Accurate Results in the Clinical Laboratory

A Guide to Error Detection and Correction

Amitava Dasgupta, Jorge L. Sepulveda

• Publisher: Elsevier
• Year: 2019
• eBook ISBN: 9780128137772
• Edition: 2
• Topic: Biological Sciences
• Subtopic: Pathology
• Index: Biological Sciences

Accurate Results in the Clinical Laboratory: A Guide to Error Detection and Correction, Second Edition, provides a comprehensive review of the factors leading to errors in all areas of clinical laboratory testing. This trusted guide addresses interference issues in all laboratory tests, including patient epigenetics, processes of specimen collection, enzymes and biomarkers. Clinicians and laboratory scientists will both benefit from this reference that applies discussions to both accurate specimen analysis and optimal patient care. Hence, this is the perfect reference for clinical laboratorians, from trainees, to experienced pathologists and directors.- Provides comprehensive coverage across endocrine, oncology, hematology, immunohistochemistry, immunology, serology, microbiology, and molecular testing- Includes new case studies that highlight clinical relevance and errors to avoid- Highlights the best titles published within a variety of medical specialties- Reviewed by medical librarians and content specialists, with key selections compiled in their annual list

II

Sources of errors in clinical chemistry laboratory

Outline

1. Chapter 9. Challenges in routine clinical chemistry testing analysis of small molecules
2. Chapter 10. Challenges in routine clinical chemistry analysis: proteins and enzymes
3. Chapter 11. Challenges in endocrinology testing
4. Chapter 12. Pitfalls in testing for common tumor markers

Chapter 9

Challenges in routine clinical chemistry testing analysis of small molecules

Jorge L. Sepulveda Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States

Abstract

Clinical chemistry is the area of laboratory medicine with the largest volume of tests, and it accounts for the majority of clinical decisions impacted by laboratory results. Although the frequency of errors in clinical chemistry has been minimized by automation and high accuracy of analytical instrumentation, contemporary assay technology, and strict quality management programs, occasional results are inconsistent with the clinical situation, indicating possible erroneous test results. In this chapter, the most frequent sources of inaccurate results in commonly ordered small molecule analytes, including creatinine, urea, ammonia, uric acid, glucose, electrolytes, blood gases, lactate, bilirubin, and lipid profiles, are discussed. Pre-analytical causes of variation, including physiologic and pathologic conditions, patient preparation, sample collection, and specimen processing, are also addressed. Common assay methodologies are discussed, highlighting common sources of interferences and analytical errors.

Keywords

Interference; Metabolic panel; Ammonia; Lactate; Glucose; Electrolytes

Introduction

General or routine chemistry is the area of laboratory medicine dealing with measuring commonly ordered analytes, usually in serum or plasma, and is responsible for the highest volume of testing in clinical laboratories. In the author's medical center (Columbia New York Presbyterian Hospital), clinical chemistry tests account for 75% of the test volume in the clinical laboratory, with the top ten chemistry tests (creatinine, glucose, urea, calcium, potassium, chloride, sodium, carbon dioxide, total protein, and alkaline phosphatase) adding to about 45% of the total test volume. The ability to handle large volumes of testing is due to the availability of highly automated, high-throughput analyzers, often linked to a robotic laboratory automation system that identifies, processes, and distributes specimens to the analyzers with high efficiency.

The analytical methods used in routine chemistry include the following assay types:

• 1. Chemical methods use chemical reactions to produce a measurable product, most commonly yielding changes in color or optical absorbance proportional to the analyte levels. An example is the Jaffe reaction to measure creatinine, in which creatinine reacts with a chromogen to form a colored product.
• 2. Electrochemical reactions result in changes in redox potential or in exchange of electrons at electrodes with consequent current generation proportional to the analyte concentration. An example is an oxygen-sensitive electrode used to measure O₂ consumed in a glucose oxidase reaction, which is proportional to the glucose concentration.
• 3. Enzymatic assays use enzymes to measure analyte concentrations or substrates to measure enzyme levels. The action of the enzyme on the substrate generates a product that can be measured by a chemical method. Sometimes a cascade of enzymes is necessary to generate a measurable product. An example of an enzymatically measured analyte is creatinine, assayed by a cascade of creatininase, creatinase, sarcosine oxidase, and peroxidase enzymes. Examples of clinically useful enzyme analytes are alanine and aspartate aminotransferases, alkaline phosphatase, creatinine kinase, lactate dehydrogenase (LDH), lipase, and amylase.
• 4. Ligand assays use proteins with high affinity for the analyte to measure its concentration. Most often, these assays are immunoassays, in which antibodies or antibody fragments are used to bind the ligand, although in a few cases, other specific-binding proteins are used. Examples of immunoassays include drug testing and monitoring assays, measurements of cardiac biomarkers such as cardiac troponins and B-type natriuretic peptides, and assays for hormones and tumor biomarkers. Examples of ligand assays using non-antibody high-affinity binding proteins include assays for folates and vitamin B₁₂. Whereas many of the low-volume ligand assays are part of “specialized chemistry” often handled in separate areas of the clinical laboratory, with the advent of multifunctional high-throughput analyzers able to handle a multitude of assay methodologies, many of the high-volume immunoassays have migrated to the highly automated routine chemistry area.

Some methods use combinations of these categories. For example, a glucose assay may use glucose oxidase to generate O₂, which is then measured by an oxygen-specific electrode in an electrochemical reaction. In this chapter, frequent sources of inaccurate results in commonly ordered small molecule analytes, focusing on common pre-analytical variables (Table 9.1) and analytical interferences (Table 9.2), are addressed. In Chapter 10, common errors in enzymes and other protein assays are reviewed. Chapters 11 and 12 focus on challenges in endocrinology testing and tumor markers testing, respectively. In many institutions, common therapeutic drug levels, as well as initial toxicology screens, are done in the core laboratory section by high-throughput analyzers and immunoassays, and these are reviewed in Chapters 13–17. Comprehensive listings of pre-analytical variables and interferences in clinical chemistry testing are available in reference books [1–3].

The most commonly ordered tests in clinical chemistry are often ordered as panels. The Centers for Medicare and Medicaid Services, formerly called Health Care Financing Administration (HCFA), recognizes six panels of tests delineated by the American Medical Association CPT editorial board (Table 9.3), of which the Basic Metabolic Panel (BMP) comprising five electrolytes (sodium, potassium, chloride, carbon dioxide, and calcium) and three small organic analytes (glucose, urea, and creatinine) is the most commonly ordered panel of tests. Note that all the test components of a panel need to be medically justified for the panel to be reimbursed.

Creatinine analysis

The small molecule creatinine is a product o...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of contributors
• Foreword (from the first edition)
• Preface
• I. Sources of errors in clinical laboratories: an overview
• II. Sources of errors in clinical chemistry laboratory
• III. Sources of errors in therapeutic drug monitoring and toxicology
• IV. Herbal medicines and laboratory testings
• V. Sources of errors in immunology laboratory
• VI. Sources of errors in molecular, genetic and related testings
• VII. Sources of errors in microbiology testings
• VIII. Sources of errors in hematology and coagulation testings
• IX. Sources of errors in transfusion medicine
• X. Sources of errors in point of care testing
• Index