Academic literature on the topic 'Platelets'
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Journal articles on the topic "Platelets"
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Beaulieu, Lea, Kahraman Tanriverdi, Jane Freedman, and Lauren Clancy. "The role of RNA uptake in platelet heterogeneity." Thrombosis and Haemostasis 117, no. 05 (2017): 948–61. http://dx.doi.org/10.1160/th16-11-0873.
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SummaryThe role of platelets in regulating vascular homeostasis has expanded beyond mediation of haemostasis and thrombosis. The discovery of platelet RNA and the presence of subpopulations of platelets containing varying amounts of RNA suggest a role for platelet transcripts in vascular function. As the RNA in anucleated platelets is biologically functional and may transfer to other vascular cells, we hypothesised that platelet RNA diminishes over the lifespan of the platelet with diminishing platelet size due to horizontal cellular transfer. The purpose of this study is to determine if platelet RNA variance is the result of horizontal cellular transfer between platelets and other vascular cells. Utilising platelet sorting and RNA sequencing, we found that smaller platelets contained a more diverse set of transcripts than larger platelets. Further investigation using fluorescence imaging, gene expression analyses and in vitro and in vivo modelling revealed that platelets take up RNA from other vascular cells in a complex manner, revealing a dynamic role for platelets in modulating vascular homeostasis through bidirectional RNA transfer. The resultant RNA profile heterogeneity suggests unique functional roles for platelets dependent on size and complexity. This study expands our basic understanding of platelet function and heterogeneity and is the first to evaluate endogenous vascular RNA uptake and its relation to platelet processes. Our findings describe a novel endogenous phenomenon that can help elucidate the platelet’s role in these non-thrombotic and haemostatic fields, as well as present potential for diagnostic and therapeutic development.Supplementary Material to this article is available online at www.thrombosis-online.com.
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Franco, Aime T., Adam Corken, and Jerry Ware. "Platelets at the interface of thrombosis, inflammation, and cancer." Blood 126, no. 5 (July 30, 2015): 582–88. http://dx.doi.org/10.1182/blood-2014-08-531582.
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Abstract Although once primarily recognized for its roles in hemostasis and thrombosis, the platelet has been increasingly recognized as a multipurpose cell. Indeed, circulating platelets have the ability to influence a wide range of seemingly unrelated pathophysiologic events. Here, we highlight some of the notable observations that link platelets to inflammation, reinforcing the platelet’s origin from a lower vertebrate cell type with both hemostatic and immunologic roles. In addition, we consider the relevance of platelets in cancer biology by focusing on the hallmarks of cancer and the ways platelets can influence multistep development of tumors. Beyond its traditional role in hemostasis and thrombosis, the platelet’s involvement in the interplay between hemostasis, thrombosis, inflammation, and cancer is likely complex, yet extremely important in each disease process. The existence of animal models of platelet dysfunction and currently used antiplatelet therapies provide a framework for understanding mechanistic insights into a wide range of pathophysiologic events. Thus, the basic scientist studying platelet function can think beyond the traditional hemostasis and thrombosis paradigms, while the practicing hematologist must appreciate platelet relevance in a wide range of disease processes.
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Krisch, Linda, Gabriele Brachtl, Sarah Hochmann, André Cronemberger Andrade, Michaela Oeller, Patricia Ebner-Peking, Katharina Schallmoser, and Dirk Strunk. "Improving Human Induced Pluripotent Stem Cell-Derived Megakaryocyte Differentiation and Platelet Production." International Journal of Molecular Sciences 22, no. 15 (July 30, 2021): 8224. http://dx.doi.org/10.3390/ijms22158224.
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Several protocols exist for generating megakaryocytes (MKs) and platelets from human induced pluripotent stem cells (hiPSCs) with limited efficiency. We observed previously that mesoderm induction improved endothelial and stromal differentiation. We, therefore, hypothesized that a protocol modification prior to hemogenic endothelial cell (HEC) differentiation will improve MK progenitor (MKP) production and increase platelet output. We further asked if basic media composition affects MK maturation. In an iterative process, we first compared two HEC induction protocols. We found significantly more HECs using the modified protocol including activin A and CHIR99021, resulting in significantly increased MKs. MKs released comparable platelet amounts irrespective of media conditions. In a final validation phase, we obtained five-fold more platelets per hiPSC with the modified protocol (235 ± 84) compared to standard conditions (51 ± 15; p < 0.0001). The regenerative potency of hiPSC-derived platelets was compared to adult donor-derived platelets by profiling angiogenesis-related protein expression. Nineteen of 24 angiogenesis-related proteins were expressed equally, lower or higher in hiPSC-derived compared to adult platelets. The hiPSC-platelet’s coagulation hyporeactivity compared to adult platelets was confirmed by thromboelastometry. Further stepwise improvement of hiPSC-platelet production will, thus, permit better identification of platelet-mediated regenerative mechanisms and facilitate manufacture of sufficient amounts of functional platelets for clinical application.
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Campbell, Robert A., Thomas H. Fischer, and Alisa S. Wolberg. "Rehydrated, Lyophilized Platelets Generate Thrombin in the Presence of Recombinant Factor VIIa." Blood 106, no. 11 (November 16, 2005): 4057. http://dx.doi.org/10.1182/blood.v106.11.4057.4057.
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Abstract The anti-bleeding therapy, recombinant factor VIIa (rFVIIa), is thought to bind to the platelet’s surface and increase thrombin generation in hemophilia. However, high plasma levels of rFVIIa are required, in part, due to the weak binding of rFVIIa to platelets. We hypothesized that the efficacy of the therapy could be improved by administering rFVIIa already bound to platelets. A recently described protocol involving pretreatment of platelets with paraformaldehyde permits platelets to be lyophilized while preserving many platelet functions. Such platelets could be used for binding rFVIIa ex vivo and then administered to hemophilic patients during a bleeding event. In this study, we have characterized the ability of reconstituted, lyophilized (RL) platelets to support thrombin generation under normal and hemophilic conditions and in the presence of rFVIIa. First, freshly-isolated (control) or RL platelets were incubated with factors IXa, VIII(a), X, V and II in the presence of 3 mM CaCl2 and assayed for thrombin generation. In these assays, both freshly-isolated and RL platelets supported thrombin generation (1.15x10−4 +/− 5.37x10−5 mOD/min2/platelet and 8.46x10−3 +/− 4.78x10−3 mOD/min2/platelet, respectively). In the absence of factor IX (hemophilia B), thrombin generation was significantly reduced on both freshly-isolated and RL platelets (4.19x10−6 +/− 4.50x10−6 mOD/min2/platelet and 8.25x10−4 +/− 1.13x10−6 mOD/min2/platelet, respectively). Interestingly, RL platelets supported 10 – 100-fold higher thrombin generation rates than fresh thrombin-activated platelets. Second, we examined the activity of rFVIIa on RL platelets in the absence of factors IX and VIII. RFVIIa increased thrombin generation on RL platelets in a rFVIIa-concentration dependent manner (between 1nM and 150nM), similar to that seen when using fresh platelets. An inhibitory anti-tissue factor (TF) antibody did not affect rFVIIa-mediated thrombin generation on RL platelets, indicating that the activity of rFVIIa on RL platelets is independent of TF. Finally, we examined the effect of different platelet agonists (thrombin, convulxin, and A23187) on fresh and RL platelets. When fresh platelets are stimulated with A23187 or co-stimulated with thrombin and convulxin, they become more procoagulant than platelets activated with thrombin alone. However, stimulation of RL platelets with A23187 or co-stimulation with thrombin and convulxin did not increase thrombin generation versus thrombin alone. RL platelets stimulated with thrombin, alone, had 3.1-fold higher activity than thrombin- and convulxin-costimulated fresh platelets, but 1.4-fold lower activity than A23187-stimulated fresh platelets. These data suggest that RL platelets are in a maximally active state prior to the addition of platelet agonists. We conclude that RL platelets are procoagulant and can support rFVIIa-mediated thrombin generation in the absence of factor IX. We hypothesize that co-administration of RL platelets with rFVIIa may increase the efficacy of rFVIIa treatment.
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Yang, Linlin, Roger Ottenheijm, Paul Worley, Marc Freichel, and Juan E. Camacho Londoño. "Reduction in SOCE and Associated Aggregation in Platelets from Mice with Platelet-Specific Deletion of Orai1." Cells 11, no. 20 (October 14, 2022): 3225. http://dx.doi.org/10.3390/cells11203225.
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Calcium signalling in platelets through store operated Ca2+ entry (SOCE) or receptor-operated Ca2+ entry (ROCE) mechanisms is crucial for platelet activation and function. Orai1 proteins have been implicated in platelet’s SOCE. In this study we evaluated the contribution of Orai1 proteins to these processes using washed platelets from adult mice from both genders with platelet-specific deletion of the Orai1 gene (Orai1flox/flox; Pf4-Cre termed as Orai1Plt-KO) since mice with ubiquitous Orai1 deficiency show early lethality. Platelet aggregation as well as Ca2+ entry and release were measured in vitro following stimulation with collagen, collagen related peptide (CRP), thromboxane A2 analogue U46619, thrombin, ADP and the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor thapsigargin, respectively. SOCE and aggregation induced by Thapsigargin up to a concentration of 0.3 µM was abrogated in Orai1-deficient platelets. Receptor-operated Ca2+-entry and/or platelet aggregation induced by CRP, U46619 or thrombin were partially affected by Orai1 deletion depending on the gender. In contrast, ADP-, collagen- and CRP-induced aggregation was comparable in Orai1Plt-KO platelets and control cells over the entire concentration range. Our results reinforce the indispensability of Orai1 proteins for SOCE in murine platelets, contribute to understand its role in agonist-dependent signalling and emphasize the importance to analyse platelets from both genders.
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Crawford, N., A. Chajara, G. Pfliegler, B. EI Gamal, L. Brewer, and L. Capron. "Targeting Platelets Containing Electro-encapsulated lloprost to Balloon Injured Aorta in Rats." Thrombosis and Haemostasis 73, no. 03 (1995): 535–42. http://dx.doi.org/10.1055/s-0038-1653809.
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SummaryDrugs can be electro-encapsulated within platelets and targeted to damaged blood vessels by exploiting the platelet’s natural haemostatic properties to adhere to collagen and other vessel wall constituents revealed by injury. A rat aorta balloon angioplasty model has been used to study the effect on platelet deposition of giving iloprost loaded platelets i.v. during the balloon injury. After labelling the circulating platelets with 111-Indium before balloon injury, time course studies showed maximum platelet deposition on the injured aorta occurred at about 1 h post-injury and the deposition remained stable over the next 2-3 h. When iloprost-loaded platelets were given i.v. during injury and the circulating platelet pool labelled with 111-Indium 30 min later, platelet deposition, measured at 2 h postinjury, was substantially and significantly reduced compared with control platelet treatment. Some antiproliferative effects of iloprost-loaded platelets given i.v. during injury have also been observed. Whereas the incorporation of [3H]-thymidine into aorta intima-media DNA at 3 days post injury was 62-fold higher in balloon injured rats than in control sham operated rats, thymidine incorporation into intima/media of rats which had received iloprost loaded platelets during injury was reduced as compared with rats subjected only to the injury procedure. The reduction was only of near significance, however, but at 14 days after injury the total DNA content of the aorta intima/media of rats given iloprost loaded platelets during injury was significantly reduced. Although iloprost loaded platelets can clearly inhibit excessive platelet deposition, other encapsulated agents may have greater anti-proliferative effects. These studies have shown that drug loaded platelets can be targeted to injured arteries, where they may be retained as depots for local release. We believe this novel drug delivery protocol may have therapeutic potential in reducing the incidence of occlusion and restenosis after angioplasty and thrombolysis treatment. Electro-encapsulation of drugs into platelets is a simple procedure and, using autologous and fully biocompatible and biodegradable platelets as delivery vehicles, might overcome some of the immunological and toxicological problems which have been encountered with other delivery vectors such as liposomes, microbeads, synthetic microcapsules and antibodies.
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Battinelli, Elisabeth M. "Platelet and Megakaryocytic Regulation of Tumor Progression." Blood 130, Suppl_1 (December 7, 2017): SCI—26—SCI—26. http://dx.doi.org/10.1182/blood.v130.suppl_1.sci-26.sci-26.
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Traditionally viewed as the bandaids of the blood, the contribution of platelets to the progression of malignancy is emerging as a compelling focus for therapeutic intervention. Complex interactions between tumor cells, and circulating platelets play an important role in tumor growth and dissemination, and a growing body of data supports a role for platelet activation and release of chemokines in metastases and neovascularization. Supporting this concept is the evidence that elevated platelet counts (thrombocytosis) at time of diagnosis with malignancy is a harbinger of an aggressive cancer with a poor prognosis. One very interesting and provocative connection between cancer and platelets is the increasing evidence that tumor cells hijack platelets to promote a more pro-malignant phenotype to drive disease progression. Our laboratories have been instrumental in establishing the pro-malignant role of platelets in metastasis and neovascularization. We have demonstrated that tumor cells can instruct platelets to release key cytokines that promote angiogenesis and metastasis of tumor cells. Perhaps the most compelling clinical evidence of the link between platelets and malignancy is the finding that anti-platelet agents can have a profound impact on malignancy. We have demonstrated previously, anti-platelet agents such as aspirin and anticoagulants suppress release of key neovascularization factors from platelets and suppress the neovascularization potential. Aspirin also suppresses the invasive properties of platelets in mouse metastasis models as well as in vitro metastasis assays. Similarly, we have also demonstrated that tamoxifen, a selective estrogen receptor modulator often used to treat breast cancer, can also diminish the ability of platelets to support malignancy by diminishing the platelet's role in promoting neovascularization as well as metastasis. Although much is understood regarding how tumors communicate with platelets less is understood about how platelets manipulate tumor cells. Our laboratory has elucidated the role of key chemokines released from platelets in response to tumor cells and how these factors promote tumor growth and metastasis. We have recently discovered that tumor cells can instruct platelets to release CCL5, a known driver of tumor cell invasion and metastasis, and have expanded the role of CCL5 not only as a regulator of metastasis but also as a central controller of platelet production. Despite this progress many questions still remain regarding the interaction between tumor cells and platelets. We are particularly interested in how tumor cells instruct megakaryocytes to increase platelet production. In addition malignancy may also reprogram megakaryocytes thereby manipulating the platelet phenotype to support tumor growth and metastasis. Because most cancer therapies focus on the tumor itself, the idea of targeting platelets in the tumor microenvironment to arrest tumor growth and metastatic spread represents a novel therapeutic strategy. Disclosures No relevant conflicts of interest to declare.
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Puricelli, Chiara, Elena Boggio, Casimiro Luca Gigliotti, Ian Stoppa, Salvatore Sutti, Mara Giordano, Umberto Dianzani, and Roberta Rolla. "Platelets, Protean Cells with All-Around Functions and Multifaceted Pharmacological Applications." International Journal of Molecular Sciences 24, no. 5 (February 26, 2023): 4565. http://dx.doi.org/10.3390/ijms24054565.
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Platelets, traditionally known for their roles in hemostasis and coagulation, are the most prevalent blood component after erythrocytes (150,000–400,000 platelets/μL in healthy humans). However, only 10,000 platelets/μL are needed for vessel wall repair and wound healing. Increased knowledge of the platelet’s role in hemostasis has led to many advances in understanding that they are crucial mediators in many other physiological processes, such as innate and adaptive immunity. Due to their multiple functions, platelet dysfunction is involved not only in thrombosis, mediating myocardial infarction, stroke, and venous thromboembolism, but also in several other disorders, such as tumors, autoimmune diseases, and neurodegenerative diseases. On the other hand, thanks to their multiple functions, nowadays platelets are therapeutic targets in different pathologies, in addition to atherothrombotic diseases; they can be used as an innovative drug delivery system, and their derivatives, such as platelet lysates and platelet extracellular vesicles (pEVs), can be useful in regenerative medicine and many other fields. The protean role of platelets, from the name of Proteus, a Greek mythological divinity who could take on different shapes or aspects, is precisely the focus of this review.
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SANTORO, S. A. "Platelets: Platelet Immunobiology." Science 245, no. 4915 (July 21, 1989): 314–15. http://dx.doi.org/10.1126/science.245.4915.314.
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Cheepala, Satish B., Kazumasa Takenaka, Tamara I. Pestina, Carl W. Jackson, and John D. Schuetz. "The Role of ABC Transporter Abcc4 in Platelets Physiologic Function and Its Impact On Collagen Meditated Platelet Aggregation." Blood 120, no. 21 (November 16, 2012): 1063. http://dx.doi.org/10.1182/blood.v120.21.1063.1063.
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Abstract Abstract 1063 Platelet activation is a highly regulated process, and cyclic nucleotide mediated signaling pathways are crucial to effective platelet activation. Vascular injury produces, exposed collagen which binds circulating platelets through the platelet's “collagen” receptor, GPVI, resulting in the activation of guanyly/adenlyl cyclases. These interactions result in the rapid alterations in the cyclic nucleotide concentration inside the platelets leading to activation of protein kinase A and G signaling pathways to modulate platelet function. While, ABCC4 functions as a plasma membrane transporter for cyclic nucleotides its contribution to platelet activation has been obscured because it was reportedly as primarily intracellular in the platelets dense granules. This original report (Jedlitschky, Tirschmann et al. 2004) evaluated ABCC4 localization by immune-fluorescence of platelets attached to collagen coated coverslips. However, attachment via collagen produces platelet activation leading to mobilization and fusion of alpha and dense granules to the plasma membrane, thus under these conditions distinguishing between plasma membrane and dense granules is not possible. We resolved this problem by labeling quiescent platelets with a cell impermeable biotinylating agent (EZ-Link Sulfo-NHS-LC-LC Biotin). Isolation of membrane and internal fraction demonstrated that of over ninety percent of Abcc4 localizes to the plasma membrane. Furthermore, confocal microscopy of platelets stained with specific antibodies against Abcc4 confirmed Abcc4 localization to the plasma membrane. We extended these studies to the Abcc4- knockout (KO) mouse model. The Abcc4- KO mouse does not have any change in the number of platelet or dense granules compared to the wild type mouse. Platelet activation in vivo can be initiated by interaction with collagen through the GPVI receptor that is expressed at the plasma membrane of the platelets. At the molecular level, the initiation of platelet activation by collagen results in an increase in the cyclic nucleotide concentration leading to activation of signaling cascade through protein kinase A or G. Expose of Abcc4-KO platelets to collagen and revealed impaired activation in response to collagen. However, Abcc4-KO platelets activated by either thrombin or ADP (which activate either G-coupled PAR receptors or P2Y12 receptor respectively) shows an aggregation profile almost identical to wildtype platelets, thus indicating the defect in Abcc4 -KO platelet aggregation is specific to the collagen pathway. To understand the basis for the impaired collagen aggregation of Abcc4-KO platelets, we investigated the collagen receptor (GPVI) signaling pathway in Abcc4-KO platelets. Interestingly, in the Abcc4-KO platelets after the platelet activation with collagen, cyclic nucleotide dependent phosphorylation of VASP through protein kinase A or G at Ser-157 or Ser-239 respectively is reduced compared to the wildtype. Notably, Abcc4-KO platelets had reduced GPVI surface expression that correlated with the reduced phosphorylation of VASP after collagen stimulation. The similar, protein levels of Syk and Plcg2, (downstream signaling molecules of GPVI signaling pathway), in the Abcc4 wildtype and KO platelets implies that GPVI expression is the primary defect in Abcc4 deficiency. These results suggest that Abcc4 plays a crucial role in regulating cyclic nucleotides in response to GPVI activation by collagen. These findings suggest ABCC4/Mrp4 loss of function or inhibition (by drugs) may disrupt platelet aggregation under conditions of vascular injury. As, many antiplatelet drugs are potent inhibitors of Abcc4 (e.g., Dipyridamole and Sildenafil) these conclusions have strong implications for not just the development of antiplatelet drugs, but also for further exploring the role of Abcc4 in regulating intracellular nucleotide levels and platelet biology. Disclosures: No relevant conflicts of interest to declare.
Dissertations / Theses on the topic "Platelets"
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MacMillan, L. J. M. "Receptor mechanisms common to platelets and platelet progenitor cells." Thesis, University of Glasgow, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233116.
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Box, Clare Louise. "Interactions between platelets and platelet derived microvesicles in inflamation." Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/5818/.
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Atherosclerosis is a chronic inflammatory disease, characterised by infiltration of leukocytes and accumulation of fatty deposits in the artery wall. Early events in this disease process include recruitment of platelets to the artery wall, which in turn aid in leukocyte recruitment. However, upon activation platelets release microvesicles (PMV), we are interested in whether PMV have a role in enhancing leukocyte recruitment. We demonstrated using whole blood that upon activation, platelets form aggregates with monocytes and neutrophils. The data suggests that upon platelet activation, PMV may be generated and subsequently may have a role in heterotypic aggregate formation observed. Interestingly, lymphocytes did not form aggregates with platelets (or PMV) as readily. We showed that blocking P-selectin leads to a significant reduction in heterotypic aggregate formation. We also demonstrated the presence of P-selectin glycoprotein ligand-1 (PSGL 1), the ligand with the highest binding affinity for P-selectin, on monocytes and neutrophils. Monocytes preferentially bound platelets or PMV. However, we found no significant increase in recruitment of these heterotypic aggregates to von Willebrand factor, under conditions of low shear stress compared to monocytes alone. These heterotypic aggregates provide a mechanism for cross-talk between cell types and have a potential role in inflammatory and thrombotic diseases.
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Taha, Mariam. "Bacterial Contamination of Platelet Concentrates: Role of Biofilm Formation and Manufacturing Process." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35192.
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Bacterial contamination of platelet concentrates (PCs) poses the highest transfusion-associated infectious risk with skin flora, such as Staphylococcus epidermidis and Staphylococcus capitis, being the predominant contaminants. These bacteria are able to form surface-attached aggregates or biofilms, which are present in the skin of healthy blood donors and can subsequently be isolated from contaminated PCs.
Disinfection of the venipuncture area before donation with a combination of 2% chlorhexidine-gluconate and 70% isopropanol is used at Canadian Blood Services. However, not all bacteria are eliminated during skin disinfection since contaminated PCs are still captured during routine PC screening. In this thesis, the ability of biofilm-forming S. epidermidis and S. capitis to resist the currently used disinfectants was explored. It was demonstrated that although a combination of chlorhexidine and isopropanol has a bactericidal effect, it is unable to completely eradicate skin flora biofilms.
Several countries have implemented Pathogen Inactivation Technologies (PITs) as a measure to help control transfusing bacterially-contaminated PCs by exposing PC units to ultra violet light. However, no investigations have been done to evaluate the ability of PITs against bacterial biofilms, which was one of the objectives of this thesis. Data revealed that the efficacy of a currently used PIT, the Mirasol® system, is similar for S. epidermidis present in PCs produced from whole blood inoculated with biofilm or non-biofilm cells. However, treatment effectiveness was strain dependent. In conclusion, further investigation to improve donor skin disinfection and PITs should be considered.
Surveillance at Canadian Blood Services shows that contamination rates in single-donor apheresis PCs (Aph-PCs) is generally higher than in four-donor buffy coat platelet pools (BC-PCs). This study investigated whether the BC-PC production method contributes to this observation as BC-PCs are derived from WB that is left to rest overnight while Aph-PCs are collected directly from the donor. Data showed that WB hold during BC-PC production does not have a broad-spectrum bactericidal effect and therefore other factors contribute to low rates of contamination in BC-PCs. The work presented in this thesis provides an insight to bacterial residence and persistence during blood product manufacturing and makes suggestions for PC safety improvements.
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Hayman, Melissa Anne. "Genomic influences on platelet function." Thesis, Queen Mary, University of London, 2018. http://qmro.qmul.ac.uk/xmlui/handle/123456789/36221.
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The study of platelet messenger and micro-RNAs is of increasing interest owing to the fact that platelets contain the machinery to splice and translate mRNA into proteins in response to inhibitory or activating signals. However, the relatively small size (roughly 4000-5000 transcripts) and short half-life of the platelet transcriptome makes this a technically challenging aspect of platelet biology to investigate. The aims of these thesis investigations were therefore to optimise protocols for the isolation of platelets for downstream RNA analyses and function testing, to investigate the functional capabilities of platelet subpopulations rich in RNA, and to understand the functional and transcriptomic impact of gene mutations predicted to influence platelet function. I found that the optimal method for isolating platelets from whole blood is to use simple single step centrifugation to obtain platelet rich plasma. This method is as effective as more involved methods at reducing white blood cell contamination whilst causing minimal platelet activation. Using this method in combination with flow cytometric cell sorting techniques I was able to isolate the newly formed reticulated platelet sub-population and to confirm the link between reticulation status and increased RNA content. Furthermore, using a range of platelet function assays I demonstrated that reticulated platelets are more reactive than non-reticulated platelets. By obtaining blood samples from a patient with a PLA2G4A mutation I was able to show that loss of cPLA2α enzymatic activity alters both platelet function and the expression of certain mRNA transcripts. My investigations using samples from a range of patients with bleeding tendencies show the benefit of combining deep platelet phenotyping with next generation sequencing to understand the causation of bleeding disorders. Together these investigations highlight the utility of genomic DNA and platelet specific mRNA studies in providing novel insights in to pathways regulating platelet reactivity.
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Hamali, Hassan A. A. "Regulation of the procoagulant activity of platelets and platelet-derived microparticles." Thesis, University of Leicester, 2011. http://hdl.handle.net/2381/10046.
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Procoagulant microparticles (MPs) in the circulation are increasingly recognized as playing a role in haemostasis and inflammation and may prove useful biomarkers for clinical studies. Platelets are known to generate MPs in response to stimulation, and platelet-derived MPs (PDMPs) form the majority of the MPs found in the normal circulation and can be elevated in a number of disease states. The current study has focused on the procoagulant activity of platelets and PDMPs following stimulation with the collagen-mimetic peptide CRP-XL. Their activity in accelerating thrombin generation can be accurately measured by the Calibrated Automated Thrombogram (CAT) assay using 1pM TF reagent to initiate the reaction, with the finding that plasma from patients with chronic renal disease has significant thrombin generation due to increased procoagulant activity of MPs. Conversely premature MI patients in a stable condition have thrombin generation comparable to matched healthy control. In all subjects, removal of MPs from plasma by filtration (>0.2 μm) eliminates this procoagulant activity, indicating the importance of MP size in driving the procoagulant response. The procoagulant activity of activated platelets and PDMPs showed a strong correlation with annexin-V binding measured using flow cytometry. Comparison of the regulatory mechanism of the procoagulant activity of platelet and PDMPs upon activation with platelets undergoing apoptosis showed that although both activation and apoptosis resulted in exposure of the procoagulant surface, apoptotic platelets did not release procoagulant MPs or show any markers of activation such as P-selectin expression, fibrinogen binding or aggregation. Reactive oxygen species (ROS) are generated during platelet activation or apoptosis mainly through the NADP(P)H oxidase pathway. The procoagulant activity of platelets and PDMPs was significantly attenuated (as measured by thrombin generation and annexin-V binding) by inhibition of the NAD(P)H oxidase pathway by apocynin, which had similar inhibition on other platelet responses including on 12-HETE generation, TxB2 production and aggregation. However antioxidants only inhibited apoptosis-induced platelet procoagulant activity. These data demonstrate significant involvement of ROS in platelet procoagulant activity induced by both activation and apoptosis and suggest the involvement of lipid peroxidation during apoptosis.
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Murphy, Christine Therese. "Mechanisms of stimulus-response coupling in platelet-activating factor stimulated platelets." Thesis, University of Bath, 1992. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304999.
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Arunima, Ghosh. "Role of CD36 in Platelet Function." Cleveland State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=csu1199991110.
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Hamad, Osama A. "Crosstalk Between Activated Platelets and the Complement System." Doctoral thesis, Uppsala universitet, Enheten för klinisk immunologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-123681.
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Several studies have shown that complement and thrombotic events co-exist. Platelets have been suspected to act as the bridge between the two cascade systems. To study the platelet-induced complement activation we developed a system in which platelets were activated by thrombin receptor activating peptide (TRAP) in platelet rich plasma (PRP) or whole blood anti-coagulated using the specific thrombin inhibitor, lepirudin. TRAP-activated platelets induced a fluid-phase complement activation measured as generation of C3a and sC5b-9, triggered by released chondroitin sulphate-A (CS-A) which interacted with C1q and activated the complement system through the classical pathway. Complement components C1q, C3, C4 and C9 were also shown to bind to TRAP-activated platelets but this binding did not seem to be due to a complement activation since blocking of complement activation at the C1q or C3 levels did not affect the binding of the complement proteins. The C3 which bound to activated platelets consisted of C3(H2O), indicating that bound C3 was not proteolytically activated. Binding of C1q was partially dependent on CS-A exposure on activated platelets. The abolished complement activation on the surface of activated platelets was suggested to be dependent on the involvement of several complement inhibitors. We confirmed the binding of C1INH and factor H to activated platelets. To this list we have added another potent complement inhibitor, C4BP. The binding of factor H and C4BP was shown to be dependent on exposure of CS-A on activated platelets. The physiological relevance of these reactions was reflected in an elevated expression of CD11b on leukocytes, and increased generation of platelet-leukocyte complexes. The platelets were involved in these events by at least two different mechanisms; generation of C5a which activated leukocytes and binding of C3(H2O)/iC3(H2O), a ligand to the intergrin CD11b/CD18 on their surface. These mechanisms add further to the understanding of how platelets interact with the complement system and will help us to understand the role of the complement system in cardiovascular disease and thrombotic conditions.Platelet Mediated Complement Activation
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Battram, Anthony Matthew. "The role and regulation of Rasa3 in platelets and platelet cell models." Thesis, University of Bristol, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.702741.
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Upon vascular insult, platelets are recruited to the site of injury, are activated, and form a haemostatic plug to prevent bleeding. However, inappropriate platelet activation can lead to the formation of occluding thrombi in arteries and veins in a process known as thrombosis. The GTPase Rap1 plays a critical role in platelet activation by regulating the affinity state of the fibrinogen receptor, integrin allbb3. The aim of this thesis was to ascertain the role and regulation of a Rap1-targeting GTPase-activating protein (GAP), Rasa3 (previously GAP1lP4BP), in platelet signal transduction and function. I first investigated possible mechanisms of Rasa3 regulation in platelets, and I found that platelet Rasa3 bound to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3), suggesting a role of PI3 kinase. Although PI(3,4,5)P3 binding had no direct effect on Rasa3 Rap1 GAP activity in vitro, Pl3 kinase did regulate Rasa3 subcellular localisation and activation of Rasa3 substrate, Rap1. Rasa3 also underwent thrombin-induced phosphorylation and associated with integrin b3. Next, to assess potential effects of Rasa3 on platelet function, I used a CHO cell model of integrin allbb3 signalling, C19 cells. I demonstrated that Rasa3 Rap1GAP activity was responsible for inhibiting integrin allbb3-mediated C19 cell spreading. I then characterised two Rasa3 mutants, H794L and G125V, found in thrombocytopaenic mouse models. I found that both mutations caused a loss of Rasa3 Rap1GAP and RasGAP activity, and Rasa3 inhibition of C19 cell spreading. Furthermore, platelets from mice expressing Rasa3 (H794L) exhibit increased spreading in a manner that is insensitive to PI3 kinase inhibition, suggesting that Pl3 kinase regulates platelet spreading by blocking Rasa3 Rap1GAP activity. I finally evaluated CMK cells as a possible cell line in which to study the effect of Rasa3 on platelet signalling and integrin allbb3 activation, and I found that they have some advantages compared to the C19 cell model. Overall, this thesis establishes a novel role for Rasa3 in platelet integrin allbb3 outside-in signalling and begins to explore the Pl3 kinase-dependent and -independent mechanisms of Rasa3 regulation.
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Eriksson, Andreas. "Platelet Adhesion to Proteins in Microplates : Applications in Experimental and Clinical Research." Doctoral thesis, Linköping : Department of Medical and Health Sciences, Linköping University, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-11733.
Full textBooks on the topic "Platelets"
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D, Michelson Alan, ed. Platelets. 2nd ed. Amsterdam: Academic Press/Elsevier, 2007.
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D, Michelson Alan, ed. Platelets. San Diego: Academic Press, 2002.
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M, Smith Dennis, and Summers Stephanie, eds. Platelets. Arlington, Va: American Association of Blood Banks, 1988.
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J, Westwick, ed. Mechanisms of stimulus-response coupling in platelets. New York: Plenum Press, 1985.
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Gibbins, Jonathan M., and Martyn P. Mahaut-Smith. Platelets and Megakaryocytes. New Jersey: Humana Press, 2004. http://dx.doi.org/10.1385/1592597823.
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Gibbins, Jonathan M., and Martyn P. Mahaut-Smith. Platelets and Megakaryocytes. New Jersey: Humana Press, 2004. http://dx.doi.org/10.1385/1592597831.
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Kessler, Christof, ed. Platelets and Atherosclerosis. Berlin, Heidelberg: Springer Berlin Heidelberg, 1991. http://dx.doi.org/10.1007/978-3-642-58225-7.
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Gibbins, Jonathan M., and Martyn P. Mahaut-Smith, eds. Platelets and Megakaryocytes. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-61779-307-3.
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Gibbins, Jonathan M., and Martyn Mahaut-Smith, eds. Platelets and Megakaryocytes. New York, NY: Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-8585-2.
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1942-, Phillips David R., and Shuman Marc A, eds. Biochemistry of platelets. Orlando: Academic Press, 1986.
Find full textBook chapters on the topic "Platelets"
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Michelson, Alan D., and Sanford J. Shattil. "The use of flow cytometry to study platelet activation." In Platelets, 111–30. Oxford University PressOxford, 1996. http://dx.doi.org/10.1093/oso/9780199635382.003.0006.
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Abstract Many common clinical conditions have been reported to be associated with platelet hyperreactivity and/or circulating activated platelets: coronary artery disease (angina pectoris, acute myocardial infarction) diabetes mellitus stroke exercise emotional stress cigarette smoking pregnancy and pre-eclampsia blood bank storage of platelets for transfusion cardiopulmonary bypass angioplasty deep vein thrombosis hyperlipoproteinaemia essential thrombocythemia adult respiratory distress syndrome However, the role of platelet activation in clinical settings is controversial, in part because the methods used to detect platelet activation (e.g. platelet aggregation and radioimmunoassays of plasma P-thromboglobulin (pTG) and/or platelet factor 4 (PF4) have major methodologic problems (1-6)).
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A. Matthay, Zachary, and Lucy Zumwinkle Kornblith. "Platelet Imaging." In Platelets. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.91736.
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The knowledge gained through imaging platelets has formed the backbone of our understanding of their biology in health and disease. Early investigators relied on conventional light microscopy with limited resolution and were primarily able to identify the presence and basic morphology of platelets. The advent of high resolution technologies, in particular, electron microscopy, accelerated our understanding of the dynamics of platelet ultrastructure dramatically. Further refinements and improvements in our ability to localize and reliably identify platelet structures have included the use of immune-labeling techniques, correlative-fluorescence light and electron microscopy, and super-resolution microscopies. More recently, the expanded development and application of intravital microscopy in animal models has enhanced our knowledge of platelet functions and thrombus formation in vivo, as these experimental systems most closely replicate native biological environments. Emerging improvements in our ability to characterize platelets at the ultrastructural and organelle levels include the use of platelet cryogenic electron tomography with quantitative, unbiased imaging analysis, and the ability to genetically label platelet features with electron dense markers for analysis by electron microscopy.
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Clemetson, Kenneth J. "Clinical aspects of platelet function." In Platelets, 299–318. Oxford University PressOxford, 1996. http://dx.doi.org/10.1093/oso/9780199635382.003.0015.
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Abstract 1. Introduction Since the primary function of platelets is haemostasis, or stopping bleeding, platelet dysfunction is generally seen as an under–or over-expression of this, i.e. in bleeding problems or in various haemostatic or thrombotic disorders. The first task of the clinician faced with such symptoms is to eliminate the possibility of the disorder being produced by a lack or defect in plasma coagulation factors such as factor VIII, von Willebrand factor, fibrinogen, factor IX, factor V, etc. which are commonly affected. Having shown that these lie within the normal range it is necessary to check for platelet-related problems. Basic parameters such as platelet count, platelet volume, and granulosity can be rapidly determined by flow cytometry. Thrombocytopenia, or low platelet count can clearly lead to bleeding problems though there is some controversy about what should be regarded as a threshold value. Normal values lie in the range 150000–400000 platelets/µl but bleeding problems may not appear until values below 10000-20000 platelets/µl are reached. There are many causes for thrombocytopenia which will be dealt with later. When necessary, basic treatment is intravenous platelet concentrates to try to restore platelet levels although the recent cloning of thrombopoietin may, when it becomes generally available, make this a preferred therapy.
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K. Poddar, Mrinal, and Soumyabrata Banerjee. "Molecular Aspects of Pathophysiology of Platelet Receptors." In Platelets. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.92856.
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Receptor is a dynamic instrumental surface protein that helps to interact with specific molecules to respond accordingly. Platelet is the smallest in size among the blood components, but it plays many pivotal roles to maintain hemostasis involving its surface receptors. It (platelet) has cell adhesion receptors (e.g., integrins and glycoproteins), leucine-rich repeats receptors (e.g., TLRs, glycoprotein complex, and MMPs), selectins (e.g., CLEC, P-selectin, and CD), tetraspanins (e.g., CD and LAMP), transmembrane receptors (e.g., purinergic—P2Y and P2X1), prostaglandin receptors (e.g., TxA2, PGH2, and PGI2), immunoglobulin superfamily receptors (e.g., FcRγ and FcεR), etc. on its surface. The platelet receptors (e.g., glycoproteins, protease-activated receptors, and GPCRs) during platelet activation are over expressed and their granule contents are secreted (including neurotransmitters, cytokines, and chemokines) into circulation, which are found to be correlated with different physiological conditions. Interestingly, platelets promote metastasis through circulation protecting from cytolysis and endogenous immune surveillance involving several platelets receptors. The updated knowledge about different types of platelet receptors in all probable aspects, including their inter- and intra-signaling mechanisms, are discussed with respect to not only its (platelets) receptor type but also under different pathophysiological conditions.
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Águila, Sonia, Ernesto Cuenca-Zamora, Constantino Martínez, and Raúl Teruel-Montoya. "MicroRNAs in Platelets: Should I Stay or Should I Go?" In Platelets. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.93181.
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In this chapter, we discuss different topics always using the microRNA as the guiding thread of the review. MicroRNAs, member of small noncoding RNAs family, are an important element involved in gene expression. We cover different issues such as their importance in the differentiation and maturation of megakaryocytes (megakaryopoiesis), as well as the role in platelets formation (thrombopoiesis) focusing on the described relationship between miRNA and critical myeloid lineage transcription factors such as RUNX1, chemokines receptors as CRCX4, or central hormones in platelet homeostasis like TPO, as well as its receptor (MPL) and the TPO signal transduction pathway, that is JAK/STAT. In addition to platelet biogenesis, we review the microRNA participation in platelets physiology and function. This review also introduces the use of miRNAs as biomarkers of platelet function since the detection of pathogenic situations or response to therapy using these noncoding RNAs is getting increasing interest in disease management. Finally, this chapter describes the participation of platelets in cellular interplay, since extracellular vesicles have been demonstrated to have the ability to deliver microRNAs to others cells, modulating their function through intercellular communication, redefining the extracellular vesicles from the so-called “platelet dust” to become mediators of intercellular communication.
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Butt, Elke, and Ulrich Walter. "Cyclic nucleotides: measurement and function." In Platelets, 259–78. Oxford University PressOxford, 1996. http://dx.doi.org/10.1093/oso/9780199635382.003.0013.
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Abstract The activation of human platelets is inhibited by a variety of agents which exert their effects through distinct mechanisms. Examples include inhibitors of thromboxane A2 generation (e.g. aspirin), inhibitors of thrombin (e.g. hirudin), scavengers of ADP (e.g. apyrase), and physiological and pharmacological cyclic nucleotide-elevating agents (1,2). Vascular endothelial cells, under basal conditions and in response to numerous vasoactive agents, synthesize and release prostacyclin (PGI2) and endothelium-derived relaxing factor, nitric oxide (EDRF; or NO), two of the most important physiological platelet inhibitors. PGI2 and EDRF/NO increase the intracellular messenger molecules cAMP and cGMP, respectively, in human platelets and other target cells. The inhibition of platelet activation caused by PGI2 and EDRF/NO is mediated by cAMP- and cGMP-dependent protein kinases (cAMP-PK, cGMP-PK), respectively. As shown in Table 1, human platelets contain par ticularly high concentrations of cAMP-PK and cGMP-PK (3). The type III cGMP-inhibited phosphodiesterase (cGI-PDE) is an additional important target for cGMP. Elevation of cAMP mediated by cGMP inhibition of the cGI-PDE contributes to the well known synergism between cGMP- and cAMP-elevating platelet inhibitors (4). In human platelets, established cAMP-PK substrates include the small molecular weight G protein rap lB, the subunit of glycoprotein lb (GPib ), the focal adhesion protein VASP, caldesmon, myosin light chain kinase (MLCK), cGI-PDE, and actin-binding protein (ABP) (2). Only the focal adhesion protein VASP is an established substrate for cGMP-PK in platelets although other substrates, perhaps also rap lB and GPib , may exist. The physiological effects of cyclic nucleotide-elevating platelet inhibitors are terminated by cyclic nucleotide-degrading phosphodiesterases (PDEs) and by protein phosphatases which dephosphorylate the cAMP-PK and cGMP-PK substrates. In human platelets, the major PDEs responsible for cAMP or cGMP hydrolysis are type III cGI-PDE and type V cGMP binding, cGMP-specific PDE (cGB-PDE), respectively (4,5).
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Mcgregor, John L., Odile Gayet, Nathalie Mercier, Lilian Mcgregor, and Elza Chignier. "Identification, isolation, and characterization of platelet glycoproteins mediating platelet adhesion." In Platelets, 131–54. Oxford University PressOxford, 1996. http://dx.doi.org/10.1093/oso/9780199635382.003.0007.
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Abstract Platelets play a vital role in haemostasis by the formation of a plug or thrombus at a site of vessel wall injury. The function of these anucleated cells is largely dependent on the presence of a number of glycoproteins. Moreover, adhesion and aggregation of platelets to disrupted atheroma plaque, leading in some cases to vessel occlusion, is also mediated by glycoproteins. The importance of glycoproteins in platelet functions has led to extensive work, using various techniques, to identify structural/functional sites on these glycoproteins implicated in interacting with various ligands. The aim of this chapter is to describe a number of techniques used in studying glycoproteins involved in platelet adhesion to extracellular matrix proteins or to leucocytes.
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Israels, Sara J., and Jon M. Gerrard. "lmmunocytochemical and electron microscopic studies of platelets." In Platelets, 279–98. Oxford University PressOxford, 1996. http://dx.doi.org/10.1093/oso/9780199635382.003.0014.
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Abstract Although platelets were one of the first types of cells to be studied using the electron microscope, a clear understanding of normal platelet architecture using electron microscopy had to await improved techniques for the isolation, preservation, and fixation of these cells. Similarly, an understanding of the changes in blood platelet fine structure during clotting required improvements in preparative techniques. The preservation and fixation of certain platelet subcellular structures, notably dense granules and contractile filaments, have presented particular challenges. In this chapter, we describe basic fixation procedures for platelet transmission electron microscopy, and for immunofluorescent and immunoelectron microscopic studies, while providing a brief overview of some other aspects of platelet electron microscopic studies.
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Wilkinson, J. Michael. "Monoclonal antibodies to platelet cell surface antigens and their use." In Platelets, 155–72. Oxford University PressOxford, 1996. http://dx.doi.org/10.1093/oso/9780199635382.003.0008.
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Abstract The introduction of the technique of monoclonal antibody (mAb) preparation in 1975 revolutionized the study of cell surface molecules, and this has been as true for platelets as for any other type of cell. mAb have been used both to characterize molecules previously defined by other methods and also to identify new molecules, by immunization of mice with whole platelets or platelet plasma membrane fractions. Like any other cell type, platelets express a wide variety of cell surface proteins whose surface density may vary from tens to tens of thousands of molecules per cell. Many of the major surface glycoproteins are involved in the wide variety of adhesive interactions which platelets are able to undergo (1) and whose activity is tightly controlled during platelet activation. This control may be by conformational changes in existing cell surface molecules, notably in GPilb-Illa to reveal its fibrinogen (Fg) binding site, or by modulation of the level of cell surface expression, as for the platelet selectin, GMP 140. Other major surface glycoproteins, such as the CD9 antigen, have, as yet, no known or well defined function. There are in addition many minor surface proteins, which include receptors of various types and many other molecules of unknown function. mAb may thus be used for the definition of those proteins which are present on the surface of either resting or activated platelets, both in qualitative or quantitative terms. They may also be used for affinity purification, as described in Chapter 7, for further structural and functional characterization. In addition, the exquisite specificity of mAb for a single epitope on a particular protein means that they can be used as probes for particular structures or functions. A variety of mAb has been described, some of which are able to inhibit aggregation and activation while others are able to promote these functions. Hence they are ideal reagents for the characterization of the activities which are responsible for the transformation of resting discoid platelets into multicellular aggregates.
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Bevers, Edouard M., Paul Comfurius, Chrisp M. Reutelingsperger, and Robert F. A. Zwaal. "Platelet procoagulant activity and its measurement." In Platelets, 319–40. Oxford University PressOxford, 1996. http://dx.doi.org/10.1093/oso/9780199635382.003.0016.
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Abstract Platelets serve an important function in the haemostatic process. Vessel wall injury causes exposure of subendothelial structures to the blood stream and initiates the process of platelet adhesion, aggregation, and release of granule contents resulting in formation of the primary haemostatic plug. Tissue thromboplastin, released by the damaged vessel wall, initiates activation of the coagulation pathway, leading to formation of thrombin. The action of thrombin on soluble plasma fibrinogen gives rise to deposition of an insoluble fibrin network which consolidates the primary haemostatic platelet plug to a stable thrombus. There exists a mutual interaction between thrombin formation and platelet activation: while thrombin is one of the most potent platelet activators, its formation is strongly enhanced in the presence of activated platelets. The latter is due to the exposure of procoagulant phospholipids at the surface of the platelet plasma membrane, known as the procoagulant response. In this chapter, we will describe two methods to measure this procoagulant response. One method concerns the direct measurement of a lipid-dependent coagulation reaction, i.e. the formation of thrombin by the enzyme complex factor Xa and factor Va, known as the prothrombinase reaction. The other method is based on the detection of surface exposed procoagulant lipid, i.e. phosphatidylserine (PS) by means of Annexin V, a protein with high affinity for anionic phospholipids.
Conference papers on the topic "Platelets"
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Jansen, J. W. C. M. "EFFECTS OF INHIBITORS ON COLLAGEN INDUCED PLATELET AGGREGATION IN SIX DIFFERENT SPECIES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643445.
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One approach to the development of antithrombotics is inhibition of platelet aggregation. The pharmacological approach often used is to test compounds on collagen induced platelet aggregation measured in platelet rich plasma. Therefore we have compared inhibitors with different mechanism of action on aggregation of platelets from six different species commonly used in pharmacological studies. Aggregation was induced with submaximal amounts of collagen (Hormone Chemie).Inhibitors of the cyclooxygenase system, aspirin and indomethacin, were very potent in inhibiting aggregation of platelets from humans guinea pig and dog (IC50 20-60 and 1-3 ¼M resp.). Aggregation of pig and rat platelets was poorly inhibited by both of these compounds (IC5: 700-900 ¼M), whereas platelets from mice showed intermediate sensitivety (IC50 ca.100 ¼M).The combined lipoxygenase/cyclooxygenase inhibitor BW755C, was extremely active on platelets of guinea pig (IC50 1 ¼M) and was poorly active in mice platelets (IC50 300 ¼M). In the other species the inhibitory activity ranged from 20-80 ¼M.The phosphodiesterase inhibitors, papaverine and BL3459 inhibited aggregation in all species (IC50 50-100 and 1-5 ¼M resp.). Dipyridamole inhibited aggregation also in all species but with lower activity (IC50 > 100 ¼M).Conclusion: remarkable species differences are present with respect to inhibition of collagen induced platelet aggregation by the various compounds e.g. rat and porcine platelet aggregation was hardly inhibited by cyclooxygenase inhibitors. The effects of the compounds on human platelets are comparable to the effects on canine plateletes.
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Ordinas, A., E. Bastida, M. Garrido, J. Monteagudo, L. de Marco, and R. Castillo. "ASIALO VON WILLEBRAND FACTOR ENHANCES PLATELET ADHESION TO VASCULAR SUBENDOTHELIUM." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644098.
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Native Von Willebrand factor (NvWF) binds to platelets activated by thrombin, ADP or ristocetin, and also supports the adhesion of platelets to subendothelium at high shear rates. In contrast, asialo von Willebrand factor (AvWF) induces platelet aggregation in absence of platelet activators. We investigated the role of AvWF in supporting the adhesion of platelets to rabbit vessel subendothelium under flow conditions at a shear rate of 2000 sec-1 for 5 min using the Baumgartner perfusion system. We also studied the effects of blockage of platelet GPIb or GPIIb/IIIa on platelet adhesion using monoclonal antibodies (Mabs),and we measured the rate of binding of 111I-labeled NvWF and AvWF to subendothelium. Perfusates consisted of washed platelts and red cells resuspended in a 4% human albumin solution to which increasing concentrations of NvWF or AvWF had been added. Platelets interacting with the perfused vessels were evaluated morphometrically using a computerized system. At a concentration of 1.2 /ig/ml the percentage of total coverage surface was 21.3 ± 4.8% and 40.0±14.6%, for NvWF and AvWF, respectively (p<0.01). Addition of either Mab against GPIb (LJlbl) or against GPIIb/IIIa (CP8) to the perfusates, reduced platelet deposition (p <0.01). The rates of binding of 111I-labeled NvWF and AvWF to perfused vessel subendothelium were similar (0.83±0.1μg and 0.95±0.1 μg ,respectively).Our results indicate that AvWF enhances the interaction of washed platelets with the vessel subendothelium under flow conditions. Furthermore, they suggest that this effect is related to the interaction of AvWF with platelets and not to an increased affinity of AvWF for subendothelium.
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Struk, A., A. Prins, M. C. L. Schaap, J. W. ten Cate, and H. van den Bosch. "SYNTHESIS OF PLATELET ACTIVATING FACTOR BY HUMAN BLOOD PLATELETS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643486.
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Synthesis of platelet activating factor (PAF) by human blood platelets is a controversial issue. Whereas some groups have reported the synthesis, induced by thrombin, collagen or Ca2--ionophore Azsio?, others were unable to obtain for instance the thrombin-induced PAF synthesis. Also, synthesis of only up to 6 pMoles PAF/10 platelets has been reported, but leucocytes may synthesize up to 6000 pMoles PAF/10 cells. Only an 0.1% leucocyte contamination would thereby explain the “ platelet PAF synthesis” . We therefore optimized the PAF synthesis by human blood platelets and leucocytes, induced by thrombin and A23i07. As platelets have been reported to show an increased PAF synthesis upon treatment with phenylmethylsulfonylfluoride (PMSF), this was also investigated.Leucocytes were optimally stimulated with 10 uM Azale? (mean ± SD 4678 ± 2033, range 1698-7058 pMoles PAF/10 cells, n=6), but could not be stimulated by thrombin. PMSF treatment itself induced PAF synthesis by these cells, but this was not influenced by thrombin or A23ia7.Platelet suspensions, with <0.005% leucocyte contamination as determined by light microscopy after Jenner-Giemsa staining, could synthesize PAF when treated with PMSF and stimulated with 2.5 IU/ml thrombin (mean ± SD 0.6 ± 0.3, range 0.3-1.0 pMoles PAF/10 platelets, n=6), but in these suspensions A23io7-induced synthesis could not be demonstrated.The results indicate that synthesis of PAF by human blood platelets is not due to contaminating leucocytes, if thrombin is used as the stimulus. These results were confirmed by 3H-acetate uptake experiments.
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Vanhoutte, Paul M. "PLATELETS, ENDOTHELIUM AND VASOSPASM." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643722.
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The endothelium can secrete both relaxing and contracting substances. One of the most powerful stimuli to the release of the former are thrombin and aggregating platelets. This contributes to the protective role of the endothelium against inappropriate intraluminal platelet aggregation and coagulation in blood vessels with an intact intima. Thrombin-induced, endothelium-dependent relaxations have been obtained in isolated arteries of different species, including humans. Endothelium-dependent relaxations can be evoked by autologous platelets in isolated blood vessels of the dog, pig and rat; they can be obtained in canine coronary arteries with human platelets. The major platelet-products involved in these endothelium-dependent relaxations are 5-hydroxytryptamine (serotonin) and the adenine nucleotides. Although platelet-activating factor (PAF) can evoke endothelium-dependent relaxation it only does so at concentrations much higher than those occurring under physiological conditions; since the relaxations are not prevented by PAF-antagonists, they are non-specific in nature.The receptor mediating the endothelium-dependent relaxations to serotonin released from the aggregating platelets can be subtyped as a S1~(5HT1) serotonergic receptor;those mediating the response to the adenine nucleotides as P2y-purinergic receptors. In the absence of the endothelium aggregating platelets cause contractions of vascular smooth muscle; these are mediated by a mixture of S1-like and S2~serotoner-gic receptors in coronary arteriesof the dog, and by S2-serotonergic receptors in those of the pig. Thus, in the porcine coronary artery, the S2-serotonergic antagonist ketanserin markedly enhances the platelet-induced endothelium-dependent relaxation. After previous (four weeks) injury, the regenerated endothelium of the porcine coronary artery loses the ability to respond to serotonin,and is unable to prevent the constrictionsevoked by aggregating platelets. The endothelium-dependent relaxations of porcine coronary arteries evoked by aggregating platelets are potentiated by chronic treatmentof the donor animals with cod liver oil. These studies emphasize the protective roleof the endothelial cells against the vasoconstriction (vasospasm) induced by aggregating platelets. This role is depressed after previous injury, and can be facilitatedby dietary adj ustments.
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Suzuki, Sozo, Kazuo Mori, Koji Sugai, Yasuyuki Akutsu, Masaaki Ishikawa, Hideaki Sakai, and Katsuhide Hiwatashi. "ELECTRONMICROSCOPIC STUDIES ON PLATELETS AND MEGAKARYOCYTES IN GIANT PLATELET SYNDROME." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644560.
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Giant platelet syndrome are characterized morphologically by many giant platelets associated with several functional abnormalities in the peripheral blood. However, the mechanism of large platelet production has not yet been clarified. In 1981, we reported acase with Bernard-Soulier syndrome(BSS) in whom giant platelets were considered to be formed by fusion of two or three platelets in the circulating blood. We examined the ultrastructure of platelets and megakaryocytes in another case with BSS (29 year-old female) and a case with May-Hegglin anomaly (31 year-old male). Whole blood and bone marrow specimens were fixed with glutaraldehyde-osmium solution. Thin sections were prepared and stained with uranyl acetate and lead cytrate. Membrane systems of platelets and megakaryocytes in a case with BSS was investigated by staining of surface coating with ruthenium red.In a case with BSS, most platelets were very large and similar in morphology to those in formerly reported case. Giant platelets contained several-fold increased number of α-granules and mitochondria. Typical dense bodies were also observed. Contents of ATP/ADP, platelet factor-4(PF-4), B-thromboglobulin(B-TG) and platelet factor-3 availability(PF-3) were increased. Disorganization of microtubules was recognized. Some giant platelet contained membrane systems similar to demarcation membranes(DM) in megakaryocytes, characteristically. In mature megakaryocytes, areas divided by DM similar in size to those in normal megakaryocytes were observed. Several of these areas appeared to fuse together to form the giant platelets containing many granules and remnants of DM. In a case with May-Hegglin anomaly, typical Dohle’s bodies were shown in neutrophilic granulocytes. Giant platelets in this case also contained large number of α-granules and some of them contained membrane systems similar to DM. Areas similar in morphology to these giant platelets were clearly noted in the cytoplasm of mature megakaryocytes.In these cases, most giant platelets in the peripheral blood may be formed in the cytoplasm of megakaryocytes by fusion of several areas divided by DM, each of which may become normal sized platelets in normal megakaryocytes.
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Yamazaki, H., K. Tanoue, K. Kuroiwa, H. Suzuki, M. Shibayama, and Y. Mano. "ACQUIRED STORAGE POOL DISEASE IN DECOMPRESSION SICKNESS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644563.
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The presence of hemostatic abnormalities has been reported in decompression sickness. It is suggested that platelets recognize air bubbles in the blood stream as a foreign surface and adhere to them with ensuing platelet aggregation. It is important to determine if consumption of platelets occurs in vivo to understand a role of platelets in the genesis of decompression sickness. To analyse the problem, platelet behavior was studied in 34 rabbits with decompression sickness which was brought about by the exposure to 6 ATA (atmospheres absolute) for 40 min followed by rapid decompression. All rabbits died within one hr after the decompression due to apnea which always preceded the cardiac arrest. Platelet counts decreased significantly during the time course of decompression. A regression line can be drawn between the changes in platelet count (Y) and the time after decompression (X): Y=100.2 - 0.8X, r= -0.876, p<0.001. Platelet counts measured just before the apnea were 56 to 72% (65.7 ± 6.1%) of the precompression value. Kinetic studies with 111 In-oxine-labeled platelets revealed shortened survivals of the circulating platelets and autoradiograms indicated the accumulation of radioactivity in the lungs after the decompression. Although there was no change in the mode volume of platelets after the decompression, the transient appearance of smaller or fragmented platelets suggested a random over-destruction of platelets. Whole and releasable adenine nucleotide contents of platelets decreased significantly after the decompression. There were no significant changes in cytoplasmic adenine nucleotide contents. Therefore, in decompression sickness, the circulating platelets behaved similarly to those of acquired storage pool disease. Platelet thrombi were found in the pulmonary artery, compatible with the accumulation of the labeled platelets. These findings suggest that circulating air-bubbles interact with circulating platelets, causing the platelet release reaction, and these activated platelets participate in the formation of thrombi in decompression sickness.
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Bryckaert, M. C., A. Wasteson, G. Tobelem, F. Rendu, and J. P. Caen. "PLATELET DERIVED GROWTH FACTOR (PDGF) BINDS TO HUMAN PLATELETS AND MODULATES PLATELET ACTIVATION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643493.
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PDGF which is released during platelet activation like the other ∝ granule components (fibrinogen, F VIII/vWF, PF4) could bind to platelet membrane Following this hypothesis, we have studied the binding of 125I pure human PDGF to washed human platelets activated by collagen. This binding was specific and time dependent and reached a plateau with 20 μg/ml of collagen. With 200 fold excess of unlabeled PDGF, the binding of 125I-PDGF decreased progressively to 10 .whereas unlabeled Epidermal Growth Factor did not compete with 125I-PDGF. Saturation curve and scatchard analysis have shown one class of sites 3,000 sites/cell with an apparent Kd = 10-8 M. The demonstration of PDGF binding to platelets led us to investigate the effects of PDGF on platelet function. PDGF inhibited the aggregation and 14C serotonin release induced by thrombin or collagen. This inhibition was dose dependent and more effective with human PDGF. A total inhibition of collagen-induced platelet aggregation was obtained with 50 ng/ml of human PDGF and 200 ng/ml of porcine PDGF. The aggregation and 14C serotonin release induced by arachidonic acid were not inhibited by PDGF. The metabolism of phosphoinositide was also investigated on washed human platelets prelabeled with 32P orthophosphate. We found that PDGF (200 ng/ml) induced a decrease of 32P associated with phosphatidylinositol 4 biphosphate (72 %) after 3 min, with a parallel increase of 32P-phosphatidylinositol 4 Phosphate (120 %) and 32P-phosphatidylinositol (120 %).In conclusion i) PDGF binds to activated platelets, ii) PDGF inhibits platelet aggregation and secretion, iii) PDGF modifies phosphoinositide metabolism. These results are in favour of a role of PDGF in a negative feed back control of platelet activation.
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Lian, E. C. Y., and F. A. Siddigui. "BINDING OF 37-DKa PLATELET AGGLUTINATING PROTEIN TO HUMAN PLATELETS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643976.
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We have previously reported the purification of a 37-KDa platelet agglutinating protein (PAP p37) from the plasma of a patient with thrombotic thrombocytopenic purpura. using 125I-labeled p37, the properties of its binding to platelets were studied. The binding of p37 to washed human platelets from 4 normal subjects and two TTP patients after recovery was specific, concentration dependent and saturable. The Scatchard analysis revealed that the binding sites for p37 was about 100,000 per platelet with a dissociation constant of 48 × 10−9 M. The binding of p37 to erythrocytes was very little and non-specific. Stimulation of platelets by thrombin or ADP did not have any effect on the binding of p37 to platelets. The monoclonal antibodies to platelet GP lb (6D1) and GP Ilb-llla (10E5)(A gift of Dr. Barry coller) did not inhibit the binding of p37 to platelets. Fibrinogen (1 mg/ml) and FVIII/vWF (250 ug/ml) reduced the binding slightly. The polyclonal antibodies to p37 as well as concanavalin-A inhibited the binding of p37 to platelets through their direct interaction with p37. Other lectins such as phytohemagglutinin, potato lectin and helix pomatia lectin did not have any effect. At 40 mM, sialic acid, α-D-(+)-glucose, D-(+)-mannose and D-fructose caused 91%,44%,79%, and 63% inhibition of p37 binding respectively. D-(+)-galactose did not interfere with the binding. It is concluded that p37 binds to platelets on the sites other than GP lb and Gp IIb-IIIa and its binding to platelets is inhibited by certain sugars.
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Bauman, J. E., J. H. Joist, G. Vogler, and S. P. Sutera. "HIGH SUSCEPTIBILITY OF RABBIT, DOG, AND PIG PLATELETS TO SHEAR-INDUCED INJURY." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642846.
Full textAbstract:
In an attempt to develop an animal model for the study of the effects of fluid shear stress on platelet in vivo survival we examined the effects of repetitive short-duration (5 sec) and continuous prolonged (5 min) shear exposure in a cone-plate viscometer and Couette rotational viscometer on platelets (in citrated platelet-rich plasma) from humans, rabbits, dogs, and pigs. Comparable platelet aggregation (PAG = loss of single platelets) (18-64%) was observed with platelets from all species, associated with dense granule release, as a function of shear stress amplitude (25-50 dyn/cm2) under the conditions used. However, whereas with human platelets, little or no platelet injury (loss of LDH) was observed, appreciable platelet LDH loss was found with platelets from all animal species studied even at the lowest shear stress used, and LDH loss progressively increased with increasing shear stress amplitude (up to 30% at 50 dyn/cm2), and duration both in the cone-plate and Couette viscometer. These findings indicate a fundamental difference in the response of rabbit, dog, and pig platelets (as compared to that of human platelets) to laminar fluid shear stress in vitro. The mechanism(s) and factors leading to the apparent increased mechanical fragility of the animal platelets as compared to human platelets are currently under investigation.
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Metzelaar, M. J., H. K. Nieuwenhuis, and J. J. Sixma. "DETECTION OF ACTIVATED PLATELETS WITH MONOCLONAL ANTIBODIES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643829.
Full textAbstract:
Blood tests reflecting in-vivo activation of platelets are potentially useful in evaluating patients with thrombotic diseases. Recently monoclonal antibodies have been described that react preferentially with activated platelets. We prepared an IgG2b antibody, designated RUU-AP 2.28, that reacted with a 53.000 MW protein that is located in a special subclass of platelet granules in unstimulated platelets and that is exposed on the surface of activated platelets. Increased numbers of platelets that expressed the 2.28 antigen on their surface were observed in patients undergoing cardiopulmonary bypass and in patients with acute deep venous thrombosis. The percentage of RUU-AP 2.28 positive platelets in the circulation was 3,9 ± 2.7 (SD)% in the controls, (n = 20), 24.6 ± 13.5% in patients after cardiopulmonary surgery (n = 10) and 8.5% in patients with acute deep venous thrombosis (n = 2).In order to detect also earlier stages of platelet activation, such as secretion-independent phenomena, we produced new monoclonal antibodies by fusing spleen cells from Balb/c mice, immunized with thrombin stimulated, paraformaldehyde fixed platelets, with Ag 8653 myeloma cells. As a screening assay we used an ELISA with freshly fixed platelets or fixed thrombin-activated platelets. We detected six monoclonal antibodies (RUU-AP 1-6) specific for thrombin-activated platelets. The results of the ELISA were confirmed by flow cytofluorometry.None of the antibodies inhibited platelet aggregation induced by ADP, collagen or ristocetin. Ascites of IgGl antibody RUU-AP 3 reacted with normal thrombin-activated platelets but did not react with thrombin-activated platelets from a patient with Glanzmann’s disease. In addition antibody RUU-AP 3 reacted with normal platelets stimulated with 1 pM of ADP. These data suggest that antibody RUU-AP 3 detects a secretion-independent conformational change in the platelet membrane glycoprotein IIb-IIIa complex.
Reports on the topic "Platelets"
1
Slichter, Sherrill J. Pathogen-Reduced, Plasmalyte-Extended Stored Platelets (PREPS). Fort Belvoir, VA: Defense Technical Information Center, October 2013. http://dx.doi.org/10.21236/ada612437.
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Michelson, A. D., M. R. Barnard, H. B. Hechtman, H. Macgregor, and R. J. Connolly. In Vivo Tracking of Platelets: Circulating Degranulated Platelets Rapidly Lose Surface P-Selectin but Continue to Circulate and Function. Fort Belvoir, VA: Defense Technical Information Center, January 1995. http://dx.doi.org/10.21236/ada360258.
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Bode, Arthur P., and Thomas H. Fisher. Immunogenicity and Stability of Lyophilized Platelets for Transfusion Medicine. Fort Belvoir, VA: Defense Technical Information Center, August 2002. http://dx.doi.org/10.21236/ada406020.
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Petrova, I. V., O. A. Trubacheva, O. S. Mangataeva, T. E. Suslova, I. V. Kovalev, and S. V. Gusakova. INFLUENCE OF HYDROGEN SULFIDE ON COLLAGEN-INDUCED AGGREGATION OF HUMAN PLATELETS. DOI CODE, 2015. http://dx.doi.org/10.18411/doicode-2023.141.
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Zuckerman, Kenneth S. Reparative Medicine: Production of Erythrocytes & Platelets from Human Embryonic Stem Cells. Fort Belvoir, VA: Defense Technical Information Center, October 2012. http://dx.doi.org/10.21236/ada566171.
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Bode, Arthur P. Evaluation of Dried Storage of Platelets for Transfusion: Physiologic Integrity and Hemostatic Functionality. Fort Belvoir, VA: Defense Technical Information Center, June 1994. http://dx.doi.org/10.21236/ada280665.
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Bode, Arthur P. Evaluation of Dried Storage of Platelets for Transfusion: Physiologic Integrity and Hemostatic Functionality. Fort Belvoir, VA: Defense Technical Information Center, October 1994. http://dx.doi.org/10.21236/ada286078.
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Bode, Arthur P., and Marjorie S. Read. Evaluation of Dried Storage of Platelets for Transfusion: Physiologic Integrity and Hemostatic Functionality. Fort Belvoir, VA: Defense Technical Information Center, June 1992. http://dx.doi.org/10.21236/ada254796.
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Bode, Arthur P. Evaluation of Dried Storage of Platelets for Transfusion: Physiologic Integrity and Hemostatic Functionality. Fort Belvoir, VA: Defense Technical Information Center, June 1993. http://dx.doi.org/10.21236/ada266958.
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Bode, Arthur P., Marjorie S. Read, and Robert L. Reddick. Evaluation of Dried Storage of Platelets for Transfusion: Physiologic Integrity and Hemostatic Functionality. Fort Belvoir, VA: Defense Technical Information Center, February 1993. http://dx.doi.org/10.21236/ada276018.
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