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Paola Patrignani, Carlo Patrono
Several lines of evidence are consistent with the hypothesis that activated platelets contribute to colorectal tumorigenesis and metastatization through direct cell-cell interactions and the release of different lipid and protein mediators, and microvesicles. This review examines the clinical pharmacology of low-dose aspirin as a basis for discussing the mechanisms underlying the contribution of platelets to neoplastic transformation and progression of cancer via the development of metastases.
July 9, 2018: Platelets
Paul Harrison, M Angelyn Bethel, Irene Kennedy, Robert Dinsdale, Ruth Coleman, Rury R Holman
The antiplatelet efficacy of aspirin (ASA) is reduced in type 2 diabetes (T2D). As the best ex vivo method of measuring ASA efficacy remains uncertain, we compared nine platelet function tests to assess responsiveness to three ASA dosing regimens in 24 T2D patients randomized in a three-treatment crossover design to ASA 100 mg/day, 200 mg/day, or 100 mg twice daily for 2-week treatment periods. Platelet function tests compared were as follows: light transmission aggregometry (LTA)-0.5 mg/mL of arachidonic acid (AA) and 10 µM adenosine diphosphate (ADP); multiplate whole blood aggregometry (WBA)-0...
July 9, 2018: Platelets
Paquita Nurden, Alan Nurden, Rémi Favier, Matthieu Gleyze
The number of genes involved in the identification of macrothrombocytopenia (MTP) is growing but the clinical consequences for the affected patients are not well determined. Here, we report the management of the bleeding risk for a patient with the newly reported and rare DIAPH1-related disease during surgery for infertility and then during her subsequent pregnancy. The R1213* DIAPH1 variant responsible for a mild bleeding syndrome in six families was considered a potential risk factor for our patient. Preliminary laparoscopic surgery was followed by neosalpingostomy to open the obstructed fallopian tube that was followed by an ectopic pregnancy requiring further surgery, tranexamic acid was used on each occasion and no bleeding complications were observed...
July 9, 2018: Platelets
Marco Ranucci, Tommaso Aloisio, Umberto Di Dedda, Maria Teresa La Rovere, Blanca Martinez Lopez De Arroyabe, Ekaterina Baryshnikova
Body mass index (BMI) and specifically overweight and obesity have been associated with an increased platelet reactivity in different series of patients. This information is derived by different laboratory platelet function tests (PFTs) like mean platelet volume (MPV), platelet microparticles, thromboxane B2 metabolites, and others. Point-of-care PFT, which are often used in cardiac surgery, are rarely addressed. The present study aims to verify platelet reactivity using multiple-electrode aggregometry (MEA) as a function of BMI in cardiac surgery patients...
July 9, 2018: Platelets
Natalia Dovlatova, Stan Heptinstall
Platelets play a crucial role in haemostasis and thrombosis and evaluation of platelet function in vitro, in particular platelet aggregation responses, has been one of the most common and useful ways of evaluating the risk of bleeding and thrombotic events and assessing the effects of various compounds and conditions on platelets. Traditional approaches to assessing platelet aggregation require specialised equipment and trained laboratory personnel and have other limitations. Studying platelet aggregation in whole blood offers a more physiologically relevant measurement...
July 9, 2018: Platelets
Malou Zuidscherwoude, Hannah L H Green, Steven G Thomas
The platelet and megakaryocyte cytoskeletons are essential for formation and function of these cells. A dynamic, properly organised tubulin and actin cytoskeleton is critical for the development of the megakaryocyte and the extension of proplatelets. Tubulin in particular plays a pivotal role in the extension of these proplatelets and the release of platelets from them. Tubulin is further required for the maintenance of platelet size, and actin is the driving force for shape change, spreading and platelet contraction during platelet activation...
June 18, 2018: Platelets
Irina Pleines, Deya Cherpokova, Markus Bender
Megakaryocytes differentiate from hematopoietic stem cells in the bone marrow. The transition of megakaryocytes to platelets is a complex process. Thereby, megakaryocytes extend proplatelets into sinusoidal blood vessels, where the proplatelets undergo fission to release platelets. Defects in platelet production can lead to a low platelet count (thrombocytopenia) with increased bleeding risk. Rho GTPases comprise a family of small signaling G proteins that have been shown to be master regulators of the cytoskeleton controlling many aspects of intracellular processes...
June 18, 2018: Platelets
Shujun Wang, Jun Yuan, Jie Yang, Na Li, Ran Liu, Jianfeng Luan, Dong Ye
Human platelets play important roles in several physiologic and pathologic processes. Any defects in platelet number and function can lead to a variety of bleeding complications; platelet transfusions are commonly used to improve platelet count and hemostatic function in these cases. However, transfusions are complicated by the short storage life of donated platelets and contamination risks. Synthetic platelet substitutes can render efficient hemostasis while allowing advantages of large-scale preparation, minimum contamination risk via effective sterilization, longer shelf-life, no need for blood type matching, and reduced risks of biologic or pathologic side effects...
June 8, 2018: Platelets
Farzaneh Dehghani, Narges Sotoude, Hossein Bordbar, M R Panjeshahin, Saied Karbalay-Doust
Platelet-rich plasma (PRP) has a potential effect on tissue repair through proliferation and differentiation of tissue progenitor cells. The aim of this study was to evaluate the effect of PRP on the testis structure and function in infertile rat model by stereological method. Thirty-two male rats were divided into four groups. Infertility was induced by the administration of busulfan (BUS) (10mg/kg, I.P., single dose). PRP (80μl, testis local injected, single dose) was administered for the subjects. After 48 days, semen analysis was performed and blood samples were taken from the heart to measure the testosterone...
June 8, 2018: Platelets
Muhammad Irfan, Dahye Jeong, Evelyn Saba, Hyuk-Woo Kwon, Jung-Hae Shin, Bo-Ra Jeon, Suk Kim, Sung-Dae Kim, Dong-Ha Lee, Seung-Yeol Nah, Man Hee Rhee
Panax ginseng (P. ginseng), one of the most valuable medicinal plants, is known for its healing and immunobooster properties and has been widely used in folk medicine against cardiovascular diseases, including stroke and heart attack. In this study, we explored the anti-platelet activity of gintonin (a recently discovered non-saponin fraction of ginseng) against agonist-induced platelet activation. In vitro effects of gintonin on agonist-induced human and rat platelet aggregation, granule secretion, integrin αIIb β3 activation, and intracellular calcium ion ([Ca2+ ]i ) mobilization were examined...
June 5, 2018: Platelets
Kathryn E Hally, Anne C La Flamme, Scott A Harding, Peter D Larsen
Platelet activation underlies the pathology of an acute myocardial infarction (AMI), and dual antiplatelet therapy (DAPT) is administered post-AMI to limit this activation. Platelets express Toll-like receptors (TLRs) 1, 2, and 4 and become potently activated in response to TLR2/1 and TLR4 stimulation. However, it is unknown whether antiplatelet agents can protect against platelet activation via these TLR pathways. This study aimed to determine the extent to which TLR-mediated platelet activation can be inhibited by currently used antiplatelet agents...
June 5, 2018: Platelets
Susanne Claudia Gruber, Matthias Karl Freynhofer, Martin Willheim, Thomas Werner Weiss, Florian Egger, Wolfgang Hübl, Kurt Huber
Long-term evidence shows an increased risk of cardiovascular events in the morning hours and recent studies in aspirin-treated patients have shown increased platelet reactivity at the end of the dosing interval. Similar pharmacodynamic analyses of adenosine-diphosphate (ADP) receptor inhibitors are scarce. We therefore investigated changes in clopidogrel-dependent platelet function and activation over 24 h and whether enhanced platelet turnover might explain diurnal variability of platelet function and activation...
June 5, 2018: Platelets
Fred G Pluthero, Jorge Di Paola, Manuel D Carcao, Walter H A Kahr
Homozygosity/compound heterozygosity for loss of function mutations in neurobeachin-like 2 (NBEAL2) is causative for Gray platelet syndrome (GPS; MIM #139090), characterized by thrombocytopenia and large platelets lacking α-granules and cargo. Most GPS-associated NBEAL2 mutations generate nonsense codons; frameshifts causing premature translation termination and/or changes in mRNA splicing have also been observed. Data regarding NBEAL2 protein expression in GPS patients is limited. We observed absence of NBEAL2 in platelets from GPS patients with 3 different genotypes, and reduced/truncated platelet NBEAL2 has been reported for others...
June 5, 2018: Platelets
Joakim Alfredsson, Eva Swahn, Kerstin M Gustafsson, Magnus Janzon, Lena Jonasson, Elisabeth Logander, Lennart Nilsson, Tomas L Lindahl
There is a large inter-individual variation in response to clopidogrel treatment, and previous studies have indicated higher risk of thrombotic events in those with high residual platelet reactivity (HPR). Less is known about individual variation over time. The aim of this prospective cohort study was to investigate intra-individual variation in platelet reactivity. Platelet aggregation in whole blood was assessed in 77 patients, at 3 days, 8 days and 6 months after admission for acute myocardial infarction and loading dose of clopidogrel...
June 5, 2018: Platelets
Lucia Stefanini, Wolfgang Bergmeier
Platelets are highly specialized cells that continuously patrol the vasculature to ensure its integrity (hemostasis). At sites of vascular injury, they are able to respond to trace amounts of agonists and to rapidly transition from an anti-adhesive/patrolling to an adhesive state (integrin inside-out activation) required for hemostatic plug formation. Pathological conditions that disturb the balance in the underlying signaling processes can lead to unwanted platelet activation (thrombosis) or to an increased bleeding risk...
June 4, 2018: Platelets
Dong Chen, Cindy B Uhl, Sandra C Bryant, Marcy Krumwiede, Ryan L Barness, Mary C Olson, Susan C Gossman, Sibel Erdogan Damgard, Scott I Gamb, Lisa A Cummins, Jon E Charlesworth, Christina M Wood-Wentz, Jeffrey L Salisbury, Elizabeth A Plumhoff, Elizabeth M Van Cott, Rong He, Deepti M Warad, Rajiv K Pruthi, John A Heit, William L Nichols, James G White
Platelet transmission electron microscopy (PTEM) is considered the gold standard test for assessing distinct ultrastructural abnormalities in inherited platelet disorders (IPDs). Nevertheless, PTEM remains mainly a research tool due to the lack of standardized procedures, a validated dense granule (DG) count reference range, and standardized image interpretation criteria. The aim of this study was to standardize and validate PTEM as a clinical laboratory test. Based on previously established methods, we optimized and standardized preanalytical, analytical, and postanalytical procedures for both whole mount (WM) and thin section (TS) PTEM...
June 4, 2018: Platelets
Katsue Suzuki-Inoue
Podoplanin is a type-I transmembrane sialomucin-like glycoprotein expressed on the surface of several kinds of tumor cells. The podoplanin receptor is a platelet activation receptor known as C-type lectin-like receptor 2 (CLEC-2), which has been identified as a receptor for the platelet-activating snake venom protein rhodocytin. CLEC-2 is highly expressed in platelets and megakaryocytes and expressed at lower levels in liver Kupffer cells. Podoplanin is expressed in certain types of tumor cells, including squamous cell carcinomas, seminomas, and brain tumors...
June 4, 2018: Platelets
Craig E Hughes
Light transmission aggregometry and lumi-aggregometry are the gold standard platelet assays both clinically and for basic research. The availability of different strains of genetically modified mice and mouse models of human disease means that often laboratories need to use mouse platelets in these assays. Overall, performing aggregometry and lumi-aggregometry with mouse platelets is similar to with human platelets, although methods need be adapted to accommodate their small size, reduced blood volume, and different protein levels...
June 4, 2018: Platelets
Musa Alzahrani, Ibrahim Alrumaih, Fahad Alhamad, Ahmed Abdel Warith
Pipercillin-tazobactam is a frequently used antibiotic that has a broad spectrum of antibacterial activity. The development of severe thrombocytopenia following the use of piperacillin-tazobactam is unusual. Several mechanisms have been proposed for the pathogenesis of thrombocytopenia in this setting which include immune and non-immune causes. Multiple case reports have shown the ability of piperacillin-tazobactam to cause drug-induced immune thrombocytopenia, likely through formation of antibodies that recognize platelets in the presence of soluble piperacillin...
June 4, 2018: Platelets
Elmina Mammadova-Bach, Maximilian Mauler, Attila Braun, Daniel Duerschmied
Platelets serotonin (5-hydroxytrytamine, 5-HT) uptake and storage in dense granules is tightly regulated by the serotonergic transport system in the blood. Several 5-HT transporters (5-HTTs) have been identified in the vasculature and blood cells, beyond them 5-HTT is the major 5-HT transporter in platelets. Abnormal 5-HT concentrations in the blood plasma or increased platelet 5-HT uptake or abnormal release contribute to the development of various diseases in the vasculature. Consequently, several clinical trials suggested the positive therapeutic effects of 5-HTT blockade in the circulation...
June 4, 2018: Platelets
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