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https://www.readbyqxmd.com/read/28328676/correlation-between-factor-f-xia-fixa-and-tissue-factor-and-trauma-severity
#1
Shannon M Prior, Mitchell J Cohen, Amanda S Conroy, Mary F Nelson, Lucy Z Kornblith, Benjamin M Howard, Saulius Butenas
BACKGROUND: It has been observed that trauma patients often display elevated procoagulant activity that could be caused, in part, by tissue factor (TF). We previously observed that trauma patients with thermal, blunt and penetrating injuries have active FIXa and FXIa in their plasma. In the current study we evaluated the effect of injury severity, with or without accompanying shock, on the frequency and concentration of TF, FIXa and FXIa in plasma from trauma patients. METHODS: Eighty trauma patients were enrolled and divided equally into 4 groups based on their injury severity score (ISS) and base deficit (BD):Group 1: Non-severe injury, no shockGroup 2: Non-severe injury, with shockGroup 3: Severe injury, no shockGroup 4: Severe injury, with shockBlood was collected at a 0 time-point (first blood draw upon arrival at hospital) and citrate plasma was prepared, frozen and stored at -80C...
March 21, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28318107/the-amplitude-of-coagulation-curves-from-thrombin-time-tests-allows-dysfibrinogenemia-caused-by-the-common-mutation-fgg-arg301-to-be-distinguished-from-hypofibrinogenemia
#2
M Jacquemin, I Vanlinthout, I Van Horenbeeck, M Debasse, J Toelen, J Schoeters, R Lavend'homme, K Freson, K Peerlinck
INTRODUCTION: Thrombin time (TT) tests are useful for diagnosing coagulation disorders involving abnormal fibrinogen but do not allow us to distinguish between qualitative and quantitative defects. However, with the widening availability of optical coagulation automates, more information about the coagulation process is becoming increasingly accessible. METHODS: In this study, we compared the coagulation curves of TT tests carried out with plasma from healthy donors with those from patients with acquired low Clauss fibrinogen levels or with dysfibrinogenemia caused by a heterozygous point mutation in the fibrinogen γ-chain that results in a p...
March 20, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28316335/complement-in-anca-associated-vasculitis-mechanisms-and-implications-for-management
#3
REVIEW
Min Chen, David R W Jayne, Ming-Hui Zhao
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of potentially life-threatening autoimmune diseases. The main histological feature in the kidneys of patients with AAV is pauci-immune necrotizing crescentic glomerulonephritis with little immunoglobulin and complement deposition in the glomerular capillary walls. The complement system was not, therefore, initially thought to be associated with the development of AAV. Accumulating evidence from animal models and clinical observations indicate, however, that activation of the complement system - and the alternative pathway in particular - is crucial for the development of AAV, and that the complement activation product C5a has a central role...
March 20, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28316004/effect-of-the-fxa-inhibitors-rivaroxaban-and-apixaban-on-platelet-activation-in-patients-with-atrial-fibrillation
#4
B Steppich, F Dobler, L C Brendel, G Hessling, S L Braun, A L Steinsiek, I Deisenhofer, A Hyseni, M Roest, I Ott
Rivaroxaban and Apixaban, increasingly used for stroke prevention in non-valvular atrial fibrillation (AF), might impact platelet reactivity directly or indirectly. By inhibition of Factor Xa (FXa) they preclude not only generation of relevant thrombin amounts but also block signalling of FXa via protease activated receptors. However, weather FXa-inhibition affects platelet haemostasis remains incompletely known. One hundred and twenty-eight patients with AF on chronic anticoagulation with either Rivaroxaban or Apixaban for at least 4 weeks were included in the study...
March 18, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28315166/effects-of-thromboprophylactic-doses-of-apixaban-and-rivaroxaban-on-coagulation-and-thrombin-generation-in-association-with-total-hip-replacement
#5
Tuukka A Helin, Lauri Virtanen, Mikko Manninen, Jarkko Leskinen, Juhana Leppilahti, Lotta Joutsi-Korhonen, Riitta Lassila
Factor Xa inhibitors (FXaI) apixaban and rivaroxaban are used for thromboprophylaxis after major elective orthopaedic surgery. Because few patient sample studies exist, we postoperatively assessed patients undergoing unilateral total hip arthroplasty, including 22 treated with apixaban (2.5 mg BID) and 20 treated with rivaroxaban (10 mg OD). We collected blood samples before and 3 h after drug intake at 4 time points, preoperatively, as well as on day 1, week 1 (day 2-8) and day 28 post-operation. APTT and PT were immediately analysed...
March 17, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28314697/demeanor-of-rivaroxaban-in-activated-inactivated-fxa
#6
Kaname Seki, Yosuke Mizuno, Toku Sakashita, Shintaro Nakano, Jun Tanno, Yasushi Okazaki, Toshihiro Muramatsu, Shigeyuki Nishimura, Takaaki Senbonmatsu
Activated factor X (FXa) plays an important role in thrombin generation and inflammation. Factor X is not converted constitutively to FXa, but only after intrinsic clotting factors are activated and/or cellular injury occurs. Although rivaroxaban is one of direct FXa inhibitors, its function in the inactivated coagulation cascade is unclear. In human umbilical vein endothelial cells that natively express protease-activated receptor-1 and -2, high dose rivaroxaban did not alter gene transcripts including pro-inflammatory genes in DNA microarray...
February 24, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28303518/potentially-life-threatening-coagulopathy-associated-with-simultaneous-reduction-in-coagulation-and-fibrinolytic-function-in-pediatric-acute-leukemia-after-hematopoietic-stem-cell-transplantation
#7
Takashi Ishihara, Keiji Nogami, Tomoko Matsumoto, Akitaka Nomura, Yasufumi Takeshita, Satoshi Ochi, Midori Shima
The pathogenesis of sinusoidal obstruction syndrome (SOS) and thrombotic microangiopathy (TMA) after hematopoietic stem cell transplantation (HSCT) is poorly understood, and limited information is available on global hemostatic function in HSCT. We assessed changes in coagulation and fibrinolysis using a simultaneous thrombin and plasmin generation assay (T/P-GA) during HSCT. Measurements of endogenous thrombin potential (T-EP) and plasmin peak height (P-Peak) using T/P-GA in six pediatric acute leukemia patients treated with HSCT were compared to normal plasma...
March 16, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28296129/comparing-thrombin-generation-in-patients-with-hemophilia-a-and-patients-on-vitamin-k-antagonists
#8
M L Y de Koning, K Fischer, B de Laat, A Huisman, M Ninivaggi, R E G Schutgens
BACKGROUND: It is unknown whether patients with hemophilia A with atrial fibrillation require treatment with vitamin K antagonists (VKA) to the same extent as the normal population. OBJECTIVE: To compare hemostatic potential in hemophilia patients and patients on VKA using thrombin generation (TG). METHODS: In this cross-sectional study, TG, initiated with 1pM tissue factor, was measured in 133 patients with severe (FVIII <1%, n=15) and non-severe (FVIII 1-50%, n=118) hemophilia A, 97 patients on VKA with an international normalized ratio (INR) ≥1...
March 15, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28294526/phase-1-dose-escalating-study-of-the-safety-pharmacokinetics-and-pharmacodynamics-of-activated-factor-x-i-16l
#9
Dana Parsons-Rich, Fei Hua, Gang Li, Constantino Kantaridis, Debra D Pittman, Steven Arkin
BACKGROUND: FXa(I16L) (PF-05230907) is a zymogen-like variant of activated coagulation factor X (FXa). It exhibits enhanced resistance to inactivation by endogenous inhibitors compared with wild-type FXa and restores hemostatic activity in nonclinical models of various bleeding conditions. OBJECTIVES: To evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of FXa(I16L) , a phase 1, first-in-human, dose escalation clinical trial in healthy adult volunteers was conducted METHODS: Participants were assigned to 1 of 6 ascending single-dose cohorts (0...
March 14, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28294177/rational-design-of-protein-c-activators
#10
Sergio Barranco-Medina, Mary Murphy, Leslie Pelc, Zhiwei Chen, Enrico Di Cera, Nicola Pozzi
In addition to its procoagulant and proinflammatory functions mediated by cleavage of fibrinogen and PAR1, the trypsin-like protease thrombin activates the anticoagulant protein C in a reaction that requires the cofactor thrombomodulin and the endothelial protein C receptor. Once in the circulation, activated protein C functions as an anticoagulant, anti-inflammatory and regenerative factor. Hence, availability of a protein C activator would afford a therapeutic for patients suffering from thrombotic disorders and a diagnostic tool for monitoring the level of protein C in plasma...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28292729/pre-analytical-effects-of-pneumatic-tube-system-transport-on-routine-haematology-and-coagulation-tests-global-coagulation-assays-and-platelet-function-assays
#11
Sandra Le Quellec, Mickaël Paris, Christophe Nougier, Frédéric Sobas, Lucia Rugeri, Sandrine Girard, Jean-Claude Bordet, Claude Négrier, Yesim Dargaud
INTRODUCTION: Pneumatic tube system (PTS) in hospitals is commonly used for the transport of blood samples to clinical laboratories, as it is rapid and cost-effective. The aim was to compare the effects on haematology samples of a newly acquired ~2km-long PTS that links 2 hospitals with usual transport (non-pneumatic tube system, NPTS). METHODS: Complete blood cell count, routine coagulation assays, platelet function tests (PFT) with light-transmission aggregometry and global coagulation assays including ROTEM® and thrombin generation assay (TGA) were performed on blood samples from 30 healthy volunteers and 9 healthy volunteers who agreed to take aspirin prior to blood sampling...
December 28, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/28287378/application-of-a-clot-based-assay-to-measure-the-procoagulant-activity-of-stored-allogeneic-red-blood-cell-concentrates
#12
Bérangère Devalet, Adeline Wannez, Nicolas Bailly, Lutfiye Alpan, Damien Gheldof, Jonathan Douxfils, Véronique Deneys, Benoît Bihin, Bernard Chatelain, Jean-Michel Dogné, Christian Chatelain, François Mullier
BACKGROUND: Thrombotic effects are possible complications of red blood cell transfusion. The generation and accumulation of procoagulant red blood cell extracellular vesicles during storage may play an important role in these thrombotic effects. The objective of this study was to assess the value of a simple phospholipid-dependent clot-based assay (STA(®)-Procoag-PPL) to estimate the procoagulant activity of stored red blood cells and changes in this activity during storage of the blood component...
March 9, 2017: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/28285202/a-novel-silver-nanocluster-in-situ-synthesized-as-versatile-probe-for-electrochemiluminescence-and-electrochemical-detection-of-thrombin-by-multiple-signal-amplification-strategy
#13
Guifen Jie, Lu Tan, Yang Zhao, Xiaochun Wang
In this work, a novel silver nanoclusters (AgNCs) were in situ synthesized and used as versatile electrochemiluminescence (ECL) and electrochemical (EL) signal probes for thrombin detection by using DNAzyme-assisted target recycling and hybridization chain reaction (HCR) multiple amplification strategy. The presence of target thrombin firstly opened the hairpin DNA, followed by DNAzyme-catalytic recycling cleavage of excess substrates, which could generate large number of substrate fragments (s1). Then these s1 fragments were captured by SH-DNA on the Au nanoparticle-modified electrode, which further triggered the subsequent HCR of the hairpin DNA probes (H1 and H2) to form the long dsDNA...
March 7, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28255906/the-impact-of-frailty-on-coagulation-and-responses-to-warfarin-in-acute-older-hospitalised-patients-with-atrial-fibrillation-a-pilot-study
#14
Tu Ngoc Nguyen, Marie-Christine Morel-Kopp, Dominic Pepperell, Robert Graham Cumming, Sarah Nicole Hilmer, Christopher Morice Ward
BACKGROUND: The evidence on coagulation changes with frailty is not consistent and clinical studies suggest that frail older people may be at an increased risk of bleeding complications with anticoagulant therapy. AIMS: This study aims to assess the impact of frailty on coagulation function and on response to warfarin. METHODS: Inpatients aged over 65 years with atrial fibrillation (AF) were recruited. Frailty was determined using the Reported Edmonton Frail Scale...
March 2, 2017: Aging Clinical and Experimental Research
https://www.readbyqxmd.com/read/28251913/elevated-hematocrit-enhances-platelet-accumulation-following-vascular-injury
#15
Bethany L Walton, Marcus Lehmann, Tyler Skorczewski, Lori A Holle, Joan D Beckman, Jeremy A Cribb, Micah J Mooberry, Adam R Wufsus, Brian C Cooley, Jonathan W Homeister, Rafal Pawlinski, Michael R Falvo, Nigel S Key, Aaron L Fogelson, Keith B Neeves, Alisa S Wolberg
Red blood cells (RBCs) demonstrate procoagulant properties in vitro, and elevated hematocrit is associated with reduced bleeding and increased thrombosis risk in humans. These observations suggest RBCs contribute to thrombus formation. However, effects of RBCs on thrombosis are difficult to assess because humans and mice with elevated hematocrit typically have co-existing pathologies. Using an experimental model of elevated hematocrit in healthy mice, we measured effects of hematocrit in two in vivo clot formation models...
March 1, 2017: Blood
https://www.readbyqxmd.com/read/28248803/1-1-transfusion-strategies-are-right-for-the-wrong-reasons
#16
Stephanie A Savage, Ben L Zarzaur, Brian L Brewer, Garrett H Lim, Ali C Martin, Louis J Magnotti, Martin A Croce, Timothy H Pohlman
INTRODUCTION: Early assessment of clot function identifies coagulopathies following injury. Abnormalities include a hypercoagulable state from excess thrombin generation, as well as an acquired coagulopathy. Efforts to address coagulopathy have resulted in earlier, aggressive use of plasma emphasizing 1:1 resuscitation. The purpose of this study was to describe coagulopathies in varying hemorrhagic profiles from a cohort of injured patients. METHODS: All injured patients who received at least one unit of packed red blood cells (PRBC) in the first 24 hours of admission from September 2013 to May 2015 were eligible for inclusion...
February 28, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28247290/determination-of-non-vitamin-k-oral-anticoagulant-noac-effects-using-a-new-generation-thrombelastography-teg-6s-system
#17
Kevin P Bliden, Rahul Chaudhary, Nafees Mohammed, Adina A Muresan, Carlos G Lopez-Espina, Eli Cohen, Gabriel Raviv, Marc Doubleday, Fowzia Zaman, Blessy Mathew, Udaya S Tantry, Paul A Gurbel
Non vitamin K oral anticoagulants (NOACs) do not require regular monitoring but information about their pharmacodynamic effect may be importantin situations like trauma, stroke oremergent surgery. Currently, no standardized point-of-care test is available to evaluate the anticoagulant effects of NOACs. We evaluated the anticoagulant effect of NOACs with the next generation point-of-care TEG assay (TEG® 6S) based on a fully-automated thrombelastography system. We used two TEG® 6S assays, the DTI assay and Anti-Factor Xa (AFXa) assay, to detect anticoagulant effects and classify NOACs...
February 28, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28239301/the-reversal-effect-of-prothrombin-complex-concentrate-pcc-activated-pcc-and-recombinant-activated-factor-vii-against-anticoagulation-of-xa-inhibitor
#18
Nina Haagenrud Schultz, Hoa Thi Tuyet Tran, Stine Bjørnsen, Carola Elisabeth Henriksson, Per Morten Sandset, Pål Andre Holme
BACKGROUND: An increasing number of patients are treated with direct-acting oral anticoagulants (DOACs), but the optimal way to reverse the anticoagulant effect is not known. Specific antidotes are not available and prothrombin complex concentrate (PCC), activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) are variously used as reversal agents in case of a major bleeding. We aimed to determine the most effective haemostatic agent and dose to reverse the effect of rivaroxaban in blood samples from patients taking rivaroxaban for therapeutic reasons...
2017: Thrombosis Journal
https://www.readbyqxmd.com/read/28236427/procoagulant-extracellular-vesicles-in-amniotic-fluid
#19
Lena Hell, Lukas Wisgrill, Cihan Ay, Andreas Spittler, Michael Schwameis, Bernd Jilma, Ingrid Pabinger, Peter Altevogt, Johannes Thaler
Embolization of amniotic fluid (AF) into the blood circulation leads to disseminated intravascular coagulation (DIC). Procoagulant phosphatidylserine (PS)- and tissue factor (TF)-exposing extracellular vesicles (EVs) might play an important role in AF embolism-induced DIC. It was the aim of the present study to perform analyses of the procoagulant properties of AF with a panel of functional coagulation assays and flow cytometry. We applied a prothrombinase assay (that quantifies PS exposure on EVs), an EV-associated TF activity assay, a fibrin generation assay, a thrombin generation assay, a whole blood clotting model, and flow cytometry in AF and control plasma...
February 4, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28229158/detection-of-procoagulant-imbalance-modified-endogenous-thrombin-potential-with-results-expressed-as-ratio-of-values-with-to-without-thrombomodulin
#20
Armando Tripodi
Each individual possesses his/her own endogenous-thrombin-potential (ETP) (i. e. the ability to generate thrombin) which depends on the relative strength of the pro- and anticoagulant drivers operating in plasma. This ability depends in turn on the clinical conditions in which the balance between the two drivers is variably affected. One of the major determinants of this balance is the factor (F)VIII-protein C(PC) axis and its effect can be conveniently explored by the thrombin generation procedures with results expressed as ETP ratio with/without thrombomodulin (TM) (ETP-TM ratio)...
February 23, 2017: Thrombosis and Haemostasis
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