ASVCP quality assurance guidelines: control of general analytical factors in veterinary laboratories

Owing to lack of governmental regulation of veterinary laboratory performance, veterinarians ideally should demonstrate a commitment to self-monitoring and regulation of laboratory performance from within the profession. In response to member concerns about quality management in veterinary laboratories, the American Society for Veterinary Clinical Pathology (ASVCP) formed a Quality Assurance and Laboratory Standards (QAS) committee in 1996. This committee recently published updated and peer-reviewed Quality Assurance Guidelines on the ASVCP website. The Quality Assurance Guidelines are intended for use by veterinary diagnostic laboratories and veterinary research laboratories that are not covered by the US Food and Drug Administration Good Laboratory Practice standards (Code of Federal Regulations Title 21, Chapter 58). The guidelines have been divided into 3 reports on 1) general analytic factors for veterinary laboratory performance and comparisons, 2) hematology and hemostasis, and 3) clinical chemistry, endocrine assessment, and urinalysis. This report documents recommendations for control of general analytical factors within veterinary clinical laboratories and is based on section 2.1 (Analytical Factors Important In Veterinary Clinical Pathology, General) of the newly revised ASVCP QAS Guidelines. These guidelines are not intended to be all-inclusive; rather, they provide minimum guidelines for quality assurance and quality control for veterinary laboratory testing. It is hoped that these guidelines will provide a basis for laboratories to assess their current practices, determine areas for improvement, and guide continuing professional development and education efforts.     

ASVCP quality assurance guidelines: control of preanalytical and analytical factors for hematology for mammalian and nonmammalian species, hemostasis, and crossmatching in veterinary laboratories

In December 2009, the American Society for Veterinary Clinical Pathology (ASVCP) Quality Assurance and Laboratory Standards committee published the updated and peer-reviewed ASVCP Quality Assurance Guidelines on the Society's website. These guidelines are intended for use by veterinary diagnostic laboratories and veterinary research laboratories that are not covered by the US Food and Drug Administration Good Laboratory Practice standards (Code of Federal Regulations Title 21, Chapter 58). The guidelines have been divided into 3 reports: (1) general analytical factors for veterinary laboratory performance and comparisons; (2) hematology, hemostasis, and crossmatching; and (3) clinical chemistry, cytology, and urinalysis. This particular report is one of 3 reports and provides recommendations for control of preanalytical and analytical factors related to hematology for mammalian and nonmammalian species, hemostasis testing, and crossmatching and is adapted from sections 1.1 and 2.3 (mammalian hematology), 1.2 and 2.4 (nonmammalian hematology), 1.5 and 2.7 (hemostasis testing), and 1.6 and 2.8 (crossmatching) of the complete guidelines. These guidelines are not intended to be all-inclusive; rather, they provide minimal guidelines for quality assurance and quality control for veterinary laboratory testing and a basis for laboratories to assess their current practices, determine areas for improvement, and guide continuing professional development and education efforts.     

ASVCP quality assurance guidelines: control of preanalytical, analytical, and postanalytical factors for urinalysis, cytology, and clinical chemistry in veterinary laboratories

In December 2009, the American Society for Veterinary Clinical Pathology (ASVCP) Quality Assurance and Laboratory Standards committee published the updated and peer-reviewed ASVCP Quality Assurance Guidelines on the Society's website. These guidelines are intended for use by veterinary diagnostic laboratories and veterinary research laboratories that are not covered by the US Food and Drug Administration Good Laboratory Practice standards (Code of Federal Regulations Title 21, Chapter 58). The guidelines have been divided into 3 reports: (1) general analytical factors for veterinary laboratory performance and comparisons; (2) hematology, hemostasis, and crossmatching; and (3) clinical chemistry, cytology, and urinalysis. This particular report is one of 3 reports and documents recommendations for control of preanalytical, analytical, and postanalytical factors related to urinalysis, cytology, and clinical chemistry in veterinary laboratories and is adapted from sections 1.1 and 2.2 (clinical chemistry), 1.3 and 2.5 (urinalysis), 1.4 and 2.6 (cytology), and 3 (postanalytical factors important in veterinary clinical pathology) of these guidelines. These guidelines are not intended to be all-inclusive; rather, they provide minimal guidelines for quality assurance and quality control for veterinary laboratory testing and a basis for laboratories to assess their current practices, determine areas for improvement, and guide continuing professional development and education efforts.     

ASVCP guidelines: allowable total error guidelines for biochemistry

As all laboratory equipment ages and contains components that may degrade with time, initial and periodically scheduled performance assessment is required to verify accurate and precise results over the life of the instrument. As veterinary patients may present to general practitioners and then to referral hospitals (both of which may each perform in‐clinic laboratory analyses using different instruments), and given that general practitioners may send samples to reference laboratories, there is a need for comparability of results across instruments and methods. Allowable total error (TE_a) is a simple comparative quality concept used to define acceptable analytical performance. These guidelines are recommendations for determination and interpretation of TE_a for commonly measured biochemical analytes in cats, dogs, and horses for equipment commonly used in veterinary diagnostic medicine. TE_a values recommended herein are aimed at all veterinary settings, both private in‐clinic laboratories using point‐of‐care analyzers and larger reference laboratories using more complex equipment. They represent the largest TEa possible without generating laboratory variation that would impact clinical decision making. TE_a can be used for (1) assessment of an individual instrument's analytical performance, which is of benefit if one uses this information during instrument selection or assessment of in‐clinic instrument performance, (2) Quality Control validation, and (3) as a measure of agreement or comparability of results from different laboratories (eg, between the in‐clinic analyzer and the reference laboratory). These guidelines define a straightforward approach to assessment of instrument analytical performance.     

Best practices for veterinary toxicologic clinical pathology,with emphasis on the pharmaceutical and biotechnology industries

The purpose of this paper by the Regulatory Affairs Committee (RAC) of the American Society for Veterinary Clinical Pathology (ASVCP) is to review the current regulatory guidances (eg, guidelines) and published recommendations for best practices in veterinary toxicologic clinical pathology, particularly in the pharmaceutical and biotechnology industries, and to utilize the combined experience of ASVCP RAC to provide updated recommendations. Discussion points include (1) instrumentation, validation, and sample collection, (2) routine laboratory variables, (3) cytologic laboratory variables, (4) data interpretation and reporting (including peer review, reference intervals and statistics), and (5) roles and responsibilities of clinical pathologists and laboratory personnel. Revision and improvement of current practices should be in alignment with evolving regulatory guidance documents, new technology, and expanding understanding and utility of clinical pathology. These recommendations provide a contemporary guide for the refinement of veterinary toxicologic clinical pathology best practices.     

ASVCP guidelines: quality assurance for point‐of‐care testing in veterinary medicine

Point‐of‐care testing (POCT) refers to any laboratory testing performed outside the conventional reference laboratory and implies close proximity to patients. Instrumental POCT systems consist of small, handheld or benchtop analyzers. These have potential utility in many veterinary settings, including private clinics, academic veterinary medical centers, the community (eg, remote area veterinary medical teams), and for research applications in academia, government, and industry. Concern about the quality of veterinary in‐clinic testing has been expressed in published veterinary literature; however, little guidance focusing on POCT is available. Recognizing this void, the ASVCP formed a subcommittee in 2009 charged with developing quality assurance (QA) guidelines for veterinary POCT. Guidelines were developed through literature review and a consensus process. Major recommendations include (1) taking a formalized approach to POCT within the facility, (2) use of written policies, standard operating procedures, forms, and logs, (3) operator training, including periodic assessment of skills, (4) assessment of instrument analytical performance and use of both statistical quality control and external quality assessment programs, (5) use of properly established or validated reference intervals, (6) and ensuring accurate patient results reporting. Where possible, given instrument analytical performance, use of a validated 1_3s control rule for interpretation of control data is recommended. These guidelines are aimed at veterinarians and veterinary technicians seeking to improve management of POCT in their clinical or research setting, and address QA of small chemistry and hematology instruments. These guidelines are not intended to be all‐inclusive; rather, they provide a minimum standard for maintenance of POCT instruments in the veterinary setting.     

ASVCP quality assurance guidelines: external quality assessment and comparative testing for reference and in‐clinic laboratories

The purpose of this document is to educate providers of veterinary laboratory diagnostic testing in any setting about comparative testing. These guidelines will define, explain, and illustrate the importance of a multi‐faceted laboratory quality management program which includes comparative testing. The guidelines will provide suggestions for implementation of such testing, including which samples should be tested, frequency of testing, and recommendations for result interpretation. Examples and a list of vendors and manufacturers supplying control materials and services to veterinary laboratories are also included.     

Subject-based reference values: biological variation, individuality, and reference change values

Subject-based reference values have been largely overlooked in veterinary medicine. These values represent longitudinal data rather than the cross-sectional data represented by standard population-based reference values. As such they provide information about biological and analytical variation. Inherent random variation of analytes around a homeostatic set point is referred to as biological variation; data on biological variation are underutilized in veterinary medicine and have multiple applications that include setting analytical goals, predicting the utility of population-based reference intervals (RIs), assessing the value of partitioning reference values, and evaluating the significance of changes in serial results. To generate these data, relatively few individuals are sampled for a short period of time. Given the difficulty of obtaining specimens from large number of healthy individuals to establish a cross-sectional RI for many veterinary species, especially exotic species, use of subject-based RIs is a practical alternative approach for the veterinary diagnostician. Furthermore, for the majority of biochemical analytes and even many hemostatic variables, population-based reference values are less sensitive than subject-based reference values for detecting pathologic changes in an individual. The focus of this review is the clinical usefulness of subject-based reference values and diagnostic implications for their use. Implementation of the concepts of biological variation, individuality, and reference change value (RCV) may allow large diagnostic laboratories to offer more sensitive reference values to assess health and detect disease.     

Canine reference intervals for the Sysmex XT-2000iV hematology analyzer

Background: The laser‐based Sysmex XT‐2000iV hematology analyzer is increasingly used in veterinary clinical pathology laboratories, and instrument‐specific reference intervals for dogs are not available. Objective: The purpose of this study was to establish canine hematologic reference intervals according to International Federation of Clinical Chemistry and Clinical and Laboratory Standards Institute guidelines using the Sysmex XT‐2000iV hematology analyzer. Methods: Blood samples from 132 healthy purebred dogs from France, selected to represent the most prevalent canine breeds in France, were analyzed. Blood smears were scored for platelet (PLT) aggregates. Reference intervals were established using the nonparametric method. PLT and RBC counts obtained by impedance and optical methods were compared. Effects of sex and age on reference intervals were determined. Results: The correlation between impedance (I) and optical (O) measurements of RBC and PLT counts was excellent (Pearson r=.99 and .98, respectively); however, there were significant differences between the 2 methods (Student's paired t‐test, P<.0001). Differences between sexes were not significant except for HCT, PLT‐I, and PLT‐O. WBC, lymphocyte, and neutrophil counts decreased significantly with age (ANOVA, P<.05). Median eosinophil counts were higher in Brittany Spaniels (1.87 × 10⁹/L), Rottweilers (1.41 × 10⁹/L), and German Shepherd dogs (1.38 × 10⁹/L) than in the overall population (0.9 × 10⁹/L). PLT aggregates were responsible for lower PLT counts by the impedance, but not the optical, method. Conclusion: Reference intervals for hematologic analytes and indices were determined under controlled preanalytical and analytical conditions for a well‐characterized population of dogs according to international recommendations.     

ASVCP guidelines: quality assurance for portable blood glucose meter (glucometer) use in veterinary medicine

Portable blood glucose meters (PBGM, glucometers) are a convenient, cost effective, and quick means to assess patient blood glucose concentration. The number of commercially available PBGM is constantly increasing, making it challenging to determine whether certain glucometers may have benefits over others for veterinary testing. The challenge in selection of an appropriate glucometer from a quality perspective is compounded by the variety of analytic methods used to quantify glucose concentrations and disparate statistical analysis in many published studies. These guidelines were developed as part of the ASVCP QALS committee response to establish recommendations to improve the quality of testing using point‐of‐care testing (POCT) handheld and benchtop devices in veterinary medicine. They are intended for clinical pathologists and laboratory professionals to provide them with background knowledge and specific recommendations for quality assurance (QA) and quality control (QC), and to serve as a resource to assist the provision of advice to veterinarians and technicians to improve the quality of results obtained when using PBGM. These guidelines are not intended to be all‐inclusive; rather they provide a minimum standard for management of PBGM in the veterinary setting.     

The Association of Shelter Veterinarians veterinary medical care guidelines for spay-neuter programs

As efforts to reduce the overpopulation and euthanasia of unwanted and unowned dogs and cats have increased, greater attention has been focused on spay-neuter programs throughout the United States. Because of the wide range of geographic and demographic needs, a wide variety of programs have been developed to increase delivery of spay-neuter services to targeted populations of animals, including stationary and mobile clinics, MASH-style operations, shelter services, feral cat programs, and services provided through private practitioners. In an effort to ensure a consistent level of care, the Association of Shelter Veterinarians convened a task force of veterinarians to develop veterinary medical care guidelines for spay-neuter programs. The guidelines consist of recommendations for preoperative care (eg, patient transport and housing, patient selection, client communication, record keeping, and medical considerations), anesthetic management (eg, equipment, monitoring, perioperative considerations, anesthetic protocols, and emergency preparedness), surgical care (eg, operating-area environment; surgical-pack preparation; patient preparation; surgeon preparation; surgical procedures for pediatric, juvenile, and adult patients; and identification of neutered animals), and postoperative care (eg, analgesia, recovery, and release). These guidelines are based on current principles of anesthesiology, critical care medicine, microbiology, and surgical practice, as determined from published evidence and expert opinion. They represent acceptable practices that are attainable in spay-neuter programs.     

Clinical pathology of amphibians: a review

Amphibian declines and extinctions have worsened in the last 2 decades. Partly because one of the main causes of the declines is infectious disease, veterinary professionals have increasingly become involved in amphibian research, captive husbandry, and management. Health evaluation of amphibians, free‐living or captive, can benefit from employing the tools of clinical pathology, something that is commonly used in veterinary medicine of other vertebrates. The present review compiles what is known of amphibian clinical pathology emphasizing knowledge that may assist with the interpretation of laboratory results, provides diagnostic recommendations for common amphibian diseases, and includes RIs for a few amphibian species estimated based on peer‐reviewed studies. We hope to encourage the incorporation of clinical pathology in amphibian practice and research, and to highlight the importance of applying veterinary medicine principles in furthering our knowledge of amphibian pathophysiology.     

Estimating clinical chemistry reference values based on an existing data set of unselected animals

In an attempt to standardise the determination of biological reference values, the International Federation of Clinical Chemistry (IFCC) has published a series of recommendations on developing reference intervals. The IFCC recommends the use of an a priori sampling of at least 120 healthy individuals. However, such a high number of samples and laboratory analysis is expensive, time-consuming and not always feasible, especially in veterinary medicine. In this paper, an alternative (a posteriori) method is described and is used to determine reference intervals for biochemical parameters of farm animals using an existing laboratory data set. The method used was based on the detection and removal of outliers to obtain a large sample of animals likely to be healthy from the existing data set. This allowed the estimation of reliable reference intervals for biochemical parameters in Sarda dairy sheep. This method may also be useful for the determination of reference intervals for different species, ages and gender.     

ACVIM consensus statement on the treatment of immune‐mediated hemolytic anemia in dogs

Immune‐mediated hemolytic anemia (IMHA) causes severe anemia in dogs and is associated with considerable morbidity and mortality. Treatment with various immunosuppressive and antithrombotic drugs has been described anecdotally and in previous studies, but little consensus exists among veterinarians as to the optimal regimen to employ and maintain after diagnosis of the disease. To address this inconsistency and provide evidence‐based guidelines for treatment of IMHA in dogs, we identified and extracted data from studies published in the veterinary literature. We developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria, explanation of treatment regimens, and validity of statistical methods. In combination with our clinical experience and comparable guidelines for humans afflicted with autoimmune hemolytic anemia, we used the conclusions of this process to make a set of clinical recommendations regarding treatment of IMHA in dogs, which we refined subsequently by conducting several iterations of Delphi review. Additionally, we considered emerging treatments for IMHA in dogs and highlighted areas deserving of future research. Comments were solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted for publication. The resulting document is intended to provide clinical guidelines for management of IMHA in dogs. These guidelines should be implemented pragmatically, with consideration of animal, owner, and veterinary factors that may vary among cases.     

Antibiotic prophylaxis in veterinary cancer chemotherapy: A review and recommendations

Bacterial infection following cancer chemotherapy‐induced neutropenia is a serious cause of morbidity and mortality in human and veterinary patients. Antimicrobial prophylaxis is controversial in the human oncology field, as any decreased incidence in bacterial infections is countered by patient adverse effects and increased antimicrobial resistance. Comprehensive guidelines exist to aid human oncologists in prescribing antimicrobial prophylaxis but similar recommendations are not available in veterinary literature. As the veterinarian's role in antimicrobial stewardship is increasingly emphasized, it is vital that veterinary oncologists implement appropriate antimicrobial use. By considering the available human and veterinary literature we present an overview of current clinical practices and are able to suggest recommendations for prophylactic antimicrobial use in veterinary cancer chemotherapy patients.     

Minimum inhibitory concentration breakpoints and disk diffusion inhibitory zone interpretive criteria for tilmicosin susceptibility testing against Pasteurella multocida and Actinobacillus pleuropneumoniae associated with porcine respiratory disease.

Tilmicosin is a novel macrolide antibiotic developed for exclusive use in veterinary medicine. Tilmicosin has been approved as a feed premix to control porcine respiratory disease associated with Pasteurella multocida and Actinobacillus pleuropneumoniae. The development of antimicrobial susceptibility testing guidelines for tilmicosin was predicated on the relationship of clinical efficacy studies that demonstrated a favorable therapeutic outcome, on pharmacokinetic data, and on in vitro test data, as recommended by the National Committee for Clinical Laboratory Standards (NCCLS). The approved breakpoints for the minimum inhibitory concentration dilution testing for both species are resistant, > or = 32 microg/ml, and susceptible, < or = 16 microg/ml. The zone of inhibition interpretive criteria for disk diffusion testing with a 15-microg tilmicosin disk are resistant, < or = 10 mm, and susceptible, > or = 11 mm.     

2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs

This report represents a scientific and working clinical consensus statement on seizure management in dogs based on current literature and clinical expertise. The goal was to establish guidelines for a predetermined, concise, and logical sequential approach to chronic seizure management starting with seizure identification and diagnosis (not included in this report), reviewing decision‐making, treatment strategies, focusing on issues related to chronic antiepileptic drug treatment response and monitoring, and guidelines to enhance patient response and quality of life. Ultimately, we hope to provide a foundation for ongoing and future clinical epilepsy research in veterinary medicine.     

Current and emerging concepts in biological and analytical variation applied in clinical practice

A single laboratory result actually represents a range of possible values, and a given laboratory result is impacted not just by the presence or absence of disease, but also by biological variation of the measurand in question and analytical variation of the equipment used to make the measurement. Biological variation refers to variability in measurand concentration or activity around a homeostatic set point. Knowledge of biological and analytical variation can be used to facilitate interpretation of patient clinicopathologic data and is particularly useful for interpreting serial patient data and data at or near reference limits or clinical decision thresholds. Understanding how biological and analytical variation impact laboratory results is of increasing importance, because veterinarians evaluate serial data from individual patients, interpret data from multiple testing sites, and use expert consensus guidelines that include decision thresholds for clinicopathologic data interpretation. The purpose of our report is to review current and emerging concepts in biological and analytical variation and discuss how biological and analytical variation data can be used to facilitate clinicopathologic data interpretation. Inclusion of veterinary clinical pathologists having expertise in laboratory quality management and biological variation on research teams and veterinary practice guideline development teams is recommended, to ensure that various considerations for clinicopathologic data interpretation are addressed.     

Interpretation of canine and feline blood smears by emergency room personnel

Background: Interpretation of blood smears is commonly used to provide rapid laboratory evaluation of animals in veterinary emergency practice, but the accuracy of results of blood smear interpretation by emergency room personnel (ERP) compared with evaluation by trained veterinary clinical pathology personnel is unknown. Objective: The goal of this study was to compare blood smear evaluation by ERP with that of clinical pathology personnel. Methods: All animals that had a CBC determined by a diagnostic laboratory and had blood smears evaluated by personnel at the Foster Hospital for Small Animals Emergency Room between September 2008 and July 2009 were eligible for study inclusion. ERP who evaluated blood smears completed standardized forms with estimates of the WBC and platelet counts and evaluation of RBC and WBC morphology. Results from point‐of‐care assessment were compared with automated or manual results reported by the veterinary diagnostic laboratory. Results: One hundred and fifty‐five blood smears were evaluated. There was moderate agreement (κ value, 0.63; 95% confidence interval [CI]: 0.52, 0.74) between estimated platelet counts by ERP and automated counts. Poor agreement was found between estimated WBC counts by ERP and automated counts (κ value, 0.48; 95% CI: 0.37, 0.60). Specific abnormalities with a high likelihood of clinical significance, eg, toxic change, nucleated RBCs, spherocytes, hemoparasites, and lymphoblasts, were not predictably identified by ERP. Conclusions: ERP interpretation of canine and feline blood smears should be used cautiously and should not replace evaluation by a veterinary diagnostic laboratory.