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Thrombosis and Haemostasis

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https://www.readbyqxmd.com/read/28726980/interdependence-between-osteoprotegerin-and-active-von-willebrand-factor-in-long-term-cardiovascular-mortality-prediction-in-patients-undergoing-percutaneous-coronary-intervention
#1
Jolanta Siller-Matula, Irene M Lang, Christian Schoergenhofer, Mark Roest, Bernd Jilma
The interdependence of the predictive accuracy of serum osteoprotegerin (OPG) and von Willebrand factor (vWF) levels for long-term cardiovascular outcomes has not been investigated so far. This was a prospective observational cohort study in 361 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). Baseline levels of OPG, vWF, active vWF (act vWF) and ristocetin cofactor activity (vWF:RICO) were measured. Cardiovascular mortality was recorded over a median of five years...
July 20, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28726978/analysis-of-the-substrate-specificity-of-factor-vii-activating-protease-fsap-and-design-of-specific-and-sensitive-peptide-substrates
#2
Emrah Kara, Dipankar Manna, Geir Åge Løset, Eric L Schneider, Charles S Craik, Sandip Kanse
Factor VII (FVII) activating protease (FSAP) is a circulating serine protease that is likely to be involved in a number of disease conditions such as stroke, atherosclerosis, liver fibrosis, thrombosis and cancer. To date, no systematic information is available about the substrate specificity of FSAP. Applying phage display and positional scanning substrate combinatorial library (PS-SCL) approaches we have characterised the specificity of FSAP towards small peptides. Results were evaluated in the context of known protein substrates as well as molecular modelling of the peptides in the active site of FSAP...
July 20, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28726976/absence-of-transforming-growth-factor-beta-1-in-murine-platelets-reduces-neointima-formation-without-affecting-arterial-thrombosis
#3
Katrin Schaefer, Eva Schütz, Magdalena L Bochenek, Dennis R Riehl, Markus Bosmann, Thomas Münzel, Stavros Konstantinides, Katrin Schäfer
Platelet degranulation at the site of vascular injury prevents bleeding and may affect the chronic vascular wound healing response. Transforming Growth Factor (TGF)-β1 is a major component of platelet α-granules known to accumulating in thrombi. It was our aim to determine the role of TGFβ1 released from activated platelets for neointima formation following arterial injury and thrombosis. Mice with platelet-specific deletion of TGFβ1 (Plt.TGFβ-KO) underwent carotid artery injury. Immunoassays confirmed the absence of active TGFβ1 in platelet releasates and plasma of Plt...
July 20, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28726972/consequences-of-warfarin-suspension-after-major-bleeding-in-very-elderly-patients-with-non-valvular-atrial-fibrillation
#4
Giacomo Zoppellaro, Serena Granziera, Giulia Bertozzo, Gentian Denas, Lucia Marigo, Florinda Petruzzellis, Seena Padayattil Jose, Katia Rossi, Giovanni Nante, Vittorio Pengo
No abstract text is available yet for this article.
July 20, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28692111/a-randomised-trial-on-the-effect-of-anti-platelet-therapy-on-the-systemic-inflammatory-response-in-human-endotoxaemia
#5
Dorien Kiers, Wouter A van der Heijden, Lisa van Ede, Jelle Gerretsen, Quirijn de Mast, André J van der Ven, Saloua El Messaoudi, Gerard A Rongen, Marc Gomes, Matthijs Kox, Peter Pickkers, Niels P Riksen
The use of acetylsalicylic acid (ASA) is associated with improved outcome in patients with sepsis, and P2Y12 inhibitors have been suggested to also have immunomodulatory effects. Therefore, we evaluated the effects of clinically relevant combinations of antiplatelet therapy on the immune response in experimental endotoxaemia in humans in vivo. Forty healthy subjects were randomised to seven days of placebo, placebo with ASA, ticagrelor and ASA, or clopidogrel and ASA treatment. Systemic inflammation was elicited at day seven by intravenous administration of Escherichia coli endotoxin...
July 6, 2017: Thrombosis and Haemostasis
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
#6
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
https://www.readbyqxmd.com/read/28692108/safety-and-efficacy-of-a-glycopegylated-rfviii-turoctocog-alpha-pegol-n8-gp-in-paediatric-patients-with-severe-haemophilia-a
#7
Sandrine Meunier, Jayanthi Alamelu, Silke Ehrenforth, Hideji Hanabusa, Faraizah Abdul Karim, Kaan Kavakli, Melanie Khodaie, Janice Staber, Oleksandra Stasyshyn, Donald L Yee, Lina Rageliene
Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsværd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder™5 is a multinational, open-label, single-arm trial to assess safety, efficacy and pharmacokinetics of N8-GP in paediatric (<12 years), previously treated patients. Boys with severe haemophilia A (<1 % FVIII), no history of inhibitors and previously treated with FVIII products (>50 exposure days [ED] for patients aged 0-5 years [younger cohort]; >150 ED for patients aged 6-11 years [older cohort]) were included...
July 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28692107/whole-blood-ristocetin-activated-platelet-impedance-aggregometry-multiplate-for-the-rapid-detection-of-von-willebrand-disease
#8
David E Schmidt, Maria Bruzelius, Ammar Majeed, Jacob Odeberg, Margareta Holmström, Anna Ågren
Von Willebrand disease (VWD) is the most common bleeding disorder, but no bedside tests specific for Von Willebrand factor are available. The objective of this study was to evaluate the diagnostic accuracy of whole blood ristocetin-induced platelet aggregometry (WB-RIPA) in VWD. WB-RIPA was performed in VWD patients (n=100) and healthy controls (n=17) using the Multiplate® platelet impedance aggregometry platform. The diagnostic properties of the test were described as sensitivity/specificity, positive and negative predictive value, and ROC area under the curve (AUC)...
July 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28692106/haemostasis-biomarkers-and-risk-of-intracerebral-haemorrhage-in-the-reasons-for-geographic-and-racial-differences-in-stroke-study
#9
Neil Zakai, Nels C Olson, Suzanne E Judd, Dawn O Kleindorfer, Brett M Kissela, George Howard, Mary Cushman
Pathologic alterations in haemostasis cause bleeding disorders, but it is unknown if variation within the normal range relates to intracerebral haemorrhage (ICH) risk. It was our objective to assess the prospective associations of haemostasis biomarkers with ICH risk. The REasons for Geographic and Racial Differences in Stroke study (REGARDS) recruited 30,239 U. S. individuals aged ≥45 years. ICH was ascertained through biannual telephone contact and review of deaths followed by medical record evaluation...
July 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28692105/prasugrel-in-critically-ill-patients
#10
Christian Schoergenhofer, Eva-Luise Hobl, Thomas Staudinger, Walter S Speidl, Gottfried Heinz, Jolanta Siller-Matula, Christian Zauner, Birgit Reiter, Jacek Kubica, Bernd Jilma
While prasugrel is indicated for the treatment of myocardial infarction, its effects in the most severely affected patients requiring intensive care is unknown, so that we measured the antiplatelet effects and sparse pharmacokinetics of prasugrel in critically ill patients. Twenty-three patients admitted to medical intensive care units, who were treated with 10 mg prasugrel once daily, were included in this prospective trial. Critically ill patients responded poorly to daily prasugrel treatment: adenosine diphosphate (ADP)-induced aggregation in whole blood classified 65 % (95 % confidence intervals (CI) 43-84 %) of patients as having high on treatment platelet reactivity, platelet function under high shear rates even 74 % (95 %CI 52-90 %)...
July 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28640324/new-paradigms-in-venous-thromboprophylaxis-of-medically-ill-patients
#11
Alex C Spyropoulos, Alex Spyropoulos, Gary E Raskob
Acutelly-ill hospitalised medical patients are at risk of venous thromboembolism (VTE), both in-hospital and in the immediate post-discharge period, and mortality from VTE is thought to be particularly high in this patient population. However, despite previous mandates from international antithrombotic guidelines such as those of the American College of Chest Physicians (ACCP) for the "universal" use of thromboprophylaxis in hospitalised medical patients, global audits suggest that implementation of thromboprophylaxis continues to be challenging because of the perceived higher risk of bleeding and lower risk of VTE than that reported in clinical trials...
June 22, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28640323/lys-42-43-44-and-arg-12-of-thrombin-activable-fibrinolysis-inhibitor-comprise-a-thrombomodulin-exosite-essential-for-its-antifibrinolytic-potential
#12
Chengliang Wu, Alan R Stafford, James C Fredenburgh, Jeffrey I Weitz, Ann Gils, Paul J Declerck, Paul Y Kim
The thrombin-thrombomodulin (TM) complex activates thrombin-activable fibrinolysis inhibitor (TAFI) more efficiently than thrombin alone. The exosite on TAFI required for its TM-dependent activation by thrombin has not been identified. Based on previous work by us and others, we generated TAFI variants with one or more of residues Lys 42, Lys 43, Lys 44 and Arg 12 within the activation peptide mutated to alanine. Mutation of one, two, or three Lys residues or the Arg residue alone decreased the catalytic efficiency of TAFI activation by thrombin-TM by 2...
June 22, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28640322/effectiveness-and-safety-of-rivaroxaban-versus-warfarin-for-treatment-and-prevention-of-recurrence-of-venous-thromboembolism
#13
Craig I Coleman, Craig Coleman, Thomas J Bunz, Alexander G G Turpie
The efficacy and safety or rivaroxaban versus enoxaparin/vitamin K antagonist for treatment and prevention recurrence of venous thromboembolism (VTE) was demonstrated in the randomised EINSTEIN trials. We assessed the effectiveness and safety of rivaroxaban versus warfarin in VTE patients managed in routine practice. Using US MarketScan claims from 1/2012-6/2015, we included adults with a primary diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) during a hospitalisation/emergency department visit, newly-initiated on rivaroxaban or warfarin within 30-days after the VTE and with ≥180-days of continuous medical/prescription benefits prior to the VTE (baseline)...
June 22, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28640321/effects-of-direct-oral-anticoagulants-on-lupus-anticoagulant-assays-in-a-real-life-setting
#14
Aleksandra Antovic, Eva-Marie Norberg, Maria Berndtsson, Agnes Rasmuson, Rickard E Malmström, Mika Skeppholm, Jovan Antovic
Laboratory diagnosis of lupus anticoagulant (LA) is based on prolongation in at least one coagulation assay (diluted Russell's viper venom time - dRVVT or activated partial thromboplastin time - aPTT), which normalises after addition of phospholipids. Both assays may be influenced by anticoagulants and therefore LA should not be tested during warfarin or heparin treatment. It has been shown (primarily in vitro) that direct oral anticoagulants (DOACs - dabigatran [DAB], rivaroxaban [RIV] and apixaban [API]) may also influence LA testing...
June 22, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28640320/molecular-signature-of-coronary-stent-thrombosis-oxidative-stress-and-innate-immunity-cells
#15
Judit Cubedo, Ana Blasco, Teresa Padro, Ilaria Ramaiola, Oriol Juan-Babot, Javier Goicolea, José Antonio Fernández-Díaz, Juan Francisco Oteo, Lina Badimon
The clinical impact of in-stent thrombosis is high because it is associated with high mortality and 20 % of the patients suffer a recurrent event within the two following years. The aim of this study was to characterise the morphologic and proteomic profile of in-stent thrombi (IST) in comparison to thrombi developed on native coronary arteries (CT) to identify a differential molecular signature. The study included 45 patients with ST-elevation-myocardial-infarction (STEMI) treated by primary-percutaneous-intervention and thrombus aspiration: 21 had IST and 24 had CT...
June 22, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28569924/is-a-normal-computed-tomography-pulmonary-angiography-safe-to-rule-out-acute-pulmonary-embolism-in-patients-with-a-likely-clinical-probability-a-patient-level-meta-analysis
#16
Tom van der Hulle, Nick van Es, Paul den Exter, Josien van Es, Inge C M Mos, Renée A Douma, Marieke J H A Kruip, Marcel M C Hovens, Marije Ten Wolde, Mathilde Nijkeuter, Hugo Ten Cate, Pieter W Kamphuisen, Harry R Büller, Menno V Huisman, Erik Klok
A normal computed tomography pulmonary angiography (CTPA) remains a controversial criterion for ruling out acute pulmonary embolism (PE) in patients with a likely clinical probability. We set out to determine the risk of VTE and fatal PE after a normal CTPA in this patient category and compare these risk to those after a normal pulmonary angiogram of 1.7 % (95 %CI 1.0-2.7 %) and 0.3 % (95 %CI 0.02-0.7 %). A patient-level meta-analysis from 4 prospective diagnostic management studies that sequentially applied the Wells rule, D-dimer tests and CTPA to consecutive patients with clinically suspected acute PE...
June 1, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28569923/interplay-between-elevated-cellular-fibronectin-and-plasma-fibrin-clot-properties-in-type-2-diabetes
#17
Małgorzata Konieczyńska, Agata Hanna Bryk, Krzysztof P Malinowski, Katarzyna Draga, Anetta Undas
Type 2 diabetes is associated with faster formation of poorly lysable, denser fibrin clots and elevated cellular fibronectin (cFn), a marker of vascular injury. We investigated whether cFn affects clot properties in type 2 diabetes. In 200 consecutive patients with type 2 diabetes and 100 control subjects matched for age and sex, we determined plasma cFn along with clot formation and degradation using turbidimetric and permeability assays. Diabetic patients had elevated cFn (median, 3.99 [interquartile range, 2...
June 1, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28569921/microvesicles-in-vascular-homeostasis-and-diseases-position-paper-of-the-european-society-of-cardiology-esc-working-group-on-atherosclerosis-and-vascular-biology
#18
Victoria C Ridger, Chantal M Boulanger, Anne Angelillo-Scherrer, Lina Badimon, Olivier Blanc-Brude, Marie-Luce Bochaton-Piallat, Eric Boilard, Edit I Buzas, Andreas Caporali, Françoise Dignat-George, Paul C Evans, Romaric Lacroix, Esther Lutgens, Daniel F J Ketelhuth, Rienk Nieuwland, Florence Toti, Jose Tunon, Christian Weber
Microvesicles are members of the family of extracellular vesicles shed from the plasma membrane of activated or apoptotic cells. Microvesicles were initially characterised by their pro-coagulant activity and described as "microparticles". There is mounting evidence revealing a role for microvesicles in intercellular communication, with particular relevance to hemostasis and vascular biology. Coupled with this, the potential of microvesicles as meaningful biomarkers is under intense investigation. This Position Paper will summarise the current knowledge on the mechanisms of formation and composition of microvesicles of endothelial, platelet, red blood cell and leukocyte origin...
June 1, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28569920/recombinant-gpvi-fc-added-to-single-or-dual-antiplatelet-therapy-in-vitro-prevents-plaque-induced-platelet-thrombus-formation
#19
Ann-Katrin Mojica Muñoz, Janina Jamasbi, Heidrun Degen, Götz Münch, Martin Ungerer, Richard Brandl, Remco Megens, Christian Weber, Reinhard Lorenz, Wolfgang Siess
The efficiency of current dual antiplatelet therapy might be further improved by its combination with a glycoprotein (GP) VI-targeting strategy without increasing bleeding. GPVI-Fc, a recombinant dimeric fusion protein binding to plaque collagen and concealing binding sites for platelet GPVI, acts as a lesion-focused antiplatelet drug, and does not increase bleeding in vivo. We investigated, whether GPVI-Fc added in vitro on top of acetylsalicylic acid (ASA), the P2Y12 antagonist ticagrelor, and the fibrinogen receptor antagonist abciximab alone or in combination would increase inhibition of platelet activation by atherosclerotic plaque...
June 1, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28569919/elevated-plasma-tfpi-activity-causes-attenuated-tf-dependent-thrombin-generation-in-early-onset-preeclampsia
#20
Karl Egan, Hugh O'Connor, Barry Kevane, Fergal Malone, Aine Lennon, Amani Al Zadjali, Sharon Cooley, Cathy Monteith, Patricia Maguire, Paulina Szklanna, Seamus Allen, Naomi McCallion, Fionnuala Ní Áinle
Early onset preeclampsia (EOP) is a pregnancy-specific proinflammatory disorder that is characterised by competing thrombotic and bleeding risks. It was the aim of this study to characterise thrombin generation, a major determinant of thrombotic and bleeding risk, in order to better understand the haemostatic balance in patients with EOP. Patients with EOP were recruited at the Rotunda Hospital, Dublin. Twenty-six cases of EOP were recruited over a 21-month period, out of 15,299 deliveries at the Rotunda. Blood samples were collected into sodium citrate plus corn trypsin inhibitor anticoagulated vacutainers, platelet-poor plasma was prepared, and calibrated automated thrombography was used to assess thrombin generation...
June 1, 2017: Thrombosis and Haemostasis
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