. Human platelets most reactive to ADP were also enriched in glycogen (3.6-fold), ATP (1.6-fold), and ADP (twofold), compared with less reactive cells. These "reactive" cells took up more 51[Cr] and contained 1.9 times more surface sialic acid. In an in vivo aging experiment, rats were injected with 75[Se]methionine. Shortly after labeling (1 day), the most reactive platelets possessed the highest amount of 75[Se]. These results reveal that functionally active platelets, which are also larger, are more active metabolically than less reactive platelets, possess a higher negative surface charge, and may be a younger population.

  7. Rapidly regulating platelet activity in vivo with an antidote controlled platelet inhibitor.

    PubMed

    Nimjee, Shahid M; Lohrmann, Jens D; Wang, Haichen; Snyder, David J; Cummings, Thomas J; Becker, Richard C; Oney, Sabah; Sullenger, Bruce A

    2012-02-01

    Millions of individuals are prescribed platelet inhibitors, such as aspirin and clopidogrel, to reduce their risk of thrombosis-related clinical events. Unfortunately many platelet inhibitors are contraindicated in surgical settings because of their inherent bleeding risk complicating the treatment of patients who require surgery. We describe the development of a potent antiplatelet agent, an RNA aptamer-termed Ch-9.14-T10 that binds von Willebrand factor (VWF) with high affinity and inhibits thrombosis in a murine carotid artery damage model. As expected, when this potent antiplatelet agent is administered, it greatly increases bleeding from animals that are surgically challenged. To improve this antiplatelet agent's safety profile, we describe the generation of antidotes that can rapidly reverse the activity of Ch-9.14-T10 and limit blood loss from surgically challenged animals. Our work represents the first antidote controllable antiplatelet agent, which could conceivably lead to improved medical management of patients requiring antiplatelet medication who also need surgery.

  8. Clot lysis time in platelet-rich plasma: method assessment, comparison with assays in platelet-free and platelet-poor plasmas, and response to tranexamic acid.

    PubMed

    Panes, Olga; Padilla, Oslando; Matus, Valeria; Sáez, Claudia G; Berkovits, Alejandro; Pereira, Jaime; Mezzano, Diego

    2012-01-01

    Fibrinolysis dysfunctions cause bleeding or predisposition to thrombosis. Platelets contain several factors of the fibrinolytic system, which could up or down regulate this process. However, the temporal relationship and relative contributions of plasma and platelet components in clot lysis are mostly unknown. We developed a clot lysis time (CLT) assay in platelet-rich plasma (PRP-CLT, with and without stimulation) and compared it to a similar one in platelet-free plasma (PFP) and to another previously reported test in platelet-poor plasma (PPP). We also studied the differential effects of a single dose of tranexamic acid (TXA) on these tests in healthy subjects. PFP- and PPP-CLT were significantly shorter than PRP-CLT, and the three assays were highly correlated (p < 0.0001). PFP- and PPP-, but more significantly PRP-CLT, were positively correlated with age and plasma PAI-1, von Willebrand factor, fibrinogen, LDL-cholesterol, and triglycerides (p < 0.001). All these CLT assays had no significant correlations with platelet aggregation/secretion, platelet counts, and pro-coagulant tests to explore factor X activation by platelets, PRP clotting time, and thrombin generation in PRP. Among all the studied variables, PFP-CLT was independently associated with plasma PAI-1, LDL-cholesterol, and triglycerides and, additionally, stimulated PRP-CLT was also independently associated with plasma fibrinogen. A single 1 g dose of TXA strikingly prolonged all three CLTs, but in contrast to the results without the drug, the lysis times were substantially shorter in non-stimulated or stimulated PRP than in PFP and PPP. This standardized PRP-CLT may become a useful tool to study the role of platelets in clot resistance and lysis. Our results suggest that initially, the platelets enmeshed in the clot slow down the fibrinolysis process. However, the increased clot resistance to lysis induced by TXA is overcome earlier in platelet-rich clots than in PFP or PPP clots. This is

  9. Platelet size in man.

    PubMed

    Paulus, J M

    1975-09-01

    The shape and parameters of platelet size distributions were studied in 50 normal persons and 97 patients in order to test the proposed thesis that platelet size heterogeneity results mainly from aging in the circulation. This thesis was contradicted (1) by size distributions of age-homogeneous, newly-born cell populations which were lognormal with increased (instead of decreased) dispersion of volumes and (2) by the macrothrombocytosis found in some populations with normal age distribution. For these reasons, thrombocytopoiesis appeared to play the major role in determining platelet size. A model was built in which the volume variation of platelet territories due to megakaryocyte growth and membrane demarcation at each step of maturation was a random proportion of the previous value of the volume. This model explains the lognormal shape of both newborn and circulating platelet size distributions. It also implies that (1) the mean and standard deviation of platelet logvolumes depend on the rates of volume change of the individual platelet territories (growth rate minus demarcation rate) as well as on megakaryocyte maturation time; (2) platelet hyperdestruction causes an increase in the mean and dispersion of the rates of territory volume change; (3) Mediterranean macrothrombocytosis and some hereditary macrothrombocytotic thrombocytopenias or dysthrombocytopoieses reflect a diminished rate of territory demarcation, and (4) platelet size heterogeneity is caused mainly by the variations in territory growth and demarcation and not by aging in the circulation.

  10. Platelets enhance neutrophil transendothelial migration

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. Thrombopoietin increases platelet adhesion under flow and decreases rolling.

    PubMed

    Van Os, Erim; Wu, Ya-Ping; Pouwels, Jos G; Ijsseldijk, Martin J W; Sixma, Jan J; Akkerman, Jan Willem N; De Groot, Philip G; Van Willigen, Gijsbert

    2003-05-01

    Thrombopoietin (TPO) is known to sensitize platelets to other agonists at 20 ng/ml, and above 100 ng/ml it is an independent activator of aggregation and secretion. In studies with a perfusion chamber, TPO, between 0.01 ng/ml and 1 ng/ml, increased platelet adhesion to surface-coated fibrinogen, fibronectin and von Willebrand Factor (VWF) but not to a collagen-coated surface. Increased adhesion was observed at shear rates of 300/s and 800/s in perfusions with whole blood as well as in suspensions of platelets and red blood cells reconstituted in plasma. The by the cyclooxygenase inhibitor, indomethacin, and the thromboxane A2-receptor blocker, SQ30741, abolished the stimulation by TPO. The effect of TPO was mimicked by a very low concentration (10 nmol/l) of the thromboxane TxA2 analogue, U46619. Real-time studies of platelet adhesion to a VWF-coated surface at a shear of 1000/s showed that about 20% of the platelets were in a rolling phase before they became firmly attached. TPO (1 ng/ml) pretreatment reduced this number to < 5%, an effect again abolished by indomethacin. Thus, TPO potentiates the direct and firm attachment of platelets to surface-coated ligands for alphaIIbbeta3, possibly by increasing the ligand affinity of the integrin.

  12. Up to date concepts about Von Willebrand disease and the diagnose of this hemostatic disorder

    PubMed Central

    Buga-Corbu, I; Arion, C

    2014-01-01

    Abstract The authors review the current data in literature regarding the recent knowledge about hemostase, coagulation and clinical and laboratory diagnostic algorithms of hemostatic disorders. They also present the pathological classification of bleeding disorders - the basis to clinical approach of these diseases. Abbreviations: AD=autosomal dominant; Ag=antigen; DNA=deoxyribonucleic acid; ADAMTS13=serum metalloproteinase; AR=autosomal recessive; Arg=arginine; RNA=ribonucleic acid; VWD=von Willebrand disease; Cys=cysteine; C1—C9=factors of the seric complement; ELISA=enzyme linked immuno assay; FI---FXIII=plasmatic factors of coagulation; Glu=glutamines; Pg=platelet glycoprotein; HMW=high molecular weight; IL=interleukin; SLE=systemic lupus erythematosus; Met=methionine; PFA=automated study test of platelets aggregation; RCo=ristocetin cofactor; RI PA=ristocetin induced platelet aggregation; Tyr=tyrosine; VWF= von Willebrand factor PMID:25408749

  13. Dynamic redistribution of major platelet surface receptors after contact-induced platelet activation and spreading. An immunoelectron microscopy study.

    PubMed Central

    Kieffer, N.; Guichard, J.; Breton-Gorius, J.

    1992-01-01

    The authors used an immunogold labeling procedure to investigate the redistribution of platelet receptors and their ligands on the surface of contact-activated adherent platelets before and after thrombin stimulation. During the initial stage of platelet adhesion, a typical segregation of receptors occurred. Gold particles identifying glycoprotein (GP) Ib (CD42b) and GPIIb-IIIa (CD41a) remained distributed over the entire platelet surface, whereas gold particles identifying GPIa-IIa (CDw 49b) and GPIV (CD36) were found essentially overlying the granulomere; p24 (CD9) was present at the peripheral platelet rim and over the cell body. An increased labeling of GPIIb-IIIa, GPIV and p24 was also observed on pseudopods, with GPIIb-IIIa and GPIV concentrated at the enlarged extremities and at sites of contact between two platelets, whereas GPIb was absent from pseudopods. After thrombin stimulation of adherent platelets, GPIb underwent a relocation to the cell center, in contrast to GPIIb-IIIa which still remained randomly distributed over the cell body. To investigate whether ligand distribution paralleled this receptor segregation, platelet released von Willebrand factor (vWF), fibrinogen (Fg) and thrombospondin (TSP) were visualized. During the early stages of platelet activation, surface labeling for all three adhesive proteins was minimal and almost undetectable. Occasionally, intragranular Fg and vWF was accessible to gold-coupled antibodies, with vWF exhibiting the typical eccentric alpha-granular localization. At later stages of activation and especially after thrombin stimulation, no surface labeling for vWF was observed, whereas immunogold particles identifying vWF were still present inside enlarged clear vacuoles. In contrast, labeling of Fg and TSP was increased over the granulomere and extended to the cell periphery and the pseudopods, but was absent from the hyalomere, despite the presence of GPIIb-IIIa molecules. Double labeling experiments showed

  14. Polyoxometalate (POM) Macroion Decorated Polymersomes

    NASA Astrophysics Data System (ADS)

    Jing, Benxin; Connor, Erin; Zhu, Y. Elaine

    2014-03-01

    Polymersomes as one of the common self-assembled forms of amphiphilic block copolymers have been widely developed for applications from drug delivery to mirco/nanoreactors. The tunability of their materials properties, such as mechanical strength and permeability often relies on the chemistry of the selected polymer in a liquid medium. We have recently employed the emergent polyoxometalate (POM) nanoclusters as macroions to control their interaction and assembly with different polymersomes. For both neutral and cationic polymersomes decorated with highly charged anionic POM nanoclusters, the dispersion stability and mechanic strength can be significantly enhanced. AFM and TEM characterization further confirms the encapsulation of POM macroions into polymersomes to form inorganic-organic hybrid complexes, which lead to new potential applications in anticancer and antibacterial medicines and catalysts.

  15. Platelet dysfunction associated with Wilms tumor and hyaluronic acid.

    PubMed

    Bracey, A W; Wu, A H; Aceves, J; Chow, T; Carlile, S; Hoots, W K

    1987-03-01

    Acquired von Willebrand disease (AVWD) has been described in two cases of nephroblastoma. We studied a patient with nephroblastoma who presented with a coagulopathy suggestive of AVWD. The subject had undetectable levels of F.VIIIR:Ag, diminished F.VIIIR:WF (16.3%), F.VIII:C activity (37%), and lack of platelet aggregation to ADP, epinephrine, collagen, and arachidonic acid. These results were associated with abnormally high serum levels (850 mg/dl) of hyaluronic acid (HA), which made the patient's serum hyperviscous. Examination of the neoplasm revealed HA in the tumor matrix. All abnormalities of coagulation resolved after chemotherapy and extirpation of the neoplasm, which produced normal serum HA levels. To study the effects of HA on platelet function, we added HA to normal platelet-poor plasma (NPP), which rendered F.VIIIR:Ag undetectable; treatment of HA with hyaluronidase eliminated F.VIIIR:Ag assay interference caused by HA. F.VIII:C activity decreased in vitro when HA was mixed with normal platelet-poor plasma (NPP). HA reduced the initial slope of normal platelet aggregation. Partial correction of platelet aggregation occurred after hyaluronidase treatment of HA-spiked PRP. Experiments in rabbits exposed to HA (serum level 400 mg/dl) demonstrated abnormalities similar to those noted in the patient. Shear rate studies of whole blood containing HA (500 mg/dl) yielded high shear stress, 27-136 dynes/cm2 over shear rates of 10-216 sec-1. We conclude that the coagulopathy demonstrated in this case is secondary to hyperviscosity produced by elevated levels of HA, which interferes with the assay for F.VIIIR:Ag. Thus the acquired coagulopathy associated with other cases of nephroblastoma may present as spurious von Willebrand disease.

  16. Function of von Willebrand factor after crossed bone marrow transplantation between normal and von Willebrand disease pigs: effect on arterial thrombosis in chimeras.

    PubMed Central

    Nichols, T C; Samama, C M; Bellinger, D A; Roussi, J; Reddick, R L; Bonneau, M; Read, M S; Bailliart, O; Koch, G G; Vaiman, M

    1995-01-01

    von Willebrand factor (vWF) is essential for the induction of occlusive thrombosis in stenosed and injured pig arteries and for normal hemostasis. To separate the relative contribution of plasma and platelet vWF to arterial thrombosis, we produced chimeric normal and von Willebrand disease pigs by crossed bone marrow transplantation; von Willebrand disease (vWD) pigs were engrafted with normal pig bone marrow and normal pigs were engrafted with vWD bone marrow. Thrombosis developed in the chimeric normal pigs that showed normal levels of plasma vWF and an absence of platelet vWF; but no thrombosis occurred in the chimeric vWD pigs that demonstrated normal platelet vWF and an absence of plasma vWF. The ear bleeding times of the chimeric pigs were partially corrected by endogenous plasma vWF but not by platelet vWF. Our animal model demonstrated that vWF in the plasma compartment is essential for the development of arterial thrombosis and that it also contributes to the maintenance of bleeding time and hemostasis. Images Fig. 2 Fig. 3 PMID:7708664

  17. Platelet additive solution - electrolytes.

    PubMed

    Azuma, Hiroshi; Hirayama, Junichi; Akino, Mitsuaki; Ikeda, Hisami

    2011-06-01

    Recent attention to solutions that replace most or all plasma in platelet concentrates, while maintaining satisfactory platelet function, is motivated by the potential of plasma reduction or depletion to mitigate various transfusion-related adverse events. This report considers the electrolytic composition of previously described platelet additive solutions, in order to draw general conclusions about what is required for platelet function and longevity. The optimal concentrations of Na(+) and Cl(-) are 69-115 mM. The presence of both K(+) and Mg(2+) in platelet suspension at nearly physiological concentrations (3-5mM and 1.5-3mM, respectively) is indispensable for good preservation capacity because both electrolytes are required to prevent platelet activation. In contrast to K(+) and Mg(2+), Ca(2+) may not be important because no free Ca(2+) is available in M-sol, which showed excellent platelet preservation capacity at less than 5% plasma concentration. The importance of bicarbonate (approximately 40 mM) can be recognized when the platelets are suspended in additive solution under less than 5% residual plasma concentration.

  18. Platelet Function Tests.

    PubMed

    Lordkipanidzé, Marie

    2016-04-01

    Traditionally developed for diagnosis of bleeding disorders, platelet function assays have become increasingly used in basic research on platelet physiology, in phenotype-genotype associations in bleeding disorders, in drug development as surrogate endpoints of efficacy of new antiplatelet therapy, and to an extent, in the monitoring of antiplatelet therapy in clinical practice to predict thrombotic and bleeding risk. A multiplicity of platelet function assays is available to measure the level of platelet activity in various settings. These include assays that are restricted to a specialized laboratory as well as point-of-care instruments meant to investigate platelet function at patient bedside. Unlike tests that determine a defined quantity or measurement of a clinical biomarker (e.g., cholesterol or blood pressure), platelet function testing assesses the dynamics of living cells, which immediately presents a series of unique problems to any laboratory or clinic. This article presents currently used platelet function assays and discusses important variables to take into account when performing these assays, including preanalytical issues and difficulties in interpreting platelet function test results.

  19. Interactions of von Willebrand factor and ADAMTS13 in von Willebrand disease and thrombotic thrombocytopenic purpura.

    PubMed

    Budde, U; Schneppenheim, R

    2014-01-01

    The function of von Willebrand factor (VWF), a huge multimeric protein and a key factor in platelet dependent primary haemostasis, is regulated by its specific protease ADAMTS13. The ADAMTS13 dependent degradation of VWF to its proteolytic fragments can be visualized as a characteristic so-called triplet structure of individual VWF oligomers by multimer analysis. Lack of VWF high molecular weight multimers (VWF-HMWM) or their pathologically enhanced degradation underlies a particular type of von Willebrand disease, VWD type 2A with a significant bleeding tendency, and may also be observed in acquired von Willebrand syndrome due to cardiovascular disease. In these conditions multimer analysis is an obligatory and powerful tool for diagnosis of VWD. The opposite condition, the persistence of ultralarge VWF (UL-VWF) multimers may cause the microangiopathic life-threatening disorder thrombotic thrombocytopenic purpura (TTP). During the course of active TTP, UL-VWF is consumed in the hyaline thrombi formed in the microvasculature which will ultimately result in the loss of UL-VWF and VWF-HMWM. Therefore, VWF multimer analysis is not a valid tool to diagnose TTP in the active phase of disease but may be helpful for the diagnosis of TTP patients in remission.

  20. Alloimmune refractoriness to platelet transfusions.

    PubMed

    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).

  1. The sticky platelet syndrome.

    PubMed

    Moncada, Benjamín; Ruíz-Arguelles, Guillermo J; Castillo-Martínez, Claudio

    2013-07-01

    The sticky platelets syndrome (SPS) is a procoagulant condition based on either arterial, venous, or capillary thrombi caused by hyperesponsive and hyperaggregable platelets. This is a frequent disease, which often remains clinically inapparent, until stressful events or combination with other factors increase the risk of developing SPS. The condition is due to a congenital platelet defect with autosomal dominant characteristics, leading to the increased platelet aggregability when they are challenged with epinephrine and adenosine diphosphate. Nowadays classification of this disorder is based on platelet reactivity to both ADP and epinephrine (SPS type 1), epinephrine alone (SPS type 2), and ADP alone (SPS type 3). The diagnoses of the syndrome depend on the functional aggregometer assay. This condition should be taken into account whenever a patient with thrombophilia is considered.

  2. Cisplatin triggers platelet activation.

    PubMed

    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.

  3. von Willebrand factor, Jedi knight of the bloodstream.

    PubMed

    Springer, Timothy A

    2014-08-28

    When blood vessels are cut, the forces in the bloodstream increase and change character. The dark side of these forces causes hemorrhage and death. However, von Willebrand factor (VWF), with help from our circulatory system and platelets, harnesses the same forces to form a hemostatic plug. Force and VWF function are so closely intertwined that, like members of the Jedi Order in the movie Star Wars who learn to use "the Force" to do good, VWF may be considered the Jedi knight of the bloodstream. The long length of VWF enables responsiveness to flow. The shape of VWF is predicted to alter from irregularly coiled to extended thread-like in the transition from shear to elongational flow at sites of hemostasis and thrombosis. Elongational force propagated through the length of VWF in its thread-like shape exposes its monomers for multimeric binding to platelets and subendothelium and likely also increases affinity of the A1 domain for platelets. Specialized domains concatenate and compact VWF during biosynthesis. A2 domain unfolding by hydrodynamic force enables postsecretion regulation of VWF length. Mutations in VWF in von Willebrand disease contribute to and are illuminated by VWF biology. I attempt to integrate classic studies on the physiology of hemostatic plug formation into modern molecular understanding, and point out what remains to be learned.

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

    DTIC Science & Technology

    2015-10-01

    trauma patients. References: 1. Slichter SJ, Harker LA. Preparation and storage of platelet concentrates . II. Storage variables influencing ...Storage variables influencing platelet viability and function. Br J Haematol 1976;34(3):403-419. 2. Becker GA, Tuccelli M, Kunicki T, et al. Studies of...platelet additive solution (PAS) to extend the life of stored platelets. Our project also aims to determine how long acceptable platelet viability can be

  5. Platelet interaction with polymerizing fibrin.

    PubMed

    Niewiarowski, S; Regoeczi, E; Stewart, G J; Senyl, A F; Mustard, J F

    1972-03-01

    Interaction of washed pig, rabbit, or human platelets with fibrinogen was studied during its transition to fibrin using photometric, isotopic, and electron microscopic techniques. Untreated fibrinogen and fully polymerized fibrin had no detectable effect on platelets. Fibrinogen, incubated with low concentrations of reptilase or thrombin, formed intermediate products which readily became associated with platelets and caused their aggregation. Neutralization of the thrombin did not prevent this interaction. In the absence of fibrinogen, reptilase did not affect platelets. The interaction of polymerizing fibrin with platelets was accompanied by small losses of platelet constituents (serotonin, adenine nucleotides, platelet factor 4, and lactic dehydrogenase). This loss did not appear to be the result of the platelet release reaction. Inhibitors of the release reaction or of adenosine diphosphate (ADP)-induced aggregation did not prevent the interaction of platelets with polymerizing fibrin. Apyrase or prostaglandin E(1) (PGE(1)) reduced the extent of platelet aggregation by polymerizing fibrin, but the amount of protein associated with platelets was slightly increased. The interaction of polymerizing fibrin with platelets was completely inhibited by ethylenediaminetetraacetate (EDTA) or ethylene glycol bis (beta-aminoethyl ether) N, N,N',N'-tetraacetic acid (EGTA).Fibers formed in solutions of polymerizing fibrin were larger in the presence than in the absence of washed platelets, suggesting that platelets affect fibrin polymerization. The adherence of platelets to polymerizing fibrin may be responsible for the establishment of links between platelets and fibrin in hemostatic plugs and thrombi.

  6. Platelet Adhesion under Flow

    PubMed Central

    Ruggeri, Zaverio M.

    2011-01-01

    Platelet adhesive mechanisms play a well-defined role in hemostasis and thrombosis, but evidence continues to emerge for a relevant contribution to other pathophysiological processes including inflammation, immune-mediated responses to microbial and viral pathogens, and cancer metastasis. Hemostasis and thrombosis are related aspects of the response to vascular injury, but the former protects from bleeding after trauma while the latter is a disease mechanism. In either situation, adhesive interactions mediated by specific membrane receptors support the initial attachment of single platelets to cellular and extracellular matrix constituents of the vessel wall and tissues. In the subsequent steps of thrombus growth and stabilization, adhesive interactions mediate platelet to platelet cohesion (aggregation) and anchoring to the fibrin clot. A key functional aspect of platelets is their ability to circulate in a quiescent state surveying the integrity of the inner vascular surface, coupled to a prompt reaction wherever alterations are detected. In many respects, therefore, platelet adhesion to vascular wall structures, to one another or to other blood cells are facets of the same fundamental biological process. The adaptation of platelet adhesive functions to the effects of blood flow is the main focus of this review. PMID:19191170

  7. Platelets in Critical Illness.

    PubMed

    Levi, Marcel

    2016-04-01

    In patients with critical illness, thrombocytopenia is a frequent laboratory abnormality. However frequent this may occur, a low platelet count is not an epiphenomenon, but a marker with further significance. It is always important to assess the proper cause for thrombocytopenia in critically ill patients because different underlying disorders may precipitate different diagnostic and therapeutic management strategies. Platelets are part of the first-line defense of the body against bleeding; hence, thrombocytopenia may increase the risk of hemorrhage. In case of systemic inflammatory syndromes, such as the response to sepsis, disseminated intravascular platelet activation may occur. This will contribute to microvascular failure and thereby play a role in the development of organ dysfunction. Platelets are circulating blood cells that will normally not interact with the intact vessel wall but that may swiftly respond to endothelial disruption (which is often part of the pathogenesis of critical illness) by adhering to subendothelial structures, followed by interaction with each other, thereby forming a platelet aggregate. The activated platelet (phospholipid) membrane may form a suitable surface on which further coagulation activation may occur. A low platelet count is a strong and independent predictor of an adverse outcome in critically ill patients, thereby facilitating a simple and practically risk assessment in these patients and potentially guiding the use of complex or expensive treatment strategies.

  8. Unwinding the von Willebrand factor strings puzzle.

    PubMed

    De Ceunynck, Karen; De Meyer, Simon F; Vanhoorelbeke, Karen

    2013-01-10

    von Willebrand factor (VWF) is amongst others synthesized by endothelial cells and stored as ultra-large (UL) VWF multimers in Weibel-Palade bodies. Although UL-VWF is proteolysed by ADAMTS13 (a disintegrin-like and metalloprotease domain with thrombospondin type-1 motif, number 13) on secretion from endothelial cells, in vitro experiments in the absence of ADAMTS13 have demonstrated that a proportion of these UL-VWF multimers remain anchored to the activated endothelium. These multimers unravel, bind platelets, and wave in the direction of the flow. These so-called VWF "strings" have also been visualized in vivo, lining the lumen of activated mesenteric veins of Adamts13(-/-) mice. Various studies have demonstrated the extraordinary length of these VWF strings, the availability of their platelet binding and ADAMTS13 cleavage sites, and the possible nature of their endothelial attachment. VWF strings are also capable of tethering leukocytes and parasite-infected red blood cells. However, the majority of studies have been performed in the absence of ADAMTS13, a condition only experienced in thrombotic thrombocytopenic purpura. A normal functional role of VWF strings in healthy persons or in other disease pathologies remains unclear. In this review, we discuss some of the puzzling characteristics of VWF strings, and we debate whether the properties of VWF strings in the absence of ADAMTS13 might be relevant for understanding (patho)physiologic mechanisms.

  9. Silver nanowire decorated heatable textiles

    NASA Astrophysics Data System (ADS)

    Doganay, Doga; Coskun, Sahin; Polat Genlik, Sevim; Emrah Unalan, Husnu

    2016-10-01

    The modification of insulating fabrics with electrically conductive nanomaterials has opened up a novel application field. With the help of Joule heating mechanism, conductive fabrics can be used as mobile heaters. In this work, heatable textiles are fabricated using silver nanowires (Ag NWs). Cotton fabrics are decorated with polyol synthesized Ag NWs via a simple dip-and-dry method. The time-dependent thermal response of the fabrics under different applied voltages is investigated. It is found that the fabrics can be heated to 50 °C under an applied power density of as low as 0.05 W cm-2. Uniform deposition of Ag NWs resulted in the homogeneous generation of heat. In addition, the stability of the fabrics with time and under different bending and washing conditions is examined. Moreover, a simple control circuit is fabricated and integrated in order to demonstrate the high potential of the fabrics for mobile applications. This work provides a roadmap for researchers who would like to work on heatable textiles with metallic NWs.

  10. Silver nanowire decorated heatable textiles.

    PubMed

    Doganay, Doga; Coskun, Sahin; Genlik, Sevim Polat; Unalan, Husnu Emrah

    2016-10-28

    The modification of insulating fabrics with electrically conductive nanomaterials has opened up a novel application field. With the help of Joule heating mechanism, conductive fabrics can be used as mobile heaters. In this work, heatable textiles are fabricated using silver nanowires (Ag NWs). Cotton fabrics are decorated with polyol synthesized Ag NWs via a simple dip-and-dry method. The time-dependent thermal response of the fabrics under different applied voltages is investigated. It is found that the fabrics can be heated to 50 °C under an applied power density of as low as 0.05 W cm(-2). Uniform deposition of Ag NWs resulted in the homogeneous generation of heat. In addition, the stability of the fabrics with time and under different bending and washing conditions is examined. Moreover, a simple control circuit is fabricated and integrated in order to demonstrate the high potential of the fabrics for mobile applications. This work provides a roadmap for researchers who would like to work on heatable textiles with metallic NWs.

  11. Increased platelet deposition on atherosclerotic coronary arteries.

    PubMed Central

    van Zanten, G H; de Graaf, S; Slootweg, P J; Heijnen, H F; Connolly, T M; de Groot, P G; Sixma, J J

    1994-01-01

    A ruptured atherosclerotic plaque leads to exposure of deeper layers of the plaque to flowing blood and subsequently to thrombus formation. In contrast to the wealth of data on the occurrence of thrombi, little is known about the reasons why an atherosclerotic plaque is thrombogenic. One of the reasons is the relative inaccessibility of the atherosclerotic plaque. We have circumvented this problem by using 6-microns cryostat cross sections of human coronary arteries. These sections were mounted on coverslips that were exposed to flowing blood in a rectangular perfusion chamber. In normal-appearing arteries, platelet deposition was seen on the luminal side of the intima and on the adventitia. In atherosclerotic arteries, strongly increased platelet deposition was seen on the connective tissue of specific parts of the atherosclerotic plaque. The central lipid core of an advanced plaque was not reactive towards platelets. The results indicate that the atherosclerotic plaque by itself is more thrombogenic than the normal vessel wall. To study the cause of the increased thrombus formation on the atherosclerotic plaque, perfusion studies were combined with immunohistochemical studies. Immunohistochemical studies of adhesive proteins showed enrichment of collagen types I, III, V, and VI, vitronectin, fibronectin, fibrinogen/fibrin, and thrombospondin in the atherosclerotic plaque. Laminin and collagen type IV were not enriched. von Willebrand Factor (vWF) was not present in the plaque. The pattern of increased platelet deposition in serial cross sections corresponded best with areas in which collagen types I and III were enriched, but there were also areas in the plaque where both collagens were enriched but no increased reactivity was seen. Inhibition of platelet adhesion with a large range of antibodies or specific inhibitors showed that vWF from plasma and collagen types I and/or III in the plaque were involved. Fibronectin from plasma and fibronectin, fibrinogen

  12. Energetische Verwertung von Biomasse

    NASA Astrophysics Data System (ADS)

    Zahoransky, Richard; Allelein, Hans-Josef; Bollin, Elmar; Oehler, Helmut; Schelling, Udo

    Etwa 0,1% der Solarenergie wandeln sich durch Photosynthese aus dem Kohlendioxid der Luft in Biomasse um. Die Biomassen sind als Festbrennstoff nutzbar oder zu gasförmigen Brennstoffen weiterverarbeitbar. Zwei Arten von Biomassen sind zu unterscheiden: Anfallende Biomasse

  13. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Shown viewing the Apollo telescope mockup are, from left to right, Charles Donlan, deputy associate administrator for manned space flight; Dr. Wernher Von Braun, Marshall Space Flight Center director; William Horton, astrionics lab; Dr. Thomas Paine, NASA deputy administrator; Warner Kuers, director of the ME lab.

  14. Platelet-delivered therapeutics.

    PubMed

    Lyde, R; Sabatino, D; Sullivan, S K; Poncz, M

    2015-06-01

    We have proposed that modified platelets could potentially be used to correct intrinsic platelet defects as well as for targeted delivery of therapeutic molecules to sights of vascular injury. Ectopic expression of proteins within α-granules prior to platelet activation has been achieved for several proteins, including urokinase, factor (F) VIII, and partially for FIX. Potential uses of platelet-directed therapeutics will be discussed, focusing on targeted delivery of urokinase as a thromboprophylactic agent and FVIII for the treatment of hemophilia A patients with intractable inhibitors. This presentation will discuss new strategies that may be useful in the care of patients with vascular injury as well as remaining challenges and limitations of these approaches.

  15. Platelets and diabetes mellitus.

    PubMed

    Santilli, Francesca; Simeone, Paola; Liani, Rossella; Davì, Giovanni

    2015-07-01

    Platelet activation plays a key role in atherothrombosis in type 2 diabetes mellitus (T2DM) and increased in vivo platelet activation with enhanced thromboxane (TX) biosynthesis has been reported in patients with impairment of glucose metabolism even in the earlier stages of disease and in the preclinical phases. In this regards, platelets appear as addresses and players carrying and transducing metabolic derangement into vascular injury. The present review critically addresses key pathophysiological aspects including (i) hyperglycemia, glycemic variability and insulin resistance as determinants and predictors of platelet activation, (ii) inflammatory mediators derived from platelets, such as soluble CD40 ligand, soluble CD36, Dickkopf-1 and probably soluble receptor for advanced glycation-end-products (sRAGE), which expand the functional repertoire of platelets from players of hemostasis and thrombosis to powerful amplifiers of inflammation by promoting the release of cytokines and chemokines, cell activation, and cell-cell interactions; (iii) molecular mechanisms underpinning the less-than-expected antithrombotic protection by aspirin (ASA), despite regular antiplatelet prophylaxis at the standard dosing regimen, and (iv) stratification of patients deserving different antiplatelet strategies, based on the metabolic phenotype. Taken together, these pathophysiological aspects may contribute to the development of promising mechanism-based therapeutic strategies to reduce the progression of atherothrombosis in diabetic subjects.

  16. Platelets and wound healing.

    PubMed

    Nurden, Alan T; Nurden, Paquita; Sanchez, Mikel; Andia, Isabel; Anitua, Eduardo

    2008-05-01

    Platelets help prevent blood loss at sites of vascular injury. To do this, they adhere, aggregate and form a procoagulant surface favoring thrombin generation and fibrin formation. In addition, platelets express and release substances that promote tissue repair and influence processes such as angiogenesis, inflammation and the immune response. They contain large secretable pools of biologically active proteins, while newly synthesized active metabolites are also released. Although anucleate, activated platelets possess a spliceosome and can synthesize tissue factor and interleukin-1beta. The binding of secreted proteins within a developing fibrin mesh or to the extracellular matrix can create chemotactic gradients favoring the recruitment of stem cells, stimulating cell migration and differentiation, and promoting repair. The therapeutic use of platelets in a fibrin clot has a positive influence in clinical situations requiring rapid healing. Dental implant surgery, orthopaedic surgery, muscle and tendon repair, skin ulcers, hole repair in eye surgery and cardiac surgery are situations where the use of autologous platelets accelerates healing. We now review the ways in which platelets participate in these processes.

  17. Nitric oxide released from activated platelets inhibits platelet recruitment.

    PubMed Central

    Freedman, J E; Loscalzo, J; Barnard, M R; Alpert, C; Keaney, J F; Michelson, A D

    1997-01-01

    Vessel injury and thrombus formation are the cause of most ischemic coronary syndromes and, in this setting, activated platelets stimulate platelet recruitment to the growing thrombus. Recently, a constitutive nitric oxide synthase (NOS) has been identified in human platelets. To further define the capacity of platelets to produce nitric oxide (NO), as well as to study the role of this NO in platelet recruitment, we adapted a NO-selective microelectrode for use in a standard platelet aggregometer, thereby permitting simultaneous measurement of platelet aggregation and NO production. Treatment of platelets with the NO synthase inhibitor -NG-nitroarginine methyl ester (L-NAME), reduced NO production by 92+/-8% in response to 5 microM ADP compared to control but increased aggregation by only 15+/-2%. In contrast, L-NAME had a more pronounced effect on platelet recruitment as evidenced by a 35+/-5% increase in the extent of aggregation, a 33+/-3% decrease in cyclic GMP content, and a 31+/-5% increase in serotonin release from a second recruitable population of platelets added to stimulated platelets at the peak of NO production. To study platelet recruitment accurately, we developed an assay that monitors two platelet populations simultaneously. Nonbiotinylated platelets were incubated with L-NAME or vehicle and activated with ADP. At peak NO production, biotinylated platelets were added. As measured by three-color flow cytometry, there was a 56+/-11% increase in the number of P selectin- positive platelets in the nonbiotinylated population treated with L-NAME as compared to control. When biotinylated platelets were added to the L-NAME-treated nonbiotinylated population, the number of P selectin positive biotinylated plate-lets increased by 180+/-32% as compared to biotinylated platelets added to the control. In summary, stimulated platelets produce NO that modestly inhibits platelet activation but markedly inhibits additional platelet recruitment. These data suggest

  18. Platelet preservation: agitation and containers.

    PubMed

    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.

  19. Expression of platelet membrane glycoproteins and alpha-granule proteins by a human erythroleukemia cell line (HEL).

    PubMed Central

    Tabilio, A; Rosa, J P; Testa, U; Kieffer, N; Nurden, A T; Del Canizo, M C; Breton-Gorius, J; Vainchenker, W

    1984-01-01

    We demonstrate that HEL, a human erythroleukemic cell line, has numerous megakaryocytic markers which were markedly enhanced following the addition of the inducers dimethyl sulfoxide or 12-O-tetradecanoylphorbol-13-acetate to the culture medium. Ultrastructural and cytochemical studies showed: (i) the presence of organelles morphologically resembling the platelet alpha-granules; and (ii) a peroxidase activity with the same characteristics as that specifically found in platelets. The platelet alpha-granule proteins (von Willebrand factor, platelet factor-4 and beta-thromboglobulin) were immunologically detected in the HEL cell cytoplasm and their amounts increased after induction. Of particular interest was the presence of platelet membrane proteins. A monoclonal antibody specific for glycoprotein Ib bound to HEL cells. Platelet membrane glycoproteins IIb and IIIa were identified on intact cells using specific antibodies in a binding assay or in cell lysates using either crossed immunoelectrophoresis or an immunoblotting procedure following SDS-polyacrylamide gel electrophoresis. Most HEL cells also expressed the platelet alloantigen PIA1. All of the platelet membrane proteins were present in higher amounts after induction. Glycophorin A, specific for the erythroid lineage, was also detected on HEL cells. Thus, while confirming the presence of erythroid markers, our studies provide evidence that the HEL cell line also expresses platelet antigens. As such, HEL cells represent a unique system with which to study the biosynthesis of platelet-specific proteins and glycoproteins. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:6201359

  20. 5. EAST ELEVATION (OFFICE BLOCK), DETAIL SHOWING DECORATIVE PILASTERS AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. EAST ELEVATION (OFFICE BLOCK), DETAIL SHOWING DECORATIVE PILASTERS AND STYLIZED EGG-AND-DART DECORATION AROUND WINDOWS OF UPPER FLOORS - Delaware, Lackawanna & Western Railroad & Ferry Terminal, Hudson Place, Hoboken, Hudson County, NJ

  1. Giant Platelets in Platelet Donors – A Blessing in Disguise?

    PubMed Central

    Choudhury, Nabajyoti; Ray, Deepanjan

    2015-01-01

    Introduction Inherited thrombocytopenias, including inherited giant platelet disorders (IGPD) are relatively rare, but their prevalence is probably underestimated. Harris platelet syndrome, the most common IGPD reported from Indian subcontinent, mostly from eastern part, is characterised by a low platelet count, high mean platelet volume (MPV) and absence of bleeding. Aim A short study was conducted to assess the prevalence of giant platelets in voluntary donors of single donor platelets (SDP) and analyse the effect of transfusion of such SDPs in patients. Materials and Methods Voluntary donors of SDPs were screened as per standard guidelines prior to the procedure. A complete blood count (including MPV) along with a peripheral smear was done. A total of 45 donors were screened for plateletpheresis. Following plateletpheresis from these donors, a platelet count from the collection bag was done after one hour. The SDP was transfused as a single unit or divided into two and transfused to the same patient at two different occasions, as per clinical need. Platelet counts on pateints were done after one hour and the platelet recovery was noted. Results Out of the 45 donors who were screened, 30 (66.67%) were found to have giant platelets. It was observed that the pre procedure platelet counts in donors having giant platelets were relatively low (1.5 -1.7 lacs) and so also the platelet yield (2.7-3x1011) compared to donors who did not, but the post transfusion platelet recovery was greater. Conclusion Since presence of giant platelets has been seen to be common in the Eastern part of India, a peripheral smear examination should always be considered during screening of plateletpheresis donors to avoid rejecting donors with giant platelets whose platelet counts are given falsely low by autoanalysers. PMID:26266124

  2. Platelet activation, adhesion, inflammation, and aggregation potential are altered in the presence of electronic cigarette extracts of variable nicotine concentrations.

    PubMed

    Hom, Sarah; Chen, Li; Wang, Tony; Ghebrehiwet, Berhane; Yin, Wei; Rubenstein, David A

    2016-11-01

    Tobacco smoke extracts prepared from both mainstream and sidestream smoking have been associated with heightened platelet activation, aggregation, adhesion, and inflammation. Conversely, it has been shown that pure nicotine inhibits similar platelet functions. In this work, we 1) evaluated the effects of e-cigarette extracts on platelet activities and 2) elucidated the differences between the nicotine-dependent and non-nicotine dependent (e.g. fine particulate matter or toxic compounds) effects of tobacco and e-cigarette products on platelet activities. To accomplish these goals, platelets from healthy volunteers (n = 50) were exposed to tobacco smoke extracts, e-cigarette vapor extracts, and pure nicotine and changes in platelet activation, adhesion, aggregation, and inflammation were evaluated, using optical aggregation, flow cytometry, and ELISA methods. Interestingly, the exposure of platelets to e-vapor extracts induced a significant up-regulation in the expression of the pro-inflammatory gC1qR and cC1qR and induced a marked increase in the deposition of C3b as compared with traditional tobacco smoke extracts. Similarly, platelet activation, as measured by a prothrombinase based assay, and platelet aggregation were also significantly enhanced after exposure to e-vapor extracts. Finally, platelet adhesion potential toward fibrinogen, von Willebrand factor, and other platelets was also enhanced after exposure to e-cigarette vapor extracts. In the presence of pure nicotine, platelet functions were observed to be inhibited, which further suggests that other constituents of tobacco smoke and electronic vapor can antagonize platelet functions, however, the presence of nicotine in extracts somewhat perpetuated the platelet functional changes in a dose-dependent manner.

  3. Calpain-controlled detachment of major glycoproteins from the cytoskeleton regulates adhesive properties of activated phosphatidylserine-positive platelets.

    PubMed

    Artemenko, Elena O; Yakimenko, Alena O; Pichugin, Alexey V; Ataullakhanov, Fazly I; Panteleev, Mikhail A

    2016-02-15

    In resting platelets, adhesive membrane glycoproteins are attached to the cytoskeleton. On strong activation, phosphatidylserine(PS)-positive and -negative platelet subpopulations are formed. Platelet activation is accompanied by cytoskeletal rearrangement, although the glycoprotein attachment status in these two subpopulations is not clear. We developed a new, flow cytometry-based, single-cell approach to investigate attachment of membrane glycoproteins to the cytoskeleton in cell subpopulations. In PS-negative platelets, adhesive glycoproteins integrin αIIbβ3, glycoprotein Ib and, as shown for the first time, P-selectin were associated with the cytoskeleton. In contrast, this attachment was disrupted in PS-positive platelets; it was retained to some extent only in the small convex regions or 'caps'. It correlated with the degradation of talin and filamin observed only in PS-positive platelets. Calpain inhibitors essentially prevented the disruption of membrane glycoprotein attachment in PS-positive platelets, as well as talin and filamin degradation. With the suggestion that detachment of glycoproteins from the cytoskeleton may affect platelet adhesive properties, we investigated the ability of PS-positive platelets to resist shear-induced breakaway from the immobilized fibrinogen. Shear rates of 500/s caused PS-positive platelet breakaway, but their adhesion stability increased more than 10-fold after pretreatment of the platelets with calpain inhibitor. In contrast, the ability of PS-positive platelets to adhere to immobilized von Willebrand's factor at 100/s was low, but this was not affected by the preincubation of platelets with a calpain inhibitor. Our data suggest that calpain-controlled detachment of membrane glycoproteins is a new mechanism that is responsible for the loss of ability of the procoagulant platelets to resist detachment from thrombi by high shear stress.

  4. Clinical uses of radiolabeled platelets

    SciTech Connect

    Datz, F.L.; Christian, P.E.; Baker, W.J.

    1985-12-01

    Platelets were first successfully radiolabeled in 1953. At that time, investigators were primarily interested in developing a technique to accurately measure platelet life span in both normal and thrombocytopenic patients. Studies using platelets labeled with /sup 51/Cr have shown shortened platelet survival times in a number of diseases including idiopathic thrombocytopenic purpura, coronary artery disease, and diabetes mellitus. More recently, labels such as /sup 111/In have been developed that allow in vivo imaging of platelets. Indium-111 platelets are being used to better understand the pathophysiology of atherosclerosis, thrombophlebitis, pulmonary embolism and clotting disorders, and to improve the clinical diagnosis of these diseases.

  5. Impaired megakaryocytopoiesis in type 2B von Willebrand disease with severe thrombocytopenia.

    PubMed

    Nurden, Paquita; Debili, Najet; Vainchenker, William; Bobe, Regis; Bredoux, Raymonde; Corvazier, Elisabeth; Combrie, Robert; Fressinaud, Edith; Meyer, Dominique; Nurden, Alan T; Enouf, Jocelyne

    2006-10-15

    In type 2B von Willebrand disease, there is spontaneous binding of mutated von Willebrand factor (VWF) multimers to platelets. Here we report a family in which severe thrombocytopenia may also be linked to abnormal megakaryocytopoiesis. A heterozygous mutation in the VWF A1 domain gave a R1308P substitution in an interactive site for glycoprotein Ibalpha (GPIbalpha). Electron microscopy showed clusters of platelets in close contact. Binding of antibodies to the GPIbalpha N-terminal domain was decreased, whereas GPIX and GPV were normally detected. In Western blotting (WB), GPIbalpha, alphaIIb, and beta3 were normally present. Proteins involved in Ca(2+) homeostasis were analyzed by quantitating platelet mRNA or by WB. Plasma membrane Ca(2+) ATPase (PMCA)-4b and type III inositol trisphosphate receptor (InsP(3)-R3) were selectively increased. The presence of degradation products of polyadenosine diphosphate (ADP)-ribose polymerase protein (PARP) suggested ongoing caspase-3 activity. These were findings typical of immature normal megakaryocytes cultured from peripheral blood CD34(+) cells with TPO. Significantly, megakaryocytes from the patients in culture produced self-associated and interwoven proplatelets. Immunolocalization showed VWF not only associated with platelets, but already on the megakaryocyte surface and within internal channels. In this family, type 2B VWD is clearly associated with abnormal platelet production.

  6. Platelets and platelet-like particles mediate intercellular RNA transfer

    PubMed Central

    Risitano, Antonina; Beaulieu, Lea M.; Vitseva, Olga

    2012-01-01

    The role of platelets in hemostasis and thrombosis is clearly established; however, the mechanisms by which platelets mediate inflammatory and immune pathways are less well understood. Platelets interact and modulate the function of blood and vascular cells by releasing bioactive molecules. Although the platelet is anucleate, it contains transcripts that may mirror disease. Platelet mRNA is only associated with low-level protein translation; however, platelets have a unique membrane structure allowing for the passage of small molecules, leading to the possibility that its cytoplasmic RNA may be passed to nucleated cells. To examine this question, platelet-like particles with labeled RNA were cocultured with vascular cells. Coculture of platelet-like particles with activated THP-1, monocytic, and endothelial cells led to visual and functional RNA transfer. Posttransfer microarray gene expression analysis of THP-1 cells showed an increase in HBG1/HBG2 and HBA1/HBA2 expression that was directly related to the transfer. Infusion of wild-type platelets into a TLR2-deficient mouse model established in vivo confirmation of select platelet RNA transfer to leukocytes. By specifically transferring green fluorescent protein, we also observed external RNA was functional in the recipient cells. The observation that platelets possess the capacity to transfer cytosolic RNA suggests a new function for platelets in the regulation of vascular homeostasis. PMID:22596260

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

    PubMed

    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.

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

    PubMed Central

    Al-Hosni, Zainab S; Al-Khabori, Murtadha; Al-Mamari, Sahimah; Al-Qasabi, Jamal; Davis, Hiedi; Al-Lawati, Hatim; Al-Riyami, Arwa Z

    2016-01-01

    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. PMID:27974955

  9. Nucleation of platelets with blood-borne pathogens on Kupffer cells precedes other innate immunity and contributes to bacterial clearance.

    PubMed

    Wong, Connie H Y; Jenne, Craig N; Petri, Björn; Chrobok, Navina L; Kubes, Paul

    2013-08-01

    Through the use of intravital imaging of the liver, we demonstrate a collaborative role for platelets with Kupffer cells (KCs) in eradicating blood-borne bacterial infection. Under basal conditions, platelets, via the platelet-adhesion receptor GPIb, formed transient 'touch-and-go' interactions with von Willebrand factor (vWF) constitutively expressed on KCs. Bacteria such as Bacillus cereus and methicillin-resistant Staphylococcus aureus (MRSA) were rapidly caught by KCs and triggered platelets to switch from 'touch-and-go' adhesion to sustained GPIIb-mediated adhesion on the KC surface to encase the bacterium. Infected GPIbα-deficient mice had more endothelial and KC damage than did their wild-type counterparts, which led to more fluid leakage, substantial polycythemia and rapid mortality. Our study identifies a previously unknown surveillance mechanism by which platelets survey macrophages that rapidly converts to a critical host response to blood-borne bacteria.

  10. Complement Activation Alters Platelet Function

    DTIC Science & Technology

    2013-10-01

    mice and mice transfused with Syk inhibitor-treated platelets . Platelet lodging was remarkably decreased in lungs of mice transfused with Syk...AD_________________ Award Number: W81XWH-12-1-0523 TITLE: Complement Activation Alters Platelet ...30September2012–29September2013 4. TITLE AND SUBTITLE Complement Activation Alters Platelet Function 5a. CONTRACT NUMBER W81XWH-12-1-0523 5b. GRANT NUMBER

  11. Recovery of Platelet Count among Apheresis Platelet Donors

    PubMed Central

    Radhakrishnan, Krishnamoorthy; Anandan, Ashwin; Panicker, Vinod Kumar

    2016-01-01

    Introduction Increase in awareness regarding use of single donor platelets and the availability of technology has resulted in increased platelet pheresis procedures. The interval between two succesive plateletpheresis donations is much less compared to whole blood donations. Plateletpheresis procedures are associated with short term and long term adverse events. The effect of plateletpheresis on haematopoietic system remains significant. Aim To study the recovery of platelet count to baseline in plateletpheresis donors. Materials and Methods Fifty, first time apheresis donors were followed for platelet count recovery. Platelet count was measured before donation and at 30 minutes, 48 hours, 7th day and 14th day post-donation. Donor platelet count recovery to baseline was observed during the two week period. Results were analysed statistically, p<0.05 was considered statistically significant. Results Platelet count recovered to baseline by 7th day post-donation in 50% of donors in groups I (Pre-donation platelet count 1.5 lacs/μl to 2.2 lacs/μl) and II (Donors with platelet count >2.2 lacs/μl to 2.75 lacs/μl), 30% of donors in group III (Donors with platelet count >2.75 lacs/μl to 3.5 lacs/μl) of the donors. Donor’s platelet count recovered to baseline in 85% of donors by day 14 in across the three groups. Recruitment of platelets from spleen was observed in donors with pre-donation platelet count on the lower limit of normal. Conclusion By day 7, donor’s platelet count recovered to baseline in majority of the donors. Allowing enough recovery periods for donor platelet count, the minimum interval between two apheresis donations can be 7 days till more prospective studies conclude on the frequency and minimum interval between plateletpheresis donations. PMID:28208861

  12. Connections on decorated path space bundles

    NASA Astrophysics Data System (ADS)

    Chatterjee, Saikat; Lahiri, Amitabha; Sengupta, Ambar N.

    2017-02-01

    For a principal bundle P → M equipped with a connection A ¯ , we study an infinite dimensional bundle PA¯ dec P over the space of paths on M, with the points of PA¯ dec P being horizontal paths on P decorated with elements of a second structure group. We construct parallel transport processes on such bundles and study holonomy bundles in this setting.

  13. 10 Ways to...Decorate Your Classroom

    ERIC Educational Resources Information Center

    Prescott, Jennifer

    2005-01-01

    Recruit the best decorating corps you have for this year's classroom makeover--your students! Not only does involving kids save money and effort on your part, teachers agree that it increases kids' sense of involvement and respect. In this article, the author presents 10 teacher-tested ideas for a classroom that shines with color and learning: (1)…

  14. Icosahedral quasicrystal decoration models. I. Geometrical principles

    SciTech Connect

    Mihalkovic, M. |; Zhu, W.; Henley, C.L.; Oxborrow, M. |

    1996-04-01

    It is proposed that quasicrystal structure determination should include the calculation of cohesive energies using realistic potentials. A class of atomic decoration models for {ital i}-AlMn is then presented, adopting the {open_quote}{open_quote}canonical-cell{close_quote}{close_quote} tiling geometry, with {open_quote}{open_quote}Mackay icosahedron{close_quote}{close_quote} clusters placed on all its nodes. The remaining atomic positions are based, as far as possible, on the known structure of {alpha}-AlMnSi. These models guarantee good local packing of the atoms, whose displacements away from {open_quote}{open_quote}ideal{close_quote}{close_quote} positions are specified by only a moderate number of parameters. Certain atomic sites are uncertain as regards their occupancy and/or chemistry; variations of the decoration rules on these sites must be compared, in order to discover the correct one. Our models are well adapted to be relaxed under an effective Hamiltonian to optimize the cohesive energy; we show how the energies found in such relaxations can be used to extract an effective tile-tile Hamiltonian, as would be needed for future studies of phason elasticity and the development of long-range order. In addition, we clarify concepts needed for decoration models in general (in particular, the ways in which elaborate, more realistic decorations may be evolved from simpler ones). We also show that these decoration models are closely related, but not identical, to quasiperiodic structures defined using six-dimensional formalism. {copyright} {ital 1996 The American Physical Society.}

  15. Developments in the diagnostic procedures for von Willebrand disease.

    PubMed

    De Jong, A; Eikenboom, J

    2016-03-01

    Von Willebrand disease (VWD) is the most common inherited bleeding disorder but its diagnosis can be challenging due to the heterogeneity of the disease. VWD is mainly associated with mild mucocutaneous bleeding, although there are more severe phenotypes with bleeding from the gastrointestinal tract or even the joints. Also, surgical interventions and trauma may lead to critical bleeding events. These bleeding episodes are all related to quantitative or qualitative defects of von Willebrand factor (VWF), a multimeric glycoprotein produced by endothelial cells and megakaryocytes, which mediates platelet adhesion and aggregation and binds factor VIII (FVIII) in the circulation. This review describes the diagnostic procedures required for correct diagnosis. Accurate diagnosis and classification is required for proper treatment and counseling. Assessment of bleeding starts with the medical history. After a positive bleeding or family history, subsequent laboratory investigations will start with a panel of standard screening tests for hemostatic defects. Patients suspected of having VWD will be tested for plasma VWF antigen levels, the ability of VWF to bind platelets and FVIII activity. When VWD is confirmed, a set of subtyping tests can classify the patients as VWD types 1, 2 (A, B, M or N) or 3. The performance of some additional assays and analyses, such as VWF propeptide measurement or genetic analysis, may help in identifying the pathological mechanism behind certain defects or can guide in the choice of treatment.

  16. Von Karman swirling flows

    NASA Astrophysics Data System (ADS)

    Zandbergen, P. J.; Dijkstra, D.

    A development history is presented for research on the problem of swirling flow infinite disks from its formulation by von Karman in 1921 through the treatments of Batchelor (1951) and Stewartson (1953) to the present, with a view to both its one-disk and two-disk forms. Attention is given to the stability of the stationary solutions for these problems, and to the case where the radii of the disks are finite. The question as to the extent to which the Karman swirling flow occurs in a finite radial geometry is noted to be of fundamental importance.

  17. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Thomas Paine, Deputy Administrator of the National Aeronautics and Space Administration, examines an ordinary man's shoe outfitted for use in the Saturn I workshop. Pictured from the left in the Saturn I workshop mockup are William Brooksbank, propulsion and vehicle engineering laboratory; Dr. Paine; Dr. Wernher Von Braun, Marshall Center director; Colonel Clare F. Farley, Executive Officer in the Office Of The Administrator; and Charles J. Donlan, Deputy Associate Administrator for Manned Space Flight, Technical. the shoe Dr. Paine is holding has a unique fastener built into the sole to allow an astronaut to move about on the workshop floor and to remain in one position if he desires.

  18. von Willebrand Disease (For Parents)

    MedlinePlus

    ... problems because the levels or functioning of these blood components needed for clotting are abnormal. continue Types of von Willebrand Disease As with many conditions, there are various forms ... of von Willebrand factor in the blood is reduced; the level of factor VIII also ...

  19. Simulation of the Effect of Red Blood Cell Collisions on Platelet Adsorption

    NASA Astrophysics Data System (ADS)

    Fitzgibbon, Sean; Zhao, Hong; Shaqfeh, Eric

    2012-11-01

    The adsorption of platelets to the endothelial wall is an important first step in the clotting process, which is critical to stopping blood loss after trauma. Initial platelet arrest is controlled by very short range interaction between two proteins, von Willibrand Factor and GPIb, so the rate of platelet adsorption is expected to be strongly dependent on the rate at which the platelets sample the wall. With Peclet numbers in the range (103 - 105) , simple diffusive arguments are not sufficient to explain the high rates of platelet adsorption. Using Stokes flow simulations, we show that the platelets' wall sampling rate is significantly increased by interactions with red blood cells. Our simulation models platelets as rigid bodies suspended in a Stokesian linear shear flow. We solve for the flow using standard boundary integral techniques with the appropriate single wall bounded Green's function. Receptor-ligand interactions are represented as Hookean springs with characteristic lifetimes, sizes, and stiffness coefficients. Drag forces are calculated with the reciprocal theorem, and RBC collisions are modelled as AR processes extracted from the large scale suspension simulations of Zhao et al.

  20. Reactions Induced by Platelet Transfusions

    PubMed Central

    Kiefel, Volker

    2008-01-01

    Summary Platelet transfusions play a central role in therapeutic regimens for patients with hematologic/oncologic diseases who develop severe thrombocytopenia either in the course of their disease or following cytostatic therapy. Like other blood components, platelet transfusions have achieved a high degree of safety as far as transmission of viral diseases is concerned. However, transfusion of platelet concentrates is accompanied by a high frequency of febrile and anaphylactoid reactions. In rare cases, recipients of platelet concentrates are threatened by severe reactions as septic complications due to bacterial contamination of platelet concentrates, transfusion-related acute lung injury and severe anaphylactic episodes. PMID:21512624

  1. Cbl proteins in platelet activation.

    PubMed

    Buitrago, Lorena; Tsygankov, Alexander; Sanjay, Archana; Kunapuli, Satya P

    2013-01-01

    Platelets play a fundamental role in hemostasis. Their functional responses have to be tightly controlled as any disturbance may lead to bleeding disorders or thrombosis. It is thus important to clearly identify and understand the signaling mechanisms involved in platelet function. An important role of c-Cbl and Cbl-b ubiquitin ligases in platelet functional responses and in hematological malignancies has been recently described. Cbl proteins perform negative and positive regulation of several signaling pathways in platelets. In this review, we explore the role of Cbl proteins in platelet functional responses.

  2. EDTA dependent pseudothrombocytopenia caused by antibodies against the cytoadhesive receptor of platelet gpIIB-IIIA.

    PubMed Central

    Casonato, A; Bertomoro, A; Pontara, E; Dannhauser, D; Lazzaro, A R; Girolami, A

    1994-01-01

    AIMS--To clarify the mechanisms involved in the development of EDTA dependent pseudothrombocytopenia, particularly the platelet receptors. METHODS--Platelets were measured in 33 patients with pseudothrombocytopenia, using different anticoagulants to collect blood samples (direct test). The results were compared with the counts obtained by adding patients' serum or immunoglobulins to normal blood samples (indirect test). The role of platelet function was explored using ASA, PGE1, and apyrase as platelet inhibitors. The contribution of platelet receptor/s was investigated using antigens to gpIb-IX and gpIIb-IIIa monoclonal antibodies. Immunoglobulin class was estimated by the ability of IgG, IgA, and IgM antibodies to prevent platelet clumping. RESULTS--Agglutinating antibodies were IgA in 40%, IgG in 30%, and IgM in 10% of patients studied. Both patients' serum and immunoglobulins induced platelet clumping in normal samples anticoagulated with EDTA (indirect test). This was prevented by incubation of blood samples at 37 degrees C and almost completely inhibited by the platelet inhibitors ASA, PGE1, and apyrase. Pseudothrombocytopenia was also entirely prevented by an antigen to gpIIb-IIIa monoclonal antibody that recognises fibrinogen and the von Willebrand factor binding site. Pseudothrombocytopenia was almost completely abolished after the addition of RGD peptide, the recognition sequence of cytoadhesive proteins. CONCLUSIONS--These findings suggest that EDTA dependent pseudothrombocytopenia is caused by agglutinating antibodies that recognise cytoadhesive receptors on platelet gpIIb-IIIa and that an efficient platelet metabolism is required. PMID:8089218

  3. Human Platelet Senescence.

    DTIC Science & Technology

    1976-04-30

    s by thP Spleen. We have recently made the interest inro o!bservat ion that the spleen preferentially sequesters mega- thrombocytes (o,7) (se...follow:ini th,’ inj,.cti(,n ,f anti-platelet antihody. Electron microscopy of blood from pati. with micrnthr’bteocyte, peaks reveal very small intact

  4. Variable content of von Willebrand factor mutant monomer drives the phenotypic variability in a family with von Willebrand disease.

    PubMed

    Chen, Junmei; Hinckley, Jesse D; Haberichter, Sandra; Jacobi, Paula; Montgomery, Robert; Flood, Veronica H; Wong, Randall; Interlandi, Gianluca; Chung, Dominic W; López, José A; Di Paola, Jorge

    2015-07-09

    Von Willebrand disease (VWD) is an inherited bleeding disorder characterized by incomplete penetrance and variable expressivity. We evaluated a 24-member pedigree with VWD type 2 caused by a T>G mutation at position 3911 that predicts a methionine to arginine (M1304R) change in the platelet-binding A1 domain of von Willebrand factor (VWF). This mutation manifests as an autosomal-dominant trait, with clinical and biochemical phenotypic variability among affected individuals, including differences in bleeding tendency and VWF quantity, activity, and multimer pattern. Sequencing of all VWF coding regions in 3 affected individuals did not identify additional mutations. When expressed in heterologous cells, M1304R was secreted in lower quantities, failed to drive formation of storage granules, and was defective in multimerization and platelet binding. When cotransfected in equal quantities with the wild-type complementary DNA, the mutant complementary DNA depressed VWF secretion, although multimerization was only mildly affected. A llama nanobody (AU/VWFa-11) that detects the mutant A1 domain demonstrated highly variable binding to VWF from different affected members, indicating that the VWF contained different percentages of mutant monomers in different individuals. Thus, the observed variability in VWD phenotypes could in part be determined by the extent of mutant monomer incorporation in the final multimer structure of plasma VWF.

  5. The function of ultra-large von Willebrand factor multimers in high shear flow controlled by ADAMTS13.

    PubMed

    Reininger, A J

    2015-01-01

    The paradigm that platelet aggregation, which contributes to bleeding arrest and also to thrombovascular disorders, initiates after signaling-induced platelet activation has been refuted in past recent years. Platelets can form aggregates independently of activation when soluble von Willebrand factor (VWF) is present and the shear rate exceeds a certain threshold where active A1 domains become exposed in soluble VWF multimers and can bind to platelet glycoprotein Ib. Subsequently - fostering each other - VWF can self-assemble into large nets combining with platelets into large conglomerates, which are entirely reversible when they enter a flow region with shear rates below the threshold. In addition the threshold changes from approximately 20 000 s⁻¹ in wall parallel flow to approximately 10 000 s⁻¹ in stagnation point flow. VWF containing ultra-large multimers - as when just released from endothelial storage sites - has been shown to have the highest binding potential to platelets and to each other, thus facilitating rapid platelet accrual to sites of vessel injury and exposed subendothelial structures, i.e. collagen. The VWF nets as well as the platelet-VWF conglomerates are controlled by the cleaving protease ADAMTS13 within minutes under high shear flow. Therewith the hemostatic potential is delivered where needed and the thrombogenic potential is highly controlled twofold: by flow and enzymatic proteolytic cleavage.

  6. Selective Inhibition of ADAM17 Efficiently Mediates Glycoprotein Ibα Retention During Ex Vivo Generation of Human Induced Pluripotent Stem Cell-Derived Platelets.

    PubMed

    Hirata, Shinji; Murata, Takahiko; Suzuki, Daisuke; Nakamura, Sou; Jono-Ohnishi, Ryoko; Hirose, Hidenori; Sawaguchi, Akira; Nishimura, Satoshi; Sugimoto, Naoshi; Eto, Koji

    2017-03-01

    Donor-independent platelet concentrates for transfusion can be produced in vitro from induced pluripotent stem cells (iPSCs). However, culture at 37°C induces ectodomain shedding on platelets of glycoprotein Ibα (GPIbα), the von Willebrand factor receptor critical for adhesive function and platelet lifetime in vivo, through temperature-dependent activation of a disintegrin and metalloproteinase 17 (ADAM17). The shedding can be suppressed by using inhibitors of panmetalloproteinases and possibly of the upstream regulator p38 mitogen-activated protein kinase (p38 MAPK), but residues of these inhibitors in the final platelet products may be accompanied by harmful risks that prevent clinical application. Here, we optimized the culture conditions for generating human iPSC-derived GPIbα(+) platelets, focusing on culture temperature and additives, by comparing a new and safe selective ADAM17 inhibitor, KP-457, with previous inhibitors. Because cultivation at 24°C (at which conventional platelet concentrates are stored) markedly diminished the yield of platelets with high expression of platelet receptors, 37°C was requisite for normal platelet production from iPSCs. KP-457 blocked GPIbα shedding from iPSC platelets at a lower half-maximal inhibitory concentration than panmetalloproteinase inhibitor GM-6001, whereas p38 MAPK inhibitors did not. iPSC platelets generated in the presence of KP-457 exhibited improved GPIbα-dependent aggregation not inferior to human fresh platelets. A thrombus formation model using immunodeficient mice after platelet transfusion revealed that iPSC platelets generated with KP-457 exerted better hemostatic function in vivo. Our findings suggest that KP-457, unlike GM-6001 or p38 MAPK inhibitors, effectively enhances the production of functional human iPSC-derived platelets at 37°C, which is an important step toward their clinical application. Stem Cells Translational Medicine 2017;6:720-730.

  7. P-selectin and von Willebrand factor in bovine mesenteric lymphatics: an immunofluorescent study.

    PubMed

    Di Nucci, A; Marchetti, C; Serafini, S; Piovella, F

    1996-03-01

    P-selectin (PADGEM, GMP-140, CD62) is an integral membrane protein specific to alpha granules of platelets and Weibel-Palade bodies of blood vascular endothelial cells. The presence in lymphatic endothelial cells of numerous Weibel-Palade bodies and their positivity to immunocytochemical reaction for von Willebrand factor have previously been characterized and described. Because von Willebrand factor and P-selectin codistribute in Weibel-Palade bodies of blood vascular endothelial cells we investigated the presence of both P-selectin and von Willebrand factor in lymphatic endothelium. Lymphatic vessels expressed positive reaction to immunocytochemical assay thereby demonstrating the presence of P-selectin in the endothelium. Distribution and intensity of the reaction were similar to those observed in bovine blood vascular endothelium.

  8. Mutational Constraints on Local Unfolding Inhibit the Rheological Adaptation of von Willebrand Factor*

    PubMed Central

    Tischer, Alexander; Campbell, James C.; Machha, Venkata R.; Moon-Tasson, Laurie; Benson, Linda M.; Sankaran, Banumathi; Kim, Choel; Auton, Matthew

    2016-01-01

    Unusually large von Willebrand factor (VWF), the first responder to vascular injury in primary hemostasis, is designed to capture platelets under the high shear stress of rheological blood flow. In type 2M von Willebrand disease, two rare mutations (G1324A and G1324S) within the platelet GPIbα binding interface of the VWF A1 domain impair the hemostatic function of VWF. We investigate structural and conformational effects of these mutations on the A1 domain's efficacy to bind collagen and adhere platelets under shear flow. These mutations enhance the thermodynamic stability, reduce the rate of unfolding, and enhance the A1 domain's resistance to limited proteolysis. Collagen binding affinity is not significantly affected indicating that the primary stabilizing effect of these mutations is to diminish the platelet binding efficiency under shear flow. The enhanced stability stems from the steric consequences of adding a side chain (G1324A) and additionally a hydrogen bond (G1324S) to His1322 across the β2-β3 hairpin in the GPIbα binding interface, which restrains the conformational degrees of freedom and the overall flexibility of the native state. These studies reveal a novel rheological strategy in which the incorporation of a single glycine within the GPIbα binding interface of normal VWF enhances the probability of local unfolding that enables the A1 domain to conformationally adapt to shear flow while maintaining its overall native structure. PMID:26677223

  9. Von Willebrand factor in patients on mechanical circulatory support - a double-edged sword between bleeding and thrombosis.

    PubMed

    Hudzik, Bartosz; Kaczmarski, Jacek; Pacholewicz, Jerzy; Zakliczynski, Michal; Gasior, Mariusz; Zembala, Marian

    2015-09-01

    Mechanical circulatory support (MCS) is an umbrella term describing the various technologies used in both short- and long-term management of patients with either end-stage chronic heart failure (HF) or acute HF. Most often, MCS has emerged as a bridge to transplantation, but more recently it is also used as a destination therapy. Mechanical circulatory support includes left ventricular assist device (LVAD) or bi-ventricular assist device (Bi-VAD). Currently, 2- to 3-year survival in carefully selected patients is much better than with medical therapy. However, MCS therapy is hampered by sometimes life-threatening complications including bleeding and device thrombosis. Von Willebrand factor (vWF) has two major functions in haemostasis. First, it plays a crucial role in platelet-subendothelium adhesion and platelet-platelet interactions (aggregation). Second, it is the carrier of factor VIII (FVIII) in plasma. Von Willebrand factor prolongs FVIII half-time by protecting it from proteolytic degradation. It delivers FVIII to the site of vascular injury thus enhancing haemostatic process. On one hand, high plasma levels of vWF have been associated with an increased risk of thrombosis. On the other, defects or deficiencies of vWF underlie the inherited von Willebrand disease or acquired von Willebrand syndrome. Here we review the pathophysiology of thrombosis and bleeding associated with vWF.

  10. Polyphosphate colocalizes with factor XII on platelet-bound fibrin and augments its plasminogen activator activity

    PubMed Central

    Lionikiene, Ausra S.; Georgiev, Georgi; Klemmer, Anja; Brain, Chelsea; Kim, Paul Y.

    2016-01-01

    Activated factor XII (FXIIa) has plasminogen activator capacity but its relative contribution to fibrinolysis is considered marginal compared with urokinase and tissue plasminogen activator. Polyphosphate (polyP) is released from activated platelets and mediates FXII activation. Here, we investigate the contribution of polyP to the plasminogen activator function of αFXIIa. We show that both polyP70, of the chain length found in platelets (60-100 mer), and platelet-derived polyP significantly augment the plasminogen activation capacity of αFXIIa. PolyP70 stimulated the autoactivation of FXII and subsequent plasminogen activation, indicating that once activated, αFXIIa remains bound to polyP70. Indeed, complex formation between polyP70 and αFXIIa provides protection against autodegradation. Plasminogen activation by βFXIIa was minimal and not enhanced by polyP70, highlighting the importance of the anion binding site. PolyP70 did not modulate plasmin activity but stimulated activation of Glu and Lys forms of plasminogen by αFXIIa. Accordingly, polyP70 was found to bind to FXII, αFXIIa, and plasminogen, but not βFXIIa. Fibrin and polyP70 acted synergistically to enhance αFXIIa-mediated plasminogen activation. The plasminogen activator activity of the αFXIIa-polyP70 complex was modulated by C1 inhibitor and histidine-rich glycoprotein, but not plasminogen activator inhibitors 1 and 2. Platelet polyP and FXII were found to colocalize on the activated platelet membrane in a fibrin-dependent manner and decorated fibrin strands extending from platelet aggregates. We show that in the presence of platelet polyP and the downstream substrate fibrin, αFXIIa is a highly efficient and favorable plasminogen activator. Our data are the first to document a profibrinolytic function of platelet polyP. PMID:27694320

  11. Platelet satellitism: an ultrastructural study.

    PubMed Central

    Payne, C. M.

    1981-01-01

    The ultrastructural morphology of platelet-polymorph (platelet-polymorphonuclear leukocyte) rosettes was investigated in EDTA-anticoagulated blood obtained from two patients who exhibited the phenomenon of platelet satellitism. Most of the platelet profiles were attached to the polymorph surface by broad areas of contact. Examination of these broad areas of contact at high magnification revealed an intercellular material of low electron density. This material appeared to form strands, which bridged the intercellular space and spanned the entire area formed by the apposing plasma membranes. Phagocytosis of entire platelets was only observed in 1 case. The platelet profiles that participated in rosette formation revealed a large number of glycogen particles, compared with unattached platelets. Ultrastructural examination of "stress" platelets obtained from five normal subjects treated with steroids similarly showed a large number of glycogen particles, although no rosette formation or phagocytosis of platelets was observed. The etiology of platelet satellitism is discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7223859

  12. Typing for human platelet alloantigens.

    PubMed

    Juji, T; Saji, H; Satake, M; Tokunaga, K

    1999-01-01

    Antibodies to platelet alloantigens, and sometimes to isoantigens, induce severe clinical problems such as neonatal alloimmune thrombocytopenia (NAIT), post-transfusion purpura (PTP) and refractoriness to platelet transfusions (PTR). For example, NAIT affects approximately 1 in 5,000 live births. It is essential, therefore, to screen pregnant women for platelet antibodies in order to save babies' lives. Almost 40 years ago, two platelet alloantigen systems were discovered using relatively simple methods, namely the platelet agglutination test and the complement fixation test. However, these methods were not sensitive enough to identify all antibodies in mothers and patients, even in those with severe clinical problems. Tremendous effort has been devoted to establish more sensitive and reliable methods. In recent years, excellent new serological and immunochemical methods have been established and several new platelet antigen systems have been discovered. Simultaneously, newly developed molecular genetic techniques have been introduced for the typing and analysis of human platelet alloantigen systems. These methods allow DNA typing for cases in which serological typing is not available. In this article, the history of studies on human platelet alloantigen systems and isoantigens, the nomenclature of platelet alloantigen systems and their alleles, the present status of antibody detection and typing techniques and, finally, ethnic variations in platelet antigen profiles are reviewed.

  13. Effects of hormones on platelet aggregation.

    PubMed

    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.

  14. John von Neumann Birthday Centennial

    SciTech Connect

    Grcar, Joseph F.

    2004-11-12

    In celebration of John von Neumann's 100th birthday, a series of four lectures were presented on the evening of February 10, 2003 during the SIAM Conference on Computational Science and Engineering in San Diego. The venue was appropriate because von Neumann spent much of the later part of his life, in the 1950's, as an unofficial ambassador for computational science. He was then the only senior American scientist who had experience with the new computers (digital, electronic, and programmable) and a vision of their future importance. No doubt he would have relished the chance to attend a meeting such as this. The first speaker, William Aspray, described the ''interesting times'' during which computers were invented. His remarks were based on his history [1] of this period in von Neumann's life. We were honored to have John von Neumann's daughter, Marina von Neumann-Whitman, as our second speaker. Other accounts of von Neumann's life can be found in books by two of his colleagues [2] and [3]. Our third speaker, Peter Lax, provided both mathematical and international perspectives on John von Neumann's career. Finally, Pete Stewart spoke about von Neumann's numerical error analysis [4] in the context of later work; this talk did not lend itself to transcription, but readers may consult the historical notes in [5]. Our thanks to all the speakers for a remarkable evening. We are grateful to the DOE Applied Mathematical Sciences (AMS) program for partially supporting these lectures. Thanks are also due to SIAM and William Kolata, to our emcee, Gene Golub, to Paul Saylor for recording and editing, and to Barbara Lytle for the transcriptions. More about von Neumann's work can be learned from the recent American Mathematical Society proceedings [6].

  15. [Tooth decoration in pre-colombian America].

    PubMed

    Pezzoli, M

    1976-01-01

    A form of body decoration that developed in precolombian America is described and examined. The vestibular face and shape of the front teeth were altered in various ways, details of which are clear from archaeological discoveries (crania, teeth, ceramics, and statues). The various technical, social and cultural aspects of this practice are discussed with reference to their place in a civilisation whose works are still admired today.

  16. von Karman Vortices

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Each of these swirling clouds is the result of a meteorological phenomenon known as a von Karman vortex. These vortices appeared over Alexander Selkirk Island in the southern Pacific Ocean. Rising precipitously from the surrounding waters, the island's highest point is nearly a mile (1.6 km) above sea level. As wind-driven clouds encounter this obstacle, they flow around it to form large, spinning eddies. This image was acquired by Landsat 7's Enhanced Thematic Mapper plus (ETM+) sensor on September 15, 1999. This is a false-color composite image made using shortwave infrared, infrared, and near-infrared wavelengths. Image provided by the USGS EROS Data Center Satellite Systems Branch.

  17. von Willebrand factor expression in osteosarcoma metastasis.

    PubMed

    Eppert, Kolja; Wunder, Jay S; Aneliunas, Vicky; Kandel, Rita; Andrulis, Irene L

    2005-03-01

    A number of genes are implicated in the initiation and progression of osteosarcoma; however, cytogenetic and comparative genomic hybridization studies indicate the involvement of additional unidentified genes. An examination of gene expression profiles in 22 high-grade osteosarcoma tumor specimens from 15 patients (including paired primary and metastatic samples from five patients) indicated that von Willebrand factor (vWF) mRNA expression may increase during tumor progression. vWF, a large glycoprotein previously considered to be expressed exclusively by endothelial cells and megakaryocytes, is involved in platelet aggregation and adhesion to the subendothelial matrix, processes critical to hematogenous tumor cell metastasis to the lung. Analysis of paired primary and metastatic osteosarcoma tumor samples from 10 patients revealed an increase in vWF gene expression in metastases (P=0.005). Immunohistochemistry showed that, in addition to the endothelial cells, vWF protein was also detected in osteosarcoma cells in vivo in 13 of 29 tumor specimens as well as in SAOS2, an osteosarcoma cell line. The tumor cell staining correlated positively with high vWF expression in the sample (P=0.006). Although vascular endothelial cells contribute to the vWF mRNA detected in the tumor samples, there was neither any correlation between vascular density (VD) and vWF mRNA expression nor between VD and clinical outcome. These findings suggest that vWF expression is deregulated in osteosarcoma tumors, potentially contributing to metastasis.

  18. Von Hippel's disease in association with von Recklinghausen's neurofibromatosis.

    PubMed Central

    Thomas, J V; Schwartz, P L; Gragoudas, E S

    1978-01-01

    Ten members of a large family who showed manifestations of either von Hippel-Lindau disease or von Recklinghausen's neurofibromatosis were examined. Three of 10 members were found to have retinal angiomas which had not been present on fundus examination 3 years previously. These angiomas were associated with ocular and systemic signs of neurofibromatosis. These cases show overlapping manifestations of different phakomatoses and provide support for the concept of a common aetiology for these diseases. Images PMID:101230

  19. Hypothermia and Platelet Dysfunction

    DTIC Science & Technology

    2007-11-02

    cardiopulmonary bypass during cardiac surgery, other major surgery, multiple trauma, cold exposure, and neonatal cold injury.1Ŗ The hemorrhagic diathesis...associated with hypothermic cardiopulmonary bypass during cardiac surgery is considered to be primarily a platelet function defect.I6,17,23 We have...cardiopulmonary bypass during cardiac surgery.,8,24 Consistent with this data, other investigators have recently reported that normothermic cardiopulmonary

  20. Holiday Decorating Contest - A Way to Meet Fellow Employees | Poster

    Cancer.gov

    The trolls from “Frozen,” a North Pole tunnel, and a Christmas tree­–shaped periodic table of elements were just a few of the decorations on display during the second annual Holiday Decorating Contest in December. The contest, sponsored by the R&W Club Frederick, awarded prizes to three groups and two individuals whose decorations were judged based on visual impact, creativity, and craftsmanship.

  1. Ascorbate inhibits platelet-endothelial adhesion in an in-vitro model of sepsis via reduced endothelial surface P-selectin expression.

    PubMed

    Secor, Dan; Swarbreck, Scott; Ellis, Christopher G; Sharpe, Michael D; Feng, Qingping; Tyml, Karel

    2017-01-01

    Plugging of the capillary bed can lead to organ failure and mortality in sepsis. We have reported that intravenous ascorbate injection reduces platelet adhesion to the capillary wall and capillary plugging in septic mice. Both platelet adhesion and capillary plugging require P-selectin, a key adhesion molecule. To elucidate the beneficial effect of ascorbate, we hypothesized that ascorbate reduces platelet-endothelial adhesion by reducing P-selectin surface expression in endothelial cells. We used mouse platelets, and monolayers of cultured microvascular endothelial cells (mouse skeletal muscle origin) stimulated with lipopolysaccharide, to examine platelet-endothelial adhesion. P-selectin mRNA expression in endothelial cells was determined by real-time PCR and P-selectin protein expression at the surface of these cells by immunofluorescence. Secretion of von Willebrand factor from cells into the supernatant (a measure of P-selectin-containing granule exocytosis) was determined by ELISA. Lipopolysaccharide (10 μg/ml, 1 h) increased platelet-endothelial adhesion. P-selectin-blocking antibody inhibited this adhesion. Lipopolysaccharide also increased P-selectin mRNA in endothelial cells, P-selectin expression at the endothelial surface, and von Willebrand factor secretion. Ascorbate pretreatment (100 μmol/l, 4 h) inhibited the increased platelet adhesion, surface expression of P-selectin, and von Willebrand factor secretion, but not the increase in P-selectin mRNA. The lipopolysaccharide-induced increase in platelet-endothelial adhesion requires P-selectin presence at the endothelial surface. Ascorbate's ability to reduce this presence could be important in reducing both platelet adhesion to the capillary wall and capillary plugging in sepsis.

  2. [Platelet count in the cat].

    PubMed

    Moritz, A; Hoffmann, C

    1997-11-01

    The technique of collecting blood samples is primarily responsible for the appearance of platelet-agglomeration in cats. Blood obtained by the conventional way ("one syringe technology", drips of blood) caused in 52% of the cases an activation of the large and therefore active thrombocytes however. Rejection of the first 2-5 ml blood for the platelet count ("two syringe technology") reduced the rate of platelet-agglomeration significantly. No big differences in platelet-agglomeration were found with regard to the place used for collecting blood (V. cephalica antebrachii/V. jugularis). Platelet-agglutination was observed with Li-Heparin, K-EDTA, Na-Citrat or ACD anticoagulated blood samples. Citrat (Na-Citrat, ACD) seemed to have a stabilizing effect on feline thrombocytes as has been described for human thrombocytes. The platelet count in cats should be performed within 30 minutes.

  3. Hyperthermia inhibits platelet haemostatic functions and selectively regulates the release of alpha-granule proteins

    PubMed Central

    Etulain, J; Lapponi, MJ; Patrucchi, SJ; Romaniuk, MA; Benzadón, R; Klement, GL; Negrotto, S; Schattner, M

    2011-01-01

    Summary Background Hyperthermia is one of the main disturbances of homeostasis occurring during sepsis or hypermetabolic states such as cancer. Platelets are important mediators of the inflammation that accompany these processes, but very little is known about the changes in platelet function that occur at different temperatures. Objectives To explore the effect of higher temperatures on platelet physiology. Methods Platelet responses including adhesion, spreading (fluorescence microscopy), αIIbbeta;3 activation (flow cytometry), aggregation (turbidimetry), ATP release (luminescence), thromboxane A2 generation, alpha-granule protein secretion (ELISA), and protein phosphorylation from different signaling pathways (immunoblotting) were studied. Results Preincubation of platelets at temperatures higher than 37°C (38.5°–42°C) inhibited thrombin-induced haemostasis including platelet adhesion, aggregation, ATP release, and thromboxane A2 generation. The expression of P-selectin and CD63, as well as vascular endothelial growth factor (VEGF) release were completely inhibited by hyperthermia, whereas von Willebrand factor (vWF) and endostatin levels remained substantially increased at high temperatures. This suggested that release of proteins from platelet granules is modulated not only by classical platelet agonists but also by microenvironmental factors. The observed gradation of response involved not only antiangiogenesis regulators, but also other cargo proteins. Some signaling pathways were more stable than others. While ERK1/2 and AKT phosphorylation were resistant to changes in temperature, Src, Syk, p38 phosphorylation as well as IkappaB degradation were decreased in a temperature-dependent fashion. Conclusions Higher temperatures, such as those observed with fever or tissue invasion, inhibit the haemostatic functions of platelets and selectively regulate the release of alpha-granule proteins. PMID:21649851

  4. Platelet adhesion and plasma protein adsorption control of collagen surfaces by He + ion implantation

    NASA Astrophysics Data System (ADS)

    Kurotobi, K.; Suzuki, Y.; Nakajima, H.; Suzuki, H.; Iwaki, M.

    2003-05-01

    He + ion implanted collagen-coated tubes with a fluence of 1 × 10 14 ions/cm 2 were exhibited antithrombogenicity. To investigate the mechanisms of antithrombogenicity of these samples, plasma protein adsorption assay and platelet adhesion experiments were performed. The adsorption of fibrinogen (Fg) and von Willebrand factor (vWf) was minimum on the He + ion implanted collagen with a fluence of 1 × 10 14 ions/cm 2. Platelet adhesion (using platelet rich plasma) was inhibited on the He + ion implanted collagen with a fluence of 1 × 10 14 ions/cm 2 and was accelerated on the untreated collagen and ion implanted collagen with fluences of 1 × 10 13, 1 × 10 15 and 1 × 10 16 ions/cm 2. Platelet activation with washed platelets was observed on untreated collagen and He + ion implanted collagen with a fluence of 1 × 10 14 ions/cm 2 and was inhibited with fluences of 1 × 10 13, 1 × 10 15 and 1 × 10 16 ions/cm 2. Generally, platelets can react with a specific ligand inside the collagen (GFOGER sequence). The results of platelets adhesion experiments using washed platelets indicated that there were no ligands such as GFOGER on the He + ion implanted collagen over a fluence of 1 × 10 13 ions/cm 2. On the 1 × 10 14 ions/cm 2 implanted collagen, no platelet activation was observed due to the influence of plasma proteins. From the above, it is concluded that the decrease of adsorbed Fg and vWf caused the antithrombogenicity of He + ion implanted collagen with a fluence of 1 × 10 14 ions/cm 2 and that plasma protein adsorption took an important role repairing the graft surface.

  5. Heteroatom substituted and decorated graphene: preparation and applications.

    PubMed

    Chen, Nan; Huang, Xianke; Qu, Liangti

    2015-12-28

    Graphenes have attracted increasing attention in a variety of scientific fields. By modification with foreign elements such as boron, sulfur, and fluorine, their unique electronic and spin structures can be effectively tuned and the substituted or decorated graphenes as promising materials have been successfully employed in electrical, optical, and catalytic fields. In this review, we summarize the recent advances of these newly derived heteroatom substituted or decorated graphenes with an emphasis on the preparation methods, applications and the mechanisms of action. We are hopeful for future developments of heteroatom substituted or decorated graphenes in precisely controlled substitution methods, and finding wide applications of heteroatom substituted or decorated graphenes in many different fields.

  6. von Braun and German Publisher

    NASA Technical Reports Server (NTRS)

    1969-01-01

    In this photograph, Guenter Ogger of Capitol Magazine, West Germany, greets Marshall Space Flight Center Director, Dr. Wernher von Braun. Mr. Ogger interviewed the famous rocket scientist for his magazine.

  7. Von Karman and JATO Team

    NASA Technical Reports Server (NTRS)

    1940-01-01

    Dr. Theodore von Karman (black coat) sketches out a plan on the wing of an airplane as his JATO engineering team looks on. From left to right: Dr. Clark B. Millikan, Dr.Martin Summerfield, Dr. Theodore von Karman, Dr. Frank J. Malina and pilot, Capt. Homer Boushey. Captain Boushey would become the first American to pilot an airplane that used JATO (Jet Assisted Take-Off) solid propellent rockets.

  8. Human blood platelets at microgravity

    NASA Technical Reports Server (NTRS)

    Surgenor, D. MACN.; Ausprunk, D.; Blevins, D.; Chao, F. C.; Curby, W.

    1987-01-01

    A set of freshly collected and separated human platelet suspensions were transported, in three types of plastic containers, on a 6 day, 2 hr mission of the orbiter Columbia to study the effect of prolonged exposure of human blood cells to microgravity. A controlled environment at a temperature of 22 + or - 1 deg with air flow was provided and another set of samples held on the ground acted as controls. Paired comparisons of platelets at ug versus controls at lxg revealed superior platelet survival at microgravity. When viewed in terms of plastic type, ug platelets in containers fabricated from PVC-TOTM displayed the best overall postflight viability.

  9. Platelet effects on ovarian cancer.

    PubMed

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

    2014-06-01

    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.

  10. Platelets can enhance vascular permeability.

    PubMed

    Cloutier, Nathalie; Paré, Alexandre; Farndale, Richard W; Schumacher, H Ralph; Nigrovic, Peter A; Lacroix, Steve; Boilard, Eric

    2012-08-09

    Platelets survey blood vessels, searching for endothelial damage and preventing loss of vascular integrity. However, there are circumstances where vascular permeability increases, suggesting that platelets sometimes fail to fulfill their expected function. Human inflammatory arthritis is associated with tissue edema attributed to enhanced permeability of the synovial microvasculature. Murine studies have suggested that such vascular leak facilitates entry of autoantibodies and may thereby promote joint inflammation. Whereas platelets typically help to promote microvascular integrity, we examined the role of platelets in synovial vascular permeability in murine experimental arthritis. Using an in vivo model of autoimmune arthritis, we confirmed the presence of endothelial gaps in inflamed synovium. Surprisingly, permeability in the inflamed joints was abrogated if the platelets were absent. This effect was mediated by platelet serotonin accumulated via the serotonin transporter and could be antagonized using serotonin-specific reuptake inhibitor antidepressants. As opposed to the conventional role of platelets to microvascular leakage, this demonstration that platelets are capable of amplifying and maintaining permeability adds to the rapidly growing list of unexpected functions for platelets.

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

    PubMed

    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

  12. Chitosan scaffold enhances growth factor release in wound healing in von Willebrand disease

    PubMed Central

    Periayah, Mercy Halleluyah; Halim, Ahmad Sukari; Saad, Arman Zaharil Mat; Yaacob, Nik Soriani; Hussein, Abdul Rahim; Karim, Faraizah Abdul; Rashid, Ahmad Hazri Abdul; Ujang, Zanariah

    2015-01-01

    Chitosan-derived biomaterials have been reported to adhere when in contact with blood by encouraging platelets to adhere, activate and aggregate at the sites of vascular injury, thus enhanced wound healing capacity. This study investigated platelet morphology changes and the expression level of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor-AB (PDGF-AB) in the adherence of two different types of chitosans in von Willebrand disease (vWD): N,O-carboxymethylchitosan (NO-CMC) and oligo-chitosan (O-C). Fourteen vWD voluntary subjects were recruited, and they provided written informed consent. Scanning electron microscopy and enzyme-linked immunosorbent assay test procedures were employed to achieve the objective of the study. The results suggest that the O-C group showed dramatic changes in the platelet’s behaviors. Platelets extended filopodia and generated lamellipodia, leading to the formation of grape-like shaped aggregation. The platelet aggregation occurred depending on the severity of vWD. O-C was bound to platelets on approximately 90% of the surface membrane in vWD type 1; there was 70% and 50% coverage in vWD type II and III, respectively. The O-C chitosan group showed an elevated expression level of TGF-β1 and PDGF-AB. This finding suggests that O-C stimulates these mediators from the activated platelets to the early stage of restoring the damaged cells and tissues. This study demonstrated that the greater expression level of O-C assists in mediating the cytokine complex networks of TGF-β1 and PDGF-AB and induces platelet activities towards wound healing in vWD. With a better understanding of chitosan’s mechanisms of action, researchers are able to accurately develop novel therapies to prevent hemorrhage. PMID:26629055

  13. Platelet secretory behaviour: as diverse as the granules … or not?

    PubMed

    Heijnen, H; van der Sluijs, P

    2015-12-01

    Platelets play a central role in the arrest of bleeding after damage to a blood vessel and in the development of thrombosis. Platelets rapidly respond after interaction with sub-endothelial components and release cargo from their storage granules. The three principal granule types of platelets are α-granules, dense granules and lysosomes. Timed release of granule contents and regulated expression of critical receptors are essential for maintenance of the platelet thrombus, yet also have important functions beyond hemostasis (i.e. inflammatory reactions and immune responses). α-granules store adhesive molecules such as von Willebrand factor and fibrinogen, growth factors and inflammatory and angiogenic mediators, which play crucial roles in inflammatory responses and tumor genesis. The α-granules comprise a group of subcellular compartments with a unique composition and ultrastructure. Recent studies have suggested that differential secretory kinetics of α-granule subtypes is responsible for a thematic release of adhesive and inflammatory mediators. In addition, new results indicate that activation-dependent synthesis and release of cytokines also contribute to the inflammatory role of platelets. We will discuss the various methods that platelets use to regulate secretory processes and how these relate to potential differential secretion patterns, thereby promoting adhesiveness and/or inflammatory functions. We will focus on the heterogenic granule population, open canalicular system (OCS) plasticity, the role of contractile and mechanobiological forces, and the fusogenic machinery.

  14. Platelet Dysfunction in Thrombosis Patients Treated with Vitamin K Antagonists and Recurrent Bleeding

    PubMed Central

    van der Meijden, Paola E. J.; Bouman, Annemieke C.; Feijge, Marion A. H.; van Oerle, René; Spronk, Henri M. H.; Hamulyák, Karly; ten Cate-Hoek, Arina J.; ten Cate, Hugo; Heemskerk, Johan W. M.

    2013-01-01

    Background Recurrent bleeding can complicate the treatment of thrombosis patients with vitamin K antagonists (VKA), even at a well-regulated level of anticoagulation. In this proof-of-principle study, we investigated whether alterations in platelet function or von Willebrand factor (vWf) contribute to a bleeding phenotype in these patients. Methods In this case-control study 33 well-regulated patients without bleeding events (controls) and 33 patients with recurrent bleeding (cases) were retrospectively included. Thrombin generation and vWf were determined in plasma. Platelet function was assessed by light transmission aggregometry and flow cytometry using a validated panel of agonists. Results Thrombin generation was similarly reduced in controls and cases, in comparison to normal plasma. Plasma vWf level was above the normal range in 85% of controls and 67% of the cases. vWf activity was similarly increased in all patients in comparison to healthy volunteers. Platelet aggregation was in the normal range for almost all patients irrespective of the type of agonist. However, in response to a low collagen dose, platelets from 21% of controls and 27% of cases showed diminished responses. Agonist-induced secretion of alpha- and dense-granules or integrin αIIbβ3 activation were affected in platelets from neither controls nor cases. Conclusion Recurrent bleeding in well-controlled patients on VKA therapy is not explained by anti-hemostatic changes in platelet or vWf function. PMID:23724024

  15. Polyethylene glycol modification of adenovirus reduces platelet activation, endothelial cell activation, and thrombocytopenia.

    PubMed

    Hofherr, Sean E; Mok, Hoyin; Gushiken, Francisca C; Lopez, Jose A; Barry, Michael A

    2007-09-01

    Thrombocytopenia is one of the complications for in vivo administration of adenovirus serotype 5 (Ad5) vectors after intravenous injection. In this paper, we investigated the mechanism of Ad5-induced thrombocytopenia and how these effects are attenuated by polyethylene glycol (PEG) modification of Ad5 (Ad-PEG). After intravenous injection, accelerated platelet loss was observed in Ad-injected mice but not in their Ad-PEG-injected counterparts. This platelet loss induced by Ad5 corresponded with increases in coagulation D-dimer levels, splenomegaly, and, later, production of megakaryocytes in the bone marrow. In contrast, these responses were blunted or ablated after injection of Ad-PEG. Ad5 activated both platelets and endothelial cells directly in vitro as evidenced by induction of P-selectin and the formation of von Willebrand factor-platelet strings and in vivo as evidenced by the induction of E-selectin messenger RNA. PEGylation blunted these observed activations. These data suggest that Ad5 may induce thrombocytopenia by direct activation of endothelial cells in addition to its direct effects on platelets. This link provides an important clue for the understanding of the mechanisms of thrombocytopenia associated with Ad5. Given that PEGylation blunted interactions of Ad with platelets and endothelial cells, reduced D-dimer formation, reduced thrombocytopenia, and reduced splenomegaly, these data suggest that this simple vector modification may have utility to improve the safety of Ad vectors for human gene therapy.

  16. Platelet abnormalities in adults with severe pulmonary arterial hypertension related to congenital heart defects (Eisenmenger syndrome).

    PubMed

    Remková, Anna; Šimková, Iveta; Valkovičová, Tatiana; Kaldarárová, Monika

    2016-12-01

    Patients with severe pulmonary arterial hypertension suffer from life-threatening thrombotic and bleeding complications. The aim of this study was to compare selected platelet, endothelial, and coagulation parameters in healthy volunteers and patients with severe pulmonary arterial hypertension because of congenital heart defects. The study included healthy volunteers (n = 50) and patients with cyanotic congenital heart defects classified as Eisenmenger syndrome (n = 41). We investigated platelet count, mean platelet volume, and platelet aggregation - spontaneous and induced by various concentrations of five agonists. Von Willebrand factor (vWF), fibrinogen, factor VIII and XII, plasminogen activator inhibitor, antithrombin, D-dimer, and antiphospholipid antibodies were also investigated. We found a decreased platelet count [190 (147-225) vs. 248 (205-295) 10 l, P < 0.0001], higher mean platelet volume [10.9 (10.1-12.0) vs. 10.2 (9.4-10.4) fl, P < 0.0001], and significantly decreased platelet aggregation (induced by five agonists, in various concentrations) in patients with Eisenmenger syndrome compared with controls. These changes were accompanied by an increase of plasma vWF antigen [141.6 (108.9-179.1) vs. 117.4 (9.2-140.7) IU/dl, P = 0.022] and serum anti-β2-glycoprotein [2.07 (0.71-3.41) vs. 0.47 (0.18-0.99) U/ml, P < 0.0001]. Eisenmenger syndrome is accompanied by platelet abnormalities. Thrombocytopenia with increased platelet size is probably due to a higher platelet turnover associated with platelet activation. Impaired platelet aggregation can reflect specific platelet behaviour in patients with Eisenmenger syndrome. These changes can be related both to bleeding and to thrombotic events. A higher vWF antigen may be a consequence of endothelial damage in Eisenmenger syndrome, but the cause for an increase of anti-β2-glycoprotein is unknown.

  17. Performance of the platelet function analyser PFA-100 in testing abnormalities of primary haemostasis.

    PubMed

    Harrison, P; Robinson, M S; Mackie, I J; Joseph, J; McDonald, S J; Liesner, R; Savidge, G F; Pasi, J; Machin, S J

    1999-01-01

    The PFA-100 device is a new instrument for the in-vitro testing of platelet function. Primary haemostasis is stimulated by recording the closure time taken for platelets to seal a 150 microm aperture in the centre of a membrane coated with collagen and either epinephrine or ADP. Patients with type 3 von Willebrand's disease (n = 4) all had infinitely prolonged closure times (> 200 s) with both types of cartridge. A patient with afibrinogenemia exhibited only slightly prolonged closure times of 111 and 166 s for the ADP and epinephrine membranes, respectively. Patients with Glanzmann's thrombasthenia (n = 6) and Bernard Soulier syndrome (n = 2) had grossly prolonged closure times (> 200 s) with both types of cartridges. These results confirmed that the PFA-100 system was highly dependent on normal von Willebrand factor, glycoprotein Ib and glycoprotein IIb/IIIa levels but not on plasma fibrinogen. Patients with storage pool disease (n = 6) and Hermansky Pudlak syndrome (n = 7) had prolonged closure times with the epinephrine cartridge. There was no evidence of enhanced platelet function in patients with antiphospholipid syndrome, in sickle-cell disease or thalassemia. However, ingestion of aspirin resulted in a near consistent and significant prolongation of the closure time for the epinephrine cartridge but not for the ADP cartridge in both normal subjects and patients. The test offers a reliable, reproducible, rapid and simple means of assessing high-shear platelet function in vitro.

  18. Nucleation of platelets with bloodborne pathogens on Kupffer cell precedes other innate immunity and contributes to bacterial clearance

    PubMed Central

    Wong, Connie H. Y.; Jenne, Craig N.; Petri, Björn; Chrobok, Navina L.; Kubes, Paul

    2016-01-01

    Using intravital imaging of the liver, we unveil a collaborative role for platelets with Kupffer cells (KCs) in eradicating bloodborne bacterial infections. Under basal conditions, platelets via glycoprotein Ib (GPIb) formed transient “touch-and-go” interactions with von Willebrand factor (vWF) constitutively expressed on KCs. Bacteria, such as Bacillus cereus and Methicillin-resistant Staphylococcus aureus (MRSA), were rapidly caught by KCs and triggered platelets to switch from “touch-and-go” to sustained GPIIb-mediated adhesion on the KC surface to encase the bacterium. Infected GpIbα−/− mice demonstrated increased endothelial and KC damage, leading to increased fluid leakage, significant polycythemia and rapid mortality. This study identifies a novel surveillance mechanism of intravascular macrophage by platelets that rapidly converts to a critical host response against bloodborne bacteria. PMID:23770641

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

    PubMed

    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.

  20. Richard von Volkmann

    PubMed Central

    Willy, Christian; Schneider, Peter; Engelhardt, Michael; Hargens, Alan R.

    2008-01-01

    Richard von Volkmann (1830–1889), one of the most important surgeons of the 19th century, is regarded as one of the fathers of orthopaedic surgery. He was a contemporary of Langenbeck, Esmarch, Lister, Billroth, Kocher, and Trendelenburg. He was head of the Department of Surgery at the University of Halle, Germany (1867–1889). His popularity attracted doctors and patients from all over the world. He was the lead physician for the German military during two wars. From this experience, he compared the mortality of civilian and war injuries and investigated the general poor hygienic conditions in civilian hospitals. This led him to introduce the “antiseptic technique” to Germany that was developed by Lister. His powers of observation and creativity led him to findings and achievements that to this day bear his name: Volkmann’s contracture and the Hueter-Volkmann law. Additionally, he was a gifted writer; he published not only scientific literature but also books of children’s fairy tales and poems under the pen name of Richard Leander, assuring him a permanent place in the world of literature as well as orthopaedics. PMID:18196438

  1. Holiday Door Decorating Contest Brings Cheer | Poster

    Cancer.gov

    By Carolynne Keenan, Contributing Writer Other than the time of year, what do the following have in common: the leg lamp from the movie “A Christmas Story,” a compilation of silly holiday jokes, a gingerbread house, and Santa on a motorcycle? All four were among the individual door winners for the Holiday Door Decorating Contest, held at NCI at Frederick in December. Employees dressed up their office doors, hallways, and even stairwells to participate. Entries for the contest included individual office doors as well as groups. Some employees even “decked the halls” of whole office buildings to participate.

  2. Platelets: production, morphology and ultrastructure.

    PubMed

    Thon, Jonathan N; Italiano, Joseph E

    2012-01-01

    Platelets are anucleate, discoid cells, roughly 2-3 μm in diameter that function primarily as regulators of hemostasis, but also play secondary roles in angiogensis and innate immunity. Although human adults contain nearly one trillion platelets in circulation that are turned over every 8-10 days, our understanding of the mechanisms involved in platelet production is still incomplete. Platelets stem from large (30-100 μm) nucleated cells called megakaryocytes that reside primarily in the bone marrow. During maturation megakaryocytes extend long proplatelet elongations into sinusoidal blood vessels from which platelets ultimately release. During this process, platelets develop a number of distinguishable structural elements including: a delimited plasma membrane; invaginations of the surface membrane that form the open canalicular system (OCS); a closed-channel network of residual endoplasmic reticulum that form the dense tubular system (DTS); a spectrin-based membrane skeleton; an actin-based cytoskeletal network; a peripheral band of microtubules; and numerous organelles including α-granules, dense-granules, peroxisomes, lysosomes, and mitochondria. Proplatelet elongation and platelet production is an elaborate and complex process that defines the morphology and ultrastructure of circulating platelets, and is critical in understanding their increasingly numerous and varied biological functions.

  3. Deciphering the human platelet sheddome

    PubMed Central

    Fong, Karen P.; Barry, Colin; Tran, Anh N.; Traxler, Elizabeth A.; Wannemacher, Kenneth M.; Tang, Hsin-Yao; Speicher, Kaye D.; Blair, Ian A.; Speicher, David W.; Grosser, Tilo

    2011-01-01

    Activated platelets shed surface proteins, potentially modifying platelet function as well as providing a source of bioactive fragments. Previous studies have identified several constituents of the platelet sheddome, but the full extent of shedding is unknown. Here we have taken a global approach, analyzing protein fragments in the supernate of activated platelets using mass spectroscopy and looking for proteins originating from platelet membranes. After removing plasma proteins and microparticles, 1048 proteins were identified, including 69 membrane proteins. Nearly all of the membrane proteins had been detected previously, but only 10 had been shown to be shed in platelets. The remaining 59 are candidates subject to confirmation. Based on spectral counts, protein representation in the sheddome varies considerably. As proof of principle, we validated one of the less frequently detected proteins, semaphorin 7A, which had not previously been identified in platelets. Surface expression, cleavage, and shedding of semaphorin 7A were demonstrated, as was its association with α-granules. Finally, cleavage of semaphorin 7A and 12 other proteins was substantially reduced by an inhibitor of ADAM17, a known sheddase. These results define a subset of membrane proteins as sheddome candidates, forming the basis for further studies examining the impact of ectodomain shedding on platelet function. PMID:20962327

  4. Biologic nanoparticles and platelet reactivity

    PubMed Central

    Miller, Virginia M; Hunter, Larry W; Chu, Kevin; Kaul, Vivasvat; Squillace, Phillip D; Lieske, John C; Jayachandran, Muthuvel

    2009-01-01

    Aim Nanosized particles (NPs) enriched in hydroxyapatite and protein isolated from calcified human tissue accelerate occlusion of endothelium-denuded arteries when injected intravenously into rabbits. Since platelet aggregation and secretory processes participate in normal hemostasis, thrombosis and vascular remodeling, experiments were designed to determine if these biologic NPs alter specific platelet functions in vitro. Methods Platelet-rich plasma was prepared from citrate anticoagulated human blood. Platelet aggregation and ATP secretion were monitored in response to thrombin receptor agonists peptide (10 μM) or convulxin (50 μg/ml) prior to and following 15 min incubation with either control solution, human-derived NPs, bovine-derived NPs or crystals of hydroxyapatite at concentrations of 50 and 150 nephelometric turbidity units. Results Incubation of platelets for 15 min with either human- or bovine-derived NPs reduced aggregation induced by thrombin receptor activator peptide and convulxin in a concentration-dependent manner. Hydroxyapatite caused a greater inhibition than either of the biologically derived NPs. Human-derived NPs increased ATP secretion by unstimulated platelets during the 15 min incubation period. Conclusion Effects of bovine-derived and hydroxyapatite NPs on basal release of ATP were both time and concentration dependent. These results suggest that biologic NPs modulate both platelet aggregation and secretion. Biologically derived NPs could modify platelet responses within the vasculature, thereby reducing blood coagulability and the vascular response to injury. PMID:19839809

  5. Platelets, inflammation and tissue regeneration.

    PubMed

    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.

  6. 21 CFR 109.16 - Ornamental and decorative ceramicware.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...-PACKAGING MATERIAL General Provisions § 109.16 Ornamental and decorative ceramicware. (a) Lead is a toxic... food may result in the leaching of lead from the glaze or decoration into the food. The provisions of... Food Use. May Poison Food,” “Not for Food Use. Glaze contains lead. Food Use May Result in...

  7. 21 CFR 109.16 - Ornamental and decorative ceramicware.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-PACKAGING MATERIAL General Provisions § 109.16 Ornamental and decorative ceramicware. (a) Lead is a toxic... food may result in the leaching of lead from the glaze or decoration into the food. The provisions of... Food Use. May Poison Food,” “Not for Food Use. Glaze contains lead. Food Use May Result in...

  8. 21 CFR 109.16 - Ornamental and decorative ceramicware.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-PACKAGING MATERIAL General Provisions § 109.16 Ornamental and decorative ceramicware. (a) Lead is a toxic... food may result in the leaching of lead from the glaze or decoration into the food. The provisions of... Food Use. May Poison Food,” “Not for Food Use. Glaze contains lead. Food Use May Result in...

  9. 21 CFR 109.16 - Ornamental and decorative ceramicware.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-PACKAGING MATERIAL General Provisions § 109.16 Ornamental and decorative ceramicware. (a) Lead is a toxic... food may result in the leaching of lead from the glaze or decoration into the food. The provisions of... Food Use. May Poison Food,” “Not for Food Use. Glaze contains lead. Food Use May Result in...

  10. 21 CFR 109.16 - Ornamental and decorative ceramicware.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-PACKAGING MATERIAL General Provisions § 109.16 Ornamental and decorative ceramicware. (a) Lead is a toxic... food may result in the leaching of lead from the glaze or decoration into the food. The provisions of... Food Use. May Poison Food,” “Not for Food Use. Glaze contains lead. Food Use May Result in...

  11. Platelet coagulation-protein interactions.

    PubMed

    Walsh, Peter N

    2004-08-01

    The biochemical mechanisms by which activated platelets participate in exposing receptors for the assembly of enzyme-cofactor-substrate complexes at all stages of the blood coagulation cascade are reviewed. Information derived from studies conducted during the last 30 years supports the concept that the initiation of blood coagulation is triggered by exposure of tissue factor at injury sites, leading to the generation of minute quantities of thrombin (limited by tissue factor pathway inhibitor), sufficient to activate platelets, factors XI, VIII, and V, and trigger the consolidation pathway (i.e., the sequential activation of factors XI, IX, X, and prothrombin on the activated platelet surface), leading to the generation of sufficient thrombin to convert fibrinogen to fibrin and effect hemostasis. Platelets localize coagulation to the hemostatic thrombus and protect coagulation enzymes from inhibition by both plasma and platelet inhibitors (e.g., protease nexin 2), thus preventing disseminated intravascular coagulation.

  12. Geometric and Electronic Properties of Edge-decorated Graphene Nanoribbons

    PubMed Central

    Chang, Shen-Lin; Lin, Shih-Yang; Lin, Shih-Kang; Lee, Chi-Hsuan; Lin, Ming-Fa

    2014-01-01

    Edge-decorated graphene nanoribbons are investigated with the density functional theory; they reveal three stable geometric structures. The first type is a tubular structure formed by the covalent bonds of decorating boron or nitrogen atoms. The second one consists of curved nanoribbons created by the dipole-dipole interactions between two edges when decorated with Be, Mg, or Al atoms. The final structure is a flat nanoribbon produced due to the repulsive force between two edges; most decorated structures belong to this type. Various decorating atoms, different curvature angles, and the zigzag edge structure are reflected in the electronic properties, magnetic properties, and bonding configurations. Most of the resulting structures are conductors with relatively high free carrier densities, whereas a few are semiconductors due to the zigzag-edge-induced anti-ferromagnetism. PMID:25123103

  13. Platelets and angiogenesis in malignancy.

    PubMed

    Sierko, Ewa; Wojtukiewicz, Marek Z

    2004-02-01

    There is increasing evidence that platelets play an important role in the process of tumor angiogenesis. Thrombocytosis is a frequent finding in cancer patients (10-57%). Although the mechanisms underlying thrombocytosis are not yet fully elucidated, tumor-derived factors with thrombopoietin-like activity and growth factors, platelet-derived microparticles, and factors secreted from bone marrow endothelial cells, as well as growth factors released by megakaryocytes (acting via an autocrine loop), are postulated to influence this process. The progression of cancer is associated with hypercoagulability, which results from direct influences of tumor cells and diverse indirect mechanisms. Activated platelets serve as procoagulant surfaces amplifying the coagulation reactions. It is well known that hemostatic proteins are involved in different steps of the angiogenic process. Furthermore, platelets adhering to endothelium facilitate adhesion of mononuclear cells (which exert various proangiogenic activities) to endothelial cells and their transmigration to the extravascular space. It was also documented that platelets induce angiogenesis in vivo. Platelets are a rich source of proangiogenic factors. They also store and release angiogenesis inhibitors. In addition, platelets express surface growth factor receptors, which may regulate the process of angiogenesis. Platelets also contribute directly to the process of basement membrane and extracellular matrix proteolysis by releasing proteinases, or indirectly via inducing endothelial cells and tumor cells to release proteolytic enzymes, as well as through the proteolytic activities of platelet-derived growth factors. The multidirectional activities of platelets in the process of new blood vessel formation during tumor development and metastasis formation may create the possibility of introducing antiplatelet agents for antiangiogenic therapy in cancer patients. Thus far experimental studies employing inhibitors of

  14. Analyzing the platelet proteome.

    PubMed

    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.

  15. Platelet function and constituents of platelet rich plasma.

    PubMed

    Pelletier, M H; Malhotra, A; Brighton, T; Walsh, W R; Lindeman, R

    2013-01-01

    Platelet Rich Plasma (PRP) therapies require blood to be processed prior to application, however, the full assessment of the output of platelet sequestration devices is lacking. In this study the products of the Autologous Fluid Concentrator (Circle BiologicsTM, Minneapolis, MN) and the Gravitational Platelet Separation System (GPS, Biomet, Warsaw, IN, USA) were evaluated in terms of platelet viability and PRP constituents. The AFC and GPS produced 6.4 (±1.0) ml and 6.3 (±0.4) ml of PRP, with platelet recovery of 46.4% (±14.7%) and 59.8% (±24.2%) producing fold increases of platelets of 4.19 (±1.62) and 5.19 (±1.62), respectively. Fibrinogen concentration was increased above baseline PPP produced with the AFC. pH was lower for both of the processed samples than for whole blood. White Blood Cell count was increased around 5 fold. Functional tests showed preserved viability with both devices. This represents essential knowledge that every treating physician should have before they can confidently administer PRP therapy produced by any method. These are the first published results of platelet function for the GPS system and the first performance results of the AFC system. The PRP produced is classified according to broad classifications as Leukocyte-PRP (L-PRP) for both devices.

  16. A genetically-engineered von Willebrand disease type 2B mouse model displays defects in hemostasis and inflammation

    PubMed Central

    Adam, Frédéric; Casari, Caterina; Prévost, Nicolas; Kauskot, Alexandre; Loubière, Cécile; Legendre, Paulette; Repérant, Christelle; Baruch, Dominique; Rosa, Jean-Philippe; Bryckaert, Marijke; de Groot, Philip G.; Christophe, Olivier D.; Lenting, Peter J.; Denis, Cécile V.

    2016-01-01

    von Willebrand disease (VWD)-type 2B is characterized by gain-of-function mutations in the von Willebrand factor (VWF) A1-domain, leading to increased affinity for its platelet-receptor, glycoprotein Ibα. We engineered the first knock-in (KI) murine model for VWD-type 2B by introducing the p.V1316M mutation in murine VWF. Homozygous KI-mice replicated human VWD-type 2B with macrothrombocytopenia (platelet counts reduced by 55%, platelet volume increased by 44%), circulating platelet-aggregates and a severe bleeding tendency. Also, vessel occlusion was deficient in the FeCl3-induced thrombosis model. Platelet aggregation induced by thrombin or collagen was defective for KI-mice at all doses. KI-mice manifested a loss of high molecular weight multimers and increased multimer degradation. In a model of VWF-string formation, the number of platelets/string and string-lifetime were surprisingly enhanced in KI-mice, suggesting that proteolysis of VWF/p.V1316M is differentially regulated in the circulation versus the endothelial surface. Furthermore, we observed increased leukocyte recruitment during an inflammatory response induced by the reverse passive Arthus reaction. This points to an active role of VWF/p.V1316M in the exfiltration of leukocytes under inflammatory conditions. In conclusion, our genetically-engineered VWD-type 2B mice represent an original model to study the consequences of spontaneous VWF-platelet interactions and the physiopathology of this human disease. PMID:27212476

  17. Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels.

    PubMed

    Al-Tamimi, Mohammad; Tan, Chee Wee; Qiao, Jianlin; Pennings, Gabrielle J; Javadzadegan, Ashkan; Yong, Andy S C; Arthur, Jane F; Davis, Amanda K; Jing, Jing; Mu, Fi-Tjen; Hamilton, Justin R; Jackson, Shaun P; Ludwig, Andreas; Berndt, Michael C; Ward, Christopher M; Kritharides, Leonard; Andrews, Robert K; Gardiner, Elizabeth E

    2012-05-03

    Ligand-induced ectodomain shedding of glycoprotein VI (GPVI) is a metalloproteinase-dependent event. We examined whether shear force, in the absence of GPVI ligand, was sufficient to induce shedding of GPVI. Human-citrated platelet-rich plasma or washed platelets were subjected to increasing shear rates in a cone-plate viscometer, and levels of intact and cleaved GPVI were examined by Western blot and ELISA. Pathophysiologic shear rates (3000-10 000 seconds(-1)) induced platelet aggregation and metalloproteinase-dependent appearance of soluble GPVI ectodomain, and GPVI platelet remnant. Shedding of GPVI continued after transient exposure to shear. Blockade of α(IIb)β(3), GPIbα, or intracellular signaling inhibited shear-induced platelet aggregation but minimally affected shear-induced shedding of GPVI. Shear-induced GPVI shedding also occurred in platelet-rich plasma or washed platelets isolated from a von Willebrand disease type 3 patient with no detectable VWF, implying that shear-induced activation of platelet metalloproteinases can occur in the absence of GPVI and GPIbα ligands. Significantly elevated levels of sGPVI were observed in 10 patients with stable angina pectoris, with well-defined single vessel coronary artery disease and mean intracoronary shear estimates at 2935 seconds(-1) (peak shear, 19 224 seconds(-1)). Loss of GPVI in platelets exposed to shear has potential implications for the stability of a forming thrombus at arterial shear rates.

  18. 14-3-3ζ regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function

    PubMed Central

    Schoenwaelder, Simone M.; Darbousset, Roxane; Cranmer, Susan L.; Ramshaw, Hayley S.; Orive, Stephanie L.; Sturgeon, Sharelle; Yuan, Yuping; Yao, Yu; Krycer, James R.; Woodcock, Joanna; Maclean, Jessica; Pitson, Stuart; Zheng, Zhaohua; Henstridge, Darren C.; van der Wal, Dianne; Gardiner, Elizabeth E.; Berndt, Michael C.; Andrews, Robert K.; James, David E.; Lopez, Angel F.; Jackson, Shaun P.

    2016-01-01

    The 14-3-3 family of adaptor proteins regulate diverse cellular functions including cell proliferation, metabolism, adhesion and apoptosis. Platelets express numerous 14-3-3 isoforms, including 14-3-3ζ, which has previously been implicated in regulating GPIbα function. Here we show an important role for 14-3-3ζ in regulating arterial thrombosis. Interestingly, this thrombosis defect is not related to alterations in von Willebrand factor (VWF)–GPIb adhesive function or platelet activation, but instead associated with reduced platelet phosphatidylserine (PS) exposure and procoagulant function. Decreased PS exposure in 14-3-3ζ-deficient platelets is associated with more sustained levels of metabolic ATP and increased mitochondrial respiratory reserve, independent of alterations in cytosolic calcium flux. Reduced platelet PS exposure in 14-3-3ζ-deficient mice does not increase bleeding risk, but results in decreased thrombin generation and protection from pulmonary embolism, leading to prolonged survival. Our studies define an important role for 14-3-3ζ in regulating platelet bioenergetics, leading to decreased platelet PS exposure and procoagulant function. PMID:27670677

  19. P-selectin can promote thrombus propagation independently of both von Willebrand factor and thrombospondin-1 in mice.

    PubMed

    Prakash, P; Nayak, M K; Chauhan, A K

    2017-02-01

    Essentials The main receptor for platelet glycoprotein (GP) Ibα is von Willebrand factor (VWF). P-selectin and thrombospondin-1 (TSP1) have been suggested as counter receptors for GPIbα. In a laser injury model, P-selectin promotes thrombus propagation independently of VWF and TSP1. In a laser injury model, thrombus persists in interleukin-4 receptor α/GPIbα-transgenic mice.

  20. Force-Sensitive Autoinhibition of the von Willebrand Factor Is Mediated by Interdomain Interactions

    PubMed Central

    Aponte-Santamaría, Camilo; Huck, Volker; Posch, Sandra; Bronowska, Agnieszka K.; Grässle, Sandra; Brehm, Maria A.; Obser, Tobias; Schneppenheim, Reinhard; Hinterdorfer, Peter; Schneider, Stefan W.; Baldauf, Carsten; Gräter, Frauke

    2015-01-01

    Von Willebrand factor (VWF) plays a central role in hemostasis. Triggered by shear-stress, it adheres to platelets at sites of vascular injury. Inactivation of VWF has been associated to the shielding of its adhesion sites and proteolytic cleavage. However, the molecular nature of this shielding and its coupling to cleavage under shear-forces in flowing blood remain unknown. In this study, we describe, to our knowledge, a new force-sensory mechanism for VWF-platelet binding, which addresses these questions, based on a combination of molecular dynamics (MD) simulations, atomic force microscopy (AFM), and microfluidic experiments. Our MD simulations demonstrate that the VWF A2 domain targets a specific region at the VWF A1 domain, corresponding to the binding site of the platelet glycoprotein Ibα (GPIbα) receptor, thereby causing its blockage. This implies autoinhibition of the VWF for the binding of platelets mediated by the A1-A2 protein-protein interaction. During force-probe MD simulations, a stretching force dissociated the A1A2 complex, thereby unblocking the GPIbα binding site. Dissociation was found to be coupled to the unfolding of the A2 domain, with dissociation predominantly occurring before exposure of the cleavage site in A2, an observation that is supported by our AFM experiments. This suggests that the A2 domain prevents platelet binding in a force-dependent manner, ensuring that VWF initiates hemostasis before inactivation by proteolytic cleavage. Microfluidic experiments with an A2-deletion VWF mutant resulted in increased platelet binding, corroborating the key autoinhibitory role of the A2 domain within VWF multimers. Overall, autoinhibition of VWF mediated by force-dependent interdomain interactions offers the molecular basis for the shear-sensitive growth of VWF-platelet aggregates, and might be similarly involved in shear-induced VWF self-aggregation and other force-sensing functions in hemostasis. PMID:25954888

  1. Shiga toxin binds to activated platelets.

    PubMed

    Ghosh, S A; Polanowska-Grabowska, R K; Fujii, J; Obrig, T; Gear, A R L

    2004-03-01

    Hemolytic uremic syndrome (HUS) is associated with acute renal failure in children and can be caused by Shiga toxin (Stx)-producing Escherichia coli. Thrombocytopenia and formation of renal thrombi are characteristic of HUS, suggesting that platelet activation is involved in its pathogenesis. However, whether Shiga toxin directly activates platelets is controversial. The present study evaluates if potential platelet sensitization during isolation by different procedures influences platelet interaction with Shiga toxin. Platelets isolated from sodium citrate anticoagulated blood were exposed during washing to EDTA and higher g forces than platelets prepared from acid-citrate-dextrose (ACD) plasma. Platelet binding of Stx was significantly higher in EDTA-washed preparations relative to ACD-derived platelets. Binding of Stx was also increased with ACD-derived platelets when activated with thrombin (1 U mL-1) and exposure of the Gb3 Stx receptor was detected only on platelets subjected to EDTA, higher g forces or thrombin. EDTA-exposed platelets lost their normal discoid shape and were larger. P-selectin (CD62P) exposure was significantly increased in EDTA-washed preparations relative to ACD-derived platelets, suggesting platelet activation. Taken together, these results suggest that direct binding of Stx occurs only on 'activated' platelets rather than on resting platelets. The ability of Stx to interact with previously activated platelets may be an important element in understanding the pathogenesis of HUS.

  2. Radioimmune assay of human platelet prostaglandin synthetase

    SciTech Connect

    Roth, G.J.; Machuga, E.T.

    1982-02-01

    Normal platelet function depends, in part, on platelet PG synthesis. PG synthetase (cyclo-oxygenase) catalyzes the first step in PG synthesis, the formation of PGH/sub 2/ from arachidonic acid. Inhibition of the enzyme by ASA results in an abnormality in the platelet release reaction. Patients with pparent congenital abnormalities in the enzyme have been described, and the effects have been referred to as ''aspirin-like'' defects of the platelet function. These patients lack platelet PG synthetase activity, but the actual content of PG synthetase protein in these individuals' platelets is unknown. Therefore an RIA for human platelet PG synthetase would provide new information, useful in assessing the aspirin-like defects of platelet function. An RIA for human platelet PG synthetase is described. The assay utilizes a rabbit antibody directed against the enzyme and (/sup 125/I)-labelled sheep PG synthetase as antigen. The human platelet enzyme is assayed by its ability to inhibit precipitation of the (/sup 125/I)antigen. The assay is sensitive to 1 ng of enzyme. By the immune assay, human platelets contain approximately 1200 ng of PG synethetase protein per 1.5 mg of platelet protein (approximately 10/sup 9/ platelets). This content corresponds to 10,000 enzyme molecules per platelet. The assay provides a rapid and convenient assay for the human platelet enzyme, and it can be applied to the assessment of patients with apparent platelet PG synthetase (cyclo-oxygenase) deficiency.

  3. Platelet Interaction with Innate Immune Cells

    PubMed Central

    Kral, Julia Barbara; Schrottmaier, Waltraud Cornelia; Salzmann, Manuel; Assinger, Alice

    2016-01-01

    Summary Beyond their traditional role in haemostasis and thrombosis, platelets are increasingly recognised as immune modulatory cells. Activated platelets and platelet-derived microparticles can bind to leukocytes, which stimulates mutual activation and results in rapid, local release of platelet-derived cytokines. Thereby platelets modulate leukocyte effector functions and contribute to inflammatory and immune responses to injury or infection. Platelets enhance leukocyte extravasation, differentiation and cytokine release. Platelet-neutrophil interactions boost oxidative burst, neutrophil extracellular trap formation and phagocytosis and play an important role in host defence. Platelet interactions with monocytes propagate their differentiation into macrophages, modulate cytokine release and attenuate macrophage functions. Depending on the underlying pathology, platelets can enhance or diminish leukocyte cytokine production, indicating that platelet-leukocyte interactions represent a fine balanced system to restrict excessive inflammation during infection. In atherosclerosis, platelet interaction with neutrophils, monocytes and dendritic cells accelerates key steps of atherogenesis by promoting leukocyte extravasation and foam cell formation. Platelet-leukocyte interactions at sites of atherosclerotic lesions destabilise atherosclerotic plaques and promote plaque rupture. Leukocytes in turn also modulate platelet function and production, which either results in enhanced platelet destruction or increased platelet production. This review aims to summarise the key effects of platelet-leukocyte interactions in inflammation, infection and atherosclerosis. PMID:27226790

  4. Platelets effects on tumor growth.

    PubMed

    Goubran, Hadi A; Stakiw, Julie; Radosevic, Mirjana; Burnouf, Thierry

    2014-06-01

    Unlike other blood cells, platelets are small anucleate structures derived from marrow megakaryocytes. Thought for almost a century to possess solely hemostatic potentials, platelets, however, play a much wider role in tissue regeneration and repair and interact intimately with tumor cells. On one hand, tumor cells induce platelet aggregation (TCIPA), known to act as the trigger of cancer-associated thrombosis. On the other hand, platelets recruited to the tumor microenvironment interact, directly, with tumor cells, favoring their proliferation, and, indirectly, through the release of a wide palette of growth factors, including angiogenic and mitogenic proteins. In addition, the role of platelets is not solely confined to the primary tumor site. Indeed, they escort tumor cells, helping their intravasation, vascular migration, arrest, and extravasation to the tissues to form distant metastasis. As expected, nonspecific or specific inhibition of platelets and their content represents an attractive novel approach in the fight against cancer. This review illustrates the role played by platelets at primary tumor sites and in the various stages of the metastatic process.

  5. Platelets in inflammation and infection.

    PubMed

    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.

  6. Studies on Human Platelet Gangliosides

    PubMed Central

    Marcus, Aaron J.; Ullman, Harris L.; Safier, Lenore B.

    1972-01-01

    Gangliosides, glycosphingolipids which contain sialic acid, were studied in human platelets. They represented 0.5% of the platelet lipids and accounted for 6% of the total neuraminic acid content of platelets. Three major ganglioside fractions were identified and characterized. Ganglioside I was hematoside (G6) and comprised 92% of the platelet gangliosides. It contained glucose, galactose, and sialic acid in molar ratios of 1:1:1 and no hexosamine. The major fatty acid was behenate (22:0). Ganglioside I was also identified in isolated platelet granules and membranes. Ganglioside II (5%) contained glucose, galactose, sialic acid, and hexosamines (molar ratios 1:2:1:1). The hexosamines were glucosamine (72%) and galactosamine (28%). It was therefore designated as ganglioside lacto-N-neotetraose. Ganglioside III (2%) contained disialosyllactosyl ceramide (G3A) as well as two other gangliosides which could not be precisely characterized. Gangliosides I, II, and III were susceptible to the action of Clostridium perfringens neuraminidase as evidenced by full recovery of sialic acid in its free form after incubation. Neutral platelet glycolipids were qualitatively examined by thin-layer chromatography. The major component was lactosyl ceramide. Interactions of gangliosides I and III and serotonin-14C were examined in an equilibrium dialysis system at 4°C. The gangliosides bound serotonin-14C in relatively small quantities, whereas control lipids were negative. The binding was essentially unchanged by reverse dialysis, ultracentrifugation and subsequent thin-layer chromatography. The results are comparable to the previously observed nonmetabolic interactions between whole platelets and serotonin in the cold. It is suggested that the orientation and specific distribution of platelet membrane glycolipids may be important determinants of the unique surface properties of platelets. Images PMID:4341436

  7. Platelet function in Takotsubo cardiomyopathy.

    PubMed

    Núñez-Gil, Iván J; Bernardo, Esther; Feltes, Gisela; Escaned, Javier; Mejía-Rentería, Hernán D; De Agustín, José Alberto; Vivas, David; Nombela-Franco, Luis; Jiménez-Quevedo, Pilar; Macaya, Carlos; Fernández-Ortiz, Antonio

    2015-05-01

    Takotsubo cardiomyopathy (TK) includes a transient left ventricular dysfunction without obstructive coronary disease, sometimes after stressful situations with elevated cathecolamines. Since catecholamines activate platelets we aimed to study the platelet influence in a TK setting. We included 32 patients with a TK diagnosis, 13 with an acute coronary syndrome (ACS) and 18 healthy volunteers. Once consent informed was obtained, blood samples were extracted and processed (at admission and after 3 months follow-up). Clinical, ecg, echocardiographic and angiographic features were thoroughly recorded.Previous treatment before admission was similar between groups. No differences were observed in clinical features or any of the acute markers studied regarding platelet reactivity between TK compared to ACS. After follow-up, aggregation levels and platelet reactivity showed differences, mainly due to the antithrombotic therapy prescribed at discharge, but similar to volunteers. Circulating epinephrine during the acute phase was significantly higher in TK (p < 0.001). Patients with higher levels of epinephrine had elevated platelet activation and aggregation after 3 months. No differences were observed in Takotsubo acute platelet aggregation compared to patients with ACS, in spite of higher blood levels of adrenaline. Takotsubo patients had elevated platelet aggregation and activation compared with ACS patients at 3 months follow-up because they were less frequently on chronic clopidogrel and ASA. However, they had similar platelet aggregation and activation levels to healthy volunteers despite treatment with low-dose ASA. Takotsubo patients who had higher levels of adrenaline in the acute phase displayed increased platelet reactivity during follow-up.

  8. Platelet and red blood cell indices in Harris platelet syndrome.

    PubMed

    Naina, Harris V K; Harris, Samar

    2010-01-01

    Inherited thrombocytopenias, including inherited giant platelet disorders (IGPD) or macro thrombocytopenias are relatively rare, but their prevalence is likely underestimated from complexities of diagnosis and a spectrum of subclinical phenotypes. Harris platelet syndrome (HPS) is the most common IGPD reported from the Indian subcontinent. Of note there are an increased number of hemoglobinopathies reported from the geographic location. We analysed red blood cell and platelet indices of blood donors with HPS from the north eastern part of India and compared them with blood indices of blood donors of south India. We found a statistically significant lower platelet count in blood donors with HPS (median, range) 132 (71-267) vs. 252 (160-478) as compared to donors from south India (P < 0.001). Mean platelet volume (MPV) was higher in donors with HPS 13.1, (range 12-21.9 fl) as compared to donors from south India 7.35 (range 6-9.2 fl) (P < 0.001). This study showed that blood donors with HPS had a low median platelet bio-mass 0.17 (0.10-0.38%) vs. 0.19 (0.13-0.28%) in donors from south India. The platelet distribution width (PDW) was 17.4 (14.9-19.6) in donors with HPS vs. 16.38 (15.2-18.5) in south Indian blood donors (P < 0.001). Thirty-three donors with HPS had a normal platelet count with MPV more than 12 fL. Only donors with HPS had giant platelets and thrombocytopenia on peripheral blood smear examination. None of these donors had Dohle body inclusion in their leukocytes. Compared to donors from south India, donors with HPS had a significantly lower hemoglobin 13.8 (12-16.3 gm/dL) vs. 14.8 (12-18) respectively (P < 0.001) while red distribution width (RDW) was higher in HPS 13.6 (11.5-16.7) vs. 12.8 (11.4-15.1). However we did not find any statistically significant difference in MCV, MCH, MCHC between the two groups. Peripheral blood smear did not show any obvious abnormal red blood cell morphology. In the blood donors with HPS we found a statistically higher MPV

  9. Von Willebrand factor and angiogenesis: basic and applied issues.

    PubMed

    Randi, A M; Laffan, M A

    2017-01-01

    The recent discovery that von Willebrand factor (VWF) regulates blood vessel formation has opened a novel perspective on the function of this complex protein. VWF was discovered as a key component of hemostasis, capturing platelets at sites of endothelial damage and synthesized in megakaryocytes and endothelial cells (EC). In recent years, novel functions and binding partners have been identified for VWF. The finding that loss of VWF in EC results in enhanced, possibly dysfunctional, angiogenesis is consistent with the clinical observations that in some patients with von Willebrand disease (VWD), vascular malformations can cause severe gastrointestinal (GI) bleeding. In vitro and in vivo studies indicate that VWF can regulate angiogenesis through multiple pathways, both intracellular and extracellular, although their relative importance is still unclear. Investigation of these pathways has been greatly facilitated by the ability to isolate EC from progenitors circulating in the peripheral blood of normal controls and patients with VWD. In the next few years, these will yield further evidence on the molecular pathways controlled by VWF and shed light on this novel and fascinating area of vascular biology. In this article, we will review the evidence supporting a role for VWF in blood vessel formation, the link between VWF dysfunction and vascular malformations causing GI bleeding and how they may be causally related. Finally, we will discuss how these findings point to novel therapeutic approaches to bleeding refractory to VWF replacement therapy in VWD.

  10. von Willebrand disease: advances in pathogenetic understanding, diagnosis, and therapy.

    PubMed

    Lillicrap, David

    2013-01-01

    von Willebrand disease (VWD) is the most common autosomally inherited bleeding disorder. The disease represents a range of quantitative and qualitative pathologies of the adhesive glycoprotein von Willebrand factor (VWF). The pathogenic mechanisms responsible for the type 2 qualitative variants of VWF are now well characterized, with most mutations representing missense substitutions influencing VWF multimer structure and interactions with platelet GPIbα and collagen and with factor VIII. The molecular pathology of type 3 VWD has been similarly well characterized, with an array of different mutation types producing either a null phenotype or the production of VWF that is not secreted. In contrast, the pathogenetic mechanisms responsible for type 1 VWD remain only partially resolved. In the hemostasis laboratory, the measurement of VWF:Ag and VWF:RCo are key components in the diagnostic algorithm for VWD, although the introduction of direct GPIbα-binding assays may become the functional assay of choice. Molecular genetic testing can provide additional benefit, but its utility is currently limited to type 2 and 3 VWD. The treatment of bleeding in VWD involves the use of desmopressin and plasma-derived VWF concentrates and a variety of adjunctive agents. Finally, a new recombinant VWF concentrate has just completed clinical trial evaluation and has demonstrated excellent hemostatic efficacy and safety.

  11. Acquired von Willebrand syndrome in patients with Gaucher disease.

    PubMed

    Mitrovic, Mirjana; Elezovic, Ivo; Miljic, Predrag; Suvajdzic, Nada

    2014-04-01

    Although various coagulation abnormalities occur in patients with Gaucher disease (GD), von Willebrand factor (vWF) deficiency has rarely been reported. A retrospective review of six treatment naïve cases with GD and concomitant vWF deficiency over a 12-year-period in a single center is presented. All patients had a personal history of prior hemorrhages. Based on both reduced level of vWF antigen (vWF:Ag, range 14-56%) and ristocetin cofactor activity (vWF:RCo, range 12-53%), with a vWF:RCo/Ag ratio >0.7, the diagnosis of type 1 von Willebrand disease was made in all six cases. During enzyme replacement therapy (ERT) of a 2-year duration all patients normalized their vWF:Ag levels. Based on the positive ERT effect on vWF:Ag levels, vWF deficiency was assumed to be acquired. It should be noted that beside vWF deficiency four patients with GD exhibited mild thrombocytopenia (range 81-131×10(9)/L) and three had additional hemostatic defects (reduced collagen platelet aggregation, FV, FXI and FXII deficiencies).

  12. The Platelet Function Defect of Cardiopulmonary Bypass.

    DTIC Science & Technology

    1992-11-24

    fibrinolytic and coagulation systems occur during CPB,1 a platelet function defect is generally considered to be the primary CPB-induced hemostatic...platelets.39 OKM5 (provided by Dr. Patricia Rao, Ortho Diagnostic Systems , Raritan, NJ) is directed against platelet membrane GPIV.40 Flow Cytometric...22 after degranulation.7-14-16-18 Utilizing washed platelet systems , Nieuwenhuis et al.14 found a modest increase during CPB of the platelet

  13. In vitro and in vivo characterization of a high-purity, solvent/detergent-treated factor VIII concentrate: evidence for its therapeutic efficacy in von Willebrand's disease.

    PubMed

    Mazurier, C; De Romeuf, C; Parquet-Gernez, A; Goudemand, M

    1989-07-01

    A factor VIII (FVIII) concentrate, virus-inactivated by the solvent/detergent procedure, was studied in vitro. In contrast with most high-purity, virus-inactivated FVIII concentrates, it contains not only high levels of von Willebrand factor (vWF) antigen and ristocetin cofactor activity but also high molecular weight forms of von Willebrand factor. Furthermore, it is able to promote platelet adhesion on collagen in a perfusion system. In vivo studies performed in patients with different types of von Willebrand's disease provided evidence that this concentrate corrects Duke's bleeding time and prevents or stops haemorrhages. Thus, the particular advantages of this FVIII/vWF preparation are safety, low content of contamination proteins, and efficacy in von Willebrand's disease.

  14. Platelet-delivered ADAMTS13 inhibits arterial thrombosis and prevents thrombotic thrombocytopenic purpura in murine models.

    PubMed

    Pickens, Brandy; Mao, Yingying; Li, Dengju; Siegel, Don L; Poncz, Mortimer; Cines, Douglas B; Zheng, X Long

    2015-05-21

    ADAMTS13 metalloprotease cleaves von Willebrand factor (VWF), thereby inhibiting platelet aggregation and arterial thrombosis. An inability to cleave ultralarge VWF resulting from hereditary or acquired deficiency of plasma ADAMTS13 activity leads to a potentially fatal syndrome, thrombotic thrombocytopenic purpura (TTP). Plasma exchange is the most effective initial therapy for TTP to date. Here, we report characterization of transgenic mice expressing recombinant human ADAMTS13 (rADAMTS13) in platelets and its efficacy in inhibiting arterial thrombosis and preventing hereditary and acquired antibody-mediated TTP in murine models. Western blotting and fluorescent resonance energy transfer assay detect full-length rADAMTS13 protein and its proteolytic activity, respectively, in transgenic (Adamts13(-/-)Plt(A13)), but not in wild-type and Adamts13(-/-), platelets. The expressed rADAMTS13 is released on stimulation with thrombin and collagen, but less with 2MesADP. Platelet-delivered rADAMTS13 is able to inhibit arterial thrombosis after vascular injury and prevent the onset and progression of Shigatoxin-2 or recombinant murine VWF-induced TTP syndrome in mice despite a lack of plasma ADAMTS13 activity resulting from the ADAMTS13 gene deletion or the antibody-mediated inhibition of plasma ADAMTS13 activity. These findings provide a proof of concept that platelet-delivered ADAMTS13 may be explored as a novel treatment of arterial thrombotic disorders, including hereditary and acquired TTP, in the presence of anti-ADAMTS13 autoantibodies.

  15. Autologous platelet-labeling in thrombocytopenia

    SciTech Connect

    Sinzinger, H.; Virgolini, I.; Vinazzer, H. )

    1990-11-01

    Field studies performed with peripheral platelets obtained from 6 male volunteers aged 23 to 29 years revealed an extraordinary dependence of labeling efficiency on incubation time and platelet concentration after {sup 111}In-oxine platelet labeling. Since the monitoring of in vivo-platelet function in patients with thrombocytopenia may cause problems due to insufficient labeling results and homologous platelets may show a different in vivo behaviour to autologous ones, we have searched for the minimal amount of platelets necessary to allow appropriate labeling and imaging in patients with thrombocytopenia. In 15 patients with untreated thrombocytopenia aged 14 to 79 years demonstrating a mean peripheral platelet count of 2.509 +/- 1.45 x 10(4) cells/microliters autologous {sup 111}In-oxine platelet labeling was performed. The results indicate that approximately 1 x 10(8) (concentrated) platelets/ml are necessary to obtain an adequate labeling efficiency and recovery. This platelet concentration can be easily achieved by drawing one more Monovette of whole blood per each 5 x 10(4) platelets/microliter peripheral platelet count less than 2 x 10(5)/microliter. It is concluded, that calculation of the required number of platelets in advance, variation of the blood volume drawn and the volume of incubation buffer allow informative, qualitative and quantitative results using autologous platelets. The method presented effectively circumvents the requirement of homologous platelets for radiolabeling in thrombocytopenia.

  16. Submonolayer growth with decorated island edges

    NASA Astrophysics Data System (ADS)

    Kotrla, Miroslav; Krug, Joachim; Šmilauer, Pavel

    2000-05-01

    We study the dynamics of island nucleation in the presence of adsorbates using kinetic Monte Carlo simulations of a two-species growth model. Adatoms (A atoms) and impurities (B atoms) are codeposited, diffuse and aggregate subject to attractive AA and AB interactions. Activated exchange of adatoms with impurities is identified as the key process to maintain decoration of island edges by impurities during growth. While the presence of impurities strongly increases the island density, a change in the scaling of island density with flux, predicted by a rate equation theory for attachment-limited growth [D. Kandel, Phys. Rev. Lett. 78 (1997) 499], is not observed. We argue that, within the present model, even completely covered island edges do not provide efficient barriers to attachment.

  17. Von Hippel-Lindau Disease

    MedlinePlus

    Von Hippel-Lindau disease (VHL) is a rare, genetic disease that causes tumors and cysts to grow in your body. The tumors can be either ... and, in men, their genital tract. Symptoms of VHL vary and depend on the size and location ...

  18. Platelet serotonin modulates immune functions.

    PubMed

    Mauler, M; Bode, C; Duerschmied, D

    2016-01-01

    This short review addresses immune functions of platelet serotonin. Platelets transport serotonin at a high concentration in dense granules and release it upon activation. Besides haemostatic, vasotonic and developmental modulation, serotonin also influences a variety of immune functions (mediated by different serotonin receptors). First, platelet serotonergic effects are directed against invading pathogens via activation and proliferation of lymphocytes, modulation of cytokine release, and recruitment of neutrophils to sites of acute inflammation by induction of selectin expression on endothelial cells. Second, serotonin levels are elevated in autoimmune diseases, such as asthma or rheumatoid arthritis, and during tissue regeneration after ischemia of myocardium or brain. Specific antagonism of serotonin receptors appears to improve survival after myocardial infarction or sepsis and to attenuate asthmatic attacks in animal models. It will be of great clinical relevance if these findings can be translated into human applications. In conclusion, targeting immune modulatory effects of platelet serotonin may provide novel therapeutic options for common health problems.

  19. Complement Activation Alters Platelet Function

    DTIC Science & Technology

    2014-10-01

    Negative T cells than B6.lpr mice. This suggests that the absence of PF4 alleviates some tissue damage in the lupus prone mice. 6...mice with PF4-/- mice may alleviate multi organ dysfunction in Lupus prone mice. Reportable Outcomes Nothing to report Conclusions We have...dysfunction in lupus models. We have evaluated the relationship between Syk and platelets and have thus far identified a role for Syk in platelet lodging in

  20. Current controversies in the diagnosis and management of von Willebrand disease

    PubMed Central

    2015-01-01

    Von Willebrand disease (VWD) is the most common inherited bleeding disorder in the world. The spectrum of VWD spans quantitative and qualitative deficiencies of von Willebrand factor (VWF), a platelet adhesive protein. It manifests primarily as mucocutaneous bleeding, but severely affected patients may suffer soft tissue bleeding and hemarthroses. There is disagreement in the multiple guidelines published regarding diagnosis, especially of type 1 VWD, which also remains the most opaque with respect to molecular characterization. Treatment with desmopressin (DDAVP) is most effective in type 1 VWD, but regimens are not standardized. It is not clear which type 2 VWD patients with qualitative deficiencies can be treated with DDAVP and which ones should receive VWF concentrates. No guidelines stipulate which patients might benefit from prophylactic VWF infusions and how they should be dosed. These are some current controversies in VWD that are discussed in this review. PMID:26288715

  1. Von Willebrand Factor Abnormalities Studied in the Mouse Model: What We Learned about VWF Functions

    PubMed Central

    Casari, Caterina; Lenting, Peter J.; Christophe, Olivier D.; Denis, Cécile V.

    2013-01-01

    Up until recently, von Willebrand Factor (VWF) structure-function relationships have only been studied through in vitro approaches. A powerful technique known as hydrodynamic gene transfer, which allows transient expression of a transgene by mouse hepatocytes, has led to an important shift in VWF research. Indeed this approach has now enabled us to transiently express a number of VWF mutants in VWF-deficient mice in order to test the relative importance of specific residues in different aspects of VWF biology and functions in an in vivo setting. As a result, mice reproducing various types of von Willebrand disease have been generated, models that will be useful to test new therapies. This approach also allowed a more precise identification of the importance of VWF interaction with subendothelial collagens and with platelets receptors in hemostasis and thrombosis. The recent advances gathered from these studies as well as the pros and cons of the technique will be reviewed here. PMID:23936618

  2. Von Willebrand disease - the 'Dos' and 'Don'ts' in surgery.

    PubMed

    Miesbach, Wolfgang; Berntorp, Erik

    2017-02-01

    Von Willebrand disease (VWD) is the most common genetic bleeding disorder. VWD is caused by a deficiency or dysfunction of von Willebrand factor (VWF), a plasma protein that mediates the initial adhesion of platelets at sites of vascular injury and binds and stabilises coagulation factor VIII (FVIII) in the blood. Prophylaxis of surgical bleeding in patients with VWD requires consideration of the individual situation, including the type of procedure and the bleeding rate, before decisions about treatment type, dose, duration and adjunctive therapy with antifibrinolytics or antithrombotic prophylaxis can be made. Although desmopressin (DDAVP)-stimulated release of endogenous VWD is an effective treatment strategy in many patients, plasma concentrates containing VWF are the preferred option for most patients undergoing surgical procedures. Recommendations for the management of surgery in patients with VWD are summarised, including the severity of VWD and the type of the surgical procedure.

  3. Future innovations in anti-platelet therapies

    PubMed Central

    Barrett, N E; Holbrook, L; Jones, S; Kaiser, W J; Moraes, L A; Rana, R; Sage, T; Stanley, R G; Tucker, K L; Wright, B; Gibbins, J M

    2008-01-01

    Platelets have long been recognized to be of central importance in haemostasis, but their participation in pathological conditions such as thrombosis, atherosclerosis and inflammation is now also well established. The platelet has therefore become a key target in therapies to combat cardiovascular disease. Anti-platelet therapies are used widely, but current approaches lack efficacy in a proportion of patients, and are associated with side effects including problem bleeding. In the last decade, substantial progress has been made in understanding the regulation of platelet function, including the characterization of new ligands, platelet-specific receptors and cell signalling pathways. It is anticipated this progress will impact positively on the future innovations towards more effective and safer anti-platelet agents. In this review, the mechanisms of platelet regulation and current anti-platelet therapies are introduced, and strong, and some more speculative, potential candidate target molecules for future anti-platelet drug development are discussed. PMID:18587441

  4. Detail view of the terracotta antefixes that decorate the roof ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail view of the terra-cotta antefixes that decorate the roof of the Justice Department Building - United States Department of Justice, Constitution Avenue between Ninth & Tenth Streets, Northwest, Washington, District of Columbia, DC

  5. 9. BASRELIEF DECORATION, 'DEFENSE', MURAL COMMEMORATING THE DEFENSE OF FORT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. BAS-RELIEF DECORATION, 'DEFENSE', MURAL COMMEMORATING THE DEFENSE OF FORT DEARBORN - Chicago River Bascule Bridge, Michigan Avenue, Spanning Chicago River at North Michigan Avenue, Chicago, Cook County, IL

  6. 11. Detail, southeast corner, showing decorative elements of main structure, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. Detail, southeast corner, showing decorative elements of main structure, and window at the second story of the hose tower. - Independent Hose Company No. 3, Nineteenth & Belmont Streets, Bellaire, Belmont County, OH

  7. DETAIL VIEW OF END OF TRUSS SHOWING CONNECTION OF DECORATIVE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL VIEW OF END OF TRUSS SHOWING CONNECTION OF DECORATIVE "KNEE", RAILING ENDPOST AND UPPER AND LOWER CHORDS - Scarlets Mill Bridge, Spanning former Reading Railroad, Scarlets Mill, Berks County, PA

  8. DETAIL OF FRONT ENTRY. SHOWING THE KNEE BRACES AND DECORATIVE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL OF FRONT ENTRY. SHOWING THE KNEE BRACES AND DECORATIVE CUT RAFTER TAILS. VIEW FACING EAST. - Hickam Field, Fort Kamehameha Officers' Housing Type Z, 19 Worchester Avenue, Honolulu, Honolulu County, HI

  9. Detail of front west entry showing telescoping pilasters and decorative ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of front west entry showing telescoping pilasters and decorative crawl space vents, facing east. - Albrook Air Force Station, Dispensary, East side of Canfield Avenue, Balboa, Former Panama Canal Zone, CZ

  10. Perspective view of the front elevation (note: decorative details such ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Perspective view of the front elevation (note: decorative details such as the brackets underpinning the deep cornice on the porch and house) - Philip T. Berry House, 1402 Thirty-first Street, Northwest, Washington, District of Columbia, DC

  11. 13. INTERIOR, SHOWING DECORATION AT THE ALTAR FOR THE REPOSE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. INTERIOR, SHOWING DECORATION AT THE ALTAR FOR THE REPOSE OF THE SOUL OF DON ALFONSO XII, KING OF SPAIN (photograph, Jan. 20, 1886) - Our Lady of Peace Cathedral, 1183 Fort Street, Honolulu, Honolulu County, HI

  12. 72. 451 MADISON AVENUE, GRAND STAIR, ZODIAC CLOCK WITH DECORATIVE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    72. 451 MADISON AVENUE, GRAND STAIR, ZODIAC CLOCK WITH DECORATIVE CARVING BY STANFORD WHITE AND AUGUSTUS SAINT-GAUDENS - Villard Houses, 451-457 Madison Avenue & 24 East Fifty-first Street, New York County, NY

  13. 9. DETAIL OF DECORATIVE MORTAR AND COBBLESTONE WORK ON TYPICAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. DETAIL OF DECORATIVE MORTAR AND COBBLESTONE WORK ON TYPICAL POST ON UPSTREAM PARAPET WALL OF UPPER EMBANKMENT. VIEW TO SOUTH. - Boise Project, Deer Flat Embankments, Lake Lowell, Nampa, Canyon County, ID

  14. ZnO nanorods decorated with ZnS nanoparticles

    SciTech Connect

    Joicy, S.; Sivakumar, P.; Thangadurai, P.; Ponpandian, N.

    2015-06-24

    In this study, ZnO nanorods (NRs) and ZnS nanoparticles decorated ZnO-NRs were prepared by a combination of hydrothermal and hydrolysis method. Structural and optical properties of the samples were studied by XRD, FE-SEM, UV-Vis DRS and photoluminescence spectroscopy. Microscopy analysis revealed that the diameter of ZnO-NRs was ∼500 nm and the length was ranging from a few hundred nm to several micrometers and their surface was decorated with ZnS nanoparticles. UV-Vis DRS showed the absorption of ZnS decorated ZnO-NRs was blue shifted with respect to pure ZnO-NRs which enhanced the separation of electron-hole pairs. PL spectrum of ZnS decorated ZnO-NRs showed a decrease in intensity of UV and green emissions with the appearance of blue emission at 436 nm.

  15. 11. DETAIL OF TERRACOTTA DECORATION, SHOWING SCROLL CONSOLE, WAVE ORNAMENT, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. DETAIL OF TERRACOTTA DECORATION, SHOWING SCROLL CONSOLE, WAVE ORNAMENT, EGG-AND-DART, NYMPH HEADS AND FOLIATE PATTERN AROUND WINDOWS - City Hall, Atlantic & Tennessee Avenues, Atlantic City, Atlantic County, NJ

  16. Detail of decorative panel featuring a monkey at Ten Mile ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of decorative panel featuring a monkey at Ten Mile River Playground comfort station, looking northwest. - Henry Hudson Parkway, Extending 11.2 miles from West 72nd Street to Bronx-Westchester border, New York County, NY

  17. 'Colored' and Decorative Contact Lenses: A Prescription Is a Must

    MedlinePlus

    ... Home For Consumers Consumer Updates 'Colored' and Decorative Contact Lenses: A Prescription Is A Must Share Tweet ... care.” back to top Where NOT to Buy Contact Lenses FDA is aware that many places illegally ...

  18. 13. Credit JTL: Detail, orthogonal view of Egyptian Revivial decorative ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. Credit JTL: Detail, orthogonal view of Egyptian Revivial decorative motifs used typically at midpoints of diagonals - Reading-Halls Station Bridge, U.S. Route 220, spanning railroad near Halls Station, Muncy, Lycoming County, PA

  19. 14. Credit JTL: Detail, oblique view of Egyptian Revival decorative ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Credit JTL: Detail, oblique view of Egyptian Revival decorative motifs used typically at midpoints of diagonals - Reading-Halls Station Bridge, U.S. Route 220, spanning railroad near Halls Station, Muncy, Lycoming County, PA

  20. 3. INTERIOR, FIRST FLOOR, VIEW OF LIGHT SHAFT SHOWING DECORATIVE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. INTERIOR, FIRST FLOOR, VIEW OF LIGHT SHAFT SHOWING DECORATIVE TRIM AROUND OPENING, VIEW FROM SOUTHWEST LOOKING UP. - 629 D Street Northwest (Commercial Building), Square 457, Washington, District of Columbia, DC

  1. DETAIL OF FRONT ENTRY. SHOWING KNEE BRACES AND DECORATIVE CUT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL OF FRONT ENTRY. SHOWING KNEE BRACES AND DECORATIVE CUT RAFTERS. PILASTERS, AND LAVA ROCK CHEEK CHEEK WALLS. VIEW FACING NORTH. - Hickam Field, Fort Kamehameha Officers' Housing Type Y, 27 Worchester Avenue, Honolulu, Honolulu County, HI

  2. INTERIOR VIEW OF THE DINING AREA, FACING EAST. THE DECORATIVE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    INTERIOR VIEW OF THE DINING AREA, FACING EAST. THE DECORATIVE DESIGN OF THE OVERHEAD BEAMS AND COLUMNS ARE FROM THE ORIGINAL CONSTRUCTION. - U.S. Naval Base, Pearl Harbor, Bachelor Officer Quarters, Dealy Circle, Pearl City, Honolulu County, HI

  3. Transport properties of zigzag graphene nanoribbon decorated with copper clusters

    SciTech Connect

    Berahman, M.; Sheikhi, M. H.

    2014-09-07

    Using non-equilibrium green function with density functional theory, the present study investigates the transport properties of decorated zigzag graphene nanoribbon with a copper cluster. We have represented the decoration of zigzag graphene nanoribbon with single copper atom and cluster containing two and three copper atoms. In all the cases, copper atoms tend to occupy the edge state. In addition, we have shown that copper can alter the current-voltage characteristic of zigzag graphene nanoribbon and create new fluctuations and negative differential resistance. These alternations are made due to discontinuity in the combination of orbitals along the graphene nanoribbon. Decoration alters these discontinuities and creates more visible fluctuations. However, in low bias voltages, the changes are similar in all the cases. The study demonstrates that in the decorated zigzag graphene nanoribbon, the edge states are the main states for transporting electron from one electrode to another.

  4. 4. Photocopy of photograph, date unknown DETAIL, DECORATIVE SWAG OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Photocopy of photograph, date unknown DETAIL, DECORATIVE SWAG OF EARS OF CORN - Thomas Asylum for Orphan & Destitute Indians, Dining Hall, Route 438, Cattaraugas Reservation, Irving, Chautauqua County, NY

  5. Stable parabolic Higgs bundles as asymptotically stable decorated swamps

    NASA Astrophysics Data System (ADS)

    Beck, Nikolai

    2016-06-01

    Parabolic Higgs bundles can be described in terms of decorated swamps, which we studied in a recent paper. This description induces a notion of stability of parabolic Higgs bundles depending on a parameter, and we construct their moduli space inside the moduli space of decorated swamps. We then introduce asymptotic stability of decorated swamps in order to study the behaviour of the stability condition as one parameter approaches infinity. The main result is the existence of a constant, such that stability with respect to parameters greater than this constant is equivalent to asymptotic stability. This implies boundedness of all decorated swamps which are semistable with respect to some parameter. Finally, we recover the usual stability condition of parabolic Higgs bundles as asymptotic stability.

  6. Antidote-controlled antithrombotic therapy targeting factor IXa and von Willebrand factor.

    PubMed

    Becker, Richard C; Oney, Sabah; Becker, Kristian C D; Sullenger, Bruce

    2009-09-01

    Thrombotic disorders and their common clinical phenotypes of acute myocardial infarction, ischemic stroke, and venous thromboembolism are the proximate cause of substantial morbidity, mortality, and health care expenditures worldwide. Accordingly, therapies designed to attenuate thrombus initiation and propagation, reflecting integrated platelet-mediated and coagulation protease-mediated events, respectively, represent a standard of care. Unfortunately, there are numerous inherent limitations of existing therapies that include target nonselectivity, variable onset and offset of pharmacodynamic effects, a narrow efficacy-safety profile, and the absence of a safe and reliable platform for either accurate titration, based on existing patient-specific, disease-specific, and clinical conditions, or active reversibility. Herein, we summarize our experience with oligonucleotide antithrombotic agents and their complementary antidotes, targeting the platelet adhesive protein von Willebrand factor and the pivotal coagulation protease factor IXa.

  7. Activity concentrations and dose rates from decorative granite countertops.

    PubMed

    Llope, W J

    2011-06-01

    The gamma radiation emitted from a variety of commercial decorative granites available for use in U.S. homes has been measured with portable survey meters as well as an NaI(Th) gamma spectrometer. The (40)K, U-nat, and (232)Th activity concentrations were determined using a full-spectrum analysis. The dose rates that would result from two different arrangements of decorative granite slabs as countertops were explored in simulations involving an adult anthropomorphic phantom.

  8. [Was Klaus von Mantrei the teacher of Hans von Gersdorff?].

    PubMed

    Vollmuth, R

    1996-01-01

    One of the most popular representatives of surgery at the end of the middle ages and the beginning modern era is the Strassburgian surgeon Hans von Gersdorff. Still we do not know very much about his life and his surgical teachers. Only one meister Nicklaus, called Mulartzt, is mentioned as such by the remarks in Gersdorffs 'Feldbuch der Wundarznei', but till today this surgeon could not be identified in more detail. This article now holds the thesis, that meister Nicklaus is probably identical with Klaus von Matrei (Metry), a well-known surgeon of the late 15th century. That cannot be fully proved yet, but a number of coinciding characteristics between the two and some further indications, that are explained, seem so significant, that the thesis can hardly be doubted.

  9. Unraveling mechanisms that control platelet production.

    PubMed

    Italiano, Joseph E

    2013-02-01

    Platelets are formed by giant precursor cells called megakaryocytes that reside within the bone marrow. The generation of platelets, and their release into the bloodstream by megakaryocytes, requires a complex series of remodeling events powered by the cytoskeleton to result in the release of many platelets from a single megakaryocyte. Abnormalities in this process can result in thrombocytopenia (low platelet count) and can lead to increased risk of bleeding. This review describes the process of platelet production in detail and discusses new insights into novel platelet biology.

  10. Detection of platelet alloimmunity with a platelet-associated IgG assay

    SciTech Connect

    Myers, T.J.; Kim, B.K.; Steiner, M.; Bishop, J.; Baldini, M.G.

    1981-06-01

    A quantitative immunofluorescence PA-IgG assay was used to detect alloimmunity to platelets. The assay identified serum alloantibodies in 10 out of 14 multitransfused patients and for two of three infants with neonatal thrombocytopenia. The correct separation of all multitransfused patients into alloimmune and nonalloimmune groups by the PA-IgG assay was substantiated with chromium-51-labeled platelet survival studies. The allogeneic nature of the serum antibodies was demonstrated by progressive absorption of the antibody with increasing numbers of allogeneic platelets but not with autologous platelets. The sensitivity of the PA-IgG assay for detection of serum alloantibodies was superior to that of platelet aggregation, platelet serotonin release, and lymphocytotoxicity testing. In dilution experiments with alloimmune serum, elevated levels of serum PA-IgG could still be detected on donor platelets when platelet aggregation and serotonin release tests became negative. Platelet survival studies with selected platelets performed in the 10 alloimmunized, multitransfused patients confirmed the results of the PA-IgG assays, predicting alloimmunity to the donor platelets. In contrast, platelet aggregation, platelet serotonin release, and lymphocytotoxicity testing indicated alloimmunity for 50% or less of the patients. Reduced platelet survival times were also seen with HLA A- and HLA B-matched donor platelets when donor-recipient incompatibility was demonstrated by the PA-IgG assay. Thus the PA-IgG assay provides a sensitive method to detect serum platelet alloantibodies and may offer a technique in platelet crossmatching.

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

    PubMed

    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.

  12. LIM kinase/cofilin dysregulation promotes macrothrombocytopenia in severe von Willebrand disease-type 2B

    PubMed Central

    Poirault-Chassac, Sonia; Adam, Frédéric; Muczynski, Vincent; Aymé, Gabriel; Casari, Caterina; Bordet, Jean-Claude; Soukaseum, Christelle; Rothschild, Chantal; Proulle, Valérie; Pietrzyk-Nivau, Audrey; Berrou, Eliane; Christophe, Olivier D.; Rosa, Jean-Philippe; Lenting, Peter J.; Bryckaert, Marijke; Baruch, Dominique

    2016-01-01

    von Willebrand disease type 2B (VWD-type 2B) is characterized by gain-of-function mutations of von Willebrand factor (vWF) that enhance its binding to platelet glycoprotein Ibα and alter the protein’s multimeric structure. Patients with VWD-type 2B display variable extents of bleeding associated with macrothrombocytopenia and sometimes with thrombopathy. Here, we addressed the molecular mechanism underlying the severe macrothrombocytopenia both in a knockin murine model for VWD-type 2B by introducing the p.V1316M mutation in the murine Vwf gene and in a patient bearing this mutation. We provide evidence of a profound defect in megakaryocyte (MK) function since: (a) the extent of proplatelet formation was drastically decreased in 2B MKs, with thick proplatelet extensions and large swellings; and (b) 2B MKs presented actin disorganization that was controlled by upregulation of the RhoA/LIM kinase (LIMK)/cofilin pathway. In vitro and in vivo inhibition of the LIMK/cofilin signaling pathway rescued actin turnover and restored normal proplatelet formation, platelet count, and platelet size. These data indicate, to our knowledge for the first time, that the severe macrothrombocytopenia in VWD-type 2B p.V1316M is due to an MK dysfunction that originates from a constitutive activation of the RhoA/LIMK/cofilin pathway and actin disorganization. This suggests a potentially new function of vWF during platelet formation that involves regulation of actin dynamics. PMID:27734030

  13. Adherence of platelets to in situ albumin-binding surfaces under flow conditions: role of surface-adsorbed albumin.

    PubMed

    Guha Thakurta, Sanjukta; Miller, Robert; Subramanian, Anuradha

    2012-08-01

    Surfaces that preferentially bind human serum albumin (HSA) were generated by grafting albumin-binding linear peptide (LP1) onto silicon surfaces. The research aim was to evaluate the adsorption pattern of proteins and the adhesion of platelets from platelet-poor plasma and platelet-rich plasma, respectively, by albumin-binding surfaces under physiological shear rate (96 and 319 s(-1)) conditions. Bound proteins were quantified using enzyme-linked immunosorbent assays (ELISAs) and two-dimensional gel electrophoresis. A ratio of ∼1000:100:1 of adsorbed HSA, human immunoglobulin (HIgG) and human fibrinogen (HFib) was noted, respectively, on LP1-functionalized surfaces, and a ratio of ∼5:2:1 of the same was noted on control surfaces, as confirmed by ELISAs. The surface-adsorbed von Willebrand factor was undetectable by sensitive ELISAs. The amount of adhered platelets correlated with the ratio of adsorbed HSA/HFib. Platelet morphology was more rounded on LP1-functionalized surfaces when compared to control surfaces. The platelet adhesion response on albumin-binding surfaces can be explained by the reduction in the co-adsorption of other plasma proteins in a surface environment where there is an excess of albumin molecules, coupled with restrictions in the conformational transitions of other surface-adsorbed proteins into hemostatically active forms.

  14. The Functions of the A1A2A3 Domains in Von Willebrand Factor Include Multimerin 1 Binding

    PubMed Central

    Parker, D’Andra N.; Tasneem, Subia; Farndale, Richard W.; Bihan, Dominique; Sadler, J. Evan; Sebastian, Silvie; De Groot, Philip G.

    2016-01-01

    Summary Multimerin 1 (MMRN1) is a massive, homopolymeric protein that is stored in platelets and endothelial cells for activation-induced release. In vitro, MMRN1 binds to the outer surfaces of activated platelets and endothelial cells, the extracellular matrix (including collagen) and von Willebrand factor (VWF) to support platelet adhesive functions. VWF associates with MMRN1 at high shear, not static conditions, suggesting that shear exposes cryptic sites within VWF that support MMRN1 binding. Modified ELISA and surface plasmon resonance were used to study the structural features of VWF that support MMRN1 binding, and determine the affinities for VWF-MMRN1 binding. High shear microfluidic platelet adhesion assays determined the functional consequences for VWF-MMRN1 binding. VWF binding to MMRN1 was enhanced by shear exposure and ristocetin, and required VWF A1A2A3 region, specifically the A1 and A3 domains. VWF A1A2A3 bound to MMRN1 with a physiologically relevant binding affinity (KD: 2.0 ± 0.4 nM), whereas the individual VWF A1 (KD: 39.3 ± 7.7 nM) and A3 domains (KD: 229 ± 114 nM) bound to MMRN1 with lower affinities. VWF A1A2A3 was also sufficient to support the adhesion of resting platelets to MMRN1 at high shear, by a mechanism dependent on VWF-GPIbα binding. Our study provides new information on the molecular basis of MMRN1 binding to VWF, and its role in supporting platelet adhesion at high shear. We propose that at sites of vessel injury, MMRN1 that is released following activation of platelets and endothelial cells, binds to VWF A1A2A3 region to support platelet adhesion at arterial shear rates. PMID:27052467

  15. Dynamic light scattering can determine platelet function

    NASA Astrophysics Data System (ADS)

    Lee, Nathan

    2011-10-01

    Platelet transfusions are life-saving procedures for patients who are bleeding or undergoing chemotherapy. The effectiveness of transfusions depends on the number of platelets transfused and the platelet function. Platelet function correlates with proportion of discoid to activated platelets, morphology response to temperature stress, and inversely correlates with microparticle content. ThromboLUX is a novel device that determines platelet function by measuring all of these characteristics using dynamic light scattering (DLS). During periods of stress, such as decreased temperature, cytoskeletal rearrangements will cause normal, discoid platelets to activate and become spiny spheres. The formation of pseudopods of various lengths facilitates the clotting cascade and also increases the apparent size of platelets. ThromboLUX uses a 37-20-37 C temperature cycle that mimics the bleeding, storage, and transfusion process. As the temperature fluctuates, DLS will measure the changing platelet hydrodynamic radius and the size of any microparticles present. ThromboLUX analysis of platelet concentrates in vitro would allow determination of high platelet function units before transfusion and would therefore improve transfusion outcomes and patient safety. This study examined how DLS is able to distinguish between discoid and activated platelets as well as measure the parameters that contribute to high platelet function.

  16. Relationships between platelet counts, platelet volumes and reticulated platelets in patients with ITP: evidence for significant platelet count inaccuracies with conventional instrument methods.

    PubMed

    Diquattro, M; Gagliano, F; Calabrò, G M; Tommasi, M; Scott, C S; Mancuso, G; Palma, B; Menozzi, I

    2009-04-01

    The platelet count has a primary role in the diagnosis and treatment of idiopathic thrombocytopenic purpura (ITP). This study analysed the accuracy of ITP patient platelet counts determined by Abbott CD-Sapphire (impedance/optical) and Bayer Advia 120 (optical) analyses, compared with a reference immunoplatelet method. Instrument platelet estimates showed broad equivalence in the higher range of observed values, but significant discrepancies against the immunoplatelet count were seen when platelet counts were <10 x 10(9)/l. CD-Sapphire mean platelet volume (MPV) results revealed increased (>12 fl) platelet volumes in eight of eight ITP patients with counts of <20 x 10(9)/l compared with 6/6 and 5/13 patients with platelet counts of 20-50 and >50 x 10(9)/l. In contrast, Bayer Advia MPV values showed no relationship with the platelet count. Increased reticulated platelets were associated with an increasing CD-Sapphire MPV (R(2) = 0.61) and a decreasing platelet count. High (>40%) reticulated platelet values were seen in 9/9 patients with immunoplatelet counts of <20 x 10(9)/l compared with 0/19 patients with platelet counts above 20 x 10(9)/l. There may be a need for caution in the interpretation of platelet counts in ITP patients obtained with conventional instrument methods, and therapeutic decisions should ideally be validated by reference immunoplatelet procedures.

  17. Platelet function tests: a comparative review.

    PubMed

    Paniccia, Rita; Priora, Raffaella; Liotta, Agatina Alessandrello; Abbate, Rosanna

    2015-01-01

    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-tried and innovative platelet function tests and their methodological features and clinical applications are considered.

  18. Platelet function tests: a comparative review

    PubMed Central

    Paniccia, Rita; Priora, Raffaella; Alessandrello Liotta, Agatina; Abbate, Rosanna

    2015-01-01

    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-tried and innovative platelet function tests and their methodological features and clinical applications are considered. PMID:25733843

  19. Homozygous Pro74-->Arg mutation in the platelet glycoprotein Ibbeta gene associated with Bernard-Soulier syndrome.

    PubMed

    Kunishima, S; Tomiyama, Y; Honda, S; Fukunishi, M; Hara, J; Inoue, C; Kamiya, T; Saito, H

    2000-07-01

    Bernard-Soulier syndrome (BSS) is an autosomal recessive bleeding disorder due to quantitative or qualitative abnormalities in the glycoprotein (GP) Ib/IX/V complex, the platelet receptor for von Willebrand factor. This complex is composed of four subunits, GPIbalpha, GPIbbeta, GPIX and GPV. We describe here the genetic basis of the disorder in a patient with BSS. Flow cytometric analysis of the patient's platelets showed greatly reduced GPIbalpha and GPIX surface expression. Immunoblot analysis disclosed absence of GPIbalpha, GPIbbeta and GPIX in the platelets. DNA sequencing analysis revealed a novel missense mutation in the GPIbbeta gene that converts Pro (CCG) to Arg (CGG) at residue 74. Homozygosity of the mutation was confirmed by allele-specific restriction analysis, chromosome 22 microsatellite analysis and quantitative Southern blotting. The mutant GPIbbeta was normally transcribed. Transient transfection studies confirmed that mutant GPIbbeta impairs surface expression of GPIb/IX, showing that the mutation is responsible for a BSS phenotype observed in the patient.

  20. Thrombotic thrombocytopenic purpura: from platelet aggregates to plasma.

    PubMed

    Marques, Marisa B; Mayfield, Charles A; Blackall, Douglas P

    2004-06-01

    Thrombotic thrombocytopenic purpura (TTP) is a syndrome of severe thrombocytopenia and microangiopathic hemolytic anemia without an alternative explanation. Although some patients also have a combination of fever and neurologic and/or renal manifestations, these are not required for the diagnosis. Thus, plasmapheresis should start as soon as TTP is placed high in the differential diagnosis to prevent significant mortality. Histopathologically, TTP is characterized by widespread platelet thrombi in the microcirculation. Ultralarge von Willebrand factor (vWf) multimers found in the patient's plasma are the basis for the platelet thrombi. Recent evidence has linked the abnormal fragments of vWf with deficiency of a plasma enzyme named vWf-cleaving protease, or ADAMTS-13. While a small percentage of patients with TTP have a constitutional defect in this enzyme, many with the acute idiopathic form have an antibody to ADAMTS-13, affecting its ability to cleave vWf. The determination of the enzyme activity and the presence of its inhibitor have emerged as a potential tool in the diagnosis and prognosis of TTP. Furthermore, it helps to differentiate TTP from the hemolytic uremic syndrome, in which the level of ADAMTS-13 is expected to be normal or only slightly decreased.

  1. Treatment of von Willebrand Disease.

    PubMed

    Curnow, Jennifer; Pasalic, Leonardo; Favaloro, Emmanuel J

    2016-03-01

    Congenital von Willebrand disease (VWD) and acquired von Willebrand syndrome (AVWS) reflect conditions caused by von Willebrand factor (VWF) deficiency and/or defects. VWD is the most common inherited bleeding disorder and AVWS arises from a variety of causes. Since VWF stabilizes and protects factor VIII (FVIII) in the circulation, this is also reduced in many patients with VWD. The treatment of VWD and AVWS therefore primarily entails replacement of VWF, and sometimes FVIII, to protect against bleeding. This may entail the use of VWF concentrates (currently plasma-derived) and/or FVIII concentrates (currently plasma-derived or more increasingly recombinant forms), and/or desmopressin to release endogenous VWF in subgroups of patients. For AVWS additional treatment of the underlying condition is also required. Adjunct therapies include antifibrinolytics. Globally, various formulations exist for both VWF and FVIII concentrates and are differentially available based on manufacturer marketing or regulatory approvals/clearances in different geographies. Also, guidelines for treatment of VWD vary for different localities and recombinant VWF is undergoing clinical trials. The current review provides an overview of the treatment of VWD as currently practiced in developed countries, and also provides a glimpse towards the future.

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

    PubMed Central

    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

  3. Current status of additive solutions for platelets.

    PubMed

    Alhumaidan, Hiba; Sweeney, Joseph

    2012-01-01

    The storage of platelets in additive solution (PAS) had lagged behind red cell concentrates, especially in North America. The partial or complete removal of anticoagulated plasma and storage of platelet concentrates in AS presents many advantages. The PAS can be formulated to optimize aerobic metabolism or decrease platelet activation, thus abrogating the platelet storage lesion and potentially improving in vivo viability. Plasma removal has been shown to reduce allergic reactions and the plasma harvested could contribute to the available plasma pool for transfusion or fractionation. PAS coupled to pathogen reduction technology results in a platelet product of equivalent hemostatic efficacy to conventionally stored platelets. Given the above, the likely future direction of platelet storage will be in new generation designer PAS with an extended shelf life and a superior safety profile to plasma stored platelets. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc.

  4. Effect of photodynamic therapy on mouse platelets

    NASA Astrophysics Data System (ADS)

    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.

  5. Dr. von Braun Briefing Walt Disney

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Dr. von Braun began his association with Walt Disney in the 1950s when the rocket scientist appeared in three Disney television productions related to the exploration of space. Years later, Dr. von Braun invited Disney and his associates to tour the Marshall Space Flight Center (MSFC) in Huntsville, Alabama. This photograph is dated April 13, 1965. From left are R.J. Schwinghamer from the MSFC, Disney, B.J. Bernight, and Dr. von Braun.

  6. Probing platelet factor 4 alpha-granule targeting.

    PubMed

    Briquet-Laugier, V; Lavenu-Bombled, C; Schmitt, A; Leboeuf, M; Uzan, G; Dubart-Kupperschmitt, A; Rosa, J-P

    2004-12-01

    The storage mechanism of endogenous secretory proteins in megakaryocyte alpha-granules is poorly understood. We have elected to study the granule storage of platelet factor 4 (PF4), a well-known platelet alpha-granule protein. The reporter protein green fluorescent protein (GFP), PF4, or PF4 fused to GFP (PF4-GFP), were transfected in the well-characterized mouse pituitary AtT20 cell line, and in the megakaryocytic leukemic DAMI cell line. These proteins were also transduced using a lentiviral vector, in human CD34+ cells differentiated into megakaryocytes in vitro. Intracellular localization of expressed proteins, and colocalization studies were achieved by laser scanning confocal microscopy and immuno-electronmicroscopy. In preliminary experiments, GFP, a non-secretory protein (no signal peptide), localized in the cytoplasm, while PF4-GFP colocalized with adrenocorticotropin hormone (ACTH)-containing granules in AtT20 cells. In the megakaryocytic DAMI cell line and in human megakaryocytes differentiated in vitro, PF4-GFP localized in alpha-granules along with the alpha granular protein von Willebrand factor (VWF). The signal peptide of PF4 was not sufficient to specify alpha-granule storage of PF4, since when PF4 signal peptide was fused to GFP (SP4-GFP), GFP was not stored into granules in spite of its efficient translocation to the ER-Golgi constitutive secretory pathway. We conclude that the PF4 storage pathway in alpha-granules is not a default pathway, but rather a regular granule storage pathway probably requiring specific sorting mechanisms. In addition PF4-GFP appears as an appropriate probe with which to analyze alpha-granule biogenesis and its alterations in the congenital defect gray platelet syndrome.

  7. Ultra-small Palladium Nanoparticle Decorated Carbon Nanotubes: Conductivity and Reactivity.

    PubMed

    Li, Xiuting; Batchelor-McAuley, Christopher; Tschulik, Kristina; Shao, Lidong; Compton, Richard G

    2015-08-03

    Carbon nanotubes decorated with ultra-small metal nanoparticles are of great value in catalysis. We report that individual multiwalled carbon nanotubes decorated with ultra-small palladium nanoparticles can be detected by using the nano-impacts method. The high conductivity and reactivity of each decorated carbon nanotube is directly evidenced; this is achieved through studying the proton-reduction reaction for the underpotential deposition of hydrogen onto the nanoparticles decorated on the carbon nanotube walls. The reductive spikes from current amplification are analyzed to estimate the approximate length of the decorated carbon nanotubes, revealing that the decorated carbon nanotubes are electroactive along its entire length of several micrometers.

  8. [Mean platelet volume: interactions with platelet aggregation activity and glycoprotein IIb-IIIa and Ib expression levels].

    PubMed

    Khaspekova, S G; Ziuriaev, I T; Iakushkin, V V; Naĭmushin, Ia A; Sirotkina, O V; Zaĭtseva, N O; Ruda, M Ia; Mazurov, A V

    2014-01-01

    Increased mean platelet volume (MPV) is an independent risk factor of thrombotic events in patients with cardiovascular diseases. Interactions of MPV with platelet aggregation activity and contents of glycoprotein (GP) IIb-IIIa (alphaIIb/beta3 integrin, fibrinogen receptor) and GP Ib (von Willebrand factor receptor) were investigated in this study. Investigation was performed in a group of healthy volunteers (n = 38) and in a group of patients with acute coronary syndrome (ACS). In patients blood was collected at days 1, 3-5 and 8-12 after ACS development. As an antiaggregant therapy all patients received acetylsalicylic acid (ASA, inhibitor of thromboxane A2 synthesis) and most of them--clopidogrel (ADP receptor antagonist) with the exception of part of the patients (n = 44) at day 1 who had not taken clopidogrel before first blood collection. In volunteers platelet aggregation was stimulated by 1.25, 2.5, 5 and 20 M ADP, and in patients--by 5 and 20 M ADP. GP IIb-IIIa and GP Ib content on platelet surface was measured using 125I-labelled monoclonal antibodies. GP IIb-IIIa and GP Ib genetic polymorphisms were determined in ACS patients. In healthy donors significant correlations between MPV and aggregation levels were revealed at 1.25 and 2.5 M ADP (coefficients of correlation (r)--0.396 and 0.373, p < 0.05) and at 5 and 20 those interactions did not reach significant level (r--0.279 and 0.205, p > 0.05). Correlations between MPV and aggregation levels were observed at day 1 of ACS in a subgroup of patients who received ASA but had not started clopidogrel treatment (r--0.526, p < 0.01 and 0.368, p < 0.05 for 5 and 20 M ADP respectively). Interactions between these parameters were not registered upon combined treatment with ASA and clopidogrel. Strong direct correlations between MPV and GP IIb-IIIa and GP Ib contents were detected in healthy donors and ACS patients (at all time points) -r from 0.439 to 0.647 (p < or = 0.001 for all correlations). Genetic

  9. von Willebrand disease type 2A phenotypes IIC, IID and IIE: A day in the life of shear-stressed mutant von Willebrand factor.

    PubMed

    Brehm, M A; Huck, V; Aponte-Santamaría, C; Obser, T; Grässle, S; Oyen, F; Budde, U; Schneppenheim, S; Baldauf, C; Gräter, F; Schneider, S W; Schneppenheim, R

    2014-07-03

    The bleeding disorder von Willebrand disease (VWD) is caused by mutations of von Willebrand factor (VWF), a multimeric glycoprotein essential for platelet-dependent primary haemostasis. VWD type 2A-associated mutations each disrupt VWF biosynthesis and function at different stages, depending on the VWF domain altered by the mutation. These effects cause considerable heterogeneity in phenotypes and symptoms. To characterise the molecular mechanisms underlying the specific VWF deficiencies in VWD 2A/IIC, IID and IIE, we investigated VWF variants with patient-derived mutations either in the VWF pro-peptide or in domains D3 or CK. Additionally to static assays and molecular dynamics (MD) simulations we used microfluidic approaches to perform a detailed investigation of the shear-dependent function of VWD 2A mutants. For each group, we found distinct characteristics in their intracellular localisation visualising specific defects in biosynthesis which are correlated to respective multimer patterns. Using microfluidic assays we further determined shear flow-dependent characteristics in polymer-platelet-aggregate formation, platelet binding and string formation for all mutants. The phenotypes observed under flow conditions were not related to the mutated VWF domain. By MD simulations we further investigated how VWD 2A/IID mutations might alter the ability of VWF to form carboxy-terminal dimers. In conclusion, our study offers a comprehensive picture of shear-dependent and shear-independent dysfunction of VWD type 2A mutants. Furthermore, our microfluidic assay might open new possibilities for diagnosis of new VWD phenotypes and treatment choice for VWD patients with shear-dependent VWF dysfunctions that are currently not detectable by static tests.

  10. Patterning surfaces for controlled platelet adhesion and detection of dysfunctional platelets.

    PubMed

    Ye, Wei; Shi, Qiang; Wong, Shing-Chung; Hou, Jianwen; Shi, Hengchong; Yin, Jinghua

    2013-06-01

    Platelets play a fundamental role in thrombus formation and in the pathogenesis of arterial thrombosis. Patterning surfaces for controlled platelet adhesion paves the way for adhesion and activation mechanisms in platelets and detection of platelet functional defects. Here, a new and simple method based on controlled polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) on the surface of styrene-block-(ethylene-co-butylene)-block-styrene (SEBS) is shown. The competition between polymerization and degradation enables platelet adhesion on SEBS to be switched on and off. The adhesive sites of the platelets can be down to single cell level, and the dysfunctional platelets can be quantitatively detected.

  11. Platelet Activation: The Mechanisms and Potential Biomarkers

    PubMed Central

    Yun, Seong-Hoon; Sim, Eun-Hye; Goh, Ri-Young; Park, Joo-In

    2016-01-01

    Beyond hemostasis and thrombosis, an increasing number of studies indicate that platelets play an integral role in intercellular communication, mediating inflammatory and immunomodulatory activities. Our knowledge about how platelets modulate inflammatory and immunity has greatly improved in recent years. In this review, we discuss recent advances in the pathways of platelet activation and potential application of platelet activation biomarkers to diagnosis and prediction of disease states. PMID:27403440

  12. Nichtlineare Rauschmodellierung von LC Tank VCOs

    NASA Astrophysics Data System (ADS)

    Thiessen, T.; Bremer, J.-K.; Mathis, W.

    2008-05-01

    Im Rahmen dieser Arbeit wird ein alternativer Ansatz zur Phasenrauschoptimierung von LC-Tank Oszillatoren (VCOs) unter Verwendung stochastischer Differentialgleichungen vorgestellt. Zunächst werden die linearen Ansätze von Leeson, Hajimiri und Lee analysiert und bewertet. Danach wird ein Konzept vorgestellt, mit dem man die Rauscheigenschaften von VCOs auf der Grundlage stochastischer Differentialgleichungen und Fokker-Planck-Gleichungen untersuchen kann. Ziel dieser Arbeit ist eine Beschreibung des Phasenrauschens auf der Basis einer nichtlinearen Rauschmodellierung, welche Parameter eines VCOs für eine Optimierung beinhaltet. Es wurde ein Matlab-Tool erstellt und die Funktionalität anhand von Simulationen verifiziert.

  13. Selection of donor platelets for alloimmunized patients using a platelet-associated IgG assay

    SciTech Connect

    Myers, T.J.; Kim, B.K.; Steiner, M.; Baldini, M.G.

    1981-09-01

    A quantitative immunofluorescence platelet-associated immunoglobulin-G (PA-IgG) assay was used to detect alloimmunity to platelets in 8/12 multitransfused patients and to perform platelet crossmatching in the 8 alloimmunized patients. The correct separation of multitransfused patients into alloimmune and nonalloimmune groups was substantiated with chromium-51-labeled platelet survival studies. For 5 alloimmunized patients, compatible and incompatible donor platelets were demonstrated by PA-IgG crossmatching and were confirmed by platelet survival studies. With the other 3 alloimmunized patients, only Pa-IgG incompatible donor platelets were found. Survival studies with 5 of these incompatible donor platelets showed markedly reduced survival times on 4 occasions. Pa-IgG compatible donor platelets survived 3.5 to 8.7 days, while Pa-IgG incompatible platelets showed survival times of 0.1 to 2.4 days.

  14. Dengue platelets meet Sir Arthur Conan Doyle.

    PubMed

    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.

  15. 21 CFR 864.6675 - Platelet aggregometer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... shape and platelet aggregation following the addition of an aggregating reagent to a platelet rich... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Platelet aggregometer. 864.6675 Section 864.6675...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6675...

  16. 21 CFR 864.6675 - Platelet aggregometer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... shape and platelet aggregation following the addition of an aggregating reagent to a platelet rich... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Platelet aggregometer. 864.6675 Section 864.6675...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6675...

  17. Automatic detection of immature platelets for decision making regarding platelet transfusion indications for pediatric patients.

    PubMed

    Saigo, Katsuyasu; Sakota, Yasuyuki; Masuda, Yukako; Matsunaga, Kyoko; Takenokuchi, Mariko; Nishimura, Kunihiro; Sugimoto, Takeshi; Sakurai, Kosuke; Hashimoto, Makoto; Yanai, Tomoko; Hayakawa, Akira; Takeshima, Yasuhiro; Nomura, Tsutomu; Kubota, Yoshitsugu; Kumagai, Shunichi

    2008-04-01

    Immature or reticulated platelets are known as a clinical marker of thrombopoiesis. Recently, an automatic method was established to detect reticulated platelets as immature platelet fraction (IPF) by means of hematology analyzer XE-2100. We assessed the effects of IPF detection after chemotherapy for various pediatric malignant disorders of 16 patients. Our results indicate that IPF should be considered a useful marker of imminent platelet recovery so that unnecessary platelet transfusion can be avoided.

  18. Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion.

    PubMed

    Feghhi, Shirin; Munday, Adam D; Tooley, Wes W; Rajsekar, Shreya; Fura, Adriane M; Kulman, John D; López, Jose A; Sniadecki, Nathan J

    2016-08-09

    Platelets bind to exposed vascular matrix at a wound site through a highly specialized surface receptor, glycoprotein (GP) Ib-IX-V complex, which recognizes von Willebrand factor (VWF) in the matrix. GPIb-IX-V is a catch bond for it becomes more stable as force is applied to it. After attaching to the wound site, platelets generate cytoskeletal forces to compact and reinforce the hemostatic plug. Here, we evaluated the role of the GPIb-IX-V complex in the transmission of cytoskeletal forces. We used arrays of flexible, silicone nanoposts to measure the contractility of individual platelets on VWF. We found that a significant proportion of cytoskeletal forces were transmitted to VWF through GPIb-IX-V, an unexpected finding given the widely held notion that platelet forces are transmitted exclusively through its integrins. In particular, we found that the interaction between GPIbα and the A1 domain of VWF mediates this force transmission. We also demonstrate that the binding interaction between GPIbα and filamin A is involved in force transmission. Furthermore, our studies suggest that cytoskeletal forces acting through GPIbα are involved in maintaining platelet adhesion when external forces are absent. Thus, the GPIb-IX-V/VWF bond is able to transmit force, and uses this force to strengthen the bond through a catch-bond mechanism. This finding expands our understanding of how platelets attach to sites of vascular injury, describing a new, to the best of our knowledge, mechanism in which the catch bonds of GPIb-IX-V/VWF can be supported by internal forces produced by cytoskeletal tension.

  19. Reflexionseigenschaften von Windenergieanlagen im Funkfeld von Funknavigations- und Radarsystemen

    NASA Astrophysics Data System (ADS)

    Sandmann, S.; Divanbeigi, S.; Garbe, H.

    2015-11-01

    Die hier behandelte Untersuchung befasst sich mit den Störungen des elektrischen Feldes einer Doppler Very High Frequency Omnidirectional Radio Range Navigationsanlage (DVOR) in der Gegenwart von Windenergieanlagen (WEA). Hierfür wird die Feldstärke auf 25 konzentrischen Kreisbahnen, sog. Orbit Flights verschiedener Höhen und mit verschiedenen Radien rund um die DVOR-Anlage numerisch simuliert. Insbesondere werden die Einflüsse diverser Parameter der WEA wie deren Anzahl, Position, Rotorwinkel, Turmhöhe und Rotordurchmesser auf die Feldverteilung herausgestellt, sowie die Anwendbarkeit der Simulationsmethode Physical Optics (PO) durch Vergleich der Simulationsergebnisse mit denen der Multi Level Fast Multipol Method (MLFMM) untersucht.

  20. Factor VIII alters tubular organization and functional properties of von Willebrand factor stored in Weibel-Palade bodies.

    PubMed

    Bouwens, Eveline A M; Mourik, Marjon J; van den Biggelaar, Maartje; Eikenboom, Jeroen C J; Voorberg, Jan; Valentijn, Karine M; Mertens, Koen

    2011-11-24

    In endothelial cells, von Willebrand factor (VWF) multimers are packaged into tubules that direct biogenesis of elongated Weibel-Palade bodies (WPBs). WPB release results in unfurling of VWF tubules and assembly into strings that serve to recruit platelets. By confocal microscopy, we have previously observed a rounded morphology of WPBs in blood outgrowth endothelial cells transduced to express factor VIII (FVIII). Using correlative light-electron microscopy and tomography, we now demonstrate that FVIII-containing WPBs have disorganized, short VWF tubules. Whereas normal FVIII and FVIII Y1680F interfered with formation of ultra-large VWF multimers, release of the WPBs resulted in VWF strings of equal length as those from nontransduced blood outgrowth endothelial cells. After release, both WPB-derived FVIII and FVIII Y1680F remained bound to VWF strings, which however had largely lost their ability to recruit platelets. Strings from nontransduced cells, however, were capable of simultaneously recruiting exogenous FVIII and platelets. These findings suggest that the interaction of FVIII with VWF during WPB formation is independent of Y1680, is maintained after WPB release in FVIII-covered VWF strings, and impairs recruitment of platelets. Apparently, intra-cellular and extracellular assembly of FVIII-VWF complex involves distinct mechanisms, which differ with regard to their implications for platelet binding to released VWF strings.

  1. Effect of ajoene, the major antiplatelet compound from garlic, on platelet thrombus formation.

    PubMed

    Apitz-Castro, R; Badimon, J J; Badimon, L

    1992-10-15

    Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, is a potent antiplatelet compound isolated from alcoholic extracts of garlic (Allium sativum). Ajoene reversibly inhibits in vitro platelet aggregation as well as release reaction induced by all known agonists. We used a well characterized cylindrical perfusion chamber to study the effect of ajoene on platelet deposition onto physiological substrates such as pig aortic subendothelium and tunica media as a model of mildly and severely damaged vessel wall respectively. Experiments were performed under flow conditions of high and low shear rate that mimic laminar blood flow in small and medium size arteries (1690 sec-1 and 212 sec-1). Our results indicate that ajoene prevents thrombus formation both at low and high shear rate in citrated whole blood. The inhibitory effect of ajoene on platelet-thrombus formation seems to be dependent on its inhibition of fibrinogen binding, since significantly higher concentrations of ajoene are needed to affect von Willebrand factor binding to GPIIb/IIIa receptors. Further, ajoene does not impair Ristocetin-induced platelet agglutination, mediated by GPIb. Our results suggest that ajoene may be useful for the acute prevention of thrombus formation induced by vascular damage.

  2. Identification of a juxtamembrane mechanosensitive domain in the platelet mechanosensor glycoprotein Ib-IX complex

    PubMed Central

    Zhang, Wei; Deng, Wei; Zhou, Liang; Xu, Yan; Yang, Wenjun; Liang, Xin; Wang, Yizhen; Kulman, John D.; Zhang, X. Frank

    2015-01-01

    How glycoprotein (GP)Ib-IX complex on the platelet surface senses the blood flow through its binding to the plasma protein von Willebrand factor (VWF) and transmits a signal into the platelet remains unclear. Here we show that optical tweezer-controlled pulling of the A1 domain of VWF (VWF-A1) on GPIb-IX captured by its cytoplasmic domain induced unfolding of a hitherto unidentified structural domain before the dissociation of VWF-A1 from GPIb-IX. Additional studies using recombinant proteins and mutant complexes confirmed its existence in GPIb-IX and enabled localization of this quasi-stable mechanosensitive domain of ∼60 residues between the macroglycopeptide region and the transmembrane helix of the GPIbα subunit. These results suggest that VWF-mediated pulling under fluid shear induces unfolding of the mechanosensitive domain in GPIb-IX, which may possibly contribute to platelet mechanosensing and/or shear resistance of VWF-platelet interaction. The identification of the mechanosensitive domain in GPIb-IX has significant implications for the pathogenesis and treatment of related blood diseases. PMID:25359992

  3. Exploratory studies of extended storage of apheresis platelets in a platelet additive solution (PAS).

    PubMed

    Slichter, Sherrill J; Corson, Jill; Jones, Mary Kay; Christoffel, Todd; Pellham, Esther; Bailey, S Lawrence; Bolgiano, Doug

    2014-01-09

    To evaluate the poststorage viability of apheresis platelets stored for up to 18 days in 80% platelet additive solution (PAS)/20% plasma, 117 healthy subjects donated platelets using the Haemonetics MCS+, COBE Spectra (Spectra), or Trima Accel (Trima) systems. Control platelets from the same subjects were compared with their stored test PAS platelets by radiolabeling their stored and control platelets with either (51)chromium or (111)indium. Trima platelets met Food and Drug Administration poststorage platelet viability criteria for only 7 days vs almost 13 days for Haemonetics platelets; ie, platelet recoveries after these storage times averaged 44 ± 3% vs 49 ± 3% and survivals were 5.4 ± 0.3 vs 4.6 ± 0.3 days, respectively. The differences in storage duration are likely related to both the collection system and the storage bag. The Spectra and Trima platelets were hyperconcentrated during collection, and PAS was added, whereas the Haemonetics platelets were elutriated with PAS, which may have resulted in less collection injury. When Spectra and Trima platelets were stored in Haemonetics' bags, poststorage viability was significantly improved. Platelet viability is better maintained in vitro than in vivo, allowing substantial increases in platelet storage times. However, implementation will require resolution of potential bacterial overgrowth during storage.

  4. Decoration of silk fibroin by click chemistry for biomedical application.

    PubMed

    Zhao, Hongshi; Heusler, Eva; Jones, Gabriel; Li, Linhao; Werner, Vera; Germershaus, Oliver; Ritzer, Jennifer; Luehmann, Tessa; Meinel, Lorenz

    2014-06-01

    Silkfibroin (SF) has an excellent biocompatibility and its remarkable structure translates into exciting mechanical properties rendering this biomaterial particularly fascinating for biomedical application. To further boost the material's biological/preclinical impact, SF is decorated with biologics, typically by carbodiimide/N-hydroxysuccinimide coupling (EDC/NHS). For biomedical application, this chemistry challenges the product risk profile due to the formation of covalent aggregates, particularly when decoration is with biologics occurring naturally in humans as these aggregates may prime for autoimmunity. Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC; click chemistry) provides the necessary specificity to avoid such intermolecular, covalent aggregates. We present a blueprint outlining the necessary chemistry rendering SF compatible with CuAAC and with a particular focus on structural consequences. For that, the number of SF carboxyl groups (carboxyl-SF; required for EDC/NHS chemistry) or azido groups (azido-SF; required for click chemistry) was tailored by means of diazonium coupling of the SF tyrosine residues. Structural impact on SF and decorated SF was characterized by Fourier transform infrared spectroscopy (FTIR). The click chemistry yielded a better controlled product as compared to the EDC/NHS chemistry with no formation of inter- and intramolecular crosslinks as demonstrated for SF decorated with fluorescent model compounds or a biologic, fibroblast growth factor 2 (FGF2), respectively. In conclusion, SF can readily be translated into a scaffold compatible with click chemistry yielding decorated products with a better risk profile for biomedical application.

  5. Magnesium nanoparticles with transition metal decoration for hydrogen storage

    NASA Astrophysics Data System (ADS)

    Pasquini, Luca; Callini, Elsa; Brighi, Matteo; Boscherini, Federico; Montone, Amelia; Jensen, Torben R.; Maurizio, Chiara; Vittori Antisari, Marco; Bonetti, Ennio

    2011-11-01

    We report on the hydrogen storage behaviour of Mg nanoparticles (NPs) (size range 100 nm-1 μm) with metal-oxide core-shell morphology synthesized by inert gas condensation and decorated by transition metal (TM) (Pd or Ti) clusters via in situ vacuum deposition. The structure and morphology of the as-prepared and hydrogenated NPs is studied by electron microscopy, X-ray diffraction including in situ experiments and X-ray absorption spectroscopy, in order to investigate the relationships with the hydrogen storage kinetics measured by the volumetric Sieverts method. With both Pd and Ti, the decoration deeply improves the hydrogen sorption properties: previously inert NPs exhibit complete hydrogenation with fast transformation kinetics, good stability and reversible gravimetric capacity that can attain 6 wt%. In the case of Pd-decoration, the occurrence of Mg-Pd alloying is observed at high temperatures and in dependence of the hydrogen pressure conditions. These structural transformations modify both the kinetics and thermodynamics of hydride formation, while Ti-decoration has an effect only on the kinetics. The experimental results are discussed in relation with key issues such as the amount of decoration, the heat of mixing between TM and Mg and the binding energy between TM and hydrogen.

  6. Platelet count and platelet indices in women with preeclampsia

    PubMed Central

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

    2016-01-01

    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 pre-eclampsia (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. PMID:27920548

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

    PubMed

    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.

  8. Mean Platelet Volume and Platelet Immunofluorescence as Indicators of Platelet Compatibility.

    DTIC Science & Technology

    1983-02-23

    Studies were performed to determine if the increase in MPV was due to the presence of alloantibodies or if it was due to ABO isoagglutinins anti-A and...blood group types (Tables IA and 1B). Sera from donors with blood group type 0 containing anti-A and anti-B isoagglutinins always caused type A...platelets to swell (range 7-24%) (Table 1A). Mixtures of B and 0 platelets with sera containing anti-A and anti-B isoagglutinins demonstrated no change or

  9. Data on the purification and crystallization of the loss-of-function von Willebrand disease variant (p.Gly1324Ser) of the von Willebrand factor A1 domain.

    PubMed

    Campbell, James C; Tischer, Alexander; Machha, Venkata; Moon-Tasson, Laurie; Sankaran, Banumathi; Kim, Choel; Auton, Matthew

    2016-06-01

    von Willebrand factor׳s (VWF) primary hemostatic responsibility is to deposit platelets at sites of vascular injury to prevent bleeding. This function is mediated by the interaction between the VWF A1 domain and the constitutively active platelet receptor, GPIbα. The crystal structure of the A1 domain harboring the von Willebrand disease (vWD) type 2M mutation p.Gly1324Ser has been recently published in the Journal of Biological Chemistry describing its effect on the function and structural stability of the A1 domain of VWF, "Mutational constraints on local unfolding inhibit the rheological adaptation of von Willebrand factor" [1]. The mutation introduces a side chain that thermodynamically stabilizes the domain by reducing the overall flexibility of the A1-GPIbα binding interface resulting in loss-of-function and bleeding due to the inability of A1 to adapt to a binding competent conformation under the rheological shear stress blood flow. In this data article we describe the production, quality control and crystallization of the p.Gly1324Ser vWD variant of the A1 domain of VWF. p.Gly1324Ser A1 was expressed in Escherichia coli as insoluble inclusion bodies. After the preparation of the inclusion bodies, the protein was solubilized, refolded, purified by affinity chromatography and crystallized. The crystal structure of the p.Gly1324Ser mutant of the A1 domain is deposited at the Protein Data Bank PDB: 5BV8.

  10. Comprehensive evaluation of haemostatic function in von Willebrand disease patients using a microchip-based flow chamber system.

    PubMed

    Ogiwara, K; Nogami, K; Hosokawa, K; Ohnishi, T; Matsumoto, T; Shima, M

    2015-01-01

    The diagnosis of von Willebrand disease (VWD) is difficult due to the wide spectrum of clinical phenotypes associated with this disorder. We have analysed and characterized haemostatic function in VWD patients using a microchip-based flow chamber system. Microchips coated with either collagen [platelet (PL)-chip] or collagen/thromboplastin [atherome (AR)-chip] were used to evaluate platelet thrombus formation at 1000 s(-1) and fibrin-rich platelet thrombus formation at 240 s(-1) respectively. Blood samples from an asymptomatic patient with VWD type 1 [von Willebrand factor (VWF): RCo 3.2%; bleeding score (BS 2] displayed normal thrombus formation in both PL- and AR-chips, whereas blood from a symptomatic type 1 patient (VWF: RCo 14%, BS 9) had significantly delayed capillary occlusion. Nearly complete suppression of the flow pressure increase was observed in symptomatic patients with VWD type 2A (BS 13) and 2N (BS 27), whereas no flow pressure was found for the type 3 patient (BS 6). Fibrin-rich platelet thrombus formation was only weakly increased by the in vitro addition of factor VIII (FVIII) to blood samples from the type 3 patient, but was normalized by the addition of VWF/FVIII. The in vivo effects of treatment with desmopressin or VWF/FVIII for the symptomatic patients were analysed using two types of microchips. The PL-chip was highly sensitive for patients' VWF-mediated platelet functions, whereas the AR-chip allowed assessment of overall haemostatic ability, including sensitivity to both VWF and FVIII. The combined analysis with PL- and AR-chips may be potentially useful for the diagnosis of VWD based on clinical phenotypes, and for monitoring drug effects.

  11. Hemolysis after ABO-incompatible platelet transfusions.

    PubMed

    Chow, M P; Yung, C H; Hu, H Y; Tzeng, C H

    1991-08-01

    An 18 year old girl, with acute myeloid leukemia, developed progressive hemolysis after receiving multiple transfusions with ABO-incompatible platelets. It was caused by passive transfusion of anti-A and -B isoagglutinin from the donor plasma. Her hemoglobin level returned to normal after giving group compatible or pooled and reduced volume platelet concentrates. Transfusing group-incompatible platelets is not contraindicated, but donor plasma reduction should be considered for those patients who need prolonged platelet support. Testing for isoagglutinin titer in group O donors is an alternate method to reduce the incidence of plasma-induced hemolysis in group-incompatible platelet transfusions.

  12. Acetal phosphatidic acids: novel platelet aggregating agents.

    PubMed

    Brammer, J P; Maguire, M H; Walaszek, E J; Wiley, R A

    1983-05-01

    1 Palmitaldehyde, olealdehyde and linolealdehyde acetal phosphatidic acids induced rapid shape change and dose-dependent biphasic aggregation of human platelets in platelet-rich plasma; aggregation was reversible at low doses and irreversible at high doses of the acetal phosphatidic acids. The palmitaldehyde congener elicited monophasic dose-dependent aggregation of sheep platelets in platelet-rich plasma.2 The threshold concentration for palmitaldehyde acetal phosphatidic acid (PGAP)-induced platelet aggregation was 2.5-5 muM for human platelets and 0.25-0.5 muM for sheep platelets. PGAP was 4-5 times as potent versus human platelets as the olealdehyde and linolealdehyde acetal phosphatidic acids, which were equipotent.3 PGAP-induced irreversible aggregation of [(14)C]-5-hydroxytryptamine ([(14)C]-5-HT)-labelled human platelets in platelet-rich plasma was accompanied by release of 44.0+/-2.4% (s.e.) of the platelet [(14)C]-5-HT; reversible aggregation was not associated with release. In contrast, PGAP-induced release of [(14)C]-5-HT-labelled sheep platelets was dose-dependent.4 The adenosine diphosphate (ADP) antagonist, 2-methylthio-AMP, and the cyclo-oxygenase inhibitor, aspirin, abolished PGAP-induced second phase aggregation and release in human platelets but did not affect the first, reversible, phase of aggregation. Both the first and second phases of PGAP-induced aggregation were abolished by chlorpromazine, by the phospholipase A(2) inhibitor, mepacrine, and by nmolar concentrations of prostaglandin E(1) (PGE(1)); these agents abolished the second, but not the first phase of ADP-induced aggregation.5 The related phospholipids, lecithin, lysolecithin and phosphatidic acid, at <100 muM, neither induced aggregation of human platelets in platelet-rich plasma, nor modified PGAP-induced aggregation; 1-palmityl lysophosphatidic acid elicited aggregation of human platelets at a threshold concentration of 100 muM.6 It is concluded that the acetal phosphatidic acids

  13. Platelet actively cooled thermal management devices

    NASA Astrophysics Data System (ADS)

    Mueggenburg, H. H.; Hidahl, J. W.; Kessler, E. L.; Rousar, D. C.

    1992-07-01

    An overview of 28 years of actively-cooled platelet thermal management devices design and development history is presented. Platelet devices are created by bonding together thin metal sheets (platelets) which contain chemically-etched coolant pasages. The bonding process produces an intricate and precise matrix of coolant passages and structural walls contained within a monolithic structure. Thirteen specific applications for platelet thermal management devices are described. These devices are cooled using convective, film, and transpiration cooling techniques. Platelet thermal management devices have been fabricated from a variety of metals, cooled with a variety of fluids, and operated at heat fluxes up to 200 Btu/sq in.-sec.

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

    PubMed

    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.

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

    SciTech Connect

    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.

  16. Splenic release of platelets contributes to increased circulating platelet size and inflammation after myocardial infarction.

    PubMed

    Gao, Xiao-Ming; Moore, Xiao-Lei; Liu, Yang; Wang, Xin-Yu; Han, Li-Ping; Su, Yidan; Tsai, Alan; Xu, Qi; Zhang, Ming; Lambert, Gavin W; Kiriazis, Helen; Gao, Wei; Dart, Anthony M; Du, Xiao-Jun

    2016-07-01

    Acute myocardial infarction (AMI) is characterized by a rapid increase in circulating platelet size but the mechanism for this is unclear. Large platelets are hyperactive and associated with adverse clinical outcomes. We determined mean platelet volume (MPV) and platelet-monocyte conjugation (PMC) using blood samples from patients, and blood and the spleen from mice with AMI. We further measured changes in platelet size, PMC, cardiac and splenic contents of platelets and leucocyte infiltration into the mouse heart. In AMI patients, circulating MPV and PMC increased at 1-3 h post-MI and MPV returned to reference levels within 24 h after admission. In mice with MI, increases in platelet size and PMC became evident within 12 h and were sustained up to 72 h. Splenic platelets are bigger than circulating platelets in normal or infarct mice. At 24 h post-MI, splenic platelet storage was halved whereas cardiac platelets increased by 4-fold. Splenectomy attenuated all changes observed in the blood, reduced leucocyte and platelet accumulation in the infarct myocardium, limited infarct size and alleviated cardiac dilatation and dysfunction. AMI-induced elevated circulating levels of adenosine diphosphate and catecholamines in both human and the mouse, which may trigger splenic platelet release. Pharmacological inhibition of angiotensin-converting enzyme, β1-adrenergic receptor or platelet P2Y12 receptor reduced platelet abundance in the murine infarct myocardium albeit having diverse effects on platelet size and PMC. In conclusion, AMI evokes release of splenic platelets, which contributes to the increase in platelet size and PMC and facilitates myocardial accumulation of platelets and leucocytes, thereby promoting post-infarct inflammation.

  17. Towards personalised therapy for von Willebrand disease: a future role for recombinant products

    PubMed Central

    Favaloro, Emmanuel J.

    2016-01-01

    von Willebrand disease (VWD) is reportedly the most common bleeding disorder and is caused by deficiencies and/or defects in the adhesive plasma protein von Willebrand factor (VWF). Functionally, normal VWF prevents bleeding by promoting both primary and secondary haemostasis. In respect to primary haemostasis, VWF binds to both platelets and sub-endothelial matrix components, especially collagen, to anchor platelets to damaged vascular tissue and promote thrombus formation. VWF also stabilises and protects factor VIII in the circulation, delivering FVIII to the site of injury, which then facilitates secondary haemostasis and fibrin formation/thrombus stabilisation. As a result of this, patients with VWD suffer a bleeding diathesis reflective of a primary defect caused by defective/deficient VWF, which in some patients is compounded by a reduction in FVIII. Management of VWD, therefore, chiefly entails replacement of VWF, and sometimes also FVIII, to protect against bleeding. The current report principally focuses on the future potential for “personalised” management of VWD, given the emerging options in recombinant therapies. Recombinant VWF has been developed and is undergoing clinical trials, and this promising therapy may soon change the way in which VWD is managed. In particular, we can envisage a personalised treatment approach using recombinant VWF, with or without recombinant FVIII, depending on the type of VWD, the extent of deficiencies, and the period and duration of treatment. PMID:27136426

  18. Structural Basis of Regulation of von Willebrand Factor Binding to Glycoprotein Ib*

    PubMed Central

    Blenner, Mark A.; Dong, Xianchi; Springer, Timothy A.

    2014-01-01

    Activation by elongational flow of von Willebrand factor (VWF) is critical for primary hemostasis. Mutations causing type 2B von Willebrand disease (VWD), platelet-type VWD (PT-VWD), and tensile force each increase affinity of the VWF A1 domain and platelet glycoprotein Ibα (GPIbα) for one another; however, the structural basis for these observations remains elusive. Directed evolution was used to discover a further gain-of-function mutation in A1 that shifts the long range disulfide bond by one residue. We solved multiple crystal structures of this mutant A1 and A1 containing two VWD mutations complexed with GPIbα containing two PT-VWD mutations. We observed a gained interaction between A1 and the central leucine-rich repeats (LRRs) of GPIbα, previously shown to be important at high shear stress, and verified its importance mutationally. These findings suggest that structural changes, including central GPIbα LRR-A1 contact, contribute to VWF affinity regulation. Among the mutant complexes, variation in contacts and poor complementarity between the GPIbα β-finger and the region of A1 harboring VWD mutations lead us to hypothesize that the structures are on a pathway to, but have not yet reached, a force-induced super high affinity state. PMID:24391089

  19. 10 CFR 1050.201 - Policy against accepting foreign gifts or decorations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... foreign gifts or decorations. (a) The Constitution of the United States, Article I, section 9, clause 8... any * * * foreign State.” In the Foreign Gifts and Decorations Act the Congress consented to...

  20. 10 CFR 1050.201 - Policy against accepting foreign gifts or decorations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... foreign gifts or decorations. (a) The Constitution of the United States, Article I, section 9, clause 8... any * * * foreign State.” In the Foreign Gifts and Decorations Act the Congress consented to...

  1. 10 CFR 1050.201 - Policy against accepting foreign gifts or decorations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... foreign gifts or decorations. (a) The Constitution of the United States, Article I, section 9, clause 8... any * * * foreign State.” In the Foreign Gifts and Decorations Act the Congress consented to...

  2. Platelet Cryopreservation Using Dimethyl Sulfoxide,

    DTIC Science & Technology

    plateletpheresis methods or cell separators. In recent studies, the corrected count increment following 66 transfusions of frozen platelets collected using the...Haemonetics Model 30 processor (Haemonetics Corp., Natick, Mass.) was 12,3000 (range 0-36,800) compared to a mean CCI of 11,7000 (0-34,900) using manual plateletpheresis technique (N = 211).

  3. Platelets and viruses: an ambivalent relationship.

    PubMed

    Flaujac, Claire; Boukour, Siham; Cramer-Bordé, Elisabeth

    2010-02-01

    Thrombocytopenia is a frequent complication of viral infections providing evidence that interaction of platelets with viruses is an important pathophysiological phenomenon. Multiple mechanisms are involved depending on the nature of the viruses involved. These include immunological platelet destruction, inappropriate platelet activation and consumption, and impaired megakaryopoiesis. Viruses bind platelets through specific receptors and identified ligands, which lead to mutual alterations of both the platelet host and the viral aggressor. We have shown that HIV-1 viruses are internalized specifically in platelets and megakaryocytes, where they can be either sheltered, unaltered (with potential transfer of the viruses into target organs), or come in contact with platelet secretory products leading to virus destruction and facilitated platelet clearance. In this issue, we have reviewed the various pathways that platelets use in order to interact with viruses, HIV and others. This review also shows that more work is still needed to precisely identify platelet roles in viral infections, and to answer the challenge of viral safety in platelet transfusion.

  4. Evidence of platelet activation in multiple sclerosis

    PubMed Central

    Sheremata, William A; Jy, Wenche; Horstman, Lawrence L; Ahn, Yeon S; Alexander, J Steven; Minagar, Alireza

    2008-01-01

    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 < 0.001) and CD62p expression was also markedly elevated (p < 0.001). Both are markers of platelet activation. Platelet-associated IgM, but not IgG, was marginally elevated in MS (p = 0.01). Protein S in MS patients did not differ significantly from normal values. 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. PMID:18588683

  5. Dr. Wernher Von Braun at a picnic.

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Wernher Von Braun, director of the Marshall Space Flight Center, stakes claim to a table for the picnic celebrating man's first lunar landing. With Dr. Von Braun are his wife, Maria (seated, right), and son, Peter (back to camera). His daughter, Margrit, was also present, but is hidden from view by friends in this view.

  6. Dr. Wernher Von Braun greeting dignitaries.

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Wernher Von Braun, left, greets vice president Spiro T. Agnew in the Launch Control Center for the Apollo 14 mission. Between Dr. Von Braun and Mr. Agnew are their Royal Highnesses, The Prince and Princess of Spain. The royal visitors greeted the launch control team in th enter after the launch of Apollo 14.

  7. Dr. von Braun Tries Out the NBS

    NASA Technical Reports Server (NTRS)

    1967-01-01

    Marshall Space Flight Center (MSFC) Director, Dr. von Braun, is shown fitted with suit and diving equipment as he prepares for a tryout in the MSFC Neutral Buoyancy Simulator (NBS). Weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

  8. Walt Disney and Dr. Wernher von Braun

    NASA Technical Reports Server (NTRS)

    1954-01-01

    Dr. Werhner von Braun, then Chief, Guided Missile Development Operation Division at Army Ballistic Missile Agency (ABMA) in Redstone Arsenal, Alabama, was visited by Walt Disney in 1954. In the 1950's, von Braun worked with Disney Studio as a technical director, making three films about space exploration for television. A model of the V-2 rocket is in background.

  9. Numerical simulation of platelet margination in microcirculation

    NASA Astrophysics Data System (ADS)

    Zhao, Hong; Shaqfeh, Eric

    2009-11-01

    The adhesion of platelets to vascular walls is the first step in clotting. This process critically depends on the preferential concentration of platelets near walls. The presence of red blood cells, which are the predominant blood constituents, is known to affect the steady state platelet concentration and the dynamic platelet margination, but the underlying mechanism is not well understood to-day. We use a direct numerical simulation to study the platelet margination process, with particular emphasis on the Stokesian hydrodynamic interactions among red cells, platelets, and vessel walls. Well-known mechanical models are used for the shearing and bending stiffness of red cell membranes, and the stiffer platelets are modeled as rigid discoids. A boundary integral formulation is used to solve the flow field, where the numerical solution procedure is accelerated by a parallel O(N N) smooth particle-mesh Ewald method. The effects of red cell hematocrit and deformability will be discussed.

  10. Thrombocytopenia and platelet transfusion in the neonate.

    PubMed

    Cremer, Malte; Sallmon, Hannes; Kling, Pamela J; Bührer, Christoph; Dame, Christof

    2016-02-01

    Neonatal thrombocytopenia is widespread in preterm and term neonates admitted to neonatal intensive care units, with up to one-third of infants demonstrating platelet counts <150 × 10(9)/L. Thrombocytopenia may arise from maternal, placental or fetal/neonatal origins featuring decreased platelet production, increased consumption, or both mechanisms. Over the past years, innovations in managing neonatal thrombocytopenia were achieved from prospectively obtained clinical data on thrombocytopenia and bleeding events, animal studies on platelet life span and production rate and clinical use of fully automated measurement of reticulated platelets (immature platelet fraction). This review summarizes the pathophysiology of neonatal thrombocytopenia, current management including platelet transfusion thresholds and recent developments in megakaryopoietic agents. Furthermore, we propose a novel index score for bleeding risk in thrombocytopenic neonates to facilitate clinician's decision-making when to transfuse platelets.

  11. Hydrogen Storage in Titanium-decorated Boron Buckyball

    NASA Astrophysics Data System (ADS)

    Li, Jia; Zhou, Gang; Duan, Wenhui; Lee, Hoonkyung; Ihm, Jisoon

    2008-03-01

    Using first-principles electronic structure calculations, we investigate the potential of Ti-decorated B80 for hydrogen storage medium. The Ti-decorated B80 has the merit of an unexpected large binding energy of a Ti atom to B80 which can overcome the problem of metal clustering. Up to four hydrogen molecules are found to be adsorbed on a single Ti atom coated on B80. At high Ti coverage, we show that the Ti-decorated B80 can adsorb up to 5 wt% hydrogen and the calculated binding energy falls in the desirable range of 0.2-0.6eV/H2 which is suitable for reversible hydrogen storage at room-temperature, near-ambient-pressure conditions.

  12. Calcium-decorated carbyne networks as hydrogen storage media.

    PubMed

    Sorokin, Pavel B; Lee, Hoonkyung; Antipina, Lyubov Yu; Singh, Abhishek K; Yakobson, Boris I

    2011-07-13

    Among the carbon allotropes, carbyne chains appear outstandingly accessible for sorption and very light. Hydrogen adsorption on calcium-decorated carbyne chain was studied using ab initio density functional calculations. The estimation of surface area of carbyne gives the value four times larger than that of graphene, which makes carbyne attractive as a storage scaffold medium. Furthermore, calculations show that a Ca-decorated carbyne can adsorb up to 6 H(2) molecules per Ca atom with a binding energy of ∼0.2 eV, desirable for reversible storage, and the hydrogen storage capacity can exceed ∼8 wt %. Unlike recently reported transition metal-decorated carbon nanostructures, which suffer from the metal clustering diminishing the storage capacity, the clustering of Ca atoms on carbyne is energetically unfavorable. Thermodynamics of adsorption of H(2) molecules on the Ca atom was also investigated using equilibrium grand partition function.

  13. Navigation Strategies of Motor Proteins on Decorated Tracks

    PubMed Central

    Bertalan, Zsolt; Budrikis, Zoe; La Porta, Caterina A. M.; Zapperi, Stefano

    2015-01-01

    Motor proteins display widely different stepping patterns as they move on microtubule tracks, from the deterministic linear or helical motion performed by the protein kinesin to the uncoordinated random steps made by dynein. How these different strategies produce an efficient navigation system needed to ensure correct cellular functioning is still unclear. Here, we show by numerical simulations that deterministic and random motor steps yield different outcomes when random obstacles decorate the microtubule tracks: kinesin moves faster on clean tracks but its motion is strongly hindered on decorated tracks, while dynein is slower on clean tracks but more efficient in avoiding obstacles. Further simulations indicate that dynein’s advantage on decorated tracks is due to its ability to step backwards. Our results explain how different navigation strategies are employed by the cell to optimize motor driven cargo transport. PMID:26323095

  14. Acquired von Willebrand syndrome in children with aorticand pulmonary stenosis

    PubMed Central

    Binnetoğlu, Fatih Köksal; Babaoğlu, Kadir; Filiz, Şayegan Güven; Zengin, Emine; Sarper, Nazan; Altun, Gürkan; Kılıç, Suar Çakı

    2016-01-01

    Summary Introduction: This prospective study was planned to investigate the frequency and relationship of acquired von Willebrand syndrome (AVWS) with aortic and pulmonary stenosis in patients. Methods: A total of 84 children, ranging from two to 18 years of age, were enrolled in this study. Of these, 28 had isolated aortic stenosis, 32 had isolated pulmonary stenosis and 24 were healthy. Children with aortic and pulmonary stenosis associated with other congenital heart diseases were excluded. Children with hypothyroidism, renal or liver disease, malignancy or autoimmune disease were also excluded. Wholeblood count, blood group, factor VIII level, prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor antigen (VWF:Ag), ristocetin co-factor (VWF:RCo), and bleeding time using a platelet-function analyser (PFA-100) were performed in all patients. All of the children in the study underwent a detailed physical examination and echocardiographic evaluation. Results: A history of bleeding was positive in 18% of the aortic stenosis group, 9% of the pulmonary stenosis group, and 4% of the control group. Seven of 60 (12%) patients had laboratory findings that implied a diagnosis of AVWS, and two of these (28%) had a history of bleeding. The frequency of AVWS was 14% in patients with aortic stenosis and 9% in those with pulmonary stenosis. Conclusion: AVWS is not rare in stenotic obstructive cardiac diseases. A detailed history of bleeding should be taken from patients with valvular disease. Even if the history is negative, whole blood count, PT and aPTT should be performed. If necessary, PFA-100 closure time and further tests should be planned for the diagnosis of AVWS. PMID:27841910

  15. Mean platelet volume as an indicator of platelet rejuvenation following bone-marrow transplantation. Master's thesis

    SciTech Connect

    Seanger, D.G.

    1986-07-01

    Thrombocytopenia of unpredictable duration and severity is an expected outcome of the radiation/chemotherapy protocols performed prior to bone-marrow transplantation. Serial evaluation of the platelet count and mean platelet volume of patients diagnosed with acute leukemia demonstrated the mean platelet volume to increase into reference limits 24 to 40 hours prior to a rise in the platelet count in those patients whose bone-marrow successfully responded to induction chemotherapy. Serial platelet counts and measurements of mean platelet volume were performed on 31 patients following bone marrow transplantation. Numerous platelet transfusions, together with sustained thrombocytopenia, inhibited accurate assessment of 29 of 31 patients. Two patients, however, demonstrated a rise in the mean platelet volume prior to an increase in the platelet count. Both of these patients received no platelet transfusions during the period preceding or following the rise in the platelet count. It was proposed that the serial evaluation of the mean platelet volume may assist practitioners in the decision-making process of deciding whether platlet transfusions are required, or an increase in the number of circulating platelets is imminent. A decision not to transfuse would have the direct benefit of decreasing patient costs, in conjunction with eliminating a potential source for the development of an antibody against platelets.

  16. Dr. Wernher von Braun Laid to Rest

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Dr. Wernher von Braun served as Marshall Space Flight Center's first director from July 1, 1960 until January 27, 1970, when he was appointed NASA Deputy Associate Administrator for Planning. Following World War II, Dr. von Braun and his German colleagues arrived in the United States under Project Paper Clip to continue their rocket development work. In 1950, von Braun and his rocket team were transferred from Ft. Bliss, Texas to Huntsville, Alabama to work for the Army's rocket program at Redstone Arsenal and later, NASA's Marshall Space Flight Center. Under von Braun's leadership, Marshall developed the Saturn V launch vehicle which took Apollo astronauts to the moon. Dr. von Braun died in Alexandria, Va., on June 16, 1977, seven years after his NASA appointment. This photo was taken at the site where he was laid to rest.

  17. Dr. Wernher von Braun In His Office

    NASA Technical Reports Server (NTRS)

    1964-01-01

    Dr. Wernher von Braun served as Marshall Space Flight Center's first director from July 1, 1960 until January 27, 1970, when he was appointed NASA Deputy Associate Administrator for Planning. Following World War II, Dr. von Braun and his German colleagues arrived in the United States under Project Paperclip to continue their rocket development work. In 1950, von Braun and his rocket team were transferred from Ft. Bliss, Texas to Huntsville, Alabama to work for the Army's rocket program at Redstone Arsenal and later, NASA's Marshall Space Flight Center. Under von Braun's leadership, Marshall developed the Saturn V launch vehicle which took Apollo astronauts to the moon. This photo depicts von Braun in his office at MSFC.

  18. Platelet Function Tests in Bleeding Disorders.

    PubMed

    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

  19. 41 CFR 102-42.125 - How is donation of gifts or decorations accomplished?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false How is donation of gifts... 42-UTILIZATION, DONATION, AND DISPOSAL OF FOREIGN GIFTS AND DECORATIONS Donation of Foreign Gifts and Decorations § 102-42.125 How is donation of gifts or decorations accomplished? The State Agencies for...

  20. Alloantibodies in von Willebrand disease.

    PubMed

    James, Paula D; Lillicrap, David; Mannucci, Pier M

    2013-08-01

    The development of alloantibodies against von Willebrand factor (VWF) represents a rare but serious complication of treatment of von Willebrand disease (VWD), occurring in ~5% to 10% of type 3 VWD patients. Affected patients can present with a range of symptoms, including lack or loss of hemostatic response to infused VWF concentrates up to anaphylactic reactions in rare cases. It is classically reported in multitransfused patients and occurs most frequently in patients with partial or complete VWF gene deletions. A positive family history of anti-VWF antibodies also appears to be a risk factor. There is a lack of standardization of laboratory methods for antibody identification and characterization. Issues of variability in laboratory approaches as well as the rarity of the complication act as a barrier to future studies. Recombinant factor VIII as well as bypassing agents and immune tolerance have been reported as effective treatments; however, aside from case reports, little exists in the literature to guide management. The imminent clinical availability of recombinant VWF has prompted a resurgence of interest in this area. Additional study is warranted to address the deficiencies in our understanding of this treatment complication.

  1. Clearance of von Willebrand factor.

    PubMed

    Denis, Cécile V; Christophe, Olivier D; Oortwijn, Beatrijs D; Lenting, Peter J

    2008-02-01

    The life cycle of von Willebrand factor (VWF) comprises a number of distinct steps, ranging from the controlled expression of the VWF gene in endothelial cells and megakaryocytes to the removal of VWF from the circulation. The various aspects of VWF clearance have been the objects of intense research in the last few years, stimulated by observations that VWF clearance is a relatively common component of the pathogenesis of type 1 von Willebrand disease (VWD). Moreover, improving the survival of VWF is now considered as a viable therapeutic strategy to prolong the half-life of factor VIII in order to optimise treatment of haemophilia A. The present review aims to provide an overview of recent findings with regard to the molecular basis of VWF clearance. A number of parameters have been identified that influence VWF clearance, including its glycosylation profile and a number of VWF missense mutations. In addition, in-vivo studies have been used to identify cells that contribute to the catabolism of VWF, providing a starting point for the identification of receptors that mediate the cellular uptake of VWF. Finally, we discuss recent data describing chemically modification of VWF as an approach to prolong the half-life of the VWF/FVIII complex.

  2. Effects of tranexamic acid on platelet function and thrombin generation (ETAPlaT): WOMAN trial sub-study

    PubMed Central

    2016-01-01

    Background. Postpartum haemorrhage (PPH) is a leading cause of maternal death. Tranexamic acid (TXA) has the potential to reduce bleeding and a large randomized placebo controlled trial of its effect in women with PPH (The WOMAN trial) is underway. TXA might also affect coagulation factors and platelets.  Objectives. To examine the effect of TXA on thrombin generation, platelet function, fibrinogen, D-dimer and coagulation factors in women with PPH.  Methods. We will conduct a sub-study within the WOMAN trial. Women with clinically diagnosed primary PPH after vaginal or caesarean delivery are eligible for inclusion. Blood samples will be collected at baseline and 30 minutes after the first dose of study treatment. Using platelet poor plasma we will measure thrombin generation, fibrinogen, D-dimer, factor V and VIII, and Von Willebrand factor. Platelet function will be evaluated in whole blood using Multiplate® tests. Outcomes. The primary outcome is the effect of TXA on thrombin generation. Secondary outcomes include the effect of TXA on platelet function, fibrinogen, D-dimer and coagulation factors. PMID:28090594

  3. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing.

    PubMed

    Eppley, Barry L; Woodell, Jennifer E; Higgins, Joel

    2004-11-01

    Growth factors released from activated platelets initiate and modulate wound healing in both soft and hard tissues. A recent strategy to promote the wound-healing cascade is to prepare an autologous platelet concentrate suspended in plasma, also known as platelet-rich plasma, that contains growth factors and administer it to wound sites. The purpose of this study was to quantitate platelet number and growth factors released from a prepared platelet concentrate. Whole blood was drawn from 10 healthy patients undergoing cosmetic surgery and concentrated into platelet-rich plasma. Platelet counts on whole blood and platelet-rich plasma were determined using a Cell-Dyn 3200. Platelet-derived growth factor-BB, transforming growth factor-beta1, vascular endothelial growth factor, endothelial growth factor, and insulin-like growth factor-1 were measured in the platelet-rich plasma using the enzyme-linked immunosorbent assay method. In addition, platelet activation during the concentration procedure was analyzed by measuring P selectin values in blood serum. An 8-fold increase in platelet concentration was found in the platelet-rich plasma compared with that of whole blood (baseline whole blood, 197 +/- 42 x 10 platelets/microl; platelet concentrate, 1600 +/- 330 x 10 platelets/microl). The concentration of growth factors also increased with increasing platelet number. However, growth factor concentration varied from patient to patient. On average for the whole blood as compared with platelet-rich plasma, the platelet-derived growth factor-BB concentration increased from 3.3 +/- 0.9 ng/ml to 17 +/- 8 ng/ml, transforming growth factor-beta1 concentration increased from 35 +/- 8 ng/ml to 120 +/- 42 ng/ml, vascular endothelial growth factor concentration increased from 155 +/- 110 pg/ml to 955 +/- 1030 pg/ml, and endothelial growth factor concentration increased from 129 +/- 61 pg/ml to 470 +/- 320 pg/ml. No increase was found for insulin-like growth factor-1. In addition, no

  4. [Pathogen inactivation of platelets: organization consequences for platelet transfusion].

    PubMed

    Chavarin, P; DePutter, C; Boussoulade, F; Acquart, S; Vidal, M; Argaud, C; Fabrigli, P; Garraud, O

    2011-08-01

    In the past few years, pathogen reduction technologies for labile blood products have been part of the enhancement of global transfusion safety regarding residual risks of transmitting infectious pathogens. Having carried out a feasibility study for the implementation of pathogen inactivation of platelet concentrates by means of the amotosalen/HCl/UVA (Intercept™) technology, and participated to a reinforced haemovigilance study, we took the opportunity to analyze the organization consequences for platelet concentrates inventory and distribution. This impact study first indicated that those novel needs forced the blood donation service, as well as the labile blood product preparation laboratory, to review and improve practices; secondly, it showed that the routine implementation has little (no major) consequence in the overall organization, independently of the economic consequences (not covered here).

  5. Arginine-glycine-aspartic acid- and fibrinogen gamma-chain carboxyterminal peptides inhibit platelet adherence to arterial subendothelium at high wall shear rates. An effect dissociable from interference with adhesive protein binding.

    PubMed Central

    Lawrence, J B; Kramer, W S; McKeown, L P; Williams, S B; Gralnick, H R

    1990-01-01

    Arg-Gly-Asp (RGD)- and fibrinogen gamma-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein IIb-IIIa complex (GP IIb-IIIa). GP IIb-IIIa, vWF, and Fn are essential for normal platelet adherence to subendothelium. We added peptides to normal citrated whole blood before perfusion over human umbilical artery subendothelium and evaluated platelet adherence morphometrically at high (2,600 s-1) and low (800 s-1) wall shear rates. We also examined the effects of the peptides on platelet adhesion to collagen in a static system. At the high wall shear rate, RGDS and GQQHHLGGAKQAGDV caused dose-dependent reduction in the surface coverage with spread and adherent platelets. Amino acid transposition and conservative substitutions of RGD peptides and the AGDV peptide significantly inhibited platelet adherence at 2,600 s-1. By contrast, the modified RGD peptides and AGDV do not affect adhesive protein binding to platelets. None of the native or modified RGD- or fibrinogen gamma-chain peptides significantly inhibited either platelet adherence to subendothelium at 800 s-1 or platelet adhesion to collagen. Our findings demonstrate that peptides that interfere with adhesive protein binding to GP IIb-IIIa inhibit platelet adherence to vascular subendothelium with flowing blood only at high wall shear rates. Platelet adherence to subendothelium at high wall shear rates appears to be mediated by different recognition specificities from those required for fluid-phase adhesive protein binding or static platelet adhesion. PMID:2243140

  6. Higher and lower active circulating VWF levels: different facets of von Willebrand disease.

    PubMed

    Casonato, Alessandra; Pontara, Elena; Morpurgo, Margherita; Sartorello, Francesca; De Groot, Philip G; Cattini, Maria G; Daidone, Viviana; De Marco, Luigi

    2015-12-01

    Most circulating von Willebrand factor (VWF) is normally inactive and incapable of binding platelets, but numerous disorders may modify the proportion of active VWF. We explored active VWF levels in patients with von Willebrand disease (VWD) whose VWF had a higher affinity for platelet glycoprotein (GP)Ib, but different susceptibilities to ADAMTS13 and multimer patterns (9 patients lacking large multimers, 10 with a normal pattern); 12 patients with VWF C2362F and R1819_C1948delinsS mutations, which make VWF resistant to ADAMTS13 were also studied. Type 2B patients with abnormal or normal multimers had significantly more active VWF (3·33 ± 1·6 and 3·74 ± 0·74, respectively; normal 0·99 ± 0·23). The type of VWF mutation influenced VWF activation: V1316M was associated with the highest levels in patients with abnormal multimers, and R1341W in those with normal multimers. Pregnancy induced gradually rising active VWF levels and declining platelet counts in one type 2B VWD patient without large multimers. Active VWF levels dropped significantly in patients homozygous for the C2362F mutation or heterozygous for R1819_C1948delinsS mutations (0·2 ± 0·03 and 0·23 ± 0·1, respectively), and less in cases heterozygous for the VWF C2362F mutation (0·55 ± 0·17). We demonstrate that VWF may be more or less activated, with or without any direct involvement of the A1 domain, and regardless of ADAMTS13.

  7. Influence of Oxidative Stress on Stored Platelets

    PubMed Central

    2016-01-01

    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. PMID:26949396

  8. Trehalose lyophilized platelets for wound healing.

    PubMed

    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.

  9. Detection of microbial contamination in platelets

    NASA Astrophysics Data System (ADS)

    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.

  10. Thrombospondin-induced adhesion of human platelets.

    PubMed Central

    Tuszynski, G P; Kowalska, M A

    1991-01-01

    Washed human unactivated platelets attached and spread on thrombospondin (TSP)-coated microtiter plates. Platelet adhesion was promoted by divalent cations Mn2+, Mg2+, and Ca2+ as compared to buffer having all divalent cations complexed with EDTA. TSP-dependent adhesion was inhibited by anti-TSP fab fragments, an anti-TSP monoclonal antibody, an RGD-containing peptide, complex-specific anti-glycoprotein (GP)IIb-IIIa monoclonal antibodies (A2A9 or AP-2) and anti-VLA-2 monoclonal antibodies (6F1 and Gi9), but not by rabbit preimmune fab fragments, mouse IgG, an anti-GPIIIa monoclonal antibody, or monoclonal antibodies against either the human vitronectin receptor, glycocalicin, or GPIV. At saturating concentrations, anti-GPIIb-IIIa inhibited adhesion by 40-60%. Glanzman's thrombasthenic platelets, which lack GPIIb-IIIa, adhered to TSP to the same extent as anti-GPIIb-IIIa-treated normal platelets or 40-60% as well as untreated normal platelets. Antibody 6F1 (5-10 micrograms/ml) inhibited platelet adhesion of both normal and thrombasthenic platelets by 84-100%. Both VLA-2 antibodies also inhibited collagen-induced platelet adhesion, but had no effect on fibronectin-induced adhesion of normal platelets. These data indicate that platelets specifically adhere to TSP and that this adhesion is mediated through GPIIb-IIIa and/or VLA-2. Images PMID:2010551

  11. Indium-111 platelet imaging for detection of platelet deposition in abdominal aneurysms and prosthetic arterial grafts

    SciTech Connect

    Ritchie, J.L.; Stratton, J.R.; Thiele, B.; Haminton, G.W.; Warrick, L.N.; Huang, T.W.; Harker, L.A.

    1981-04-01

    Thirty-four platelet imaging studies were performed in 23 patients to determine whether platelet deposition could be detected in patients with vascular aneurysms (18 patients) or in patients in whom Dacron prosthetic grafts had been placed (5 patients). In patients in whom abnormal platelet deposition was detected, the effect of administration of platelet-active drugs on platelet deposition was examined. Of the 18 patients with an aneurysm, 12 had equivocally positive studies on initial imaging and 2 had equivocally positive images. Of five patients with Dacron arterial grafts in place, four had diffuse platelet deposition in the grafts; the fifth patient had a platelet deposition only in a pseudoaneurysm. Eight patients with an abdominal aneurysm and positive or equivocally positive baseline images were restudied during platelet-active drug therapy either with aspirin plus dipyridamole (seven patients) or with sulfinpyrazone (four patients). No patient studied during treatment with aspirin plus dipyridamole had detectably decreased platelet deposition compared with baseline determinations. In contrast, two of four patients studied while receiving sulfinpyrazone showed decreased platelet deposition. Thus, platelet imaging may be of value for studying platelet physiology in vivo and for assessing platelet-active drugs and the thrombogenicity of prosthetic graft materials in human beings.

  12. Effect of sildenafil on platelet function and platelet cGMP of patients with erectile dysfunction.

    PubMed

    Akand, M; Gencer, E; Yaman, Ö; Erişgen, G; Tekin, D; Özdiler, E

    2015-12-01

    To investigate the effect of sildenafil on platelet function and cyclic guanosine monophosphate (cGMP) levels in patients with erectile dysfunction, we evaluated the association between erectile function and platelet responses after administration of 100 mg sildenafil. Erectile responses were monitored after 8 daily doses of the drug. Adenosine diphosphate (ADP) and collagen-induced platelet aggregation and simultaneous adenosine triphosphate (ATP) release and cGMP levels were determined before and after sildenafil therapy. Basal levels for platelet aggregation, ATP release and cGMP were compared with age-matched controls. There was no difference among basal levels of platelet responses between patients and controls, except for ADP-induced platelet aggregation (P = 0.04). It was significantly higher in the patient group. Analysis of the responses to sildenafil revealed that for the patients who showed a positive erectile response, there was a significant increase in platelet cGMP (P = 0.028) and a decrease in ADP-induced platelet aggregation (P = 0.04). However, for those who showed a negative or poor erectile response, there was no change in platelet cGMP levels and platelet functions. Sildenafil did not affect collagen-induced platelet responses although cGMP levels of the responders increased. It is concluded that sildenafil increases platelet cGMP in the patients with positive erectile response. Therefore, it has been speculated that platelet cGMP may be used as an index for erectile response.

  13. Flow and delta-P dictate where thrombin, fibrin, and von Willebrand Factor will be found.

    PubMed

    Diamond, Scott L

    2016-05-01

    Hemostasis occurs in two different topological scenarios: complete severing of a vessel or disruption of the vessel wall. Either to meet the daily rigors of active life or during an acute trauma, hemostasis involves the regulated and self-limiting production of thrombin to stop bleeding. In contrast, arterial and venous thrombosis typically involves the unregulated, intraluminal growth of a clot, in the absence of bleeding. For either hemostasis or thrombosis, the presence of flow and pressure gradients (delta-P, ΔP) dictates when and where thrombin and fibrin are located and in what quantity. For hemostatic clots, fibrin formation helped limit clot growth. We found that γ'-fibrinogen had a role in limiting clot growth via anti-thrombin activity at venous, but not arterial conditions. For hemophilic blood, severe factor deficiency (<1% healthy) led to a defect in both platelet and fibrin deposition under flow. However, moderate deficiency, which is associated with a less severe bleeding phenotype, had normalized platelet function but still lacked fibrin production. We conclude signaling levels of thrombin can be generated during moderate hemophilia to sufficiently activate platelets to achieve primary hemostasis, even if fibrin formation remains defective. Finally, as a clot grows, shear stresses can become sufficiently extreme in diseased arteries to drive von Willebrand Factor self-association into massive fibers, potentially the final burst of clot growth towards full thrombotic occlusion.

  14. Force sensing by the vascular protein von Willebrand factor is tuned by a strong intermonomer interaction

    PubMed Central

    Müller, Jochen P.; Mielke, Salomé; Löf, Achim; Obser, Tobias; Beer, Christof; Bruetzel, Linda K.; Pippig, Diana A.; Vanderlinden, Willem; Lipfert, Jan; Schneppenheim, Reinhard; Benoit, Martin

    2016-01-01

    The large plasma glycoprotein von Willebrand factor (VWF) senses hydrodynamic forces in the bloodstream and responds to elevated forces with abrupt elongation, thereby increasing its adhesiveness to platelets and collagen. Remarkably, forces on VWF are elevated at sites of vascular injury, where VWF’s hemostatic potential is important to mediate platelet aggregation and to recruit platelets to the subendothelial layer. Adversely, elevated forces in stenosed vessels lead to an increased risk of VWF-mediated thrombosis. To dissect the remarkable force-sensing ability of VWF, we have performed atomic force microscopy (AFM)-based single-molecule force measurements on dimers, the smallest repeating subunits of VWF multimers. We have identified a strong intermonomer interaction that involves the D4 domain and critically depends on the presence of divalent ions, consistent with results from small-angle X-ray scattering (SAXS). Dissociation of this strong interaction occurred at forces above ∼50 pN and provided ∼80 nm of additional length to the elongation of dimers. Corroborated by the static conformation of VWF, visualized by AFM imaging, we estimate that in VWF multimers approximately one-half of the constituent dimers are firmly closed via the strong intermonomer interaction. As firmly closed dimers markedly shorten VWF’s effective length contributing to force sensing, they can be expected to tune VWF’s sensitivity to hydrodynamic flow in the blood and to thereby significantly affect VWF’s function in hemostasis and thrombosis. PMID:26787887

  15. 5. VIEW OF THE LAMP HOUSE LOOKING EAST. DECORATIVE BRICK ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW OF THE LAMP HOUSE LOOKING EAST. DECORATIVE BRICK CORBELING AND PILASTERS DIVIDE THE BAYS. BRICK CORBELING ACCENTS THE EAVES. CONCRETE LINTELS ABOVE THE WINDOW OPENINGS PROVIDE ADDITIONAL DETAILING. - Tower Hill No. 2 Mine, Approximately 0.47 mile Southwest of intersection of Stone Church Road & Township Route 561, Hibbs, Fayette County, PA

  16. VIEW THROUGH DECORATIVE GRILLE OF LIVING ROOM, WITH SLIDING DOORS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW THROUGH DECORATIVE GRILLE OF LIVING ROOM, WITH SLIDING DOORS ON THE LEFT HAND SIDE. VIEW FACING NORTH - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Three-Bedroom Single-Family Type 9, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  17. 5. VIEW OF INTERIOR OF BUILDING 220, DECORATIVE FLOOR AT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW OF INTERIOR OF BUILDING 220, DECORATIVE FLOOR AT ENTRANCE. VINYL TILE INLAID FLOOR WITH A RED BACKGROUND, GREEN EMBLEM, BROWN AND WHITE EAGLE, RED AND WHITE SHIELD, BLACK ANCHOR, RED ARROWS AND LETTERING. - U.S. Naval Base, Pearl Harbor, Brig, Neville Way near Ninth Street at Marine Barracks, Pearl City, Honolulu County, HI

  18. Sugar-decorated hydroxyapatite: an inorganic material bioactivated with carbohydrates.

    PubMed

    Russo, Laura; Landi, Elena; Tampieri, Anna; Natalello, Antonino; Doglia, Silvia M; Gabrielli, Luca; Cipolla, Laura; Nicotra, Francesco

    2011-09-06

    An efficient method for the direct and covalent decoration of granules of nanostructured apatite with a sample monosaccharide is presented; the hydroxyapatite material was directly functionalised with a short azido-containing spacer arm, to which α-propargyl glucopyranoside has been chemoselectively ligated by Huisgen-type cycloaddition. The 'glycosylated' hydroxypatite was characterised by its ability to interact with glucose recognising lectins.

  19. Hydrogen adsorption in metal-decorated silicon carbide nanotubes

    NASA Astrophysics Data System (ADS)

    Singh, Ram Sevak; Solanki, Ankit

    2016-09-01

    Hydrogen storage for fuel cell is an active area of research and appropriate materials with excellent hydrogen adsorption properties are highly demanded. Nanotubes, having high surface to volume ratio, are promising storage materials for hydrogen. Recently, silicon carbide nanotubes have been predicted as potential materials for future hydrogen storage application, and studies in this area are ongoing. Here, we report a systematic study on hydrogen adsorption properties in metal (Pt, Ni and Al) decorated silicon carbide nanotubes (SiCNTs) using first principles calculations based on density functional theory. The hydrogen adsorption properties are investigated by calculations of adsorption energy, electronic band structure, density of states (DOS) and Mulliken charge population analysis. Our findings show that hydrogen adsorptions on Pt, Ni and Al-decorated SiCNTs undergo spontaneous exothermic reactions with significant modulation of electronic structure of SiCNTs in all cases. Importantly, according to the Mulliken charge population analysis, dipole-dipole interaction causes chemisorptions of hydrogen in Pt, Ni and Al decorated SiCNTs with formation of chemical bonds. The study is a platform for the development of metal decorated SiCNTs for hydrogen adsorption or hydrogen storage application.

  20. The mechanism by which arabinoxylanases can recognize highly decorated xylans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The enzymatic degradation of plant cell walls is an important biological process of increasing environmental and industrial significance. Xylan, a major component of the plant cell wall, consists of a backbone of beta 1,4-xylose (Xylp) units that are often decorated with arabinofuranose (Araf) side ...

  1. LANAI OF UNIT B. NOTE THE DECORATIVE PROTRUDING CONCRETE MASONRY. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    LANAI OF UNIT B. NOTE THE DECORATIVE PROTRUDING CONCRETE MASONRY. VIEW FACING WEST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, U-Shaped Two-Bedroom Duplex Type 1, Acacia Road, Birch Circle, and Cedar Drive, Pearl City, Honolulu County, HI

  2. 5. DETAIL VIEW OF THE EGYPTIAN MOTIF DECORATIVE ELEMENTS OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. DETAIL VIEW OF THE EGYPTIAN MOTIF DECORATIVE ELEMENTS OF BUILDING 1'S MAIN ENTRY TOWER (INCLUDING THE ENGAGED COLUMN CAPITALS, PILASTERS & CAPITALS, CORNICES, AND TERRA COTTA EAGLES); LOOKING SW FROM THE E WING ROOF. (Ryan) - Veterans Administration Medical Center, Building No. 1, Old State Route 13 West, Marion, Williamson County, IL

  3. 25. LOBBY FIREPLACE. NOTE THE GEYSER DECORATING THE FIREPLACE SCREEN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    25. LOBBY FIREPLACE. NOTE THE GEYSER DECORATING THE FIREPLACE SCREEN AND THE WEIGHTS AND PENDULUM HANGING FROM THE CLOCK DESIGNED BY ARCHITECT ROBERT C. REAMER. - Old Faithful Inn, 900' northeast of Snowlodge & 1050' west of Old Faithful Lodge, Lake, Teton County, WY

  4. Breaking Monotony: A Reflective Study of Teaching Decorative Pot Making

    ERIC Educational Resources Information Center

    Nortey, Samuel; Okai, Frederick E.; Bodjawah, Edwin K.

    2013-01-01

    In art, the idea of pots being circular and cylindrical is an intuitive proposition that defines why potters have, up to the present, made wonderful decorations in the round. It is believed that potters do not want to subvert or break away from their tradition, perhaps because the art started as family craft. In this study, the authors describe…

  5. CLOSEUP OF THE DECORATIVE FEATURES OF THE WINDOW AND DOOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    CLOSE-UP OF THE DECORATIVE FEATURES OF THE WINDOW AND DOOR AREA ON THE NORTH SIDE OF BLDG 662. NOTE THE CAST CONCRETE ORNAMENTAL FEATURES FROM THE ORIGINAL CONSTRUCTION. - U.S. Naval Base, Pearl Harbor, Bachelor Officer Quarters, Dealy Circle, Pearl City, Honolulu County, HI

  6. Silver decorated multiwalled carbon nanotubes and their characterization

    NASA Astrophysics Data System (ADS)

    Gahlot, Swati; Kulshrestha, Vaibhav; Shahi, V. K.

    2014-04-01

    Deposition of silver nanoparticles on functionalized multiwalled carbon nanotubes is done in the present study. To decorate silver nanoparticles on CNT walls silver nitrate (AgNO3) was used as precursor. Finally prepared nanotubes (Ag-CNT) were analyzed by TEM, XRD and FTIR for the structural and chemical characterization.

  7. A double commutant theorem for Murray–von Neumann algebras

    PubMed Central

    Liu, Zhe

    2012-01-01

    Murray–von Neumann algebras are algebras of operators affiliated with finite von Neumann algebras. In this article, we study commutativity and affiliation of self-adjoint operators (possibly unbounded). We show that a maximal abelian self-adjoint subalgebra of the Murray–von Neumann algebra associated with a finite von Neumann algebra is the Murray–von Neumann algebra , where is a maximal abelian self-adjoint subalgebra of and, in addition, is . We also prove that the Murray–von Neumann algebra with the center of is the center of the Murray–von Neumann algebra . Von Neumann’s celebrated double commutant theorem characterizes von Neumann algebras as those for which , where , the commutant of , is the set of bounded operators on the Hilbert space that commute with all operators in . At the end of this article, we present a double commutant theorem for Murray–von Neumann algebras. PMID:22543165

  8. Complement Activation Alters Platelet Function

    DTIC Science & Technology

    2015-12-01

    2004; Danese et al., 2003). Recent studies have demonstrated a role for platelets in the development of both innate and adaptive immune responses...mediated modulation of adaptive immunity. A communication link between innate and adaptive immune compartments. Immunity 19:9-19. 4. Fleming, S.D., M...Monestier, and G.C. Tsokos. 2004. Accelerated ischemia/reperfusion- induced injury in autoimmunity-prone mice. Journal of immunology 173:4230-4235

  9. Platelets: cell proliferation and atherosclerosis.

    PubMed

    Ross, R

    1979-04-01

    Intimal smooth muscle proliferation is the hallmark of the lesions of atherosclerosis. Endothelial injury is postulated to precede this intimal smooth muscle proliferative response, which is mediated by a potent mitogenic factor derived from adherence, aggregation, and release by platelets at sites of endothelial injury. Smooth muscle proliferation is accompanied by varying amounts of connective tissue formation and intracellular and extracellular lipid deposition, dependent upon the risk factors encountered in each patient. The platelet-derived mitogen (PF) is a stable, cationic, relatively low molecular weight (10,000-30,000) protein that has been partially purified by ion exchange chromotography and gel filtration. Less than 100 ng of PF/ml culture medium can stimulate sparse 3T3 cells or smooth muscle cells, but not endothelial cells, to undergo multiple cell divisions in the presence of 5% cell-free, plasma-derived serum. The latter contains no mitogenic activity. The interaction of the platelet mitogen and plasma-derived components, including lipoproteins, plays a critical role in smooth muscle proliferation in vitro and in vivo in the induction of the lesions of atherosclerosis.

  10. Indikatorenbasierte Bewertung von Entwurfsentscheidungen auf Systemebene

    NASA Astrophysics Data System (ADS)

    Freier, M.; Wenzler, A.; Mayer, T.; Gerlach, J.; Rosenstiel, W.

    2013-07-01

    Bei dem Entwurf von anwendungsspezifischen integrierten Schaltungen muss ein Entwickler zusätzliche Funktionen integrieren und die zunehmende Komplexität bewältigen. Für die Reduzierung der Kosten bleibt weiterhin die Verkürzung der benötigten Entwicklungszeit ein Ziel. Ein entscheidender Faktor dabei ist die zuverlässige Absicherung von Entwurfsentscheidungen in einer frühen Entwurfsphase. In der vorliegenden Arbeit wird eine Methode vorgestellt, die eine Bewertung von Entwurfsentscheidungen bei Systemmodellen mittels automatisch ermittelter Indikatoren ermöglichen soll. Die Systemmodelle können mit der Entwurfsumgebung MATLAB/Simulink oder in SystemC beschrieben sein.

  11. Regulation of actin polymerization by tropomodulin-3 controls megakaryocyte actin organization and platelet biogenesis.

    PubMed

    Sui, Zhenhua; Nowak, Roberta B; Sanada, Chad; Halene, Stephanie; Krause, Diane S; Fowler, Velia M

    2015-07-23

    The actin cytoskeleton is important for platelet biogenesis. Tropomodulin-3 (Tmod3), the only Tmod isoform detected in platelets and megakaryocytes (MKs), caps actin filament (F-actin) pointed ends and binds tropomyosins (TMs), regulating actin polymerization and stability. To determine the function of Tmod3 in platelet biogenesis, we studied Tmod3(-/-) embryos, which are embryonic lethal by E18.5. Tmod3(-/-) embryos often show hemorrhaging at E14.5 with fewer and larger platelets, indicating impaired platelet biogenesis. MK numbers are moderately increased in Tmod3(-/-) fetal livers, with only a slight increase in the 8N population, suggesting that MK differentiation is not significantly affected. However, Tmod3(-/-) MKs fail to develop a normal demarcation membrane system (DMS), and cytoplasmic organelle distribution is abnormal. Moreover, cultured Tmod3(-/-) MKs exhibit impaired proplatelet formation with a wide range of proplatelet bud sizes, including abnormally large proplatelet buds containing incorrect numbers of von Willebrand factor-positive granules. Tmod3(-/-) MKs exhibit F-actin disturbances, and Tmod3(-/-) MKs spreading on collagen fail to polymerize F-actin into actomyosin contractile bundles. Tmod3 associates with TM4 and the F-actin cytoskeleton in wild-type MKs, and confocal microscopy reveals that Tmod3, TM4, and F-actin partially colocalize near the membrane of proplatelet buds. In contrast, the abnormally large proplatelets from Tmod3(-/-) MKs show increased F-actin and redistribution of F-actin and TM4 from the cortex to the cytoplasm, but normal microtubule coil organization. We conclude that F-actin capping by Tmod3 regulates F-actin organization in mouse fetal liver-derived MKs, thereby controlling MK cytoplasmic morphogenesis, including DMS formation and organelle distribution, as well as proplatelet formation and sizing.

  12. The impact of platelet transfusion characteristics on posttransfusion platelet increments and clinical bleeding in patients with hypoproliferative thrombocytopenia.

    PubMed

    Triulzi, Darrell J; Assmann, Susan F; Strauss, Ronald G; Ness, P M; Hess, John R; Kaufman, Richard M; Granger, Suzanne; Slichter, Sherrill J

    2012-06-07

    Platelet characteristics, such as platelet dose, platelet source (apheresis vs pooled), platelet donor-recipient ABO compatibility, and duration of platelet storage, can affect posttransfusion platelet increments, but it is unclear whether these factors impact platelet transfusion efficacy on clinical bleeding. We performed secondary analyses of platelet transfusions given in the prospective randomized Platelet Dose Study, which included 1272 platelet-transfused hematology-oncology patients who received 6031 prophylactic platelet transfusions. The primary outcome of these analyses was time from first transfusion to first World Health Organization ≥ grade 2 bleeding. Platelet transfusion increments were assessed at 0.25 to 4 hours and 16 to 32 hours after platelet transfusion. There were 778 patients evaluable for analysis of time to bleeding. Adjusted models showed that randomized dose strategy, platelet source, ABO compatibility, and duration of storage did not predict this outcome. Platelet increments were generally higher for transfusions of apheresis platelets, ABO-identical platelets, and platelets stored 3 days versus 4 to 5 days. Thus, although platelet source, ABO compatibility, and duration of storage exert a modest impact on both absolute and corrected posttransfusion platelet increments, they have no measurable impact on prevention of clinical bleeding. This trial was registered at www.clinicaltrials.gov as #NCT00128713.

  13. Therapeutic platelet reduction: Use in postsplenectomy thrombocytosis

    PubMed Central

    Negi, Gita; Talekar, Manjubala S.; Verma, Sanjiv Kumar; Rehmani, Babar; Gupta, Vibha; Agarwal, Amit; Harsh, Meena

    2015-01-01

    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. PMID:25722581

  14. Mean platelet volume in acute rheumatic fever.

    PubMed

    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.

  15. Nouvelle cuisine: platelets served with inflammation.

    PubMed

    Kapur, Rick; Zufferey, Anne; Boilard, Eric; Semple, John W

    2015-06-15

    Platelets are small cellular fragments with the primary physiological role of maintaining hemostasis. In addition to this well-described classical function, it is becoming increasingly clear that platelets have an intimate connection with infection and inflammation. This stems from several platelet characteristics, including their ability to bind infectious agents and secrete many immunomodulatory cytokines and chemokines, as well as their expression of receptors for various immune effector and regulatory functions, such as TLRs, which allow them to sense pathogen-associated molecular patterns. Furthermore, platelets contain RNA that can be nascently translated under different environmental stresses, and they are able to release membrane microparticles that can transport inflammatory cargo to inflammatory cells. Interestingly, acute infections can also result in platelet breakdown and thrombocytopenia. This report highlights these relatively new aspects of platelets and, thus, their nonhemostatic nature in an inflammatory setting.

  16. The Role of Platelets in Venous Thromboembolism.

    PubMed

    Montoro-García, Silvia; Schindewolf, Marc; Stanford, Sophia; Larsen, Ole Halfdan; Thiele, Thomas

    2016-04-01

    Multiple factors contribute to the risk of venous thromboembolism (VTE). Platelets have attracted much interest in arterial cardiovascular disease, whereas their role in VTE has received much less attention. Recent evidence suggests that platelets may play a more important role in VTE than previously anticipated. This review discusses the mechanisms that link platelets with venous thrombotic disease and their potential applications as novel risk factors for VTE. In addition, animal studies and randomized clinical trials that highlight the potential effect of antiplatelet therapy in venous thrombosis are evaluated to assess the role of platelets in VTE. The clinical significance of platelets for VTE risk assessment in specific patient cohorts and their role as a suitable therapeutic target for VTE prevention is acknowledged. The role of platelets in VTE is a promising field for future research.

  17. Anti-platelets in diabetes management.

    PubMed

    Grantham, N M; Magliano, D J; Tai, G; Cohen, N; Shaw, J E

    2010-06-01

    This study aimed to determine the prevalence of anti-platelet use, and the extent to which contraindications to anti-platelet therapy prevent its use, in 726 diabetic patients attending a private clinic. Among those who reported a history of cardiovascular disease (CVD), 87.1% were on anti-platelet therapy. Of those without prior CVD but with at least one CVD risk factor, 59.8% were not on anti-platelet therapy, but only 7.1% of these had a contraindication to anti-platelet therapy. This study showed that high usage of anti-platelet therapy in diabetic patients with prior CVD is achievable, and that contraindications did not explain low use in those without prior CVD.

  18. Blood platelet aggregation and personality traits.

    PubMed

    Jenkins, C D; Thomas, G; Olewine, D; Zyzanski, S J; Simpson, M T; Hames, C G

    1975-12-01

    Changes in blood platelet aggregation may precipitate episodes of arterial occlusive diseases. Little is known, however, regarding the influence of psychological traits, emotional states and other behavioral stressors on platelet aggregation phenomena. This study examined 46 healthy college men at rest and after submaximal treadmill exercise. Associations were found between the duration of platelet aggregation and a number of scores from the California Psychological Inventory and self-administered anxiety scales. The more socially adequate, poised and dominant persons--those with more mature ego development and less overt anxiety--had platelets with more prolonged aggregation reactions to the in vitro introduction of noradrenalin. Irreversible aggregation of platelets occurred more regularly to lower in vitro concentrations of noradrenalin in platelet samples drawn from subjects who were less anxious and tended to be more rigidly defensive. It is premature to attempt to derive clinical implications from this exploratory work, but some implications for the design of future research are discussed.

  19. Molecular and cellular biology of von Willebrand factor.

    PubMed

    Denis, Cécile V

    2002-01-01

    von Willebrand factor (VWF) is a plasma protein that performs 2 main functions in hemostasis: it mediates platelet adhesion to the injured vessel wall, and it carries and protects coagulation factor VIII. VWF is synthesized through a multistep process in endothelial cells and megakaryocytes as a very large polymer composed of identical disulfide-linked 250-kd subunits. In endothelial cells, VWF not only directs the formation of its own storage granules, the Weibel-Palade bodies, but it also acts as a chaperone molecule to direct other proteins, such as P-selectin, into these granules. Upon stimulation of the endothelium, the Weibel-Palade bodies will be translocated to the plasma membrane, and their contents will be secreted into the plasma milieu. The expression of VWF can be regulated at different levels by a number of genetic and environmental factors, resulting in control of its activity. New roles for VWF, especially in inflammatory processes, have recently been suggested, indicating that some aspects of this well-studied protein remain to be investigated.

  20. Keeping von Willebrand Factor under Control: Alternatives for ADAMTS13.

    PubMed

    Tersteeg, Claudia; Fijnheer, Rob; Pasterkamp, Gerard; de Groot, Philip G; Vanhoorelbeke, Karen; de Maat, Steven; Maas, Coen

    2016-02-01

    Von Willebrand factor (VWF) is one of the most important proteins of the hemostatic system. Its multimeric state is essential for its natural function to guide platelets to sites of injury. ADAMTS13 is the key protease that regulates the multimeric state of VWF. Without ADAMTS13, VWF multimers can grow to pathologically large sizes. This is a risk factor for the life-threatening condition thrombotic thrombocytopenic purpura (TTP). In this condition, VWF-rich thrombi occlude the microvasculature of various tissues. Intriguingly, a complete ADAMTS13 deficiency does not cause continuous TTP, either in patients or genetically targeted mice. Instead, TTP occurs in episodes of disease, separated by extended periods of remission. This indicates that regulating factors beyond ADAMTS13 are likely involved in this pathologic cascade of events. This raises the question of what really happens when ADAMTS13 is (temporarily) unavailable. In this review, we explore the possible role of complementary mechanisms that are capable of modifying the thrombogenic potential of VWF.

  1. Allosteric activation of ADAMTS13 by von Willebrand factor.

    PubMed

    Muia, Joshua; Zhu, Jian; Gupta, Garima; Haberichter, Sandra L; Friedman, Kenneth D; Feys, Hendrik B; Deforche, Louis; Vanhoorelbeke, Karen; Westfield, Lisa A; Roth, Robyn; Tolia, Niraj Harish; Heuser, John E; Sadler, J Evan

    2014-12-30

    The metalloprotease ADAMTS13 cleaves von Willebrand factor (VWF) within endovascular platelet aggregates, and ADAMTS13 deficiency causes fatal microvascular thrombosis. The proximal metalloprotease (M), disintegrin-like (D), thrombospondin-1 (T), Cys-rich (C), and spacer (S) domains of ADAMTS13 recognize a cryptic site in VWF that is exposed by tensile force. Another seven T and two complement C1r/C1s, sea urchin epidermal growth factor, and bone morphogenetic protein (CUB) domains of uncertain function are C-terminal to the MDTCS domains. We find that the distal T8-CUB2 domains markedly inhibit substrate cleavage, and binding of VWF or monoclonal antibodies to distal ADAMTS13 domains relieves this autoinhibition. Small angle X-ray scattering data indicate that distal T-CUB domains interact with proximal MDTCS domains. Thus, ADAMTS13 is regulated by substrate-induced allosteric activation, which may optimize VWF cleavage under fluid shear stress in vivo. Distal domains of other ADAMTS proteases may have similar allosteric properties.

  2. Size Dependent Platelet Subpopulations: Relationship of Platelet Volume to Ultrastructure Enzymatic Activity, and Function.

    DTIC Science & Technology

    1983-03-10

    of the present apheresis instruments to separate the larger more functional platelets from the smaller ones. The selective isolation of large... PLATELET VOLUME T. -(U) BOSTON UNIV MA SCHOOL OF I MEDICINE C B THOMPSON ET RL 10 MAR 83 BUSM-93-89 UNIIDN919CA89 /68 6ilfflfllflflflflll l...N00014-79-C-0168 TECHNICAL REPORT NO. 83-08 SIZE DEPENDENT PLATELET SUBPOPULATIONS: RELATIONSHIP OF PLATELET VOLUME TO ULTRASTRUCTURE. ENZYMATIC ACTIVITY

  3. Extending The Shelf Life Of Blood Platelets

    NASA Technical Reports Server (NTRS)

    Surgenor, Douglas M.

    1988-01-01

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

  4. Status Report on Cryopreservation of Human Platelets.

    DTIC Science & Technology

    1979-03-27

    Platelets." In: Erythrocytes, Path.44:678, 1965. lets contributed to our excellent re- Thrombocytes and Leukocytes. Eds. * suits. The observations in...the methodsof measurement: 80% when the platelet counts were made by phase microscopy ,85% by Coulter counter, and 60% by the Technicon. These... microscopy , 85’/ by Coulter counter, and 60% by the Technicon. These platelets had 5 1 Cr survival values in viv’o about 50’le of those observed for

  5. Platelet mimicry: The emperor's new clothes?

    PubMed

    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 to include in vivo targeting of damaged blood vessels and binding to platelet-adhering opportunistic pathogens. We present views for improved, and pharmaceutically viable nanoparticle design strategies.

  6. The role of RNA uptake in platelet heterogeneity.

    PubMed

    Clancy, Lauren; Beaulieu, Lea M; Tanriverdi, Kahraman; Freedman, Jane E

    2017-03-09

    The role of platelets in regulating vascular homeostasis has expanded beyond mediation of haemostasis and thrombosis. The discovery of platelet RNA and the presence of subpopulations of platelets containing varying amounts of RNA suggest a role for platelet transcripts in vascular function. As the RNA in anucleated platelets is biologically functional and may transfer to other vascular cells, we hypothesised that platelet RNA diminishes over the lifespan of the platelet with diminishing platelet size due to horizontal cellular transfer. The purpose of this study is to determine if platelet RNA variance is the result of horizontal cellular transfer between platelets and other vascular cells. Utilising platelet sorting and RNA sequencing, we found that smaller platelets contained a more diverse set of transcripts than larger platelets. Further investigation using fluorescence imaging, gene expression analyses and in vitro and in vivo modelling revealed that platelets take up RNA from other vascular cells in a complex manner, revealing a dynamic role for platelets in modulating vascular homeostasis through bidirectional RNA transfer. The resultant RNA profile heterogeneity suggests unique functional roles for platelets dependent on size and complexity. This study expands our basic understanding of platelet function and heterogeneity and is the first to evaluate endogenous vascular RNA uptake and its relation to platelet processes. Our findings describe a novel endogenous phenomenon that can help elucidate the platelet's role in these non-thrombotic and haemostatic fields, as well as present potential for diagnostic and therapeutic development.

  7. Comparison of inhibitory and binding characteristics of an antibody causing acquired von Willebrand syndrome: an assay for von Willebrand factor binding by antibody.

    PubMed

    Fricke, W A; Brinkhous, K M; Garris, J B; Roberts, H R

    1985-09-01

    An acquired inhibitor of von Willebrand factor (vWF) activity occurring in a patient with benign gammopathy and von Willebrand syndrome (vWS) has been partially characterized. The inhibitor-induced syndrome resulted in low to undetectable plasma levels of vWF/ristocetin, vWF/botrocetin, FVIIIR:Ag, and FVIII:C with a normal to slightly prolonged bleeding time. Platelet vWF was normal. Intensive and continuous infusion of a heat-treated factor VIII concentrate (Hemofil-T, Hyland, Glendale, Calif) elevated the FVIII:C plasma levels to about 100%, with an increase in FVIIIR:Ag levels to about 340% and vWF/ristocetin levels to about 40%, much lower than expected based on the dose of Hemofil-T and its content of vWF and FVIII:C activities. The inhibitor bound to staphylococcal protein A (SpA) with high affinity, indicating an IgG antibody (Ab). An assay for the vWF-binding capacity was developed on the basis of absorption of the Ab from serially diluted plasma by SpA and removal of vWF and FVIII:C activities from normal plasma by the SpA-Ab complex. The Ab-binding site was on the vWF component of the factor VIII complex. The Ab was unable to bind isolated FVIII:C. The combined use of the new vWF-binding assay and a battery of tests for inhibition of vWF-dependent platelet aggregation with ristocetin (which detects high molecular weight vWF), with botrocetin (which detects high and low molecular weight vWF), and with platelet-aggregating factor (which detects high molecular weight vWF) provided a means of analysis of Ab effect on in vitro vWF function. Using these tests, a comparison was made of the effects of the vWS Ab with those of an Ab inhibitor occurring in homozygous von Willebrand's disease. The Ab of the vWS patient had weak inhibitory action on vWF/ristocetin without having an effect on vWF/botrocetin and platelet-aggregating factor, a high titer vWF-binding capacity, and no anamnestic response following concentrate therapy. These findings contrasted with those

  8. Platelet function tests, independent of platelet count, are associated with bleeding severity in ITP.

    PubMed

    Frelinger, Andrew L; Grace, Rachael F; Gerrits, Anja J; Berny-Lang, Michelle A; Brown, Travis; Carmichael, Sabrina L; Neufeld, Ellis J; Michelson, Alan D

    2015-08-13

    Immune thrombocytopenia (ITP) patients with similarly low platelet counts differ in their tendency to bleed. To determine if differences in platelet function in ITP patients account for this variation in bleeding tendency, we conducted a single-center, cross-sectional study of pediatric patients with ITP. Bleeding severity (assessed by standardized bleeding score) and platelet function (assessed by whole blood flow cytometry) with and without agonist stimulation was evaluated in 57 ITP patients (median age, 9.9 years). After adjustment for platelet count, higher levels of thrombin receptor activating peptide (TRAP)-stimulated percent P-selectin- and activated glycoprotein (GP)IIb-IIIa-positive platelets were significantly associated with a lower bleeding score, whereas higher levels of immature platelet fraction (IPF), TRAP-stimulated platelet surface CD42b, unstimulated platelet surface P-selectin, and platelet forward light scatter (FSC) were associated with a higher bleeding score. Thus, platelet function tests related to platelet age (IPF, FSC) and activation through the protease activated receptor 1 (PAR1) thrombin receptor (TRAP-stimulated P-selectin, activated GPIIb-IIIa, and CD42b), independent of platelet count, are associated with concurrent bleeding severity in ITP. These tests may be useful markers of future bleeding risk in ITP.

  9. Response of Northern Elephant Seal platelets to pressure and temperature changes: a comparison with human platelets.

    PubMed

    Field, Cara L; Tablin, Fern

    2012-08-01

    Mammalian blood platelets are activated by physiological agonists such as collagen or thrombin, or by physical stimuli such as cold temperatures and rapid decompression. Marine mammals regularly experience cold temperatures, high pressures and rapid decompression while diving, yet do not appear to suffer from thrombotic events during routine dive activity. We evaluated the effects of cold temperature and high pressure excursions on Northern Elephant Seal (NES) platelets and compared NES platelet response to that of human platelets subjected to identical stimuli. NES platelets undergo cold-induced activation when chilled to 4 °C, and 3 distinct phase transitions can be measured using Fourier Transform Infrared Spectroscopy. NES platelet membrane lipid composition was determined using thin layer chromatography and NES platelets were found to have three times the amount of cholesterol (21% by weight) as human platelets. When exposed to high pressure-rapid decompression excursion, NES platelets did not undergo morphological shape change nor bind increased amounts of fibrinogen, while human platelets were significantly activated by the same excursion. These results demonstrate that while NES platelets are activated by the physical stimulus of cold temperatures, they are resistant to decompression-induced activation. We suggest that the composition of NES platelet membranes may play an important role in preventing pressure-related activation.

  10. Platelet activation of platelet concentrates derived from buffy coat and apheresis methods.

    PubMed

    Ali, Soleimany Ferizhandy

    2011-02-01

    Preparation for storage may cause platelet activation. The quality of platelet concentrates plays an important role in transfusion therapy. Platelet concentrates are produced by different centrifugation methods; buffy coat (buffy coat-derived platelet concentrates-BC) and plateletpheresis (apheresis-derived platelet concentrates-APC). Their quality was assessed using the following parameters: platelet, WBC and RBC counts pH, volume, platelet factor 4 (PF4) and Annexin V. The present paper compares the quality of both platelet preparations in vitro. In this experimental study, 30 platelet concentrates were harvested with the Haemonetics MCS plus and 30 units via the buffy coat (BC) method. The percentages of Annexin V expression, PF4 levels, platelet, WBC and RBC counts, pH and volume were measure immediately after collection and after 3 days of storage. During storage for up to 3 days, BC units displayed, no significant pH or RBC, difference in comparison with apheresis preparations (p>0.05). During storage for up to 3 days, BC units displayed a significant increase in the PF4 and Annexin V expression, compared to the apheresis preparations on day three (p<0.05). The kinetics of PF4 and Annexin V levels are influenced by the method used to prepare platelets for storage. The different levels of PF4 and Annexin V in BCs and APCs clearly demonstrates a progressive activation of BC platelets exceeding that of APC. However, in vivo studies should be performed to confirm these findings.

  11. Mean platelet volume in patients with fibromyalgia.

    PubMed

    Haliloğlu, S; Carlioglu, A; Sahiner, E; Karaaslan, Y; Kosar, A

    2014-10-01

    Fibromyalgia is a syndrome characterised by chronic widespread pain at multiple tender points, as well as joint stiffness and systemic symptoms. The aetiology and pathogenesis of fibromyalgia still remain unclear, although many contributory factors have been suggested. The presence of some common features between fibromyalgia and cardiovascular risk factors (e.g. depression and sleep disturbance) led to question of whether there is there a relationship between fibromyalgia and cardiovascular disease and/or atherosclerosis. Mean platelet volume, which is a determinant of platelet activation, is a newly emerging independent risk factor for cardiovascular disease.The present study was designed to evaluate levels of mean platelet volume in patients with fibromyalgia; the study population consisted of 283 individuals with this syndrome, who were compared with 72 healthy controls. Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, platelet count and mean platelet volume levels were retrospectively recorded via the computerised patient database. The levels of mean platelet volume were significantly higher in the fibromyalgia group than in the control group (8.09 ± 0.84 fl and 7.73 ± 0.65 fl, respectively, p < 0.001). There were no statistical differences between groups with regard to platelet count and other parameters. These results suggest that an early atherosclerosis marker, mean platelet volume, is elevated in patients with fibromyalgia. This indicates increased platelet activation and therefore a higher risk of future cardiovascular disease.

  12. Platelet antibodies in idiopathic thrombocytopenic purpura.

    PubMed Central

    Veenhoven, W A; Van der Schans, G S; Nieweg, H O

    1980-01-01

    An immunofluorescence (IF) technique for the detection of antibodies was applied to idiopathic thrombocytopenic purpura (ITP). Serum platelet antibodies were found in thirteen out of twenty-two patients (59 percent) with active disease, but in only four out of fifteen patients (27 percent) who had attained remission. Direct tests for platelet-associated IgG were positive in 36 and 44 percent of these patients respectively. In two cases IgM was observed on the patients' platelet membranes. C3 was not detedted on patients' platelets. Platelet-associated IgG was also found in several other disorders and its occurrence is not therefore diagnostic of ITP. In addition, serum platelet antibodies do not indicate specifically ITP as they may also be due to previous isoimmunization. Antibodies in the sera of patients with ITP generally did not fix Clq and in most cases bound to platelets only in the presence of EDTA. In contrast, isoantibodies often fixed Clq and they had equal affinity for platelets suspended in ACD or EDTA plasma. This was confirmed by quantitative data on IgG binding by platelets obtained by measuring 125-I-labelled protein A uptake. The simplicity of the IF technique permits its routine application and the technique may give useful information with respect to the nature of the antibodies. It must, however, be considered of limited value in the diagnosis of ITP. PMID:6991171

  13. Modulatory effect of coffee on platelet function.

    PubMed

    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 < 0.05) decrease in mean platelet volume, platelet crit and platelet distribution width as compared to high fat diet (HFD) group. The concentration of malondialdehyde in platelets increased in atherosclerotic group indicates the increased thromboxane A2 (TXA2) 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 < 0.05) decrease in aggregation in 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.

  14. [Cardiology. Platelet function testing for clinicians].

    PubMed

    Pellaton, Cyril; Eeckhout, Eric; Silvain, Johanne; Montalescot, Gilles; Collet, Jean-Phillipe

    2014-01-15

    Platelet P2YI2 receptor inhibition with clopidogrel, prasugrel or ticagrelor plays a key role to prevent recurrent ischaemic events after percutaneous coronary intervention in acute coronary syndromes or elective settings. The degree of platelet inhibition depends on the antiplatelet medication used and is influenced by clinical and genetic factors. A concept of therapeutic window exists. On one side, efficient anti-aggregation is required in order to reduce cardio-vascular events. On the other side, an excessive platelet inhibition represents a risk of bleeding complications. This article describes the current knowledge about some platelet function tests and genetic tests and summarises their role in the clinical practice.

  15. Cancer and Thrombosis: The Platelet Perspective

    PubMed Central

    Meikle, Claire K. S.; Kelly, Clare A.; Garg, Priyanka; Wuescher, Leah M.; Ali, Ramadan A.; Worth, Randall G.

    2017-01-01

    Platelets are critical to hemostatic and immunological function, and are key players in cancer progression, metastasis, and cancer-related thrombosis. Platelets interact with immune cells to stimulate anti-tumor responses and can be activated by immune cells and tumor cells. Platelet activation can lead to complex interactions between platelets and tumor cells. Platelets facilitate cancer progression and metastasis by: (1) forming aggregates with tumor cells; (2) inducing tumor growth, epithelial-mesenchymal transition, and invasion; (3) shielding circulating tumor cells from immune surveillance and killing; (4) facilitating tethering and arrest of circulating tumor cells; and (5) promoting angiogenesis and tumor cell establishment at distant sites. Tumor cell-activated platelets also predispose cancer patients to thrombotic events. Tumor cells and tumor-derived microparticles lead to thrombosis by secreting procoagulant factors, resulting in platelet activation and clotting. Platelets play a critical role in cancer progression and thrombosis, and markers of platelet-tumor cell interaction are candidates as biomarkers for cancer progression and thrombosis risk. PMID:28105409

  16. Ultrastructural studies of the gray platelet syndrome.

    PubMed

    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.

  17. Identification of platelet refractoriness in oncohematologic patients

    PubMed Central

    Ferreira, Aline Aparecida; Zulli, Roberto; Soares, Sheila; de Castro, Vagner; Moraes-Souza, Helio

    2011-01-01

    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. PMID:21437433

  18. Effect of photodynamic therapy on mouse platelets

    NASA Astrophysics Data System (ADS)

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

    1993-03-01

    Normal mice received hematoporphyrin derivative (10 mg/kg iv) immediately, 24 or 48 hrs prior to red light irradiation. The blood was collected and the platelet-rich plasma was irradiated by red light (100 J/cm2). The platelets were fixed immediately, 8 or 16 hrs after irradiation, and processed for EM examination. In comparison with those of control mice, the platelets of all experimental mice showed structural changes: 16 hrs after irradiation all platelets were necrotized; 8 hrs after irradiation almost 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 deformed, often with many cytoplasmic projections and considerable dilatation of the canalicular membrane system. Our findings provided a clear evidence that platelets are highly sensitive to PDT action and can be directly and rapidly injured by PDT even in the absence of vascular endothelial cells. Our results give firm support to the hypothesis that both endothelial cells and platelets may play an important role in the initiation of early vascular damage and microcirculatory alterations induced by PDT in vivo.

  19. Aging of platelets stored for transfusion.

    PubMed

    Smethurst, Peter A

    2016-09-01

    A goal of platelet storage is to maintain the quality of platelets from the point of donation to the point of transfusion - to suspend the aging process. This effort is judged by clinical and laboratory measures with varying degrees of success. Recent work gives encouragement that platelets can be maintained ex vivo beyond the current 5 -7 day shelf life whilst maintaining their quality, as measured by posttransfusion recovery and survival. However, additional measures are needed to validate the development of technologies that may further reduce the aging of stored platelets, or enhance their hemostatic properties.

  20. Pitfalls in Interventional Pain Medicine: Hyponatremia after DDAVP for a Patient with Von Willebrand Disease Undergoing an Epidural Steroid Injection

    PubMed Central

    2017-01-01

    Desmopressin (DDAVP), a synthetic analog of vasopressin, has been used in patients with von Willebrand disease (VWD), mild hemophilia A, and platelet dysfunction to reduce the risk of bleeding associated with surgical and interventional procedures. We report the case of a patient with VWD presenting with a bulging disc and radicular pain that underwent transforaminal epidural steroid injections. Her course was complicated with the interval development of headaches and dizziness symptomatic of moderate hyponatremia, likely due to excessive fluid intake. This report highlights a relatively rare side effect of DDAVP when used for prophylaxis in patients with VWD and reinforces the need for vigilance in these patients. PMID:28392945

  1. A simple method for activating the platelets used in microfluidic platelet aggregation tests: Stirring-induced platelet activation

    PubMed Central

    Lee, Hoyoon; Kim, Gyehyu; Lim, Chaeseung; Lee, ByoungKwon; Shin, Sehyun

    2016-01-01

    High-shear stimulation is well known as one of the key factors affecting platelet activation and aggregation, which can lead to the formation of a thrombus. In one of our previous studies, we introduced migration distance-based platelet function analysis in a microfluidic system. In this study, we set out to examine the effects of stirring on shear-induced platelet activation and aggregation in a chamber system by using a rotating stirrer. We found that the rotating stirrer caused not only rotational shear flow but also a strong radial secondary flow. The latter flow led to efficient mixing in the chamber. Moreover, the rotational flow led to the generation of shear stress, the magnitude of which can be controlled to activate the platelets. Activated platelets tend to aggregate themselves. The maximum platelet aggregation was observed at a critical shear rate of 3100 s−1, regardless of the stirrer shape. Furthermore, the time taken to attain maximum aggregation was significantly shortened when using a wide stirrer (30 s) instead of a narrow one (180 s). When using a flat stirrer, the non-uniform shear field in the chamber system was resolved with the radial secondary flow-induced mixing; thus, most of the platelets were homogenously activated. The stirring-induced platelet activation mechanism was experimentally confirmed in a microfluidic system for a platelet aggregation test while monitoring the migration distance until the microfluidic channel is occluded. Our findings indicate that the present system, consisting of a rotating stirrer and a confined chamber, provides effective shear stimulation for activating platelets and inducing platelet aggregates. PMID:28058084

  2. A simple method for activating the platelets used in microfluidic platelet aggregation tests: Stirring-induced platelet activation.

    PubMed

    Lee, Hoyoon; Kim, Gyehyu; Lim, Chaeseung; Lee, ByoungKwon; Shin, Sehyun

    2016-11-01

    High-shear stimulation is well known as one of the key factors affecting platelet activation and aggregation, which can lead to the formation of a thrombus. In one of our previous studies, we introduced migration distance-based platelet function analysis in a microfluidic system. In this study, we set out to examine the effects of stirring on shear-induced platelet activation and aggregation in a chamber system by using a rotating stirrer. We found that the rotating stirrer caused not only rotational shear flow but also a strong radial secondary flow. The latter flow led to efficient mixing in the chamber. Moreover, the rotational flow led to the generation of shear stress, the magnitude of which can be controlled to activate the platelets. Activated platelets tend to aggregate themselves. The maximum platelet aggregation was observed at a critical shear rate of 3100 s(-1), regardless of the stirrer shape. Furthermore, the time taken to attain maximum aggregation was significantly shortened when using a wide stirrer (30 s) instead of a narrow one (180 s). When using a flat stirrer, the non-uniform shear field in the chamber system was resolved with the radial secondary flow-induced mixing; thus, most of the platelets were homogenously activated. The stirring-induced platelet activation mechanism was experimentally confirmed in a microfluidic system for a platelet aggregation test while monitoring the migration distance until the microfluidic channel is occluded. Our findings indicate that the present system, consisting of a rotating stirrer and a confined chamber, provides effective shear stimulation for activating platelets and inducing platelet aggregates.

  3. Minimum wound size for clotting: flowing blood coagulates on a single collagen fiber presenting tissue factor and von Willebrand factor.

    PubMed

    Zhu, Shu; Tomaiuolo, Maurizio; Diamond, Scott L

    2016-08-08

    It is unknown if a lower size limit exists for human blood coagulation under flow over physiological vessel wall triggers as small as a single collagen fiber. Prior determinations of the smallest sized surface stimuli necessary for clotting of human blood, defined as the patch size threshold, have not deployed whole blood, hemodynamic flow, and platelet adhesive stimuli. For whole blood perfused in microfluidic devices, we report that steady venous flow (wall shear rate, 100 s(-1)) was sufficient to drive platelet deposition on 20 micron long zones of collagen fibers or on a single fiber. With tissue factor (TF)-coated collagen, flowing blood generated robust platelet deposits, platelet-localized thrombin, and fibrin on a single collagen fiber, thus demonstrating the absence of a physiological patch size threshold under venous flow. In contrast, at arterial wall shear rate (1000 s(-1)) with TF present, essentially no platelet or fibrin deposition occurred on 20 micron collagen zones or on a single collagen fiber, demonstrating a patch threshold, which was overcome by pre-coating the collagen with von Willebrand factor (vWF). For venous flows, human blood can clot on one of the smallest biological units of a single collagen fiber presenting TF. For arterial flows, vWF together with TF allows human blood to generate thrombin and fibrin on a patch stimulus as limited as a single collagen fiber. vWF-dependent platelet adhesion represents a particle-based sensing mechanism of micron-scale stimuli that then allows amplification of the molecular components of TF-driven thrombin and fibrin production under arterial flow.

  4. Physiologic and pathologic changes of platelets in pregnancy.

    PubMed

    Valera, Marie-Cecile; Parant, Olivier; Vayssiere, Christophe; Arnal, Jean-François; Payrastre, Bernard

    2010-01-01

    Platelets are key players in haemostasis and thrombus formation. Defects affecting platelets during pregnancy can lead to heterogeneous complications, such as thrombosis, first trimester miscarriage and postpartum haemorrhage. The incidence of complications is increased in women who have heritable platelet function disorders. Modifications of platelet count or platelet functions during normal pregnancy and preeclampsia will be summarized and the management of pregnant women with heritable platelet function disorders will be discussed.

  5. Childhood Picture of Dr. von Braun

    NASA Technical Reports Server (NTRS)

    1912-01-01

    This is a childhood picture of Dr. von Braun (center) with his brothers. Dr. Wernher von Braun was born in Wirsitz, Germany, March 23, 1912. His childhood dreams of marned space flight were fulfilled when giant Saturn rockets, developed under his direction at NASA's Marshall Space Flight Center, boosted the manned Apollo spacecraft to the Moon. His life was dedicated to expanding man's knowledge through the exploration of space.

  6. Dr. von Braun With Management Team

    NASA Technical Reports Server (NTRS)

    1961-01-01

    Dr. von Braun is shown in this photograph, which was probably taken in the early 1960s, with members of his management team. Pictured from left to right are, Werner Kuers, Director of the Manufacturing Engineering Division; Dr. Walter Haeussermarn, Director of the Astrionics Division; Dr. William Mrazek, Propulsion and Vehicle Engineering Division; Dr. von Braun; Dieter Grau, Director of the Quality Assurance Division; Dr. Oswald Lange, Director of the Saturn Systems Office; and Erich Neubert , Associate Deputy Director for Research and Development.

  7. Platelet function in the postprandial period

    PubMed Central

    2012-01-01

    Background Postprandial hyperlipidemia and hyperglycemia have been related to cardiovascular events. Among different underlying mechanisms platelet activation seems to be responsible too. No comparable data between various tests in normo- vs. hyperlipidemics before and at different time intervals are available after a fat meal. We aimed to compare 9 of them within the same patients at several time points in postprandial hyperlipidemia. Results For some tests baseline values between the groups were significantly different (TXB2, platelet sensitivity, sedimentation and WU-test). However, hyperlipidemia revealed a variable influence on the tests examined. Some of the available tests apparently sensitive to show platelet activation reflect the increase in triglycerides (TG), such as the sedimentation index. ADP-induced platelet aggregatory activity in count adjusted washed isolated platelet samples during postprandial hyperlipidemia indicates mildly enhanced platelet activity, but does not seem to induce significant changes in aggregation. In patients with severe hypertriglyceridemia (> 400 mg/dl fasting) changes in platelet function are more pronounced due to delayed decay and may last up to 16 hours paralleling TG reaching the prevalue. The overwhelming majority of platelet function tests do not significantly respond to postprandial hyperlipidemia. The correlation between the tests applied is poor. For standardization purpose, platelet aggregation tests, aimed to examine proaggregatory capacity in atherosclerosis, should only be performed at the same time of the day after a fasting period > 6 hours. The great variation in preanalytical work-up on comparison of various tests, large number of platelet tests available and their respective potential value are discussed. Conclusions At present, the suspicion that platelet function is significantly activated in the postprandial period cannot be supported by any of the tests used. The information provided is valuable to

  8. Evaluation of platelet turnover by flow cytometry.

    PubMed

    Salvagno, G L; Montagnana, M; Degan, M; Marradi, P L; Ricetti, M M; Riolfi, P; Poli, G; Minuz, P; Santonastaso, C L; Guidi, G C

    2006-05-01

    The number of circulating newly produced platelets depends on the thrombopoietic capacity of bone marrow as well as platelet removal from the bloodstream. Flow cytometric analysis with thiazole orange (TO), a fluorescent dye that crosses platelet membranes and binds intracellular RNA, has been used to measure circulating reticulated platelets (RPs) with high RNA content as an index of platelet turnover. We first assessed the specificity of TO flow cytometry and then applied this method in the diagnosis of thrombocytopenia caused by impaired platelet production or increased destruction. We also explored the utility of TO flow cytometry to predict thrombocytopoiesis after chemotherapy-induced bone marrow aplasia. Venous blood, anticoagulated with K(2)EDTA, was incubated with 0.6 microg/ml TO plus an anti-GPIIIa monoclonal antibody. The mean percentage of RPs in control subjects (n = 23) was 6.13 +/- 3.09%. RPs were 10.41 +/- 9.02% in patients (n = 10) with hematological malignancies during aplasia induced by chemotherapy and a significant increase in RPs (35.45 +/- 6.11%) was seen in the recovery phase. In 10 patients with idiopathic thrombocytopenic purpura, the percentage of TO positive platelets was 67.81 +/- 18.79 (P < 0.001 vs. controls). In patients with thrombocytopenia associated with hepatic cirrhosis (n = 21; 21.04 +/- 16.21%, P < 0.001 vs. controls) or systemic lupus erythematosus (n = 6, 29.08 +/- 15.57%; P < 0.001 vs. controls) increases in TO-stained platelets were also observed. Measurement of TO positive platelets may be a reliable tool for the laboratory identification of platelet disorders, with a higher sensitivity than measurement of platelet volume. Measurement of RPs may also prove useful to recognize the underlying pathogenetic mechanisms in thrombocytopenia.

  9. Redistribution of von Willebrand factor in porcine carotid arteries after balloon angioplasty.

    PubMed

    Giddings, J C; Banning, A P; Ralis, H; Lewis, M J

    1997-10-01

    von Willebrand factor (VWF) is a well-characterized multimeric glycoprotein present in platelets and plasma and synthesized by vascular endothelial cells and megakaryocytes. Its role in platelet-vessel wall interactions has been studied extensively, but its involvement in intravascular events after balloon angioplasty has not been clarified. VWF antigen is not present in porcine arterial endothelium (except for the pulmonary artery) but is readily detected in porcine venous endothelial cells. We have examined the localization of VWF in porcine vessel walls during neointima formation after bilateral carotid balloon-angioplasty. Endothelium was denuded by balloon injury but regenerated by 7 days and was fully confluent by 42 days. VWF was detected at the site of injury in localized, adherent platelet aggregates at 10 minutes after angioplasty that were not present at later time points. A well-demarcated homogeneous layer of VWF was observed on the luminal surface from 30 minutes to day 7, but there was a progressive shift of positive staining from the lumen to the outer media from days 1 to 7. VWF was also strongly detected at sites proximal and distal to the balloon injury from 30 minutes to day 7, although endothelial disruption was minimal and the monolayer remained substantially intact at these sites. Regrowing endothelial cells appeared to contain granular VWF from days 12 to 21, but this was not readily evident at later time points. The results suggest that balloon injury is associated with deposition and medial absorption of plasma or platelet VWF in this porcine model over a time period that precedes and overlaps vascular smooth muscle proliferation and endothelial recoverage. The findings provide evidence to support the concept of a wider role for VWF in tissue injury responses.

  10. BIODEGRADABLE NANOPARTICLES MIMICKING PLATELET BINDING AS A TARGETED AND CONTROLLED DRUG DELIVERY SYSTEM

    PubMed Central

    Kona, Soujanya; Dong, Jing-Fei; Liu, Yaling; Tan, Jifu

    2012-01-01

    This research aims to develop targeted nanoparticles as drug carriers to the injured arterial wall under fluid shear stress by mimicking the natural binding ability of platelets via interactions of glycoprotein Ib-alpha (GP Ibα) of platelets with P-selectin of damaged endothelial cells (ECs) and/or with von Willebrand factor (vWF) of the subendothelium. Drug-loaded poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles were formulated using a standard emulsion method and conjugated with glycocalicin, the external fraction of platelet GPIbα, via carbodiimide chemistry. Surface-coated and cellular uptake studies in ECs showed that conjugation of PLGA nanoparticles with GPIb significantly increased nanoparticle adhesion to P-selectin- and vWF-coated surfaces as well as nanoparticle uptake by activated ECs under fluid shear stresses. In addition, effects of nanoparticle size and shear stress on adhesion efficiency were characterized through parallel flow chamber studies. The observed decrease in bound nanoparticle density with increased particle sizes and shear stresses is also explained through a computational model. Our results demonstrate that the GPIb-conjugated PLGA nanoparticles can be used as a targeted and controlled drug delivery system under flow conditions at the site of vascular injury. PMID:22172292

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

    PubMed Central

    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

    2014-01-01

    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. PMID:24599546

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

    PubMed

    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.

  13. Cryopreservation of buffy-coat-derived platelet concentrates in dimethyl sulfoxide and platelet additive solution.

    PubMed

    Johnson, L N; Winter, K M; Reid, S; Hartkopf-Theis, T; Marks, D C

    2011-04-01

    Platelets prepared in plasma can be frozen in 6% dimethyl sulfoxide (Me(2)SO) and stored for extended periods at -80°C. The aim of this study was to reduce the plasma present in the cryopreserved product, by substituting plasma with platelet additive solution (PAS; SSP+), whilst maintaining in vitro platelet quality. Buffy coat-derived pooled leukoreduced platelet concentrates were frozen in a mixture of SSP+, plasma and 6% Me(2)SO. The platelets were concentrated, to avoid post-thaw washing, and frozen at -80°C. The cryopreserved platelet units (n=9) were rapidly thawed at 37°C, reconstituted in 50% SSP+/plasma and stored at 22°C. Platelet recovery and quality were examined 1 and 24h post-thaw and compared to the pre-freeze samples. Upon thawing, platelet recovery ranged from 60% to 80%. However, there were differences between frozen and liquid-stored platelets, including a reduction in aggregation in response to ADP and collagen; increased CD62P expression; decreased viability; increased apoptosis and some loss of mitochondrial membrane integrity. Some recovery of these parameters was detected at 24h post-thaw, indicating an extended shelf-life may be possible. The data suggests that freezing platelets in 6% Me(2)SO and additive solution produces acceptable in vitro platelet quality.

  14. Transfusion of ABO-mismatched platelets leads to early platelet refractoriness.

    PubMed

    Carr, R; Hutton, J L; Jenkins, J A; Lucas, G F; Amphlett, N W

    1990-07-01

    Forty-three consecutive patients previously unexposed to platelets and undergoing treatment for acute leukaemia or autografting for relapsed Hodgkin's lymphoma were randomized to receive transfused platelets of either their own ABO group (OG) or of a major mismatched group (MMG). The 26 evaluable patients were equally distributed between the two study groups. Nine of 13 (69%) MMG patients became refractory with a median onset at transfusion 7 (15 d), compared with only one of 13 (8%) OG patients (P = 0.001). Refractoriness was associated with the formation of high titre isoagglutinins, anti-HLA and platelet specific antibodies. In one patient refractoriness appeared to be due to high titre isoagglutinins alone. Six other patients developed an increase in isoagglutinin titre sufficient to adversely affect platelet increments. Patients receiving ABO-mismatched platelets had a higher incidence of anti-HLA antibodies (5 v. 1) and platelet specific antibodies (4 v. 1). ABO-mismatched platelets transfused prior to the onset of refractoriness resulted in increments similar to those achieved by ABO-matched platelets. The study demonstrates that ABO-mismatched platelets are as effective as matched platelets in patients with low titre isoagglutinins requiring only few transfusions. However, the greater incidence of early refractoriness induced in MMG patients indicates that ABO-mismatched platelets should not be given to patients with marrow failure requiring long-term support.

  15. Reelin is a platelet protein and functions as a positive regulator of platelet spreading on fibrinogen.

    PubMed

    Tseng, Wei-Lien; Huang, Chien-Ling; Chong, Kowit-Yu; Liao, Chang-Huei; Stern, Arnold; Cheng, Ju-Chien; Tseng, Ching-Ping

    2010-02-01

    Abnormalities of platelet functions have been linked to reelin-impaired neuronal disorders. However, little attention has been given to understanding the interplay between reelin and platelet. In this study, reelin was found to present in the human platelets and megakaryocyte-like leukemic cells. Reelin-binding assays revealed that extracellular reelin can interact with platelets through the receptor belonging to the low density lipoprotein receptor gene family. The reelin-to-platelet interactions enhance platelet spreading on fibrinogen concomitant with the augmentation of lamellipodia formation and F-actin bundling. In contrast, reelin has no effect on integrin alphaIIbbeta3 activation and agonist-induced platelet aggregation. Molecular analysis revealed that the up-regulation of Rac1 activity and the inhibition of protein kinase C delta-Thr505 phosphorylation are important for reelin-mediated enhancement of platelet spreading on fibrinogen. These findings demonstrate for the first time that reelin is present in platelets and the reelin-to-platelet interactions play a novel role in platelet signaling and functions.

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

    PubMed

    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.

  17. Selectin-like kinetics and biomechanics promote rapid platelet adhesion in flow: the GPIb(alpha)-vWF tether bond.

    PubMed Central

    Doggett, Teresa A; Girdhar, Gaurav; Lawshé, Avril; Schmidtke, David W; Laurenzi, Ian J; Diamond, Scott L; Diacovo, Thomas G

    2002-01-01

    The ability of platelets to tether to and translocate on injured vascular endothelium relies on the interaction between the platelet glycoprotein receptor Ib alpha (GPIb(alpha)) and the A1 domain of von Willebrand factor (vWF-A1). To date, limited information exists on the kinetics that govern platelet interactions with vWF in hemodynamic flow. We now report that the GPIb(alpha)-vWF-A1 tether bond displays similar kinetic attributes as the selectins including: 1) the requirement for a critical level of hydrodynamic flow to initiate adhesion, 2) short-lived tethering events at sites of vascular injury in vivo, and 3) a fast intrinsic dissociation rate constant, k(0)(off) (3.45 +/- 0.37 s(-1)). Values for k(off), as determined by pause time analysis of transient capture/release events, were also found to vary exponentially (4.2 +/- 0.8 s(-1) to 7.3 +/- 0.4 s(-1)) as a function of the force applied to the bond (from 36 to 217 pN). The biological importance of rapid bond dissociation in platelet adhesion is demonstrated by kinetic characterization of the A1 domain mutation, I546V that is associated with type 2B von Willebrand disease (vWD), a bleeding disorder that is due to the spontaneous binding of plasma vWF to circulating platelets. This mutation resulted in a loss of the shear threshold phenomenon, a approximately sixfold reduction in k(off), but no significant alteration in the ability of the tether bond to resist shear-induced forces. Thus, flow dependent adhesion and rapid and force-dependent kinetic properties are the predominant features of the GPIb(alpha)-vWF-A1 tether bond that in part may explain the preferential binding of platelets to vWF at sites of vascular injury, the lack of spontaneous platelet aggregation in circulating blood, and a mechanism to limit thrombus formation. PMID:12080112

  18. Relation of platelet density to platelet age: survival of low- and high-density 111indium-labeled platelets in baboons

    SciTech Connect

    Savage, B.; McFadden, P.R.; Hanson, S.R.; Harker, L.A.

    1986-08-01

    The relationship between platelet density and platelet age has been studied using continuous linear Percoll density gradients and 111In-labeling of autologous platelets in baboons. To investigate changes in platelet density during senescence in the circulation, baboons were infused with 111In-labeled autologous platelets, and blood was collected at one hour postinfusion and twice daily thereafter for six days. Platelets were isolated from these samples in high yield (greater than 95%) and separated in continuous linear Percoll density gradients following density equilibrium centrifugation. Although at one hour postinfusion the density distribution of radiolabeled platelets coincided closely with the distribution of the total platelet population, a detectable symmetrical shift toward higher densities was observed after five days. The relative specific radioactivity (RSR) of high-density platelets (1.064 to 1.067 g/mL) decreased at a slower rate than that of the total platelet population (platelets of all densities), whereas the RSR of low-density platelets (1.053 to 1.056 g/mL) showed a more immediate and rapid decrease. These results give rise to one of two interpretations: (1) low-density platelets have a shorter survival time than more dense platelets and are therefore cleared from the circulation at a faster rate, or (2) platelets of all densities increase in density upon aging in the circulation. To determine the explanation for changing RSR of different density fractions we studied the in vivo disappearance characteristics of low- and high-density 111In-labeled platelets. There were no significant differences between the mean survival times of low-density platelets (5.0 +/- 0.49 days, +/- 1 SD, n = 6), high-density platelets (4.9 +/- 0.56 days, n = 6), or control platelets representing platelets of all densities (4.9 +/- 0.38 days, n = 6).

  19. The omnipotent platelet. Part II: Further observations.

    PubMed

    Steinberg, L A

    1997-07-01

    Observation of platelet responses during acute injury or pathology can provide important information. The initial response is thrombocytopenia followed by thrombocytosis. In the case of injury with negative X-ray and appropriate thrombocytosis, a bone scan is indicated. The platelet responds like a sedimentation rate, which indicates the course of the injury or pathology.

  20. Synthetic materials for platelet quality control.

    PubMed

    Lott, J A; Hartzell, R K; Longberry, J

    1983-01-01

    At present, the quality control of platelet counting by semi-automated and automated methods does not meet ideal standards. Controls prepared from human or animal platelets have limited stability, and some synthetic platelet controls that are available do not have the size distribution of fresh platelets. The platelet control materials described here are wholly synthetic; however, their particle size distribution is like that of normal human platelets, and the dispersing medium has the viscosity and surface tension of plasma. Two types of products are described. The first type are dilutions of the synthetic platelets which are handled like 3000-fold dilutions of platelet-rich plasma and are intended for direct use on instruments like the Coulter ZBI. The two dilution levels gave counts of about 50,000 and 200,000/microL on the Coulter ZBI and were found to be stable for at least 30 days at - 20C, 4C, and 37C, and at least eight months at 25C. The second type of product is handled like whole blood and is intended for direct use on instruments like the Coulter Model S-Plus. This product gave counts of about 200,000/microL and was found to be stable for at least 120 days at - 20C, 4C, 25C, and 37C. Freezing at - 20C produced some aggregates that dispersed after thawing and standing for several days prior to testing.

  1. Daily prickly pear consumption improves platelet function.

    PubMed

    Wolfram, R; Budinsky, A; Efthimiou, Y; Stomatopoulos, J; Oguogho, A; Sinzinger, H

    2003-07-01

    Prickly pear is traditionally used by Pima Indians as a dietary nutrient against diabetes mellitus. We examined the effect of daily consumption of 250 g in 8 healthy volunteers and 8 patients with mild familial heterozygous hypercholesterolemia on various parameters of platelet function. Beside its action on lipids and lipoproteins, prickly pear consumption significantly reduced the platelet proteins (platelet factor 4 and beta-thromboglobulin), ADP-induced platelet aggregation and improved platelet sensitivity (against PGI2 and PGE1) in volunteers as well as in patients. Also plasma 11-DH-TXB2 and the WU-test showed a significant improvement in both patients and volunteers. In contrast, collagen-induced platelet aggregation and the number of circulating endothelial cells showed a significant response in patients only. No influence of prickly pear ingestion on peripheral platelet count was monitored. The dietary run-in period did not influence any of the parameters of haemostasis examined. No sex difference was seen. Prickly pear may induce at least part of its beneficial actions on the cardiovascular system via decreasing platelet activity and thereby improving haemostatic balance.

  2. Fractal and Euclidean descriptors of platelet shape.

    PubMed

    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).

  3. Clinica use of platelet additive solutions.

    PubMed

    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.

  4. Short-term exposure of platelets to glucose impairs inhibition of platelet aggregation by cyclooxygenase inhibitors.

    PubMed

    Kobzar, Gennadi; Mardla, Vilja; Samel, Nigulas

    2011-01-01

    Aspirin treatment reduces cardiovascular events and deaths in high-risk non-diabetic patients, but not in patients suffering from diabetes. In these patients, hyperglycemia has been found to cause reduced platelet sensitivity to aspirin. It is supposed that long-term exposure of platelets to glucose leads to non-enzymatic glycosylation and impairs aspirin inhibition of platelet aggregation. On the other hand, short-term exposure of platelets to glucose also attenuates the effect of aspirin on platelets. The aim of the present work was to analyse the effect of short-term exposure of glucose on the inhibition of platelet aggregation by aspirin and other cyclooxygenase (COX) inhibitors. Already a 15 min exposure of platelets to glucose impaired aspirin inhibition of the platelet aggregation induced by collagen, thrombin, adenosine diphosphate (ADP), and arachidonic acid (AA). Aspirin inhibition of platelet aggregation in platelet-rich plasma (PRP) was attenuated by 5.6, 11.2, 16.8, and 22.4 mM of glucose in a concentration-dependent way. The same effect was observed with indomethacin and acetaminophen used as cyclooxygenase inhibitors instead of aspirin. N-methyl-L-arginine, an inhibitor of nitric oxide synthase, prevented the effect of glucose on aspirin, indomethacin and acetaminophen inhibition of platelet aggregation. Other monosaccharides, for example fructose and galactose, impaired aspirin inhibition as did glucose. Lactic acid (0.1, 0.2, 0.4, 0.8 mM), the end product of anaerobic glycolysis in platelets, impaired the inhibition of platelet aggregation with aspirin in a concentration-dependent way but did not affect indomethacin. It is suggested that lactic acid might be a mediator of the effect of glucose on aspirin inhibition in platelets.

  5. Dynamic adhesion of eryptotic erythrocytes to immobilized platelets via platelet phosphatidylserine receptors.

    PubMed

    Walker, Britta; Towhid, Syeda T; Schmid, Evi; Hoffmann, Sascha M; Abed, Majed; Münzer, Patrick; Vogel, Sebastian; Neis, Felix; Brucker, Sara; Gawaz, Meinrad; Borst, Oliver; Lang, Florian

    2014-02-01

    Glucose depletion of erythrocytes triggers suicidal erythrocyte death or eryptosis, which leads to cell membrane scrambling with phosphatidylserine exposure at the cell surface. Eryptotic erythrocytes adhere to endothelial cells by a mechanism involving phosphatidylserine at the erythrocyte surface and CXCL16 as well as CD36 at the endothelial cell membrane. Nothing has hitherto been known about an interaction between eryptotic erythrocytes and platelets, the decisive cells in primary hemostasis and major players in thrombotic vascular occlusion. The present study thus explored whether and how glucose-depleted erythrocytes adhere to platelets. To this end, adhesion of phosphatidylserine-exposing erythrocytes to platelets under flow conditions was examined in a flow chamber model at arterial shear rates. Platelets were immobilized on collagen and further stimulated with adenosine diphosphate (ADP, 10 μM) or thrombin (0.1 U/ml). As a result, a 48-h glucose depletion triggered phosphatidylserine translocation to the erythrocyte surface and augmented the adhesion of erythrocytes to immobilized platelets, an effect significantly increased upon platelet stimulation. Adherence of erythrocytes to platelets was blunted by coating of erythrocytic phosphatidylserine with annexin V or by neutralization of platelet phosphatidylserine receptors CXCL16 and CD36 with respective antibodies. In conclusion, glucose-depleted erythrocytes adhere to platelets. The adhesive properties of platelets are augmented by platelet activation. Erythrocyte adhesion to immobilized platelets requires phosphatidylserine at the erythrocyte surface and CXCL16 as well as CD36 expression on platelets. Thus platelet-mediated erythrocyte adhesion may foster thromboocclusive complications in diseases with stimulated phosphatidylserine exposure of erythrocytes.

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

    PubMed

    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.

  7. Increased platelet adhesion under flow conditions is induced by both thalassemic platelets and red blood cells.

    PubMed

    Goldschmidt, Neta; Spectre, Galia; Brill, Alexander; Zelig, Orly; Goldfarb, Ada; Rachmilewitz, Eliezer; Varon, David

    2008-11-01

    Thromboembolic complications are not uncommon in thalassemia. Previous studies suggest increased platelet aggregation and a potential role of pathological changes in the red blood cell (RBC) lipid membrane, induced by oxidative stress. In the present study, platelet adhesion and the effect of thalassemic RBC on platelet adhesion under flow conditions were evaluated, using the Cone and Plate (let) Analyzer(CPA). Twenty-two beta-thalassemia patients and 22 blood type-matched healthy controls were studied. An increased platelet adhesion (% surface coverage, SC), was observed in patients as compared to controls (p < 0.05). When platelet count and haematocrit were normalized by autologous reconstitution, a significant increase in platelet aggregation (average size, AS) was observed (p < 0.05). Increased platelet adhesion (SC and AS), was demonstrated in six patients with a history of thrombosis as compared to 16 patients without any history of thrombosis (p < or = 0.007) and in 17 splenectomized patients as compared to five non-splenectomized patients (p = 0.003). In reconstitution studies, thalassemic RBC mixed with normal platelet-rich plasma significantly increased platelet adhesion compared to normal RBC (SC p < 0.03, AS p < 0.02). Thalassemic platelets reconstituted with normal RBC, had increased aggregation (AS, p < 0.004) in comparison with normal platelets. The results indicate that increased platelet adhesion in beta-thalassemia is induced by both platelets and RBC. Increased platelet adhesion correlated with clinical thrombotic events and thus may suggest a mechanism of thrombosis in thalassemic patients. The potential application of the CPA in identifying thalassemic patients with high risk for thrombosis should be studied prospectively in a larger cohort of patients.

  8. EXTENDED STORAGE OF BUFFY-COAT PLATELET CONCENTRATES IN PLASMA OR A PLATELET ADDITIVE SOLUTION

    PubMed Central

    Slichter, Sherrill J.; Bolgiano, Doug; Corson, Jill; Jones, Mary Kay; Christoffel, Todd; Bailey, S. Lawrence; Pellham, Esther

    2014-01-01

    Background Platelet concentrates prepared from whole blood in the U.S. are made using the platelet-rich-plasma (PRP) method. The platelet concentrates must be made within 8 hours of blood collection and stored for only 5 days. In Europe and Canada, platelet concentrates are made using the buffy-coat (BC) method from whole blood held overnight at 22°C and storage times may be up to 7 days. Our studies were designed to determine how long BC platelets can be stored in plasma or Plasmalyte while meeting the FDA’s post-storage viability criteria. Study Design, Materials, And Methods Normal subjects donated whole blood that was stored at 22°C for 22 ± 2 hours prior to preparation of BC platelets. Platelets were stored for 5 to 8 days in either plasma or Plasmalyte concentrations of 65% or 80%. Radiolabeled autologous stored versus fresh platelet recoveries and survivals were assessed as well as post-storage in vitro assays. Results BC platelets stored in either plasma or 65% Plasmalyte met FDA post-storage platelet recovery criteria for 7 days but survivals for only 6 days, while storage in 80% Plasmalyte gave very poor results. Both stored platelet recoveries and survivals correlated with the same donor’s fresh results, but the correlation was much stronger between recoveries than survivals. In vitro measures of extent of shape change, morphology score, and pH best predicted post-storage platelet recoveries, while annexin V binding best predicted platelet survivals. Conclusion BC platelets stored in either plasma or 65% Plasmalyte meet FDA’s post-storage viability criteria for 6 days. PMID:24673482

  9. Proteomic approaches to dissect platelet function: half the story

    PubMed Central

    Gnatenko, Dmitri V.; Perrotta, Peter L.; Bahou, Wadie F.

    2006-01-01

    Platelets play critical roles in diverse hemostatic and pathologic disorders and are broadly implicated in various biological processes that include inflammation, wound healing, and thrombosis. Recent progress in high-throughput mRNA and protein profiling techniques has advanced our understanding of the biological functions of platelets. Platelet proteomics has been adopted to decode the complex processes that underlie platelet function by identifying novel platelet-expressed proteins, dissecting mechanisms of signal or metabolic pathways, and analyzing functional changes of the platelet proteome in normal and pathologic states. The integration of transcriptomics and proteomics, coupled with progress in bioinformatics, provides novel tools for dissecting platelet biology. In this review, we focus on current advances in platelet proteomic studies, with emphasis on the importance of parallel transcriptomic studies to optimally dissect platelet function. Applications of these global profiling approaches to investigate platelet genetic diseases and platelet-related disorders are also addressed. PMID:16926286

  10. Statistics of Gaussian packets on metric and decorated graphs.

    PubMed

    Chernyshev, V L; Shafarevich, A I

    2014-01-28

    We study a semiclassical asymptotics of the Cauchy problem for a time-dependent Schrödinger equation on metric and decorated graphs with a localized initial function. A decorated graph is a topological space obtained from a graph via replacing vertices with smooth Riemannian manifolds. The main term of an asymptotic solution at an arbitrary finite time is a sum of Gaussian packets and generalized Gaussian packets (localized near a certain set of codimension one). We study the number of packets as time tends to infinity. We prove that under certain assumptions this number grows in time as a polynomial and packets fill the graph uniformly. We discuss a simple example of the opposite situation: in this case, a numerical experiment shows a subexponential growth.

  11. Decoration of vertical graphene with aerosol nanoparticles for gas sensing

    NASA Astrophysics Data System (ADS)

    Cui, Shumao; Guo, Xiaoru; Ren, Ren; Zhou, Guihua; Chen, Junhong

    2015-08-01

    A facile method was demonstrated to decorate aerosol Ag nanoparticles onto vertical graphene surfaces using a mini-arc plasma reactor. The vertical graphene was directly grown on a sensor electrode using a plasma-enhanced chemical vapor deposition (PECVD) method. The aerosol Ag nanoparticles were synthesized by a simple vapor condensation process using a mini-arc plasma source. Then, the nanoparticles were assembled on the surface of vertical graphene through the assistance of an electric field. Based on our observation, nonagglomerated Ag nanoparticles formed in the gas phase and were assembled onto vertical graphene sheets. Nanohybrids of Ag nanoparticle-decorated vertical graphene were characterized for ammonia gas detection at room temperature. The vertical graphene served as the conductance channel, and the conductance change upon exposure to ammonia was used as the sensing signal. The sensing results show that Ag nanoparticles significantly improve the sensitivity, response time, and recovery time of the sensor.

  12. Statistics of Gaussian packets on metric and decorated graphs

    PubMed Central

    Chernyshev, V. L.; Shafarevich, A. I.

    2014-01-01

    We study a semiclassical asymptotics of the Cauchy problem for a time-dependent Schrödinger equation on metric and decorated graphs with a localized initial function. A decorated graph is a topological space obtained from a graph via replacing vertices with smooth Riemannian manifolds. The main term of an asymptotic solution at an arbitrary finite time is a sum of Gaussian packets and generalized Gaussian packets (localized near a certain set of codimension one). We study the number of packets as time tends to infinity. We prove that under certain assumptions this number grows in time as a polynomial and packets fill the graph uniformly. We discuss a simple example of the opposite situation: in this case, a numerical experiment shows a subexponential growth. PMID:24344346

  13. [Tooth decoration back after a long and forgotten history 2].

    PubMed

    Dijs, F

    2004-11-01

    After the last ice-age modern man started to remove, file, dye and inlay teeth. The teeth had such a central role in the imagination that the habit of more or less ritual decoration by incurable manipulation of the teeth spread all over the world. The most skillful and artistic work was done by craftsmen of the Maya. Between 1500 and 1900 CE modern researchers classified the habits as primitive and barbarian but during the twentieth century some of them took the question serious. In the last decennium tooth jewellery is sold more and more often. In two articles the history of teeth decoration is outlined. In the first article the significance of the manipulations was emphasized. This second article will focus on the changing appreciation of the phenomenon.

  14. [Teeth decoration back after a long and forgotten history].

    PubMed

    Dijs, F

    2004-09-01

    After the last ice-age modern man started to remove, file, dye and inlay teeth. The teeth had such a central role in the imagination that the habit of more or less ritual decoration by incurable manipulation of the teeth spread all over the world. The most skillful and artistic work was done by craftsmen of the Maya. Between 1500 and 1900 modern researchers classified the habits as primitive and barbarian but during the twentieth century some of them took the question seriously. In the last decennium tooth jewelery is sold more and more often. In two articles the history of teeth decoration is outlined. In this article the significance of the manipulations is emphasized. The second will focus on the changing appreciation of the phenomenon.

  15. Von Karman re-visited

    NASA Astrophysics Data System (ADS)

    McEligot, Donald M.; Nolan, Kevin P.; Walsh, Edmond J.

    2012-11-01

    A number of authors have presented extended versions of the integral momentum equation, allowing for perturbations or fluctuations in the boundary layer. ``Conventional wisdom'' is that these added terms can be neglected and one can apply the von Karman version directly. For two-dimensional turbulent boundary layers at high Reynolds numbers, experience shows this assumption to be reasonable. However, recent examination of entropy generation in bypass transition with zero pressure gradient shows a term for turbulence energy convection can be important in determining the energy dissipation coefficient [Walsh et al., JFE 2011]. The present study employs the direct numerical simulations of Zaki and Durbin [JFM 2006] for bypass transition with streamwise pressure gradients to quantify the additional normal stress term when estimating the skin friction coefficient via a momentum balance. It is found that this term becomes noticeable in the pre-transitional laminar boundary layer and can exceed forty per cent of Cf in the transition region. Thus, it should be included in such calculations. Partly supported by U. S. DoE EPSCoR office.

  16. Relationship between potential platelet activation and LCS

    NASA Astrophysics Data System (ADS)

    Shadden, Shawn

    2010-11-01

    In the study of blood flow, emphasis is often directed at understanding shear stress at the vessel wall due to its potentially disruptive influence on the endothelium. However, it is also known that shear stress has a potent effect on platelet activation. Platelet activation is a precursor for blood clotting, which in turn is the cause of most forms of death. Since most platelets are contained in the flow domain, it is important to consider stresses acting on the platelet as they are convected. Locations of high stress can correspond to boundaries between different dynamic regions and locations of hyperbolic points in the Eulerian sense. In the computation of LCS, strain in typically considered in the Lagrangian sense. In this talk we discuss the relationship between locations of potential platelet activation due to increased stress and locations of LCS marking increase Lagrangian deformation.

  17. Platelet bioreactor-on-a-chip.

    PubMed

    Thon, Jonathan N; 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

    2014-09-18

    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.

  18. Platelet storage pool deficiency in Jacobsen syndrome.

    PubMed

    White, James G

    2007-11-01

    Jacobsen syndrome and Paris-Trousseau Syndrome share similar congenital anomalies, thrombocytopenia, giant platelet alpha granules resulting from fusion of smaller organelles, and an 11q terminal deletion at 11q23.3. Similarities in the two cohorts have suggested that the Paris-Trousseau Syndrome is a variant of Jacobsen syndrome, or the same disorder. The present study has pointed out a significant difference between the two syndromes. Platelets from six patients with Jacobsen syndrome were markedly diminished in serotonin adenine nucleotide rich dense bodies, indicating the presence of platelet storage pool deficiency. Since platelet dense bodies are reported to be normal in size, number and distribution in the Paris-Trousseau Syndrome, the presence of platelet storage pool deficiency in six patients evaluated in the present study may distinguish the two disorders.

  19. [Platelet antigens: immunology and immuno-allergology].

    PubMed

    de Sousa, J C; Palma-Carlos, A G

    1996-02-01

    Platelet immunology allows the understanding of clinical findings in a genetic and serologic basis. Blood platelets bear common antigens and same specific antigens, classified in five groups (HPA 1 to 5), that are localized on membrane glycoproteins Ia, Ib alpha, IIb and IIIa. Antiplatelet autoimmunization is generally due to IgG antibodies against membrane complexes IIb/IIIa or Ib/lX. Antiplatelet alloimmunization, clinically resulting in Posttransfusion Purpura and Neonatal Thrombocytopenia is more frequently associated with anti-IIb/IIIa antibodies, either anti-HPA-1a or HPA-1b. Finally, platelet participation in immunoallergic reactions is discussed, focusing both platelet activation by allergen itself and platelet recruitment by other inflammatory cells.

  20. Contact- and agonist-regulated microvesiculation of human platelets.

    PubMed

    Zhang, Yanjun; Liu, Xiao; Liu, Li; Zaske, Ana-Maria; Zhou, Zhou; Fu, Yuanyuan; Yang, Xi; Conyers, Jodie L; Li, Min; Dong, Jing-fei; Zhang, Jianning

    2013-08-01

    After exposure to an agonist, platelets are activated and become aggregated. They also shed membrane microparticles that participate in the pathogenesis of thrombosis, hyper-coagulation and inflammation. However, microvesiculation can potentially disrupt the integrity of platelet aggregation by shedding the membrane receptors and phosphatidylserine critical for forming and stabilising a platelet clot. We tested the hypothesis that adhesion and microvesiculation are functions of different subsets of platelets at the time of haemostasis by real-time monitoring of agonist-induced morphological changes and microvesiculation of human platelets.We identified two types of platelets that are adherent to fibrinogen: a high density bubble shape (HDBS) and low-density spread shape (LDSS). Adenosine diphosphate (ADP) predominantly induced HDBS platelets to vesiculate, whereas LDSS platelets were highly resistant to such vesiculation. Thrombin-receptor activating peptide (TRAP) stabilised platelets against microvesiculation by promoting a rapid HDBS-to-LDSS morphological transition. These activities of ADP and TRAP were reversed for platelets in suspension, independent of an engagement integrin αIIbβ3. As the result of membrane contact, LDSS platelets inhibited the microvesiculation of HDBS platelets in response to ADP. Aspirin and clopidogrel inhibited ADP-induced microvesiculation through different mechanisms. These results suggest that platelet aggregation and microvesiculation occur in different subsets of platelets and are differently regulated by agonists, platelet-platelets and platelet-fibrinogen interactions.

  1. Memristor device based on carbon nanotubes decorated with gold nanoislands

    NASA Astrophysics Data System (ADS)

    Radoi, A.; Dragoman, M.; Dragoman, D.

    2011-08-01

    Memristors are passive nanoelectronics devices with applications in memories and switches which, although not containing magnetic components, have as distinct signature a hysteresis loop in the current-voltage dependence. Even if the prototype material for memristors is a binary oxide, we demonstrate that such devices can be easily implemented using carbon nanotubes decorated with metallic nanoislands, where the hysteretic action is a result of the thermionic emission of electrons trapped in the gold nanoislands.

  2. Quantum Hall effect in graphene decorated with disordered multilayer patches

    SciTech Connect

    Nam, Youngwoo; Sun, Jie Lindvall, Niclas; Kireev, Dmitry; Yurgens, August; Jae Yang, Seung; Rae Park, Chong; Woo Park, Yung

    2013-12-02

    Quantum Hall effect (QHE) is observed in graphene grown by chemical vapour deposition using platinum catalyst. The QHE is even seen in samples which are irregularly decorated with disordered multilayer graphene patches and have very low mobility (<500 cm{sup 2}V{sup −1}s{sup −1}). The effect does not seem to depend on electronic mobility and uniformity of the resulting material, which indicates the robustness of QHE in graphene.

  3. Cangrelor attenuates coated-platelet formation.

    PubMed

    Norgard, Nicholas B; Hann, Callie L; Dale, George L

    2009-01-01

    P2Y(12) inhibitors were introduced clinically as effective inhibitors of adenosine-5'-diphosphate (ADP) mediated platelet activation and aggregation. This class of pharmacological agents has enjoyed considerable success. Cangrelor is a recently developed P2Y(12) inhibitor that has the advantage of being an active drug not requiring metabolic conversion, although it is not orally available. Coated-platelets are a subclass of activated platelets generated on dual agonist activation with collagen plus thrombin; the primary hallmark of coated-platelets is their ability to support prothrombinase activity. Interestingly, we recently observed that the relatively weak agonist ADP potentiates the production of coated-platelets by the very strong agonists collagen plus thrombin, a previously unknown role for ADP. The authors sought in this study to determine if P2Y(12) inhibitors, such as cangrelor, were capable of attenuating this augmentation of coated-platelet generation. Cangrelor, at physiologically relevant concentrations, was able to eliminate the ADP-dependent increase in coated-platelet production with an IC(50) of 1.4 nM. Cangrelor, however, had no effect on thrombin-dependent platelet activation as measured by P-selectin expression. Although this in vitro study does not address the question of whether the effectiveness of cangrelor in vivo is partially due to an attenuation of coated-platelet production in addition to its documented antiaggregatory effects, it does reveal an unexpected action of cangrelor. Additional studies will be required to determine if all P2Y(12) inhibitors are equally effective in attenuating coated-platelet production.

  4. Platelet derivatives in regenerative medicine: an update.

    PubMed

    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.

  5. Dirac cones in the spectrum of bond-decorated graphenes

    SciTech Connect

    Van den Heuvel, Willem Soncini, Alessandro

    2014-06-21

    We present a two-band model based on periodic Hückel theory, which is capable of predicting the existence and position of Dirac cones in the first Brillouin zone of an infinite class of two-dimensional periodic carbon networks, obtained by systematic perturbation of the graphene connectivity by bond decoration, that is by inclusion of arbitrary π-electron Hückel networks into each of the three carbon–carbon π-bonds within the graphene unit cell. The bond decoration process can fundamentally modify the graphene unit cell and honeycomb connectivity, representing a simple and general way to describe many cases of graphene chemical functionalization of experimental interest, such as graphyne, janusgraphenes, and chlorographenes. Exact mathematical conditions for the presence of Dirac cones in the spectrum of the resulting two-dimensional π-networks are formulated in terms of the spectral properties of the decorating graphs. Our method predicts the existence of Dirac cones in experimentally characterized janusgraphenes and chlorographenes, recently speculated on the basis of density functional theory calculations. For these cases, our approach provides a proof of the existence of Dirac cones, and can be carried out at the cost of a back of the envelope calculation, bypassing any diagonalization step, even within Hückel theory.

  6. Raman spectroscopic analysis of a belltower commemorative wall decoration

    NASA Astrophysics Data System (ADS)

    Fernandes, R. F.; de Oliveira, L. F. C.; Edwards, H. G. M.; Brooke, C. J.; Pepper, M.

    2017-02-01

    The Raman spectroscopic analysis of a rare wall decoration in a church belltower, depicting the initials of couples married there in circular roundels over some 230 years, since 1777, has been undertaken prior to their impending restoration. The spectral data indicate that the red pigment is exclusively haematite which has been applied to plaster which exhibits the signatures variously of calcite, gypsum, anhydrite, calcium phosphate and dolomitic limestone; evidence of amorphous carbon is attributed to the deposition of soot from candle illumination, which has been recorded in historical documentation. The presence of biosignatures attributed to carotenoids in several samples is evidence of biological colonisation and potential deterioration which requires special treatment in the restoration strategies. The blackened areas near the upper edges of the wall decoration indicate carbon deposition and organic contamination. The latest addition to the decoration accomplished in 2008 shows that haematite has been used over a calcite ground. In earlier dated specimens, the presence of limewash is evident, which has only been partially converted into calcite by aerial attack from carbon dioxide in moist conditions.

  7. Radon exhalation from building materials for decorative use.

    PubMed

    Chen, Jing; Rahman, Naureen M; Abu Atiya, Ibrahim

    2010-04-01

    Long-term exposure to radon increases the risk of developing lung cancer. There is considerable public concern about radon exhalation from building materials and the contribution to indoor radon levels. To address this concern, radon exhalation rates were determined for 53 different samples of drywall, tile and granite available on the Canadian market for interior home decoration. The radon exhalation rates ranged from non-detectable to 312 Bq m(-2) d(-1). Slate tiles and granite slabs had relatively higher radon exhalation rates than other decorative materials, such as ceramic or porcelain tiles. The average radon exhalation rates were 30 Bq m(-2) d(-1) for slate tiles and 42 Bq m(-2) d(-1) for granite slabs of various types and origins. Analysis showed that even if an entire floor was covered with a material having a radon exhalation rate of 300 Bq m(-2) d(-1), it would contribute only 18 Bq m(-3) to a tightly sealed house with an air exchange rate of 0.3 per hour. Generally speaking, building materials used in home decoration make no significant contribution to indoor radon for a house with adequate air exchange.

  8. Preparation and antibacterial property of silver decorated carbon microspheres

    NASA Astrophysics Data System (ADS)

    Li, Sha; Yan, Xiaoliang; Yang, Zhi; Yang, Yongzhen; Liu, Xuguang; Zou, Jing

    2014-02-01

    Carbon microspheres (CMSs) were prepared by glucose hydrothermal method. The effects of glucose concentration and reaction time on the size and morphology of CMSs were studied. CMSs with surface area of 642.5 m2/g and pore size of 0.8 nm were exploited to design hybrid material of CMSs with Ag decoration by radio frequency plasma (RF plasma). A series of investigations using X-ray diffraction, UV-vis spectrometry, Fourier transform infrared spectrometry, X-ray photoelectron spectrometry, thermogravimetric analysis, scanning electron microscopy, energy dispersive X-ray spectroscopy, and transmission electron microscopy was carried out to characterize the Ag decorated CMSs. RF plasma was employed to reduce Ag+ ions to metallic nano-particles with the particle size of 10-20 nm and form a clean metal-support (Ag-CMSs) interface. The mechanism for the structure formation of Ag decorated CMSs was discussed. Plasma produced Ag/CMSs showed antibacterial property and proved suitable for potential biological and environmental applications.

  9. Aegyptin, a Novel Mosquito Salivary Gland Protein Specifically Binds to Collagen and Prevents its Interaction with Glycoprotein VI, Integrin α2β1 and von Willebrand Factor

    PubMed Central

    Calvo, Eric; Tokumasu, Fuyuki; Marinotti, Osvaldo; Villeval, Jean-Luc; Ribeiro, José M. C.; Francischetti, Ivo M. B.

    2010-01-01

    Blood-sucking arthropods have evolved a number of inhibitors of platelet aggregation and blood coagulation. In this report we have molecularly and functionally characterized aegyptin, a member of the family of 30-kDa salivary allergens from Aedes aegypti, whose function remained elusive thus far. Aegyptin displays a unique sequence characterized by glycine, glutamic acid, and aspartic acid repeats and was shown to specifically block collagen-induced human platelet aggregation and granule secretion. Plasmon resonance experiments demonstrate that aegyptin binds to collagen types I-V (Kd ≈ 1 nM) but does not interact with vitronectin, fibronectin, laminin, fibrinogen, and von Willebrand factor (vWf). In addition, aegyptin attenuates platelet adhesion to soluble or fibrillar collagen. Furthermore, aegyptin inhibits vWf interaction with collagen type III under static conditions and completely blocks platelet adhesion to collagen under flow conditions at high shear rates. Notably, aegyptin completely prevents collagen but not convulxin binding to recombinant glycoprotein VI. These findings indicate that aegyptin recognizes specific binding sites for glycoprotein VI, integrin α2β1, and vWf, thereby preventing collagen interaction with its three major ligands. Aegyptin is a novel tool to study collagen-platelet interaction and a prototype for development of molecules with antithrombotic properties. PMID:17650501

  10. Inhibitory effect of trichothecene mycotoxins on bovine platelets stimulated by platelet activating factor.

    PubMed Central

    Gentry, P A; Ross, M L; Bondy, G S

    1987-01-01

    Several species of fungi, which infect cereals and grains, can produce a class of compounds, known as trichothecene mycotoxins, which is characterized by a substituted epoxy-trichothecene ring structure. Cattle are susceptible to intoxication from feeds contaminated with T-2 toxin, one of the more potent trichothecene mycotoxins, while swine refuse to ingest feed contaminated with T-2 toxin. The bovine platelet has been used as a model cell system to evaluate the effects of T-2 toxin and its natural metabolites, HT-2 toxin and T-2 tetraol, on cell function in vitro. Due to the lipophilic nature of these mycotoxins, a biologically active phospholipid was used to stimulate the platelets in the presence and absence of the toxins. The mycotoxin T-2 toxin and its major metabolite HT-2 toxin inhibited platelet activating factor-stimulated bovine platelets, suspended in homologous plasma, in a concentration but not time dependent manner. Significant inhibition of platelet function (p less than 0.01) occurred with 135 ng T-2 toxin per 10(6) platelets and with 77 ng HT-2 toxin per 10(6) platelets. These mycotoxins exerted an additive inhibitory effect on the platelet aggregation response. In contrast, the minor metabolite T-2 tetraol had no inhibitory effect on platelet function and had no influence on the responses of T-2 toxin or HT-2 toxin when the mycotoxins were present together in the platelet suspensions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3453270

  11. The effects of drugs used in anaesthesia on platelet membrane receptors and on platelet function.

    PubMed

    Kozek-Langenecker, Sibylle A

    2002-06-01

    Platelet dysfunctions are known origins of perioperative bleeding disorders which are a major concern in the management of surgical patients. Among multiple factors, interactions of drugs used in anaesthesia with platelets have been implicated to aggravate the risk of haemorrhagic complications. This paper reviews in vitro and in vivo studies which have examined the effects of inhalational, intravenous, and local anaesthetics, opioids, and muscle relaxants on platelets. A brief summary of platelet physiology, function tests, and flow cytometric assessment of membrane receptors is included. Although the results of many studies have been conflicting, it appears that halothane, sevoflurane, and propofol inhibit platelet function in a reversible and dose-related manner at concentrations used clinically. Ilalothane affects the intracellular activating second messenger inositol triphosphate, platelet calcium homeostasis, thromboxane A2 formation, and the inhibiting signal transduction pathway including cyclic adenosine monophosphate. The proposed platelet inhibiting mechanism of sevoflurane involves the suppression of thromboxane A2 formation. Propofol appears to cause platelet dysfunctions by inhibiting calcium mobilisation upon agonist stimulation. Nitrous oxide causes a modest suppression of calcium mobilisation. An interaction of local anaesthetics with components in the platelet membrane appears to account for their inhibiting effect, but only at concentrations far higher than that found during clinical use. A clinically relevant antithrombotic effect of regional anaesthesia has been observed, though. Isoflurane, enflurane, desflurane, barbiturates, etomidate, opioids, and muscle relaxants seem to have negligible effects on platelets at therapeutic concentrations. Anaesthetists should be aware of the potential impairment of the coagulation profile by anaesthetic agents.

  12. Surface-decorated silicon nanowires: a route to high-ZT thermoelectrics.

    PubMed

    Markussen, Troels; Jauho, Antti-Pekka; Brandbyge, Mads

    2009-07-31

    Based on atomistic calculations of electron and phonon transport, we propose to use surface-decorated silicon nanowires for thermoelectric applications. Two examples of surface decorations are studied to illustrate the underlying ideas: nanotrees and alkyl functionalized silicon nanowires. For both systems we find (i) that the phonon conductance is significantly reduced compared to the electronic conductance leading to high thermoelectric figure of merit ZT, and (ii) for ultrathin wires, surface decoration leads to significantly better performance than surface disorder.

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

    PubMed Central

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

    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 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. PMID:23874839

  14. An MRI Von Economo - Koskinas atlas.

    PubMed

    Scholtens, Lianne H; de Reus, Marcel A; de Lange, Siemon C; Schmidt, Ruben; van den Heuvel, Martijn P

    2016-12-28

    The cerebral cortex displays substantial variation in cellular architecture, a regional patterning that has been of great interest to anatomists for centuries. In 1925, Constantin von Economo and George Koskinas published a detailed atlas of the human cerebral cortex, describing a cytoarchitectonic division of the cortical mantle into over 40 distinct areas. Von Economo and Koskinas accompanied their seminal work with large photomicrographic plates of their histological slides, together with tables containing for each described region detailed morphological layer-specific information on neuronal count, neuron size and thickness of the cortical mantle. Here, we aimed to make this legacy data accessible and relatable to in vivo neuroimaging data by constructing a digital Von Economo - Koskinas atlas compatible with the widely used FreeSurfer software suite. In this technical note we describe the procedures used for manual segmentation of the Von Economo - Koskinas atlas onto individual T1 scans and the subsequent construction of the digital atlas. We provide the files needed to run the atlas on new FreeSurfer data, together with some simple code of how to apply the atlas to T1 scans within the FreeSurfer software suite. The digital Von Economo - Koskinas atlas is easily applicable to modern day anatomical MRI data and is made publicly available online.

  15. Manual of Military Decorations and Awards: General Information, Medal of Honor, and Defense/Joint Decorations and Awards. Volume 1

    DTIC Science & Technology

    2010-11-23

    and Defense/Joint Decorations and Awards 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT NUMBER 5e...TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) Department of Defense,1400 Defense Pentagon,Washington,DC,20301...1400 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME( S ) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM( S ) 11. SPONSOR

  16. Platelets

    MedlinePlus

    ... an inherited gene mutation that limits the normal regulation and control, the complement system can damage our ... email: Evaren-Page@ouhsc.edu ), Department of Biostatistics & Epidemiology, College of Public Health, OUHSC Dee Terrell, PhD, ...

  17. Autophagy regulates endothelial cell processing, maturation and secretion of von Willebrand factor

    PubMed Central

    Torisu, Takehiro; Torisu, Kumiko; Lee, In Hye; Liu, Jie; Malide, Daniela; Combs, Christian A.; Wu, Xufeng S.; Rovira, Ilsa I.; Fergusson, Maria M.; Weigert, Roberto; Connelly, Patricia S.; Daniels, Mathew P; Komatsu, Masaaki; Cao, Liu; Finkel, Toren

    2013-01-01

    Endothelial secretion of von Willebrand factor (VWF) from intracellular organelles known as Weibel-Palade bodies (WPBs) is required for platelet adhesion to the injured vessel wall. Here, we demonstrate that WPBs are in some cases found near or within autophagosomes and that endothelial autophagosomes contain abundant VWF protein. Pharmacological inhibitors of autophagy, or knockdown of the essential autophagy genes Atg5 or Atg7, inhibits the in vitro secretion of VWF. Furthermore, while mice with an endothelial specific deletion of Atg7 have normal vessel architecture and capillary density, these animals exhibit impaired epinephrine-stimulated VWF release, reduced levels of high molecular weight VWF multimers and a corresponding elevation of their bleeding times. Endothelial deletion of Atg5 or pharmacological inhibition of autophagic flux results in a similar in vivo alteration of hemostasis. Thus, autophagy regulates endothelial VWF secretion and transient pharmacological inhibition of autophagic flux may be a useful strategy to prevent thrombotic events. PMID:24056772

  18. Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein.

    PubMed Central

    Iliopoulos, O; Levy, A P; Jiang, C; Kaelin, W G; Goldberg, M A

    1996-01-01

    Inactivation of the von Hippel-Lindau protein (pVHL) has been implicated in the pathogenesis of renal carcinomas and central nervous system hemangioblastomas. These are highly vascular tumors which overproduce angiogenic peptides such as vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). Renal carcinoma cells lacking wild-type pVHL were found to produce mRNAs encoding VEGF/VPF, the glucose transporter GLUT1, and the platelet-derived growth factor B chain under both normoxic and hypoxic conditions. Reintroduction of wild-type, but not mutant, pVHL into these cells specifically inhibited the production of these mRNAs under normoxic conditions, thus restoring their previously described hypoxia-inducible profile. Thus, pVHL appears to play a critical role in the transduction of signals generated by changes in ambient oxygen tension. Images Fig. 1 Fig. 2 Fig. 3 PMID:8855223

  19. Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic review and meta-analysis.

    PubMed

    Sonneveld, Michelle A H; de Maat, Moniek P M; Leebeek, Frank W G

    2014-07-01

    Von Willebrand Factor (VWF) plays an important role in hemostasis by mediating platelet adhesion and aggregation. Ultralarge VWF multimers are cleaved by ADAMTS13 in smaller, less procoagulant forms. An association between high VWF levels and cardiovascular disease has frequently been reported, and more recently also an association has been observed between low ADAMTS13 levels and arterial thrombosis. We reviewed the current literature and performed meta-analyses on the relationship between both VWF and ADAMTS13 with arterial thrombosis. Most studies showed an association between high VWF levels and arterial thrombosis. It remains unclear whether ADAMTS13 is a causal independent risk factor because the association between low ADAMTS13 and arterial thrombosis is so far only shown in case-control studies. Prospective studies are awaited. A causal role for ADAMTS13 is supported by mice studies of cerebral infarction where the infusion of recombinant human ADAMTS13 reduced the infarct size.

  20. Sulfation of von Willebrand factor

    SciTech Connect

    Carew, J.A.; Browning, P.J.; Lynch, D.C. )

    1990-12-15

    von Willebrand factor (vWF) is a multimeric adhesive glycoprotein essential for normal hemostasis. We have discovered that cultured human umbilical vein endothelial cells incorporate inorganic sulfate into vWF. Following immunoisolation and analysis by polyacrylamide or agarose gel electrophoresis, metabolically labeled vWF was found to have incorporated (35S)-sulfate into all secreted multimer species. The time course of incorporation shows that sulfation occurs late in the biosynthesis of vWF, near the point at which multimerization occurs. Quantitative analysis suggests the presence, on average, of one molecule of sulfate per mature vWF subunit. Virtually all the detectable sulfate is released from the mature vWF subunit by treatment with endoglycosidases that remove asparagine-linked carbohydrates. Sulfated carbohydrate was localized first to the N-terminal half of the mature subunit (amino acids 1 through 1,365) by partial proteolytic digestion with protease V8; and subsequently to a smaller fragment within this region (amino acids 273 through 511) by sequential digestions with protease V8 and trypsin. Thus, the carbohydrate at asparagine 384 and/or 468 appears to be the site of sulfate modification. Sodium chlorate, an inhibitor of adenosine triphosphate-sulfurylase, blocks sulfation of vWF without affecting either the ability of vWF to assemble into high molecular weight multimers or the ability of vWF multimers to enter Weible-Palade bodies. The stability of vWF multimers in the presence of an endothelial cell monolayer also was unaffected by the sulfation state. Additionally, we have found that the cleaved propeptide of vWF is sulfated on asparagine-linked carbohydrate.

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

    PubMed

    Gowert, Nina S; Donner, Lili; Chatterjee, Madhumita; Eisele, Yvonne S; Towhid, Seyda T; Münzer, Patrick; Walker, Britta; Ogorek, Isabella; Borst, Oliver; Grandoch, Maria; Schaller, Martin; Fischer, Jens W; Gawaz, Meinrad; Weggen, Sascha; Lang, Florian; Jucker, Mathias; Elvers, Margitta

    2014-01-01

    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.

  2. 21 CFR 864.5700 - Automated platelet aggregation system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... addition of an aggregating reagent to a platelet-rich plasma. (b) Classification. Class II (performance... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Automated platelet aggregation system. 864.5700... § 864.5700 Automated platelet aggregation system. (a) Identification. An automated platelet...

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

    ERIC Educational Resources Information Center

    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…

  4. 21 CFR 864.5700 - Automated platelet aggregation system.

    Code of Federal Regulations, 2010 CFR

    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...

  5. CALiPER Benchmark Report: Performance of Incandescent A Type and Decorative Lamps and LED Replacements

    SciTech Connect

    Lingard, R. D.; Myer, M. A.; Paget, M. L.

    2008-11-01

    This benchmark report addresses common omnidirectional incandescent lamps - A-type and small decorative, candelabra-type lamps - and their commercially available light-emitting diode (LED) replacements.

  6. Diffraction analysis of decorated Fibonacci chains in the average unit-cell approach.

    PubMed

    Wolny, J; Pytlik, L

    2000-01-01

    A novel approach to diffraction analysis of decorated quasicrystals is discussed. An average unit cell has been constructed for a decorated Fibonacci chain and used for analysis of its diffraction pattern. After some transformation of the scattering vectors, all the diffraction peaks are described by a single envelope function which is characteristic of a given decoration. It has been shown that by knowing several diffraction intensities, in a limited range of the scattering vector, it is possible to reconstruct the envelope function successfully and distinguish between different decorated structures.

  7. Improved thermal conductivity of Ag decorated carbon nanotubes water based nanofluids

    NASA Astrophysics Data System (ADS)

    Farbod, Mansoor; Ahangarpour, Ameneh

    2016-12-01

    The effect of Ag decoration of carbon nanotubes on thermal conductivity enhancement of Ag decorated MWCNTs water based nanofluids has been investigated. The pristine and functionalized MWCNTs were decorated with Ag nanoparticles by mass ratios of 1%, 2% and 4% and used to prepare water based nanofluids with 0.1 vol.%. An enhancement of 1-20.4 percent in thermal conductivity was observed. It was found that the decoration of functionalized MWCNTs can increase the thermal conductivity about 0.16-8.02 percent compared to the undecorated ones. The maximum enhancement of 20.4% was measured for the sample containing 4 wt.% Ag at 40 °C.

  8. Dr. Wernher Von Braun with Dr. Christian Barnard.

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Christian Barnard Tours Marshall Space Flight Center. Shown in Dr. Von Braun's office are (left to right): Dr. Ernst Sthulinger, a representative from General Electric, Dr. Wernher Von Braun, Dr. Christian Barnard, and Dr. Eberhard Rees.

  9. Aspirin treatment reduces platelet resistance to deformation.

    PubMed

    Burris, S M; Smith, C M; Rao, G H; White, J G

    1987-01-01

    The present investigation has evaluated the influence of aspirin, its constituents, and other nonsteroidal anti-inflammatory agents on the resistance of human platelets to aspiration into micropipettes. Aspirin increased the length of platelet extensions into the micropipette over the entire negative tension range of 0.04 to 0.40 dynes/cm after exposure to the drug in vitro or after ingestion of the agent. Other cyclooxygenase inhibitors, ibuprofen and indomethacin, did not increase platelet deformability. The influence of aspirin was mimicked to some degree by high concentrations of salicylic acid, but acetylation of platelets with acetic anhydride had little influence on platelet deformability. Incubation of platelets with both salicylic acid and acetic anhydride had no more effect than salicylic acid alone. Benzoic acid, chemically similar to salicylic acid, had a minimal effect. The studies demonstrate that aspirin makes platelets more deformable, while components of the drug or other nonsteroidal antiinflammatory agents and cyclooxygenase inhibitors do not have the same influence on resistance to deformation.

  10. The York Platelet Syndrome: a third case.

    PubMed

    White, James G; Gunay-Aygun, Meral

    2011-01-01

    Our present study has described a third patient with the York Platelet Syndrome (YPS). The condition consists of a mitochondrial myopathy associated with unique platelet pathology. Their mitochondrial myopathy has not been completely delineated and will be the subject of further study. Platelet pathology in the new patient is essentially identical to that described in the first two patients. Thin sections of her thrombocytes reveal a normal complement of α and δ granules (dense bodies) in some, a decreased number in others and complete absence in a few. The unique pathological feature is the presence of giant organelles, including an intensely electron dense, huge body, the opaque organelle (OO) and a multilayered large body, the target organelle. In addition platelets from the new patient contain large masses and coils of smooth endoplasmic reticulum present infrequently in platelets of the first two patients. The giant opaque and target organelles appear to develop in rough and smooth endoplasmic reticulum of the parent megakaryocyte and mature in the dense tubular system of circulating platelets. The relationship of the unique platelet pathology and mitochondrial myopathy has not been defined.

  11. Platelet thrombosis in cardiac-valve prostheses

    SciTech Connect

    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.

  12. Platelet ITAM Signaling and Vascular Integrity

    PubMed Central

    Boulaftali, Yacine; Hess, Paul R.; Kahn, Mark L.; Bergmeier, Wolfgang

    2014-01-01

    Platelets are well-known for their critical role in hemostasis, i.e. the prevention of blood loss at sites of mechanical vessel injury. Inappropriate platelet activation and adhesion, however, can lead to thrombotic complications, such as myocardial infarction and stroke. To fulfill its role in hemostasis, the platelet is equipped with various G protein-coupled receptors (GPCRs) that mediate the response to soluble agonists such as thrombin, ADP, and thromboxane A2. In addition to GPCRs, platelets express three glycoproteins (GP) that belong to the family of immunoreceptor tyrosine-based activation motif (ITAM) receptors: Fc receptor (FcR) γ chain, which is non-covalently associated with the GPVI collagen receptor, C-type lectin 2 (CLEC2), the receptor for podoplanin, and FcγRIIA, a low-affinity receptor for immune complexes. While both genetic and chemical approaches have documented a critical role for platelet GPCRs in hemostasis, the contribution of ITAM receptors to this process is less defined. Studies performed over the last decade, however, have identified new roles for platelet ITAM signaling in vascular integrity in utero and at sites of inflammation. The purpose of this review is to summarize recent findings on how platelet ITAM signaling controls vascular integrity, both in the presence and absence of mechanical injury. PMID:24677237

  13. Platelet antibody: review of detection methods

    SciTech Connect

    Schwartz, K.A.

    1988-10-01

    The driving force behind development of in vitro methods for platelet antibodies is identification of plasma factors causing platelet destruction. Early methods relied on measurement of platelet activation. Current methods are more specific and use a purified antibody against immunoglobulin or complement, which is usually labeled with /sup 125/I or tagged with an enzyme or fluorescein. Comparisons of quantitation of platelet-associated IgG show wide variability between different methods. The disparate results can be related both to differences in binding of secondary antibodies to immunoglobulin in solution compared to immunoglobulins attached to platelets and to the improper assumption that the binding ratio between the secondary detecting and primary antiplatelet antibody is one. Most assays can 1) identify neonatal isoimmune thrombocytopenia and posttransfusion purpura, 2) help to differentiate between immune and nonimmune thrombocytopenias, 3) help to sort out the offending drug when drug-induced thrombocytopenia is suspected, and 4) identify platelet alloantibodies and potential platelet donors via a cross match assay for refractory patients. However, the advantages of quantitative assays over qualitative methods with respect to predictions of patients clinical course and response to different treatments remain to be investigated. 61 references.

  14. Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles.

    PubMed Central

    Barry, O. P.; Pratico, D.; Lawson, J. A.; FitzGerald, G. A.

    1997-01-01

    Microparticles are released during platelet activation in vitro and have been detected in vivo in syndromes of platelet activation. They have been reported to express both pro- and anticoagulant activities. Nevertheless, their functional significance has remained unresolved. To address the mechanism(s) of cellular activation by platelet microparticles, we examined their effects on platelets and endothelial cells. Activation of human platelets by diverse stimuli (thrombin, 0.1 U/ml; collagen, 4 microg/ml; and the calcium ionophore A23187, 1 microM) results in shedding of microparticles. Pretreatment of these particles, but not membrane fractions from resting platelets, with (s)PLA2 evokes a dose-dependent increase in platelet aggregation, intracellular [Ca2+] movement, and inositol phosphate formation. These effects localize to the arachidonic acid fraction of the microparticles and are mimicked by arachidonic acid isolated from them. However, platelet activation requires prior metabolism of microparticle arachidonic acid to thromboxane A2. Thus, pretreatment of platelets with the cyclooxygenase (COX) inhibitor, indomethacin (20 microM), the thromboxane antagonist SQ29,548 (1 microM), or the protein kinase C inhibitor GF109203X (5 microM) prevents platelet activation by microparticles. However, platelet microparticles fail to evoke an inositol phosphate response directly, via either of the cloned thromboxane receptor isoforms stably expressed in human embryonic kidney (HEK) 293 cells. Prelabeling platelets with [2H(8)] arachidonate was used to demonstrate platelet metabolism of the microparticle-derived substrate to thromboxane. Platelet microparticles can also induce expression of COX-2 and prostacyclin (PGI2) production, but not expression of COX-1, in human endothelial cells. These effects are prevented by pretreatment with actinomycin D (12 microM) or cycloheximide (5 microg/ml). Expression of COX-2 is again induced by the microparticle arachidonate fraction

  15. Regulating billions of blood platelets: glycans and beyond

    PubMed Central

    Grozovsky, Renata; Giannini, Silvia; Falet, Hervé

    2015-01-01

    The human body produces and removes 1011 platelets daily to maintain a normal steady state platelet count. Platelet production must be regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. Multifaceted and complex mechanisms control platelet production and removal in physiological and pathological conditions. This review will focus on different mechanisms of platelet senescence and clearance with specific emphasis on the role of posttranslational modifications. It will also briefly address platelet transfusion and the role of glycans in the clearance of stored platelets. PMID:26330242

  16. Regulating billions of blood platelets: glycans and beyond.

    PubMed

    Grozovsky, Renata; Giannini, Silvia; Falet, Hervé; Hoffmeister, Karin M

    2015-10-15

    The human body produces and removes 10(11) platelets daily to maintain a normal steady state platelet count. Platelet production must be regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. Multifaceted and complex mechanisms control platelet production and removal in physiological and pathological conditions. This review will focus on different mechanisms of platelet senescence and clearance with specific emphasis on the role of posttranslational modifications. It will also briefly address platelet transfusion and the role of glycans in the clearance of stored platelets.

  17. Imipramine binding in subpopulations of normal human blood platelets

    SciTech Connect

    Arora, R.C.; Meltzer, H.Y.

    1984-02-01

    Imipramine binding was studied in platelet membranes isolated with different proportions of heavy (young) and light (old) platelets. The B/sub max/, a measure of the number of binding sites, was greater in the heavier platelets than in the light platelets. However, the dissociation constant K/sub d/ (a reflection of the affinity of imipramine binding) was greater in the lighter platelets compared to the heavy platelets. These results indicate that differences in K/sub d/ and B/sub max/ in particular membrane preparation, could be due to the differences in the relative proportion of heavy and light platelets.

  18. Viability and functional integrity of washed platelets

    SciTech Connect

    Pineda, A.A.; Zylstra, V.W.; Clare, D.E.; Dewanjee, M.K.; Forstrom, L.A.

    1989-07-01

    The viability and functional integrity of saline- and ACD-saline-washed platelets were compared with those of unwashed platelets. After template bleeding time (TBT) was measured, 15 healthy volunteers underwent plateletpheresis and ingested 600 mg of aspirin. Autologous /sup 111/In-labeled platelets were transfused: unwashed (n = 5), washed with 0.9 percent saline solution (SS) (n = 5), and washed with a buffered 12.6 percent solution of ACD-A in 0.9 percent saline solution (n = 5). After transfusion, we measured TBT at 1, 4, and 24 hours; platelet survival at 10 minutes and 1, 4, and 24 hours and daily for 6 days; and the percentage of uptake in liver and spleen by quantitative whole-body radionuclide scintigraphy at 24 and 190 hours. We found that saline washing affected platelet recovery, 23.47 +/- 12 percent (p less than 0.001) as compared to 52.43 +/- 17 percent (p less than 0.002) for ACD-saline and 73.17 +/- 8 percent for control; that saline washing resulted in a greater liver uptake than control and ACD-saline-washed platelets (31.9 +/- 8% (p less than 0.001) vs 17.7 +/- 4.1 and 19.3 +/- 2.1% (p greater than 0.1), respectively); that, unlike control and ACD-saline-washed platelets, saline-washed platelets did not shorten bleeding time; and that neither type of washing affected survival. Although ACD-saline washing affects recovery, it also results in intact function, normal survival, higher recovery than SS platelets, and no significant liver uptake.

  19. Technological advances in diagnostic testing for von Willebrand disease: new approaches and challenges.

    PubMed

    Hayward, C P M; Moffat, K A; Graf, L

    2014-06-01

    Diagnostic tests for von Willebrand disease (VWD) are important for the assessment of VWD, which is a commonly encountered bleeding disorder worldwide. Technical innovations have been applied to improve the precision and lower limit of detection of von Willebrand factor (VWF) assays, including the ristocetin cofactor activity assay (VWF:RCo) that uses the antibiotic ristocetin to induce plasma VWF binding to glycoprotein (GP) IbIXV on target platelets. VWF-collagen-binding assays, depending on the type of collagen used, can improve the detection of forms of VWD with high molecular weight VWF multimer loss, although the best method is debatable. A number of innovations have been applied to VWF:RCo (which is commonly performed on an aggregometer), including replacing the target platelets with immobilized GPIbα, and quantification by an enzyme-linked immunosorbent assay (ELISA), immunoturbidimetric, or chemiluminescent end-point. Some common polymorphisms in the VWF gene that do not cause bleeding are associated with falsely low VWF activity by ristocetin-dependent methods. To overcome the need for ristocetin, some new VWF activity assays use gain-of-function GPIbα mutants that bind VWF without the need for ristocetin, with an improved precision and lower limit of detection than measuring VWF:RCo by aggregometry. ELISA of VWF binding to mutated GPIbα shows promise as a method to identify gain-of-function defects from type 2B VWD. The performance characteristics of many new VWF activity assays suggest that the detection of VWD, and monitoring of VWD therapy, by clinical laboratories could be improved through adopting newer generation VWF assays.

  20. Liouville-von Neumann molecular dynamics

    NASA Astrophysics Data System (ADS)

    Jakowski, Jacek; Morokuma, Keiji

    2009-06-01

    We present a novel first principles molecular dynamics scheme, called Liouville-von Neumann molecular dynamics, based on Liouville-von Neumann equation for density matrices propagation and Magnus expansion of the time-evolution operator. The scheme combines formally accurate quantum propagation of electrons represented via density matrices and a classical propagation of nuclei. The method requires a few iterations per each time step where the Fock operator is formed and von Neumann equation is integrated. The algorithm (a) is free of constraint and fictitious parameters, (b) avoids diagonalization of the Fock operator, and (c) can be used in the case of fractional occupation as in metallic systems. The algorithm is very stable, and has a very good conservation of energy even in cases when a good quality conventional Born-Oppenheimer molecular dynamics trajectories is difficult to obtain. Test simulations include initial phase of fullerene formation from gaseous C2 and retinal system.