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https://www.readbyqxmd.com/read/28526142/anticoagulant-reversal-and-anesthetic-considerations
#1
REVIEW
Joseph Meltzer, Joseph R Guenzer
Bleeding complications are a common concern with the use of anticoagulant agents. In many situations, reversing of neutralizing their effects may be warranted. Prothrombin complex concentrate replaces coagulation factors lowered by warfarin, as does fresh frozen plasma, but in a more concentrated form. Protamine negates the effect of heparin and combines chemically with heparin molecules to form an inactive salt. It also partially reverses the effects of low-molecular-weight heparin. Recombinant activated factor VII is a nonspecific procoagulant that activates the extrinsic clotting pathway, resulting in thrombin generation, but does not directly neutralize the activity of any of the new oral anticoagulants...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28523947/potentiation-of-trap-6-induced-platelet-dense-granule-release-by-blockade-of-p2y12-signaling-with-mrs2395
#2
Annachiara Mitrugno, Rachel A Rigg, Nicole B Laschober, Anh T P Ngo, Jiaqing Pang, Craig D Williams, Joseph E Aslan, Owen J T McCarty
The release of ADP from platelet dense granules and its binding to platelet P2Y12 receptors is key to amplifying the initial hemostatic response and propagating thrombus formation. P2Y12 has thus emerged as a therapeutic target to safely and effectively prevent secondary thrombotic events in patients with acute coronary syndrome or a history of myocardial infarction. Pharmacological inhibition of P2Y12 receptors represents a useful approach to better understand the signaling mediated by these receptors and to elucidate the role of these receptors in a multitude of platelet hemostatic and thrombotic responses...
May 19, 2017: Platelets
https://www.readbyqxmd.com/read/28522812/selection-and-characterization-of-a-dna-aptamer-inhibiting-coagulation-factor-xia
#3
David A Donkor, Varsha Bhakta, Louise J Eltringham-Smith, Alan R Stafford, Jeffrey I Weitz, William P Sheffield
Factor XIa (FXIa) is a serine protease that catalyzes the activation of Factor IX (FIX) in the blood coagulation cascade. FXIa and its precursor FXI are emergent therapeutic targets for the development of safer anticoagulant agents. Here, we sought a novel DNA-based agent to inhibit FXIa. Towards this goal, an 80 base, single-stranded DNA aptamer library (containing a 40 base randomized core) was screened for FXIa-binding candidates, using ten rounds of positive and negative selection. After selection, 6 of 89 different sequences inhibited FXIa-mediated chromogenic substrate S2366 cleavage...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28521572/tissue-factor-activity-in-women-with-preeclampsia-or-sga-a-potential-explanation-for-the-excessive-thrombin-generation-in-these-syndromes
#4
Offer Erez, Roberto Romero, Edi Vaisbuch, Nandor Gabor Than, Juan Pedro Kusanovic, Shali Mazaki-Tovi, Francesca Gotsch, Pooja Mittal, Zhong Dong, Tinnakorn Chaiworapongsa, Chong Jai Kim, Chia-Ling Nhan-Chang, Sun Kwon Kim, Lami Yeo, Moshe Mazor, Sonia S Hassan
OBJECTIVE: The aim of this study was to determine whether the activity of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the plasma of women with preeclampsia (PE) and small for gestational age (SGA) neonate differ from that of normal pregnant women and whether they are related to specific placental lesions. METHODS: This cross-sectional study included the following groups: (1) normal pregnancy (n = 68); (2) PE (n= 128); and (3) SGA (n = 56)...
May 19, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28505525/thrombin-generation-and-intracranial-atherosclerotic-disease-in-patients-with-a-transient-ischaemic-attack
#5
Elisabetta Favaretto, Michelangelo Sartori, Cristina Legnani, Francesca Rondelli, Michela Cini, Maria Guarino, Benilde Cosmi
BACKGROUND: Intracranial atherosclerotic disease (ICAD) is responsible for at least 10% of transient ischaemic attacks (TIA). Thrombin generation has been shown to be associated with several atherosclerotic conditions and may be relevant in the pathogenesis of TIA from ICAD. OBJECTIVE: To evaluate the association between thrombin generation and ICAD in patients with TIA. MATERIALS AND METHODS: Consecutive patients with confirmed diagnosis of TIA by vascular neurologist were enrolled...
May 9, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28503774/effect-of-the-injectable-contraceptive-depot-medroxyprogesterone-acetate-on-coagulation-parameters-in-new-users
#6
Vaneska Melhado-Kimura, Joyce Maria Annichino Bizzacchi, Susan Kelly Picoli Quaino, Silmara Montalvao, Luis Bahamondes, Arlete Fernandes
AIM: The aim of this study was to assess the effects of the injectable depot-medroxyprogesterone acetate (DMPA) contraceptive on selected blood coagulation parameters in young, healthy new users. METHODS: The prospective study included 39 healthy women aged 20-39 years, with a body mass index (BMI; kg/m(2) ) < 30, who were never users of DMPA, and who opted to use DMPA (21 women) or a copper intrauterine device (IUD; 18 women). The women in the two groups were matched for age (±1 year) and BMI (±1)...
May 15, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28503126/in-vitro-and-ex-vivo-measurement-of-prophylactic-dabigatran-concentrations-with-a-new-ecarin-based-thromboelastometry-test
#7
Mareike Kristina Körber, Elisabeth Langer, Martin Köhr, Klaus-Dieter Wernecke, Wolfgang Korte, Christian von Heymann
BACKGROUND: An increasing number of oral anticoagulants has been approved, including dabigatran etexilate (DE). DE is a direct thrombin inhibitor that requires no routine monitoring, but, if necessary (e.g. urgent surgery etc.), the diluted thrombin time measured with Hemoclot® has shown reliable results. So far, no point-of-care (PoC) assay is available to measure DE effects. The EcaTEM assay uses ecarin to initiate the coagulation cascade at the step of thrombin generation and measures the clotting time (CT) by thromboelastometry...
April 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28501713/an-in-situ-photocrosslinkable-platelet-rich-plasma-complexed-hydrogel-glue-with-growth-factor-controlled-release-ability-to-promote-cartilage-defect-repair
#8
Xiaolin Liu, Yunlong Yang, Xin Niu, Qiuning Lin, Bizeng Zhao, Yang Wang, Linyong Zhu
The repair of articular cartilage injury is a great clinical challenge. Platelet-rich plasma (PRP) has attracted much attention for the repair of articular cartilage injury, because it contains various growth factors that are beneficial for wound repair. However, current administration methods of PRP face many shortcomings, such as unstable biological fixation and burst release of growth factors, all of which will bring troubles to its application in the repair of articular cartilage and compromise its therapeutic efficacy...
May 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28500649/a-comparative-study-using-thrombin-generation-and-three-different-inr-methods-in-patients-on-vitamin-k-antagonist-treatment
#9
N Riva, K Vella, S Meli, K Hickey, D Zammit, C Calamatta, M Makris, S Kitchen, W Ageno, A Gatt
INTRODUCTION: Vitamin K antagonist (VKA) treatment requires routine monitoring using the international normalized ratio (INR). However, different INR assays may vary in their results. The aim of this study was to assess the agreement of three different INR methods, compared with thrombin generation, in patients on VKA treatment. METHODS: Sixty patients attending the Anticoagulation Clinic at Mater Dei Hospital (Msida, Malta) for VKA monitoring between August and September 2015 were enrolled...
May 12, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28499196/binding-induced-dna-walker-for-signal-amplification-in-highly-selective-electrochemical-detection-of-protein
#10
Yuhang Ji, Lei Zhang, Longyi Zhu, Jianping Lei, Jie Wu, Huangxian Ju
A binding-induced DNA walker-assisted signal amplification was developed for highly selective electrochemical detection of protein. Firstly, the track of DNA walker was constructed by self-assembly of the high density ferrocene (Fc)-labeled anchor DNA and aptamer 1 on the gold electrode surface. Sequentially, a long swing-arm chain containing aptamer 2 and walking strand DNA was introduced onto gold electrode through aptamers-target specific recognition, and thus initiated walker strand sequences to hybridize with anchor DNA...
May 4, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28497580/the-evaluation-of-the-relevance-of-thrombin-generation-and-procoagulant-activity-in-thrombotic-risk-assessment-in-bcr-abl-negative-myeloproliferative-neoplasm-patients
#11
H Baccouche, M Ben Jemaa, A Chakroun, S Chadi, S Mahjoub, I Sfar, Y Gorgi, N Ben Romdhane
INTRODUCTION: It has been recently suggested that microparticles (MP) play a role in the pathogenesis of thrombotic complications. This study aimed to assess the contribution of procoagulant activity expressed by circulating MP in thrombotic events in MPN patients. METHODS: Seventy-four MPN patients were enrolled in a trans-sectional study. The MP procoagulant activity was measured using two assays: (i) the thrombin generation (TG) assay used in different conditions with the addition of both tissue factor (TF) and phospholipids (PL) and with the addition of TF or PL alone and (ii) the PROCOAG-PPL assay...
May 12, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28497494/global-assays-of-fibrinolysis
#12
REVIEW
A Ilich, I Bokarev, N S Key
Fibrinolysis is an important and integral part of the hemostatic system. Acting as a balance to blood coagulation, the fibrinolytic system protects the body from unwanted thrombus formation and occlusion of blood vessels. As long as blood coagulation and fibrinolysis remain in equilibrium, response to injury, such as vessel damage, is appropriately regulated. However, alterations in this balance may lead to thrombosis or bleeding. A variety of methods have been proposed to assess fibrinolytic activity in blood or its components, but due to the complexity of the system, the design of a "gold standard" assay that reflects overall fibrinolysis has remained an elusive goal...
May 12, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28481998/minimally-invasive-heart-valve-surgery-influence-on-coagulation-and-inflammatory-response%C3%A2
#13
Domenico Paparella, Crescenzia Rotunno, Pietro Guida, Mattia Travascia, Micaela De Palo, Andrea Paradiso, Alessandro Carrozzo, Ruggero Rociola
OBJECTIVES: Minimally invasive valve surgery (MIVS) is associated with improved clinical outcome but longer cardiopulmonary bypass (CPB) time. The aim of the present study is to compare inflammatory and coagulation parameters in patients undergoing minimally invasive or standard valve surgery. METHODS: A prospective non-randomized study was performed enrolling 79 patients undergoing mitral (20 right mini-thoracotomy and 18 standard sternotomy) and aortic valve (20 mini-sternotomy and 21 standard sternotomy) procedures...
May 6, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/28481865/effect-of-hemodilution-in-vitro-with-hydroxyethyl-starch-on-hemostasis
#14
Shanliang Jin, Guifang Yu, Ruijiao Hou, Boxiong Shen, Hong Jiang
BACKGROUND Hydroxyethyl starch (HES) solutions are used for volume expansion during surgery. We aimed to investigate how 6%HES 130/0.4 affects hemostasis. MATERIAL AND METHODS Blood samples were collected from 12 healthy adult volunteers, diluting with 6%HES 130/0.4 (HES group) or Ringer lactate solution (RL control group). The hemodilution ratio (HR) of citrated blood volume to plasma substitute volume was 10: 0 (undiluted), 10: 2, 10: 4, and 10: 6. Clotting factors activity was measured. Thrombin generation was monitored...
May 8, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28475272/recombinant-factor-viia-addition-to-haemophilic-blood-perfused-over-collagen-tissue-factor-can-sufficiently-bypass-the-factor-ixa-viiia-defect-to-rescue-fibrin-generation
#15
R Li, K A Panckeri, P F Fogarty, A Cuker, S L Diamond
INTRODUCTION: Factor VIII (FVIII) or factor IX (FIX)-deficient haemophilic patients display deficits in platelet and fibrin deposition under flow detectable in microfluidics. Compared to fibrin generation, decreased platelet deposition in haemophilic blood flow is more easily rescued with recombinant factor VIIa (rFVIIa), whereas rFVIIa requires FXIIa participation to generate fibrin when tissue factor (TF) is absent. AIMS: Perfusion of haemophilic whole blood (WB) over collagen/TF surfaces was used to determine whether rFVIIa/TF was sufficient to bypass poor FIXa/FVIIIa function in blood from patients with haemophilia A and B...
May 5, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28474722/highly-selective-and-rapidly-activatable-fluorogenic-thrombin-sensors-and-application-in-human-lung-tissue
#16
Alicia Megia-Fernandez, Bethany Mills, Chesney Michels, Sunay V Chankeshwara, Kevin Dhaliwal, Mark Bradley
A library of FRET-based peptides were prepared and studied as Thrombin substrates. This identified probes that showed selective activation by Thrombin, low fluorescent background signals, stability to Factor Xa, matrix metalloproteases, and primary human inflammatory cell lysates and supernatant. These were selected for further optimization, creating a second generation of fluorogenic probes with improved solubility and Plasmin resistance. The optimised probe allowed the detection of Thrombin activity in ex vivo fibrotic human tissue...
May 5, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28473975/increased-clot-formation-in-the-absence-of-increased-thrombin-generation-in-patients-with-peripheral-arterial-disease-a-case-control-study
#17
Marie-Claire F Kleinegris, Joke Konings, Jan W Daemen, Yvonne Henskens, Bas de Laat, Henri M H Spronk, Arina J Ten Cate-Hoek, Hugo Ten Cate
BACKGROUND: In peripheral arterial disease (PAD), activation of the hemostatic system may contribute to atherosclerosis progression and atherothrombotic events. OBJECTIVE: This case-control study assesses the overall coagulation status in PAD patients by evaluating coagulation markers in combination with thrombin generation potential, whole blood (WB) clot formation, and fibrinolysis. METHODS: In blood from 40 PAD patients (n = 20 with cardiovascular event within 1 year after initial diagnosis, n = 20 without) and 40 apparently healthy controls, thrombin generation was determined in WB and platelet-poor plasma...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28473418/aggregation-of-thrombin-derived-c-terminal-fragments-as-a-previously-undisclosed-host-defense-mechanism
#18
Jitka Petrlova, Finja C Hansen, Mariena J A van der Plas, Roland G Huber, Matthias Mörgelin, Martin Malmsten, Peter J Bond, Artur Schmidtchen
Effective control of endotoxins and bacteria is crucial for normal wound healing. During injury, the key enzyme thrombin is formed, leading to generation of fibrin. Here, we show that human neutrophil elastase cleaves thrombin, generating 11-kDa thrombin-derived C-terminal peptides (TCPs), which bind to and form amorphous amyloid-like aggregates with both bacterial lipopolysaccharide (LPS) and gram-negative bacteria. In silico molecular modeling using atomic resolution and coarse-grained simulations corroborates our experimental observations, altogether indicating increased aggregation through LPS-mediated intermolecular contacts between clusters of TCP molecules...
May 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28472132/decreased-prothrombin-conversion-and-reduced-thrombin-inactivation-explain-rebalanced-thrombin-generation-in-liver-cirrhosis
#19
Romy M W Kremers, Marie-Claire Kleinegris, Marisa Ninivaggi, Bas de Laat, Hugo Ten Cate, Ger H Koek, Rob J Wagenvoord, H Coenraad Hemker
Impaired coagulation factor synthesis in cirrhosis causes a reduction of most pro- and anticoagulant factors. Cirrhosis patients show no clear bleeding or thrombotic phenotype, although they are at risk for both types of hemostatic event. Thrombin generation (TG) is a global coagulation test and its outcome depends on underlying pro- and anticoagulant processes (prothrombin conversion and thrombin inactivation). We quantified the prothrombin conversion and thrombin inactivation during TG in 30 healthy subjects and 52 Child-Pugh (CP-) A, 15 CP-B and 6 CP-C cirrhosis patients to test the hypothesis that coagulation is rebalanced in liver cirrhosis patients...
2017: PloS One
https://www.readbyqxmd.com/read/28472104/prediction-of-bleeding-risk-in-patients-taking-vitamin-k-antagonists-using-thrombin-generation-testing
#20
Saartje Bloemen, Suzanne Zwaveling, Hugo Ten Cate, Arina Ten Cate-Hoek, Bas de Laat
Until recently, vitamin K antagonists (VKAs) were the mainstay of oral anticoagulant treatment with bleeding as the most prevalent adverse effect. One to four percent of patients experience major bleeding episodes, while clinically relevant bleeding occurs in up to 20%. At this moment no laboratory assays are available to identify patients at risk for bleeding. With this study we aimed to investigate whether thrombin generation tests might identify a bleeding risk in patients taking VKAs. This prospective cohort study included 129 patients taking VKAs for more than three months...
2017: PloS One
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