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Clemens Feistritzer, Stefan Schmidt
During the 57(th) annual meeting of the American Society of Hematology 2015 in Orlando, Florida, various aspects in the field of hemostaseology were presented. The Choosing Wisely® campaign pointed out the importance of the critical use of diagnostic tools to rule out pulmonary embolism and questioned the relevance of thrombophilia testing in women undergoing routine infertility evaluation. Furthermore, the approval of idarucizumab, a specific antidote for the reversal of the anticoagulant effects of the direct thrombin inhibitor dabigatran, was highlighted...
2016: Memo
Nis Halland, Jörg Czech, Werngard Czechtizky, Andreas Evers, Markus Follmann, Markus Kohlmann, Herman A Schreuder, Christopher Kallus
Previously disclosed TAFIa inhibitors having a urea zinc-binding motif were used as the starting point for the development of a novel class of highly potent inhibitors having a sulfamide zinc-binding motif. High-resolution X-ray cocrystal structures were used to optimize the structures and reveal a highly unusual sulfamide configuration. A selected sulfamide was profiled in vitro and in vivo and displayed a promising ADMET profile.
October 17, 2016: Journal of Medicinal Chemistry
William B Hillegass, Gregory S Bradford
No abstract text is available yet for this article.
September 2016: Journal of Thoracic Disease
Jung-Hae Shin, Hyuk-Woo Kwon, Hyun-Jeong Cho, Man Hee Rhee, Hwa-Jin Park
BACKGROUND: Glycoprotein IIb/IIIa (αIIb/β3) is involved in platelet adhesion, and triggers a series of intracellular signaling cascades, leading to platelet shape change, granule secretion, and clot retraction. In this study, we evaluated the effect of ginsenoside Ro (G-Ro) on the binding of fibrinogen to αIIb/β3. METHODS: We investigated the effect of G-Ro on regulation of signaling molecules affecting the binding of fibrinogen to αIIb/β3, and its final reaction, clot retraction...
October 2016: Journal of Ginseng Research
Thomas Broggini, Lisa Schnell, Ali Ghoochani, José María Mateos, Michael Buchfelder, Kurt Wiendieck, Michael K Schäfer, Ilker Y Eyupoglu, Nicolai E Savaskan
The Plasticity Related Gene family covers five, brain-specific, transmembrane proteins (PRG1-5, also termed LPPR1-5) that operate in neuronal plasticity during development, aging and brain trauma. Here we investigated the role of the PRG family on axonal and filopodia outgrowth. Comparative analysis revealed the strongest outgrowth induced by PRG3 (LPPR1). During development, PRG3 is ubiquitously located at the tip of neuronal processes and at the plasma membrane and declines with age. In utero electroporation of PRG3 induced dendritic protrusions and accelerated spine formations in cortical pyramidal neurons...
October 15, 2016: Aging
Ibrahim Eker, Soner Yilmaz, Rıza Aytac Cetinkaya, Aytekin Unlu, Aysel Pekel, Cengizhan Acikel, Sebahattin Yilmaz, Orhan Gursel, İsmail Yaşar Avci
BACKGROUND: Platelet suspensions (PSs) are stored at room temperature. However, recent reports show that PSs stored at 4 °C possess superior hemostatic properties. We compared the viabilities and thrombin generation capacities of PSs stored either at 4 °C or 22 °C hours. MATERIALS AND METHODS: Twenty units of apheresis derived platelets (ADPs) from 20 male donors and 20 units of random platelet suspensions (RPSs) from another 20 male donors were obtained...
September 28, 2016: Transfusion and Apheresis Science
P Gueret, S Combe, C Krezel, E Fuseau, P L M van Giersbergen, M Petitou, E Neuhart
INTRODUCTION: EP217609 is a representative of a new class of synthetic parenteral anticoagulants with a dual mechanism of action. It combines in a single molecule a direct thrombin inhibitor and an indirect factor Xa inhibitor. EP217609 can be neutralized by a specific antidote avidin, which binds to the biotin moiety of EP217609. PURPOSE: The primary objective was to assess the neutralization of EP217609 by avidin in healthy subjects. Secondary objectives were to define the optimal avidin monomer/EP217609 molar ratio to achieve an adequate neutralization of EP217609 and to assess the safety and tolerability of EP217609 and avidin...
October 15, 2016: European Journal of Clinical Pharmacology
Ryan Hakimi, Ankur Garg
PURPOSE OF REVIEW: Hemorrhagic stroke comprises approximately 15% to 20% of all strokes. This article provides readers with an understanding of the indications and significance of various neuroimaging techniques available for patients presenting with hemorrhagic strokes of distinct causes. RECENT FINDINGS: The most common initial neuroimaging study is a noncontrast head CT, which allows for the identification of hemorrhage. Once an intracranial hemorrhage has been identified, the pattern of blood and the patient's medical history, neurologic examination, and laboratory studies lead the practitioner to pursue further neuroimaging studies to guide the medical, surgical, and interventional management...
October 2016: Continuum: Lifelong Learning in Neurology
Sophie Braga-Lagache, Natasha Buchs, Mircea-Ioan Iacovache, Benoit Zuber, Christopher Benjamin Jackson, Manfred Heller
BACKGROUND: Cells of the vascular system release spherical vesicles, called microparticles, in the size range of 0.1-1μm induced by a variety of stress factors resulting in variable concentrations between health and disease. Furthermore, microparticles have intercellular communication/signaling properties and interfere with inflammation and coagulation pathways. Today's most used analytical technology for mecroparticle characterization, flow cytometry, is lacking sensitivity and specificity, which might have led to the publication of contradicting results in the past...
October 12, 2016: Molecular & Cellular Proteomics: MCP
Martin Ponschab, Martijn van Griensven, Stefan Heitmeier, Volker Laux, Christoph J Schlimp, Andreas Calatzis, Soheyl Bahrami, Heinz Redl, Herbert Schöchl
BACKGROUND: Platelets play a pivotal role in coagulation, inflammation and wound healing. Suitable animal models that have the potential to mimic human platelet function are limited. The objective of the current study was to compare platelet aggregation response in the whole blood of baboons and humans using impedance aggregometry. METHODS: Blood was drawn from 24 anesthetised male baboons and 25 healthy volunteers. The platelet aggregation response was determined by impedance aggregometry (Multiplate®)...
October 6, 2016: Thrombosis Research
Nasim Shahidi Hamedani, Heiko Rühl, Julia Janina Zimmermann, Tim Heiseler, Johannes Oldenburg, Günter Mayer, Bernd Pötzsch, Jens Müller
Activated protein C (APC) is a critical regulator of thrombin formation and thereby protects against thrombosis. On the other hand, overwhelming formation of APC increases the risk of bleeding such as in trauma-induced coagulopathy. Thus, pharmacological inhibition of APC activity may improve blood clottability in certain clinical situations. In this study, we demonstrate that the DNA aptamer HS02-52G binds with fast onset (1.118 ± 0.013 × 10(5) M(-1) s(-1)) to APC and possesses a long residence time of 13...
October 13, 2016: Nucleic Acid Therapeutics
Jamshed J Dalal, Anil Dhall, Abhay Bhave
Oral vitamin K antagonists (VKA) such as warfarin have been the mainstay of therapy for stroke prevention in patients with non valvular atrial fibrillation (NVAF) while low-molecular-weight heparin, fondaparinux and adjusted-dose warfarin or aspirin have been routinely used for thromboembolism (VTE) prophylaxis in patients undergoing total hip or knee replacement. However, VKAs are associated with considerable limitations, including increased risk of bleeding and narrow therapeutic window. Novel oral anticoagulants (NOACs, now referred as Non Vit K dependent oral anticoagulants), including the direct thrombin inhibitor dabigatran and direct Factor Xa inhibitors such as rivaroxaban and apixaban are now approved alternatives to warfarin for prophylaxis of stroke and systemic embolic events (SEE) in patients with NVAF and treatment and prophylaxis of VTE...
April 2016: Journal of the Association of Physicians of India
X Qi, G Han, X Guo, V De Stefano, K Xu, Z Lu, H Xu, A Mancuso, W Zhang, X Han, D C Valla, D Fan
BACKGROUND: China may have the largest number of Budd-Chiari syndrome (BCS) cases in the world (at least 1914 original papers were published, and at least 20 191 BCS patients were reported). Considering the discrepancy in the clinical profiles and preferred treatment selection of primary BCS between the West and China, understanding its aetiology in these two different regions is very important. AIM: To review the data from large cohort studies and meta-analyses to illustrate the epidemiology of risk factors for BCS in the West and China...
October 13, 2016: Alimentary Pharmacology & Therapeutics
Jessica W Skelley, C Whitney White, Angela R Thomason
To review the use of the direct oral anticoagulant (DOAC) agents in inherited thrombophilia based on the literature. MEDLINE, International Pharmaceutical Abstracts, and Google Scholar searches (1970-May 2016) were conducted for case reports, case series, retrospective cohorts, or clinical trials using the key words: protein C deficiency, protein S deficiency, antithrombin deficiency, activated protein C resistance, Factor V Leiden, hypercoagulable, NOACs, dabigatran, apixaban, rivaroxaban, betrixaban, edoxaban, Xa inhibitor, direct thrombin inhibitor...
October 12, 2016: Journal of Thrombosis and Thrombolysis
Oleg Palygin, Daria V Ilatovskaya, Alexander Staruschenko
Protease-activated receptors (PARs) are a well-known family of transmembrane G-protein-coupled receptors (GPCRs). To date, four PARs have been identified and PAR1 and PAR2 are the most abundant receptors, which were shown to be expressed in the kidney vascular and tubular cells. PAR signaling is mediated by an N-terminus tethered ligands that can be unmasked by serine protease cleavage. PARs are activated by endogenous serine proteases, such as thrombin (acts on PARs 1, 3 and 4) and trypsin (PAR2). PARs can be involved in glomerular, microvascular and inflammatory regulation of renal function in both normal and pathological conditions...
October 12, 2016: American Journal of Physiology. Renal Physiology
Tomoko Matsumoto, Keiji Nogami, Midori Shima
Patients with mild/moderate hemophilia (H)A, acquired HA (AHA) and lupus anticoagulants (LA), have prolonged aPTTs with low levels of factor (F)VIII activity, but the differentiation of these disorders is complex and time consuming. We established an approach to quickly differentiate these disorders using comprehensive coagulation tests. Patients' plasmas with mild/moderate HA, AHA, LA without anti-phospholipid syndrome [LA-APS(-)], and LA with APS [LA-APS(+)] were examined using clot waveform analysis (CWA) and thrombin generation test (TGT)...
October 11, 2016: International Journal of Hematology
Takumi Aota, Hideo Wada, Naoki Fujimoto, Yoshiki Yamashita, Takeshi Matsumoto, Kohshi Ohishi, Kei Suzuki, Hiroshi Imai, Masanobu Usui, Shuji Isaji, Toshimasa Uchiyama, Yoshinobu Seki, Naoyuki Katayama
We evaluated the diagnostic criteria for disseminated intravascular coagulation (DIC), which was published by the Japanese Society of Thrombosis and Hemostasis (JSTH), in 232 patients with suspected DIC without hematopoietic injury or infection. The diagnoses of the patients were as follows: DIC (n = 116), pre-DIC (n = 54), and non-DIC (n = 63). The efficacy of the diagnostic criteria for DIC was evaluated using a receiver operating characteristic analysis. The area under the curve and odds ratio for the global coagulation test (GCT) scores in the diagnosis of "DIC" were high, whereas those for the diagnosis of "DIC and pre-DIC" were low, suggesting that the addition of a reduced platelet count (RPC), antithrombin (AT), and soluble fibrin (SF)/thrombin AT (TAT) complex was required to diagnose DIC and pre-DIC...
October 11, 2016: Clinical and Applied Thrombosis/hemostasis
Luke Miller, Jason A Ferreira, Calvin Tucker
BACKGROUND: The development of novel oral anticoagulants (NOACs) has revolutionized oral anticoagulation. Rapid incorporation of NOACs into general practice has heightened the demand for directed reversal agents. Idarucizumab is a targeted reversal agent that is approved for the urgent reversal of the anticoagulant effects of dabigatran. While it is a welcome addition to reversal strategies of dabigatran, a number of clinical questions exist regarding its place in therapy. OBJECTIVE: We describe controversies regarding the use of idarucizumab therapy in patients with dabigatran-associated bleeding...
October 8, 2016: Journal of Emergency Medicine
Jian Wang, Yanjun Zhang, Jiqing Ye, Zhou Jiang
When excited at 435 nm, tetra-sulfonate zinc phthalocyanine (ZnPcS4 ) emitted dual fluorescence at 495 and 702 nm. The abnormal fluorescence at 495 nm was experimentally studied and analyzed in detail for the first time. The abnormal fluorescence at 495 nm was deduced to originate from triplet-triplet (T-T) energy transfer of excited phthalocyanine ((3) *ZnPcS4 ). Furthermore, graphene quantum dots (GQDs) enhanced the 495 nm fluorescence quantum yield (Q) of ZnPcS4 . The fluorescence properties of ZnPcS4 -GQDs conjugate were retained in a cellular environment...
October 10, 2016: Luminescence: the Journal of Biological and Chemical Luminescence
Alice Trinchero, Marina Marchetti, Cinzia Giaccherini, Carmen J Tartari, Laura Russo, Anna Falanga
BACKGROUND: Patients with thalassaemia may have thromboembolic events and, even without thrombosis, they have a subclinical hypercoagulable state. In this setting, several coagulation laboratory abnormalities have been described, but thus far no studies have explored the contribution of platelet adhesive and procoagulant properties to blood clotting activation. In this study, we dissected the platelet procoagulant effect and influence of blood transfusions on haemostasis and platelet function in thalassaemic patients...
October 4, 2016: Blood Transfusion, Trasfusione del Sangue
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