BOOK
Henry's Clinical Diagnosis and Management by Laboratory Methods E-Book
Richard A. McPherson | Matthew R. Pincus
(2017)
Additional Information
Book Details
Abstract
Recognized as the definitive reference in laboratory medicine since 1908, Henry's Clinical Diagnosis continues to offer state-of-the-art guidance on the scientific foundation and clinical application of today's complete range of laboratory tests. Employing a multidisciplinary approach, it presents the newest information available in the field, including new developments in technologies and the automation platforms on which measurements are performed.
- Provides guidance on error detection, correction, and prevention, as well as cost-effective test selection.
- Features a full-color layout, illustrations and visual aids, and an organization based on organ system.
- Features the latest knowledge on cutting-edge technologies of molecular diagnostics and proteomics.
- Includes a wealth of information on the exciting subject of omics; these extraordinarily complex measurements reflect important changes in the body and have the potential to predict the onset of diseases such as diabetes mellitus.
- Coverage of today's hottest topics includes advances in transfusion medicine and organ transplantation; molecular diagnostics in microbiology and infectious diseases; point-of-care testing; pharmacogenomics; and the microbiome.
- Toxicology and Therapeutic Drug Monitoring chapter discusses the necessity of testing for therapeutic drugs that are more frequently being abused by users.
Table of Contents
Section Title | Page | Action | Price |
---|---|---|---|
Front Cover | cover | ||
Endsheet 2 | IFC1 | ||
Half title page | i | ||
Associate Editors | ii | ||
Henry's Clinical Diagnosis and Management by Laboratory Methods | iii | ||
Copyright Page | iv | ||
Table Of Contents | v | ||
Contributors | viii | ||
Preface | xiv | ||
Acknowledgments | xvii | ||
1 The Clinical Laboratory | 1 | ||
1 General Concepts and Administrative Issues | 2 | ||
Key Points | 2 | ||
Leadership and Management | 2 | ||
Strategic Planning | 3 | ||
Quality Systems Management | 3 | ||
Human Resource Management | 5 | ||
Laboratory Design and Service Models | 5 | ||
Regulation, Accreditation, and Legislation | 6 | ||
Safety | 7 | ||
Biological Hazards | 8 | ||
Chemical Hazards | 9 | ||
Ergonomic Hazards | 10 | ||
References | 10 | ||
Selected References | 10 | ||
References | 10.e1 | ||
2 Optimizing Laboratory Workflow and Performance | 11 | ||
Key Points | 11 | ||
Understanding Workflow | 11 | ||
Data Collection Techniques | 11 | ||
Sample and Test Mapping | 11 | ||
Tube Analysis | 12 | ||
Workstation Analysis | 12 | ||
Instrument Audit | 13 | ||
Test Menu | 14 | ||
Processing Mode and Load Balancing. | 14 | ||
Interviews | 14 | ||
Task Mapping | 14 | ||
Workflow Analysis | 14 | ||
Workflow Modeling | 15 | ||
Pneumatic Tube Transport of Specimens | 16 | ||
Understanding Technology | 16 | ||
The Role of Technology: Principles and Pitfalls | 16 | ||
Optimizing Performance | 17 | ||
References | 19 | ||
Selected References | 19 | ||
References | 19.e1 | ||
3 Preanalysis | 20 | ||
Key Points | 20 | ||
Precollection Variables | 20 | ||
Physiologic Factors | 20 | ||
Common Interferences | 21 | ||
In Vivo | 21 | ||
Tobacco Smoking | 21 | ||
In Vitro | 22 | ||
Collection-Associated Variables | 22 | ||
Special Issues That May Impact Analysis | 22 | ||
Immunoassays | 22 | ||
Specimen Matrix Effects | 23 | ||
Molecular Diagnostics | 23 | ||
Effects of Drugs | 23 | ||
Specimen Collection | 23 | ||
The Test Order | 23 | ||
Time of Collection | 23 | ||
Specimen Acceptability and Identification Issues | 24 | ||
Blood Collection Overview | 24 | ||
Anticoagulants and Additives | 24 | ||
Blood Collection Devices | 25 | ||
Blood Storage and Preservation | 26 | ||
Importance of Policies and Procedures | 26 | ||
Blood Collection Techniques | 27 | ||
Arterial Puncture | 27 | ||
Arterial Puncture Technique | 27 | ||
Finger or Heel Skin Puncture | 27 | ||
Central Venous Access Devices | 28 | ||
CVA Collection Technique | 28 | ||
Urine and Other Body Fluids Collection | 28 | ||
Urine | 28 | ||
Special Urine Collection Techniques | 29 | ||
Urine Storage and Preservation | 29 | ||
Other Body Fluids | 29 | ||
Cerebrospinal Fluid | 29 | ||
Synovial Fluid | 30 | ||
Pleural Fluid, Pericardial Fluid, and Peritoneal Fluid | 30 | ||
Specimen Transport | 30 | ||
Specimen Processing | 31 | ||
Precentrifugation Phase | 31 | ||
Centrifugation Phase | 31 | ||
Equipment | 31 | ||
References | 31 | ||
Selected References | 31 | ||
References | 32.e1 | ||
4 Analysis | 33 | ||
Key Points | 33 | ||
Principles of Instrumentation | 33 | ||
Spectrophotometry | 33 | ||
Velocity of Propagation | 34 | ||
Energy of EMR | 34 | ||
Scattering of Radiation | 34 | ||
Rayleigh Scattering | 35 | ||
Tyndall Effect | 35 | ||
Raman Scattering | 35 | ||
Beer-Lambert Law | 35 | ||
Components of a Spectrophotometer | 36 | ||
Radiant Energy Sources | 36 | ||
Wavelength Selectors | 37 | ||
Filters | 37 | ||
Sample Containers (Cuvets) | 39 | ||
Photodetectors | 39 | ||
Photodiode Arrays. | 40 | ||
Charge-Transfer Devices. | 40 | ||
Signal Processors and Readout | 40 | ||
Quality Assurance in Spectrophotometry | 40 | ||
Types of Photometric Instruments | 40 | ||
Reflectometry | 41 | ||
Reflectometers | 42 | ||
Molecular Luminescence Spectroscopy (Fluorometry) | 42 | ||
Principle | 42 | ||
Components of Fluorometers and Spectrophotofluorometers | 42 | ||
Nephelometry and Turbidimetry | 43 | ||
Principle | 43 | ||
Nephelometer | 43 | ||
Turbidimetry | 43 | ||
Refractometry | 43 | ||
Osmometry | 43 | ||
Principle of Freezing-Point Osmometry | 44 | ||
Freezing-Point Osmometer | 44 | ||
Flow Cytometry | 44 | ||
Instrument Components | 44 | ||
Electrochemistry | 44 | ||
Potentiometry | 44 | ||
Reference Electrodes | 44 | ||
Ion-Selective Electrode | 45 | ||
pH Electrode | 45 | ||
pCO2 Electrode | 46 | ||
Coulometry | 46 | ||
Amperometry | 46 | ||
pO2 Gas-Sensing Electrode | 46 | ||
Voltammetry | 46 | ||
Conductance | 46 | ||
Impedance | 46 | ||
Electrophoresis and Densitometry | 46 | ||
Isoelectric Focusing | 47 | ||
Chromatography | 47 | ||
Gas Chromatography | 48 | ||
Liquid Chromatography | 49 | ||
Mass Spectrometry | 49 | ||
Atomic Weights (amu and Da) | 50 | ||
Mass/Charge Ratio | 50 | ||
Basic Components | 50 | ||
Ion Source Unit | 50 | ||
Mass Spectrometer Analyzer Unit | 50 | ||
Ion Detector | 50 | ||
Scintillation Counter | 51 | ||
Capillary Electrophoresis | 52 | ||
Nuclear Magnetic Resonance Spectroscopy | 53 | ||
General Analytic Methods and Issues | 53 | ||
Chemicals | 53 | ||
Water | 54 | ||
Types of Water Purity | 54 | ||
Purification | 54 | ||
Monitoring Water Purity | 54 | ||
Once Your System Has Been Installed | 54 | ||
Measurement of Mass | 54 | ||
Types of Balances | 54 | ||
Unequal-Arm Substitution Balances | 54 | ||
Magnetic Force Restoration Balance | 54 | ||
Top-Loading Balances | 55 | ||
Electronic Balances | 55 | ||
Calibration | 55 | ||
Handling Weights Used for Testing Accuracy | 55 | ||
Environmental Concerns for Best Weighing Accuracy | 55 | ||
Balance Specifications | 55 | ||
Laboratory Glassware and Plasticware | 55 | ||
Types of Glassware | 55 | ||
Types of Plasticware | 55 | ||
Volumetric Laboratoryware | 56 | ||
Pipets | 56 | ||
Class A Designation | 56 | ||
Types of Pipets | 56 | ||
Micropipets | 56 | ||
Pipet Calibration | 56 | ||
Volumetric Flasks | 56 | ||
Calibration of Volumetric Glassware | 56 | ||
Thermometry | 56 | ||
Types of Thermometers | 56 | ||
Special Applications of Temperature-Sensing Devices | 57 | ||
Mercury-Free Laboratories | 57 | ||
Thermometer Calibration | 57 | ||
Water Baths | 57 | ||
Maintenance | 57 | ||
Quality Control | 57 | ||
Heating Blocks, Dry-Bath Incubators, and Ovens | 57 | ||
Mixing | 57 | ||
Single-Tube Mixers | 57 | ||
Multiple-Tube Mixers | 57 | ||
Aqueous Solution | 58 | ||
Molarity | 58 | ||
Millimoles | 58 | ||
Normality | 58 | ||
Molal | 58 | ||
Dilutions | 58 | ||
Acids, Alkalis, and pH | 59 | ||
References | 59 | ||
Selected References | 59 | ||
References | 59.e1 | ||
5 Analysis | 60 | ||
Key Points | 60 | ||
Evolution of Automation | 60 | ||
Preanalytic and Postanalytic Automation | 61 | ||
Automated Delivery | 61 | ||
Automated Specimen Processing | 61 | ||
Postanalytic Processing | 61 | ||
Emerging Technologies in Preanalytic and Postanalytic Processing | 62 | ||
Automated Specimen Inspection | 62 | ||
Radio-Frequency Identification | 62 | ||
The Automated Chemistry Analyzer: Core Components | 62 | ||
Sampling | 62 | ||
Reagent Handling | 62 | ||
Mixing and Incubation | 63 | ||
Detection | 63 | ||
Data Processing and Real-Time Monitoring | 63 | ||
The Continuum of Chemistry Automation | 63 | ||
Workstation | 63 | ||
Workcell | 63 | ||
Total Laboratory Automation | 63 | ||
Laboratory Automation in Other Sections of the Lab | 64 | ||
Hematology | 64 | ||
Microbiology | 64 | ||
Planning for Laboratory Automation | 64 | ||
References | 65 | ||
Selected References | 65 | ||
References | 65.e1 | ||
6 Point-of-Care Testing and Physician Office Laboratories | 66 | ||
Key Points | 66 | ||
Introduction: Definition of Point-of-Care Testing | 66 | ||
Regulatory Requirements | 66 | ||
Laboratory Directorship | 67 | ||
Compliance | 68 | ||
Types of Point-of-Care Testing | 68 | ||
Hematology | 68 | ||
Chemistry | 68 | ||
Microbiology | 69 | ||
Advantages and Disadvantages of Point-of-Care Testing | 69 | ||
Connectivity and Data Management | 69 | ||
Implementation of a Point-of-Care Testing Program | 70 | ||
Physician Offices | 70 | ||
Hospitals and Medical Centers | 70 | ||
Point-of-Care Committee and Management Team | 70 | ||
Selection of Appropriate Tests | 71 | ||
Selection of Appropriate Testing Devices and Methods | 71 | ||
Policies and Procedures | 71 | ||
Method Validations | 71 | ||
Oversight of Training and Competency | 71 | ||
Maintenance of a Point-of-Care Testing Program | 72 | ||
Quality Assurance Program | 72 | ||
Conclusions | 72 | ||
References | 72 | ||
Selected References | 72 | ||
References | 72.e1 | ||
7 Postanalysis | 73 | ||
Key Points | 73 | ||
Assessment of Analytic Correctness of Results | 73 | ||
Alarms and Flags | 73 | ||
Flags for Problem Specimens | 74 | ||
Flags for Specimens That Require Additional Analysis with Another Method | 74 | ||
Flags for Problematic Results | 74 | ||
Delta Checks | 74 | ||
Assessment of Clinical Significance of Results | 74 | ||
Critical Values | 74 | ||
Reference Ranges | 74 | ||
Definition of Reference Intervals | 74 | ||
Factors That Influence Reference Ranges | 75 | ||
Determination of Reference Ranges | 75 | ||
Variability of Laboratory Results | 75 | ||
General Principles for the Interpretation of Laboratory Results | 75 | ||
Diagnostic Accuracy | 75 | ||
Truth Table | 75 | ||
Sensitivity and Specificity | 75 | ||
Effect of Altering the Test Cutoff | 77 | ||
The Need for High Sensitivity versus High Specificity | 77 | ||
Predictive Value and Prevalence of Disease | 77 | ||
Predictive Value and Accuracy | 78 | ||
Bayes Theorem | 78 | ||
Likelihood Ratio | 79 | ||
Receiver Operator Characteristic Curves | 80 | ||
Positivity Criterion | 80 | ||
Evidence-Based Medicine | 81 | ||
Systematic Reviews of Clinical Effectiveness Research and Clinical Practice Guidelines | 82 | ||
Systematic Reviews | 82 | ||
Clinical Practice Guidelines | 82 | ||
References | 83 | ||
Selected References | 83 | ||
References | 83.e1 | ||
8 Interpreting Laboratory Results | 84 | ||
Key Points | 84 | ||
Interpreting and Correlating Abnormal Laboratory Values | 84 | ||
General Considerations | 84 | ||
Fundamental Principles in Interpretation of Values | 84 | ||
Abnormalities in the Hematology Profile | 85 | ||
Anemias | 85 | ||
Microcytic Anemia | 85 | ||
Serum Ferritin Levels | 86 | ||
Use of Serum Iron and Iron-Binding Capacity | 86 | ||
Use of Red Blood Cell Distribution Width | 86 | ||
Normocytic Anemia | 86 | ||
Hyperproliferative Normocytic Anemias | 86 | ||
Hemolytic Anemia | 86 | ||
Microangiopathic Hemolytic Anemia | 87 | ||
Hypoproliferative Normocytic Anemias | 87 | ||
Bone Marrow Hypoplasia/Aplastic Anemia | 87 | ||
Myelodysplastic Syndrome | 87 | ||
Anemia of Renal Failure | 88 | ||
Macrocytic Anemia | 88 | ||
Quantitative White Blood Cell Abnormalities | 88 | ||
Infection | 88 | ||
Elevated WBC Due to Leukemoid Reaction | 88 | ||
Elevated WBC Due to Chronic Myelogenous Leukemia | 89 | ||
Elevated WBC Due to Chronic Lymphocytic Leukemia | 89 | ||
Leukocytosis Due to Acute Leukemias | 89 | ||
Low White Cell Counts | 89 | ||
Aplastic Anemia | 89 | ||
Gram-Negative Sepsis as a Cause of Leukopenia | 89 | ||
Coagulation Disorders | 89 | ||
Abnormalities in Clinical Chemistry: Chemical Pathology | 90 | ||
Electrolyte Abnormalities | 90 | ||
Hyponatremia | 90 | ||
Pseudohyponatremia | 91 | ||
Hypernatremia | 91 | ||
Hypokalemia | 91 | ||
Hyperkalemia | 92 | ||
Renal Disease | 92 | ||
BUN and Creatinine | 92 | ||
Calcium and Phosphate | 92 | ||
Calcium and Albumin | 93 | ||
Blood Gas Abnormalities | 93 | ||
Anion Gap | 93 | ||
Oxygenation | 94 | ||
Glucose Abnormalities | 94 | ||
Other Abnormal Laboratory Findings in Diabetes Mellitus | 95 | ||
Liver Function Tests | 95 | ||
Correlations of Liver Function Test Results with Other Laboratory Findings | 96 | ||
Cardiac Function Tests | 96 | ||
Diagnosis of Myocardial Infarction and Acute Coronary Syndrome | 96 | ||
Diagnosis of Congestive Heart Failure | 97 | ||
Skeletal Muscle Function | 97 | ||
Pancreatic Function Tests | 97 | ||
Markers for Inflammatory Conditions | 97 | ||
Endocrine Function Testing | 97 | ||
Principle | 97 | ||
Thyroid Function | 97 | ||
Adrenal Function | 98 | ||
Parathyroid Hormone and Vitamin D | 98 | ||
Vitamin D | 98 | ||
Examples of Clinical Cases with Clinicopathological Correlations | 99 | ||
Case A: Electrolyte Disorder | 99 | ||
Evaluation | 99 | ||
Case B: Complex Electrolyte Disorder | 99 | ||
2 Clinical Chemistry | 161 | ||
14 Evaluation of Renal Function, Water, Electrolytes, and Acid-Base Balance | 162 | ||
Key Points | 162 | ||
Introduction | 162 | ||
Volume and Osmolality of Body Fluid | 163 | ||
Measurement of Body Fluid Volumes | 163 | ||
Body Fluid Volumes | 163 | ||
Composition of the Body Fluid | 164 | ||
Extracellular Composition | 164 | ||
Intracellular Composition | 164 | ||
Measurement of Plasma Osmolality | 165 | ||
Effect of Hyperglycemia on Serum Na | 165 | ||
Tonicity | 166 | ||
Osmolality and Specific Gravity | 166 | ||
Regulation of Extracellular Volume | 166 | ||
Nonrenal Control of Water and Electrolyte Balance | 167 | ||
Insensible Loss of Water from the Skin | 167 | ||
Loss of Respiratory Water | 167 | ||
Loss of Water in the Gastrointestinal Tract | 167 | ||
Measurement of Renal Function | 167 | ||
Concept of Clearance | 167 | ||
Quick Formulas for the Calculation of Clearance | 168 | ||
Conversion of Clearance in L/week to mL/min | 168 | ||
Measurement of Glomerular Filtration Rate | 168 | ||
Measurement of GFR with Exogenous Substances | 168 | ||
Measurement of GFR with Endogenous Substances | 168 | ||
Creatinine as a Measure of Renal Function | 168 | ||
Creatinine Measurement | 169 | ||
Cimetidine-Enhanced Creatinine Clearance | 169 | ||
The Effect of Drugs on Serum Creatinine | 169 | ||
Formulas to Estimate Creatinine Clearance as an Estimate of GFR | 169 | ||
Urea as Measure of Renal Function | 170 | ||
Measurement of Urea | 170 | ||
Other Measures of GFR | 170 | ||
Cystatin C | 170 | ||
Beta-2 Microglobulin | 171 | ||
Beta Trace Protein | 171 | ||
Tryptophan Glycoconjugate | 171 | ||
Urea Clearance and Urea/Creatinine Ratio in Serum | 171 | ||
Glomerular Filtration Rate (GFR), Renal Plasma Flow (RPF), and Filtration Fraction (FF) | 171 | ||
Fractional Excretion (FE) | 172 | ||
Renal Failure Index (RFI) | 172 | ||
Fractional Reabsorption (FR) | 172 | ||
Free Water Clearance and Negative Free Water Clearance | 172 | ||
Biomarkers of Acute Kidney Injury (AKI) | 172 | ||
Kidney Injury Molecule-1 (KIM-1) | 173 | ||
Neutrophil Gelatinase-Associated Lipocalin (NGAL) | 173 | ||
Interleukin-18 (IL-18) | 173 | ||
Fatty Acid–Binding Protein (FABP) | 173 | ||
Disorders of Potassium | 174 | ||
Control of Transcellular Flux of Potassium | 174 | ||
Control of Renal Excretion of Potassium | 174 | ||
Plasma Renin Activity (PRA), Plasma Aldosterone Concentration (PA), and Abnormalities in Potassium Metabolism | 175 | ||
Causes and Pathogenesis of Hypokalemia | 175 | ||
Differential Diagnosis of Hypokalemia | 176 | ||
Causes and Pathogenesis of Hyperkalemia | 176 | ||
Differential Diagnosis of Hyperkalemia | 177 | ||
Disorders of Water, Sodium, and Antidiuretic Hormone (ADH) Metabolism | 178 | ||
Regulation of Thirst and ADH Release | 178 | ||
Urine Concentration and Dilution | 178 | ||
Polyuria | 179 | ||
Osmotic Diuresis | 179 | ||
Water Diuresis | 179 | ||
Causes and Pathogenesis of Hyponatremia | 180 | ||
Causes and Pathogenesis of Hypernatremia | 181 | ||
Acid-Base Disorders | 181 | ||
Bicarbonate and CO2 Buffer System | 181 | ||
Definitions of Acid and Base | 181 | ||
Whole-Body Acid-Base Balance | 181 | ||
Net Acid Production | 182 | ||
Net Acid Excretion | 182 | ||
Metabolic Acidosis | 182 | ||
Classification | 182 | ||
Renal Acidosis | 182 | ||
Organic Acidosis | 183 | ||
Lactic Acidosis | 183 | ||
d-Lactic Acidosis | 183 | ||
Ketoacidosis | 183 | ||
Serum Anion Gap (AG) | 184 | ||
Differential Diagnosis | 184 | ||
3 Urine and Other Bodily Fluids | 441 | ||
28 Basic Examination of Urine | 442 | ||
Key Points | 442 | ||
Urine Formation | 442 | ||
Components of Basic (Routine) Urinalysis | 443 | ||
Specimen Evaluation | 443 | ||
Gross/Physical Examination | 443 | ||
Appearance | 443 | ||
Color | 443 | ||
Red Urine. | 443 | ||
Yellow-Brown or Green-Brown Urine. | 444 | ||
Orange-Red or Orange-Brown Urine. | 444 | ||
Dark Brown or Black Urine. | 444 | ||
Blue, Green, or Blue-Green Urine. | 444 | ||
Clarity (Character) | 444 | ||
Chyluria. | 445 | ||
Lipiduria. | 445 | ||
Odor | 445 | ||
Urine Volume | 445 | ||
Increases in Urine Volume | 445 | ||
Defective Hormonal Regulation of Volume Homeostasis. | 445 | ||
Defective Renal Salt/Water Absorption. | 445 | ||
Osmotic Diuresis. | 445 | ||
Decreases in Urine Volume | 445 | ||
Prerenal. | 445 | ||
Postrenal. | 445 | ||
Renal Parenchymal Disease. | 445 | ||
Specific Gravity and Osmolality | 445 | ||
Specific Gravity | 446 | ||
4 Hematology and Transfusion Medicine | 509 | ||
30 Basic Examination of Blood and Bone Marrow | 510 | ||
Key Points | 510 | ||
Hematology Principles and Procedures | 510 | ||
Hemoglobin | 510 | ||
Hemoglobin Derivatives | 510 | ||
Hemiglobin (Methemoglobin) | 510 | ||
Sulfhemoglobin | 511 | ||
Carboxyhemoglobin | 511 | ||
Measurement of Hb Concentration (Manual Technique of Hemoglobinometry) | 511 | ||
Hemiglobincyanide Method | 511 | ||
Principle. | 511 | ||
Reagent. | 511 | ||
Method. | 512 | ||
Errors in Hemoglobinometry | 512 | ||
Errors Inherent in the Sample. | 512 | ||
Errors Inherent in the Method. | 512 | ||
Errors Inherent in the Equipment. | 512 | ||
Spectrophotometric Identification of Hemoglobins | 512 | ||
Hematocrit (Packed Cell Volume) | 512 | ||
Gross Examination | 513 | ||
Hematocrit Measurement by Micromethod | 513 | ||
Equipment | 513 | ||
Procedure | 513 | ||
Interpretation of Results | 513 | ||
Sources of Error | 513 | ||
Centrifugation. | 513 | ||
Sample. | 513 | ||
Other Errors. | 513 | ||
Erythrocyte Indices | 513 | ||
Mean Cell Volume | 513 | ||
Mean Cell Hemoglobin | 513 | ||
Mean Cell Hemoglobin Concentration | 513 | ||
Manual Blood Cell Counts | 514 | ||
Erythrocyte Counts: Manual | 514 | ||
Semiautomated Methods | 514 | ||
Reticulocyte Count: Manual | 514 | ||
Principle | 514 | ||
Reagent. | 514 | ||
Controls. | 514 | ||
Procedure | 514 | ||
Reference Values | 514 | ||
Interpretation | 514 | ||
Sources of Variation | 514 | ||
Physiologic Variation in Erythrocytes | 514 | ||
Leukocyte Counts: Manual | 515 | ||
Specimen Collection | 515 | ||
Hemocytometer Method | 515 | ||
Counting Chamber. | 516 | ||
Diluting Fluid. | 516 | ||
Procedure | 516 | ||
Sources of Error. | 516 | ||
Errors due to the nature of the sample. | 516 | ||
Operator’s errors. | 516 | ||
Errors due to equipment. | 516 | ||
Inherent or field errors. | 516 | ||
Nucleated red blood cells. | 516 | ||
Reference Value. | 516 | ||
Physiologic Variation in Leukocytes | 516 | ||
Platelet Counts | 516 | ||
Hemocytometer Method—Phase-Contrast Microscope | 517 | ||
Specimen. | 517 | ||
Diluent Solution. | 517 | ||
Procedure | 517 | ||
Calculation. | 518 | ||
Sources of Error. | 518 | ||
Falsely elevated counts. | 518 | ||
Falsely low counts. | 518 | ||
Reticulated Platelets | 518 | ||
Physiologic Variation in Platelets | 519 | ||
Instrument Technology | 519 | ||
Hematology Analyzers | 519 | ||
Electrical Impedance | 519 | ||
Radiofrequency Conductivity | 519 | ||
Light Scattering | 519 | ||
Cytochemistry | 519 | ||
Reporting/Flagging | 520 | ||
Sources of Error | 520 | ||
Automated Differential Leukocyte Counting | 520 | ||
Digital Image Processing | 520 | ||
Automated Reticulocyte Counting | 521 | ||
Blood Film Examination | 521 | ||
Examination of Wet Preparations | 521 | ||
Making and Staining Blood Films | 521 | ||
Wedge Method | 521 | ||
Cover Glass Method | 521 | ||
Spinner Method | 521 | ||
Blood Stains | 521 | ||
Wright’s Stain | 521 | ||
Procedure | 522 | ||
Staining Problems | 522 | ||
Excessively blue stain. | 522 | ||
Excessively pink stain. | 522 | ||
Other staining problems. | 522 | ||
Other Stains | 522 | ||
Reference Method | 522 | ||
Automated Slide Stainer | 522 | ||
Review of Peripheral Smear | 522 | ||
Erythrocytes | 522 | ||
Color | 522 | ||
Hemoglobin Content | 522 | ||
Polychromatophilia | 523 | ||
Size | 523 | ||
Shape | 524 | ||
Structure | 525 | ||
Basophilic Stippling (Punctate Basophilia) | 525 | ||
Howell-Jolly Bodies | 526 | ||
Cabot Rings | 526 | ||
Malarial Stippling | 526 | ||
Rouleaux Formation | 526 | ||
Nucleated Red Cells | 526 | ||
Significance of Nucleated Red Cells | 527 | ||
Leukoerythroblastic Reaction | 527 | ||
Leukocytes on Peripheral Blood Smear Examination | 527 | ||
Leukocytes Normally Present in Blood | 527 | ||
Neutrophil (Polymorphonuclear Neutrophilic Leukocyte; Segmented Neutrophilic Granulocyte) | 527 | ||
Eosinophil (Eosinophilic Granulocyte) | 528 | ||
Basophil (Basophilic Granulocyte) | 528 | ||
Monocyte | 529 | ||
Lymphocyte | 529 | ||
Artifacts | 529 | ||
Broken Cells | 529 | ||
Degenerative Changes | 530 | ||
Contracted Cells | 530 | ||
Endothelial Cells | 530 | ||
Radial Segmentation of the Nuclei | 531 | ||
Vacuolation | 531 | ||
“Pseudophagocytosis” | 531 | ||
Sources of Error in the Differential Leukocyte Count | 531 | ||
Platelets on Peripheral Blood Smear Examination | 531 | ||
Erythrocyte Sedimentation Rate | 531 | ||
Plasma Factors | 532 | ||
Red Cell Factors | 532 | ||
Stages in the ESR | 532 | ||
Methods | 532 | ||
Westergren Method | 532 | ||
Equipment. | 532 | ||
Reagent. | 532 | ||
Procedure | 532 | ||
Modified Westergren Method | 532 | ||
Sources of Error | 532 | ||
Alternative Methods and Technologies to Measure ESR | 533 | ||
Application | 533 | ||
Bone Marrow Examination | 533 | ||
Indications for Marrow Study | 533 | ||
Preparation of the Aspirate and Biopsy Section | 534 | ||
Marrow Films | 534 | ||
Direct Films | 534 | ||
Imprints | 534 | ||
Crush Preparations | 534 | ||
Special Studies | 534 | ||
Histologic Sections | 534 | ||
Staining Marrow Preparations | 534 | ||
Romanowsky’s Stain | 534 | ||
Perls’ Test for Iron | 534 | ||
Procedure | 534 | ||
Interpretation | 534 | ||
Sections | 534 | ||
Examination of Marrow | 536 | ||
Peripheral Blood | 536 | ||
Cellularity of the Marrow | 536 | ||
Distribution of Cells | 536 | ||
Maturation | 536 | ||
Presence of Rare Cell Types or Abnormal Cells | 536 | ||
Evaluation of the Biopsy Specimen | 538 | ||
Interpretation | 538 | ||
References | 538 | ||
Selected References | 539 | ||
References | 539.e1 | ||
31 Hematopoiesis | 540 | ||
Key Points | 540 | ||
Stem Cells | 540 | ||
Hematopoietic Stem Cells and Progenitors | 540 | ||
Hematopoietic Growth Factors | 541 | ||
Hematopoietic Tissues | 542 | ||
Embryonic and Fetal Hematopoiesis | 542 | ||
Postnatal Hematopoiesis | 542 | ||
Erythrocyte Production | 542 | ||
Normoblastic Maturation | 542 | ||
Megaloblastic Maturation | 544 | ||
Regulation of Erythrocyte Production | 544 | ||
Synthesis of Hemoglobin | 544 | ||
Heme Synthesis | 544 | ||
Globin Synthesis | 544 | ||
Structure and Function of Hemoglobin | 546 | ||
Erythrocyte Destruction | 546 | ||
Degradation of Hemoglobin | 546 | ||
Erythrokinetics | 546 | ||
Measurements of Total Production of Erythrocytes or Hemoglobin | 547 | ||
Measurements of Total Destruction of Erythrocytes or Hemoglobin | 547 | ||
Measurements of Effective Production of Erythrocytes: Reticulocyte Count | 547 | ||
Measurements of Effective Survival of Erythrocytes in Blood | 547 | ||
Summary | 547 | ||
Neutrophils | 547 | ||
Morphology of Neutrophil Precursors | 547 | ||
Distribution and Kinetics | 550 | ||
Function | 550 | ||
Eosinophils | 550 | ||
Morphology of Eosinophil Precursors | 550 | ||
Distribution and Kinetics | 551 | ||
Function | 551 | ||
Basophils and Mast Cells | 551 | ||
Morphology | 551 | ||
Distribution and Kinetics | 552 | ||
Function | 552 | ||
Monocytes and Macrophages | 552 | ||
Morphology | 552 | ||
Distribution and Kinetics | 553 | ||
Function | 553 | ||
Megakaryocytes | 553 | ||
Morphology | 553 | ||
Megakaryocytes in Blood | 553 | ||
Distribution and Kinetics | 554 | ||
Function | 554 | ||
Lymphocytes | 554 | ||
Primary Lymphoid Tissue | 554 | ||
B Cell Development: Bone Marrow | 554 | ||
T Cell Development: Thymus | 556 | ||
Natural Killer Cells: Bone Marrow | 556 | ||
Secondary Lymphoid Tissue | 556 | ||
Lymphocyte Function and Physiology | 556 | ||
References | 557 | ||
Selected References | 558 | ||
References | 558.e1 | ||
32 Erythrocytic Disorders | 559 | ||
Key Points | 559 | ||
Anemias | 559 | ||
General Manifestations | 559 | ||
Impaired Production—Iron Deficiency Anemia | 559 | ||
Iron Metabolism (Beutler, 2010) | 559 | ||
Iron Deficiency Anemia (IDA) | 560 | ||
Clinical Features | 561 | ||
Laboratory Features | 561 | ||
Blood. | 561 | ||
Marrow. | 561 | ||
Serum Iron. | 562 | ||
Serum (Total) Iron-Binding Capacity. | 562 | ||
Percent Saturation of TIBC. | 562 | ||
Serum Ferritin. | 562 | ||
Erythrocyte Porphyrins. | 562 | ||
Serum Transferrin Receptors. | 562 | ||
Serum Transferrin Receptor–to–Serum Ferritin Ratio. | 562 | ||
Reticulocyte Hemoglobin Content. | 562 | ||
Hepcidin Level. | 562 | ||
Differential Diagnosis | 562 | ||
Management | 563 | ||
Iron-Refractory Iron Deficiency Anemia (IRIDA) | 563 | ||
Impaired Production— Megaloblastic Anemia | 563 | ||
Macrocytosis with Normoblastic Marrow | 563 | ||
Megaloblastic Anemia | 563 | ||
Blood | 563 | ||
Marrow. | 563 | ||
Erythrokinetics. | 564 | ||
Cobalamin (Vitamin B12) Metabolism | 564 | ||
Cobalamin Deficiency | 564 | ||
Inadequate Intake | 564 | ||
Defective Production of Intrinsic Factor | 564 | ||
Pernicious Anemia | 564 | ||
Clinical Features | 564 | ||
Gastric Findings | 564 | ||
Immune Abnormalities | 565 | ||
Pernicious Anemia in Children | 565 | ||
Gastrectomy | 565 | ||
Defective Absorption of Cobalamin | 565 | ||
Malabsorption Syndromes. | 565 | ||
Lack of Availability of Cobalamin. | 565 | ||
Diagnosis of Cobalamin Deficiency | 565 | ||
Therapeutic Trial. | 565 | ||
Serum Cobalamin Assay. | 565 | ||
Methylmalonic Acid and Homocysteine Assays. | 565 | ||
Deoxyuridine Suppression Test. | 565 | ||
Detecting the Cause of Cobalamin Deficiency | 566 | ||
Folic Acid Metabolism | 566 | ||
The Folate–Cobalamin Relationship | 566 | ||
Folic Acid Deficiency (Green, 2010) | 566 | ||
Inadequate Intake of Folate | 566 | ||
Evolution of Laboratory Abnormalities. | 566 | ||
Nutritional Folate Deficiency. | 566 | ||
Liver Disease. | 566 | ||
Defective Absorption of Folate | 566 | ||
Increased Requirement for Folate | 567 | ||
Inadequate Utilization of Folate | 567 | ||
Diagnosis of Folate Deficiency | 567 | ||
Serum and Red Cell Folate. | 567 | ||
Urinary Formiminoglutamic Acid (FIGLU) | 567 | ||
Deoxyuridine Suppression Test. | 567 | ||
Plasma Homocysteine Assay. | 567 | ||
Acute Megaloblastic Anemia | 567 | ||
Therapy for Megaloblastic Anemia | 567 | ||
Other Defects of Nucleoprotein Synthesis | 567 | ||
Congenital Defects | 568 | ||
Synthetic Inhibitors | 568 | ||
Refractory Anemias | 568 | ||
Impaired Production—Other | 568 | ||
Anemia of Chronic Disease (Means, 2003; Nemeth & Ganz, 2014) | 568 | ||
Anemia of Renal Insufficiency | 568 | ||
Anemia in Liver Disease | 568 | ||
Anemia in Endocrine Disease | 569 | ||
Anemia Associated with Bone Marrow Infiltration (Myelophthisic Anemia) | 569 | ||
Aplastic Anemia | 569 | ||
Clinical Features | 569 | ||
Etiology | 569 | ||
Pathogenesis | 569 | ||
Prognosis | 569 | ||
Management | 570 | ||
Idiopathic Acquired Aplastic Anemia | 570 | ||
Blood | 570 | ||
Bone Marrow. | 570 | ||
Erythrokinetics. | 570 | ||
Acquired Aplastic Anemia Associated with Chemical or Physical Agents | 570 | ||
Toxic Aplastic Anemias. | 570 | ||
Ionizing Radiation. | 570 | ||
Hypersensitive Aplastic Anemias. | 570 | ||
Acquired Aplastic Anemia Associated with Other Disease | 570 | ||
Infection. | 570 | ||
Paroxysmal Nocturnal Hemoglobinuria. | 571 | ||
Pregnancy. | 571 | ||
Thymoma. | 571 | ||
Immunologic Diseases. | 571 | ||
Inherited Aplastic Anemia | 571 | ||
Fanconi’s Anemia. | 571 | ||
Other Inherited Aplastic Anemias. | 571 | ||
Pure Red Cell Aplasia | 571 | ||
Transitory Arrest of Erythropoiesis (Transient Aplastic Crises) | 571 | ||
Transient Erythroblastopenia of Childhood | 571 | ||
Congenital Red Cell Aplasia (Diamond-Blackfan Anemia; Congenital Hypoplastic Anemia) | 571 | ||
Acquired Pure Red Cell Aplasia | 572 | ||
Sideroblastic Anemia | 572 | ||
Hereditary Sideroblastic Anemias | 572 | ||
Acquired Sideroblastic Anemias | 572 | ||
Refractory Anemia with Ring Sideroblasts. | 572 | ||
Secondary (Drug- or Toxin-Induced) Sideroblastic Anemia | 572 | ||
Refractory Anemia | 572 | ||
Congenital Dyserythropoietic Anemias | 572 | ||
Blood Loss Anemia | 573 | ||
Acute Posthemorrhagic Anemia | 573 | ||
Chronic Posthemorrhagic Anemia | 573 | ||
Hemolysis—General | 573 | ||
Erythrocyte Survival Studies | 573 | ||
Hemoglobin Destruction | 573 | ||
Blood Film | 574 | ||
Bone Marrow | 574 | ||
Hemolysis—Membrane Disorders | 575 | ||
Hereditary Spherocytosis | 575 | ||
Osmotic Fragility Test | 575 | ||
Autohemolysis Test | 575 | ||
Additional Tests | 575 | ||
Hereditary Elliptocytosis | 576 | ||
Common HE | 576 | ||
Hereditary Pyropoikilocytosis | 576 | ||
Spherocytic HE | 576 | ||
Southeast Asian Ovalocytosis | 576 | ||
Hereditary Stomatocytosis | 576 | ||
Paroxysmal Nocturnal Hemoglobinuria | 576 | ||
Laboratory Diagnosis | 576 | ||
Hemolysis—Hemoglobin Disorders | 577 | ||
Normal Hemoglobins | 577 | ||
Hb A (α2β2) | 577 | ||
Hb F (α2γ2) | 577 | ||
Hb A2 (α2δ2) | 577 | ||
Embryonic Hemoglobins. | 577 | ||
The Globin Gene Clusters. | 577 | ||
Glycosylated Hemoglobins. | 577 | ||
Laboratory Investigation of Hemoglobinopathies and Thalassemias | 578 | ||
Cation-Exchange HPLC and Capillary Electrophoresis. | 578 | ||
Hemoglobin Electrophoresis and Isoelectric Focusing. | 578 | ||
Acid Elution Slide Test for F Cells. | 578 | ||
Detection of F cells by Flow Cytometry. | 578 | ||
Hb A2 Quantitation. | 578 | ||
Sickling Test—Metabisulfite Slide Test. | 578 | ||
Sickle Solubility Test. | 578 | ||
DNA Analysis. | 578 | ||
Structural Hemoglobin Variants | 578 | ||
Abnormal Hemoglobin Syndromes | 579 | ||
Sickling Disorders | 581 | ||
Sickle Cell Trait (Hb AS) | 581 | ||
Sickle Cell Disease (Hb SS) | 582 | ||
Complications. | 582 | ||
Diagnosis. | 584 | ||
Hemoglobin SC Disease | 584 | ||
Hb S/β-Thalassemia | 584 | ||
Hb SS/α-Thalassemia | 584 | ||
Hemoglobin SD Disease (Hb S/D–Los Angeles). | 584 | ||
Hb S/O Arab. | 584 | ||
Other Compound Heterozygosities with Hb S. | 584 | ||
Other Common β-Chain Variants | 584 | ||
Hb C Trait (β6 glu→lys). | 584 | ||
Hb C Disease. | 585 | ||
Hb C/β+-Thalassemia. | 585 | ||
Hb C/β0-Thalassemia. | 585 | ||
Hb E (β 26 glu→lys). | 585 | ||
Hb E Trait (Hb AE). | 585 | ||
Hemoglobin E Disease. | 585 | ||
Hb E/β-Thalassemia. | 585 | ||
Hb D Los Angeles (Punjab) (β121 glu→gln). | 585 | ||
Common α-Chain Variants | 585 | ||
Hb G Philadelphia (α 68asn→lys). | 585 | ||
Disorders of Hemoglobin Function and Stability | 586 | ||
Hemoglobins Associated with High Oxygen Affinity and Polycythemia | 586 | ||
Hemoglobins Associated with Low Oxygen Affinity | 586 | ||
M Hemoglobins: Pseudocyanosis | 586 | ||
Unstable Hemoglobins | 586 | ||
Heat Instability Test. | 586 | ||
Isopropanol Precipitation Test. | 586 | ||
Thalassemias | 586 | ||
Molecular Defects | 587 | ||
β-Thalassemias | 587 | ||
Homozygous β-Thalassemia (Thalassemia Major; Cooley’s Anemia) | 587 | ||
Heterozygous β-Thalassemia (β-Thalassemia Trait; Thalassemia Minor; Cooley’s Trait) | 588 | ||
β-Thalassemia Trait with Normal Hb A2 | 589 | ||
δβ0-Thalassemia | 589 | ||
δβ+-Thalassemia: Lepore Hemoglobins | 589 | ||
Hereditary Persistence of Fetal Hemoglobin | 589 | ||
Deletional Pancellular HPFH | 589 | ||
Hb Kenya | 589 | ||
Nondeletional Pancellular HPFH | 589 | ||
Heterocellular or Swiss-type HPFH | 589 | ||
α-Thalassemias | 590 | ||
α-Thalassemia Syndromes | 590 | ||
Hemoglobin Bart’s Hydrops Fetalis (− −/− −). | 590 | ||
Hemoglobin H Disease (−α/− −). | 590 | ||
Hemoglobin H preparation. | 590 | ||
α-Thalassemia Trait: Heterozygous α0-Thalassemia (− −/αα) or Homozygous α+-Thalassemia (−α/−α). | 590 | ||
Silent Carrier α-Thalassemia (Heterozygous α+-Thalassemia) (αα/−α). | 591 | ||
Hemoglobin Constant Spring (αCSα/). | 591 | ||
Screening and Prenatal Diagnosis of Hemoglobin Disorders | 591 | ||
Hemolysis—Metabolic Disorders | 591 | ||
Erythrocyte Metabolism | 591 | ||
Glucose-6-Phosphate Dehydrogenase Deficiency | 591 | ||
Heinz Bodies | 593 | ||
Ascorbate Cyanide Test | 593 | ||
Fluorescent Spot Test | 593 | ||
Quantitative Assay of G6PD. | 593 | ||
Pyruvate Kinase (PK) Deficiency | 593 | ||
Fluorescent Spot Test. | 594 | ||
Quantitative Assay of PK. | 594 | ||
Other Glycolytic Enzyme Deficiencies | 594 | ||
Pyrimidine-5′-Nucleotidase Deficiency | 594 | ||
Hemolysis—Acquired; Extrinsic | 594 | ||
Chemical Agents | 594 | ||
Agents Hemolytic to Normal Cells | 594 | ||
Agents Hemolytic to Abnormal Cells | 594 | ||
Physical Agents | 594 | ||
Heat | 594 | ||
Traumatic Hemolysis | 594 | ||
Macroangiopathic Hemolytic Anemia (Cardiac Valvular Disease and Prostheses). | 594 | ||
Thrombotic Microangiopathy (Microangiopathic Hemolytic Anemia). | 595 | ||
Hemolytic-Uremic Syndrome | 595 | ||
Thrombotic Thrombocytopenic Purpura (TTP) | 595 | ||
Preeclampsia/Eclampsia | 595 | ||
Infectious Agents | 595 | ||
Immune Hemolytic Anemias | 596 | ||
Autoimmune Hemolytic Anemia | 596 | ||
Etiology and Pathophysiology. | 596 | ||
AIHA Associated with Warm Antibody. | 596 | ||
AIHA Associated with Cold Antibody. | 597 | ||
Cold Agglutinin Disease | 597 | ||
Paroxysmal Cold Hemoglobinuria | 597 | ||
AIHA Associated with Warm and Cold Antibodies | 597 | ||
Alloimmune Hemolytic Disease of the Newborn | 597 | ||
Drug-Induced Immune Hemolytic Anemia | 598 | ||
Formation of Ternary Complexes (Neoantigen Formation). | 598 | ||
Adsorption of Drug to Red Cell Membrane. | 598 | ||
Induction of Autoantibody by Drugs. | 598 | ||
Nonimmunologic Adsorption of Immunoglobulins to Red Cell Membrane. | 598 | ||
Laboratory Investigations of Anemia | 599 | ||
Macrocytic Anemia (Increased MCV) | 599 | ||
Megaloblastic Marrow | 599 | ||
Nonmegaloblastic Marrow | 599 | ||
Microcytic and Hypochromic Anemias (Decreased MCV and MCH) | 599 | ||
Normocytic and Normochromic Anemias (Normal MCV) | 600 | ||
Optimal Marrow Response: Reticulocyte Production Index Greater Than Two | 600 | ||
Direct Antiglobulin (Coombs’) Test. | 600 | ||
Inadequate Marrow Response: Reticulocyte Production Index Less Than Two | 600 | ||
Polycythemia | 600 | ||
Relative Polycythemia | 601 | ||
Absolute Polycythemia | 601 | ||
Appropriately Increased Erythropoietin Production Due to Hypoxia | 601 | ||
Arterial Oxygen Unsaturation | 601 | ||
High Oxygen Affinity Hemoglobinopathy | 601 | ||
Inappropriate Erythropoietin Production | 601 | ||
Neoplasms | 601 | ||
Renal Disorders | 601 | ||
Familial Polycythemia | 601 | ||
Polycythemia Vera | 601 | ||
Measurement of Erythrocyte and Plasma Volume | 601 | ||
Erythrocyte Volume | 601 | ||
Plasma Volume | 602 | ||
Interpretation | 602 | ||
The Porphyrias | 602 | ||
Physiology | 602 | ||
Approach to the Porphyrias | 602 | ||
Clinical Porphyrias and Their Biochemical Basis | 602 | ||
Neurovisceral Symptoms in Isolation | 602 | ||
Acute Intermittent Porphyria (AIP) | 602 | ||
Aminolevulinic Acid Dehydratase Deficiency Porphyria (ADP) | 604 | ||
Neurovisceral Symptoms Plus Photosensitivity | 604 | ||
Variegate Porphyria (VP) | 604 | ||
Hereditary Coproporphyria (HCP) | 604 | ||
Photosensitivity Plus Hemolytic Anemia | 604 | ||
Porphyria Cutanea Tarda (PCT) | 604 | ||
Congenital Erythropoietic Porphyria (CEP) | 604 | ||
Photosensitivity in Isolation | 604 | ||
Erythropoietic Protoporphyria (EPP) and X-linked Porphyria (XLP) | 604 | ||
Analytic Techniques | 605 | ||
References | 605 | ||
Selected References | 605 | ||
References | 605.e1 | ||
33 Leukocytic Disorders | 606 | ||
Key Points | 606 | ||
Leukocytes | 606 | ||
Nonneoplastic Disorders | 606 | ||
Granulocytic and Monocytic Disorders | 606 | ||
Neutrophilia | 606 | ||
Mechanisms | 606 | ||
Determinants | 607 | ||
Neutropenia | 607 | ||
Morphologic Alterations in Neutrophils | 608 | ||
Toxic Granulation | 608 | ||
Döhle Inclusion Bodies | 608 | ||
May-Hegglin Anomaly | 608 | ||
Alder-Reilly Anomaly | 609 | ||
Pelger-Huët Anomaly | 610 | ||
Chédiak-Higashi Syndrome | 610 | ||
Functional Disorders of Neutrophils | 610 | ||
Leukocyte Adhesion Deficiency (LAD) Diseases | 610 | ||
Eosinophilia | 611 | ||
Basophilia | 611 | ||
Monocytosis | 611 | ||
Monocytopenia | 612 | ||
Lymphocytic and Plasmacytic Disorders | 612 | ||
Lymphocytes in Normal Individuals | 612 | ||
Lymphocytosis | 612 | ||
Lymphocytosis Associated with Viral Infection | 612 | ||
Pertussis | 612 | ||
Chronic Lymphocytosis/Persistent Polyclonal B Cell Lymphocytosis | 612 | ||
Retrovirus-Associated Diseases and Conditions | 613 | ||
Infectious Mononucleosis and Epstein-Barr Virus Infection | 613 | ||
Etiology and Pathophysiology. | 613 | ||
Clinical Features. | 614 | ||
Complications. | 614 | ||
Hematologic Features. | 614 | ||
Serologic Findings in Immunocompetent Patients. | 614 | ||
Differential Diagnosis. | 614 | ||
Course. | 614 | ||
Cytomegalovirus Infection | 614 | ||
Toxoplasmosis | 614 | ||
Autoimmune Lymphoproliferative Syndrome | 615 | ||
Other Nonneoplastic Causes of Lymphadenopathy | 615 | ||
Lymphocytopenia | 615 | ||
Acquired Immunodeficiency Syndrome | 615 | ||
Etiology. | 615 | ||
Hematologic Features. | 615 | ||
Plasmacytosis | 615 | ||
Leukemoid Reactions | 616 | ||
Congenital Neutrophilia. | 616 | ||
Neutrophilic Leukemoid Reactions. | 616 | ||
Eosinophilic Leukemoid Reactions. | 616 | ||
Leukoerythroblastosis. | 616 | ||
Lymphocytic Leukemoid Reactions. | 616 | ||
Neoplastic Disorders Primarily Involving Leukocytes | 616 | ||
Overview of Hematopoietic Neoplasms | 616 | ||
Chronic Myeloproliferative Disorders | 617 | ||
Chronic Myelogenous Leukemia | 617 | ||
Clinical Features | 617 | ||
Laboratory Features | 617 | ||
Blood. | 617 | ||
5 Hemostasis and Thrombosis | 793 | ||
39 Coagulation and Fibrinolysis | 794 | ||
Key Points | 794 | ||
Overview of Coagulation and Fibrinolysis | 794 | ||
Physiologic Hemostasis | 795 | ||
Endothelium and Platelets | 795 | ||
Coagulation Protein System | 796 | ||
Characterization of Coagulation Proteins | 796 | ||
Physiologic Protein Assemblies | 796 | ||
The Formation of Fibrin and the Fibrinolytic System | 797 | ||
The Anticoagulation Protein Systems | 798 | ||
Protein C/Protein S System | 798 | ||
Antithrombin | 799 | ||
Tissue Factor Pathway Inhibitor | 799 | ||
Prostacyclins and Nitric Oxide and Thrombospondin-5 | 799 | ||
Current Hypothesis for Initiation of the Hemostatic System | 799 | ||
Clinical Laboratory Hemostasis | 800 | ||
Physiologic Hemostasis Versus Clinical Assays | 800 | ||
Screening Tests for Coagulation Disorders | 800 | ||
Activated Partial Thromboplastin Time | 800 | ||
Prothrombin Time | 801 | ||
Thrombin Time | 801 | ||
Assays Used in Clinical Coagulation Testing | 801 | ||
Practical Approach to Patients with Coagulation Disorders | 801 | ||
Global Hemostasis Assays | 804 | ||
Thrombin Generation | 804 | ||
Overall Hemostasis Potential | 804 | ||
Hereditary Coagulation Protein Defects | 804 | ||
Deficiency of Factor VIII (Hemophilia a) or Factor IX (Hemophilia B) | 804 | ||
Evaluation of Carriers | 805 | ||
Treatment of Hemophilia | 805 | ||
Complications of Treatment | 806 | ||
Hereditary Deficiencies of Other Coagulation Factors | 806 | ||
Disorders with Prolonged APTT and Normal PT | 807 | ||
Factor XI | 807 | ||
FXII, Prekallikrein, and High Molecular Weight Kininogen | 807 | ||
Disorders with Prolonged APTT and PT | 807 | ||
Disorders of Fibrinogen | 807 | ||
FII Deficiency | 808 | ||
FV Deficiency | 808 | ||
FX Deficiency | 808 | ||
Combined Deficiency of FV and FVIII | 808 | ||
Combined Deficiency of Vitamin K–Dependent Clotting Factors | 808 | ||
Disorders with Normal APTT and Prolonged PT | 809 | ||
FVII Deficiency | 809 | ||
Disorders with Normal APTT and PT | 809 | ||
FXIII Deficiency | 809 | ||
Hereditary Hemorrhagic Disorders of Fibrinolysis | 809 | ||
Acquired Coagulation Disorders | 809 | ||
Thrombotic Disorders and Disseminated Intravascular Coagulation | 809 | ||
Liver Disease | 810 | ||
Vitamin K Deficiency | 810 | ||
Massive Transfusion | 810 | ||
Acquired Coagulation Protein Inhibitors and Lupus Anticoagulant | 810 | ||
References | 811 | ||
Selected References | 811 | ||
References | 811.e1 | ||
40 Platelet Disorders and von Willebrand Disease | 812 | ||
Key Points | 812 | ||
Normal Platelet Biology | 812 | ||
Platelet Structure | 812 | ||
Platelet Membrane Glycoproteins and Phospholipids | 813 | ||
Role of Platelets in Hemostasis and Platelet-Activation Mechanisms | 813 | ||
Platelet Activation and Signaling Events (see Fig. 40-2) | 813 | ||
Platelet Coagulant Activity | 814 | ||
Laboratory Evaluation of Platelet Function Disorders | 814 | ||
Initial Laboratory Evaluation | 814 | ||
Studies of Platelet Function | 814 | ||
Bleeding Time | 814 | ||
PFA-100/200 | 816 | ||
Platelet Aggregation and Secretion Studies | 816 | ||
Evaluation of Platelet Function Using Flow Cytometry | 816 | ||
Quantitative Platelet Disorders | 816 | ||
Thrombocytopenia | 816 | ||
Congenital Thrombocytopenias | 817 | ||
Autosomal Dominant Thrombocytopenias | 817 | ||
Autosomal Recessive Thrombocytopenias | 819 | ||
Sex-Linked Inherited Thrombocytopenias | 819 | ||
Immune Thrombocytopenias | 819 | ||
Drug-Induced Immune Thrombocytopenia (DITP) | 820 | ||
Thrombocytosis | 821 | ||
Inherited Disorders of Platelet Function | 821 | ||
Overview | 821 | ||
Disorders of Platelet Adhesion | 822 | ||
Bernard-Soulier Syndrome | 822 | ||
Disorders of Platelet Aggregation | 823 | ||
Glanzmann Thrombasthenia | 823 | ||
Disorders of Platelet Secretion and Granules | 823 | ||
Deficiency of Granule Stores | 823 | ||
δ-Storage Pool Deficiency | 823 | ||
Gray Platelet Syndrome | 824 | ||
Quebec Platelet Syndrome | 824 | ||
Disorders of Platelet Secretion and Signaling Pathways | 824 | ||
Defects in Receptors | 824 | ||
Defects in G-Proteins and Their Activation | 824 | ||
Defects in Phospholipase C Activation, Calcium Mobilization, and Protein Phosphorylation | 825 | ||
Abnormalities in Arachidonic Acid Metabolism and Thromboxane Synthesis | 825 | ||
Defects in Cytoskeletal Linking Proteins | 825 | ||
Wiskott-Aldrich Syndrome | 825 | ||
Kindlin-3 Deficiency–Leukocyte Adhesion Deficiency | 825 | ||
Disorders of Platelet Procoagulant Activities: Scott Syndrome | 825 | ||
Transcription Factor Mutations and Associated Platelet Dysfunction | 825 | ||
RUNX1/CBFA2 Mutations (Familial Platelet Disorder with Predisposition to Acute Myelogenous Leukemia) | 825 | ||
GATA-1 Mutations | 825 | ||
FLI1 | 825 | ||
GFI1B | 826 | ||
Relative Frequencies of Various Inherited Platelet Disorders | 826 | ||
Evaluation of Patients with Suspected Congenital Platelet Disorders | 826 | ||
Therapy of Congenital Platelet Function Defects | 826 | ||
Acquired Disorders of Platelet Function | 826 | ||
Myeloproliferative Neoplasms | 826 | ||
Acute Leukemias and Myelodysplastic Syndromes | 827 | ||
Dysproteinemias | 827 | ||
Uremia | 827 | ||
Acquired Storage Pool Disease | 827 | ||
Antiplatelet Antibodies and Platelet Function | 828 | ||
Drugs That Inhibit Platelet Function | 828 | ||
Von Willebrand Factor, von Willebrand Disease, and Thrombotic Thrombocytopenic Purpura | 829 | ||
Von Willebrand Factor Biology | 829 | ||
Laboratory Tests for von Willebrand Factor | 830 | ||
Von Willebrand Disease | 830 | ||
Type 1 vWD: Partial Quantitative Abnormality | 830 | ||
Type 3 vWD: Severe Quantitative Abnormality | 831 | ||
Qualitative Abnormalities: Type 2A, Type 2B, Type 2M, and Type 2N vWD | 831 | ||
Type 2A | 831 | ||
Type 2B | 831 | ||
Type 2M | 831 | ||
Type 2N (Normandy) | 831 | ||
Platelet-Type vWD | 831 | ||
Acquired von Willebrand Syndrome | 831 | ||
Thrombotic Thrombocytopenic Purpura | 832 | ||
References | 833 | ||
Selected References | 833 | ||
References | 833.e1 | ||
41 Laboratory Approach to Thrombotic Risk | 834 | ||
Key Points | 834 | ||
Endogenous Anticoagulant Pathways | 834 | ||
Thrombophilic Proteins or Factors | 835 | ||
Antithrombin | 835 | ||
Protein C | 837 | ||
Protein S | 837 | ||
Activated Protein C Resistance and Factor VLeiden | 838 | ||
Prothrombin g20210a | 838 | ||
Elevation of Other Coagulation Factor Levels | 838 | ||
Tissue Factor Pathway Inhibitor | 838 | ||
Dysfibrinogenemia | 839 | ||
Annexin A5 | 839 | ||
Hypofibrinolytic Mechanisms | 839 | ||
Acquired Hypercoagulable States | 839 | ||
Antiphospholipid Syndrome and Lupus Anticoagulant | 839 | ||
Other Coagulation Abnormalities | 840 | ||
Hyperhomocysteinemia | 841 | ||
General Aspects of the Laboratory Evaluation for Thrombotic Risk | 841 | ||
References | 841 | ||
Selected References | 841 | ||
References | 841.e1 | ||
42 Antithrombotic Therapy | 842 | ||
Key Points | 842 | ||
Vitamin K Antagonists | 842 | ||
Antithrombin-Dependent Parenteral Anticoagulants | 845 | ||
Unfractionated Heparin | 845 | ||
Heparin Resistance | 846 | ||
Low Molecular Weight Heparin | 846 | ||
Fondaparinux | 846 | ||
Heparin-Induced Thrombocytopenia | 846 | ||
Target-Specific Anticoagulants | 849 | ||
Parenteral Agents | 849 | ||
Oral Agents | 849 | ||
Antiplatelet Therapy | 851 | ||
Aspirin | 851 | ||
P2Y12 Inhibitors | 852 | ||
Glycoprotein IIb/IIIa Inhibitors | 853 | ||
References | 853 | ||
Selected References | 853 | ||
References | 853.e1 | ||
6 Immunology and Immunopathology | 855 | ||
43 Overview of the Immune System and Immunologic Disorders | 856 | ||
Key Points | 856 | ||
Lymphoid Cells | 856 | ||
T Lymphocytes | 856 | ||
B Lymphocytes | 857 | ||
Antigen-Presenting Cells | 857 | ||
Natural Killer Cells | 857 | ||
Nonlymphoid Cells | 857 | ||
Neutrophils and Eosinophils | 857 | ||
Basophils and Mast Cells | 857 | ||
Humoral Factors | 857 | ||
Immunoglobulins | 857 | ||
Complement | 858 | ||
Cytokines | 858 | ||
Histocompatibility Antigens | 858 | ||
Mechanisms of Immunologic Injury | 859 | ||
Laboratory Applications of Immunologic Assessment | 859 | ||
Therapeutics in Immunology | 860 | ||
References | 861 | ||
Selected References | 861 | ||
References | 861.e1 | ||
44 Immunoassays and Immunochemistry | 862 | ||
Immunoassays and Immunochemistry | 862 | ||
General Characteristics of Antigen–Antibody Reaction | 862 | ||
Characteristics of Antigens | 863 | ||
Characteristics of Antibodies | 863 | ||
Polyclonal Antibodies | 863 | ||
Monoclonal Antibodies | 863 | ||
Antibody Production by Recombinant Technology | 863 | ||
Kinetics of Antigen–Antibody Reaction | 863 | ||
Overview of General Principles of Immunoassays | 863 | ||
Classes of Immunoassays | 863 | ||
Conjugation Chemistry | 864 | ||
Characteristics of the Solid Phase | 864 | ||
Precipitin and Nephelometric Immunoassays | 865 | ||
Background and Principles of Precipitin Reaction | 865 | ||
Nephelometric Immunoassays | 866 | ||
Particle Immunoassay | 866 | ||
Principle of Particle Agglutination | 866 | ||
Hemagglutination | 866 | ||
Gelatin Particle Agglutination | 868 | ||
Latex Agglutination | 868 | ||
Latex Turbidimetric Assay | 868 | ||
Particle-Counting Immunoassay | 868 | ||
Other Particle Immunoassays | 868 | ||
Summary | 868 | ||
Radioimmunoassay | 870 | ||
Background | 870 | ||
Assay Principles and Methods | 870 | ||
Summary | 872 | ||
Enzyme Immunoassay | 872 | ||
Background and Classification | 872 | ||
Heterogeneous Enzyme Immunoassays | 872 | ||
Colorimetric Enzyme Immunoassay | 873 | ||
Fluorescent Enzyme Immunoassay | 873 | ||
Chemiluminescent Enzyme Immunoassay | 873 | ||
Homogeneous Enzyme Immunoassays | 874 | ||
Background | 874 | ||
Enzyme-Multiplied Immunoassay Technique | 874 | ||
Substrate-Labeled Fluorescent Immunoassay | 875 | ||
Apoenzyme Reactivation Immunoassay | 875 | ||
Enzyme Inhibitory Homogeneous Immunoassay | 875 | ||
Cloned Enzyme Donor Immunoassay | 877 | ||
Summary | 878 | ||
Fluorescent Immunoassay | 878 | ||
Background and Classification | 878 | ||
Heterogeneous Fluorescent Immunoassay | 878 | ||
Fluoroimmunometric Method | 878 | ||
Radial Partition Immunofluorometric Assay | 879 | ||
Time-Resolved Fluoroimmunoassay | 879 | ||
Homogeneous Fluorescent Immunoassay | 879 | ||
Fluorescence Polarization Assay | 879 | ||
Fluorescence Excitation Transfer Immunoassay | 880 | ||
Fluorescent Protection Immunoassay | 880 | ||
Chemiluminescent Immunoassay | 880 | ||
Background | 880 | ||
Chemiluminescent Immunoassay Using Acridinium Esters as Labels | 880 | ||
Electrochemiluminescent Immunoassay | 880 | ||
Noncompetitive Immunoassay for Small Molecules | 881 | ||
Background | 881 | ||
Anti-Idiotype Antibody-Based Immunoassay | 881 | ||
Open-Sandwich Immunoassay | 882 | ||
Antimetatype Antibody–Based Immunoassay | 882 | ||
Sensitive Immunoassay Using Specimen-Pretreatment Methods | 882 | ||
Background | 882 | ||
Highly Sensitive Immunoassay for Viral Antigen Using Specimen-Pretreatment Method | 882 | ||
Instrument Automation and Modulation of Assay Systems | 883 | ||
Homogeneous Assay Systems | 883 | ||
Heterogeneous Immunoassay Systems | 883 | ||
Practical Flow of the Immunoassay in the Analytic System | 883 | ||
Instrumentation and Key Points for Heterogeneous Immunoassay | 884 | ||
Reaction Cuvette | 884 | ||
Sampling and Fluid Delivery Type | 884 | ||
Carryover | 884 | ||
Bound/Fixed Separation and Washing Systems | 884 | ||
High-Throughput Fully Automated Heterogeneous Immunoassay Systems | 884 | ||
Remote Maintenance | 885 | ||
Rapid and Simple Test Devices for Point-of-Care Testing | 885 | ||
Background | 885 | ||
Immunochromatographic Devices | 885 | ||
Magnetic Biosensor Assay | 886 | ||
Summary | 887 | ||
Simultaneous Multiple Immunoassays | 887 | ||
Background | 887 | ||
Microspot Assay | 887 | ||
Multianalyte Microarray Immunoassay | 887 | ||
Flow Cytometric Immunoassay | 887 | ||
Microchannel Assay Using Compact Discs | 888 | ||
7 Medical Microbiology | 1071 | ||
56 Viral Infections | 1072 | ||
Key Points | 1072 | ||
Introduction | 1072 | ||
Cell Culture | 1074 | ||
Antigen Detection | 1074 | ||
Nucleic Acid Amplification Testing (NAAT) | 1074 | ||
Viral Serology | 1076 | ||
Clinical Viral Infectious Syndromes | 1076 | ||
Herpetic Mucocutaneous Infections | 1077 | ||
Specimen Collection and Handling Guidelines | 1078 | ||
Cell Culture Isolation of Herpes Simplex Virus | 1078 | ||
Direct Detection of Herpes Simplex Virus | 1079 | ||
Nucleic Acid–Based Detection of Herpes Simplex | 1079 | ||
Serologic Diagnosis | 1079 | ||
Pediatric and Adult Viral Respiratory Syndromes | 1079 | ||
Influenza | 1081 | ||
Bronchiolitis | 1081 | ||
Croup | 1081 | ||
Metapneumovirus | 1082 | ||
Adenovirus | 1082 | ||
Coronavirus | 1083 | ||
Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) | 1083 | ||
Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) | 1083 | ||
Bocaviruses | 1083 | ||
Rhinoviruses (HRV) | 1083 | ||
Specimen Collection | 1083 | ||
Virus Antigen Assays | 1083 | ||
Virus Isolation | 1084 | ||
Molecular Detection Methods | 1084 | ||
Infectious Mononucleosis and Related Infections | 1084 | ||
Diagnosis of Infectious Mononucleosis | 1084 | ||
Heterophile-Negative Infectious Mononucleosis | 1085 | ||
Chronic Fatigue Syndrome | 1085 | ||
Congenital and Perinatal Viral Infections | 1085 | ||
Cytomegalovirus | 1086 | ||
Rubella | 1087 | ||
Herpes Simplex Virus | 1087 | ||
Human Immunodeficiency Virus, Parvovirus, Enterovirus, and Hepatitis B Virus | 1087 | ||
Viral Meningitis and Encephalitis | 1088 | ||
Laboratory Diagnosis | 1089 | ||
Viral Exanthems and Common Cutaneous Infections | 1090 | ||
Viral Gastroenteritis | 1091 | ||
Laboratory Diagnosis | 1092 | ||
Viral Hepatitis | 1092 | ||
Hepatitis A Virus (HAV) | 1092 | ||
Hepatitis E Virus (HEV) | 1092 | ||
Hepatitis B Virus (HBV) | 1092 | ||
Hepatitis C Virus (HCV) | 1093 | ||
Acquired Immunodeficiency Syndrome | 1093 | ||
Virus-Associated Neoplasia | 1097 | ||
Human Papilloma Viruses (HPV) | 1097 | ||
Emerging Infections | 1097 | ||
Ebola Viral Disease (EVD) | 1097 | ||
References | 1097 | ||
Selected References | 1098 | ||
Websites and E-Mail Addresses | 1098 | ||
References | 1098.e1 | ||
57 Chlamydial, Rickettsial, and Mycoplasmal Infections | 1099 | ||
Key Points | 1099 | ||
Chlamydial Infections | 1099 | ||
Structure | 1099 | ||
Replication | 1099 | ||
Chlamydia trachomatis | 1100 | ||
Epidemiology, Pathology, and Clinical Manifestations | 1100 | ||
Chlamydophila (Formerly Chlamydia) psittaci | 1101 | ||
8 Molecular Pathology | 1299 | ||
65 Introduction to Molecular Pathology | 1300 | ||
Key Points | 1300 | ||
The Molecular Biology Revolution and Its Impact on the Practice of Pathology | 1300 | ||
Discussion of Diagnostic Molecular Pathology | 1300 | ||
Application of Molecular Pathology to Detection of Cancer | 1301 | ||
Implications of Molecular Diagnostics on the Practice of Pathology and Medicine | 1301 | ||
Redefining Disease | 1301 | ||
Use of Molecular Biology in the Treatment of Disease | 1301 | ||
Data Analysis | 1301 | ||
Quality Assurance | 1302 | ||
Some Caveats | 1302 | ||
References | 1302 | ||
Selected References | 1302 | ||
References | 1302.e1 | ||
66 Molecular Diagnostics | 1303 | ||
Key Points | 1303 | ||
Nucleic Acid Biochemistry and Biology | 1303 | ||
Molecular Composition and Structure | 1303 | ||
Nucleic Acid–Associated Enzymes | 1305 | ||
Replication of DNA | 1305 | ||
Transcription of DNA to RNA | 1306 | ||
Posttranscriptional Modification | 1306 | ||
Translation of RNA to Protein | 1306 | ||
Transcriptional Control | 1306 | ||
Gene Regulation Mediated by Small RNA | 1307 | ||
Epigenetics and Gene Regulation | 1307 | ||
Mechanisms of DNA Repair | 1307 | ||
DNA Mutations | 1308 | ||
Nucleic Acid Analyses | 1308 | ||
Electrophoretic Separation | 1309 | ||
Nucleic Acid Hybridization | 1309 | ||
Hybridization Assays: Basic Components | 1309 | ||
Probe | 1310 | ||
Sample | 1311 | ||
Controlled Conditions Permissive for Complementary Base Pairing | 1311 | ||
Detection of Hybrids | 1311 | ||
Hybridization Assay Formats | 1311 | ||
Liquid or Solution Phase Hybridization | 1311 | ||
Solid-Support Hybridization | 1312 | ||
Dot or Linear Array Hybridization | 1312 | ||
Southern and Northern Hybridizations | 1312 | ||
Microarray Hybridization (“DNA Chip Technology” or “Bead Arrays”) | 1312 | ||
In Situ Hybridization | 1312 | ||
Amplification Methods | 1313 | ||
Polymorphism Detection Assays | 1313 | ||
DNA Sequencing | 1313 | ||
Relationship to Laboratory Evaluation of Disease | 1313 | ||
Molecular Diagnosis | 1313 | ||
Beyond Diagnosis | 1314 | ||
References | 1314 | ||
Selected References | 1315 | ||
References | 1315.e1 | ||
67 Polymerase Chain Reaction and Other Nucleic Acid Amplification Technology | 1316 | ||
Key Points | 1316 | ||
Target Amplification Methods | 1316 | ||
Polymerase Chain Reaction | 1316 | ||
Reverse-Transcriptase Polymerase Chain Reaction | 1316 | ||
Nested Polymerase Chain Reaction | 1317 | ||
Multiplex Polymerase Chain Reaction | 1317 | ||
End-Point Quantitative Polymerase Chain Reaction | 1318 | ||
Real-Time (Homogeneous, Kinetic) Polymerase Chain Reaction | 1319 | ||
Rapid-Cycle Polymerase Chain Reaction | 1321 | ||
Digital Polymerase Chain Reaction | 1321 | ||
Transcription-Based Amplification | 1321 | ||
Strand-Displacement Amplification | 1322 | ||
Loop-Mediated Amplification | 1323 | ||
Helicase-Dependent Amplification | 1324 | ||
Nicking Endonuclease Amplification | 1324 | ||
Probe Amplification Methods | 1324 | ||
Cleavase/Invader Technology | 1324 | ||
Signal Amplification Methods | 1324 | ||
Branched DNA | 1326 | ||
Hybrid Capture Assays | 1326 | ||
Summary | 1326 | ||
References | 1326 | ||
Selected References | 1326 | ||
References | 1327.e1 | ||
68 Hybridization Array Technologies | 1328 | ||
Key Points | 1328 | ||
Array Technologies | 1328 | ||
Macroarrays | 1329 | ||
Microarrays | 1329 | ||
Microarray Substrates | 1329 | ||
Microarray Fabrication | 1329 | ||
Delivery Technologies | 1329 | ||
In Situ Synthesis | 1330 | ||
Oligonucleotide Microarrays | 1330 | ||
CDNA Microarrays | 1331 | ||
Sequencing Arrays | 1331 | ||
Hybrid Capture | 1331 | ||
Reverse Line-Blot Hybridization | 1332 | ||
Hybridization, Detection, and Image Analysis | 1332 | ||
Bioinformatics | 1333 | ||
Intellectual Property Issues | 1334 | ||
Clinical Applications of Array Technology | 1335 | ||
Array Technology in the Clinical Laboratory | 1335 | ||
Array Technology in Clinical Disease | 1335 | ||
Limitations | 1335 | ||
References | 1336 | ||
Selected References | 1336 | ||
References | 1336.e1 | ||
69 Applications of Cytogenetics in Modern Pathology | 1337 | ||
Key Points | 1337 | ||
Definitions | 1337 | ||
Cytogenetics | 1338 | ||
Chromosomes | 1338 | ||
Chromosome Structure | 1338 | ||
Cell Culture | 1338 | ||
Specimens | 1338 | ||
Cell Culture Technique | 1339 | ||
Staining | 1340 | ||
Karyotype Analysis | 1340 | ||
Computer-Assisted Imaging | 1340 | ||
Fluorescence in Situ Hybridization | 1341 | ||
Technique | 1341 | ||
Multicolor Fluorescence in Situ Hybridization | 1343 | ||
Microarray Technology | 1343 | ||
Chromosome Abnormalities | 1344 | ||
Numerical Abnormalities | 1345 | ||
Euploidy | 1345 | ||
Aneuploidy | 1345 | ||
Structural Chromosome Abnormalities | 1345 | ||
Conclusions | 1349 | ||
Nomenclature | 1349 | ||
Clinical Applications | 1350 | ||
CONSTITUTIONAL CYTOGENICS | 1350 | ||
Prenatal | 1350 | ||
Postnatal | 1351 | ||
Childhood and Adult | 1352 | ||
Cancer Genetics | 1352 | ||
Cytogenetic Disorders | 1353 | ||
Chromosomal Aneuploidy Syndromes | 1353 | ||
Autosomal Aneuploidies | 1353 | ||
Sex Chromosome Aneuploidies | 1354 | ||
Other Sex Chromosome Abnormalities | 1356 | ||
Structural Chromosome Anomalies | 1356 | ||
Microdeletion Syndromes and Contiguous Gene Syndromes | 1356 | ||
Other Cytogenetic Phenomena | 1358 | ||
Fragile X Syndrome | 1358 | ||
Breakage Syndromes | 1358 | ||
Summary | 1358 | ||
References | 1358 | ||
Selected References | 1359 | ||
Further Reading | 1359 | ||
References | 1359.e1 | ||
70 Establishing a Molecular Diagnostics Laboratory | 1360 | ||
Key Points | 1360 | ||
Special Considerations for Molecular Diagnostics Laboratories | 1361 | ||
Infectious Disease | 1361 | ||
Cancer | 1361 | ||
Inherited Disorders | 1361 | ||
Regulation and Regulatory Agencies | 1362 | ||
Clinical Laboratory Improvement Acts of 1988 and 2003 | 1362 | ||
Genetic Information Nondiscrimination Act | 1362 | ||
Food and Drug Administration | 1362 | ||
Analyte-Specific Reagents | 1363 | ||
In Vitro Multivariate Index Assay or IVDMIA Draft Guidance | 1363 | ||
Laboratory Design and Requirements | 1363 | ||
Laboratory Design | 1364 | ||
Practices to Aid in Contamination Control | 1364 | ||
Equipment | 1365 | ||
Personnel | 1365 | ||
Laboratory Director | 1365 | ||
Technical Supervisor | 1365 | ||
Medical Technologists and Molecular Biology Technicians | 1365 | ||
Certification of Personnel in Molecular Diagnostics | 1366 | ||
Financial Management | 1366 | ||
Reimbursement for Molecular Diagnostics Tests | 1366 | ||
Patent Issues | 1367 | ||
Laboratory Information System | 1367 | ||
Test Management | 1368 | ||
Menu/Selection | 1368 | ||
Methods | 1368 | ||
Clinical Test Formats | 1368 | ||
Automated Platforms for Molecular Testing | 1369 | ||
Quality Assurance and Quality Control of the Testing Process | 1369 | ||
Quality Assurance | 1369 | ||
Assay Design and Development | 1370 | ||
New Test Verification/Validation | 1371 | ||
Analytical Verification | 1371 | ||
Clinical Verification | 1375 | ||
Quality Control of the Testing Process | 1375 | ||
Quality Control of Equipment | 1375 | ||
Conclusion | 1376 | ||
Selected References | 1376 | ||
References | 1376.e1 | ||
71 Molecular Diagnosis of Genetic Diseases | 1377 | ||
Key Points | 1377 | ||
Choice of Techniques | 1378 | ||
Choice of Applications | 1379 | ||
Special Concepts Unique to Molecular Genetic Disorders | 1381 | ||
Molecular Heterogeneity | 1381 | ||
Variable Penetrance and Expressivity | 1381 | ||
Uniparental Disomy | 1381 | ||
Imprinting | 1381 | ||
Anticipation | 1381 | ||
Epigenetic Influences and Nonmendelian Inheritance | 1382 | ||
Allele Frequencies and Mass Population Screening | 1382 | ||
Predictive Genetic Testing | 1382 | ||
Specific Disease Examples | 1382 | ||
Cystic Fibrosis | 1382 | ||
Duchenne Muscular Dystrophy | 1383 | ||
Sickle Cell Anemia and Other Hemoglobinopathies | 1384 | ||
Hereditary Thrombophilias | 1384 | ||
Trinucleotide Repeat Expansion Disorders | 1385 | ||
Fragile XA and Fragile XE Syndromes | 1385 | ||
Neurodegenerative Disorders: Huntington Disease, X-linked Spinal and Bulbar Muscular Atrophy, Spinocerebellar Ataxias, and Dentatorubral-Pallidoluysian Atrophy | 1386 | ||
Myotonic Dystrophy | 1386 | ||
Friedreich Ataxia | 1386 | ||
Laboratory Testing for Trinucleotide Repeat Disorders | 1388 | ||
Prader-Willi and Angelman Syndromes | 1388 | ||
Familial Cancers | 1388 | ||
Tumor Suppressor Genes: Retinoblastoma as a Paradigm | 1389 | ||
Oncogenes: Multiple Endocrine Neoplasia Type 2 as a Paradigm | 1390 | ||
Hereditary Breast-Ovarian Cancer | 1390 | ||
The Hereditary Colorectal Cancer Syndromes | 1390 | ||
Hereditary Nonpolyposis Colorectal Cancer | 1390 | ||
Familial Adenomatous Polyposis and Attenuated Familial Adenomatous Polyposis | 1391 | ||
MYH-Associated Polyposis | 1391 | ||
Laboratory Testing for Familial Cancer Mutations | 1391 | ||
Hemochromatosis | 1391 | ||
Spinal Muscular Atrophy | 1392 | ||
Mitochondrial DNA Disorders | 1392 | ||
Other Targets of Molecular Genetic Testing and Screening | 1392 | ||
The New Frontier of Diagnostic Molecular Genetics: Genome-Level DNA Sequencing | 1393 | ||
References | 1394 | ||
Selected References | 1394 | ||
References | 1395.e1 | ||
72 Identity Analysis | 1396 | ||
Key Points | 1396 | ||
Historical Background | 1396 | ||
Advantages of DNA | 1397 | ||
Genetic Markers | 1397 | ||
Samples and Specimen Collection | 1397 | ||
DNA Extraction and Quantification | 1398 | ||
Test Methods and Marker Systems | 1398 | ||
Short Tandem Repeats | 1398 | ||
X and Y Chromosome Markers | 1400 | ||
Mitochondrial DNA Sequencing | 1400 | ||
Other Systems | 1400 | ||
Analysis and Use of Test Data | 1401 | ||
DNA in the Crime Laboratory | 1401 | ||
DNA in the Pathology Laboratory | 1401 | ||
Exclusion of Parentage | 1401 | ||
Probability of Exclusion | 1402 | ||
Combined Probability of Exclusion | 1403 | ||
Inclusion of Parentage | 1403 | ||
Paternity Index Calculation | 1403 | ||
Likelihood of Parentage | 1404 | ||
Estimating Parentage with an Absent Parent | 1404 | ||
Reconstruction of Families | 1405 | ||
Software Systems | 1405 | ||
Quality Assurance Standards | 1405 | ||
Conclusion | 1405 | ||
References | 1406 | ||
Selected References | 1406 | ||
References | 1406.e1 | ||
73 Pharmacogenomics and Personalized Medicine | 1407 | ||
Key Points | 1407 | ||
Overview | 1407 | ||
Basic Concepts | 1407 | ||
Drug-Metabolizing Enzyme Pharmacogenomics | 1408 | ||
Phase I Enzymes | 1408 | ||
Phase II Enzymes | 1410 | ||
Uridine Diphosphate Glucuronosyltransferases | 1410 | ||
Sulfotransferases | 1412 | ||
Glutathione S-Transferases | 1412 | ||
N-Acetyltransferase | 1412 | ||
Thiopurine S-Methyltransferase | 1412 | ||
Drug-Transporter Pharmacogenomics | 1413 | ||
ATP-Binding Cassette (ABC) Transporters | 1414 | ||
ABCB1 | 1414 | ||
ABCC1 and ABCC2 | 1414 | ||
ABCG2 | 1416 | ||
Solute Carrier Transporters | 1416 | ||
Organic Anion Transporting Polypeptides | 1416 | ||
Organic Cation Transporters (OCTs) | 1417 | ||
Organic Anion Transporters (OATs) | 1418 | ||
Drug Target Pharmacogenomics | 1418 | ||
DNA Repair Genes | 1418 | ||
Thymidylate Synthase | 1418 | ||
Epidermal Growth Factor Receptor | 1419 | ||
Human Leukocyte Antigen Pharmacogenomics | 1423 | ||
Pharmacogenomics in Cancer Chemotherapy | 1424 | ||
5-Fluorouracil | 1424 | ||
Irinotecan | 1425 | ||
Tamoxifen | 1426 | ||
Pharmacogenomics in Other Diseases | 1428 | ||
Diabetes | 1428 | ||
Human Immunodeficiency Virus | 1428 | ||
Osteoporosis | 1429 | ||
Psychiatric and Cognitive Disorders | 1429 | ||
Epigenomics | 1429 | ||
Conclusion | 1430 | ||
References | 1430 | ||
Selected References | 1430 | ||
References | 1430.e1 | ||
9 Molecular Pathology | 1431 | ||
74 Diagnosis and Management of Cancer Using Serologic and Other Body Fluid Markers | 1432 | ||
Key Points | 1432 | ||
Serum Markers as an Effective Tool for Diagnosis and Monitoring of Cancer | 1433 | ||
Functional Classification of Tumor Markers | 1433 | ||
Oncoproteins are Markers for Cell Proliferation | 1434 | ||
Tumor Suppressors/Cell Differentiation | 1434 | ||
Adhesion Molecules and Metastasis | 1434 | ||
Monoclonal Antibody–Defined Tumor Markers | 1434 | ||
Other Markers | 1434 | ||
Clinical Applications | 1435 | ||
Screening | 1435 | ||
Diagnosis | 1435 | ||
Prognosis: Recurrence, Metastasis, and Survival | 1435 | ||
Monitoring Treatment Response | 1436 | ||
Recommendations for Ordering Tumor Marker Tests | 1436 | ||
Individual Tumor Markers | 1438 | ||
α-Fetoprotein | 1438 | ||
Angiogenic Factors | 1438 | ||
β2-Microglobulin | 1438 | ||
Serum Free Light Chain Determinations | 1439 | ||
Carcinoembryonic Antigen | 1440 | ||
CA 15-3 and CA 27.29 | 1440 | ||
CA 19-9, CA 50, and CA 19-5 | 1440 | ||
CA 125 | 1441 | ||
CA 72-4 | 1441 | ||
Calcitonin | 1441 | ||
Chromogranin A | 1441 | ||
Cytokeratin 19 Fragment | 1441 | ||
Human Chorionic Gonadotropin | 1441 | ||
HER2/neu (c-erbB-2) ONCOPROTEIN | 1442 | ||
p53 | 1442 | ||
Parathyroid Hormone–Related Peptide | 1442 | ||
Serum Markers for Prostate Cancer | 1442 | ||
Serum Prostate-Specific Antigen | 1442 | ||
Methods to Improve the Performance of Serum PSA Measurement for the Early Detection of Prostate Cancer | 1443 | ||
Free PSA, Complex PSA, and Percentage of Free PSA | 1443 | ||
proPSA and Prostate Health Index | 1444 | ||
PSA Doubling Time, Velocity, and Density | 1444 | ||
Circulating Tumor Cells in Peripheral Blood | 1444 | ||
Circulating Nucleic Acids in Peripheral Blood | 1445 | ||
Cell-Free Nucleic Acid Testing in Cancer | 1445 | ||
Gene Arrays Detecting Oncoprotein Abnormalities | 1446 | ||
Circulating microRNA | 1446 | ||
Gene Mutations | 1446 | ||
Microsatellite Alterations | 1446 | ||
Promoter Hypermethylation | 1446 | ||
Cell DNA Testing for Cancer Using Fluorescence in Situ Hybridization | 1447 | ||
Markers in Other Body Fluids | 1447 | ||
Urine Markers for Prostate Cancer | 1447 | ||
Urine Prostate Cancer Antigen 3 | 1447 | ||
Urine TMPRSS2:ERG and Mi-Prostate Score | 1447 | ||
Prostarix | 1447 | ||
Urine Hypermethylated Glutathione S-Transferase pi 1 Gene | 1448 | ||
Urine Metabolic Test for Adenomatous Polyps of Colon | 1448 | ||
Fecal Occult Blood Testing and Mutant Protein Markers in Stool | 1448 | ||
Conclusions | 1448 | ||
References | 1448 | ||
Selected References | 1449 | ||
References | 1449.e1 | ||
75 Oncoproteins and Early Tumor Detection | 1450 | ||
Key Points | 1450 | ||
Overview | 1450 | ||
Cell Biology and Mitogenesis | 1450 | ||
Signal Transduction Pathways | 1451 | ||
Oncoproteins in Tumor Detection | 1451 | ||
Growth Factors | 1452 | ||
Transforming Growth Factors α and β | 1452 | ||
Platelet-Derived Growth Factor | 1453 | ||
Basic Fibroblast Growth Factor | 1453 | ||
Epidermal Growth Factor and Hepatocyte Growth Factor | 1453 | ||
Growth Factor Receptors | 1454 | ||
Epidermal Growth Factor Receptor | 1455 | ||
HER2/neu Receptor | 1455 | ||
HER2/neu Detects Pulmonary Neoplasms | 1455 | ||
HER2/neu in the Detection of Hepatocellular Carcinomas | 1455 | ||
p185erbB-2 ECD in Other Tumors | 1455 | ||
E-Cadherin | 1456 | ||
Metalloproteases in Pancreatic Cancer | 1456 | ||
G-Proteins | 1456 | ||
ras-p21 Protein | 1456 | ||
ras-p21 in Lung and Colon Cancer | 1456 | ||
ras-p21 in Angiosarcoma | 1457 | ||
ras-p21 in Pancreatic Cancer | 1457 | ||
Cytosolic Mitogenic Kinases | 1457 | ||
Raf | 1457 | ||
Nuclear Oncoproteins | 1457 | ||
p53 and c-myc Proteins | 1457 | ||
Detection of Malignancies by Assaying for p53 Protein | 1457 | ||
Hepatocellular Carcinoma. | 1457 | ||
Breast and Lung Cancers. | 1457 | ||
Colon Cancer. | 1458 | ||
Bladder Cancer. | 1458 | ||
Leukemia. | 1458 | ||
Circulating Anti-p53 Antibodies in Tumor Detection | 1458 | ||
Negative Regulator of p53, S100, as a Tumor Marker for Malignant Melanoma. | 1458 | ||
Antibodies to p53 Are Present in the Sera of Many Patients with Epithelial Cell Tumors and Lymphomas. | 1458 | ||
Anti-p53 in Ovarian Cancer. | 1458 | ||
Anti-p53 in Hepatocellular Carcinoma. | 1458 | ||
Anti-p53 in Oral and Esophageal Cancers. | 1458 | ||
Anti-p53 in Lung Cancers. | 1458 | ||
Anti-p53 Predicts Cancer Occurrence in Patients with Asbestos Exposure. | 1458 | ||
Anti-p53 in Colorectal Cancer. | 1459 | ||
myc Oncogene–Encoded Protein in Tumor Detection | 1459 | ||
Serum Anti–c-myc Protein Antibodies in Tumor Detection in Breast Cancer, Ovarian Cancer, Leukemias, and Lymphomas | 1459 | ||
Combined Oncogene Marker Proteins for Detection of Colorectal Cancer | 1459 | ||
Nuclear Matrix Proteins and Detection of Bladder Cancer | 1459 | ||
NMP-22 Is an Excellent Biomarker for Bladder and Urothelial Cancers | 1459 | ||
Bladder Tumor Antigen | 1459 | ||
Minichromosome Maintenance Proteins | 1460 | ||
Use of Multiple Oncoprotein Markers in the Diagnosis of Cancer | 1460 | ||
Multiple Oncoprotein Assay in Patients at Risk for Tumor Development in Patients with Pneumoconiosis | 1460 | ||
Oncoprotein Arrays Likewise Hold Promise in Detecting Antioncoprotein Antibodies in Sera | 1460 | ||
Proteomic Approaches to Early Detection of Cancer in Serum | 1460 | ||
Application of the Proteomic Approach to the Diagnosis of Cancers | 1461 | ||
Ovarian Cancer | 1461 | ||
Prostate Cancer | 1461 | ||
Proteomics Show Promise in Early Tumor Detection | 1461 | ||
Protein Arrays for Specific Types of Cancer | 1461 | ||
Squamous Cell Carcinomas of the Head and Neck | 1461 | ||
Breast Cancer | 1461 | ||
Lung Cancer | 1461 | ||
Diagnostic Efficacy of Serum Oncoproteins | 1461 | ||
How Specific Is Oncoprotein Expression for Different Cancer Types? | 1461 | ||
Sensitivities of Oncoprotein Expression | 1463 | ||
Origins of Malignancies | 1463 | ||
Tumor Size and Oncoprotein Levels | 1463 | ||
Evaluation and Conclusions | 1463 | ||
References | 1463 | ||
Selected References | 1463 | ||
References | 1464.e1 | ||
76 Molecular Diagnosis of Hematopoietic Neoplasms | 1465 | ||
Key Points | 1465 | ||
Role of Clinical Molecular Diagnostics in Hematologic Cancers | 1465 | ||
Molecular Diagnosis of Leukemias | 1466 | ||
Gene Fusion Concept in Leukemia and the Basis for Reverse-Transcription Polymerase Chain Reaction Analysis | 1466 | ||
Acute Myeloid Leukemias | 1467 | ||
Acute Promyelocytic Leukemia: t(15;17)(q22;q21)/PML-RARA Abnormality | 1468 | ||
Core Binding Factor–Related Acute Myeloid Leukemias: t(8;21)(q22;q22)/RUNX1-RUNX1T1 and Inv(16)(p13q22) or t(16;16)(p13;q22)/ CBFB-MYH11 Abnormalities | 1470 | ||
Acute Myeloid Leukemia with Other Translocations | 1470 | ||
AML with 11q23/MLL | 1470 | ||
AML with t(6;9)(p23;q34)/DEK-NUP214 | 1471 | ||
AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2)/RPN1-EVI1 | 1471 | ||
AML (Megakaryoblastic) with t(1;22)(p13;q13)/RBM15-MKL1 | 1471 | ||
Acute Myeloid Leukemias with FLT3, NPM1, and CEBPA Gene Mutations | 1471 | ||
FLT3 Mutations in Acute Myeloid Leukemia | 1471 | ||
NPM1 Mutations in Acute Myeloid Leukemia | 1472 | ||
CEBPA Mutations in Acute Myeloid Leukemia | 1472 | ||
Other Gene Mutations in Acute Myeloid Leukemias | 1472 | ||
WT1 Mutations in Acute Myeloid Leukemias | 1472 | ||
Acute Lymphoblastic Leukemia/Lymphoma—B and T Cell Lineage | 1473 | ||
B Cell Lymphoblastic Leukemia/Lymphoma (Precursor B Cell Acute Lymphoblastic Leukemia, B-ALL) | 1473 | ||
Major Translocation Fusion Gene Abnormalities in B Cell ALL | 1473 | ||
Prenatal Origins of Childhood Leukemias | 1476 | ||
BCR-ABL1–Like B-Acute Lymphoblastic Leukemia | 1476 | ||
T Cell Lymphoblastic Leukemia/Lymphoma | 1476 | ||
Molecular Diagnosis of Myeloproliferative Neoplasms | 1477 | ||
Chronic Myelogenous Leukemia with t(9;22)(q34;q11)/BCR-ABL1 Positive | 1477 | ||
Ph-Negative Myeloproliferative Neoplasms: Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis—JAK2, MPL Gene, and CALR Mutations | 1478 | ||
Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia with CSF3R Gene Mutation | 1480 | ||
Mastocytosis and the KIT D816V Gene Mutation | 1480 | ||
Neoplastic Disorders Associated with Eosinophilia | 1480 | ||
Molecular Diagnosis of Non-Hodgkin Lymphomas | 1481 | ||
Rationale for Molecular Genetic Analysis in the Lymphoid Disorders | 1481 | ||
Antigen Receptor Gene Rearrangements for Clonality Determination | 1481 | ||
Mechanism of Antigen Receptor Gene Rearrangements | 1481 | ||
Techniques to Detect Antigen Receptor Gene Rearrangements: Southern Blot Hybridization | 1481 | ||
Advantages and Shortcomings of Southern Blot Hybridization and Polymerase Chain Reaction for Lymphoid Clonality Assessment | 1481 | ||
Molecular Detection and Significance of Common Lymphoma-Associated Chromosomal Translocations | 1484 | ||
t(14;18)/BCL2-IGH@ Abnormality in Follicular and Diffuse Large B Cell Lymphomas | 1484 | ||
t(11;14)/CCND1-IGH@ Abnormality in Mantle Cell Lymphoma | 1485 | ||
MALT1, BCL10, and FOXP1 Gene Abnormalities in Extranodal Marginal Zone B Cell Lymphomas | 1486 | ||
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Molecular and Cytogenetic Prognostic Markers | 1486 | ||
Diffuse Large B Cell Lymphomas: Role of BCL6 and MYC Gene Abnormalities and Classification Based on Gene Expression Profiling | 1487 | ||
MYC Gene Translocations in Burkitt Lymphomas and “High-Grade” B Cell Lymphomas, Unclassifiable | 1487 | ||
MYD88 Mutation in Non-Hodgkin B Cell Lymphoma | 1488 | ||
ALK Gene Abnormalities in Anaplastic Large Cell Lymphomas | 1488 | ||
TCL1A Gene Abnormalities in T Cell Prolymphocytic Leukemia | 1489 | ||
The Implication of Next Gene Sequencing (NGS) in Hematolymphoid Lesions | 1489 | ||
Emerging Technologies Impacting Molecular Diagnosis and Prognosis Prediction in Hematolymphoid Neoplasia | 1489 | ||
References | 1491 | ||
Selected References | 1491 | ||
References | 1491.e1 | ||
77 Molecular Genetic Pathology of Solid Tumors | 1492 | ||
Key Points | 1492 | ||
Molecular Genetic Pathology of Specific Solid Tumors by Major Organ | 1493 | ||
Brain Tumor | 1493 | ||
Glioblastoma Multiforme | 1493 | ||
Oligodendroglioma | 1493 | ||
Rhabdoid Tumor | 1496 | ||
Breast Cancer | 1496 | ||
Sporadic, Nonhereditary Breast Cancer | 1497 | ||
Hereditary Breast Cancer | 1499 | ||
Thyroid Cancer | 1499 | ||
Papillary Thyroid Carcinoma | 1499 | ||
Follicular Carcinoma | 1500 | ||
Medullary Carcinoma | 1500 | ||
Lung Cancer | 1500 | ||
Hepatocellular Carcinoma | 1501 | ||
Hepatic Adenomas | 1502 | ||
Gastric Cancer | 1503 | ||
Colorectal Cancer | 1504 | ||
Hereditary Colonic Cancer Syndrome | 1505 | ||
Familial Adenomatous Polyposis Syndrome | 1505 | ||
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) | 1505 | ||
Familial Juvenile Polyposis Syndrome | 1506 | ||
Peutz-Jeghers Syndrome | 1506 | ||
Serrated Polyposis Syndrome (Formerly Known as Hyperplastic Polyposis Syndrome) | 1506 | ||
MYH Polyposis and Inherited Colon Cancer Due to MYH Inactivation | 1506 | ||
Pancreatic Cancer (Non-Neuroendocrine Tumor) | 1506 | ||
Kidney Tumor | 1507 | ||
Clear Cell Renal Cell Carcinoma (RCC) | 1507 | ||
Papillary RCC | 1508 | ||
Chromophobe Tumors | 1508 | ||
Micropthalmia Transcription Factor (MiT) Family Translocation Renal Cell Carcinoma | 1508 | ||
Xp11 Translocation or TFE 3-Associated RCC | 1508 | ||
(6;11) Translocation TFEB-Associated RCC | 1508 | ||
Succinate Dehydrogenase B (SDHB) Mutation–Associated RCC | 1508 | ||
ALK Translocation RCC | 1509 | ||
Hereditary Renal Cell Carcinoma Syndromes | 1509 | ||
Gene Expression Profiling by Affymetrix in RCC | 1509 | ||
Bladder Cancer | 1509 | ||
Prostate Cancer | 1510 | ||
Cervical Cancer | 1510 | ||
Endometrial Cancer | 1511 | ||
Ovarian Cancer | 1511 | ||
Histologic Subtypes of Serous Carcinoma | 1512 | ||
Molecular Classification of Ovarian Cancer | 1512 | ||
Clear Cell Ovarian Carcinoma | 1512 | ||
BRCA1 and BRCA2 in Ovarian Cancer | 1512 | ||
Melanoma | 1512 | ||
Molecular Genetic Pathology of Sarcoma | 1513 | ||
Sarcomas with Fusion Genes | 1513 | ||
Fusion Genes Involving TET Genes | 1513 | ||
Ewing’s Sarcoma/Primitive Peripheral Neuroectodermal Tumor | 1513 | ||
Clear Cell Sarcoma | 1513 | ||
Extraskeletal Myxoid Chondrosarcoma | 1513 | ||
Atypical Lipomatous Tumor, Well-Differentiated and Dedifferentiated Liposarcoma | 1513 | ||
Myxoid/Round Cell Liposarcoma | 1514 | ||
Low-Grade Fibromyxoid Sarcoma | 1514 | ||
Hemangioma of Bone | 1514 | ||
Fusion Genes Involving Receptor Tyrosine Kinase Genes | 1514 | ||
Sarcoma with Fusion Genes Involving Chromatin Remodeling Genes | 1514 | ||
Sarcoma with Fusion Genes Involving Growth Factors | 1514 | ||
Sarcoma with Other Types of Fusion Genes | 1514 | ||
Epithelioid Hemangioendothelioma | 1514 | ||
Sarcomas with Oncogenic Mutations | 1515 | ||
KIT and PDGFRA in Gastrointestinal Stromal Tumor | 1515 | ||
Sarcomas with Variable Other Specific Pattern | 1515 | ||
Nodular Fasciitis | 1515 | ||
Inflammatory Myofibroblastic Tumor | 1515 | ||
Aneurysmal Bone Cyst | 1515 | ||
Sarcomas with Variable Complex Genetic Alterations with No Specific Pattern | 1515 | ||
Molecular Genetic Pathology of Multiple Endocrine Neoplasia | 1515 | ||
Cancers of Unknown Origin | 1517 | ||
miRNA in Cancer | 1518 | ||
Clinical Application of Next-Generation Sequencing | 1518 | ||
References | 1519 | ||
Selected References | 1519 | ||
References | 1519.e1 | ||
78 High-Throughput Genomic and Proteomic Technologies in the Postgenomic Era | 1520 | ||
Key Points | 1520 | ||
Overview | 1520 | ||
The Human Genome Project | 1521 | ||
Public Sequencing Effort (Hierarchical Shotgun Sequencing) | 1521 | ||
Private Sequencing Effort (Whole-Genome Shotgun Sequencing) | 1522 | ||
Finishing the Sequence of the Human Genome | 1522 | ||
High-Throughput Technologies | 1522 | ||
Genomic | 1522 | ||
Serial Analysis of Gene Expression | 1523 | ||
Microarray | 1523 | ||
Real Competitive Polymerase Chain Reaction | 1524 | ||
Multiplex PCR | 1527 | ||
xTAG Technology | 1527 | ||
High-Resolution Melting Analysis | 1527 | ||
Proteomic | 1528 | ||
Mass Spectrometry | 1528 | ||
Protein Arrays | 1528 | ||
Secretome | 1528 | ||
Molecular Markers for the Diagnosis of Human Neoplasia | 1528 | ||
Genomic | 1528 | ||
Proteomic | 1529 | ||
Diagnostic Cancer Applications | 1529 | ||
Small, Round Blue Cell Tumors | 1529 | ||
Barrett’s Esophagus | 1530 | ||
Thyroid Carcinoma | 1530 | ||
Distinguishing Follicular Thyroid Carcinoma from Adenoma | 1530 | ||
Adenocarcinoma | 1531 | ||
Pancreatic Cancer | 1531 | ||
Other Cancers | 1531 | ||
Prognostic Molecular Markers of Disease | 1531 | ||
Genomic | 1531 | ||
Diffuse Large B-Cell Lymphoma (see also Chapter 76) | 1531 | ||
Follicular Lymphoma | 1532 | ||
Acute Myeloid Leukemia | 1532 | ||
Breast Cancer | 1533 | ||
Integrating Genomics and Proteomics | 1533 | ||
Pitfalls of Molecular Markers for Both Prognostics and Diagnostics | 1533 | ||
Microarray Data Sets | 1533 | ||
“Overfitting” The Predictor | 1533 | ||
The “Bystander” Effect | 1534 | ||
Limitations of Proteomic Techniques | 1534 | ||
Conclusion and Future Challenges | 1534 | ||
References | 1534 | ||
Selected References | 1534 | ||
References | 1534.e1 | ||
Appendix 1 Physiologic Solutions, Buffers, Acid-Base Indicators, Standard Reference Materials, and Temperature Conversions | e1 | ||
Physiologic Solutions | e1 | ||
Buffers* | e1 | ||
Example 1 | e1 | ||
Example 2 | e1 | ||
Sorensen’s Phosphate Buffers | e1 | ||
Tris(hydroxymethyl)aminomethane Buffer* | e1 | ||
Acid-Base Indicators | e1 | ||
Standard Reference Materials | e2 | ||
Temperature Conversion | e2 | ||
Selected References | e4 | ||
Appendix 2 Desirable Weights, Body Surface Area, and Body Mass Index | e5 | ||
Appendix 3 Approximations of Total Blood Volume | e9 | ||
Adults | e9 | ||
Children | e9 | ||
Selected References | e9 | ||
Appendix 4 Periodic Table of the Elements | e10 | ||
References | e10 | ||
Appendix 5 SI Units | e11 | ||
References | e26 | ||
Appendix 6 Common Chimeric Genes Identified in Human Malignancies | e27 | ||
References | e29 | ||
Appendix 7 Disease/Organ Panels | e31 | ||
AMA Designated Disease/Organ Panels | e32 | ||
References | e32 | ||
Index | 1535 | ||
A | 1535 | ||
B | 1538 | ||
C | 1539 | ||
D | 1543 | ||
E | 1544 | ||
F | 1545 | ||
G | 1546 | ||
H | 1547 | ||
I | 1549 | ||
J | 1551 | ||
K | 1551 | ||
L | 1551 | ||
M | 1553 | ||
N | 1555 | ||
O | 1556 | ||
P | 1557 | ||
Q | 1559 | ||
R | 1559 | ||
S | 1560 | ||
T | 1562 | ||
U | 1564 | ||
V | 1564 | ||
W | 1565 | ||
X | 1565 | ||
Y | 1565 | ||
Z | 1565 | ||
Guidelines for Ordering Blood for Elective Surgery | IBC2 | ||
Also Referred to as Maximum Surgical Blood Order Schedule (MSBOS) | IBC2 | ||
Cardiopulmonary/Cardiothoracic | IBC2 | ||
General Surgery | IBC2 | ||
Gynecology | IBC2 | ||
Neurosurgery | IBC2 | ||
Orthopedics | IBC2 | ||
Otorhinolaryngology/Head and Neck Surgery | IBC3 | ||
Plastic Surgery | IBC3 | ||
Renal Transplantation | IBC3 | ||
Urology | IBC3 | ||
Vascular Surgery | IBC3 | ||
References | IBC3 |