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thrombin generation

Ki-Young Yoo, Soo-Young Jung, Sung-Ho Hwang, Su-Min Lee, Jong-Ho Park, Hyun-Ja Nam
Background: Korean National Health Insurance reimburses factor VIII (FVIII) and factor IX (FIX) clotting factor concentrate (CFC) infusions to discrepant activity levels, allowing elevation of FVIII activity to 60 IU/dL and FIX to 40 IU/dL. We aimed to assess hemostatic response to these target levels using global hemostatic assays. Methods: We enrolled 34 normal healthy men, 34 patients with hemophilia A, and 36 with hemophilia B, with residual factor activity of 3 IU/dL or less and without inhibitors...
March 2018: Blood Research
N Akman, T Braunschweig, M Honickel, K Schütt, H Schöchl, C Stoppe, R Rossaint, O Grottke
BACKGROUND: Idarucizumab is licensed to reverse dabigatran in life-threatening haemorrhage. Establishment of venous access can be challenging, and the intraosseous (IO) route is a potentially life-saving alternative. In this study, we compared the efficacy and safety of IO or intravenous (i.v.) idarucizumab for dabigatran reversal in a porcine polytrauma model. METHODS: Male pigs (n=21) received oral dabigatran etexilate (30 mg kg-1 bid) for 3 days. On the 4th day, animals received dabigatran infusion and were randomised 1:1:1 to receive IO saline (control), i...
May 2018: British Journal of Anaesthesia
J Fitzgerald, M Lenihan, J Callum, S A McCluskey, C Srinivas, A van Rensburg, K Karkouti
BACKGROUND: An important cause of coagulopathy in cardiac surgery is impaired thrombin generation. While plasma is often used to correct this element of the coagulopathy, studies in vitro suggest that prothrombin complex concentrates (PCCs) might be more effective. Comparative data, however, are scant. METHODS: We compared the outcomes of those who received only plasma with those who received PCCs (with or without plasma) for management of coagulopathy in patients who underwent cardiac surgery with cardiopulmonary bypass at a single institution from 2012 to 2016...
May 2018: British Journal of Anaesthesia
Samir N Babayev, Mohammed Kanchwala, Chao Xing, Yucel Akgul, Bruce R Carr, Ruth Ann Word
Vaginal bleeding and subchorionic hematomas are associated with increased risk of both early and late pregnancy loss. Thrombin generation may play a pivotal role in the development of these complications. To determine the effects of thrombin on human endometrial stromal cells (hESCs), cells were treated with thrombin at baseline or during decidualization with cyclic adenosine monophosphate (cAMP)+medroxyprogesterone acetate (MPA). Next-generation RNA sequencing revealed that markers of decidualization (IGF-1, IGFBP-1, and prolactin [PRL]) were induced after the initiation of decidualization, whereas thrombin suppressed insulin-like growth factor ( IGF)-1, Insulin-like growth factor binding protein ( IGFBP)-1, and PRL gene expression at baseline and during decidualization...
January 1, 2018: Reproductive Sciences
John Alfred Carr
BACKGROUND: Omega-3 fatty acids are widely used. This article reviews the coagulopathic effects of fish oil. METHODS: A review was performed of all English articles that addressed the topic from 1980 to 2017. RESULTS: Fish oil induces an in vitro coagulopathy in humans due to inhibitory effects in platelet-to-platelet adhesion and platelet-stimulated thrombin generation. The effect from fish oil alone is weak, but it is enhanced and may become clinically noticeable in patients taking antiplatelet therapy, and, to a lesser extent, in patients on factor Xa inhibitors and warfarin...
April 4, 2018: Annals of Thoracic Surgery
Jourdi Georges, Lefèbvre Sebastien, Le Bonniec Bernard, Curis Emmanuel, Gaussem Pascale, Lattard Virginie, Siguret Virginie
Vitamin K antagonist rodenticide pharmacodynamics (PD) is studied in rodents with traditional laboratory tests. We wondered if thrombin generation test (TGT) could add value. Difethialone (10 mg/kg) was administered per os to 97 OFA-Sprague Dawley rats. PD was studied over a 72 h-period using the Calibrated Automated Thrombogram on platelet poor plasma before and after intoxication (3 female and 3 male rats for each 13 time points) and TGT parameters were compared with the prothrombin time (PT) and vitamin K dependent factor activities previously reported...
April 2018: Pesticide Biochemistry and Physiology
Christina Weidhofer, Meyer Elias, Ristl Robin, Helmut Wiedemann, Janne Cadamuro, Kipman Ulrike, Jakob Zierk, Christoph Male, Peter Quehenberger, Elisabeth Haschke-Becher, Elisa Einwallner
INTRODUCTION: Practical and ethical challenges as well as time and costs have restricted the generation of pediatric reference intervals. Therefore, pediatric reference intervals on coagulation parameters based on solid evidence are still scarce. Furthermore, reference intervals by age-group cannot reflect the dynamics of age and sex specific coagulation values during childhood. This study is the first to close this gap and provide continuous age and sex dependent reference intervals during childhood in hemostasis...
April 4, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Li Guo, Dongxia Tong, Muxin Yu, Yan Zhang, Tao Li, Chunxu Wang, Peng Zhou, Jiaqi Jin, Baorong Li, Yingmiao Liu, Ruipeng Liu, Valerie A Novakovic, Zengxiang Dong, Ye Tian, Junjie Kou, Yayan Bi, Jin Zhou, Jialan Shi
Multiple myeloma (MM) is characterized by an increased incidence of thromboembolic events, particularly when treated with immunomodulatory drugs (IMiDs) in combination with dexamethasone. The optimal prophylactic strategy to prevent the hypercoagulable state of patients with MM is still debated. The aim of the current study was to investigate the definitive role of phosphatidylserine (PS) in supporting procoagulant activity (PCA) in patients with MM. Patients with MM (n=20) and healthy subjects (n=15) were recruited for the present study...
April 3, 2018: International Journal of Oncology
Sarah Goldman, Paulina Frączek, Krzysztof Szklanny, Elżbieta Papuga-Szela, Andrzej Stanisz, Anetta Undas
BACKGROUND:  Prothrombotic clot phenotype may characterize patients developing deep vein thrombosis (DVT) despite pharmacological thromboprophylaxis. We studied the role of fibrin clot properties and its potential determinants in individuals who experienced DVT after lower limb injury. METHODS:  In a case-control study, we assessed 50 patients who developed DVT despite prophylactic use of low-molecular-weight heparins (the failed thromboprophylaxis group) after a lower limb injury, and three age- and sex-matched control groups, 50 patients each: (1) patients with trauma-related DVT without prior thromboprophylaxis; (2) individuals with unprovoked DVT; (3) patients without history of DVT (the no-DVT controls)...
April 2018: Thrombosis and Haemostasis
Simon Chang, Jon J Rasmussen, Mikkel N Frandsen, Morten Schou, Marie L Johansen, Jens Faber, Anna-Marie B Münster, Johannes J Sidelmann, Caroline Kistorp
BACKGROUND:  Anabolic androgenic steroid (AAS) abusers are considered at increased risk of cardiovascular morbidity and mortality. We hypothesized that current and former AAS abuse would induce a procoagulant shift in the haemostatic balance. METHODS:  Men 18 to 50 years of age were included as current AAS abusers, former AAS abusers or controls. Morning blood samples were collected after overnight fasting. Thrombin generation (lag time, time to peak, peak height, and endogenous thrombin potential [ETP]) and coagulation factor II (prothrombin), VII and X, antithrombin, protein C, free protein S and tissue factor pathway inhibitor (TFPI) were assessed...
April 2018: Thrombosis and Haemostasis
Verena C Mulder, Jeroen Bastiaans, Cornelis J M van Leuven, Jan C van Meurs, Cornelis Kluft
PURPOSE: To measure prothrombin fragments (F1+2) and thrombin-antithrombin complex (TAT) in vitreous and subretinal fluid (SRF) of rhegmatogenous retinal detachment (RRD) patients and to validate and further specify our earlier finding of increased thrombin activity in patients with proliferative vitreoretinopathy (PVR). METHODS: F1+2 and TAT were measured in 31 vitreous and 16 SRF samples using the Enzygnost® immunoassays. RESULTS: We found significant levels of F1+2 and TAT in the vitreous of all patients with RRD compared to patients with macular hole or macular pucker...
April 4, 2018: Ophthalmologica. Journal International D'ophtalmologie
Jing Zhu, Haiying Gan, Jie Wu, Huangxian Ju
A bipedal molecular machine powered surface programmatic chain reaction was designed for electrochemical signal amplification and highly sensitive electrochemical detection of protein. The bipedal molecular machine was built through aptamer-target specific recognition for the binding of one target protein with two DNA probes, which hybridized with surface-tethered hairpin DNA 1 (H1) via proximity effect to expose prelocked toehold domain of H1 for the hybridization of ferrocene-labeled hairpin DNA 2 (H2-Fc)...
April 4, 2018: Analytical Chemistry
Camille Faes, Erica M Sparkenbaugh, Rafal Pawlinski
Chronic activation of coagulation is one of the features of sickle cell disease (SCD). Increased tissue factor expression, phosphatidylserine exposure, thrombin generation and fibrinolysis, as well as decreased levels of natural anticoagulants have been reported in SCD patients and in the mouse models of SCD. Consistent with this, patients with SCD are prone to develop thrombotic complications. In addition, the altered morphology of sickle red blood cells (RBC) may also alter the properties and dynamics of clot formation in SCD patients...
2018: Clinical Hemorheology and Microcirculation
Marina Panova-Noeva, Andreas Schulz, Henri M Spronk, Aline Beicht, Dagmar Laubert-Reh, Rene van Oerle, Natalie Arnold, Jürgen H Prochaska, Maria Blettner, Manfred Beutel, Norbert Pfeiffer, Thomas Münzel, Karl J Lackner, Hugo Ten Cate, Philipp S Wild
The tendency of a plasma sample to generate thrombin, a central enzyme in blood coagulation, might be an important indicator of prothrombotic risk linked to cardiovascular disease (CVD), but the presence of platelets may be a critical determinant. Clinical data, laboratory markers and thrombin generation (TG), investigated in both platelet-rich plasma (PRP) and platelet-free plasma (PFP) at 1 pM TF, were available in 407 individuals from the Gutenberg Health Study. Given the well-known effect of anticoagulants on TG, subjects taking anticoagulants ( n  = 15) have been excluded resulting in 392 subjects for further analysis...
April 3, 2018: Thrombosis and Haemostasis
Cécile H Kicken, Marisa Ninivaggi, Joke Konings, Martijn Moorlag, Dana Huskens, Jasper A Remijn, Saartje Bloemen, Marcus D Lancé, Bas De Laat
INTRODUCTION:  Epidemiological studies suggest that hypobaric hypoxia at high altitude poses a risk for developing venous thromboembolism. The cause of this observed hypercoagulability remains unclear. Therefore, this study aimed to investigate the effect of hypobaric hypoxia at 3,883 m above sea level on thrombin generation and platelet activation. METHODS:  After complying with medical ethical procedures, 18 participants were recruited, of whom 1 had to leave the study prematurely due to mild acute mountain sickness...
April 3, 2018: Thrombosis and Haemostasis
Benjamin R Huebner, Ernest E Moore, Hunter B Moore, Eduardo Gonzalez, Marguerite R Kelher, Angela Sauaia, Anirban Banerjee, Christopher C Silliman
BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is a major regulator of the fibrinolytic system, covalently binding to tissue plasminogen activator and blocking its activity. Fibrinolysis shutdown is evident in the majority of severely injured patients in the first 24 h and is thought to be due to PAI-1. The source of this PAI-1 is thought to be predominantly endothelial cells, but there are known organ-specific differences, with higher levels thought to be in the liver. Thrombin generation is also elevated in injured patients and is a potent stimulus for PAI-1 release in human umbilical endothelial cells...
May 2018: Journal of Surgical Research
Yuanyuan Liu, Yanhua Zhao, Qi Fan, Malik Saddam Khan, Xiaojian Li, Yong Zhang, Hongmin Ma, Qin Wei
An electrochemiluminescent (ECL) aptamer based assay is described for thrombin. It is based on the use of carbon dots (C-dots) placed on polydopamine nanospheres loaded with silver nanoparticles (PDANS@Ag) and with probe DNA (pDNA). The PDANS possess high specific surface and can load a large number of C-dots. The AgNPs, in turn, enhance the ECL emission of the C-dots. Platinum functionalized graphene (Gr-Pt) can connect capture DNA (cDNA). The ECL nanoprobe consisting of PDANS@Ag/C-dots was placed on a glassy carbon electrode modified with Gr-Pt/cDNA/BSA via hybridization between cDNA and pDNA...
January 8, 2018: Mikrochimica Acta
Michal Zabczyk, Joanna Natorska, Anetta Undas
Defective clot contraction has been postulated to contribute to thrombosis. We aimed to evaluate the association of residual vein obstruction (RVO) with erythrocyte compression within the whole-blood clot. We studied 32 patients with venous thromboembolism (VTE) taking vitamin K antagonists (VKAs) for at least 3 months (median time in therapeutic range 60%), including 12 (37.5%) with RVO, and 32 age- and sex-matched controls. In all study participants we evaluated whole blood clot retraction, expressed as the erythrocyte compression index (ECI), defined as a ratio of mean polyhedrocyte area to mean native erythrocyte area, along with clot area covered by polyhedrocytes, plasma clot permeability (Ks), clot lysis time (CLT), and thrombin generation...
March 27, 2018: Journal of Thrombosis and Thrombolysis
Oliver Borst, Patrick Münzer, Nada Alnaggar, Sascha Geue, Roland Tegtmeyer, Dominik Rath, Michal Droppa, Peter Seizer, Stefan Heitmeier, Johan W M Heemskerk, Lisa K Jennings, Robert F Storey, Dominick J Angiolillo, Bianca Rocca, Henri Spronk, Hugo Ten Cate, Meinrad Gawaz, Tobias Geisler
Very low-dose (VLD) factor Xa (FXa) inhibition, in combination with acetylsalicylic acid (ASA) and clopidogrel, is associated with improved outcomes in patients with acute coronary syndrome (ACS) with a tolerable bleeding risk profile. To date, there are no data documenting platelet inhibition and the anticoagulatory effects of VLD FXa inhibition on top of guideline-adherent dual-antiplatelet therapy (DAPT) in patients with ACS. Patients with non-ST-elevation myocardial infarction (NSTEMI) receiving oral DAPT (ASA + clopidogrel, n = 20; or ASA + ticagrelor, n = 20) were prospectively enrolled in a nonrandomized study...
March 27, 2018: Blood Advances
Benoît Cuq, Shauna L Blois, R Darren Wood, Gabrielle Monteith, Anthony C Abrams-Ogg, Christian Bédard, Geoffrey A Wood
BACKGROUND: Thrombin plays a central role in hemostasis and thrombosis. Calibrated automated thrombography (CAT), a thrombin generation assay, may be a useful test for hemostatic disorders in dogs. OBJECTIVES: To describe CAT results in a group of healthy dogs, and assess preanalytical variables and biological variability. ANIMALS: Forty healthy dogs were enrolled. METHODS: Lag time (Lag), time to peak (ttpeak), peak thrombin generation (peak), and endogenous thrombin potential (ETP) were measured...
March 26, 2018: Veterinary Clinical Pathology
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