Evaluation of the safety and tolerability of rivaroxaban in dogs with presumed primary immune-mediated hemolytic anemia.

OBJECTIVE: To evaluate the safety and tolerability of rivaroxaban (RIV), an oral direct factor Xa inhibitory drug, in dogs with presumed primary immune-mediated hemolytic anemia (pIMHA). DESIGN: Prospective, multicenter, positive-controlled, unblinded clinical trial. Client-owned dogs were enrolled between October 2012 and March 2014. SETTING: Private referral centers. ANIMALS: Twenty-four client-owned dogs with pIMHA. Enrolled dogs were randomized in 2 treatment groups to receive by mouth RIV or clopidogrel (CL) and low-dose aspirin (LDA). All dogs were monitored for 90 days from the enrollment in the study. INTERVENTIONS: Enrolled dogs were given a standardized immunosuppressive protocol and RIV or CL and LDA. MEASUREMENTS AND MAIN RESULTS: There was no identifiable adverse drug reaction, evidence of hemorrhage, significant prolongation of prothrombin time or activated partial thromboplastin time, or increase in transfusion requirements associated with RIV therapy compared to CL and LDA in dogs with pIMHA. There was no significant difference between treatment groups with respect to thrombotic events, survival rates to discharge, at 1 month and 3 months from diagnosis. CONCLUSIONS: This study suggests that RIV at a median dose of 0.89 mg/kg by mouth once daily was safe and well tolerated in a small group of dogs with presumed pIMHA able to tolerate oral medications and treated with a standardized immunosuppressive treatment protocol. Conclusions regarding the relative efficacy of RIV as compared to CL and LDA cannot be made due to the small size of the treatment groups and because pharmacodynamic effects were not assessed.

Mechanisms of injury and emergency care of acute spinal cord injury in dogs and cats.

OBJECTIVES: To review the literature in regards to the pathophysiology of acute spinal cord injury, and to describe current concepts in regards to patient assessment, diagnostic, and therapeutic measures with a special emphasis on emergency and critical care considerations. ETIOLOGY: Acute spinal cord injury occurs in 2 phases. The primary injury occurs at the time of initial injury and may include intervertebral disk herniation, vertebral fracture or luxation, penetrating injury, and vascular anomalies such as fibrocartilaginous embolic myelopathy. Secondary injury occurs following primary injury and is multifactorial encompassing numerous biochemical and vascular events that result in progression of injury. DIAGNOSIS: The diagnosis is based on history and physical examination findings. A neurologic examination should be performed following initial patient assessment and stabilization. Further diagnostics to characterize acute spinal injury include radiographs and advanced imaging modalities such as myelography, computed tomography, or magnetic resonance imaging. THERAPY: Initial treatment should focus on addressing the patient's cardiovascular and respiratory system. Supportive measures to support systemic perfusion are vital to minimizing secondary injury. Specific therapy toward minimizing secondary injury in veterinary medicine remains controversial, especially in regards to the utilization of methylprednisolone. Other therapies are either in need of additional research or have failed to document clinical difference. PROGNOSIS: The prognosis for acute spinal injury is varied and is dependent upon the presence of concurrent trauma, location, and type of primary injury sustained, and extent of neurologic impairment at the time of initial presentation. The etiology of the underlying trauma is of great importance in determining prognosis and outcome. Loss of deep pain is generally accepted as a poor prognostic indicator; however, even these patients can recover depending on their response to treatment.

Elevation of alanine transaminase and gallbladder wall abnormalities as biomarkers of anaphylaxis in canine hypersensitivity patients.

OBJECTIVE: The purpose of the study was to evaluate alanine transaminase (ALT) and gallbladder wall abnormalities as possible biomarkers for anaphylaxis in dogs presented for acute hypersensitivity reactions. DESIGN: Pilot study. SETTING: A private practice, small animal, 24-hour emergency and specialty hospital. ANIMALS: Ninety-six dogs presenting 101 times on an emergency basis for hypersensitivity reactions from March 2007 through March 2009. INTERVENTIONS: Veterinarians acquired a history, physical exam, serum chemistry panel, blood pressure, and ultrasound image of the gallbladder. MEASUREMENTS AND MAIN RESULTS: Dogs were then divided into 2 groups: dogs fulfilling the definition for anaphylaxis (moderate and severe systemic hypersensitivity) and dogs that did not fulfill the definition and were classified as allergic reactions (local hypersensitivity and mild systemic hypersensitivity). Elevated ALT was significantly associated with anaphylaxis (P<0.001). Increased gallbladder wall thickness and a striated wall pattern were significantly associated with anaphylaxis (P<0.001) and these changes were readily apparent to first-responder veterinarians. Decreased body temperature (P<0.001) and hypothermia (P=0.006) were significantly associated with anaphylaxis. There was no significant difference between groups regarding age, heart rate, or presence of respiratory signs. Lower blood pressure was significantly associated with anaphylaxis (P<0.001) but hypotension was not significantly different (P=0.09) between groups. Cutaneous signs were significantly associated with the allergic reactions group (P<0.001) and, when seen with anaphylaxis, were subtle. CONCLUSIONS: This study showed an elevated ALT and an abnormal gallbladder wall to be biomarkers significantly associated with anaphylaxis in dogs with acute hypersensitivity reactions.

The role of tissue factor and tissue factor pathway inhibitor in health and disease states.

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.