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https://www.readbyqxmd.com/read/28731874/novel-targets-for-anticoagulants-lacking-bleeding-risk
#1
Julia K Bickmann, Trevor Baglin, Joost C M Meijers, Thomas Renné
PURPOSE OF REVIEW: Arterial and venous thromboembolic diseases are associated with significant morbidity and mortality and present a major medical burden. Currently used anticoagulants for the prevention or treatment of thromboembolic events including heparins, vitamin K-antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for hemostatic mechanisms to terminate blood loss at injury sites...
July 20, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28730526/direct-oral-anticoagulants-use-in-antiphospholipid-syndrome-are-these-drugs-an-effective-and-safe-alternative-to-warfarin-a-systematic-review-of-the-literature-comment
#2
REVIEW
Hannah Cohen, Beverley J Hunt, Maria Efthymiou, Ian J Mackie, Munther Khamashta, David A Isenberg
We respond to comments by Dufrost et al. about the RAPS trial, in particular, showing that the trial did achieve its target sample size; pointing out that thrombin potential is not synonymous with overall thrombin generation; confirming that overall, no increased thrombotic risk was evident comparing rivaroxaban with warfarin; and that high-risk patients (28% were triple positive, representative of patients with venous thromboembolism requiring standard-intensity anticoagulation) were included; and clarifying our rationale for using a laboratory surrogate primary outcome measure instead of a clinical one...
August 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28729433/selective-factor-viii-activation-by-the-tissue-factor-factor-viia-factor-xa-complex
#3
Yuichi Kamikubo, G Loredana Mendolicchio, Antonella Zampolli, Patrizia Marchese, Andrea S Rothmeier, Jennifer Nagrampa Orje, Andrew J Gale, Sriram Krishnaswamy, András Gruber, Henrik Østergaard, Lars C Petersen, Wolfram Ruf, Zaverio M Ruggeri
Safe and effective antithrombotic therapy requires understanding of mechanisms that contribute to pathological thrombosis but have lesser impact on hemostasis. We found that the extrinsic tissue factor (TF) coagulation initiation complex can selectively activate the anti-hemophilic cofactor, FVIII, triggering the hemostatic intrinsic coagulation pathway independently of thrombin feedback loops. In a mouse model with a relatively mild thrombogenic lesion, TF-dependent FVIII activation sets the threshold for thrombus formation through contact phase-generated FIXa...
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28727490/comparison-of-the-release-of-micrornas-and-extracellular-vesicles-from-platelets-in-response-to-different-agonists
#4
Ashley R Ambrose, Mohammed A Alsahli, Sameer A Kurmani, Alison H Goodall
On activation platelets release microRNAs and extracellular vesicles (EV) into circulation. The release of EV from platelets has been shown to be dependent on the agonist; in this study, we investigated whether the microRNA profile or EV released from platelets was also agonist specific. Washed platelets from healthy subjects were maximally stimulated with agonists specific for the receptors for collagen (Glycoprotein VI (GPVI)), thrombin (PAR1/PAR4), or ADP (P2Y1/P2Y12) with/without inhibiting secondary mediators, using aspirin to block cyclooxygenase-1 and apyrase to remove ADP...
July 20, 2017: Platelets
https://www.readbyqxmd.com/read/28723962/surface-functionalization-specific-binding-of-coagulation-factors-by-zinc-oxide-nanoparticles-delays-coagulation-time-and-reduces-thrombin-generation-potential-in-vitro
#5
Jun-Young Yang, Jiyeong Bae, Ayoung Jung, Seonyeong Park, Seungtae Chung, Jihyun Seok, Hangsik Roh, Youngju Han, Jae-Min Oh, Soojung Sohn, Jayoung Jeong, Wan-Seob Cho
Zinc oxide nanoparticles (ZnO NPs) have many biomedical applications such as chemotherapy agents, vaccine adjuvants, and biosensors but its hemocompatibility is still poorly understood, especially in the event of direct contact of NPs with blood components. Here, we investigated the impact of size and surface functional groups on the platelet homeostasis. ZnO NPs were synthesized in two different sizes (20 and 100 nm) and with three different functional surface groups (pristine, citrate, and L-serine). ZnO NPs were incubated with plasma collected from healthy rats to evaluate the coagulation time, kinetics of thrombin generation, and profile of levels of coagulation factors in the supernatant and coronated onto the ZnO NPs...
2017: PloS One
https://www.readbyqxmd.com/read/28723117/versatile-barometer-biosensor-based-on-au-pt-core-shell-nanoparticle-probe
#6
Qiangqiang Fu, Ze Wu, Dan Du, Chengzhou Zhu, Yuehe Lin, Yong Tang
There is a high global demand for sensitive, portable, user-friendly, and cost-effective biosensors. In this work, we introduce a barometer-based biosensor for the detection of a broad range of targets. The device is operated by measuring the pressure change produced by oxygen (O2) generation in a limited chamber using a portable barometer. The design employs core-shell Au@Pt nanoparticles (Au@PtNPs) as the bioassay probe to catalyze the decomposition of H2O2 and the release of O2. As a proof of concept, we developed barometer-based immunosensors to detect carcinoembryonic antigen (CEA) and ractopamine (Rac)...
June 23, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28719611/rna-sequencing-to-determine-the-contribution-of-kinase-receptor-transactivation-to-g-protein-coupled-receptor-signalling-in-vascular-smooth-muscle-cells
#7
Danielle Kamato, Venkata Vijayanand Bhaskarala, Nitin Mantri, Tae Gyu Oh, Dora Ling, Reearna Janke, Wenhua Zheng, Peter J Little, Narin Osman
G protein coupled receptor (GPCR) signalling covers three major mechanisms. GPCR agonist engagement allows for the G proteins to bind to the receptor leading to a classical downstream signalling cascade. The second mechanism is via the utilization of the β-arrestin signalling molecule and thirdly via transactivation dependent signalling. GPCRs can transactivate protein tyrosine kinase receptors (PTKR) to activate respective downstream signalling intermediates. In the past decade GPCR transactivation dependent signalling was expanded to show transactivation of serine/threonine kinase receptors (S/TKR)...
2017: PloS One
https://www.readbyqxmd.com/read/28712479/antiplatelet-aggregation-activity-of-walnut-hull-extract-via-suppression-of-reactive-oxygen-species-generation-and-caspase-activation
#8
Azadeh Meshkini, Masoumeh Tahmasbi
Walnut hull (wal hull) is an agricultural by-product that is widely used in traditional medicine for alleviating pain and treating skin diseases, however, recently it has gained much attention in modern pharmacology due to its antioxidant properties. The current study was aimed to determine the total phenolic, flavonoid, and tannin content of Persian wal hull extract and evaluate its biological effects on platelet function. Experimental data showed that acetone extract of wal hulls has a high content of polyphenolic compounds and antioxidant properties...
June 2017: Journal of Acupuncture and Meridian Studies
https://www.readbyqxmd.com/read/28711993/clinical-risk-assessment-in-the-antiphospholipid-syndrome-current-landscape-and-emerging-biomarkers
#9
REVIEW
Shruti Chaturvedi, Keith R McCrae
PURPOSE OF REVIEW: Laboratory criteria for the classification of antiphospholipid syndrome include the detection of a lupus anticoagulant and/or anticardiolipin and anti-β2-glycoprotein I antibodies. However, the majority of patients who test positive in these assays do not have thrombosis. Current risk-stratification tools are largely limited to the antiphospholipid antibody profile and traditional thrombotic risk factors. RECENT FINDINGS: Novel biomarkers that correlate with disease activity and potentially provide insight into future clinical events include domain 1 specific anti-β2GPI antibodies, antibodies to other phospholipids or phospholipid/protein antigens (such as anti-PS/PT), and functional/biological assays such as thrombin generation, complement activation, levels of circulating microparticles, and annexin A5 resistance...
July 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28711012/osteopontin-in-hepatocellular-carcinoma-a-possible-biomarker-for-diagnosis-and-follow-up
#10
Manuela Cabiati, Melania Gaggini, Maria Michela Cesare, Chiara Caselli, Paolo De Simone, Franco Filipponi, Giuseppina Basta, Amalia Gastaldelli, Silvia Del Ry
Recently osteopontin (OPN), a protein of the extracellular matrix, has generated in hepatocellular carcinoma (HCC) a significant interest as a prognostic factor. Aim of this study was to confirm, in liver tissues of subjects with HCV-positive HCC undergoing liver transplantation (RL, n=10) and of donors (DL, n=14), the increase of OPN plasma and tissue concentration, the OPN splicing isoforms expression profiling together with those of thrombin, and to evaluate a possible association between OPN measurements...
July 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28705901/temporal-contribution-of-the-platelet-body-and-balloon-to-thrombin-generation
#11
Ejaife O Agbani, Ingeborg Hers, Alastair W Poole
No abstract text is available yet for this article.
July 13, 2017: Haematologica
https://www.readbyqxmd.com/read/28703014/thrombin-receptor-agonist-peptide-induced-platelet-aggregation-is-reduced-in-patients-receiving-dabigatran
#12
Frantisek Nehaj, Juraj Sokol, Michal Mokan, Jela Ivankova, Maros Mokan
The availability of direct oral anticoagulants has caused a paradigm shift in thrombosis management. The direct thrombin inhibitor dabigatran seems to obstruct tenase complex by inhibiting thrombin generated in the initial phase and feed back to the amplification phase of cell-based coagulation reactions. However, it is still not fully understood if and how dabigatran impact platelet function. This observational study aimed to assess in vitro platelet function in patients with atrial fibrillation receiving dabigatran...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28696568/reproducibility-of-studies-with-genetically-modified-mice
#13
H R Lijnen
In their Editorial in the May issue of JTH, Rosendaal and Reitsma address different factors that may contribute to irreproducible results. They also refer to the Recommendation and Guidelines article by Colin Longstaff where Shiny apps are discussed as a tool to simplify and standardize data analysis for global assays such as thrombin generation and euglobulin clot lysis assays. However, I believe that also for in vivo biomedical studies, in particular with genetically modified mice, the problem of reproducibility of data describing a specific phenotype is becoming a major concern...
July 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28694452/phosphatidylserine-mediated-platelet-clearance-by-endothelium-decreases-platelet-aggregates-and-procoagulant-activity-in-sepsis
#14
Ruishuang Ma, Rui Xie, Chengyuan Yu, Yu Si, Xiaoming Wu, Lu Zhao, Zhipeng Yao, Shaohong Fang, He Chen, Valerie Novakovic, Chunyan Gao, Junjie Kou, Yayan Bi, Hemant S Thatte, Bo Yu, Shufen Yang, Jin Zhou, Jialan Shi
The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28692840/normal-pregnancy-is-associated-with-an-increase-in-thrombin-generation-from-the-very-early-stages-of-the-first-trimester
#15
C N Bagot, E Leishman, C C Onyiaodike, F Jordan, D J Freeman
BACKGROUND: Pregnancy is a hypercoagulable state associated with an increased risk of venous thrombosis, which begins during the first trimester, but the exact time of onset is unknown. Thrombin generation, a laboratory marker of thrombosis risk, increases during normal pregnancy but it is unclear exactly how early this increase occurs. METHODS: We assessed thrombin generation by Calibrated Automated Thrombography in women undergoing natural cycle in vitro fertilization, who subsequently gave birth at term following a normal pregnancy (n=22)...
June 29, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28692682/low-thrombin-generation-predicts-poor-prognosis-in-ischemic-stroke-patients-after-thrombolysis
#16
Renáta Hudák, Edina G Székely, Katalin R Kovács, Attila Nagy, Gergely Hofgárt, Ervin Berényi, László Csiba, János Kappelmayer, Zsuzsa Bagoly
Thrombolysis by intravenous recombinant tissue plasminogen activator (rt-PA) is an effective therapy in acute ischemic stroke (AIS). Thrombin generation test (TGT) is a global hemostasis test providing information about the speed and amount of generated thrombin in plasma. Here we aimed to find out whether results of this test before the initiation of thrombolysis might predict outcomes. Study population included 120 consecutive AIS patients, all within 4.5 hours of their symptom onset, who underwent thrombolysis by rt-PA...
2017: PloS One
https://www.readbyqxmd.com/read/28692575/rendering-factor-xa-zymogen-like-as-a-therapeutic-strategy-to-treat-bleeding
#17
Nabil K Thalji, Rodney M Camire
PURPOSE OF REVIEW: New therapies are needed to control bleeding in a range of clinical conditions. This review will discuss the biochemical properties of zymogen-like factor Xa, its preclinical assessment in different model systems, and future development prospects. RECENT FINDINGS: Underlying many procoagulant therapeutic approaches is the rapid generation of thrombin to promote robust clot formation. Clinically tested prohemostatic agents (e.g., factor VIIa) can provide effective hemostasis to mitigate bleeding in hemophilia and other clinical situations...
July 7, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28692431/differing-mechanisms-of-thrombin-generation-in-live-haematological-and-solid-cancer-cells-determined-by-calibrated-automated-thrombography
#18
Mufuliat Adeola Adesanya, Anthony Maraveyas, Leigh Madden
: Calibrated automated thrombography (CAT) is emerging as a reliable tool for real-time estimation of thrombin generation potential. There is a clinical need for knowledge about the pathways underlying the thrombotic phenotype of different malignancies. Cells from solid (e.g. pancreatic cancer; n = 7) and malignant haematological cell lines (e.g. multiple myeloma; n = 5) were evaluated for thrombin generation, using CAT, with the addition of control plasma (NormTrol; Helena Biosciences, Gateshead, UK)) or plasma deficient in coagulation factors VII and XII...
July 7, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28692314/long-term-low-molecular-weight-heparin-anticoagulant-therapy-modulates-thrombin-generation-and-d-dimer-in-patients-with-cancer-and-venous-thromboembolism
#19
Andrea D'Alessio, Marina Marchetti, Carmen Julia Tartari, Laura Russo, Sara Cecchini, Kim W F M Lambregts, Daniela di Mauro, Anna Falanga
We enrolled 62 consecutive patients with advanced stage cancers and venous thromboembolism (VTE), prospectively followed until 1 year. All patients received 6 month low-molecular-weight heparin (LMWH) therapy. We evaluated thrombin generation (TG) and D-dimer levels at different time points, to determine whether they were sensitive to LMWH and explore a possible association with VTE recurrence, bleeding, and overall survival. During LMWH, levels of TG and D-dimer significantly dropped. No VTE recurrences occurred, one patient had cancer-related intestinal hemorrhage...
July 10, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28692110/plasma-carboxypeptidase-u-cpu-cpb2-tafia-generation-during-in-vitro-clot-lysis-and-its-interplay-between-coagulation-and-fibrinolysis
#20
Dorien Leenaerts, Jef Aernouts, Pieter Van Der Veken, Yani Sim, Anne-Marie Lambeir, Dirk Hendriks
Carboxypeptidase U (CPU, CPB2, TAFIa) is a basic carboxypeptidase that is able to attenuate fibrinolysis. The inactive precursor procarboxypeptidase U is converted to its active form by thrombin, the thrombin-thrombomodulin complex or plasmin. The aim of this study was to investigate and characterise the time course of CPU generation in healthy individuals. In plasma of 29 healthy volunteers, CPU generation was monitored during in vitro clot lysis. CPU activity was measured by means of an enzymatic assay that uses the specific substrate Bz-o-cyano-Phe-Arg...
July 6, 2017: Thrombosis and Haemostasis
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