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Red blood cell morphology and indices: The clinical chemistry interface

Abstract Background A fundamental understanding of the basis and clinical significance of standard laboratory tests in hematology and associated peripheral blood smear findings is essential for analysis and interpretation of certain chemistry test results. The overlap between hematology and chemistry is also an important aspect in most chemistry and hematology laboratories. Rigorous quality control ensuring accuracy and precision applies to both. These inter-relationships are bidirectional; perturbations…

Leukocyte morphology in blood and bone marrow *

Abstract Background Leukocytes comprise a wide variety of cell types, and evaluation of these components is critical in medical and clinical laboratory practice. Although sensitive laboratory methods may offer strong clues about leukocyte abnormalities, accurate morphologic evaluation of these cells is key in confirming suspicion for a pathologic process and in guiding clinical decision making. However, proper assessment of these cells requires understanding of normal quantitative…

Automated hematology

Abstract Background The roots of automated hematology began with manual microscopy and laborious cell counting techniques. Using the Coulter principle and advances in laboratory methodology, automated hematology is now rapid and inexpensive with the complete blood cell count (CBC) being one of the most commonly ordered tests in medicine. Content This chapter describes the principles of automated hematology, including how we measure red blood cells (RBCs),…

Pharmacogenetics

Abstract Background Pharmacogenetics describes how genes influence drug response. Genes can impact either the pharmacokinetics or pharmacodynamics of a drug to influence the dose required and associated therapeutic or toxic effects. Pharmacogenetic testing performed before drug administration may guide the selection of drugs and drug dosing. Post-therapeutic pharmacogenetic testing can explain an adverse drug reaction, including therapeutic failure. Content This chapter reviews pharmacokinetics and pharmacodynamics, the…

Circulating nucleic acids for prenatal diagnostics

Abstract Background Prenatal diagnosis is becoming an essential part of prenatal care for a growing number of patients. To make a definitive diagnosis, traditional methods of sampling fetal genetic material, such as chorionic villus sampling and amniocentesis, are invasive and introduce a risk of spontaneous miscarriage. The discovery of cell-free fetal DNA (cffDNA) in the circulation of pregnant women led to the possibility of noninvasive genetic…

Circulating tumor cells and circulating nucleic acids in oncology

Abstract Background The analysis of circulating tumor cells (CTCs) and tumor cell products (DNA, RNA, extracellular vesicles) released into the blood may provide clinically relevant information as a “liquid biopsy” and provide new insights into tumor biology. Content CTCs are complementary to other liquid biopsy biomarkers such as circulating cell-free DNA (ctDNA), circulating microRNAs, extracellular vessels, and tumor-educated platelets. Validation of liquid biopsy assays is essential…

Hematopathology

Abstract Background The field of hematology has long been at the forefront in the use of histopathology combined with ancillary laboratory methods, including genetic testing, to improve clinical outcomes. The benefits of these efforts for patients with hematopoietic malignancies have been numerous. They include improved diagnostic accuracy, refined prognostication, and identification of potential new therapeutic targets. Molecular testing methods such as polymerase chain reaction (PCR), Sanger…

Solid tumors

Abstract Background Once thought of as a simple clonal expansion of abnormal cells, cancer is now recognized as a complex, multifactorial, and polygenic syndrome. Many cancer types have been reclassified due to new understanding of molecular-based phenotypes and tumor-host interactions. Since the initial human genome reference sequence in 2004, cancer genomics research has focused on using this reference as a template for characterizing the somatic genomic…

Genetics

Abstract Background The invention of the polymerase chain reaction (PCR) over 30 years ago along with the chemistry of fluorescently labeled molecules; high-density DNA single nucleotide polymorphism arrays; massively parallel sequencing (MPS) technology for exomes, genomes, and transcriptomes; chromosomal microarrays; the availability of public databases; and advances in bioinformatics have revolutionized the field of human genetics. The collective use of these technologies for nucleic acid analysis…

Molecular microbiology

Abstract Background Nucleic acid (NA) amplification techniques are now routinely used to diagnose and manage patients with infectious diseases. The growth in the number of US Food and Drug Administration–approved/cleared and European CE-IVD tests has facilitated the use of molecular technology in clinical laboratories. Technological advances in NA amplification techniques, automation, NA sequencing, and multiplex analysis have reinvigorated the field and created new opportunities for growth.…

Clinical genome sequencing

Abstract Background Soon after whole genome sequencing was developed, it was validated for use in a clinical setting, now known as clinical genome sequencing or cGS. Mostly cGS is used for rare, undiagnosed diseases, where the patient’s symptoms and/or family history are consistent with an inherited disease. Although costs seem high, ending a diagnostic odyssey using cGS may be cost-effective in overall health care costs. While…

Genomes, variants, and massively parallel methods

Abstract Background One of the defining achievements of the early 21st century is the sequencing and alignment of more than 90% of the human genome. Of course, there is not a single human genome: individuals differ from each other by about 0.1% and from other primates by about 1%. Variation comes in many different forms, including single base changes and copy number differences in large segments…

Nucleic acid techniques

Abstract Background Nucleic acid techniques as applied to molecular diagnostics have enabled the laboratorian to modify, amplify, detect, discriminate, and sequence nucleic acids with levels of sensitivity and specificity unparalleled by other laboratory techniques. Molecular diagnostic techniques continue to produce results that are faster, better, and cheaper, a trend that translates into better patient care and that fully supports precision medicine initiatives. Content Molecular diagnostic techniques…

Nucleic acid isolation

Abstract Background Effective isolation of nucleic acids (NAs) is important for sensitive and accurate clinical molecular methods that interrogate deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). There are many different techniques and methods (including commercial kits) available for NA isolation, or sample preparation, and the choice often depends on the source of NA and downstream analytical method. The most common procedures in clinical and research laboratories…

Principles of molecular biology

Abstract Background Molecular diagnostics and its parent field, molecular pathology, examine the origins of disease at the molecular level, primarily by studying nucleic acids. Deoxyribonucleic acid (DNA), which contains the blueprint for constructing a living organism, is the centerpiece for research and clinical analysis. Molecular pathology is an outgrowth of the enormous amount of successful research in the field of molecular biology that has discovered over…

Inborn errors of metabolism: Disorders of complex molecules

Abstract Background Inborn errors of metabolism (IEM) caused by defective processing of complex molecules comprise a specific subgroup of genetic disorders. Since these disorders are clinically heterogeneous, their diagnosis requires a high index of clinical suspicion combined with targeted laboratory testing. Content This chapter focuses on IEM arising from defective metabolism of “complex molecules.” This IEM group is largely caused by defects in biological processes within…

Newborn screening and inborn errors of metabolism

Abstract Background Newborn screening can detect many metabolic disorders, allowing early initiation of treatment to prevent morbidity and mortality. The introduction of tandem mass spectrometry (MS/MS) has dramatically increased the number of conditions detectable at birth to include several inborn errors of amino acid metabolism, fatty acid oxidation, and organic acidemias. Content This chapter describes a range of metabolic disorders amenable to newborn screening. Amino acids…

Pregnancy and its disorders

Abstract Background The clinical laboratory has an important role in monitoring pregnancy when an expectant mother is being treated. In contrast to most clinical situations in which a physician is caring for one patient, the physician must simultaneously care for both a mother and her fetus. The usual results for many clinical measurements no longer apply during pregnancy, further complicating the management of the patients. Content…

Reproductive endocrinology and related disorders

Abstract Background The field of reproductive endocrinology encompasses the hormones of the hypothalamic-pituitary-gonadal axis and the adrenal glands that are crucial for reproductive function. Hypothalamic gonadotropin-releasing hormone (GnRH) directs the pituitary to synthesize and release follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which in turn stimulate gonadal synthesis of the sex steroids that govern the development and maintenance of secondary sex characteristics. In states of reproductive…

Thyroid disorders

Abstract Background The ability to accurately diagnose thyroid disease using a blood test is arguably one of the greatest triumphs of modern clinical chemistry. Thyroid function tests are now among the most widely requested laboratory investigations. This is because of the relatively high incidence of thyroid disease, the symptoms of the disease often being nonspecific, and effective treatment options for the most common forms of thyroid…