The effect of ε-aminocaproic acid on blood product requirement, outcome and thromboelastography parameters in severely thrombocytopenic dogs

Background: No treatment other than platelet administration is known to protect against spontaneous hemorrhage in thrombocytopenic dogs. Objectives: Primary: determine if treatment with ε-aminocaproic acid (EACA) decreases the requirement for blood transfusions and improves outcome in dogs with severe thrombocytopenia. Secondary: find evidence of hyperfibrinolysis and determine the effect EACA administration on rapid (rTEG) and tissue plasminogen activator-spiked (tPA-rTEG) thromboelastography parameters. Animals: Twenty-seven dogs with severe thrombocytopenia were treated with EACA, and data from an additional 33 were obtained from the hospital database as historical control (HC) cohort. Methods: Single arm clinical trial with HCs. The EACA group dogs received EACA (100 mg/kg IV followed by a constant-rate infusion [CRI] of 400 mg/kg/24 hours). Thromboelastography before and during EACA infusion, hospitalization days, number of transfusions, and mortality were compared. Results: No difference was found in number of transfusions per dog (median, interquartile range; 1, 0-2.5 vs 0.9, 0-2; P =.5) and hospitalization days (4, 4-6 vs 4.5, 3.75-6; P =.83) between HC and EACA groups, respectively, and no difference in survival was identified by log-rank analysis (P =.15). Maximum amplitude on both rTEG and tPA-rTEG increased after EACA administration (rTEG baseline: 23.6, 9.6-38.9; post-EACA: 27.3, 19.8-43.2; P &lt;.001; tPA-rTEG baseline: 23, 10.9-37.2; post-EACA: 24.7, 16.7-44.8; P &lt;.002). Conclusions and Clinical Importance: Although EACA increased clot strength, there was no effect on outcome. Treatment with EACA at this dosage cannot be recommended as a routine treatment but may be considered for dogs with severe ongoing hemorrhage.</p

Evaluation of thrombin generation in dogs administered clopidogrel

IntroductionThe antiplatelet effect of clopidogrel can vary between patients. A modified thromboelastography (TEG) protocol (TEG-Platelet Mapping assay® [TEG-PM]) can be used for clopidogrel monitoring but is not widely available. Thrombin generation (TG) assays could offer a novel alternative. The main objective of this pilot study was to assess TG assay variables (lag time, peak, endogenous thrombin potential [ETP]) in dogs before and after 7 days of clopidogrel administration and compare with TEG-PM variables (maximum amplitude [MA]-ADP and percentage (%) inhibition).MethodsSix healthy mix-breed dogs were enrolled in this pilot study. Blood samples for platelet count, TG assays, and TEG-PM were obtained at two time points, corresponding to baseline, and after 7 days of clopidogrel administration (mean 2.3 +/− 0.3 mg/kg PO q24 hours). Data were then compared with a Student’s t-test.ResultsThere was no significant change in TG assay variables performed on platelet poor plasma after 7 days of clopidogrel administration: lag time (Day 1: 1.8 +/− 0.2 min, Day 7: 1.8 +/− 0.2 min, p = 0.42); peak (Day 1: 76 +/− 7 nM, Day 7: 72 +/− 10 nM, p = 0.49); and ETP (Day 1: 399 +/− 27 nM*min, Day 7: 392 +/− 32 nM*min; p = 0.49). There were significant changes in TEG MA-ADP (Day 1: 19 +/− 8 mm, Day 7: 9 +/− 6 mm, p = 0.04) and % inhibition (Day 1: 58 +/− 27, Day 7: 99 +/− 0.3, p = 0.02).DiscussionClopidogrel administration did not lead to changes in TG assay variables performed on platelet poor plasma samples, despite concomitant changes in TEG-PM variables consistent with platelet inhibition. Based on this pilot study, thrombin generation performed on platelet poor plasma may not be a useful antiplatelet monitoring tool in dogs

The effect of ε‐aminocaproic acid on blood product requirement, outcome and thromboelastography parameters in severely thrombocytopenic dogs

Abstract Background No treatment other than platelet administration is known to protect against spontaneous hemorrhage in thrombocytopenic dogs. Objectives Primary: determine if treatment with ε‐aminocaproic acid (EACA) decreases the requirement for blood transfusions and improves outcome in dogs with severe thrombocytopenia. Secondary: find evidence of hyperfibrinolysis and determine the effect EACA administration on rapid (rTEG) and tissue plasminogen activator‐spiked (tPA‐rTEG) thromboelastography parameters. Animals Twenty‐seven dogs with severe thrombocytopenia were treated with EACA, and data from an additional 33 were obtained from the hospital database as historical control (HC) cohort. Methods Single arm clinical trial with HCs. The EACA group dogs received EACA (100 mg/kg IV followed by a constant‐rate infusion [CRI] of 400 mg/kg/24 hours). Thromboelastography before and during EACA infusion, hospitalization days, number of transfusions, and mortality were compared. Results No difference was found in number of transfusions per dog (median, interquartile range; 1, 0‐2.5 vs 0.9, 0‐2; P = .5) and hospitalization days (4, 4‐6 vs 4.5, 3.75‐6; P = .83) between HC and EACA groups, respectively, and no difference in survival was identified by log‐rank analysis (P = .15). Maximum amplitude on both rTEG and tPA‐rTEG increased after EACA administration (rTEG baseline: 23.6, 9.6‐38.9; post‐EACA: 27.3, 19.8‐43.2; P < .001; tPA‐rTEG baseline: 23, 10.9‐37.2; post‐EACA: 24.7, 16.7‐44.8; P < .002). Conclusions and Clinical Importance Although EACA increased clot strength, there was no effect on outcome. Treatment with EACA at this dosage cannot be recommended as a routine treatment but may be considered for dogs with severe ongoing hemorrhage

Deep Underground Neutrino Experiment (DUNE), Far Detector Technical Design Report, Volume I Introduction to DUNE

International audienceThe preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE's physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology

Deep Underground Neutrino Experiment (DUNE), Far Detector Technical Design Report, Volume II: DUNE Physics

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay -- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. DUNE is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume II of this TDR, DUNE Physics, describes the array of identified scientific opportunities and key goals. Crucially, we also report our best current understanding of the capability of DUNE to realize these goals, along with the detailed arguments and investigations on which this understanding is based. This TDR volume documents the scientific basis underlying the conception and design of the LBNF/DUNE experimental configurations. As a result, the description of DUNE's experimental capabilities constitutes the bulk of the document. Key linkages between requirements for successful execution of the physics program and primary specifications of the experimental configurations are drawn and summarized. This document also serves a wider purpose as a statement on the scientific potential of DUNE as a central component within a global program of frontier theoretical and experimental particle physics research. Thus, the presentation also aims to serve as a resource for the particle physics community at large