Hydroxyethyl starches (HES) are the most routinely used synthetic colloids during fluid resuscitation and have reported effects on coagulation. The overall goal of the investigation in this thesis was to evaluate the effects of tetrastarch administration on hemodynamic, laboratory, and hemostatic variables in healthy dogs and dogs with systemic inflammation. The objectives were to compare hemodynamic and laboratory variables in dogs receiving an isotonic crystalloid (0.9% NaCl) or tetrastarch during health and after induction of systemic inflammation; to compare the hemostatic effects of an isotonic crystalloid (0.9% NaCl) and synthetic colloid (tetrastarch) in healthy dogs and dogs with induced systemic inflammation; to compare two different protocols for TEG® activation and to determine the correlation between TEG® variables and traditional coagulation test results. Sixteen adult purpose-bred Beagles were randomized into one of two groups receiving fluid resuscitation with either 40 mL/kg IV isotonic crystalloid (0.9% NaCl) or synthetic colloid (tetrastarch) after administration of lipopolysaccharide (LPS; 5 μg/kg, IV) or an equal volume of placebo (0.9% NaCl, IV). Blood samples, for analysis, were collected at 0, 1, 2, 4, and 24 hours from the time of fluid resuscitation. After a 14-day washout period, the study was repeated such that dogs received the opposite treatment (LPS or placebo) and the same resuscitation fluid. Resuscitation with equal volumes of 0.9% NaCl and tetrastarch caused similar changes in hemodynamic and laboratory variables in dogs with LPS-induced systemic inflammation; however, larger increases in HR and blood pressure were seen within the first 2 hours following tetrastarch administration compared to 0.9% NaCl. Tetrastarch administration increased COP in all dogs, despite a decrease in TS. Tetrastarch bolus administration to dogs with LPS-induced systemic inflammation also resulted in a transient hypocoagulability characterized by a prolonged PTT, decreased clot formation speed and clot strength, and acquired type 1 von Willebrand disease. Considering the limited additional benefit of tetrastarch administration on hemodynamic variables demonstrated, as well as the transient adverse hemostatic effects of tetrastarch administration, the increased cost associated with the use of tetrastarch likely negates its use as a first line treatment during fluid resuscitation in dogs. / Pet Trust Fund

La thromboélastométrie (TEM) rotative est un examen évaluant les propriétés viscoélastiques du sang dans des conditions de faible cisaillement. La TEM est capable d'apprécier dynamiquement la fonction hémostatique globale d'un patient depuis la formation du caillot à sa lyse. Le profil obtenu par cette technique peut être classé en hypercoagulable, normal ou hypocoagulable. Les études de ce travail révèlent que le sexe et la stérilisation n'affectent pas la valeur des différents paramètres TEM. L'âge est associé à l'apparition de profils hypercoagulables et à une diminution de l'activité fibrinolytique chez le beagle en bonne santé. La présence d'une inflammation évoluant à bas bruit semble impliquée dans ce processus. L'âge devrait être considéré comme un facteur de complications thromboemboliques chez le Chien. Par ailleurs, la TEM semble peu sensible dans le monitorage biologique des effets anticoagulants de l'énoxaparine sodique, une héparine à bas poids moléculaire, chez le beagle en bonne santé. Enfin, la TEM s'avère utile dans la description et la caractérisation des désordres de l'hémostase chez des chiens souffrant de leptospirose. Un profil hypocoagulable est associé à la présence de saignements et les paramètres TEM sont significativement différents entre les chiens avec et sans coagulation intravasculaire disséminée. Certains paramètres et indices TEM ont une valence pronostique à l'admission de ces chiens, un profil hypocoagulable étant associé à une augmentation du taux de mortalité / Rotational thromboelastometry (TEM) can be used to assess the viscoelastic properties of clot formation in whole blood under low shear conditions, which provides information on global hemostatic function from the beginning of clot formation through fibrinolysis. The shape of the TEM profile defines a patient’s hemostatic condition as normal, hypercoagulable, or hypocoagulable. First, the studies of this work emphasize that sex and neutered status does not affect the values of TEM parameters. The second study demonstrated an age-related hypercoagulable profile that was associated with decreased fibrinolysis ability in healthy Beagles. Low-grade inflammation seemed to be involved in this process. The incidence of thromboembolic diseases remains to be established in old dogs, but age should be considered a primary risk factor. Third, TEM is insensitive to detect the biological activities of a particular low molecular weight heparin, sodium enoxaparin, in healthy Beagles. Finally, TEM is useful for the description of hemostatic disorders in dogs with naturally occurring leptospirosis. A hypocoagulable profile is associated with bleeding diatheses and the measured TEM parameters are significantly different between dogs with and without disseminated intravascular coagulation. Some measured TEM parameters and calculated indices are associated with outcomes: a hypocoagulable profile is correlated with a higher mortality rate

No description available.

No description available.

<p>  </p> <p>Thrombosis is the pathological formation of a blood clot in the body that blocks blood circulation, leading to high morbidity and mortality rates. Thrombolytic drugs that offer rapid clot dissolution are promising treatments yet current drugs are often associated with limited efficacy and high bleeding risks. While numerous animal thrombosis models have been developed for drug screening, the translation of therapeutic agents into and through clinical trials remains limited. This is largely due to animal models’ poor reproducibility and distinctive physiology to that of humans. <em>In-vitro</em> flow models that utilize both human blood components and physiologically relevant flow conditions can provide for a more representative testing environment to screen thrombolytic drugs. Developing better <em>in-vitro</em> models may not eliminate the need for preclinical animal testing but can help exclude inefficient agents earlier in the drug development pipeline to expedite the drug evaluation process. Existing <em>in-vitro</em> thrombolysis flow models are not ideal as they either adopt over-simplified clot substrates or utilize small-length-scale geometries that insufficiently mimic native hemodynamics. Thus, we propose to first develop a static fluorescently labeled clot lysis assay for an initial high throughput screening of thrombolytic drugs, and ultimately engineer a highly reproducible, physiological scale, flowing clot lysis model for more human relevant drug efficacy evaluation. Developing the static clot lysis assay not only helps to understand the mechanism of how diversified clotting conditions affect clot properties but also offer a chance to well-characterize fluorescence conjugations to fibrins. The ultimate flow model combines an <em>in-vivo</em>-like fluorescence incorporated synthetic clot (FISC) and a human-relevant flow system. Guided by results from static clotting experiments diversified FISCs are fluorescently optimized and fabricated dynamically using a Chandler loop setup at various conditions. The flow system is a tubing-based structure that comprises of a peristaltic pump, and a well-controlled flow chamber to provide for physiological shear and pulsatile levels. Therefore, the proposed synthetic clot model is a versatile platform that can mimic a variety of thrombosis conditions and offer representative drug testing and dosing results across numerous thrombolytic agents.</p>

Trauma-induced coagulopathy (TIC) is a recently described condition which traditionally has been diagnosed by the common coagulation tests (CCTs) such as prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), platelet count, and fibrinogen levels. The varying sensitivity and specificity of these CCTs have led trauma coagulation researchers and clinicians to use Viscoelastic Tests (VET) such as Thromboelastography (TEG) to provide Targeted Thromboelastographic Hemostatic and Adjunctive Therapy (TTHAT) in a goal directed fashion to those trauma patients in need of hemostatic resuscitation. This review describes the utility of VETs, in particular, TEG, to provide TTHAT in trauma and acquired non-trauma-induced coagulopathy.