Characterization of a canine freeze-dried platelet-derived hemostatic agent: A preclinical model for surgical and traumatic hemorrhage.

INTRODUCTION: A freeze-dried, platelet-derived hemostatic agent (FPH) was developed for acute hemorrhage. The canine product (cFPH) was developed for use in preclinical models supporting human product (hFPH) investigations. MATERIALS AND METHODS: A carotid artery bypass graft (CABG) study in dogs compared 3 dosages of cFPH to canine liquid stored platelets (cLSP) and vehicle (VEH) control groups. Histopathological analysis and blood loss assessments were completed. A separate ex-vivo synthetic graft study assessed thrombogenicity via blood from human and canine donors that was combined with species-specific FPH or apheresis platelets. Characterization of cFPH and hFPH included thrombin generation, total thrombus formation, and scanning electron microscopy. RESULTS: Blood loss was reduced in CABG dogs receiving standard of care (cLSP) or cFPH treatment compared to VEH control; a cFPH dose effect signal was observed. Further, cFPH dosing up to 5 × 109 cells/kg was not associated with increased mortality or occlusion of the anastomosis sites, and histopathologic evidence of off-target thrombosis was not detected. When passed through a synthetic graft (ex vivo), whole blood combined with species-specific FPH did not result in thrombosis beyond that of whole blood control. In vitro testing and imaging of cFPH and FPH were comparable. CONCLUSIONS: A single dose of cFPH or cLSP reduced blood loss in a pilot surgical study and was well tolerated with no related adverse events. Further, the hemostatic activity and characteristics of cFPH are comparable to that of hFPH, suggesting that research findings from the canine product are likely to inform the development of the human product.

The Effects of Health Disparities on Neonatal Outcomes.

The history of racism in the United States was established with slavery, and the carry-over effect continues to impact health care through structural and institutional racism. Racial segregation and redlining have impacted access to quality health care, thereby impacting prematurity and infant mortality rates. Health disparities also impact neonatal morbidities such as intraventricular hemorrhage and necrotizing enterocolitis and the family care experience including the establishment of breastfeeding and health care provider interactions.

Case report: Utility, complications, and short-term outcomes in three dogs managed with percutaneous pigtail cystostomy catheters for urethral obstruction.

Objective: This study aimed to describe the utility, complications, and short-term outcomes of three dogs managed with percutaneous pigtail cystostomy catheters placed in the emergency room (ER). Case summary: Three dogs were presented separately to the ER for unalleviated mechanical urethral obstruction secondary to urolithiasis and urethral neoplasia. Retrograde urinary catheterization and urohydropulsion were not successful after multiple attempts. Percutaneous pigtail cystostomy catheters were placed under sedation to achieve temporary urinary diversion, and were successful in two of the three dogs. Complications encountered include mild abdominal effusion, unsuccessful placement resulting in hemorrhagic abdominal effusion, steatitis, abdominal pain, and kinking of the catheter. The two dogs diagnosed with urolithiasis were discharged from the hospital, and the dog diagnosed with urethral neoplasia was humanely euthanized due to poor prognosis. New or unique information provided: When successful, the placement of pigtail cystostomy catheters allowed for temporary urinary diversion until definitive treatment could be performed and were well tolerated. Short-term outcomes were good. Complications arising from this procedure were common and increased morbidity. The risk of unsuccessful catheter placement may be increased when the procedure is performed in an over conditioned patient or by an inexperienced operator. Careful case selection and risk-benefit analysis should be considered before attempting this procedure. Further studies are necessary to evaluate the ideal technique, incidence of complications, and outcomes of this procedure.

Healthcare Equity and Leadership: Implementation of Diversity, Equity, and Inclusion Training for Pharmacy Residents.

BackgroundPharmacy training programs infrequently include formal training in the areas of diversity, equity, and inclusion (DEI). Hence, the purpose of this report is to offer perspectives gained from the delivery of a DEI curriculum within a pharmacy residency program aimed at expanding experiential learning focused on DEI and health equity. Program Implementation: Pharmacy residents at an academic medical center were invited to participate in a longitudinal DEI/equity seminar series that was thoughtfully and strategically developed by a team of residents and program leadership based on a six-step process. Residents were offered 9 individual seminars covering 4 major focus areas to facilitate enhanced awareness, learning, and vulnerability. Participants were invited to provide evaluations of each seminar and the overall series. Program Assessment: A total of 41 residents (100%) participated in at least one of the 9 seminars that were offered and approximately 50% completed the post-series survey. Resident-perceived benefit of each individual session was consistently favorable. Additionally, greater than 70% of participants responded favorably when asked about the impact of each session on their awareness, resources provided, and ability to apply the learnings to their practice. Conclusion: Our inaugural experience with the integration of a DEI seminar series into a pharmacy residency program suggests that there is a clear benefit to including DEI/health equity into pharmacy residency training. This data may suggest that adoption of DEI-focused experiential training may increase cultural awareness and the availability of resources to better equip pharmacy residents in applying concepts of DEI into their practice.

2022 Update of the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) Domain 6: Defining rational use of thrombolytics.

OBJECTIVES: To systematically review available evidence and establish guidelines related to the use of thrombolytics for the management of small animals with suspected or confirmed thrombosis. DESIGN: PICO (Population, Intervention, Control, and Outcome) questions were formulated, and worksheets completed as part of a standardized and systematic literature evaluation. The population of interest included dogs and cats (considered separately) and arterial and venous thrombosis. The interventions assessed were the use of thrombolytics, compared to no thrombolytics, with or without anticoagulants or antiplatelet agents. Specific protocols for recombinant tissue plasminogen activator were also evaluated. Outcomes assessed included efficacy and safety. Relevant articles were categorized according to level of evidence, quality, and as to whether they supported, were neutral to, or opposed the PICO questions. Conclusions from the PICO worksheets were used to draft guidelines, which were subsequently refined via Delphi surveys undertaken by the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) working group. RESULTS: Fourteen PICO questions were developed, generating 14 guidelines. The majority of the literature addressing the PICO questions in dogs is experimental studies (level of evidence 3), thus providing insufficient evidence to determine if thrombolysis improves patient-centered outcomes. In cats, literature was more limited and often neutral to the PICO questions, precluding strong evidence-based recommendations for thrombolytic use. Rather, for both species, suggestions are made regarding considerations for when thrombolytic drugs may be considered, the combination of thrombolytics with anticoagulant or antiplatelet drugs, and the choice of thrombolytic agent. CONCLUSIONS: Substantial additional research is needed to address the role of thrombolytics for the treatment of arterial and venous thrombosis in dogs and cats. Clinical trials with patient-centered outcomes will be most valuable for addressing knowledge gaps in the field.

Case Report: Successful Reperfusion of Pulmonary Thromboembolism Using tPA in a Cat.

Pulmonary thromboembolism is a potentially life threatening condition that is uncommonly recognized in cats. Thrombolytic agents have been described as a treatment for this condition in human and canine patients, particularly in cases where hemodynamic instability is persistent despite supportive care. This report describes the clinical course, echocardiographic diagnosis, and successful thrombolysis of a cat with pulmonary thromboembolism. Despite confirmed reperfusion, the cat succumbed to thromboembolic disease highlighting the dearth of knowledge about optimal treatment of this disease process in small animals, particularly in cats.

Focused Ultrasound of Vascular System in Dogs and Cats-Thromboembolic Disease.

In small animals, point-of-care ultrasound can be used by nonradiologist sonographers to identify thrombosis at several anatomic sites. Dogs and cats are well-suited for vascular interrogation using ultrasound because of their small body size. Ultrasound can be used to investigate targeted vessels based on clinical signs. The safety and tolerability of the examination makes this a useful modality to evaluate critical patients for evidence thromboembolic disease. Once vascular imaging techniques are learned they can be easily coupled with other point-of-care examinations such as focused cardiac ultrasound, Vet Blue, AFAST, and TFAST.

Lessons Learned From the Battlefield and Applicability to Veterinary Medicine - Part 2: Transfusion Advances.

Since the inception of recent conflicts in Afghanistan and Iraq, transfusion practices in human military medicine have advanced considerably. Today, US military physicians recognize the need to replace the functionality of lost blood in traumatic hemorrhagic shock and whole blood is now the trauma resuscitation product of choice on the battlefield. Building on wartime experiences, military medicine is now one of the country's strongest advocates for the principle of hemostatic resuscitation using whole blood or balanced blood components as the primary means of resuscitation as early as possibly following severe trauma. Based on strong evidence to support this practice in human combat casualties and in civilian trauma care, military veterinarians strive to practice similar hemostatic resuscitation for injured Military Working Dogs. To this end, canine whole blood has become increasingly available in forward environments, and non-traditional storage options for canine blood and blood components are being explored for use in canine trauma. Blood products with improved shelf-life and ease of use are not only useful for military applications, but may also enable civilian general and specialty practices to more easily incorporate hemostatic resuscitation approaches to canine trauma care.

In Vitro Compatibility of Canine and Human Blood: A Pilot Study.

Military working dogs (MWDs) are force multipliers that are exposed to the same risks as their human counterparts on the battlefield. Hemostatic resuscitation using blood products is a cornerstone of damage control resuscitation protocols for both humans and dogs. Canine-specific blood products are in short supply in mature theaters due to logistic and regulatory concerns and are almost nonexistent in austere environments, whereas human blood products are readily available at most surgical facilities. The objective of this study was to evaluate the in vitro compatibility of human and canine blood by using standard crossmatching techniques with the canine blood acting as the recipient and the human blood acting as the donor. Blood samples were collected from 20 government-owned canines (GOCs) and 7 healthy human volunteers in addition to washed red blood cells (RBCs) from a commercial blood typing kit. Major and minor crossmatches were conducted as well as a protein denatured crossmatch. All samples in this study showed strong cross-reactivity, with the majority demonstrating profound hemolysis and a minority showing substantial agglutination. Based on the results of this study, transfusion of human blood to an MWD cannot be recommended at this time.

A pilot study documenting increased thrombin generation following abrupt withdrawal of heparin therapy in healthy dogs.

OBJECTIVE: To document if a transient hypercoagulable state occurs in healthy dogs following abrupt cessation of unfractionated heparin (UFH) therapy. DESIGN: Prospective experimental pilot study. SETTING: University research facility. ANIMALS: Seven adult random-source male dogs. INTERVENTION: Thromboelastography (TEG) and thrombin-antithrombin (TAT) complex formation were used to assess coagulation status in healthy dogs. Seven adult research dogs received 200-300 IU/kg subcutaneous UFH every 8 hours for 4 days. A final IV bolus of 100 IU/kg was given on day 4 and the peak measured heparin concentration 1 hour later is defined as the start of heparin withdrawal (time 0). Citrated whole blood samples were collected at baseline (prior to heparin administration) and 3, 6, 12, 30, and 48 hours after UFH withdrawal. At all time points, a kaolin-activated TEG was performed and citrated plasma for measurement of TAT concentration was collected for batch analysis. Fibrinogen concentration, PCV, total plasma proteins, and platelet count were measured at baseline and 48 hours after heparin withdrawal. MEASUREMENTS AND MAIN RESULTS: Compared to baseline, TAT was increased 12 hours after heparin withdrawal and returned to baseline by 30 hours. TEG clot formation time (K) was decreased 30 and 48 hours after heparin withdrawal. CONCLUSION: TAT results suggest that a transient increase in thrombin generation developed 12 hours after withdrawal of UFH therapy. Though clot kinetics were rapid compared to baseline beginning 30 hours after heparin withdrawal, a return to baseline was not documented. Future studies are warranted to determine the clinical relevance of these results and to evaluate the effect of UFH withdrawal in critically ill animals.