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1.
Objective – To review the veterinary and human literature on the role of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in health and disease states.
Data Sources – Original research articles and scientific reviews from both human and veterinary literature were searched for relevance to TF and TFPI.
Human Data Synthesis – Interest in both TF and TFPI has grown widely over the last several years. The impact TF plays in coagulation, inflammation, angiogenesis, tumor metastasis, and cellular signaling has become apparent. Treatment with TFPI for severe sepsis has been examined and is still currently under investigation. Inhibition of the TF pathway is being studied as an aid in the treatment of neoplasia. The important physiologic and pathophysiologic role these molecules play has only begun to be understood.
Veterinary Data Synthesis – There is a paucity of publications that discuss the importance of TF and TFPI in veterinary medicine. An enhanced understanding of the TF pathway in human medicine, in experimental animal models treating sepsis with TFPI, and in animal models demonstrating the proangiogenic properties of TF provides relevance to veterinary medicine.
Conclusion – It is apparent that TF and TFPI are important in health and disease. An enhanced understanding of the physiologic and pathophysiologic roles of these factors provides better insight into coagulation, inflammation, angiogenesis, disseminated intravascular coagulation, and tumor metastasis. This greater understanding may provide for the development of therapeutics for sepsis, disseminated intravascular coagulation, and neoplasia.  相似文献   

2.
Objective: To provide evidence that naturally occurring sepsis in dogs provides a unique opportunity to test new therapies in clinically relevant settings. Data sources: Human and veterinary literature. Human data synthesis: Sepsis is a devastating condition responsible for most intensive care unit deaths. Most clinical trials targeting inflammatory mediators of sepsis have failed to improve outcome in clinical patients despite promising results in laboratory animal models. Animal models of sepsis fail to reproduce the clinical syndrome and therefore lead to conclusions that may not be relevant to clinical care. Veterinary data synthesis: Sepsis is recognized but not well‐characterized in companion animal species. Despite some species variability, the cardiopulmonary response to sepsis in dogs is similar to humans. Additionally, inflammatory and coagulation changes that accompany canine sepsis are consistent with those documented in humans. Sepsis secondary to canine parvoviral infection offers the advantages of relative population homogeneity, predictable course, and easy early diagnosis. The disadvantages of canine parvovirus are that it affects a predominantly young and healthy population and results in low mortality with aggressive supportive care. Septic peritonitis and pneumonia have high mortality but can be challenging to diagnose, have a variable course, and affect a heterogeneous population, which can be an advantage or a disadvantage. Conclusions: Similar to trials currently being performed in canine cancer patients, veterinary clinical trials of new sepsis therapeutics may provide a unique opportunity to advance the treatment of sepsis in dogs, humans, and other species. Spontaneous sepsis from canine parvovirus, peritonitis, and pneumonia are common clinical conditions in which therapeutics can be tested.  相似文献   

3.
Objective: To review the human and veterinary literature on the physiological role and effects of therapeutic albumin supplementation. Data sources: Data from human and veterinary literature was reviewed. Human data synthesis: Hypoalbuminemia often occurs in a variety of critical illnesses, and contributes to the development of life‐threatening complications, including pulmonary edema, delayed wound healing, feeding intolerance, hypercoaguability, and multiple organ dysfunction. Serum albumin concentration has been used as a prognostic indicator in cases of chronic hypoalbuminemia. The use of albumin replacement therapy in humans is sometimes controversial, but may be associated with improved morbidity and decreased mortality. Veterinary data synthesis: Unlike human literature, there is a paucity of controlled clinical studies in the literature regarding albumin supplementation in veterinary patients. Rather, the majority of published studies were performed in experimental animals or via retrospective analyses. One recent study evaluated the use of plasma to improve albumin concentration in dogs with hypoalbuminemia. Other older studies investigated wound healing in dogs with experimentally induced hypoalbuminemia. As in human medicine, serum albumin concentration may be helpful as a prognostic indicator in critically ill dogs. Conclusion: Albumin is one of the most important proteins in the body because of its role in maintenance of colloid oncotic pressure, substrate transport, buffering capacity, as a mediator of coagulation and wound healing, and free‐radical scavenging. Albumin replacement in veterinary medicine is difficult, but until prospective clinical trials determine the efficacy of albumin replacement are conducted, a suggested clinical guideline would be to maintain albumin concentration at or above 2.0 g/dl utilizing fresh frozen plasma.  相似文献   

4.
Objective: To review the current understanding of the mechanisms responsible for primary hemostasis and to give an overview of primary hemostatic syndromes in small animal patients. Current and future therapeutic options for dysfunction of primary hemostasis are discussed. Data sources: A thorough search of the human and veterinary literature using the keywords platelets, primary hemostasis, von Willebrand factor (vWF), von Willebrand disease, aspirin, thromboxane, and aggregation, were performed. Databases searched included OVID Medline, Pubmed, and CAB abstracts. Conclusions: Primary hemostasis occurs when platelets adhere to an injured or disrupted endothelial surface. Adherence is followed by activation, or the release of platelet granule contents. The agonists released from platelet granules recruit additional platelets and induce their activation and aggregation. Adhesion, activation, and aggregation are mediated by different receptors and ligands depending on the local blood flow conditions. vWF and adenosine diphosphate are the primary mediators of adhesion, activation, and aggregation under high shear conditions. During low shear conditions collagen, fibronectin, and laminin mediate adhesion, thromboxane A2 promotes activation, while aggregation is mediated by glycoprotein Ib‐IX‐V (GP Ib–IX–V) and fibrinogen. Knowledge of the receptor interactions during different blood flow conditions is crucial to the understanding of the various inhibitors of primary hemostasis available to clinicians.  相似文献   

5.
6.
Objective: To review the effects of critical illness on hypothalamic–pituitary–adrenal (HPA) function in human and veterinary medicine. Data sources: Data from human and veterinary literature was reviewed. Human data synthesis: Relative adrenal insufficiency (RAI) appears to be common in critically ill human patients with sepsis or septic shock. Hypotension that is refractory to fluid therapy and requires vasopressors is the most common presentation of RAI in the human intensive care unit (ICU). Many investigators now advocate the use of a low‐dose adrenocorticotropin hormone stimulation test to diagnose RAI. It is important to evaluate for the presence of adrenal dysfunction, because current data suggest that treatment with ‘stress’ or low doses of glucocorticoids (200–300 mg hydrocortisone daily) may improve patient outcome in humans. Veterinary data synthesis: There is a paucity of controlled studies in the veterinary literature regarding the effects of critical illness on HPA function. The results of these studies are varied. However, research models of sepsis and hemorrhagic shock suggest the existence of RAI in animals. Prospective clinical studies are needed to further examine pituitary–adrenal response to severe illness in veterinary patients, and to determine if there are therapeutic options, including glucocorticoid administration, which will improve patient outcome in animals. Conclusions: RAI is well documented in critically ill human patients, yet little is known about adrenal dysfunction in veterinary critically ill patients. A small number of studies suggest that RAI may exist in certain subpopulations of veterinary patients. The syndrome of RAI could be considered as a differential diagnosis in seriously ill veterinary patients that fail to respond to appropriate therapy, especially when hypotension refractory to fluid and vasopressor therapy is encountered. This disorder may represent a previously unidentified syndrome in critically ill veterinary patients with important therapeutic implications.  相似文献   

7.
Use of viscoelastic point-of-care (POC) coagulation instrumentation is relatively new to veterinary medicine. In human medicine, this technology has recently undergone resurgence owing to its capacity to detect hypercoagulability. The lack of sensitive tests for detecting hypercoagulable states, along with our current understanding of in vivo coagulation, highlights the deficiencies of standard coagulation tests, such as prothrombin and partial thromboplastin times, which are performed on platelet-poor plasma. Viscoelastic coagulation analyzers can provide an assessment of global coagulation, from the beginning of clot formation to fibrinolysis, utilizing whole blood. In people, use of this technology has been reported to improve management of hemostasis during surgery and decrease usage of blood products and is being used as a rapid screen for hypercoagulability. In veterinary medicine, clinical use of viscoelastic technology has been reported in dogs, cats, foals, and adult horses. This article will provide an overview of the technology, reagents and assays, applications in human and veterinary medicine, and limitations of the 3 viscoelastic POC analyzers in clinical use.  相似文献   

8.
Sepsis is associated with substantial morbidity and mortality in dogs. Alterations in hemostasis by systemic inflammation play an important role in the pathophysiology of sepsis. To evaluate the functional hemostatic changes in sepsis, we evaluated coagulation profiles and flow cytometric measurement of P-selectin (CD62P) expression on platelets, as well as platelet-leukocyte aggregation from a lipopolysaccharide (LPS)-induced endotoxemia model in dogs (n = 7). A sublethal dose of LPS [1 mg/kg body weight (BW)] induced thrombocytopenia and increased activated partial thromboplastin time (aPTT), prothrombin time (PT), and D-dimer concentrations. Flow cytometry analysis showed a significant increase in P-selectin expression on platelets between 1 and 24 h of a total 48 h of the experiment. In addition, platelet-leukocyte aggregation was significantly increased in the early stage of endotoxemia (at 1 and < 6 h for platelet-monocyte aggregation and at 3 h for platelet-neutrophil aggregation). Our results suggest that CD62P expression on platelets and platelet-leukocyte aggregation, as measured by flow cytometry, can be useful biomarkers of disseminated intravascular coagulation (DIC) in canine sepsis. These functional changes contribute to our understanding of the pathophysiology of hemostasis in endotoxemia.  相似文献   

9.
Objective – To review the hemostasis literature relevant to development of coagulopathy in the critically ill equine patient.
Data Source – Original scientific and review articles.
Human Data Synthesis – Inflammation plays a critical role in the activation and amplification of clot formation, as well as the impairment of physiologic anticoagulant mechanisms, and fibrinolysis. Earlier identification of coagulopathy in patients at risk and restoration of physiologic hemostasis may result in better outcome. Development of scoring systems based on information other than coagulation markers alone may better identify patients with subclinical coagulopathy.
Veterinary Data Synthesis – Critically ill equine patients commonly at risk for coagulopathy include those with severe gastrointestinal disease, septic foals, and adults subjected to severe systemic inflammatory response syndrome. Publications provide information regarding coagulation markers helpful for identification of hemostatic dysfunction in specific patient populations, as well as information regarding the influence of coagulopathy on outcome. Data regarding clinically relevant information on therapeutic intervention are lacking.
Conclusions – The relationship between inflammation and endotoxemia and development of coagulopathy is better understood in both human patients and the critically ill equine patient. Prospective clinical trials evaluating clinically relevant and financially feasible approaches to treatment are still needed.  相似文献   

10.
Objective: To describe the technique of thromboelastography (TEG) and review the applications of this coagulation test in humans and small animals. Data sources: Data sources included scientific reviews and original research publications. Human data synthesis: TEG in humans has been used for documentation of hypercoagulable and hypocoagulable states and has been shown to be beneficial in patient management. Veterinary data synthesis: Clinical evaluation of TEG in veterinary medicine is limited; however, recent reports have documented evidence of hypercoagulability in dogs with parvovirus and protein‐losing nephropathy. Additionally, many of the research models may be relevant to veterinary patients. Conclusions: TEG provides information about coagulation that is not available through routine coagulation tests. The application of TEG monitoring to veterinary patients shows promise; however, prospective clinical studies are needed.  相似文献   

11.
Objectives – To review the role of thrombin in physiology and clinical disease and to discuss the pharmacology of antithrombosis.
Data Sources – Original research articles, scientific reviews, textbooks.
Human Data Synthesis – Thrombin and thrombin receptors are involved in a variety of physiologic and pathologic processes resulting in a great deal of interest in thrombin-related pharmacologic intervention.
Veterinary Data Synthesis – Although there is little clinical research data available on thrombin specifically in veterinary patients, some of the original research on protease activated receptors was performed at veterinary institutions and many of the human molecular biology studies have been done on animals including dogs.
Conclusion – Thrombin plays a significant role in coagulation, anticoagulation, and fibrinolysis. Antithrombotic treatment is focused on preventing thrombosis while maintaining hemostasis. Pharmaceutical agents are selected for the specific component of the coagulation pathway associated with a specific disease process, for a proven prophylactic benefit with procedures that carry a risk of thromboembolism, for rapidity of onset and ease of reversibility, for limited monitoring requirements, and for oral formulation and bioavailablity. Recent insight into other aspects of thrombin physiology presents an opportunity for pharmacologic intervention in a variety of other processes such as inflammation and sepsis, peripheral blood cell activation and chemotaxis, vascular endothelial and smooth muscle activity, cellular development and tissue repair, mitogenesis, neoplasia, and the function of nervous tissue following injury.  相似文献   

12.
Objective – To review the use of IV lipid emulsion (ILE) for the treatment of toxicities related to fat‐soluble agents; evaluate current human and veterinary literature; and to provide proposed guidelines for the use of this emerging therapy in veterinary medicine and toxicology. Data Sources – Human and veterinary medical literature. Human Data Synthesis – Human data are composed mostly of case reports describing the response to treatment with ILE as variant from mild improvement to complete resolution of clinical signs, which is suspected to be due to the variability of lipid solubility of the drugs. The use of ILE therapy has been advocated as an antidote in cases of local anesthetic and other lipophilic drug toxicoses, particularly in the face of cardiopulmonary arrest and unsuccessful cardiopulmonary cerebral resuscitation. Veterinary Data Synthesis – The use of ILE therapy in veterinary medicine has recently been advocated by animal poison control centers for toxicoses associated with fat‐soluble agents, but there are only few clinical reports documenting successful use of this therapy. Evidence for the use of ILE in both human and veterinary medicine is composed primarily from experimental animal data. Conclusions – The use of ILE appears to be a safe therapy for the poisoned animal patient, but is warranted only with certain toxicoses. Adverse events associated with ILE in veterinary medicine are rare and anecdotal. Standard resuscitation protocols should be exhausted before considering this therapy and the potential side effects should be evaluated before administration of ILE as a potential antidote in cases of lipophilic drug toxicoses. Further research is waranted.  相似文献   

13.
Coagulation profiles in 27 horses with large colon volvulus   总被引:3,自引:3,他引:0  
Objective: The objective of this study was to evaluate coagulation profiles in horses with surgical treatment of large colon volvulus (LCV), and determine if an association exists between hemostatic dysfunction and outcome. Design: Prospective clinical investigation from February to December 2000. Setting: Large animal intensive care unit in a veterinary teaching hospital. Interventions: Blood was collected from horses intra‐operatively, 24, and 48 hours following surgical treatment for LCV. Measurements: Coagulation profiles, thrombin–antithrombin (TAT) levels, and D‐dimer concentrations were determined for each time point. The number of tests abnormal in the standard coagulation profile, defined as the degree of hemostatic dysfunction, was determined for each horse for the duration of the study period. The association between each test and outcome, as well as the degree of hemostatic dysfunction for each horse and outcome, was determined using univariate analysis and logistic regression. TAT levels and D‐dimer concentrations were compared to the results of the standard coagulation profile and to patient outcome using univariate analysis and logistic regression. Main results: Seventy percent of horses evaluated with surgical treatment of LCV had evidence of hemostatic dysfunction (3/6 tests abnormal). Only 18% of those patients had clinical signs recognized by the attending clinician as a coagulopathy. There was an association between the development of a coagulopathy and outcome, with horses with 4/6 tests abnormal being more likely to be euthanized, and those with 3/6 tests abnormal having a prolonged hospital stay. Platelet count, prothrombin time, and TAT levels may be helpful in predicting outcome in horses with LCV. Conclusions: Hemostatic function should be evaluated in horses with surgical treatment of LCV to detect subclinical coagulopathies and direct subsequent intervention.  相似文献   

14.
Objective: To review the human and companion animal veterinary literature on nosocomial infections and antimicrobial drug resistance as they pertain to the critically ill patient. Data sources: Data from human and veterinary sources were reviewed using PubMed and CAB. Human data synthesis: There is a large amount of published data on nosocomially‐acquired bloodstream infections, pneumonia, urinary tract infections and surgical site infections, and strategies to minimize the frequency of these infections, in human medicine. Nosocomial infections caused by multi‐drug‐resistant (MDR) pathogens are a leading cause of increased patient morbidity and mortality, medical treatment costs, and prolonged hospital stay. Epidemiology and risk factor analyses have shown that the major risk factor for the development of antimicrobial resistance in critically ill human patients is heavy antibiotic usage. Veterinary data synthesis: There is a paucity of information on the development of antimicrobial drug resistance and nosocomially‐acquired infections in critically ill small animal veterinary patients. Mechanisms of antimicrobial drug resistance are universal, although the selection effects created by antibiotic usage may be less significant in veterinary patients. Future studies on the development of antimicrobial drug resistance in critically ill animals may benefit from research that has been conducted in humans. Conclusions: Antimicrobial use in critically ill patients selects for antimicrobial drug resistance and MDR nosocomial pathogens. The choice of antimicrobials should be prudent and based on regular surveillance studies and accurate microbiological diagnostics. Antimicrobial drug resistance is becoming an increasing problem in veterinary medicine, particularly in the critical care setting, and institution‐specific strategies should be developed to prevent the emergence of MDR infections. The collation of data from tertiary‐care veterinary hospitals may identify trends in antimicrobial drug resistance patterns in nosocomial pathogens and aid in formulating guidelines for antimicrobial use.  相似文献   

15.
Diagnosis of Disseminated Intravascular coagulation (DIC) is controversial in both human and veterinary medicine. This article reviews the available literature in human and veterinary medicine regarding the etiology, pathophysiology, and diagnosis of DIC with emphasis on the diagnosis of DIC in dogs. Controversy surrounding the diagnosis of DIC arises from the complex nature of the disease itself, in addition to the absence of a consensus strategy for laboratory testing. The available literature indicates that dogs diagnosed with DIC possessed various hemostatic function testing abnormalities, typically possessed an underlying disease that predisposed to DIC, but may or may not have had clinically identifiable hemorrhage or thrombosis. Additionally, the hemostatic function testing utilized in diagnosis is not uniform. Generalizations about the usefulness of individual assays or diagnostic strategies cannot be formulated because of the marked diversity of the types of cases studied, as well as the small number of cases reported in the literature. (Vet Emerg & Crit Care, 1998; 8: 29–45)  相似文献   

16.
Inherited disorders of hemostasis encompass abnormalities in primary hemostasis, coagulation, and fibrinolysis resulting from genetic mutations. There is significant variation in the phenotype expressed ranging from life limiting to the absence of overt clinical signs. Von Willebrand disease is the most common primary hemostatic disorder in dogs, and hemophilia A is the most common coagulation factor disorder. The diagnosis of inherited bleeding disorders is made by functional and/or quantitative evaluation. Genetic testing has added to the knowledge base, allowing prevention through targeted breeding. Avoidance of trauma and injury is paramount in the prevention of bleeding in animals diagnosed with inherited hemostatic disorders. Current therapeutic options include platelet transfusions, broad replacement of coagulation factors (e.g., plasma), targeted factor replacement (e.g., cryoprecipitate), antifibrinolytic agents and specific factor replacement, and treatment of the symptoms (i.e., bleeding) with blood transfusions.  相似文献   

17.
Objective: To review the current understanding of dopamine and its use in the prevention and treatment of acute renal failure (ARF). Data sources: Original research articles and scientific reviews. Human data synthesis: Low‐dose dopamine administration has been shown to increase natriuresis and urinary output in both healthy individuals and in a few small studies in human patients with renal insufficiency. However, in several large meta‐analyses, dopamine treatment did not change mortality or the need for dialysis. Due to the potential side effects, the use of dopamine for prevention and treatment of ARF is no longer recommended in human medicine. Veterinary data synthesis: Low‐dose dopamine increases urinary output in healthy animals and animal models of ARF if given before the insult. There are no available studies looking at the effect of low‐dose dopamine therapy in naturally occurring ARF in dogs or cats. Conclusion: Due to the potential side effects of low‐dose dopamine therapy, the results from large human trials, and the lack of information in veterinary medicine, the use of dopamine for treatment of ARF in veterinary patients should be further evaluated.  相似文献   

18.
Background – To review the physics of helium with regard to airway physiology, as well as known human and potential veterinary applications of administration of inhaled helium‐oxygen gas‐carrier mixture (heliox). Data Sources – Human and veterinary studies. Human Data Synthesis – Helium‐oxygen mixtures have been used in human medicine for over 70 years as an adjunct therapy in various upper and lower respiratory disorders. Helium's low density promotes laminar flow through partially obstructed airways, resulting in a decreased work of breathing. Veterinary Data Synthesis – Little to no evidence‐based medicine exists to support or oppose the use of heliox in veterinary species. However, domestic animal species and humans share several common pathophysiologic aspects of various obstructive airway disorders. Thus, veterinary patients may also ultimately and significantly benefit from this novel therapy. Conclusion – Prospective studies are needed in veterinary medicine to determine the utility of heliox in clinical scenarios.  相似文献   

19.
Objective: To review the clinical and pathophysiologic aspects of acute respiratory distress syndrome (ARDS) in dogs and cats. Data sources: Data from human and veterinary literature were reviewed through Medline and CAB as well as manual search of references listed in articles pertaining to acute lung injury (ALI)/ARDS. Human data synthesis: Since the term ARDS was first coined in 1967, there has been a abundance of literature pertaining to this devastating syndrome in human medicine. More complete understanding of the complex interactions between inflammatory cells, soluble mediators (e.g., tumor necrosis factor, interleukin (IL)‐6, IL‐8, platelet activating factor) and the clinical patient has provided for timely recognition and mechanistically based protective strategies decreasing morbidity and mortality in human patients with ARDS. Veterinary data synthesis: Although little is known, ARDS is becoming a more commonly recognized sequela in small animals. Initial case reports and retrospective studies have provided basic clinical characterization of ARDS in dogs and cats. Additionally, information from experimental models has expanded our understanding of the inflammatory mechanisms involved. It appears that the inflammatory processes and pathologic changes associated with ARDS are similar in dogs, cats, and humans. Conclusions: Unfortunately, current mortality rates for ARDS in small animals are close to 100%. As our capability to treat patients with advanced life‐threatening disease increases, it is vital that we develop a familiarity with the pathogenesis of ARDS. Understanding the complex inflammatory interactions is essential for determining effective preventative and management strategies as well as designing novel therapies for veterinary patients.  相似文献   

20.
Objective: The objective of this article is to review the human and veterinary literature and provide evidence for the potential beneficial effects of intravenous (IV) lidocaine hydrochloride in preventing post‐ischemic–reperfusion injury, the systemic inflammatory response syndrome (SIRS), and subsequent multiple organ dysfunction syndrome (MODS). Human data synthesis: Lidocaine is a local anesthetic and antiarrhythmic agent that has been used for years in human and veterinary medicine for the treatment of ventricular dysrhythmias associated with blunt cardiac trauma, myocardial ischemia, and cardiac surgery. More recently, the drug has been touted as a scavenger of reactive oxygen species (ROS), and has been used to prevent reperfusion dysrhythmias after treatment of myocardial infarction, cross‐clamping of the aorta, and in trauma medicine. Veterinary data synthesis: Although no clinical experiments with prophylactic intravenous lidocaine exist in veterinary medicine, there is a large body of evidence from experimental animals that support the use of lidocaine as a Na+/Ca2+ channel blocker, superoxide and hydroxyl radical scavenger, inflammatory modulator, and potent inhibitor of granulocyte functions. Lidocaine is being used in some clinical situations in an attempt to prevent the SIRS in veterinary trauma patients. a,b, a,b Conclusions: A large body of experimental evidence exists supporting the use of lidocaine as an anti‐oxidant and inflammatory modulator useful in preventing reperfusion injury. With the lack of cost‐effective and safe treatments for reperfusion injury in veterinary and human trauma medicine, the use of IV lidocaine to prevent the ensuing inflammatory response and MODS makes it an attractive addition to existing treatments. Therefore, it is essential that prospective clinical trials involving lidocaine as a treatment for prevention of reperfusion injury be performed in companion animals to demonstrate its safety and efficacy.  相似文献   

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