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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. 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

  13. 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.

  14. Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen

    PubMed Central

    Ni, Heyu; Denis, Cécile V.; Subbarao, Sangeetha; Degen, Jay L.; Sato, Thomas N.; Hynes, Richard O.; Wagner, Denisa D.

    2000-01-01

    We used intravital microscopy to observe the formation of platelet plugs in ferric chloride–injured arterioles of live mice. With this model, we evaluated thrombus growth in mice lacking von Willebrand factor (vWF) and fibrinogen (Fg), the two key ligands known to mediate platelet adhesion and aggregation. In vWF–/– mice, despite the presence of arterial shear, delayed platelet adhesion occurred and stable thrombi formed. In many mice, a persisting high-shear channel never occluded. Abundant thrombi formed in Fg–/– mice, but they detached from the subendothelium, which ultimately caused downstream occlusion in all cases. Surprisingly, mice deficient in both vWF and Fg successfully formed thrombi with properties characteristic of both mutations, leading to vessel occlusion in the majority of vessels. Platelets of these doubly deficient mice specifically accumulated fibronectin in their α-granules, suggesting that fibronectin could be the ligand supporting the platelet aggregation. PMID:10930441

  15. 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.

  16. Low shear stress can initiate von Willebrand factor-dependent platelet aggregation in patients with type IIB and platelet-type von Willebrand disease.

    PubMed Central

    Murata, M; Fukuyama, M; Satoh, K; Fujimura, Y; Yoshioka, A; Takahashi, H; Handa, M; Kawai, Y; Watanabe, K; Ikeda, Y

    1993-01-01

    Platelets exposed to shear stress aggregate in the absence of exogenously added agonists, utilizing distinct platelet membrane receptors and ligands depending upon the level of shear stress applied. Using a modified cone and plate type viscometer, we previously demonstrated that, under low shear stress (18 dyn/cm2), aggregation is mediated by platelet membrane glycoprotein (GP) IIb-IIIa and fibrinogen, whereas aggregation induced by high shear stress (108 dyn/cm2) requires the binding of von Willebrand factor (vWF) to both GPIb-IX and GPIIb-IIIa (Ikeda, Y., M. Handa, K. Kawano, T. Kamata, M. Murata, Y. Araki, H. Anbo, Y. Kawai, K. Watanabe, I. Itagaki, et al. 1991. J. Clin. Invest. 87:1234-1240). Here we report that vWF-dependent aggregation occurs under low shear stress in citrated platelet-rich plasma (PRP) from two types of congenital bleeding disorders, platelet-type von Willebrand disease (vWD) and type IIB vWD, in both of which ristocetin-induced aggregation is known to be heightened. Aggregation induced by low shear stress was enhanced in both types of disorders compared to normal controls, and the enhancement was completely abolished by anti-vWF monoclonal antibody NMC-4, which blocks the GPIb-binding site on vWF. Under high shear stress, the extent of maximal aggregation was not different between controls and the patient groups although maximal aggregation was reached much more quickly in the latter. When citrated PRP was exposed to a gradient of shear stress (6 to 108 dyn/cm2 over a 5-min period), vWF-dependent aggregation, as judged from the inhibitory effect of NMC-4, first occurred at 14 dyn/cm2 in platelet-type vWD and at 10-12 dyn/cm2 in type IIB vWD, as compared with more than 81 +/- 20.1 dyn/cm2 in control platelets. These results suggest that an abnormality in either vWF or GPIb-IX triggers the aggregation-inducing interaction of the two molecules under low shear stress, which might explain the intravascular platelet clumping, that presumably

  17. 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.

  18. 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

  19. Von Willebrand factor availability in platelet concentrates stored for 5 days.

    PubMed

    Cesar, J M; García-Avello, A; Monteagudo, J; Espinosa, J I; Lodos, J C; Castillo, R; Navarro, J L

    1994-02-01

    Von Willebrand factor (vWF) availability was assessed in platelet concentrates (PCs). After 5 days of storage, 82 +/- 9% of basal levels of ristocetin cofactor activity (vWF:RCo) remained in PCs. vWF antigen (vWF:Ag) increased up to 166 +/- 38% (P < 0.05) in the same period. Autoradiograph pattern of vW:Ag showed an increase in low molecular weight multimers, and fast migrating multimeric forms were visualized by crossed immunoelectrophoresis on day 5. Studies carried out in platelet free plasma stored as PCs showed similar changes in vWF:RCo but increments in vWF:Ag were not detected. These data indicate that PCs maintain vWF:RCo levels of clinical value even after 5 days of storage and suggest that vWF comes out from platelets to plasma during storage.

  20. Enhanced Local Disorder in a Clinically Elusive von Willebrand Factor Provokes High-Affinity Platelet Clumping.

    PubMed

    Tischer, Alexander; Machha, Venkata R; Frontroth, Juan P; Brehm, Maria A; Obser, Tobias; Schneppenheim, Reinhard; Mayne, Leland; Walter Englander, S; Auton, Matthew

    2017-07-07

    Mutation of the cysteines forming the disulfide loop of the platelet GPIbα adhesive A1 domain of von Willebrand factor (VWF) causes quantitative VWF deficiencies in the blood and von Willebrand disease. We report two cases of transient severe thrombocytopenia induced by DDAVP treatment. Cys1272Trp and Cys1458Tyr mutations identified by genetic sequencing implicate an abnormal gain-of-function phenotype, evidenced by thrombocytopenia, which quickly relapses back to normal platelet counts and deficient plasma VWF. Using surface plasmon resonance, analytical rheology, and hydrogen-deuterium exchange mass spectrometry (HXMS), we decipher mechanisms of A1-GPIbα-mediated platelet adhesion and resolve dynamic secondary structure elements that regulate the binding pathway. Constrained by the disulfide, conformational selection between weak and tight binding states of A1 takes precedence and drives normal platelet adhesion to VWF. Less restrained through mutation, loss of the disulfide preferentially diverts binding through an induced-fit disease pathway enabling high-affinity GPIbα binding and firm platelet adhesion to a partially disordered A1 domain. HXMS reveals a dynamic asymmetry of flexible and ordered regions common to both variants, indicating that the partially disordered A1 lacking the disulfide retains native-like structural dynamics. Both binding mechanisms share common structural and thermodynamic properties, but the enhanced local disorder in the disease state perpetuates high-affinity platelet agglutination, characteristic of type 2B VWD, upon DDAVP-stimulated secretion of VWF leading to transient thrombocytopenia and a subsequent deficiency of plasma VWF, characteristic of type 2A VWD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. 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

  2. Variability in platelet- and collagen-binding defects in type 2M von Willebrand disease.

    PubMed

    Larsen, D M; Haberichter, S L; Gill, J C; Shapiro, A D; Flood, V H

    2013-07-01

    Type 2M von Willebrand disease (VWD) includes qualitative defects in von Willebrand factor (VWF) function, with normal multimer distribution but a defect in VWF activity with respect to platelet or collagen binding. We characterized novel VWF gene mutations found in type 2M VWD subjects enrolled in the Zimmerman Program for the Molecular and Clinical Biology of VWD. Subjects were enrolled based on a pre-existing diagnosis of type 2M VWD. Testing included full-length gene sequencing, VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen binding and multimer distribution. Recombinant VWF variants were synthesized using site-directed mutagenesis and expressed in HEK293T cells. Platelet binding was measured by flow cytometry with fixed platelets and ELISA with recombinant glycoprotein Ibα (GPIbα). Four novel VWF A1 domain mutations were found in individuals with type 2M VWD: S1358N, S1387I, S1394F and Q1402P. All subjects had a history of bleeding, VWF:RCo < 40 IU dL(-1) , VWF:RCo/VWF:Ag ratios <0.6 and normal multimer distribution. No defect in expression, secretion, or multimerization was found for any of the mutations. All showed decreased binding to intact platelets, and decreased or absent binding to a mutant GPIbα construct with spontaneous VWF binding. 1387I had decreased binding to all collagen types tested. 1402P had reduced binding exclusively to type VI collagen. Type 2M VWD is a heterogeneous category comprised of both collagen- and platelet-binding defects. Understanding the precise defect for each mutation may ultimately lead to better diagnosis and treatment. © 2013 John Wiley & Sons Ltd.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. Conformational energy analysis of the substitution of Val for Gly 233 in a functional region of platelet GPIb alpha in platelet-type von Willebrand disease.

    PubMed

    Pincus, M R; Dykes, D C; Carty, R P; Miller, J L

    1991-09-23

    Platelet-type von Willebrand disease (PT-vWD) is an autosomal dominant bleeding disorder in which patient platelets exhibit an abnormally increased binding of circulating von Willebrand factor (vWF). We have recently shown that this abnormality is associated with a point mutation resulting in substitution of Val for Gly 233 in platelet membrane glycoprotein Ib alpha (GPIb alpha), a major component of the platelet GPIb/IX receptor for vWF. To investigate the effect of this substitution on the three-dimensional structure of this region of the protein, we have generated the allowed (low energy) conformations of the region of the GPI alpha protein containing residues 228-238 (with 5 residues on either side of the critical residue 233) with Gly 233 (wild type) and Val 233 (PT-vWD) using the computer program ECEPP (Empirical Conformational Energies of Peptides Program). The wild-type sequence is Tyr-Val-Trp-Lys-Gln-Gly-Val-Asp-Val-Lys-Ala. We find that the Gly 233-containing peptide can exist in two low energy conformers. The lowest energy conformer is a structure containing a beta-turn at Gln 232-Gly 233 while the alternative conformation is an amphipathic helical structure. Only the amphipathic helical structure is allowed for the Val 233-containing peptide which contains a hydrophobic 'face' consisting of Val 229, Val 233 and Val 236 and another hydrophilic surface composed of such residues as Lys 231 and Asp 235. No such surfaces exist for the lowest energy bend conformer for the Gly 233-containing peptide, but do exist in the higher energy helical structure. The amphipathic surfaces in the 228-238 region of the Val 233-containing GPIb alpha protein may associate strongly with complementary surfaces during vWF binding to the GPIb/IX receptor complex and may help explain heightened association of vWF with this receptor in PT-vWD.

  10. 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.

  11. 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.

  12. 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.

  13. Key role of glycoprotein Ib/V/IX and von Willebrand factor in platelet activation-dependent fibrin formation at low shear flow

    PubMed Central

    Cosemans, Judith M. E. M.; Schols, Saskia E. M.; Stefanini, Lucia; de Witt, Susanne; Feijge, Marion A. H.; Hamulyák, Karly; Deckmyn, Hans; Bergmeier, Wolfgang

    2011-01-01

    A microscopic method was developed to study the role of platelets in fibrin formation. Perfusion of adhered platelets with plasma under coagulating conditions at a low shear rate (250−1) resulted in the assembly of a star-like fibrin network at the platelet surface. The focal fibrin formation on platelets was preceded by rises in cytosolic Ca2+, morphologic changes, and phosphatidylserine exposure. Fibrin formation was slightly affected by αIIbβ3 blockage, but it was greatly delayed and reduced by the following: inhibition of thrombin or platelet activation; interference in the binding of von Willebrand factor (VWF) to glycoprotein Ib/V/IX (GpIb-V-IX); plasma or blood from patients with type 1 von Willebrand disease; and plasma from mice deficient in VWF or the extracellular domain of GpIbα. In this process, the GpIb-binding A1 domain of VWF was similarly effective as full-length VWF. Prestimulation of platelets enhanced the formation of fibrin, which was abrogated by blockage of phosphatidylserine. Together, these results show that, in the presence of thrombin and low shear flow, VWF-induced activation of GpIb-V-IX triggers platelet procoagulant activity and anchorage of a star-like fibrin network. This process can be relevant in hemostasis and the manifestation of von Willebrand disease. PMID:21037087

  14. Platelet adhesion to collagen type I, collagen type IV, von Willebrand factor, fibronectin, laminin and fibrinogen: rapid kinetics under shear.

    PubMed

    Polanowska-Grabowska, R; Simon, C G; Gear, A R

    1999-01-01

    Extracellular matrix proteins in the blood vessel wall fulfill an essential role in haemostasis by promoting platelet adhesion at the site of vessel injury. We have combined a continuous-flow system with affinity chromatography to study platelet adhesion under conditions mimicking arterial flow and have examined the adhesion kinetics of unstimulated platelets to collagens type I and IV, von Willebrand factor (vWf), fibronectin, laminin and to fibrinogen. In the absence of red cells, in ACD-prepared plasma adhesion to collagens type I and IV or vWf was rapid, efficient (>50% in <1 s ) and independent of shear rates from 650 to 3400 s(-1) with kinetics following an inverse exponential decay curve. We introduced a simple mathematical model in which this type of kinetics arises, and which may be more generally applicable to various adhesion processes under flow conditions. The model is characterized by the rate of platelet deposition on the adhesive surface being proportional to the number of platelets in the flow. Adhesion to fibronectin was independent of shear rate, but revealed a lag phase of approximately 1.5 s before significant adhesion began. Laminin and fibrinogen supported efficient adhesion at low shear rates (650-1000 s(-1)), but a lag phase of approximately 1.5 s was seen at high shear rates (1700-3400 s(-1)). Control proteins (albumin and gelatin) supported minimal adhesion. Nonspecific adhesion to poly-L-lysine differed from that to other substrate proteins in that the kinetics were linear. In conclusion, human platelets adhered specifically, rapidly (within seconds) and efficiently to several proteins under flow conditions and the kinetics of adhesion depended on the protein serving as substrate as well as on shear rate.

  15. A molten globule intermediate of the von Willebrand factor A1 domain firmly tethers platelets under shear flow.

    PubMed

    Tischer, Alexander; Madde, Pranathi; Blancas-Mejia, Luis M; Auton, Matthew

    2014-05-01

    Clinical mutations in patients diagnosed with Type 2A von Willebrand disease (VWD) have been identified that break the single disulfide bond linking N- and C-termini in the vWF A1 domain. We have modeled the effect of these mutations on the disulfide-bonded structure of A1 by reducing and carboxy-amidating these cysteines. Solution biophysical studies show that loss of this disulfide bond induces a molten globule conformational state lacking global tertiary structure but retaining residual secondary structure. The conformational dependence of platelet adhesion to these native and molten globule states of A1 is quantitatively compared using real-time high-speed video microscopy analysis of platelet translocation dynamics under shear flow in a parallel plate microfluidic flow chamber. While normal platelets translocating on surface-captured native A1 domain retain the catch-bond character of pause times that increase as a function of shear rate at low shear and decrease as a function of shear rate at high shear, platelets that interact with A1 lacking the disulfide bond remain stably attached and do not translocate. Based on these findings, we propose that the shear stress-sensitive regulation of the A1-GPIb interaction is due to folding the tertiary structure of this domain. Removal of the tertiary structure by disrupting the disulfide bond destroys this regulatory mechanism resulting in high-strength interactions between platelets and vWF A1 that are dependent only on residual secondary structure elements present in the molten globule conformation. Copyright © 2013 Wiley Periodicals, Inc.

  16. A molten globule intermediate of the Von Willebrand Factor A1 domain firmly tethers platelets under shear flow

    PubMed Central

    Tischer, Alexander; Madde, Pranathi; Blancas-Mejia, Luis. M.; Auton, Matthew

    2014-01-01

    Clinical mutations in patients diagnosed with Type 2A von Willebrand disease (vWD) have been identified that break the single disulfide bond linking N- and C-termini in the vWF A1 domain. We have modeled the effect of these mutations on the disulfide-bonded structure of A1 by reducing and carboxy-amidating these cysteines. Solution biophysical studies show that loss of this disulfide bond induces a molten globule conformational state lacking global tertiary structure but retaining residual secondary structure. The conformational dependence of platelet adhesion to these native and molten globule states of A1 is quantitatively compared using real-time high-speed video microscopy analysis of platelet translocation dynamics under shear flow in a parallel plate micro-fluidic flow chamber. While normal platelets translocating on surface-captured native A1 domain retain the catch-bond character of pause times that increase as a function of shear rate at low shear and decrease as a function of shear rate at high shear, platelets that interact with A1 lacking the disulfide bond remain stably attached and do not translocate. Based on these findings, we propose that the shear stress-sensitive regulation of the A1-GPIb interaction is due to folding the tertiary structure of this domain. Removal of the tertiary structure by disrupting the disulfide bond destroys this regulatory mechanism resulting in high-strength interactions between platelets and vWF A1 that are dependent only on residual secondary structure elements present in the molten globule conformation. PMID:24265179

  17. Platelets

    MedlinePlus

    ... common disorder of platelet function is caused by aspirin. Aspirin blocks one of the steps required for platelets to stick together. This effect of aspirin is what makes it an effective treatment for ...

  18. 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

  19. Effect of the Novel Biodegradable N, O-Carboxymethylchitosan and Oligo-Chitosan on the Platelet Thrombogenicity Cascade in von Willebrand Disease.

    PubMed

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

    2015-09-01

    Von Willebrand disease (vWD) is the second least common hemostatic disorder in Malaysia, and it has a low prevalence. This study examined the underlying platelet thrombogenicity cascades in the presence of different formulations of chitosan-derivatives in vWD patients. This paper aimed to determine the significant influence of chitosan biomaterial in stimulating the platelet thrombogenicity cascades that involve the von Willebrand factor, Factor 8, Thromboxane A2, P2Y12 and Glycoprotein IIb/IIIa in vWD. Variable chitosan formulations of N,O-Carboxymethylchitosan (NO-CMC) and Oligo-Chitosan (O-C) were tested. Fourteen vWD subjects voluntarily participated in this study after signing informed consent forms. The patient's demographic profiles, family history, type of vWD, clinical symptoms and laboratory profiles were recorded and analyzed. Enzyme-linked immunosorbent assay, flow cytometry and Western blot tests were used to determine the level of the chitosan-adhered-platelet-mechanisms. The study revealed that most patients were predominantly affected by vWD type I. The O-C group of chitosan's scaffold pores is sufficient to allow for nutrients and cells. The O-C-stimulated-mediators are capable of initiating the platelet actions and were detected to expedite the blood coagulation processes. The oligo-group of chitosans was capable of amplifying and triggering more platelet activator's pathways via the studied mediators. The present findings suggest that the ability of each type of chitosan to coagulate blood varies depending on its chemical composition. The oligo group of chitosans is potentially capable of triggering platelet thrombogenicity cascades by activating platelets in vWD patients to form a platelet plug for hemostasis process. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. 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.

  1. von Willebrand factor interaction with the glycoprotein IIb/IIa complex. Its role in platelet function as demonstrated in patients with congenital afibrinogenemia.

    PubMed Central

    De Marco, L; Girolami, A; Zimmerman, T S; Ruggeri, Z M

    1986-01-01

    We have studied three afibrinogenemic patients, who had only trace amounts of plasma and platelet fibrinogen as measured by radioimmunoassay, and demonstrate here that the residual aggregation observed in their platelet-rich plasma is dependent upon von Willebrand factor (vWF) binding to the platelet membrane glycoprotein (GP)IIb/IIIa complex. The abnormality of aggregation was more pronounced when ADP, rather than thrombin, collagen, or the combination of ADP plus adrenaline was used to stimulate platelets. With all stimuli, nevertheless, the platelet response was completely inhibited by a monoclonal antibody (LJP5) that is known to block vWF, but not fibrinogen binding to GPIIb/IIIa. Addition of purified vWF to the afibrinogenemic plasma resulted in marked increase in the rate and extent of aggregation, particularly when platelets were stimulated with ADP. This response was also completely blocked by LJP5. Addition of fibrinogen, however, restored normal aggregation even in the presence of LJP5, a finding consistent with the knowledge that antibody LJP5 has no effect on platelet aggregation mediated by fibrinogen binding to GPIIb/IIIa. Two patients gave their informed consent to receiving infusion of 1-desamino-8-D-arginine vasopressin (DDAVP), a vasopressin analogue known to raise the vWF levels in plasma by two- to fourfold. The bleeding time, measured before and 45 min after infusion, shortened from greater than 24 min to 12 min and 50 s in one patient and from 16 min to 9 min and 30 s in the other. Concurrently, the rate and extent of ADP-induced platelet aggregation improved after DDAVP infusion. The pattern, however, reversed to baseline levels within 4 h. The concentration of plasma vWF increased after DDAVP infusion, but that of fibrinogen remained at trace levels. We conclude that vWF interaction with GPIIb/IIIa mediates platelet-platelet interaction and may play a role in primary hemostasis. PMID:3007578

  2. The important role of von Willebrand factor in platelet-derived FVIII gene therapy for murine hemophilia A in the presence of inhibitory antibodies.

    PubMed

    Shi, Q; Schroeder, J A; Kuether, E L; Montgomery, R R

    2015-07-01

    Our previous studies have demonstrated that targeting FVIII expression to platelets results in FVIII storage together with von Willebrand factor (VWF) in platelet α-granules and that platelet-derived FVIII (2bF8) corrects the murine hemophilia A phenotype even in the presence of high-titer anti-FVIII inhibitory antibodies (inhibitors). To explore how VWF has an impact on platelet gene therapy for hemophilia A with inhibitors. 2bF8 transgenic mice in the FVIII(-/-) background (2bF8(tg+/-) F8(-/-) ) with varying VWF phenotypes were used in this study. Animals were analyzed by VWF ELISA, FVIII activity assay, Bethesda assay and tail clip survival test. Only 18% of 2bF8(tg+/-) F8(-/-) VWF(-/-) animals, in which VWF was deficient, survived the tail clip challenge with inhibitor titers of 3-8000 BU mL(-1) . In contrast, 82% of 2bF8(tg+/-) F8(-/-) VWF(+/+) mice, which had normal VWF levels, survived tail clipping with inhibitor titers of 10-50,000 BU mL(-1) . All 2bF8(tg+/-) F8(-/-) VWF(-/-) mice without inhibitors survived tail clipping and no VWF(-/-) F8(-/-) mice survived this challenge. Because VWF is synthesized by endothelial cells and megakaryocytes and is distributed in both plasma and platelets in peripheral blood, we further investigated the effect of each compartment of VWF on platelet-FVIII gene therapy for hemophilia A with inhibitors. In the presence of inhibitors, 42% of animals survived tail clipping in the group with plasma-VWF and 50% survived in the platelet-VWF group. VWF is essential for platelet gene therapy for hemophilia A with inhibitors. Both platelet-VWF and plasma-VWF are required for optimal platelet-derived FVIII gene therapy for hemophilia A in the presence of inhibitors. © 2015 International Society on Thrombosis and Haemostasis.

  3. 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 ...

  4. 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

  5. Ristocetin-mediated interaction of human von Willebrand factor with platelet glycoprotein lb evokes a transient calcium signal: observations with Fura-PE3.

    PubMed

    Milner, E P; Zheng, Q; Kermode, J C

    1998-01-01

    High shear stress in narrowed arteries causes von Willebrand factor (vWf) to bind to its platelet receptor, glycoprotein Ib (GpIb). This binding is reported to promote an increase in intracellular free calcium concentration ((Ca2+)i), which may be responsible for platelet activation. The present study examined the platelet (Ca2+)i signal that arises when ristocetin mediates vWf-GpIb binding. Platelet (Ca2+)i was monitored with Fura-PE3 (Vorndran C, Minta A, Poenie M. Biophys J 1995;69:2112-24), a new ratiometric calcium indicator. Fura-PE3 has calcium-binding characteristics (Kd = 146 nmol/L) and fluorescent properties similar to those of Fura-2. However, its zwitterionic nature ensured much slower extrusion from the platelet (0.2% per minute) than that for Fura-2. This eliminated one of the technical problems that seriously distorted previous measurements of vWf-induced changes in platelets (Ca2+)i. Design of a novel stirring arrangement avoided the other major problem, which is the tendency of platelet aggregates to settle to the bottom of the cuvette, beneath the detection zone of the spectrofluorometer. With Fura-PE3 and the new stirrer used in the present study, vWf-induced changes in (Ca2+)i could be measured reliably in aggregating platelets. Ristocetin-mediated vWf-GpIb binding induced a transient increase in platelet (Ca2+)i. This increase occurred after a significant lag phase; platelet (Ca2+)i rose gradually, followed by a decline to almost the resting level. Binding of vWf to platelet Gplb was responsible for the (Ca2+)i signal. A similar signal was found in the absence of extracellular calcium. These characteristics differ substantially from those described in previous reports, in which the vWf-induced rise in (Ca2+)i was attributed to calcium influx through channels in the plasma membrane. Data from those earlier studies, however, were severely distorted by indicator extrusion and loss of platelet aggregates. The present findings are a more accurate

  6. 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

  7. 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.

  8. 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.

  9. Von Willebrand factor-A1 domain binds platelet glycoprotein Ibα in multiple states with distinctive force-dependent dissociation kinetics

    PubMed Central

    Ju, Lining; Chen, Yunfeng; Zhou, Fangyuan; Lu, Hang; Cruz, Miguel A.; Zhu, Cheng

    2015-01-01

    Circulating von Willebrand factor (VWF) adopts a closed conformation that shields the platelet glycoprotein Ibα (GPIbα) binding site in the VWF-A1 domain. Immobilized at sites of vascular injury, VWF is activated by its interaction with collagen and the exertion of increased hemodynamic forces. Studies on native VWF strings and isolated A1 domains suggest the existence of multiple A1 binding states in different biophysical contexts. In this single-molecule study, we have used a biomembrane force probe (BFP) and a flow chamber to identify and characterize a collagen binding induced conformation with a higher affinity to platelet GPIbα. As force increases, our results show that collagen binding increases the stability of GPIbα bond with both VWF and isolated A1 domain. However, the collagen 2D binding affinity for VWF-A3 domain is 10 times of that for A1 domain, suggesting the initial VWF capture is mediated by A3–collagen interaction while A1–collagen regulates the subsequent VWF activation. Our results revealed the molecular mechanism of collagen-regulated, A1-mediated platelet adhesion enhancement. Characterization of different A1 states provides insights into binding heterogeneity of VWF in different scenarios of inflammation and thrombosis. PMID:26213126

  10. 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.

  11. von Willebrand Factor Test

    MedlinePlus

    ... Was this page helpful? Also known as: VWF:Ag; VWF:RCo; von Willebrand Panel; Ristocetin Cofactor Formal ... may include: Ratio of VWF:RCo to VWF:Ag Factor VIII binding assay Platelet VWF studies Collagen ...

  12. 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

  13. Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke.

    PubMed

    McCabe, Dominick J H; Murphy, Stephen J X; Starke, Richard; Harrison, Paul; Brown, Martin M; Sidhu, Paul S; Mackie, Ian J; Scully, Marie; Machin, Samuel J

    2015-01-15

    Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied. In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)). Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels. ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD. Copyright © 2014 Elsevier B.V. All rights

  14. Platelets, glycoprotein Ib-IX, and von Willebrand factor are required for FeCl3-induced occlusive thrombus formation in the inferior vena cava of mice

    PubMed Central

    Joglekar, M.; Ware, Jerry; Xu, Jin; Fitzgerald, Malinda E. C.; Gartner, T. Kent

    2013-01-01

    Venous thromboembolism is a leading cause of death from cardiovascular disease. Despite the importance of the glycoprotein (GP) Ib-IX/von Willebrand factor (vWF) axis in arterial thrombosis, its requirement in venous, not venule thrombosis in response to endothelial injury (not stenosis or stasis) is uncharacterized. GPIbα-vWF participation in FeCl3-induced thrombus formation was evaluated in the inferior vena cava (IVC). Stable, occlusive thrombus formation in response to FeCl3-induced injury of the IVC was studied. FeCl3 (20% FeCl3, 10 minutes)-induced occlusive thrombosis required platelets as confirmed by a lack of occlusion in thrombocytopenic mice, and stable occlusion in control animals. No IVC occlusion was observed using GPIbα-deficient animals, a model of the human Bernard-Soulier syndrome (BSS). Transgenic IL-4R/GPIbα mice (lack murine GPIbα, but express the extracellular domain of the human interleukin (IL)-4 receptor fused to the transmembrane and cytoplasmic domains of human GPIbα), were studied to determine if the absence of IVC occlusion in the BSS mouse was caused by GPIbα extracellular domain deficiency rather than platelet BSS phenotype associated abnormalities. As with GPIbα knock-out (KO) mice, no occlusion was observed in the IVC of IL-4R/GPIbα mice. The IVC of vWF-deficient mice also failed to occlude in response to FeCl3 treatment. The chimeric protein GPIbα(2V)-Fc prevented occlusion, demonstrating that GPIbα-vWF A1 domain interaction is required for FeCl3-induced stable thrombus formation in the IVC. Therefore, FeCl3-induced stable, occlusive thrombus formation in the IVC is platelet, GPIbα-vWF interaction-dependent despite the large diameter and low venous flow rate in the IVC. PMID:22720736

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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…

  20. 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…

  1. 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.

  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. 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.

  6. 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);…

  7. 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);…

  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. Ceramics with decorative aspect

    NASA Astrophysics Data System (ADS)

    Voica, Cezara

    2009-08-01

    The last decades brought the development of bone china techniques used for producing the decorative articles. These products can be glazed with a transparent and thin glaze layer, even with more special (decorative) ones which gives new aesthetic aspect. The present article presents the results obtained after the studies performed for matte glazes for decorative bone china. As microcrystalization agent were used zinc oxide; the content of this oxide bring some changes of the basic glaze thus the chemical composition must be adjusted as the fluxes would present the desired properties after the heating process.

  10. [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.

  11. 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.

  12. 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 ...

  13. 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.

  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. 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.

  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. Understanding platelet function through signal transduction.

    PubMed

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

    2003-01-01

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

  19. 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.

  20. 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

  1. Platelet fibrinogen

    PubMed Central

    Castaldi, P. A.; Caen, J.

    1965-01-01

    Platelet fibrinogen has been studied in normal, thrombasthenic, and hypofibrinogenaemic subjects. It has been differentiated into adsorbed (plasma) and extractable (intraplatelet) fractions. Isotopic studies suggest that exchange does not occur between intraplatelet and plasma fibrinogen and it appears possible that the intra-platelet fraction may be derived from the megakaryocyte. Six of nine thrombasthenic patients were found to have a severe deficiency of both adsorbed and extractable fibrinogen. Since the remaining three had near-normal platelet fibrinogen and all nine failed to aggregate it is improbable that the failure to adsorb fibrinogen is responsible for the defect in aggregation. Magnesium partially corrects adhesion to fibrin and clot retraction by these platelets, but has not been found to influence their fibrinogen adsorption. It is considered that the basic platelet surface defect, of varying severity, is responsible for the abnormalities of adsorption, aggregation, and adhesion in thrombasthenia. In the case of congenital hypofibrinogenaemia, fibrinogen transfusion corrects the long bleeding time, platelet-adsorbed fibrinogen, and the ability of platelets to spread on glass. It is possible that fibrinogen influences the surface properties of human platelets, although the final mechanism is not determined. Images PMID:5835438

  2. 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.

  3. 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 (

  4. 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 ...

  5. Alpha granule proteins in type I von Willebrand's disease.

    PubMed

    McKeown, L P; Williams, S B; Shafer, B; Murray, N; Gralnick, H R

    1993-02-01

    Platelet von Willebrand factor (vWf) is located in the alpha granules. Individuals with type I von Willebrand's disease (vWd) with prolonged bleeding times are best discriminated from those who have normal bleeding times by the normal level of platelet vWf ristocetin cofactor activity (vWf activity) and, to a lesser extent, by their platelet vWf antigen content. We have studied the content of adhesive proteins and platelet factor-4 (PF-4), and beta-thromboglobulin (beta TG) in the platelet alpha granules of types I and III vWd patients to determine if other alterations in alpha granule contents of proteins occur in vWd. We found that type I vWd patients with prolonged or normal bleeding times could not be differentiated on the basis of their platelet levels of beta TG, PF-4, fibronectin, or fibrinogen. The levels of the alpha granule constituents in the type I vWd patient were similar to normal except for the platelet fibrinogen concentration. Patients with type I vWd, regardless of the level of platelet vWf activity of antigen, had increased levels of platelet fibrinogen. The patients with type III vWd who had undetectable levels of platelet and plasma vWf also had increased levels of platelet fibrinogen. In our study we could not attribute the variation in the platelet vWf activity and antigen in type I vWd to the size of the alpha granule pool as determined by the measurement of other alpha granule proteins. The mechanism(s) of increased platelet fibrinogen in these vWd patients is at present unknown.

  6. 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

  7. 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

  8. PLATELET FORMATION

    PubMed Central

    Thon, Jonathan N.; Italiano, Joseph E.

    2010-01-01

    Thrombocytopenia is the underlying cause of a number of major clinical conditions and genetic disorders worldwide. While therapeutic agents that bind and stimulate the thrombopoietin receptor are currently available, the development of drugs that directly stimulate megakaryocytes to generate platelets has lagged behind. To improve the management of thrombocytopenia, we will need to define the cell biological pathways that drive the production of platelets from megakaryocytes. This review integrates the latest research of platelet biogenesis and focuses on the molecular pathways that power and regulate proplatelet production. PMID:20620432

  9. 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.

  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. 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.

  13. 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

  14. 22 CFR 3.7 - Decorations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Decorations. 3.7 Section 3.7 Foreign Relations DEPARTMENT OF STATE GENERAL GIFTS AND DECORATIONS FROM FOREIGN GOVERNMENTS § 3.7 Decorations. (a) Decorations tendered in recognition of active field service in time of combat operations or awarded for other...

  15. The effect of desmopressin on platelet function: a selective enhancement of procoagulant COAT platelets in patients with primary platelet function defects.

    PubMed

    Colucci, Giuseppe; Stutz, Monika; Rochat, Sophie; Conte, Tiziana; Pavicic, Marko; Reusser, Marianne; Giabbani, Evelyne; Huynh, Anh; Thürlemann, Charles; Keller, Peter; Alberio, Lorenzo

    2014-03-20

    1-deamino-8-d-arginine vasopressin (desmopressin [DDAVP]) is clinically efficacious in patients with mild platelet function disorders but it is not known which mechanisms mediate this effect. Our aim was to evaluate the impact of in vivo DDAVP administration in these patients. We assessed von Willebrand factor (VWF), factor VIII, platelet activation and aggregation, platelet-dependent thrombin generation, and platelet intracellular Na(+)/Ca(2+) fluxes, before and 2 and 4 hours after DDAVP (0.3 µg/kg). We found (1) no significant changes for P-selectin expression, PAC-1 binding, δ-granule content and secretion, and platelet-aggregation; (2) significant decreases of secretion of α-granules and GPIIb-IIIa activation induced by adenosine 5'-diphosphate, convulxin, and thrombin; (3) significant increases of procoagulant platelets induced by convulxin/thrombin and platelet-dependent thrombin generation; and (4) significant increases of intracellular Na(+)/Ca(2+) concentrations. We show that in vivo DDAVP selectively and markedly enhances the ability to form procoagulant platelets and increases platelet-dependent thrombin generation by enhancing Na(+)/Ca(2+) mobilization. This report indicates that the beneficial hemostatic effect of DDAVP is not limited to an increase in large VWF multimers. An enhancement of platelet procoagulant activity appears to be an additional and (at least in platelet disorders) -possibly clinically relevant mechanism of DDAVP's action.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  2. 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.

  3. Assessment of neonatal platelet adhesion, activation, and aggregation

    PubMed Central

    Baker-Groberg, Sandra M.; Lattimore, Susan; Recht, Michael; McCarty, Owen J.T.; Haley, Kristina M.

    2016-01-01

    SUMMARY Background Acquired and inherited bleeding disorders may present in the neonatal period with devastating lifelong effects. Diagnosing bleeding disorders in the neonatal population could aid in preventing and treating the associated complications. However, currently available platelet function testing is limited in neonates owing to difficulties obtaining adequate blood volume, lack of normal reference ranges, and an incomplete understanding of the neonatal platelet functional phenotype. Objective Develop small-volume, whole blood platelet function assays to quantify and compare neonatal and adult platelet function. Methods and Results Peripheral blood was obtained from healthy, full-term neonates at 24-hours of life. Platelet activation, secretion, and aggregation were measured via flow cytometry. Platelet adhesion and aggregation were assessed under static and flow conditions. As compared to adult platelets, peripheral neonatal platelet P-selectin expression and integrin glycoprotein (GP) IIbIIIa activation was significantly reduced in response to the G protein-coupled receptor (GPCR)-agonists thrombin receptor activator peptide-6 (TRAP-6), adenosine 5′-diphosphate (ADP), and U46619 and the immunoreceptor tyrosine-based activation motif (ITAM)-signaling pathway agonists collagen-related peptide (CRP) and rhodocytin. Neonatal platelet aggregation was markedly reduced in response to TRAP-6, ADP, U46619, CRP, and rhodocytin compared to adult platelets. The extent of neonatal and adult platelet adhesion and aggregate formation under static and shear conditions on collagen and von Willebrand factor (VWF) were similar. Conclusions As compared to adult platelets, we found neonatal platelet activation and secretion were blunted in response to GPCR- or ITAM-agonists, while the extent of neonatal platelet adhesion and aggregate formation was similar to adult platelets. PMID:26806373

  4. Wernher von Braun

    NASA Image and Video Library

    1967-06-06

    Throughout his career, Dr. von Braun received numerous awards for his contributions to space flight. On June 6, 1967, Dr. Fred L. Whipple, Director of the Smithsonian Astrophysical Observatory, presented Dr. von Braun with the Smithsonian Langley Medal.

  5. 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

  6. Wernher von Braun

    NASA Image and Video Library

    1945-04-01

    Dr. Wernher von Braun surrenders to U.S. Army Counterintelligence persornel of the 44th Infantry Division in Ruette, Bavaria on May 2, 1945. Left to right are Charles Stewart, CIC agent; Dr. Herbert Axster; Dieter Huzel; Dr. von Braun (arm in cast); Magnus von Braun (brother); and Hans Lindenberg.

  7. 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.

  8. 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

  9. Enhanced viscoelastic property of iron oxide nanoparticle decorated organoclay fluid under magnetic field

    NASA Astrophysics Data System (ADS)

    Son, You-Hwan; Jung, Youngsoo; Roh, Heesuk; Lee, Jung-Kun

    2017-08-01

    Stable hydrophobic nanocomposites of magnetic nanoparticles and clay are prepared by the self-assembly of magnetite (Fe3O4) nanoparticles on surfaces of exfoliated clay platelets. Due to the attractive interaction between hydrophobic groups, oleic acid coated nanoparticles are strongly attached to the surface of cetyl trimethylammonium cation coated clay platelets in organic media. Crystal structure and magnetic property of composite particles are examined using electron microscopy, x-ray diffractometer and vibration sample magnetometer. In addition, composite particles are dispersed in mineral oil and rheological properties of composite particle suspensions are characterized using steady-state and oscillatory measurements. Magnetite nanoparticle decorated organoclay forms a tunable network in mineral oil. When a magnetic field is applied, the composite particle fluid exhibits higher storage modulus and maintains a solid-like property at larger strain. Our results show that the viscoelastic property of the magnetite nanoparticle decorated organoclay fluid is controlled by applying external magnetic field.

  10. 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.

  11. 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 ...

  12. 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

  13. Platelet-like nanoparticles: mimicking shape, flexibility, and surface biology of platelets to target vascular injuries.

    PubMed

    Anselmo, Aaron C; Modery-Pawlowski, Christa Lynn; Menegatti, Stefano; Kumar, Sunny; Vogus, Douglas R; Tian, Lewis L; Chen, Ming; Squires, Todd M; Sen Gupta, Anirban; Mitragotri, Samir

    2014-11-25

    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.

  14. 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.

  15. Blood platelet kinetics and platelet transfusion

    PubMed Central

    Aster, Richard H.

    2013-01-01

    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. PMID:24177466

  16. Christmas decorations in the SM

    NASA Image and Video Library

    2012-12-23

    ISS034-E-009706 (23 Dec. 2012) --- Ornaments adorn the Russian segment of the International Space Station in preparation for Christmas. This scene is in the Zvezda module, but not too far away, on the NASA side of the outpost, stockings and other decorations were soon being prepared for the holiday.

  17. 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

  18. 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.

  19. Proteasome proteolysis supports stimulated platelet function and thrombosis.

    PubMed

    Gupta, Nilaksh; Li, Wei; Willard, Belinda; Silverstein, Roy L; McIntyre, Thomas M

    2014-01-01

    Proteasome inhibitors used in the treatment of hematologic cancers also reduce thrombosis. Whether the proteasome participates in platelet activation or function is unclear because little is known of the proteasome in these terminally differentiated cells. Platelets displayed all 3 primary proteasome protease activities, which MG132 and bortezomib (Velcade) inhibited. Proteasome substrates are marked by ubiquitin, and platelets contained a functional ubiquitination system that modified the proteome by monoubiquitination and polyubiquitination. Systemic MG132 strongly suppressed the formation of occlusive, platelet-rich thrombi in FeCl3-damaged carotid arteries. Transfusion of platelets treated ex vivo with MG132 and washed before transfusion into thrombocytopenic mice also reduced carotid artery thrombosis. Proteasome inhibition reduced platelet aggregation by low thrombin concentrations and ristocetin-stimulated agglutination through the glycoprotein Ib-IX-V complex. This receptor was not appropriately internalized after proteasome inhibition in stimulated platelets, and spreading and clot retraction after MG132 exposure also were decreased. The effects of proteasome inhibitors were not confined to a single receptor as MG132 suppressed thrombin-stimulated, ADP-stimulated, and lipopolysaccharide-stimulated microparticle shedding. Proteasome inhibition increased ubiquitin decoration of cytoplasmic proteins, including the cytoskeletal proteins Filamin A and Talin-1. Mass spectrometry revealed a single MG132-sensitive tryptic cleavage after R1745 in an extended Filamin A loop, which would separate its actin-binding domain from its carboxy terminal glycoprotein Ibα-binding domain. Platelets contain a ubiquitin/proteasome system that marks cytoskeletal proteins for proteolytic modification to promote productive platelet-platelet and platelet-wall interactions.

  20. Wernher von Braun

    NASA Image and Video Library

    1970-02-24

    In 1970 Marshall Space Flight Center (MSFC) Director Dr. Wernher von Braun (right) was reassigned to NASA Headquarters to serve as Deputy Associate Administrator for Plarning. Prior to his transfer, Dr. von Braun was honored for his career in Huntsville, Alabama, with the celebration of "Wernher von Braun Day." Among those participating were Alabama Governor Albert Brewer (left) and Alabama Senator John Sparkman (center). (Courtesy of Huntsville/Madison County Public library)

  1. Wernher von Braun

    NASA Image and Video Library

    1954-01-01

    Marshall Center Director Dr. Wernher Von Braun is pictured with Walt Disney during a visit to the Marshall Space Flight Center in 1954. In the 1950s, Dr. Von Braun while working in California on the Saturn project, also worked with Disney studios as a technical director in making three films about Space Exploration for television. Disney's tour of Marshall in 1965 was Von Braun's hope for a renewed public interest in the future of the Space Program at NASA.

  2. 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.

  3. Wernher von Braun

    NASA Image and Video Library

    1970-02-24

    In February 1970, MSFC Director Dr. von Braun was named NASA Deputy Associate Administrator for Plarning and transferred to the Agency's Headquarters in Washington D.C. Prior to his departure, Huntsvillians, along with state local dignitaries, honored his years of service to the Army and NASA with a series of events. One included unveiling a plaque in von Braun's honor. Pictured with Dr. von Braun are (left to right), his daughter Iris, wife Maria, U.S. Senator John Sparkman and Alabama Governor Albert Brewer, Dr. von Braun, son Peter, and daughter Margrit.

  4. Rheologie von Beschichtungen

    NASA Astrophysics Data System (ADS)

    Schäffler, Michael

    Die Rheologie beschreibt die Fließ- und Deformationseigenschaften von Materialien. Der Begriff Rheologie ist aus dem Griechischen abgeleitet: rhein - fließen. Erst im Jahre 1930 entwickelte E.C. Bingham und M. Reiner in Easton (USA) die Rheologie zu einer eigenständigen Wissenschaft. Aber bereits seit dem 17. Jahrhundert wurden wesentliche Einzelbeiträge zu Fließphänomenen veröffentlich, so z.B. 1676 von R. Hooke (Hookesches Gesetz) und 1687 von I. Newton (Newtonsches Gesetz). Die Rheologie hat sich bis heute immer mehr zu einer interdisziplinären Wissenschaft entwickelt, die die mechanischen Eigenschaften von Materialien charakterisiert.

  5. Wernher von Braun

    NASA Image and Video Library

    1959-01-01

    This photograph of Dr. von Braun, shown here to the left of General Bruce Medaris, was taken in the fall of 1959, immediately prior to Medaris' retirement from the Army. At the time, von Braun and his associates worked for the Army Ballistics Missile Agency in Huntsville, Alabama. Those in the photograph have been identified as Ernst Stuhlinger, Frederick von Saurma, Fritz Mueller, Hermarn Weidner, E.W. Neubert (partially hidden), W.A. Mrazek, Karl Heimburg, Arthur Rudolph, Otto Hoberg, von Braun, Oswald Lange, Medaris, Helmut Hoelzer, Hans Maus, E.D. Geissler, Hans Heuter, and George Constan.

  6. Wernher von Braun

    NASA Image and Video Library

    1960-01-01

    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 Plarning. 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.

  7. 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.

  8. 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 ...

  9. 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)

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

    PubMed Central

    Jurak Begonja, Antonija; Hoffmeister, Karin M.; Hartwig, John H.

    2011-01-01

    Filamin A (FlnA) is a large cytoplasmic protein that crosslinks actin filaments and anchors membrane receptors and signaling intermediates. FlnAloxP 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 FlnAloxP PF4-Cre mice and reveals the desintegration of FlnA-null platelets into microvesicles, a process that occurs spontaneously during storage. FlnAloxP 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. PMID:21652675

  11. 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.

  12. Human Platelet Senescence.

    DTIC Science & Technology

    1976-04-30

    electrophoresis platelet subpopulations membranes enrichment of platelet collections with miigathrombocytes 20. A DST RAC T (Cpntinue on reverse&. "~gaU...label which enters megakaryocytes but not peripheral blood platelets. Platelets re- leased from the bone marrow however, do contain the isotope . With...their own platelet-rich plasma (anticoagulated with ACD-A) at 800 RP’M) 1200 RPM, 1600 RPM, 1800 RPM and 2000 RPM in a Sorvall RC3 Centrifugue . The

  13. [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.

  14. 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.

  15. 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

  16. 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.

  17. Wernher von Braun

    NASA Image and Video Library

    1959-01-01

    Five of the seven original astronauts are seen with Dr. von Braun inspecting the Mercury-Redstone hardware in the Fabrication Laboratory of Army Ballistic Missile Agency (ABMA) in 1959. Left to right: Astronauts Walter Schirra, Alan Shepard, John Glenn, Scott Carpenter, Gordon Cooper, and Dr. von Braun.

  18. Wernher von Braun

    NASA Image and Video Library

    1963-03-01

    This is a portrait of Maria von Braun, wife of the famous Marshall Space Flight Center (MSFC) director Wernher von Braun. Her husband, Wernher, who led America to the Moon, served as MSFC’s first director from July 1, 1960 until January 27, 1970.

  19. Wernher von Braun

    NASA Image and Video Library

    1967-11-14

    Astronaut L. Gordon Cooper checks the neck ring of a space suit worn by Marshall Space Flight Center (MSFC) Director, Dr. von Braun before he submerges into the water of the MSFC Neutral Buoyancy Simulator (NBS). Wearing a pressurized suit and weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

  20. Wernher von Braun

    NASA Image and Video Library

    1967-11-14

    Marshall Space Flight Center (MSFC) Director, Dr. von Braun, submerges after spending some time under water 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.

  1. Wernher von Braun

    NASA Image and Video Library

    1967-11-14

    Marshall Space Flight Center (MSFC) Director, Dr. von Braun, is shown leaving the suiting-up van wearing a pressure suit prepared 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.

  2. Wernher von Braun

    NASA Image and Video Library

    1967-11-14

    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.

  3. Wernher von Braun

    NASA Image and Video Library

    1968-01-22

    Dr. Wernher Von Braun, stands in front of a Saturn IB Launch Vehicle at Kennedy Space Center (KSC). Dr. Von Braun was Marshall's first Center Director (1960-1970). Under his leadership Marshall was responsible for the development of the Saturn rockets, the Skylab project and getting the United States into Space and landing on the moon with the Apollo missions.

  4. Wernher von Braun

    NASA Image and Video Library

    1970-02-24

    Dr. von Braun was noted for his public speeches and presentations. In this photograph, Dr. von Braun gave a speech during a series of events to honor him prior to his relocation to Washington where he was assigned to his new duty as NASA's Deputy Associate Administrator for Plarning at NASA Headquarters.

  5. 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.

  6. 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).

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

    PubMed Central

    Castaman, Giancarlo; Goodeve, Anne; Eikenboom, Jeroen

    2013-01-01

    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). PMID:23633542

  8. Wernher von Braun

    NASA Image and Video Library

    2004-04-15

    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.

  9. 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.

  10. 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.

  11. Wernher von Braun

    NASA Image and Video Library

    1977-06-16

    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.

  12. 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.

  13. Src family kinases: at the forefront of platelet activation

    PubMed Central

    Mazharian, Alexandra; Mori, Jun

    2014-01-01

    Src family kinases (SFKs) play a central role in mediating the rapid response of platelets to vascular injury. They transmit activation signals from a diverse repertoire of platelet surface receptors, including the integrin αIIbβ3, the immunoreceptor tyrosine–based activation motif–containing collagen receptor complex GPVI-FcR γ-chain, and the von Willebrand factor receptor complex GPIb-IX-V, which are essential for thrombus growth and stability. Ligand-mediated clustering of these receptors triggers an increase in SFK activity and downstream tyrosine phosphorylation of enzymes, adaptors, and cytoskeletal proteins that collectively propagate the signal and coordinate platelet activation. A growing body of evidence has established that SFKs also contribute to Gq- and Gi-coupled receptor signaling that synergizes with primary activation signals to maximally activate platelets and render them prothrombotic. Interestingly, SFKs concomitantly activate inhibitory pathways that limit platelet activation and thrombus size. In this review, we discuss past discoveries that laid the foundation for this fundamental area of platelet signal transduction, recent progress in our understanding of the distinct and overlapping functions of SFKs in platelets, and new avenues of research into mechanisms of SFK regulation. We also highlight the thrombotic and hemostatic consequences of targeting platelet SFKs. PMID:25115887

  14. 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.

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

    PubMed Central

    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.

    2012-01-01

    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 Adam17ΔZn/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. PMID:22101895

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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…

  2. 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…

  3. 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…

  4. Wernher von Braun

    NASA Image and Video Library

    1959-03-03

    Dr. von Braun, Director of the Development Operations Divisons, and Dr. Debus, Director of the Missile Firing Laboratory; Army Ballistic Missile Agency (ABMA), in the blockhouse during the launch of the Pioneer IV, March 3, 1959.

  5. Wernher von Braun

    NASA Image and Video Library

    1960-11-03

    Marshall Space Flight Center’s (MSFC) Director, Dr. Wernher von Braun, is pictured here with Army Ballistic Missile Agency’s (ABMA) Commanding General, J.B. Medaris, before a display of Army missles at the ABMA test lab.

  6. Wernher von Braun

    NASA Image and Video Library

    1970-06-27

    Marshall Space Flight Center (MSFC) Director Dr. Eberhard Rees conversing with former Center Director, Dr. Wernher von Braun, who along with his wife and son, participated in MFSC's Tenth Anniversary Celebration Picnic held at the Center's picnic area.

  7. Wernher von Braun

    NASA Image and Video Library

    1959-01-01

    Marshall Space Flight Center Director Wernher von Braun presents General J.B. Medaris with a new golf bag. General Medaris, (left) was a Commander of the Army Ballistic Missile Agency (ABMA) in Redstone Arsenal, Alabama during 1955 to 1958.

  8. Wernher von Braun

    NASA Image and Video Library

    1962-09-11

    Marshall Space Flight Center Director Dr. Wernher von Braun explains a detail from a Saturn IB mockup and engine to President John F. Kennedy, Vice President Lyndon Johnson and other guests, September 11, 1962.

  9. Wernher von Braun

    NASA Image and Video Library

    1960-09-08

    President Dwight D. Eisenhower and MSFC Director Dr. Wernher von Braun share a joke as other dignitaries look on. Eisenhower was visiting Marshall to participate in the September 8, 1960 dedication ceremony.

  10. Wernher von Braun

    NASA Image and Video Library

    1962-09-11

    President John F. Kennedy, Vice President Lyndon B. Johnson and Marshall Space Flight Center Director Dr. Wernher von Braun at the Redstone Arsenal Airfield, September 11, 1962. Kennedy and Johnson visited the Marshall Center to tour national space facilities.

  11. Wernher von Braun

    NASA Image and Video Library

    1967-08-28

    Marshall Space Flight Center’s (MSFC) director, Dr. Wernher von Braun (right), inspects a component of a laser experiment being conducted in MSFC’s Space Sciences Laboratory during a tour on August 28, 1967.

  12. Wernher von Braun

    NASA Image and Video Library

    1969-06-04

    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.

  13. Wernher von Braun

    NASA Image and Video Library

    1962-01-01

    Dr. Wernher von Braun, Director of the Marshall Space Flight Center (MSFC), during his tour of the Space information Division of North American Aviation (NAA) in Downey, California, where the Saturn SII stage was developed.

  14. Wernher von Braun

    NASA Image and Video Library

    1967-10-17

    Dr. von Braun, Director of the Marshall Space Flight Center, listens attentively to a briefing on the metal forming techniques by Dr. Mathias Siebel of the Manufacturing and Engineering Laboratory at MSFC on October 17, 1967.

  15. Wernher von Braun

    NASA Image and Video Library

    1965-11-05

    In this photograph, Marshall Space Flight Center Director, Dr. Wernher von Braun, presents a Co-Inventor’s award to MSFC employee Martin Hall of the Mechanical Engineering Laboratory during the NASA Anniversary ceremony.

  16. Wernher von Braun

    NASA Image and Video Library

    1961-10-01

    Dr. Wernher von Braun, Director of Marshall Space Flight Center (MSFC), teams up with Senator Robert S. Kerr, a chairman of the Senate Committee on Aeronautical and Space Sciences to break ground for MSFC's new Central Laboratory and Office Facility.

  17. Wernher von Braun

    NASA Image and Video Library

    1964-10-14

    This photograph, dated October 14, 1964, was taken at the Marned Spacecraft Center, now the Johnson Space Center in Houston, Texas. Dr. von Braun is shown looking over consoles in the Manned Spaceflight Control Center.

  18. Wernher von Braun

    NASA Image and Video Library

    1964-10-14

    This is a photograph that was made on October 14, 1964 of Dr. von Braun while he toured the Marned Spacecraft Center, now the Johnson Space Center in Houston, Texas. He is shown inspecting a Gemini-Agena Docking Simulator.

  19. 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.

  20. Ristocetin-Induced Platelet Aggregation (RIPA) and RIPA Mixing Studies.

    PubMed

    Frontroth, Juan Pablo; Favaloro, Emmanuel J

    2017-01-01

    Ristocetin-induced platelet aggregation (RIPA) is used as an in vitro test to determine the presence and integrity of the platelet glycoprotein (GP) Ibα-V-IX complex and von Willebrand factor (VWF) interaction and is usually performed using platelet-rich plasma (PRP). Impairment in the response of VWF/GPIbα-V-IX is measured with reference to several established concentrations of ristocetin and may indicate defects in VWF or in GPIbα-V-IX function. RIPA-based mixing studies comprise an additional approach to testing this interaction to help define whether defects identified by RIPA lie in VWF or in GPIbα-V-IX. For example, the correction of an abnormal RIPA trace after mixing PRP with normal plasma and rechallenging with ristocetin at 1.0 mg/mL suggests VWF function/quantity defect. RIPA mixing studies at lower doses of ristocetin (0.5 mg/mL) are recommended for discrimination of von Willebrand disease type 2B (VWD2B) from the rarer platelet-type (PT) VWD and for the phenotypic laboratory diagnosis of VWD2B. The demonstration of a plasma factor capable of inducing platelet aggregation at such low doses of ristocetin represents the hallmark for the phenotypic laboratory diagnosis of VWD2B. Moreover, since both VWD2B and PT-VWD may present with thrombocytopenia, RIPA-based mixing studies are also useful in thrombocytopenic patients in whom RIPA testing is difficult to assess.

  1. Wernher von Braun

    NASA Image and Video Library

    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.

  2. Wernher von Braun

    NASA Image and Video Library

    1970-02-24

    Dr. von Braun was honored with a series of farewell events and ceremonies prior to his reassignment to NASA Headquarters in Washington, D.C. Alabama Governor Brewer greets Dr. von Braun following his speech at the front of the Madison County Courthouse in Huntsville, Alabama on February 24, 1970. Behind are Madison County Commissioner James Record, Huntsville Mayor Joe Davis, and U.S. Senator Sparkman.

  3. 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.

  4. 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.

  5. Wernher von Braun

    NASA Image and Video Library

    1964-03-24

    Marshall Space Flight Center Director Dr. Wernher von Braun presents Lady Bird Johnson with an inscribed hard hat during the First Lady's March 24, 1964 visit. While at the Marshall Center, Mrs. Johnson addressed Center employees, toured facilities and witnessed test firings of a Saturn I first stage and an F-1 engine. Dr. von Braun is wearing a Texas hat presented to him months earlier by Lyndon Johnson during a visit to the Johnson ranch in Texas.

  6. Wernher von Braun

    NASA Image and Video Library

    1930-01-01

    Dr. von Braun was among a famous group of rocket experimenters in Germany in the 1930s. This photograph is believed to be made on the occasion of Herman Oberth's Kegelduese liquid rocket engine being certified as to performance during firing. From left to right are R. Nebel, Dr. Ritter, Mr. Baermueller, Kurt Heinish, Herman Oberth, Klaus Riedel, Wernher von Braun, and an unidentified person.

  7. 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.

  8. 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

  9. Fibrin formation by staphylothrombin facilitates Staphylococcus aureus-induced platelet aggregation.

    PubMed

    Vanassche, Thomas; Kauskot, Alexandre; Verhaegen, Jan; Peetermans, Willy E; van Ryn, Joanne; Schneewind, Olaf; Hoylaerts, Marc F; Verhamme, Peter

    2012-06-01

    Interactions of Staphylococcus aureus (S. aureus) and platelets play an important role in the pathogenesis of intravascular infections such as infective endocarditis (IE). A typical feature of S. aureus is the ability to generate thrombin activity through the secretion of two prothrombin activating molecules, staphylocoagulase and von Willebrand factor-binding protein (vWbp), which bind to human prothrombin to form the enzymatically active staphylothrombin complex. The role of staphylothrombin in the interaction between S. aureus and platelets has not yet been studied. We found that in contrast with thrombin, staphylothrombin did not directly activate human platelets. However, the staphylothrombin-mediated conversion of fibrinogen to fibrin initiated platelet aggregation and secondary activation and facilitated S. aureus-platelet interactions. Both the genetic absence of staphylocoagulase and vWbp and pharmacological inhibition of staphylothrombin increased the lag time to aggregation, and reduced platelet trapping by S. aureus in high shear stress conditions. The combined inhibition of staphylothrombin and immunoglobulin binding to platelets completely abolished the ability of S. aureus to aggregate platelets in vitro. In conclusion, although staphylothrombin did not directly activate platelets, the formation of a fibrin scaffold facilitated bacteria-platelet interaction, and the inhibition of staphylothrombin resulted in a reduced activation of platelets by S. aureus.

  10. Red Blood Cell Hematocrit Influences Platelet Adhesion Rate in a Microchannel

    NASA Astrophysics Data System (ADS)

    Spann, Andrew; Campbell, James; Fitzgibbon, Sean; Rodriguez, Armando; Shaqfeh, Eric

    2014-11-01

    The creation of a blood clot to stop bleeding involves platelets forming a plug at the site of injury. Red blood cells indirectly play a role in ensuring that the distribution of platelets across the height of the channel is not uniform - the contrast in deformability and size between platelets and red blood cells allows the platelets to preferentially marginate close to the walls. We perform 3D boundary integral simulations of a suspension of platelets and red blood cells in a periodic channel with a model that allows for platelet binding at the walls. The relative rate of platelet activity with varying hematocrit (volume fraction of red blood cells) is compared to experiments in which red blood cells and platelets flow through a channel coated with von Willebrand factor. In the simulations as well as the experiments, a decrease in hematocrit of red blood cells is found to reduce the rate at which platelets adhere to the channel wall in a manner that is both qualitatively and quantitatively similar. We conclude with a discussion of the tumbling and wobbling motions of platelets in 3D leading up to the time at which the platelets bind to the wall. Funded by Stanford Army High Performance Computing Research Center, experiments by US Army Institute of Surgical Research.

  11. 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.

  12. [Effect of API 0134 on platelet membrane glycoprotein expression in patients with hyperlipemia].

    PubMed

    Wang, Hong-wei; Li, Shu-sheng; Wang, Guo-ping

    2004-05-01

    By observing the effect of API 0134, an active ingredient of green chiretta, on platelet membrane glycoprotein (GP) in patients with hyperlipemia to explore the mechanism of the anti-platelet aggregation effect of API. The mean immunofluorescent intensity (MFI) of the platelet membrane glycoprotein GP II b/III a, GPIb, P-selectin (GMP-140) and von Willebrand's factor (vWF) in resting platelet, activated platelet (untreated or treated with API 0134 of different concentrations) were detected in 30 randomly selected patients with hyperlipemia, using immunofluorescent marker and flow cytometry. API of all concentrations (25 mg/L, 50 mg/L and 100 mg/L) could significantly decrease the MFI of GP II b/III a in a positive dose-dependent manner, as compared with that in activated platelet untreated with API; API of 50 mg/L and 100 mg/L could also reduce the MFI of GMP-140 and vWF in activated platelet (P < 0.01); but API of 100 mg/L showed insignificant influence on GPIb expression in activated platelet membrane. API 0134 exerts obvious anti-platelet GP II b/III a effect on activated platelets, middle or large dose of API also shows inhibiting effect on GMP-140 and vWF expression in platelet.

  13. 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.

  14. Thioredoxin Inhibitors Attenuate Platelet Function and Thrombus Formation.

    PubMed

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

    2016-01-01

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

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Sources of Variability in Platelet Accumulation on Type 1 Fibrillar Collagen in Microfluidic Flow Assays

    PubMed Central

    Neeves, Keith B.; Onasoga, Abimbola A.; Hansen, Ryan R.; Lilly, Jessica J.; Venckunaite, Diana; Sumner, Meghan B.; Irish, Andrew T.; Brodsky, Gary; Manco-Johnson, Marilyn J.; Di Paola, Jorge A.

    2013-01-01

    Microfluidic flow assays (MFA) that measure shear dependent platelet function have potential clinical applications in the diagnosis and treatment of bleeding and thrombotic disorders. As a step towards clinical application, the objective of this study was to measure how phenotypic and genetic factors, as well as experimental conditions, affect the variability of platelet accumulation on type 1 collagen within a MFA. Whole blood was perfused over type 1 fibrillar collagen at wall shear rates of 150, 300, 750 and 1500 s−1 through four independent channels with a height of 50 µm and a width of 500 µm. The accumulation of platelets was characterized by the lag time to 1% platelet surface coverage (LagT), the rate of platelet accumulation (VPLT), and platelet surface coverage (SC). A cohort of normal donors was tested and the results were correlated to plasma von Willebrand factor (VWF) levels, platelet count, hematocrit, sex, and collagen receptors genotypes. VWF levels were the strongest determinant of platelet accumulation. VWF levels were positively correlated to VPLT and SC at all wall shear rates. A longer LagT for platelet accumulation at arterial shear rates compared to venous shear rates was attributed to the time required for plasma proteins to adsorb to collagen. There was no association between platelet accumulation and hematocrit or platelet count. Individuals with the AG genotype of the GP6 gene had lower platelet accumulation than individuals with the AA genotype at 150 s−1 and 300 s−1. Recalcified blood collected into sodium citrate and corn trypsin inhibitor (CTI) resulted in diminished platelet accumulation compared to CTI alone, suggesting that citrate irreversibly diminishes platelet function. This study the largest association study of MFA in healthy donors (n = 104) and will likely set up the basis for the determination of the normal range of platelet responses in this type of assay. PMID:23355889

  20. Sources of variability in platelet accumulation on type 1 fibrillar collagen in microfluidic flow assays.

    PubMed

    Neeves, Keith B; Onasoga, Abimbola A; Hansen, Ryan R; Lilly, Jessica J; Venckunaite, Diana; Sumner, Meghan B; Irish, Andrew T; Brodsky, Gary; Manco-Johnson, Marilyn J; Di Paola, Jorge A

    2013-01-01

    Microfluidic flow assays (MFA) that measure shear dependent platelet function have potential clinical applications in the diagnosis and treatment of bleeding and thrombotic disorders. As a step towards clinical application, the objective of this study was to measure how phenotypic and genetic factors, as well as experimental conditions, affect the variability of platelet accumulation on type 1 collagen within a MFA. Whole blood was perfused over type 1 fibrillar collagen at wall shear rates of 150, 300, 750 and 1500 s⁻¹ through four independent channels with a height of 50 µm and a width of 500 µm. The accumulation of platelets was characterized by the lag time to 1% platelet surface coverage (Lag(T)), the rate of platelet accumulation (V(PLT)), and platelet surface coverage (SC). A cohort of normal donors was tested and the results were correlated to plasma von Willebrand factor (VWF) levels, platelet count, hematocrit, sex, and collagen receptors genotypes. VWF levels were the strongest determinant of platelet accumulation. VWF levels were positively correlated to V(PLT) and SC at all wall shear rates. A longer Lag(T) for platelet accumulation at arterial shear rates compared to venous shear rates was attributed to the time required for plasma proteins to adsorb to collagen. There was no association between platelet accumulation and hematocrit or platelet count. Individuals with the AG genotype of the GP6 gene had lower platelet accumulation than individuals with the AA genotype at 150 s⁻¹ and 300 s⁻¹. Recalcified blood collected into sodium citrate and corn trypsin inhibitor (CTI) resulted in diminished platelet accumulation compared to CTI alone, suggesting that citrate irreversibly diminishes platelet function. This study the largest association study of MFA in healthy donors (n = 104) and will likely set up the basis for the determination of the normal range of platelet responses in this type of assay.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. Wernher von Braun

    NASA Image and Video Library

    1958-01-31

    Jet Propulsion Laboratory Director Dr. James Pickering, Dr. James van Allen of the State University of Iowa, and Army Ballistic missionile Agency Technical Director Dr. Wernher von Braun triumphantly display a model of the Explorer I, America's first satellite, shortly after the satellite's launch on January 31, 1958. The Jet Propulsion Laboratory packed and tested the payload, a radiation detection experiment designed by Dr. van Allen. Dr. von Braun's rocket team at Redstone Arsenal in Huntsville, Alabama, developed the Juno I launch vehicle, a modified Jupiter-C.

  10. Wernher von Braun

    NASA Image and Video Library

    1969-02-28

    Marshall Space Flight Center’s (MSFC) Dr. Ernst Stuhlinger, Director of Research Projects Office; and Dr. Wernher von Braun, center director, along with others, took a swim in the Neutral Buoyancy Simulator (NBS) at MSFC. A safety diver adjusts scuba equipment worn by von Braun, while Stuhlinger adjusts his weight belt prior to entering the tank. In the NBS, subjects were weighted to a neutrally buoyant condition underwater to perform and practice tasks in a simulated weightless condition as would be encountered in space.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. Platelets enhance neutrophil transendothelial migration

    USDA-ARS?s Scientific Manuscript database

    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...

  18. 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.

  19. Wernher von Braun

    NASA Image and Video Library

    1950-01-01

    Dr. von Braun stands beside a model of the upper stage (Earth-returnable stage) of the three-stage launch vehicle built for the series of the motion picture productions of space flight produced by Walt Disney in the mid-1950's.

  20. Wernher von Braun

    NASA Image and Video Library

    1960-01-01

    This is a photograph of Dr. von Braun in front of a Saturn rocket hardware transporter. He appears to be addressing a group. Behind him are workers and other NASA officials. There is no date on the photograph. It may have been taken in the late 1960s.

  1. Wernher von Braun

    NASA Image and Video Library

    1959-03-04

    Dr. Wernher von Braun, Director of the U.S. Army Ballistic Missile Agency's (ABMA) Development Operations Division, talks to Huntsville Mayor R. B. "Speck" Searcy, center, and Army Ordnance Missile Command (ARMC) Major General John B. Medaris, right, during "Moon Day" celebrations in downtown Huntsville, Alabama. (Courtesy of Huntsville/Madison County Public Library)

  2. Wernher von Braun

    NASA Image and Video Library

    1959-01-01

    In this picture, Dr. Wernher von Braun, who was serving as Director of the Army Ballistic Missile Agency's (ABMA) Development Operations Division, is shown posed with his Mercedes 220SE automobile in front of Redstone Building 4488, which houses the ABMA.

  3. 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.

  4. Wernher von Braun

    NASA Image and Video Library

    1961-01-01

    During his tenure as Director of the Marshall Space Flight Center (MSFC), Dr. von Braun enjoyed personally touring the Center's many space-related laboratories and facilities. This photo taken about 1961 shows him examining a test set up in the Center's Manufacturing Engineering Laboratory.

  5. Wernher von Braun

    NASA Image and Video Library

    1962-04-16

    Dr. von Braun (right) and Astronaut John Glenn examine a model of a lunar landing stage during a talk on the manned lunar exploration program by about sixty key officials of the nation's space program at the Marshall Space Flight Center (MSFC).

  6. Wernher von Braun

    NASA Image and Video Library

    1961-01-01

    Dr. von Braun tried out a floating platform in the Marshall Space Flight Center Manufacturing Engineering Laboratory. This was a test rig to help determine how future astronauts will be able to perform maintenance tasks in the weightlessness in space. This photograph is believed to have been taken in 1961.

  7. Wernher von Braun

    NASA Image and Video Library

    1954-07-01

    Dr. Wernher von Braun (center), then Chief of the Guided Missile Development Division at Redstone Arsenal, Alabama, discusses a "bottle suit" model with Dr. Heinz Haber (left), an expert on aviation medicine, and Willey Ley, a science writer on rocketry and space exploration. The three men were at the Disney studios appearing in the motion picture, entitled "Man in Space."

  8. Wernher von Braun

    NASA Image and Video Library

    1971-01-31

    Dr. Wernher von Braun, NASA Deputy Associate Administrator for Future Programs, uses binoculars to monitor data on the closed-circuit TV screen in the Firing Room of the Launch Control Center at Kennedy Space Center (KSC) during the final preparation for the Apollo 14 launch.

  9. Wernher von Braun

    NASA Image and Video Library

    1969-02-28

    Dr. E. Stuhlinger, Dr. W. von Braun, and Dr. J. Piccard, along with others, take a swim in the Neutral Buoyancy Simulator (NBS) at the Marshall Space Flight Center. The NBS was instrumental in providing a zero-gravity environment where astronauts could practice tasks assigned for up coming space flights.

  10. 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.

  11. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Marshall Space Flight Center director Wernher Von Braun and his family were honored with a series of events prior to his relocation to Washington, D.C. where he was assigned duties at NASA headquarters as deputy associate administrator for planning. Here he is shown with General Richard Drury and Hazel Toftoy, widow of General H.N. Toftoy.

  12. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    A camerman catches Dr. Wernher Von Braun, Director of the Marshall Space Flight Center, his son, Peter, and daughter, Martgrit, as they arrive at the employee picnic held to celebrate man's first landing on the moon 6 days earlier. In the foreground is David R. Newby, Director of Administration and Technical Services at the Marshall Space Flight Center.

  13. Wernher von Braun

    NASA Image and Video Library

    1961-03-01

    Dr. von Braun, Director of the Marshall Space Flight Center, spoke of the progress in the Saturn Program during his appearance before the Senate Committee on Aeronautical and Space Sciences. He was accompanied by Dr. Robert C. Seamans, Jr., Associate Administrator of the National Aeronautics and Space Administration (NASA).

  14. Wernher von Braun

    NASA Image and Video Library

    1965-04-13

    Walt Disney toured the West Test Area during his visit to the Marshall Space Flight Center on April 13, 1965. The three in center foreground are Karl Heimburg, Director, Test Division; Dr. von Braun, Director, MSFC; and Walt Disney. The Dynamic Test Stand with the S-1C stage being installed is in the background.

  15. 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

  16. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Marshall Space Flight Center director Wernher Von Braun and his family were honored with a series of events prior to his relocation to Washington, D.C. where he was assigned duties at NASA headquarters as deputy associate administrator for planning. Here he is shown with General Richard Drury and Hazel Toftoy, widow of General H.N. Toftoy.

  17. 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

  18. 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.

  19. Platelets support extracellular sialylation by supplying the sugar donor substrate.

    PubMed

    Lee, Melissa M; Nasirikenari, Mehrab; Manhardt, Charles T; Ashline, David J; Hanneman, Andrew J; Reinhold, Vernon N; Lau, Joseph T Y

    2014-03-28

    Sizable pools of freely circulating glycosyltransferases are in blood, but understanding their physiologic contributions has been hampered because functional sources of sugar donor substrates needed to drive extracellular glycosylation have not been identified. The blood-borne ST6Gal-1 produced and secreted by the liver is the most noted among the circulatory glycosyltransferases, and decorates marrow hematopoietic progenitor cells with α2,6-linked sialic acids and restricts blood cell production. Platelets, upon activation, secrete a plethora of bioactive molecules including pro- and anti-inflammatory mediators. Cargos of sugar donor substrates for glycosyltransferase activity have also been reported in platelets. Here, we implemented a cell-based system to interrogate platelets for their ability to deliver effectively the sugar donor substrate for extracellular ST6Gal-1 to function. We report that thrombin-activated platelets, at physiologic concentration and pH, can efficiently and effectively substitute for CMP-sialic acid in extracellular ST6Gal-1-mediated sialylation of target cell surfaces. Activated platelets can also supply the sialic acid donor to sialylate the synthetic acceptor, Gal(β1,4)GlcNAcα-o-benzyl, with the product Sia(α2,6)Gal(β1,4)GlcNAcα-o-benzyl structurally confirmed by LC/MS. Platelet-secreted donor substrate was recovered in the 100,000 × g sediment, strongly suggesting the association of this otherwise soluble substrate, putatively CMP-sialic acid, within platelet microparticles. Sequestration within microparticles may facilitate delivery of glycosylation substrate at effective dosages to sites of extracellular glycosylation while minimizing excessive dilution.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. Effects of in-vitro adult platelet transfusions on neonatal hemostasis

    PubMed Central

    Ferrer-Marin, Francisca; Chavda, Chaitanya; Lampa, Michael; Michelson, Alan D.; Frelinger, Andrew L.; Sola-Visner, Martha

    2011-01-01

    Background Thrombocytopenia is frequent among neonates, and 20-25% of affected infants are treated with platelet transfusions. These are frequently given for mild thrombocytopenia (platelets 50-100×109/L), largely due to the known hyporeactivity of neonatal platelets. In tests of primary hemostasis, however, neonates have shorter bleeding and closure times (CTs) than adults. This has been attributed to their higher hematocrits, higher von Willebrand factor (VWF) concentrations, and predominance of longer VWF polymers. Objective To determine whether the “transfusion” of adult (relatively hyper-reactive) platelets into neonatal blood results in a hypercoagulable profile. Methods Cord blood (CB) and adult peripheral blood (PB) were separated (using a modified buffy-coat method) to generate miniaturized platelet concentrates (PCs) and thrombocytopenic blood. PB- and CB-derived PCs (n=7 per group) were then “transfused” in-vitro into thrombocytopenic CB and PB. The effects of autologous vs. allogeneic (developmentally mismatched) “transfusions” were evaluated using whole blood aggregometry, platelet function analyzer (PFA-100), and thromboelastography (TEG). Results Adult platelets aggregated significantly better than neonatal platelets in response to TRAP, ADP and collagen, regardless of the blood into which they were transfused. The “transfusion” of adult platelets into thrombocytopenic CB resulted in shorter CTs-Epi (PFA-100) and higher clot strength and firmness (TEG), compared to “transfusion” of neonatal autologous platelets. Conclusions In vitro “transfusion” of adult platelets into neonatal blood results in shorter CTs than “transfusion” with neonatal platelets. Our findings should raise awareness of the differences between the neonatal and adult hemostatic system and the potential “developmental mismatch” associated with platelet transfusions on neonatal hemostasis. PMID:21320282

  7. 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.

  8. Wernher von Braun

    NASA Image and Video Library

    1960-01-01

    Edward O. Buckbee, the first Director of the Alabama Space Science Center (left), and Dr. Wernher von Braun (right) view a demonstration of a simulated spacecraft which uses an actual hybrid rocket engine for liftoff, hover, and landing. The display was presented to the Alabama Space Science Center, later renamed the U.S. Space and Rocket Center, by United Technology Center, a division of United Aircraft.

  9. Wernher von Braun

    NASA Image and Video Library

    1967-10-01

    Dr. von Braun encouraged his laboratory directors and other managers at the Marshall Space Flight Center (MSFC) to adopt a "hands-on" approach to managing the technical challenges they confronted in developing the Saturn rockets for the Marned Lunar Landing Program. He is shown here asking a question about welding in an MSFC manufacturing and engineering laboratory. This photograph was made on or about October 17, 1967.

  10. Wernher von Braun

    NASA Image and Video Library

    1963-03-28

    Dr. von Braun, Director of the Marshall Space Flight Center (MSFC), and Dr. Debus, Director of the Launch Operations Center, at Complex 34 prior to the Launch of the SA-4 (the fourth flight of Saturn I), March 28, 1963. The mission conducted the second "Project Highwater" experiment, which the upper stage ejected 30,000 gallons of ballast water in the upper atmosphere for a physics experiment.

  11. Wernher von Braun

    NASA Image and Video Library

    1966-06-21

    Dr. Joseph Randall, a laser expert at Marshall Space Flight Center (MSFC), explains one of the projects he is working on to a group composed of Federal Republic of Germany and MSFC officials. From left are: Dr. Randall; Minister for Scientific Research of Federal Republic of Germany, Dr. Gerhard Stolenberg; Director of MSFC Astrionics Lab, Dr. Walter Haeusserman; Head of Space Research Federal Republic of Germany, Max Mayer; MSFC Director Dr. von Braun; MSFC Deputy Director Dr. Elberhard Rees.

  12. Wernher von Braun

    NASA Image and Video Library

    1968-10-01

    Dr. von Braun inside the KC-135 in flight. The KC-135 provide NASA's Reduced-Gravity Program the unique weightlessness or zero-g environment of space flight for testing and training of human and hardware reactions. The recent version, KC-135A, is a specially modified turbojet transport which flies parabolic arcs to produce weightlessness periods of 20 to 25 seconds and its cargo bay test area is approximately 60 feet long, 10 feet wide, and 7 feet high.

  13. Wernher von Braun

    NASA Image and Video Library

    1960-01-01

    In this photo, Director of the US Army Ballistic Missile Agency (ABMA) Development Operations Division, Dr. Wernher von Braun, is standing before a display of Army missiles celebrating ABMA's Fourth Open House. The missiles in the background include (left to right) a satellite on a Juno II shroud with a Nike Ajax pointing left in front of a Jupiter missile. The Lacrosse is in front of the Juno II. The Nike Hercules points skyward in front of the Juno II and the Redstone.

  14. 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.

  15. 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.

  16. Taurine and platelet aggregation

    SciTech Connect

    Nauss-Karol, C.; VanderWende, C.; Gaut, Z.N.

    1986-03-01

    Taurine is a putative neurotransmitter or neuromodulator. The endogenous taurine concentration in human platelets, determined by amino acid analysis, is 15 ..mu..M/g. In spite of this high level, taurine is actively accumulated. Uptake is saturable, Na/sup +/ and temperature dependent, and suppressed by metabolic inhibitors, structural analogues, and several classes of centrally active substances. High, medium and low affinity transport processes have been characterized, and the platelet may represent a model system for taurine transport in the CNS. When platelets were incubated with /sup 14/C-taurine for 30 minutes, then resuspended in fresh medium and reincubated for one hour, essentially all of the taurine was retained within the cells. Taurine, at concentrations ranging from 10-1000 ..mu..M, had no effect on platelet aggregation induced by ADP or epinephrine. However, taurine may have a role in platelet aggregation since 35-39% of the taurine taken up by human platelets appears to be secreted during the release reaction induced by low concentrations of either epinephrine or ADP, respectively. This release phenomenon would imply that part of the taurine taken up is stored directly in the dense bodies of the platelet.

  17. Lovastatin induces platelet apoptosis.

    PubMed

    Zhao, Qing; Li, Ming; Chen, Mengxing; Zhou, Ling; Zhao, Lili; Hu, Renping; Yan, Rong; Dai, Kesheng

    2016-03-01

    Statins are widely used in the prevention of atherosclerosis and treatment of coronary artery disease because of pleiotropic effects on thrombosis. Thrombocytopenia and hemorrhage occurred in some statin-treated patients, but the reason remains unclear. In the current study, we show that lovastatin dose-dependently induces depolarization of mitochondrial inner transmembrane potential, leading to up-regulation of Bak, down-regulation of Bcl-XL, and activation of caspase-3/8/9. Lovastatin treatment did not increase the surface expression of P-selectin or PAC-1 binding but led to strongly reduced collagen- and thrombin-induced platelet aggregation. The integrin αIIbβ3 antagonist, RGDS, inhibited lovastatin-induced apoptosis in both human platelets and Chinese hamster ovary (CHO) cells stably expressing integrin αIIbβ3. The number of circulating platelets in mice was significantly reduced after intraperitoneal injections with lovastatin. Taken together, these data indicate that lovastatin induced caspase-dependent platelet apoptosis. Lovastatin does not incur platelet activation, whereas impairs platelet function and reduces circulating platelets in vivo, suggesting the possible pathogenesis of thrombocytopenia and hemorrhage in patients treated with statins. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. 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

  19. 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

  20. Eltrombopag enhances platelet adhesion by upregulating the expression of glycoprotein VI in patients with chronic immune thrombocytopenic purpura.

    PubMed

    Chiou, Tzeon-Jye; Chang, Yi-Fang; Wang, Ming-Chung; Kao, Chen-Wei; Lin, Hsuan-Yu; Chen, Tsai-Yun; Hsueh, Erh-Jung; Lan, Yii-Jenq; Sung, Yung-Chuan; Lin, Sheng-Feng; Bai, Li-Yuan; Chen, Caleb G

    2015-12-01

    Eltrombopag, a thrombopoietin receptor agonist, has been approved for the treatment of patients with immune thrombocytopenia because of its abilities to enhance platelet production and reduce hemorrhage. Both platelet count and platelet adhesion are crucial to stop bleeding. Although eltrombopag is known to improve platelet counts, its effects on platelet adhesion are not yet known. This study aimed to assess the efficacy of eltrombopag on platelet production and platelet adhesive affinity. To evaluate the efficacy of low-dose eltrombopag (25 mg) for patients with chronic refractory immune thrombocytopenic purpura (ITP) and to determine the ex vivo platelet adhesion ability before and after treatment with eltrombopag, we conducted an open-label, multicenter study in which 25 Taiwanese patients with chronic ITP were enrolled. During the 6-month evaluation, the starting and maximum doses of eltrombopag were 25 and 50 mg, respectively, to maintain the platelet count of ≥50,000 per μL. Flow-based adhesion assay was used to detect the percentage of platelets adhering to immobilized von Willebrand factor-collagen on microslides. Of the enrolled patients, 48% achieved a platelet count of ≥50,000 per μL. Interestingly, 83% of all responders required 25 mg of eltrombopag daily to achieve the target platelet count. In addition, the percentage of bleeding patients was significantly reduced in both responders and nonresponders by 50% from the baseline level throughout the treatment period. The ex vivo platelet adhesion capacity was elevated after the 6-month eltrombopag treatment in both responders and nonresponders. Furthermore, glycoprotein VI (GPVI) expression was significantly upregulated after treatment with eltrombopag. Low-to-intermediate dose of eltrombopag showed good efficacy to expedite platelet production and augment platelet adhesion. These 2 factors might explain the efficacy of eltrombopag in ameliorating hemorrhage in patients with ITP. Copyright © 2015

  1. 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

  2. 10 CFR 1050.203 - Acceptance of decorations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Acceptance of decorations. 1050.203 Section 1050.203 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) FOREIGN GIFTS AND DECORATIONS Guidelines for Acceptance..., retain and wear a decoration tendered by a foreign government in recognition of active field service in...

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Effect of splenectomy on platelet activation and decompression sickness outcome in a rat model of decompression.

    PubMed

    Lambrechts, Kate; Pontier, Jean-Michel; Mazur, Aleksandra; Buzzacott, Peter; Goanvec, Christelle; Wang, Qiong; Theron, Michaël; Belhomme, Marc; Guerrero, François

    2014-09-01

    Splenic platelets have been recognized to have a greater prothrombotic potential than others platelets. We studied whether platelets released by splenic contraction could influence the severity and outcome of decompression sickness (DCS) and bubble-induced platelet activation. Sixteen, male Sprague-Dawley rats were randomly assigned to either a control or a splenectomized group. Both groups were compressed to 1,000 kPa (90 metres' sea water) for 45 min while breathing air before staged decompression (5 min at 200 kPa, 5 min at 160 kPa and 10 min at 130 kPa). The onset time of DCS symptoms and of death were recorded during a 60-min observation period post dive. Parameters measured were platelet factor 4 (PF4) for platelet activation, thiobarbituric acid reactive substances (TBARS) for oxidative stress status and Von Willebrand factor (VWf) for endothelial activation. There were no differences between the groups in DCS outcome or in PF4, TBARS and VWf concentrations. These results do not support that the spleen and its exchangeable platelet pool is involved in DCS pathogenesis in a rat model, invalidating the hypothesis that increased decompression-induced platelet aggregation could be influenced by splenic contraction and then play a role in DCS outcome.

  8. 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

  9. 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.

  10. 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.

  11. Wernher von Braun

    NASA Image and Video Library

    1959-03-01

    In this photo, Director of the U.S. Army Ballistic Missile Agency's (ABMA) Development Operations Division, Dr. Wernher von Braun, and Director of Missile Firing Division, Dr. Kurt Debus, are shown with unidentified individuals, discussing two components that would make up the Pioneer IV Lunar Probe. The mercury batteries (left) were used to power the radio transmitter, cosmic radiation counter and other instruments in Pioneer IV. The conical shroud placed over the instruments of Pioneer IV was plated with gold to improve conductivity. The metal surface also served as the anterna for the probe's instruments signaling back to the Earth receiving stations.

  12. 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.

  13. In Dialogue with the Decorative Arts

    ERIC Educational Resources Information Center

    Powell, Olivia

    2017-01-01

    How can museum educators create dialogical experiences with European decorative arts? This question frames my essay and stems from the challenges I have faced introducing objects whose original functions seem to overshadow their aesthetic and interpretive value. Repeated efforts to spark rich dialogue and collective interpretation around pieces of…

  14. 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.

  15. Quantum decoration transformation for spin models

    SciTech Connect

    Braz, F.F.; Rodrigues, F.C.; Souza, S.M. de; Rojas, Onofre

    2016-09-15

    It is quite relevant the extension of decoration transformation for quantum spin models since most of the real materials could be well described by Heisenberg type models. Here we propose an exact quantum decoration transformation and also showing interesting properties such as the persistence of symmetry and the symmetry breaking during this transformation. Although the proposed transformation, in principle, cannot be used to map exactly a quantum spin lattice model into another quantum spin lattice model, since the operators are non-commutative. However, it is possible the mapping in the “classical” limit, establishing an equivalence between both quantum spin lattice models. To study the validity of this approach for quantum spin lattice model, we use the Zassenhaus formula, and we verify how the correction could influence the decoration transformation. But this correction could be useless to improve the quantum decoration transformation because it involves the second-nearest-neighbor and further nearest neighbor couplings, which leads into a cumbersome task to establish the equivalence between both lattice models. This correction also gives us valuable information about its contribution, for most of the Heisenberg type models, this correction could be irrelevant at least up to the third order term of Zassenhaus formula. This transformation is applied to a finite size Heisenberg chain, comparing with the exact numerical results, our result is consistent for weak xy-anisotropy coupling. We also apply to bond-alternating Ising–Heisenberg chain model, obtaining an accurate result in the limit of the quasi-Ising chain.

  16. Spin configurations on a decorated square lattice

    SciTech Connect

    Mert, Gülistan; Mert, H. Şevki

    2016-06-08

    Spin configurations on a decorated square lattice are investigated using Bertaut’s microscopic method. We have obtained collinear and non-collinear (canted) modes for the given wave vectors in the ground state. We have found ferromagnetic and antiferromagnetic commensurate spin configurations. We have found canted incommensurate spin configurations.

  17. 22 CFR 3.7 - Decorations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Decorations. 3.7 Section 3.7 Foreign Relations... Office of Congressional and Public Liaison (for domestic employees), and by the Director of Area Offices... designated depository office of the employing agency a request for review of the case. This request should...

  18. 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)…

  19. 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 ...

  20. 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.

  1. 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.

  2. 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

  3. 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.}

  4. Metal decorated graphdiyne: A first principle study

    NASA Astrophysics Data System (ADS)

    Nayebi, Payman; Zaminpayma, Esmaeil

    2017-09-01

    In this work, we performed first principles calculations based on self-consistent charge density functional tight-binding to investigate mechanical and electronic properties of the optimized graphdiyne sheet, nanoribbons and transition metal decorated with Ag, Fe and Co atoms in the different sites. Then we calculated electronic properties of the graphdiyne sheet under uniaxial elastic strain in two different crystal directions. It is shown that the carbon bond length values for the graphdiyne structure are agreeable with experimental and other theoretical values. Our results show that the charge transferred to the graphdiyne from Ag and Fe atoms but to the Co decorated charge transferred to the Co atom from the graphdiyne. From the results, it can be seen that the graphdiyne is a direct semiconductor with doubly degenerated for both the valence band maximum and the conduction band minimum in the 6C hole site. Also, by Metal decorated of the graphdiyne, the structures become also direct semiconductor for the Ag decorated and indirect for Co and Fe decorated for the 6C- hole, top and bridge sites while the structure have metallic behavior for the 18C- hole site. Our results from the band structure of the GDY nanoribbons with the size of N = 1, 2, 3 and 4, indicate that all of them are nonzero band gaps at the Γ point. It can be seen that the energy gap decreases with increasing of nanoribbons size. Finally, we found that the gap energy increase with applying strain and also the structure remain direct semiconductor.

  5. 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.

  6. Diagnosing von Willebrand disease: a short history of laboratory milestones and innovations, plus current status, challenges, and solutions.

    PubMed

    Favaloro, Emmanuel J

    2014-07-01

    von Willebrand disease (VWD) is a disorder characterized by deficiency of, or defects in, von Willebrand factor (VWF). VWD was originally identified by Erik Adolf von Willebrand, who in early 1924 investigated a large family suffering from a bleeding disorder that seemed to differ from hemophilia. Erik von Willebrand undertook some initial laboratory investigations to conclude the involvement of a plasma factor, the lack of which prolonged the bleeding time, but failed to impair coagulation times and clot retraction. By the end of the 1960s, VWD was accepted as a combined deficiency of factor VIII (FVIII) and another plasma factor responsible for normal platelet adhesion. Just how these two functions were related to each other was less clear and the diagnostic tests available at the time were poorly reproducible, cumbersome, and unreliable; thus, VWD was poorly delineated from other coagulation and platelet disorders. The early 1970s saw a revolution in diagnostics when ristocetin was identified to induce platelet aggregation, and this formed the basis of the first consistent and reliable VWF "activity" test, permitting quantification of the platelet adhesive function missing in VWD. Concurrently, immunoprecipitating techniques specific for VWF were defined, and the application of such technologies permitted a clearer understanding of both VWF and VWD heterogeneity. Continued exploration of the structure and function of VWF contributed greatly to the understanding of platelet physiology, ligand receptor interaction and pathways of cellular interaction and activation. Recently, additional assays evaluating other functions of VWF, including collagen binding, platelet glycoprotein Ib binding, and FVIII binding, have improved the diagnosis of VWD. The purpose of this narrative review is to explore the history of phenotypic VWD diagnostics, with a focus on laboratory milestones from the past as well highlighting recent and ongoing innovations, and ongoing challenges and

  7. 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.

  8. Echicetin Coated Polystyrene Beads: A Novel Tool to Investigate GPIb-Specific Platelet Activation and Aggregation

    PubMed Central

    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. PMID:24705415

  9. Flow-induced elongation of von Willebrand factor precedes tension-dependent activation.

    PubMed

    Fu, Hongxia; Jiang, Yan; Yang, Darren; Scheiflinger, Friedrich; Wong, Wesley P; Springer, Timothy A

    2017-08-23

    Von Willebrand factor, an ultralarge concatemeric blood protein, must bind to platelet GPIbα during bleeding to mediate hemostasis, but not in the normal circulation to avoid thrombosis. Von Willebrand factor is proposed to be mechanically activated by flow, but the mechanism remains unclear. Using microfluidics with single-molecule imaging, we simultaneously monitored reversible Von Willebrand factor extension and binding to GPIbα under flow. We show that Von Willebrand factor is activated through a two-step conformational transition: first, elongation from compact to linear form, and subsequently, a tension-dependent local transition to a state with high affinity for GPIbα. High-affinity sites develop only in upstream regions of VWF where tension exceeds ~21 pN and depend upon electrostatic interactions. Re-compaction of Von Willebrand factor is accelerated by intramolecular interactions and increases GPIbα dissociation rate. This mechanism enables VWF to be locally activated by hydrodynamic force in hemorrhage and rapidly deactivated downstream, providing a paradigm for hierarchical mechano-regulation of receptor-ligand binding.Von Willebrand factor (VWF) is a blood protein involved in clotting and is proposed to be activated by flow, but the mechanism is unknown. Here the authors show that VWF is first converted from a compact to linear form by flow, and is subsequently activated to bind GPIbα in a tension-dependent manner.

  10. Platelet interactions with Candida albicans.

    PubMed Central

    Skerl, K G; Calderone, R A; Sreevalsan, T

    1981-01-01

    The interaction of human platelets and Candida albicans was studied. Platelet-rich plasma was obtained from freshly drawn blood or outdated platelet concentrates. From the platelet-rich plasma, a platelet extract was derived which stimulated germ tube formation by C. albicans when incubated with yeast cells at 37 degrees C. The active component(s) was heat stable, trypsin sensitive, and ribonuclease and deoxyribonuclease insensitive, and possessed cationic properties since it readily attached to carboxymethyl-Sephadex. The active component(s) seemed to bind to heparin also, since germ tube-promoting activity was eluted from a heparin-cyanogen bromide-activated Sepharose 4B column. In addition, platelet-derived growth factor (Collaborative Research, Inc.) stimulated germination when incubated with low amounts (0.4% final concentration) of bovine calf serum. The aggregation of platelets, prepared as platelet-rich plasma by C. albicans cell wall or alkali-extracted cell wall fractions, was also studied. Aggregation of platelets was observed when cell wall or cell wall fractions were incubated with platelet-poor plasma at 37 degrees C for 20 min and then added to platelet-rich plasma. The component of platelet-poor plasma which promoted aggregation of platelets by C. albicans cell wall or alkali-extracted fractions was inactivated at 56 degrees C (30 min) and by cobra venom factor, indicating a role for the alternate complement pathway in the aggregation response. PMID:7037646

  11. 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.

  12. Platelets in infectious disease.

    PubMed

    Middleton, Elizabeth; Rondina, Matthew T

    2016-12-02

    Sepsis is a dynamic, acute, infectious disease syndrome characterized by dysregulated thrombo-inflammatory responses. The high mortality associated with sepsis has been recognized since the earliest clinicians' writings. Despite this, advances in the treatment of sepsis have been more modest. This is limited, in part, by the heterogeneity in the definition, population, presentation, and causal factors of infectious syndromes. Given the persistently high morbidity and mortality associated with sepsis, a better understanding of the dysregulated cellular biology underpinning sepsis is needed. Platelets are small, anucleate cells that have hemostatic, inflammatory, and immune-mediating properties. Platelets are the second most common circulating blood cell, and emerging evidence suggests that platelets serve as sentinel and effector cells during infectious syndromes. Nevertheless, the molecular and functional changes that occur in platelets during sepsis, and their impact on the clinical course of infected patients, remain incompletely understood. In this review, we first highlight the complex and dynamic pathophysiology characteristics of acute, systemic infections and we then discuss established and emerging evidence of the roles of platelets in sepsis. © 2016 by The American Society of Hematology. All rights reserved.

  13. 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

  14. Platelet interaction with bacteria. V. Ultrastructure of congenital afibrinogenemic platelets.

    PubMed Central

    Clawson, C. C.; White, J. G.

    1980-01-01

    Platelets from a patient with congenital afibrinogenemia (CA) were tested in their native plasma for reactivity in vitro to Staphylococcus aureus 502A. Previous studies of the interactions between normal human platelets and this organism have shown rapid irreversible aggregation responses in which the bacteria were regularly trapped between aggregating platelets. Engulfment of microbes by single normal platelets in a process akin to phagocytosis was a very rare occurrence. In contrast, CA platelets showed a delayed aggregation response to contact with this microorganism. The CA platelets were also much more sensitive to the concentration of bacteria than were normal platelets. Electron microscopy showed that individual CA platelets often engulfed the stimulatory organism rather than participating in aggregation. Postfixation staining with a colloidal tracer, lanthanum nitrate, indicated that the bacteria were sequestered in the open canalicular system of the CA platelets in a manner analogous to that previously observed with latex particles. Restoration of normal levels of human fibrinogen to the CA platelet-rich plasma corrected the delay in aggregation but did not eliminate the frequent engulfment of bacteria by the CA platelets. These findings indicate that fibrinogen is an important, although not essential, cofactor in the response of human platelets to contact with this common bacterial pathogen. Images p[209]-a Figures 6 and 7 Figures 8 and 9 Figures 10 and 11 Figures 12 and 13 Figure 1 Figure 2 Figure 3 PMID:7350814

  15. 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.

  16. Spleen function and platelet kinetics.

    PubMed Central

    Klonizakis, I; Peters, A M; Fitzpatrick, M L; Kensett, M J; Lewis, S M; Lavender, J P

    1981-01-01

    In patients suffering from various platelet abnormalities, quantitative scanning after injection of indium-111 (111In) labelled platelets showed three different patterns of platelet destruction and distribution. In patients with a normal platelet life span but with evidence of increased splenic pooling, the spleen tended to be the main site of destruction. In patients with a moderately reduced platelet life span, the distribution of destruction in the system and variable destruction in the marrow. However, because of its rapidity this destruction was difficult to quantify, and it was difficult in these cases to distinguish reliably between spleen pool, sequestration, and destruction. Destruction of platelets on the liver appeared to be unimportant in all three groups. 111In, because of its physical characteristics, is preferable to chromium-51 as a platelet label in the assessment of abnormal platelet kinetics. Images PMID:7240424

  17. 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].

  18. 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

  19. Human Platelets and Factor XI

    PubMed Central

    Lipscomb, Myatt S.; Walsh, Peter N.

    1979-01-01

    Because human platelets participate in the contact phase of intrinsic coagulation and contain a Factor XI-like coagulant activity, the nature of the Factor XI-like activity was examined and compared with purified plasma Factor XI. The platelet factor XI-like activity was sedimented with the particulate fraction of a platelet lysate, was inactivated by heat (t1/2 3.5 min, 56°C), was not a nonspecific phospholipid activity, and was destroyed by treatment with Triton X-100. Isolated platelet membranes were four-fold enriched in Factor XI activity and similarly enriched in plasma membrane marker enzymes. The Factor XI-like activity of platelet membranes was detected only when assayed in the presence of kaolin, which suggests that it is present in an unactivated form and can participate in contact activation. Concanavalin A inhibited the Factor XI-like activity of platelet lysates and platelet membranes but not of plasma or purified Factor XI. A platelet membrane-Factor XI complex was isolated after incubation of membranes with purified Factor XI. The Factor XI activity of the platelet membrane-plasma Factor XI complex was inhibited by concanavalin A, whereas unbound plasma Factor XI retained activity. An antibody raised against plasma Factor XI inhibited the in vitro Factor XI activity of plasma and of the platelet membrane-plasma Factor XI complex but had no effect on the endogenous Factor XI-like activity of washed lysed platelets or isolated platelet membranes. Washed platelets and isolated platelet membranes obtained from a Factor XI-deficient donor without a history of excessive bleeding had normal quantities of platelet Factor XI-like activity and normal behavior in the contact phase of coagulation (collagen-induced coagulant activity). These results indicate that platelet membranes contain an endogenous Factor XI-like activity that is functionally distinct from plasma Factor XI. PMID:447822

  20. 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.

  1. 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

  2. Wernher von Braun

    NASA Image and Video Library

    1960-09-08

    On September 8, 1960 President Dwight D. Eisenhower visited Huntsville, Alabama to dedicate a new NASA field center in honor of General George C. Marshall, Eisenhower's wartime colleague and the founder of the famous Marshall Plan for European recover after World War II. The new George C. Marshall Space Flight Center was placed under the control of Dr. Wernher Von Braun shown here talking with President Eisenhower. As parto f his remarks dedicating the center, President Eisenhowe refereed to General Marshall as a "man of yar, yet a builder of peace". the Marshall Center's first major assignment including building the huge Saturn V rocket that launched human beings on their first journey to the surface of the moon in 1969.

  3. 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.

  4. Wernher von Braun

    NASA Image and Video Library

    1971-07-26

    During the Apollo 15 launch activities in the launch control center's firing room 1 at Kennedy Space Center, Dr. Wernher von Braun, NASA's Deputy Associate Administrator for planning, takes a closer look at the launch pad through binoculars. The fifth manned lunar landing mission, Apollo 15 (SA-510), carrying a crew of three astronauts: Mission commander David R. Scott, Lunar Module pilot James B. Irwin, and Command Module pilot Alfred M. Worden Jr., lifted off on July 26, 1971. Astronauts Scott and Irwin were the first to use a wheeled surface vehicle, the Lunar Roving Vehicle, or the Rover, which was designed and developed by the Marshall Space Flight Center, and built by the Boeing Company. Astronauts spent 13 days, nearly 67 hours, on the Moon's surface to inspect a wide variety of its geological features.

  5. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1960-01-01

    On September 8, 1960 President Dwight D. Eisenhower visited Huntsville, Alabama to dedicate a new NASA field center in honor of General George C. Marshall, Eisenhower's wartime colleague and the founder of the famous Marshall Plan for European recover after World War II. The new George C. Marshall Space Flight Center was placed under the control of Dr. Wernher Von Braun shown here talking with President Eisenhower. As parto f his remarks dedicating the center, President Eisenhowe refereed to General Marshall as a 'man of yar, yet a builder of peace'. the Marshall Center's first major assignment including building the huge Saturn V rocket that launched human beings on their first journey to the surface of the moon in 1969.

  6. Primary arrest of circulating platelets on collagen involves phosphorylation of Syk, cortactin and focal adhesion kinase: studies under flow conditions.

    PubMed Central

    Arderiu, Gemma; Díaz-Ricart, Maribel; Buckley, Byron; Escolar, Ginés; Ordinas, Antonio

    2002-01-01

    After a vessel wall injury, platelets adhere to the subendothelium following a sequence of events: arrest of single platelets on the surface, progression to platelet spreading and final aggregation. Primary arrest of circulating platelets on subendothelial components occurs through platelet glycoprotein (GP) Ib and collagen receptors; then platelets spread and aggregate through a GPIIb-IIIa-dependent mechanism. A series of strategies were applied to analyse the tyrosine-phosphorylation mechanisms occurring at the different stages of platelet adhesion on subendothelial components under flow conditions, with special attention to primary arrest. To evaluate spread platelets, samples were exposed to acetylsalicylic acid, which blocks aggregate formation. To study single platelets in contact, a monoclonal antibody specific for GPIIb-IIIa was used to prevent platelet spreading and further aggregation. This experimental situation was also investigated using blood from two patients with Glanzmann's thrombasthenia (i.e. lacking GPIIb-IIIa). Results demonstrated that blockade of both spreading and aggregation results in significant changes in the tyrosine-phosphorylation patterns. Arrest of single platelets on collagen-rich surfaces resulted in phosphorylation of p125, identified as focal adhesion kinase (FAK), the 80/85 kDa doublet (cortactin), and p72, identified as Syk. Arrest of single platelets on von Willebrand factor as adhesive substrate showed that interaction through GPIb induces Syk phosphorylation, but not that of cortactin and FAK. Our data indicate that the initial arrest of platelets on subendothelial components involves Syk phosphorylation, which seems to be GPIb-dependent, and this is followed by activation and phosphorylation of cortactin and FAK. These processes seem to occur before GPIIb-IIIa becomes activated. PMID:11988077

  7. [Platelets and arterial thrombosis].

    PubMed

    Cazenave, Jean-Pierre; Gachet, Christian; Lanza, François; Wiesel, Marie-Louise

    2003-01-01

    The pathological mechanisms involved in arterial thrombus formation are similar to the mechanisms involved in physiological hemostasis. Arterial thrombosis is initiated following lesion of the vessel wall, either through rupture of an atherosclerotic plaque containing lipids, adhesive proteins and tissue factor or after angioplasty exposing the thrombogenic subendothelial matrix. Platelets play a major role in arterial thrombus formation through ADP secretion and thrombin generation on their activated surface. Arterial thrombosis is a frequent complication of atherosclerotic lesions and leads to acute ischemic events. These events are therapeutic emergencies which require administration of antithrombotic drugs inhibiting platelet functions and thrombin.

  8. Thrombocytopenia: A Destruction of Platelets.

    PubMed

    Greenberg, Edythe M

    Platelets, or megakaryocytes, are irregular, disk-shaped cell fragments circulating in the blood. They are a primary component in maintaining hemostasis. Low platelet counts, or thrombocytopenia, leave patients at an increased risk of hemorrhage. This article discusses various etiologies of disorders of low platelets and current therapies for management.

  9. 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

  10. 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.

  11. Engineering and characterization of a chimeric anti-platelet glycoprotein Ibalpha monoclonal antibody and preparation of its Fab fragment.

    PubMed

    Yang, Jianfeng; Ji, Shundong; Dong, Ningzheng; Zhao, Yiming; Ruan, Changgeng

    2010-04-01

    Glycoprotein Ibalpha (GPIbalpha) is a platelet-specific membrane protein. It mediates platelet adhesion to collagen exposed at the vascular injury site by binding to von Willebrand factor (VWF) in plasma. This process is crucial for arterial thrombus formation. Blocking interaction between GPIbalpha and VWF may prevent platelet adhesion and thrombus formation. We previously generated a high affinity monoclonal antibody against human platelet GPIbalpha, SZ2, which inhibits both ristocetin- and botrocetin-induced platelet aggregation in vitro. To convert SZ2 into mouse/human chimeric antibody for anti-platelet therapy in humans, in this study, we constructed a mouse/human chimeric antibody derived from the hybridoma cells producing murine antibody against platelet glycoprotein Ibalpha, conducted its expression in dihydrofolate reductase-deficient Chinese hamster ovary (CHO) cells, and prepared its chimeric Fab fragment. Results from ELISA and Western blot analysis showed that the chimeric antibody was secreted from the cells and that the heavy and light chains were assembled correctly. Flow cytometry analysis confirmed specific binding of the chimeric antibody to the GPIb-expressing CHO cells. In vitro functional studies revealed that the chimeric antibody and its Fab fragment prevented platelet adhesion to VWF under high shear stress and inhibited ristocetin-induced platelet aggregation in a dose-dependent manner. These results demonstrated that the chimeric antibody was successfully engineered and suggested that the Fab fragment of chimeric antibody against GPIbalpha is a promising therapeutic antibody more suitable for prevention and treatment of human arterial thrombosis.

  12. [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.

  13. Platelet hyperreactivity explains the bleeding abnormality and macrothrombocytopenia in a murine model of sitosterolemia

    PubMed Central

    Kanaji, Sachiko; Montgomery, Robert R.; Newman, Peter J.

    2013-01-01

    Sitosterolemia is a rare, autosomal recessive disease caused by mutations in the adenosine triphosphate-binding cassette transporter genes ABCG5 or ABCG8 that result in accumulation of xenosterols in the body. Clinical manifestations include tendon xanthomas, premature coronary artery disease, hemolytic anemia, macrothrombocytopenia, and bleeding. Although the effect of sterol accumulation on the predisposition for atherosclerosis is evident, how xenosterol accumulation leads to defects in platelet physiology is unknown. Sitosterolemia induced in Abcg5- and Abcg8-deficient mice fed a high plant sterol diet resulted in accumulation of free sterols in platelet plasma membranes, leading to hyperactivatable platelets characterized by constitutive binding of fibrinogen to its αIIbβ3 integrin receptor, internalization of the αIIbβ3 complex, generation of platelet-derived microparticles, and changes in the quantity and subcellular localization of filamin. The latter was associated with macrothrombocytopenia, shedding of GPIbα, impaired platelet adhesion to von Willebrand factor, and inability to form stable thrombi. Plasma levels of soluble GPIbα were strongly correlated with plasma sitosterol levels in samples from human sitosterolemic patients, implicating a similar mechanism of sterol-induced platelet passivation in the human disease. Intercalation of plant sterols into the plasma membrane therefore results in dysregulation of multiple platelet activation pathways, leading to macrothrombocytopenia and bleeding. PMID:23926302

  14. 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.

  15. 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.

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

    SciTech Connect

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

    2015-12-16

    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 better 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.

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

    DOE PAGES

    Tischer, Alexander; Campbell, James C.; Machha, Venkata R.; ...

    2015-12-16

    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 limitedmore » 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 better 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.« less

  18. 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

  19. 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.

  20. 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.

  1. Delayed-onset of procoagulant signalling revealed by kinetic analysis of COAT platelet formation.

    PubMed

    Alberio, Lorenzo; Ravanat, Catherine; Hechler, Béatrice; Mangin, Pierre H; Lanza, François; Gachet, Christian

    2017-06-02

    The combined action of collagen and thrombin induces the formation of COAT platelets, which are characterised by a coat of procoagulant and adhesive molecules on their surface. Although recent work has started to highlight their clinical relevance, the exact mechanisms regulating the formation of procoagulant COAT platelets remain unclear. Therefore, we employed flow cytometry in order to visualise in real time surface and intracellular events following simultaneous platelet activation with convulxin and thrombin. After a rapid initial response pattern characterised by the homogenous activation of the fibrinogen receptor glycoprotein IIb/IIIa in all platelets, starting with a delay of about 2 minutes an increasing fraction transforms to procoagulant COAT platelets. Their surface is characterised by progressive loss of PAC-1 binding, expression of negative phospholipids and retention of α-granule von Willebrand factor. Intracellular events in procoagulant COAT platelets are a marked increase of free calcium into the low micromolar range, concomitantly with early depolarisation of the mitochondrial membrane and activation of caspase-3, while non-COAT platelets keep the intracellular free calcium in the nanomolar range and maintain an intact mitochondrial membrane. We show for the first time that the flow-cytometrically distinct fractions of COAT and non-COAT platelets differentially phosphorylate two signalling proteins, PKCα and p38MAPK, which may be involved in the regulation of the different calcium fluxes observed in COAT versus non-COAT platelets. This study demonstrates the utility of concomitant cellular and signalling evaluation using flow cytometry in order to further dissect the mechanisms underlying the dichotomous platelet response observed after collagen/thrombin stimulation.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Rho GTPases in platelet function.

    PubMed

    Aslan, J E; McCarty, O J T

    2013-01-01

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

  9. 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.

  10. 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.

  11. Wernher von Braun

    NASA Image and Video Library

    1969-07-01

    This photograph depicts Dr. von Braun (fourth from far right) and other NASA officials surveying the deep-sea research submarine "Ben Franklin." Named for American patriot and inventor Ben Franklin, who discovered the Gulf Steam, the 50-foot Ben Franklin was built between 1966 and 1968 in Switzerland for deep-ocean explorer Jacques Piccard and the Grumman Aircraft Engineering Corporation. The submersible made a famous 30-day drift dive off the East Coast of the United States and Canada in 1969 mapping the Gulf Stream's currents and sea life, and also made space exploration history by studying the behavior of aquanauts in a sealed, self-contained, self-sufficient capsule for NASA. On July 14, 1969, the Ben Franklin was towed to the high-velocity center of the Stream off the coast of Palm Beach, Florida. With a NASA observer on board, the sub descended to 1,000 feet off of Riviera Beach, Florida and drifted 1,400 miles north with the current for more than four weeks, reemerging near Maine. During the course of the dive, NASA conducted exhaustive analyses of virtually every aspect of onboard life. They measured sleep quality and patterns, sense of humor and behavioral shifts, physical reflexes, and the effects of a long-term routine on the crew. The submarine's record-shattering dive influenced the design of Apollo and Skylab missions and continued to guide NASA scientists as they devised future marned space-flight missions.

  12. Wernher von Braun

    NASA Image and Video Library

    1969-07-01

    This photograph depicts Dr. von Braun (at right, showing his back) and other NASA officials surveying the deep-sea research submarine "Ben Franklin." Named for American patriot and inventor Ben Franklin, who discovered the Gulf Steam, the 50-foot Ben Franklin was built between 1966 and 1968 in Switzerland for deep-ocean explorer Jacques Piccard and the Grumman Aircraft Engineering Corporation. The submersible made a famous 30-day drift dive off the East Coast of the United States and Canada in 1969 mapping the Gulf Stream's currents and sea life, and also made space exploration history by studying the behavior of aquanauts in a sealed, self-contained, self-sufficient capsule for NASA. On July 14, 1969, the Ben Franklin was towed to the high-velocity center of the Stream off the coast of Palm Beach, Florida. With a NASA observer on board, the sub descended to 1,000 feet off of Riviera Beach, Florida and drifted 1,400 miles north with the current for more than four weeks, reemerging near Maine. During the course of the dive, NASA conducted exhaustive analyses of virtually every aspect of onboard life. They measured sleep quality and patterns, sense of humor and behavioral shifts, physical reflexes, and the effects of a long-term routine on the crew. The submarine's record-shattering dive influenced the design of Apollo and Skylab missions and continued to guide NASA scientists as they devised future marned space-flight missions.

  13. 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

  14. 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

  15. 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

  16. Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue

    PubMed Central

    Teixeira-Ferreira, André; Carvalho, Paulo Costa; Salazar, Gustavo Adolfo; Zimmerman, Guy A.; Perales, Jonas

    2017-01-01

    Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV) infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood. Here we used quantitative proteomics to investigate the protein content of platelets in clinical samples from patients with dengue compared to platelets from healthy donors. Our assays revealed a set of 252 differentially abundant proteins. In silico analyses associated these proteins with key molecular events including platelet activation and inflammatory responses, and with events not previously attributed to platelets during dengue infection including antigen processing and presentation, proteasome activity, and expression of histones. From these results, we conducted functional assays using samples from a larger cohort of patients and demonstrated evidence for platelet activation indicated by P-selectin (CD62P) translocation and secretion of granule-stored chemokines by platelets. In addition, we found evidence that DENV infection triggers HLA class I synthesis and surface expression by a mechanism depending on functional proteasome activity. Furthermore, we demonstrate that cell-free histone H2A released during dengue infection binds to platelets, increasing platelet activation. These findings are consistent with functional importance of HLA class I, proteasome subunits, and histones that we found exclusively in proteome analysis of platelets in samples from dengue patients. Our study provides the first in-depth characterization of the platelet proteome in dengue

  17. Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue.

    PubMed

    Trugilho, Monique Ramos de Oliveira; Hottz, Eugenio Damaceno; Brunoro, Giselle Villa Flor; Teixeira-Ferreira, André; Carvalho, Paulo Costa; Salazar, Gustavo Adolfo; Zimmerman, Guy A; Bozza, Fernando A; Bozza, Patrícia T; Perales, Jonas

    2017-05-01

    Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV) infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood. Here we used quantitative proteomics to investigate the protein content of platelets in clinical samples from patients with dengue compared to platelets from healthy donors. Our assays revealed a set of 252 differentially abundant proteins. In silico analyses associated these proteins with key molecular events including platelet activation and inflammatory responses, and with events not previously attributed to platelets during dengue infection including antigen processing and presentation, proteasome activity, and expression of histones. From these results, we conducted functional assays using samples from a larger cohort of patients and demonstrated evidence for platelet activation indicated by P-selectin (CD62P) translocation and secretion of granule-stored chemokines by platelets. In addition, we found evidence that DENV infection triggers HLA class I synthesis and surface expression by a mechanism depending on functional proteasome activity. Furthermore, we demonstrate that cell-free histone H2A released during dengue infection binds to platelets, increasing platelet activation. These findings are consistent with functional importance of HLA class I, proteasome subunits, and histones that we found exclusively in proteome analysis of platelets in samples from dengue patients. Our study provides the first in-depth characterization of the platelet proteome in dengue

  18. Spontaneous platelet aggregation in patients with acute coronary syndrome.

    PubMed

    Mazurov, A V; Khaspekova, S G; Yakushkin, V V; Khachikyan, M V; Zyuryaev, I T; Ruda, M Ya

    2013-05-01

    Spontaneous platelet aggregation was evaluated in patients with acute coronary syndrome on days 1, 3-5, and 8-12 of the disease. On day 1, aggregation was analyzed after aspirin, but before clopidogrel administration; during other periods after both antiaggregants. The mean levels of spontaneous aggregation after antithrombotic therapy did not change during different periods after the onset of acute coronary syndrome, in contrast to ADP-induced aggregation that decreased after the development of clopidogrel effects (days 3-5 and 8-12). Spontaneous aggregation during different periods directly correlated (r>0.4, p<0.01) with spontaneous and ADP-induced aggregation during different periods (r=0.372, r=0.447, and r=0.543 on days 1, 3-5, and 8-12, respectively; p<0.01). No relationship between spontaneous aggregation and plasma concentration of von Willebrand's factor was detected. Spontaneous aggregation was completely suppressed after in vitro addition of prostaglandin E1 (platelet activation inhibitor), slightly (by ≈20%) decreased in the presence of antibodies to glycoprotein Ib, blocking its reactions with von Willebrand's factor, and did not change in the presence of aptamer inhibiting thrombin activity.

  19. 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.

  20. 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

  1. 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.

  2. Screening for von Willebrand disease: contribution of an automated assay for von Willebrand factor activity.

    PubMed

    Lasne, D; Dey, C; Dautzenberg, M-D; Cherqaoui, Z; Monge, F; Aouba, A; Torchet, M-F; Geloen, D; Landais, P; Rothschild, C

    2012-05-01

    Measuring von Willebrand factor (VWF) activity is essential to the diagnosis of von Willebrand disease (VWD). The VWF activity is usually assessed based on measurement of the ristocetin cofactor (VWF:RCo). However, that test is technically challenging and has high intra- and inter-assay variabilities. The HemosIL VWF activity (VWF:AC) is a fully automated assay, recently proposed as a good alternative to VWF:RCo for VWD diagnosis. This study was undertaken to assess this new method. First, the analytical performance of VWF:AC on an automated coagulo-meter (ACLTop) was determined, and then this new method was compared with VWF:RCo and the platelet function analyzer (PFA100) for 160 patients referred for VWD screening. The VWF:AC achieved acceptable precision with within-run and between-run coefficients of variation ranging from 2.3% to 14.1%, and linearity from 10% to 100%. Despite some marked differences between VWF:AC and VWF:RCo for 10 plasmas tested, their agreement for VWD diagnosis was good. The VWF:AC had sensitivity similar to that of PFA100 (close to 100%), but better specificity (97.7% vs. 66% or 60%, depending on the cartridge used). The good analytical performance, and the sensitivity and specificity of VWF:AC to detect VWF deficiency renders it a suitable method for VWD screening. Our findings support VWF:AC use for the diagnostic work-up of VWD, paying close attention to concomitant clinical signs and bleeding score, as recommended for VWD. © 2011 Blackwell Publishing Ltd.

  3. Factor VIII-von Willebrand factor binding defects in autosomal recessive von Willebrand disease type Normandy and in mild hemophilia A. New insights into factor VIII-von Willebrand factor interactions.

    PubMed

    Jacquemin, Marc

    2009-01-01

    This concise review is focused on genetic, molecular and clinical aspects of von Willebrand disease (VWD) type 2N and of mild hemophilia A due to mutations impairing FVIII-von Willebrand factor (VWF) interactions. Missense mutations in the VWF gene impairing the binding to FVIII do not impair the structure of VWF multimers nor the ability of VWF to aggregate platelets but causes an accelerated clearance of FVIII. Missense mutations in the FVIII gene impairing the binding to VWF are a common cause of mild/moderate hemophilia A. The implications of these observations for the treatment of patients with coagulation factor concentrates and desmopressin are discussed. Copyright (c) 2009 S. Karger AG, Basel.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Estrogen, inflammation, and platelet phenotype.

    PubMed

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

    2008-01-01

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

  11. [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.

  12. 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...

  13. Contextual view of the Palace of Fine and Decorative Arts ...

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

    Contextual view of the Palace of Fine and Decorative Arts from Yerba Buena Island, showing Hall of Transportation at far right, camera facing northwest - Golden Gate International Exposition, Palace of Fine and Decorative Arts & Annex, California Avenue, Treasure Island, San Francisco, San Francisco County, CA

  14. Molecular cloning and characterization of rhesus monkey platelet glycoprotein Ibα, a major ligand-binding subunit of GPIb-IX-V complex.

    PubMed

    Qiao, Jianlin; Shen, Yang; Shi, Meimei; Lu, Yanrong; Cheng, Jingqiu; Chen, Younan

    2014-05-01

    Through binding to von Willebrand factor (VWF), platelet glycoprotein (GP) Ibα, the major ligand-binding subunit of the GPIb-IX-V complex, initiates platelet adhesion and aggregation in response to exposed VWF or elevated fluid-shear stress. There is little data regarding non-human primate platelet GPIbα. This study cloned and characterized rhesus monkey (Macaca Mullatta) platelet GPIbα. DNAMAN software was used for sequence analysis and alignment. N/O-glycosylation sites and 3-D structure modelling were predicted by online OGPET v1.0, NetOGlyc 1.0 Server and SWISS-MODEL, respectively. Platelet function was evaluated by ADP- or ristocetin-induced platelet aggregation. Rhesus monkey GPIbα contains 2,268 nucleotides with an open reading frame encoding 755 amino acids. Rhesus monkey GPIbα nucleotide and protein sequences share 93.27% and 89.20% homology respectively, with human. Sequences encoding the leucine-rich repeats of rhesus monkey GPIbα share strong similarity with human, whereas PEST sequences and N/O-glycosylated residues vary. The GPIbα-binding residues for thrombin, filamin A and 14-3-3ζ are highly conserved between rhesus monkey and human. Platelet function analysis revealed monkey and human platelets respond similarly to ADP, but rhesus monkey platelets failed to respond to low doses of ristocetin where human platelets achieved 76% aggregation. However, monkey platelets aggregated in response to higher ristocetin doses. Monkey GPIbα shares strong homology with human GPIbα, however there are some differences in rhesus monkey platelet activation through GPIbα engagement, which need to be considered when using rhesus monkey platelet to investigate platelet GPIbα function. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Osmotic stability of blood platelets.

    PubMed

    Fantl, P

    1968-09-01

    1. Hypotonic solutions added to human platelet-containing plasma cause a transient decrease of absorbancy of light at 610 mmu which is followed by a gradual increase of absorbancy.2. When platelets are stored for 7 hr at 4 degrees C the absorbancy changes with variations of osmolarity and their aggregation with adenosine diphosphate (ADP) remain the same. However, the reversal of absorbancy declines during storage of platelet-containing plasma.3. Platelets are not aggregated by stearate. Platelets appear to be only slightly affected by stearate concentration higher than 0.8 mM, but oleate has no effect.4. Hypertonic solutions of NaCl and urea cause increase in absorbancy of platelet-containing human plasma. Hypertonic sucrose solutions produce no more change than isotonic solutions. Hypertonic NaCl produces permanent increases in absorbancy. In human platelet-containing plasma the increased absorbancy caused by hypertonic urea is transient and declines.5. The osmotic platelet changes occur in isolated platelets as well as in platelet-containing plasma.6. The absorbancy of frozen and thawed platelet-containing plasma is not significantly altered by hypotonic solutions but the absorbancy changes caused by hypertonic solutions are similar to that of unfrozen plasma.7. The immediate absorbancy changes caused by hypo- and by hypertonic solutions are the same at 5 degrees C and 30 degrees C and are therefore probably of a physical nature. The reversal of absorbancy and aggregation of platelets by added adenosine diphosphate have Q(10) > 1 and are therefore probably of a chemical-enzymic nature.8. Divalent cations and contact activation are not required for the osmotic platelet changes and 10(-3)M-Cu(2+) and Zn(2+) do not interfere. Inhibitors of oxidative phosphorylation, electron transfer, sodium, potassium activated adenosine triphosphatases and adenosine triphosphate do not inhibit reversal of absorbancy of platelets exposed to hypotonic solutions. Cyanide, 5 x 10

  20. 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.

  1. 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.

  2. 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.

  3. Osmotic stability of blood platelets

    PubMed Central

    Fantl, P.

    1968-01-01

    1. Hypotonic solutions added to human platelet-containing plasma cause a transient decrease of absorbancy of light at 610 mμ which is followed by a gradual increase of absorbancy. 2. When platelets are stored for 7 hr at 4° C the absorbancy changes with variations of osmolarity and their aggregation with adenosine diphosphate (ADP) remain the same. However, the reversal of absorbancy declines during storage of platelet-containing plasma. 3. Platelets are not aggregated by stearate. Platelets appear to be only slightly affected by stearate concentration higher than 0·8 mM, but oleate has no effect. 4. Hypertonic solutions of NaCl and urea cause increase in absorbancy of platelet-containing human plasma. Hypertonic sucrose solutions produce no more change than isotonic solutions. Hypertonic NaCl produces permanent increases in absorbancy. In human platelet-containing plasma the increased absorbancy caused by hypertonic urea is transient and declines. 5. The osmotic platelet changes occur in isolated platelets as well as in platelet-containing plasma. 6. The absorbancy of frozen and thawed platelet-containing plasma is not significantly altered by hypotonic solutions but the absorbancy changes caused by hypertonic solutions are similar to that of unfrozen plasma. 7. The immediate absorbancy changes caused by hypo- and by hypertonic solutions are the same at 5° C and 30° C and are therefore probably of a physical nature. The reversal of absorbancy and aggregation of platelets by added adenosine diphosphate have Q10 > 1 and are therefore probably of a chemical-enzymic nature. 8. Divalent cations and contact activation are not required for the osmotic platelet changes and 10-3 M-Cu2+ and Zn2+ do not interfere. Inhibitors of oxidative phosphorylation, electron transfer, sodium, potassium activated adenosine triphosphatases and adenosine triphosphate do not inhibit reversal of absorbancy of platelets exposed to hypotonic solutions. Cyanide, 5 × 10-3 M, fluoride, 1

  4. Comparison of platelet counting technologies in equine platelet concentrates.

    PubMed

    O'Shea, Caitlin M; Werre, Stephen R; Dahlgren, Linda A

    2015-04-01

    (1) To compare the performance of 4 platelet counting technologies in equine platelet concentrates and (2) to evaluate the ability of the Magellan platelet rich plasma (PRP) system to concentrate equine platelets. Experimental study to assess method agreement. Adult mixed breed horses (n = 32). Acid citrate dextrose-A anti-coagulated whole blood was collected and PRP produced using the Magellan system according to the manufacturer's instructions. Platelets were quantified using 4 counting methods: optical scatter (Advia 2120), impedance (CellDyn 3700), hand counting, and fluorescent antibody flow cytometry. Platelet concentrations were compared using Passing and Bablok regression analyses and mixed model ANOVA. Significance was set at P < .05. Platelet concentrations measured in identical PRP samples were consistently higher for the Advia 2120 than the CellDyn 3700. Systematic and proportional biases were observed between these 2 automated methods when analyzed by regression analysis of the larger sample size. No bias (systematic or proportional) was observed among any of the other counting methods. Despite the bias detected between the 2 automated systems, there were no significant differences on average among the 4 counting methods evaluated, based on the ANOVA. The Magellan system consistently generated high platelet concentrations as well as higher than expected WBC concentrations. The Magellan system delivered desirably high platelet concentrations; however, WBC concentrations may be unacceptably high for some orthopedic applications. All 4 platelet counting methods tested were equivalent on average and therefore suitable for quantifying platelets in equine PRP used for clinical applications. © Copyright 2014 by The American College of Veterinary Surgeons.

  5. 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.

  6. Synthesis of polymer latex particles decorated with organically-modified laponite clay platelets via emulsion polymerization.

    PubMed

    Herrera, Norma Negrete; Persoz, Stéphanie; Putaux, Jean-Luc; David, Laurent; Bourgeat-Lami, Elodie

    2006-02-01

    We report a new route to colloidal nanocomposites consisting of polymer latex particles covered with Laponite clay nanoplatelets. These composite particles are prepared by seeded emulsion (co)polymerization of styrene and butyl acrylate from Laponite clay suspensions previously functionalized by ion exchange using either a free radical initiator: 2,2-azobis (2-methylpropionamidine) hydrochloride (AIBA) or a cationic vinyl monomer: 2-(methacryloyloxy) ethyl trimethyl ammonium chloride (MADQUAT). The successful intercalation of the cationic reactive molecules was confirmed by elemental analysis, FTIR, 13C solid-state NMR and WAXD. The organically-modified clays were dispersed into water with the help of tetrasodium pyrophosphate and an anionic surfactant. stable latexes, produced under different experimental conditions, were successfully obtained from the clay suspensions. Cryo-TEM images of the resulting latexes showed spherical composite particles with diameters in the 50-250 nm range with clay sheets located on their surface. This paper reports on the effect of the processing conditions on the particle morphology and latex stability, and describes the mechanism of formation of the nanocomposite particles.

  7. Subpopulations in purified platelets adhering on glass.

    PubMed

    Donati, Alessia; Gupta, Swati; Reviakine, Ilya

    2016-06-22

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

  8. 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.

  9. Organophosphorus Flame Retardants and Plasticizers in Building and Decoration Materials and Their Potential Burdens in Newly Decorated Houses in China.

    PubMed

    Wang, Yan; Hou, Minmin; Zhang, Qiaonan; Wu, Xiaowei; Zhao, Hongxia; Xie, Qing; Chen, Jingwen

    2017-10-03

    Organophosphorus flame retardants (OPFRs) have been increasingly used in various building and decoration materials to fulfill fire safety standards since the phasing out of polybrominated diphenyl ethers. We determined OPFR concentrations in the most commonly used building and decoration materials available in local markets and online in China. The OPFR concentrations varied significantly, from 14.78 ng/g (putty powder) to 9649000 ng/g (expanded polystyrene panel (EPS)). Relatively high concentrations of OPFRs were found in foam samples, followed by nonwoven and polyvinyl chloride (PVC) wallpaper, PVC pipes, sealing materials, boards, and paints. Low concentrations were found mostly in wall decoration powders, suggesting that no OPFRs had been added to these powders. Tris(1-chloro-2-propyl) phosphate and tris(1,3-dichloro-2-propyl) phosphate were the most detected halogenated OPFRs, while tri-n-butyl phosphate and tris(2-butoxyethyl) phosphate were the dominant nonhalogenated OPFRs, implying that they are commonly used in building and decoration materials. The estimated OPFR burden in interior decoration using nonwoven wallpaper was 330- and 2110-fold higher than that using latex paint and diatomite, respectively. The emission periods of OPFRs from nonwoven and PVC wallpaper may be greater than 13 years. We estimated that the total burden of OPFRs for decoration using wallpaper in newly decorated houses in China is ∼63 t/y. Significantly higher concentrations of OPFRs in interior decoration materials, especially nonwoven wallpaper, pose potential health risks to the people using the buildings.

  10. 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

  11. [Pheochromocytoma and von Recklinghausen's disease].

    PubMed

    Rabii, R; Fekak, H; Moufid, K; Joual, A; Bennani, S; el Mrini, M; Benjelloun, S

    2002-07-01

    The association between von Recklinghausen's disease and pheochromocytoma is present about 10% of cases. We report a case of 49 years old women who presented with elevated blood pressure and von Recklinghausen's neurofibromatosis. Laboratory examination showed a marked level in the urinary excretion of cathecholamine. The computed tomography showed a right adrenal tumor suggesting a pheochromocytoma. The adrenalectomy was realised by transabdominal approach and the histological examination confirmed a benign pheochromocytoma. The authors discuss the pathogenetic hypothesis of this rare pathological association, the diagnostic methods and the therapeutic procedure.

  12. [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.

  13. 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

  14. Platelets as delivery systems for disease treatments

    PubMed Central

    Shi, Qizhen; Montgomery, Robert R.

    2010-01-01

    Platelets are small, anucleate, discoid shaped blood cells that play a fundamental role in hemostasis. Platelets contain a large number of biologically active molecules within cytoplasmic granules that are critical to normal platelet function. Because platelets circulate in blood through out the body, release biological molecules and mediators on demand, and participate in hemostasis as well as many other pathophysiologic processes, targeting expression of proteins of interest to platelets and utilizing platelets as delivery systems for disease treatment would be a logical approach. This paper reviews the genetic therapy for inherited bleeding disorders utilizing platelets as delivery system, with a particular focus on platelet-derived FVIII for hemophilia A treatment. PMID:20619307

  15. 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.

  16. 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

  17. Autosomal dominant C1149R von Willebrand disease: phenotypic findings and their implications

    PubMed Central

    Pérez-Rodríguez, Almudena; García-Rivero, Aranzazu; Lourés, Esther; López-Fernández, Maria Fernanda; Rodríguez-Trillo, Angela; Batlle, Javier

    2009-01-01

    Background Mutation C1149R in the von Willebrand factor (VWF) gene has been thought to cause autosomal dominant severe type 1 von Willebrand disease (VWD). Design and Methods Eight patients from three unrelated families with this mutation were included in the present study who had distinct VWF abnormalities, not described in earlier studies. Results The patients showed notably low levels of VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen binding (VWF:CB), and a reduced ristocetin-induced platelet aggregation (RIPA). VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios were lower than 0.7. At basal conditions, all the VWF multimers were decreased in plasma, with a clearly lower relative proportion of the high molecular weight VWF multimers (HMWM). In high-resolution agarose gels, a large decrease in the relative proportions of the satellite bands was seen. The patients had a brief good response to desmopressin (DDAVP) administration, but the released VWF half-life was shorter than normal, indicating an accelerated clearance of their VWF. Platelet VWF was abnormal. Conclusions We conclude from the results obtained in these patients for plasma phenotypic data that this mutation should be classified as a VWD type 2A (IIE). DDAVP therapy may be somewhat helpful for this mutation, at least for mild to moderate bleeding. These data provide evidence that for VWD classification factors other than basal VWF, such as DDAVP response and platelet VWF, should be considered. PMID:19286880

  18. 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 ...

  19. 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.

  20. 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.

  1. 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).

  2. Platelets actively sequester angiogenesis regulators

    PubMed Central

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

    2009-01-01

    Clinical trials with antiangiogenic agents have not been able to validate plasma or serum levels of angiogenesis regulators as reliable markers of cancer presence or therapeutic response. We recently reported that platelets contain numerous proteins that regulate angiogenesis. We now show that accumulation of angiogenesis regulators in platelets of animals bearing malignant tumors exceeds significantly their concentration in plasma or serum, as well as their levels in platelets from non–tumor-bearing animals. This process is selective, as platelets do not take up a proportional amount of other plasma proteins (eg, albumin), even though these may be present at higher concentrations. We also find that VEGF-enriched Matrigel pellets implanted subcutaneously into mice or the minute quantities of VEGF secreted by microscopic subcutaneous tumors (0.5-1 mm3) result in an elevation of VEGF levels in platelets, without any changes in its plasma levels. The profile of other angiogenesis regulatory proteins (eg, platelet-derived growth factor, basic fibroblast growth factor) sequestered by platelets also reflects the presence of tumors in vivo before they can be macroscopically evident. The ability of platelets to selectively take up angiogenesis regulators in cancer-bearing hosts may have implications for the diagnosis and management of many angiogenesis-related diseases and provide a guide for antiangiogenic therapies. PMID:19036702

  3. Platelet compatibility of magnesium alloys.

    PubMed

    Yahata, Chie; Mochizuki, Akira

    2017-09-01

    Lately, Mg alloys have been investigated as a new class of biomaterials owing to their excellent biodegradability and biocompatibility. It has previously been reported that the in vitro compatibility of a Mg alloy containing aluminum and zinc (AZ) alloy with the blood coagulation system is excellent due to Mg(2+) ions eluting from the alloy. In this study, the compatibility of the AZ alloy with platelets was evaluated by scanning electron microscopy (SEM) and flow cytometry. In the flow cytometry analysis, the platelets were stained using PAC-1 and P-selectin antibodies. SEM images and PAC-1 analyses showed no negative effects on the platelets, whereas P-selectin analysis showed marked platelet activation. To understand these contradictory results, the amount of β-thromboglobulin (β-TG) released from the platelets was investigated. From that investigation, it was concluded that platelets are markedly activated by the alloys. In addition to clarifying divergent results depending on the analysis method used, the effects of Mg(2+) ions and pH on platelet activation were studied. These results show that platelet activation is caused by an increase in pH at the alloy surface owing to the erosion of the alloy. Copyright © 2017 Elsevier B.V. All rights reserved.

  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: 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. [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.

  15. 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.

  16. 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.

  17. Mechanisms of hemolysis-associated platelet activation

    PubMed Central

    Helms, C. C.; Marvel, M.; Zhao, W.; Stahle, M.; Vest, R.; Kato, G. J.; Lee, J. S.; Christ, G.; Gladwin, M. T.; Hantgan, R. R.; Kim-Shapiro, D. B.

    2013-01-01

    Summary Background Intravascular hemolysis occurs after blood transfusion, in hemolytic anemias and other conditions, and is associated with hypercoagulable states. Hemolysis has been shown to potently activate platelets in vitro and in vivo and several mechanisms have been suggested to account for this including (1) direct activation by hemoglobin, (2) increase in reactive oxygen species (ROS), (3) scavenging of nitric oxide by released hemoglobin, and (4) release of intraerythrocytic ADP. Objective The aim of the current study is to elucidate the mechanism of hemolysis-mediated platelet activation. Methods We used flow cytometry to detect PAC-1 binding to activated platelets for in vitro experiments and a Siemens’ Advia 120 hematology system to assess platelet aggregation using platelet counts from in vivo experiments in a rodent model. Results We show that Hb does not directly activate platelets. However, ADP bound to Hb can cause platelet activation. Furthermore, platelet activation due to shearing of RBCs is reduced in the presence of apyrase which metabolizes ADP to AMP. Use of ROS scavengers did not affect platelet activation. We also show that cell free Hb does enhance platelet activation by abrogating the inhibitory effect of NO on platelet activation. In vivo infusions of ADP and purified (ADP-free) Hb as well as hemolysate result in platelet aggregation as evidenced by decreased platelet counts. Conclusion Two primary mechanisms account for red blood cell hemolysis-associated platelet activation: ADP release which activates platelets and cell-free hemoglobin release which enhances platelet activation by lowering NO bioavailability. PMID:24119131

  18. 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

  19. 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.

  20. 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

  1. 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.

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

    PubMed

    Neff, Anne T

    2015-08-01

    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.

  3. 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

  4. 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

  5. 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

  6. 18. DETAIL VIEW OF RAILING BRACKETING AND DECORATIVE ART DECO ...

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

    18. DETAIL VIEW OF RAILING BRACKETING AND DECORATIVE ART DECO FEATURES. - East Pendleton Overcrossing, Southeast Court Avenue between Southeast Tenth & Southeast Fifteenth Streets, Pendleton Highway (U.S. Route 30), Pendleton, Umatilla County, OR

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 42. DETAIL OF TRIPLE WINDOW ELEMENT WITH DECORATIVE BRICK SURROUND, ...

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

    42. DETAIL OF TRIPLE WINDOW ELEMENT WITH DECORATIVE BRICK SURROUND, ON EAST SIDE OF 1931 SECTION, TAKEN FROM THE EAST. - James Russell Lowell Elementary School, 4501 Crittenden Drive, Louisville, Jefferson County, KY

  17. Detail view of the decorative element at the peak of ...

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

    Detail view of the decorative element at the peak of the gabled dormer of the northwest corner bay of the west façade - Oregon State Fairgrounds Grandstand, 2330 Seventeenth Avenue, Northeast, Salem, Marion, OR

  18. 36. DETAIL OF WINDOW ELEMENT WITH DECORATIVE BRICK PATTERN ON ...

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

    36. DETAIL OF WINDOW ELEMENT WITH DECORATIVE BRICK PATTERN ON MAIN FRONT OF 1931 SECTION, TAKEN FROM THE NORTH. - James Russell Lowell Elementary School, 4501 Crittenden Drive, Louisville, Jefferson County, KY

  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. 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

  1. VIEW OF EUREKA NO. 36 HOUSING. YARD AND GARDEN DECORATED ...

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

    VIEW OF EUREKA NO. 36 HOUSING. YARD AND GARDEN DECORATED FOR EASTER, REFLECTING AN ATTEMPT TO BEAUTIFY HOMES. HILL IN BACKGROUND IS A REPLANTED BONEY PILE. - Town of Eureka No. 36, Northeast of Windber, Windber, Somerset County, PA

  2. '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 ...

  3. 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

  4. 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

  5. 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

  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 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. The use of lasers for decorative tattoo removal.

    PubMed

    Mariwalla, K; Dover, J S

    2006-06-01

    As the incidence of tattoo placement continues to increase, so does the demand for tattoo removal, with more than 10 million people in the US alone with a tattoo. Used in an appropriate clinical setting, Q-switched lasers provide relatively efficacious clearance of decorative tattoo pigment with minimal side-effects. We present our clinical experience along with literature findings on decorative tattoo removal and the important issues practitioners should consider in the management of tattoos.

  15. Hormonal contraception and platelet function.

    PubMed

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

    1995-05-15

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

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. Self-assessment of attractiveness of persons with body decoration.

    PubMed

    Kozieł, S; Sitek, A

    2013-08-01

    Tattoos and body piercing are forms of body decoration that have been known for ages. The use of such ornamentation is becoming more and more common. Researchers attempt to explain the meaning of this phenomenon within the discipline of behavioural ecology, attributing a sexual selection aspect to body decoration, and thus interpreting it in an evolutionary sense. The hypothesis that superior biological quality of individuals is indicated by body modification is becoming more and more popular. In the present study, this hypothesis is tested on the basis of physical attractiveness as an indicator of genotype quality. The total of 64 males and 52 females with tattoos and body piercings were subjected to tests consisting of the self-assessment of the attractiveness of their bodies. The control group comprised 86 subjects (38 males and 48 females) without body decoration. The results confirm that both women and men with body decoration assess the attractiveness of different parts of their bodies higher (regardless whether the decoration is located there or not) than people without tattoos and body piercing. Thus, the hypothesis has been confirmed that body decoration is a signal of superior biological quality of individuals. Copyright © 2013 Elsevier GmbH. All rights reserved.

  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. Effects of Prostacyclin, Indomethacin, and Heparin on Cerebral Blood Flow and Platelet Adhesion After Multifocal Ischemia of Canine Brain

    DTIC Science & Technology

    1988-06-01

    VIII-von Willebrand factor bound to the subendothelium. Paf-acether antagonists in experimental arterial thrombosis Nature 1979;279:636-638...hypothesis that ie salutary effect of treatment on recovery of neuronal function and cerebral blood flow ( CB1 $)after ischemla Is coupled to the inhibition of...aggregating agents. Br J Haemtatol 19M0~46: Platelet activating factor receptor blockade enhances recovery 455-46 after multifocal brain ischemia. Life Sci

  3. Inherited platelet disorders and oral health.

    PubMed

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

    2013-02-01

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

  4. 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.

  5. Fibrinogen-independent platelet adhesion and thrombus formation on subendothelium mediated by glycoprotein IIb-IIIa complex at high shear rate.

    PubMed Central

    Weiss, H J; Hawiger, J; Ruggeri, Z M; Turitto, V T; Thiagarajan, P; Hoffmann, T

    1989-01-01

    Platelet adhesion and thrombus formation on subendothelium, studied at a shear rate of 2,600 s-1, were inhibited by two synthetic peptides known to interact with GPIIb-IIIa. One peptide (HHLGGAKQAGDV) corresponds to the carboxyl terminal segment of the fibrinogen gamma-chain (gamma 400-411) and the other (RGDS) contains the amino acid sequence Arg-Gly-Asp (RGD) common to fibronectin, von Willebrand factor, vitronectin and the alpha-chain of fibrinogen. Neither platelet adhesion nor thrombus formation were decreased in a patient with severe congenital fibrinogen deficiency and this was equally true when his blood was further depleted of the small amounts of fibrinogen present utilizing an anti-fibrinogen antibody. In normal subjects, adhesion and thrombus formation were inhibited by the Fab' fragments of a monoclonal anti-GPIIb-IIIa antibody (LJ-CP8), which interferes with the interaction of platelets with all four adhesive proteins in both the fluid and solid phase. However, another anti-GPIIb-IIIa antibody (LJ-P5) that had minimal effects on the interaction of platelets with fibrinogen, but inhibited to varying degrees platelet interaction with other adhesive proteins, was equally effective. The findings demonstrate that, at a shear rate of 2,600 s-1, adhesive proteins other than fibrinogen are involved in GPIIb-IIIa-mediated platelet adhesion and thrombus formation on subendothelium. In addition, since LJ-P5 inhibited the binding of soluble von Willebrand factor and vitronectin, these adhesive proteins may be involved in platelet thrombus formation. In contrast to the results obtained at a shear rate of 2,600 s-1, fibrinogen could play a role in mediating platelet-platelet interactions with weak agonists or lower shear rates. PMID:2910912

  6. 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

  7. 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.

  8. 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.

  9. 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.

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

    PubMed

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

    2006-03-01

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

  11. 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

  12. Platelets interact with tissue factor immobilized on surfaces: effects of shear rate.

    PubMed

    Tonda, R; Lopez-Vilchez, I; Navalon, F; Pino, M; Hernandez, M R; Escolar, G; Galan, A M

    2008-01-01

    While procoagulant activities of Tissue Factor (TF) have been widely investigated, its possible pro-adhesive properties towards platelets have not been studied in detail. We explored the interaction of platelets with human Tissue Factor (hTF) firmly adsorbed on a synthetic surface of polyvinilidene difluoride (PVDF) using different shear rates. For studies at 250 and 600 s(-1), TF firmly adsorbed was exposed to flowing anticoagulated blood in flat perfusion devices. Deposition of platelets and fibrin were evaluated by morphometric, immunocytochemical and ultrastructural methods. Prothrombin fragment 1 + 2 (F1 + 2) levels were also measured. Experiments at 5000 s(-1), were performed on the Platelet Function Analyzer (PFA-100) with experimental cartridges with collagen (COL) or collagen-hTF (COL + TF). Haemostatic effect of recombinant activated FVIIa (rFVIIa) was assessed in the same experimental settings. Platelet deposition on hTF reached 19.8 +/- 1.3% and 26.1 +/- 3.4% of the total surface, at 250 and 600 s(-1), respectively. Fibrin formation was significantly higher at 250 s(-1) than at 600 s(-1) (P < 0.05). The addition of rFVIIa did not influence platelet deposition but raised fibrin formation and thrombin generation at both shear rates (P < 0.05). At 5000 s(-1), closure times (CT) in the PFA-100 were significantly shortened in the presence of hTF (154.09 +/- 14.69 s vs. 191.45 +/- 16.09 s COL alone; P < 0.05). Addition of rFVIIa did not cause a further reduction of CT. Our studies demonstrate that hTF is an adhesive substrate for platelets and suggest that the von Willebrand factor could mediate these interactions. At low and intermediate shear rates, rFVIIa enhanced the procoagulant action of hTF, but this effect was not observed at very high shear rates.

  13. 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.

  14. Direct observation of von Willebrand factor elongation and fiber formation on collagen during acute whole blood exposure to pathological flow.

    PubMed

    Colace, Thomas V; Diamond, Scott L

    2013-01-01

    In severe stenosis, von Willebrand factor (vWF) experiences millisecond exposures to pathological wall shear rates (γ(w)). We sought to evaluate the deposition of vWF onto collagen surfaces under flow in these environments. Distinct from viscometry experiments that last many seconds, we deployed microfluidic devices for single-pass perfusion of whole blood or platelet-free plasma over fibrillar type 1 collagen (<50 ms transit time) at pathological γ(w) or spatial wall shear rate gradients (grad γ(w)). Using fluorescent anti-vWF, long thick vWF fibers (>20 μm) bound to collagen were visualized at constant γ(w)>30000 s(-1) during perfusion of platelet-free plasma, a process enhanced by EDTA. Rapid acceleration or deceleration of EDTA platelet-free plasma at grad γ(w)=±1.1×10(5) to ±4.3×10(7) s(-1)/cm did not promote vWF deposition. At 19400 s(-1), EDTA blood perfusion resulted in rolling vWF-platelet nets, although blood perfusion (normal Ca(2+)) generated large vWF/platelet deposits that repeatedly embolized and were blocked by anti-glycoprotein Ib or the α(IIb)β(3) inhibitor GR144053 and did not require grad γ(w). Blood perfusion at venous shear rate (200 s(-1)) produced a stable platelet deposit that was a substrate for massive but unstable vWF-platelet aggregates when flow was increased to 7800 s(-1). Triggered by collagen and enhanced by platelet glycoprotein Ib and α(IIb)β(3), vWF fiber formation occurred during acute exposures to pathological γ(w) and did not require gradients in wall shear rate.

  15. 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

  16. [Platelet-washing solution optimization].

    PubMed

    Grossin, E; Chamfly, V

    2005-10-01

    Different washing and homogénéisation solutions are hereby analysed by comparing the evolution of functional indicators during the preservation of washed aphaeresis platelet concentrates: physiological pH 4.5 and 6 solutions, buffered physiological pH 6.8 glucose solution, and two physiological pH 7 citrate solutions with acetate. Prior acidification of platelet concentrates proved to be essential. Two washings with manual or automated technique, guarantee residual proteins at a level of less than 0.5 g. Solutions T-Sol Baxter or SSP Macopharma allow us to obtain a product that meet the PSL specifications. Routine since June 2004, washings are done with a physiological pH 6 solution, then homogeneised with T-Sol solution. Platelet recovery, swirling phenomenon, lack of agrgegates, pH maintenance, low increase in the platelet average volume and maintenance of intra-cell potassium level, suggest that platelet entirety is preserved beyond the product's expiration date. The platelet transfusion yield of these products is satisfactory.

  17. 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.

  18. 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

  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. Phallic decoration in paleolithic art: genital scarification, piercing and tattoos.

    PubMed

    Angulo, Javier C; García-Díez, Marcos; Martínez, Marc

    2011-12-01

    The primitive anthropological meaning of genital ornamentation is not clearly defined and the origin of penile intervention for decorative purposes is lost in time. Corporeal decoration was practiced in the Upper Paleolithic period. We discuss the existing evidence on the practice of phallic piercing, scarring and tattooing in prehistory. We studied the archaeological and artistic evidence regarding explicit genital male representations in portable art made in Europe approximately 38,000 to 11,000 years ago with special emphasis on decorations suggesting genital ornamentation. Archaeological evidence that has survived to our day includes 42 phallic pieces, of which 30 (71.4%) show intentional marks to a different extent with a probable decorative purpose. Of these ornamental elements 18 (60%) were recovered from the upper Magdalenian period (11,000 to 12,700 years ago) in France and Spain, and 23 (76.7%) belong to the category of perforated batons. Decorations show lines (70% of objects), plaques (26.7%), dots/holes (23.3%) or even human/animal forms (13.3%). These designs most probably represent skin scarification, cutting, piercing and tattooing. Notably there are some technical similarities between the motifs represented and some designs present in symbolic cave wall art. This evidence may show the anthropological origin of current male genital piercing and tattooing. European Paleolithic art shows decoration explicitly represented in a high proportion of portable art objects with a phallic form that have survived to our day. Decorative rituals of male genital tattooing, piercing and scarification may have been practiced during Paleolithic times. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  1. 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.

  2. 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.

  3. 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. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  4. Platelets: essential components of the immune system

    PubMed Central

    Ali, Ramadan A.; Wuescher, Leah M.; Worth, Randall G.

    2016-01-01

    Platelets are anucleate cell fragments known for their central role in coagulation and vascular integrity. However, it is becoming increasingly clear that platelets contribute to diverse immunological processes extending beyond the traditional view of platelets as fragmentary mediators of hemostasis and thrombosis. There is recent evidence that platelets participate in: 1) intervention against microbial threats; 2) recruitment and promotion of innate effector cell functions; 3) modulating antigen presentation; and 4) enhancement of adaptive immune responses. In this way, platelets should be viewed as the underappreciated orchestrator of the immune system. This review will discuss recent and historical evidence regarding how platelets influence both innate and adaptive immune responses. PMID:27818580

  5. 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.

  6. 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.

  7. Reduced expression of platelet surface glycoprotein receptor IIb/IIIa at hyperthermic temperatures.

    PubMed

    Pasha, R; Benavides, M; Kottke-Marchant, K; Harasaki, H

    1995-09-01

    Hyperthermic temperatures exist from the heat dissipation of the implantable energy source of an artificial heart. This procedure as well as therapies for cancer and thermal injuries pose a new medical problem. Among many reported effects of heat on biologic systems, platelet functions such as maximal aggregation and adhesion are known to be reduced. Using flow cytometry, we have studied platelet dysfunction at elevated temperatures and have gained a mechanistic comprehension of the loss of platelet function. Platelet rich plasma was incubated at differing temperatures for 1 hour. Immediately after, the platelets were stained using mAb against glycoprotein IIb/IIIa (GPIIb-IIIa) (CD41a) and other platelet surface glycoproteins (GP) involved in aggregation and adhesion. Relative fluorescence intensity was measured using single-labeled, laser flow cytometry to determine changes in GP surface expression. In addition, scanning electron microscopy was used to evaluate morphologic changes. Hyperthermic temperatures between 40 and 44 degrees C significantly lowered the mAb cell surface binding in vitro of GP that participate in aggregation and adhesion. The most dramatic temperature-dependent loss of mAb binding was demonstrated by anti-GPIIb-IIIa, the mAb against the fibrinogen receptor. mAb binding to this receptor at 44 degrees C was decreased to 6.2% of a base-line fluorescence intensity of 654 (arbitrary units). The ADP-induced aggregation of platelets incubated at the same temperature also decreased to 2.1% of maximum aggregation. Other mAb, such as those against the von Willebrand factor receptor (GPIb) (CD42b), the thrombospondin receptor (GPIV) (CD36), and GPIIIa (CD61), also showed statistically significant reduction of mAb binding but to a lesser degree. Finally, scanning electron microscopy as well as side-scatter density plots from flow cytometry revealed that platelets became more spherical after incubation at 44 degrees C. The significant reduction in m

  8. Current management of von Willebrand disease and von Willebrand syndrome.

    PubMed

    Stone, Marc E; Mazzeffi, Michael; Derham, Jeffrey; Korshin, Andre

    2014-06-01

    Anesthesiologists frequently care for patients with altered hemostasis and coagulation. Where a clear history of familial and personal bleeding exists, a thoughtful plan can be developed in advance to manage the issue perioperatively. However, in some cases, it may not be known that the patient has a disorder until excessive bleeding is noted during or after surgery. Recognition of the issue and appropriate targeted therapy are the keys to successful management. With an estimated prevalence approaching 1% of the population, von Willebrand disease (vWD) is the most common hereditary bleeding diathesis, but the estimated prevalence of acquired vWD (often termed von Willebrand syndrome or vWS) is now believed to be significantly higher, especially in patients with malignancies, autoimmune diseases, cardiac valvular lesions, and in patients on mechanical circulatory support devices. Acquired vWD may also occur with certain medications. The mainstay of the diagnosis of vWD is laboratory testing. Preoperative clinical assessment and a high level of suspicion are often effective to alert the anesthesiologist to the possibility of vWS, thus allowing for appropriate testing and potential prophylaxis in elective situations, as well as appropriately targeted therapy of unexpected bleeding when a hemostatic derangement was not anticipated preoperatively.

  9. Von Karman Streets Chaotic Simulation

    NASA Astrophysics Data System (ADS)

    Skiadas, C. H.

    In this paper we model and simulate the so-called Von Karman Streets, a characteristic form of turbulent (vortex) flow that appears in small or large systems. Very interesting examples are the large turbulent formations in the sea or in the clouds that have been viewed and photographed from the space (from satellites). The modeling approach is based on the Rotation-Reflection-Translation theory developed in the recent book [1]. The related theory was already applied in various fields and especially in flows.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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...

  7. 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...

  8. 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...

  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. Decoration of heparin and bovine serum albumin on polysulfone membrane assisted via polydopamine strategy for hemodialysis.

    PubMed

    Xie, Bingwu; Zhang, Ranran; Zhang, Huan; Xu, Anxiu; Deng, Yi; Lv, Yalin; Deng, Feng; Wei, Shicheng

    2016-06-01

    Renal failure brings about abnormality of waste and toxins and deposition in the body. In clinic, the waste and toxins in vitro are eliminated by hemodialysis device with polysulfone (PSF) porous membranes. In the work, decoration of heparin (Hep) and bovine serum albumin (BSA) on PSF membranes would be beneficial to improve the hemocompatibility and reduce the anaphylatoxin formation during hemodialysis. The PSF porous membranes are surface-modified by simply dipping them into dopamine aqueous solution for 8 h. Then, Hep and BSA are immobilized covalently onto the resultant membrane. Attenuated total reflectance Fourier transform infrared spectra (ATR-FTIR) confirms that Hep and BSA are successfully introduced onto the surface of PSF membranes. Scanning electronic microscopy (SEM) and atomic force microscopy (AFM) display the changes of surface morphologies after modification. The result of water contact angle measurement shows that the hydrophilicity of PSF membranes is remarkably improved after coating polydopamine (pDA) and binding Hep and BSA. The experiments of hemocompatibility indicate that Hep and BSA grafted onto membranes suppress the adhesion of platelet and enhance the anticoagulation ability of PSF membranes. Furthermore, the protein adsorption tests reveal that Hep and BSA immobilized onto membranes depress the protein absorption and develop antifouling-protein ability of pristine membrane. This study proves a convenient and simple approach to graft two functional organic polymers which, respectively, play a vital role and then improve the hemocompatibility and biocompatibility of PSF membranes for their biomedical and blood-contacting applications.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. [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

  18. EXTENDED STORAGE OF PLATELET-RICH PLASMA PREPARED PLATELET CONCENTRATES IN PLASMA OR PLASMALYTE

    PubMed Central

    Slichter, Sherrill J.; Bolgiano, Doug; Corson, Jill; Jones, Mary Kay; Christoffel, Todd

    2010-01-01

    Background Using bacterial detection or pathogen reduction, extended platelet storage may be licensed if platelet viability is maintained. FDA's post-storage platelet acceptance guidelines are that autologous stored platelet recoveries and survivals should be ≥66% and ≥58%, respectively, of each donor's fresh platelet data. Study Design And Methods Non-leukoreduced platelet concentrates were prepared from whole blood donations. Autologous platelet concentrates from 62 subjects were stored in 100% plasma (n=44) or 20% plasma/80% Plasmalyte (n=18), an acetate based, non-glucose containing crystalloid solution previously used for platelet storage.(1-3) Fresh platelets were obtained on the day the donor's stored platelets were to be transfused. The fresh and stored platelets were alternately radiolabeled with either 51Chromium or 111Indium, and in vitro measurements were performed on the stored platelets. Results FDA's platelet recovery criterion was met for 7 days of plasma storage, but platelet survivals maintained viability for only 6 days. Plasmalyte stored platelets did not meet either acceptance criteria after 6 days of storage. After 7 days of storage, platelet recoveries averaged 43 ± 4% and 30 ± 4% and survivals 4.1 ± 0.4 days and 2.0 ± 0.2 days for plasma and Plasmalyte-stored platelets, respectively (p=0.03 for recoveries and p<0.001 for survivals). Post-storage platelet recoveries correlated with the commonly-used in vitro platelet quality measurements of HSR and Annexin V binding, while survivals correlated with ESC, morphology score, and pH. Conclusion There is a progressive decrease in recoveries and survivals of plasma stored platelets over time. Platelet viability is better maintained in plasma than Plasmalyte. PMID:20456703

  19. 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.

  20. Enhanced hydrogen storage by using lithium decoration on phosphorene

    SciTech Connect

    Yu, Zhiyuan; Wan, Neng E-mail: lsy@seu.edu.cn; Lei, Shuangying E-mail: lsy@seu.edu.cn; Yu, Hong

    2016-07-14

    The hydrogen storage characteristics of Li decorated phosphorene were systematically investigated based on first-principle density functional theory. It is revealed that the adsorption of H{sub 2} on pristine phosphorene is relatively weak with an adsorption energy of 0.06 eV. While this value can be dramatically enhanced to ∼0.2 eV after the phosphorene was decorated by Li, and each Li atom can adsorb up to three H{sub 2} molecules. The detailed mechanism of the enhanced hydrogen storage was discussed based on our density functional theory calculations. Our studies give a conservative prediction of hydrogen storage capacity to be 4.4 wt. % through Li decoration on pristine phosphorene. By comparing our calculations to the present molecular dynamic simulation results, we expect our adsorption system is stable under room temperature and hydrogen can be released after moderate heating.