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https://www.readbyqxmd.com/read/28943410/loss-of-reelin-protects-mice-against-arterial-thrombosis-by-impairing-integrin-activation-and-thrombus-formation-under-high-shear-conditions
#1
Nina Sarah Gowert, Irena Krüger, Meike Klier, Lili Donner, Friederike Kipkeew, Michael Gliem, Nicholas J Bradshaw, David Lutz, Sabrina Köber, Harald Langer, Sebastian Jander, Kerstin Jurk, Michael Frotscher, Carsten Korth, Hans H Bock, Margitta Elvers
Reelin is a secreted glycoprotein and essential for brain development and plasticity. Recent studies provide evidence that Reelin modifies platelet actin cytoskeletal dynamics. In this study we sought to dissect the contribution of Reelin in arterial thrombus formation. Here we analyzed the impact of Reelin in arterial thrombosis ex vivo and in vivo using Reelin deficient (reeler) and wildtype mice. We found that Reelin is secreted upon platelet activation and mediates signaling via glycoprotein (GP)Ib, the amyloid precursor protein (APP) and apolipoprotein E receptor 2 (ApoER2) to induce activation of Akt, extracellular signal-regulated kinase (Erk), SYK and Phospholipase Cγ2...
September 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28931100/-venous-thromboembolism-vte-current-diagnosis-and-therapy-with-special-attention-towards-oncologic-patients
#2
György Pfliegler
Deep vein thrombosis (DVT), pulmonary embolism (PE), or with the common name venous thromboembolism (VTE) are frequent manifestations of pathologic hemostasis in malignancies, thereby contributing to the large number of patients despite recent developments in thrombosis prevention. In the present paper up-to-date practice of diagnosis and therapy will be discussed partly based on the author's previous publications on epidemiology and prophylaxis of VTE in oncological patients.
September 20, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28930569/the-biology-of-the-platelet-with-special-reference-to-inflammation-wound-healing-and-immunity
#3
Alan T Nurden
While platelets have long been known to be essential for maintaining hemostasis in the vasculature, their role in tissue repair, inflammation and innate and adaptive immunity is a more recent science. The ability of platelets to attach to the vessel wall, form aggregates and promote fibrin formation, key elements of blood clotting, has been said to both favor and dampen inflammation, to fight infection and to assure an adequate immune response. To fulfill their different roles platelets often synchronize with leukocytes and cells of the immune system...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28928125/ck2%C3%AE-critically-regulates-thrombopoiesis-and-ca-2-triggered-platelet-activation-in-arterial-thrombosis-in-vivo
#4
Patrick Münzer, Britta Walker-Allgaier, Sascha Geue, Friederike Langhauser, Eva Geuss, David Stegner, Katja Aurbach, Daniela Semeniak, Madhumita Chatterjee, Irene Gonzalez Menendez, Melanie Märklin, Leticia Quintanilla-Martinez, Helmut R Salih, David W Litchfield, Thierry Buchou, Christoph Kleinschnitz, Florian Lang, Bernhard Nieswandt, Irina Pleines, Harald Schulze, Meinrad Gawaz, Oliver Borst
Platelets, anucleated megakaryocyte-derived cells, play a major role in hemostasis and arterial thrombosis. While protein kinase Casein Kinase 2 (CK2) is readily detected in megakaryocytes and platelets, the impact of CK2-dependent signaling on megakaryocyte/platelet (patho-) physiology has remained elusive. The present study explored the impact of the CK2 regulatory β-subunit on platelet biogenesis and activation. Megakaryocyte/platelet-specific genetic deletion of CK2β (ck2β(-/-) ) in mice resulted in a significant macrothrombocytopenia and an increased extramedullar megakaryopoiesis with enhanced proportion of premature platelets...
September 19, 2017: Blood
https://www.readbyqxmd.com/read/28917273/mechanisms-and-risk-factors-of-thrombosis-in-cancer
#5
REVIEW
Anna Falanga, Laura Russo, Viola Milesi, Alfonso Vignoli
The close relationship between cancer and thrombosis is known since more than a century. Venous thromboembolism (VTE) may be the first manifestation of an occult malignancy in an otherwise healthy individual. Cancer patients commonly present with abnormalities of laboratory coagulation tests, indicating an ongoing subclinical hypercoagulable condition. The results of laboratory tests demonstrate that a process of fibrin formation and removal parallels the development of malignancy, which is of particular interest since fibrin and other clotting products are important for both thrombogenesis and tumor progression...
October 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28915447/oxidative-stress-induced-modulation-of-platelet-integrin-%C3%AE-2b%C3%AE-3-expression-and-shedding-may-predict-the-risk-of-major-bleeding-in-heart-failure-patients-supported-by-continuous-flow-left-ventricular-assist-devices
#6
Nandan K Mondal, Zengsheng Chen, Jaimin R Trivedi, Erik N Sorensen, Si M Pham, Mark S Slaughter, Bartley P Griffith, Zhongjun J Wu
INTRODUCTION: Oxidative stress and platelet integrin α2bβ3 plays important role in the process of hemostasis and thrombosis. We hypothesized that device-induced patient specific oxidative stress and integrin α2bβ3 shedding may be linked to major bleeding complication (MBC) in heart failure (HF) patients supported by continuous flow left ventricular assist devices (CF-LVADs). MATERIALS AND METHODS: We recruited 47patients implanted with CF-LVADs and 15 healthy volunteers...
September 8, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28915383/force-activatable-biosensor-enables-single-platelet-force-mapping-directly-by-fluorescence-imaging
#7
Yongliang Wang, Dana N LeVine, Margaret Gannon, Yuanchang Zhao, Anwesha Sarkar, Bailey Hoch, Xuefeng Wang
Integrin-transmitted cellular forces are critical for platelet adhesion, activation, aggregation and contraction during hemostasis and thrombosis. Measuring and mapping single platelet forces are desired in both research and clinical applications. Conventional force-to-strain based cell traction force microscopies have low resolution which is not ideal for cellular force mapping in small platelets. To enable platelet force mapping with submicron resolution, we developed a force-activatable biosensor named integrative tension sensor (ITS) which directly converts molecular tensions to fluorescent signals, therefore enabling cellular force mapping directly by fluorescence imaging...
September 8, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28887505/impaired-fibrinolysis-and-lower-levels-of-plasma-%C3%AE-2-macroglobulin-are-associated-with-an-increased-risk-of-severe-asthma-exacerbations
#8
Stanislawa Bazan-Socha, Lucyna Mastalerz, Agnieszka Cybulska, Lech Zareba, Romy Kremers, Michal Zabczyk, Grazyna Pulka, Teresa Iwaniec, Jan G Bazan, Coenraad Hemker, Anetta Undas
Recently we have reported that asthma is associated with enhanced plasma thrombin formation, impaired fibrinolysis and platelet activation. In the present study we investigated whether described prothrombotic blood alterations might predispose to thromboembolic events or asthma exacerbations. In 164 adult asthmatics we assessed clinical events during 3-year follow-up and analyzed their associations with measured at baseline prothrombotic blood parameters. Data were obtained from 157 (95.7%) of the asthma patients...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28883275/successful-management-of-intraperitoneal-bleeding-with-platelet-apheresis-and-von-willebrand-factor-supplementation-in-a-patient-with-essential-thrombocythemia-and-acquired-von-willebrand-syndrome
#9
Toshimitsu Ueki, Kanako Takeshige, Masahiko Sumi, Mayumi Ueno, Naoaki Ichikawa, Hikaru Kobayashi
A 36-year-old woman with essential thrombocythemia (ET) was admitted to our hospital for acute lower abdominal pain. Given no family history of bleeding disorder, she was diagnosed with acquired von Willebrand syndrome. Despite having a medical history of venous thrombosis, she had never been treated for ET because of her preferences. On admission, CT scan revealed massive hemorrhage in the ascending colon with the leakage of a contrast agent. Furthermore, a delayed enhancement of fluid collection in the Douglas fossa followingcontrast CT indicated bloody ascites...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28882875/class-iii-pi3k-positively-regulates-platelet-activation-and-thrombosis-via-pi-3-p-directed-function-of-nadph-oxidase
#10
Yangyang Liu, Mengjiao Hu, Dongjiao Luo, Ming Yue, Shuai Wang, Xiaoyan Chen, Yangfan Zhou, Yi Wang, Yanchun Cai, Xiaolan Hu, Yuehai Ke, Zhongzhou Yang, Hu Hu
OBJECTIVE: Class III phosphoinositide 3-kinase, also known as vacuolar protein sorting 34 (VPS34), is a highly conserved enzyme regulating important cellular functions such as NADPH oxidase (NOX) assembly, membrane trafficking, and autophagy. Although VPS34 is expressed in platelets, its involvement in platelet activation remains unclear. Herein, we investigated the role of VPS34 in platelet activation and thrombus formation using VPS34 knockout mice. APPROACH AND RESULTS: Platelet-specific VPS34-deficient mice were generated and characterized...
September 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28867175/thrombo-hemorrhagic-liability-in-children-with-congenital-heart-diseases
#11
REVIEW
Shebl Said Shebl, Walid Ahmed Naguib El-Shehaby, Amira Hamed Darwish, Yasmin Shebl Said, Nabeh Helal Elfadaly, Eman Amer
BACKGROUND: The precise mechanisms of the increased incidence of hemostatic abnormalities in congenital heart disease (CHD) have not been determined. The aim of the study was to evaluate some indicators of activation of platelets and vascular endothelial cells in patients with CHD, evaluation of bleeding liability of these patients, and correlation with the clinical presentation of these patients. METHODS: This work was carried out on 20 patients with cyanotic congenital heart disease (CCHD), 20 patients with cyanotic congenital heart disease (ACHD), and 20 healthy children who served as the control group, aged between 1 and 10years...
August 26, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28863985/targeting-12-lipoxygenase-as-a-potential-novel-antiplatelet-therapy
#12
REVIEW
Benjamin E Tourdot, Michael Holinstat
Platelets are key contributors to the formation of occlusive thrombi; the major underlying cause of ischemic heart disease and stroke. Antiplatelet therapy has reduced the morbidity and mortality associated with thrombotic events; however, the utility of current antiplatelet therapies is limited by the concomitant risk of an adverse bleeding event. Novel antiplatelet therapies that are more efficacious at inhibiting thrombosis while minimally affecting hemostasis are required. Platelet-type 12-(S)-lipoxygenase (12-LOX), an oxygenase shown to potentiate platelet activation, represents a novel antiplatelet target...
August 29, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28860945/%C3%AE-3-phosphorylation-of-platelet-%C3%AE-iib%C3%AE-3-is-crucial-for-stability-of-arterial-thrombus-and-microparticle-formation-in-vivo
#13
Weiyi Feng, Manojkumar Valiyaveettil, Tejasvi Dudiki, Ganapati H Mahabeleshwar, Patrick Andre, Eugene A Podrez, Tatiana V Byzova
BACKGROUND: It is well accepted that functional activity of platelet integrin αIIbβ3 is crucial for hemostasis and thrombosis. The β3 subunit of the complex undergoes tyrosine phosphorylation shown to be critical for outside-in integrin signaling and platelet clot retraction ex vivo. However, the role of this important signaling event in other aspects of prothrombotic platelet function is unknown. METHOD: Here, we assess the role of β3 tyrosine phosphorylation in platelet function regulation with a knock-in mouse strain, where two β3 cytoplasmic tyrosines are mutated to phenylalanine (DiYF)...
2017: Thrombosis Journal
https://www.readbyqxmd.com/read/28856043/whole-blood-clot-optical-clearing-for-nondestructive-3d-imaging-and-quantitative-analysis
#14
Peter Höök, Teresa Brito-Robinson, Oleg Kim, Cody Narciso, Holly V Goodson, John W Weisel, Mark S Alber, Jeremiah J Zartman
A technological revolution in both light and electron microscopy imaging now allows unprecedented views of clotting, especially in animal models of hemostasis and thrombosis. However, our understanding of three-dimensional high-resolution clot structure remains incomplete since most of our recent knowledge has come from studies of relatively small clots or thrombi, due to the optical impenetrability of clots beyond a few cell layers in depth. Here, we developed an optimized optical clearing method termed cCLOT that renders large whole blood clots transparent and allows confocal imaging as deep as one millimeter inside the clot...
August 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/28855423/plant-based-food-cyanidin-3-glucoside-modulates-human-platelet-glycoprotein-vi-signaling-and-inhibits-platelet-activation-and-thrombus-formation
#15
Yanling Yao, Yanqiu Chen, Reheman Adili, Thomas McKeown, Pingguo Chen, Guangheng Zhu, Dan Li, Wenhua Ling, Heyu Ni, Yan Yang
Background: Platelets play an important role in hemostasis, thrombosis, and atherosclerosis. Glycoprotein VI (GPVI) is a major platelet receptor that interacts with exposed collagen on injured vessel walls. Our previous studies have shown that anthocyanins (a type of natural plant pigment) attenuate platelet function; however, whether anthocyanins affect collagen-induced GPVI signaling remains unknown.Objective: The objective of this study was to explore the effects of cyanidin-3-glucoside (Cy-3-g, one of the major bioactive compounds in anthocyanins) on platelet activation and thrombosis and the GPVI signaling pathway...
August 30, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28835439/management-of-rivaroxaban-or-apixaban-associated-major-bleeding-with-prothrombin-complex-concentrates-a-cohort-study
#16
Ammar Majeed, Anna Ågren, Margareta Holmström, Maria Bruzelius, Roza Chaireti, Jacob Odeberg, Eva-Lotta Hempel, Maria Magnusson, Tony Frisk, Sam Schulman
There is uncertainty regarding the effectiveness and occurrence of thromboembolic events in patients treated with prothrombin complex concentrates (PCC) for management of major bleeding events (MBE) on rivaroxaban or apixaban. We investigated the effectiveness of PCC given for management of MBE on rivaroxaban or apixaban. Between 1/1/2014 and 1/10/2016, we prospectively included patients treated with PCC for management of MBE on rivaroxaban or apixaban. The effectiveness of PCC was assessed using the International Society of Thrombosis and Hemostasis' Scientific and Standardization Subcommittee criteria for the assessment of effectiveness of major bleeding management...
August 23, 2017: Blood
https://www.readbyqxmd.com/read/28835437/clec-2-contributes-to-hemostasis-independently-of-classical-hemitam-signaling-in-mice
#17
Elizabeth J Haining, Deya Cherpokova, Karen Wolf, Isabelle C Becker, Sarah Beck, Johannes A Eble, David Stegner, Steve P Watson, Bernhard Nieswandt
C-type lectin-like receptor 2 (CLEC 2) is a platelet receptor that is critical during development in blood-lymph separation and implicated in thrombus stability in thrombosis and hemostasis. It is the only known platelet activatory receptor that participates in both these aspects of platelet function and is the only one to signal through a hemi-immunoreceptor tyrosine-based activation motif (hemITAM). Current investigations into the function of CLEC 2 in vivo have focused on knock-out studies in which both the receptor and its signaling are deleted, making it impossible to explore the possible signaling independent functions of the receptor which are indicated by its only known physiological ligand, podoplanin, being an integral membrane protein...
August 23, 2017: Blood
https://www.readbyqxmd.com/read/28833193/coagulation-and-fibrinolysis-in-gastric-cancer
#18
REVIEW
Ombretta Repetto, Valli De Re
Coagulation is a highly conserved process occurring after an injury to a blood vessel and resulting in hemostasis. In the thrombus microenvironment, finely orchestrated events restore vessel integrity through platelet activation, adhesion, and aggregation (primary hemostasis), followed by the coagulation cascades, thrombin generation, and fibrin clot deposition (secondary hemostasis). Several studies on cancer have provided insight into dramatic changes to coagulation-related events (i.e., fibrin clot deposition, fibrinolysis) during tumor pathogenesis, progression, and metastasis, in addition to a tumor-driven systemic activation of hemostasis and thrombosis (Trousseau's syndrome)...
August 22, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28831047/flow-induced-elongation-of-von-willebrand-factor-precedes-tension-dependent-activation
#19
Hongxia Fu, Yan Jiang, Darren Yang, Friedrich Scheiflinger, Wesley P Wong, Timothy A Springer
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...
August 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28829426/investigating-von-willebrand-factor-pathophysiology-using-a-flow-chamber-model-of-von-willebrand-factor-platelet-string-formation
#20
Alison Michels, Laura L Swystun, Jeffrey Mewburn, Silvia Albánez, David Lillicrap
Von Willebrand factor (VWF) is a multimeric glycoprotein coagulation factor that mediates platelet adhesion and aggregation at sites of endothelial damage and that carries factor VIII in the circulation. VWF is synthesized by endothelial cells and is either released constitutively into the plasma or is stored in specialized organelles, called Weibel-Palade bodies (WPBs), for on-demand release in response to hemostatic challenge. Procoagulant and proinflammatory stimuli can rapidly induce WPB exocytosis and VWF release...
August 14, 2017: Journal of Visualized Experiments: JoVE
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