BOOK
Henry's Clinical Diagnosis and Management by Laboratory Methods E-Book
Richard A. McPherson | Matthew R. Pincus
(2011)
Additional Information
Book Details
Abstract
Recognized as the definitive book in laboratory medicine since 1908, Henry’s Clinical Diagnosis and Management by Laboratory Methods, edited by Richard A. McPherson, MD and Matthew R. Pincus, MD, PhD, is a comprehensive, multidisciplinary pathology reference that gives you state-of-the-art guidance on lab test selection and interpretation of results. Revisions throughout keep you current on the latest topics in the field, such as biochemical markers of bone metabolism, clinical enzymology, pharmacogenomics, and more! A user-friendly full-color layout puts all the latest, most essential knowledge at your fingertips.
- Update your understanding of the scientific foundation and clinical application of today's complete range of laboratory tests.
- Get optimal test results with guidance on error detection, correction, and prevention as well as cost-effective test selection.
- Reference the information you need quickly and easily thanks to a full-color layout, many new color illustrations and visual aids, and an organization by organ system.
- Master all the latest approaches in clinical laboratory medicine with new and updated coverage of:
- the chemical basis for analyte assays and common interferences;
- lipids and dyslipoproteinemia;
- markers in the blood for cardiac injury evaluation and related stroke disorders;
- coagulation testing for antiplatelet drugs such as aspirin and clopidogrel;
- biochemical markers of bone metabolism;
- clinical enzymology;
- hematology and transfusion medicine;
- medical microbiology;
- body fluid analysis;
- and many other rapidly evolving frontiers in the field.
- Effectively monitor the pace of drug clearing in patients undergoing pharmacogenomic treatments with a new chapter on this groundbreaking new area.
- Apply the latest best practices in clinical laboratory management with special chapters on organization, work flow, quality control, interpretation of results, informatics, financial management, and establishing a molecular diagnostics laboratory.
- Confidently prepare for the upcoming recertification exams for clinical pathologists set to begin in 2016.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front cover | cover | ||
| Half title page | i | ||
| Associate Editors | ii | ||
| Henry's Clinical Diagnosis and Management by Laboratory Methods | iii | ||
| Copyright page | iv | ||
| Table of contents | v | ||
| Dedication | viii | ||
| Contributors | xi | ||
| Preface | xvii | ||
| Acknowledgments | xxi | ||
| PART 1 The Clinical Laboratory | 1 | ||
| CHAPTER 1 General Concepts and Administrative Issues | 3 | ||
| Key Points | 3 | ||
| Leadership and Management | 3 | ||
| Strategic Planning | 3 | ||
| Quality Systems Management | 4 | ||
| Human Resource (HR) Management | 6 | ||
| Laboratory Design and Service Models | 7 | ||
| Regulation, Accreditation, and Legislation | 7 | ||
| Safety | 9 | ||
| Biological Hazards | 10 | ||
| Chemical Hazards | 10 | ||
| Ergonomic Hazards | 11 | ||
| Selected References | 12 | ||
| References | e1 | ||
| References | 12 | ||
| CHAPTER 2 Optimizing Laboratory Workflow and Performance | 13 | ||
| Key Points | 13 | ||
| Understanding Workflow | 13 | ||
| Data Collection Techniques | 13 | ||
| Sample and Test Mapping | 13 | ||
| Tube Analysis | 14 | ||
| Workstation Analysis | 15 | ||
| Instrument Audit | 15 | ||
| Test Menu | 16 | ||
| Processing Mode and Load Balancing. | 16 | ||
| Interviews | 16 | ||
| Task Mapping | 16 | ||
| Workflow Analysis | 16 | ||
| Workflow Modeling | 18 | ||
| Pneumatic Tube Transport of Specimens | 18 | ||
| Understanding Technology | 18 | ||
| The Role of Technology: Principles and Pitfalls | 18 | ||
| Is technology needed? | 18 | ||
| Technology is a means to an end, not an end. | 19 | ||
| Overbuying—the cardinal sin. | 19 | ||
| Do you understand what you are buying? | 19 | ||
| Optimizing Performance | 20 | ||
| Consolidation. | 20 | ||
| Standardization. | 20 | ||
| Integration. | 21 | ||
| Six Sigma and Lean. | 21 | ||
| Managing Utilization. | 21 | ||
| Evaluating Excess Capacity | 22 | ||
| Philosophy and Mission. | 22 | ||
| Physical Resource Assessment. | 22 | ||
| Personnel. | 22 | ||
| Expansion and Economy of Scale. | 22 | ||
| Selected References | 23 | ||
| References | e2 | ||
| References | 23 | ||
| CHAPTER 3 PreAnalysis | 24 | ||
| Key Points | 24 | ||
| PreCollection Variables | 24 | ||
| Physiologic Factors | 24 | ||
| Exercise. | 24 | ||
| Diet. | 25 | ||
| Stress. | 25 | ||
| Posture. | 25 | ||
| Age. | 25 | ||
| Gender. | 25 | ||
| Common Interferences | 26 | ||
| In Vivo | 26 | ||
| Tobacco Smoking | 26 | ||
| In Vitro | 26 | ||
| Collection-Associated Variables | 26 | ||
| Specimen Collection | 26 | ||
| The Test Order | 26 | ||
| Time of Collection | 27 | ||
| Specimen Rejection | 27 | ||
| Blood Collection Overview | 27 | ||
| Anticoagulants and Additives | 28 | ||
| Blood Collection Devices | 29 | ||
| Blood Storage and Preservation | 29 | ||
| Importance of Policies and Procedures | 30 | ||
| Blood Collection Techniques | 30 | ||
| Arterial Puncture | 30 | ||
| Arterial Puncture Technique | 31 | ||
| Finger or Heel Skin Puncture | 31 | ||
| Central Venous Access Devices | 31 | ||
| CVA Collection Technique | 31 | ||
| urine and Other Body Fluids Collection | 32 | ||
| urine | 32 | ||
| Special urine Collection Techniques | 32 | ||
| urine Storage and Preservation | 32 | ||
| Other Body Fluids | 33 | ||
| Cerebrospinal Fluid | 33 | ||
| Synovial Fluid | 33 | ||
| Pleural Fluid, Pericardial Fluid, and Peritoneal Fluid | 33 | ||
| Specimen Transport | 34 | ||
| Specimen Processing | 34 | ||
| Precentrifugation Phase | 34 | ||
| Centrifugation Phase | 34 | ||
| Equipment | 35 | ||
| Interferences | 35 | ||
| Specimen Collection | 35 | ||
| Optical Interferences | 35 | ||
| Immunoassays | 35 | ||
| Specimen Matrix Effects | 35 | ||
| Molecular Diagnostics | 36 | ||
| Effects of Drugs | 36 | ||
| Selected References | 36 | ||
| References | e3 | ||
| References | 36 | ||
| CHAPTER 4 Analysis: | 37 | ||
| Key Points | 37 | ||
| Principles of Instrumentation | 38 | ||
| Spectrophotometry | 38 | ||
| Example 4-1. | 38 | ||
| Velocity of Propagation | 38 | ||
| Example 4-2. | 38 | ||
| Solution | 38 | ||
| Energy of EMR | 38 | ||
| Example 4-3. | 39 | ||
| Solution | 39 | ||
| Scattering of Radiation | 39 | ||
| Rayleigh Scattering | 39 | ||
| Tyndall Effect | 40 | ||
| Raman Scattering | 40 | ||
| Beer–Lambert Law | 40 | ||
| Example 4-4. | 40 | ||
| Solution | 40 | ||
| Components of a Spectrophotometer | 40 | ||
| Radiant Energy Sources | 41 | ||
| Wavelength Selectors | 41 | ||
| Filters | 41 | ||
| Pre-Sample Filters (Bender, 1987). | 41 | ||
| Post-Sample Filters. | 43 | ||
| Sample Containers (Cuvets) | 43 | ||
| Photodetectors | 43 | ||
| Photomultiplier Tubes (PMTs). | 43 | ||
| Photovoltaic or Barrier Layer Cell. | 43 | ||
| Vacuum Phototubes. | 43 | ||
| Silicon Diode Transducers. | 43 | ||
| Multichannel Photon Transducers. | 44 | ||
| Photodiode Arrays. | 44 | ||
| Charge-Transfer Devices. | 44 | ||
| Signal Processors and Readout | 44 | ||
| Quality Assurance in Spectrophotometry | 44 | ||
| Types of Photometric Instruments | 45 | ||
| Reflectometry | 46 | ||
| Reflectometers | 46 | ||
| Molecular Luminescence Spectroscopy (Fluorometry) | 46 | ||
| Principle | 46 | ||
| Components of Fluorometers and Spectrophotofluorometers | 46 | ||
| Nephelometry and Turbidimetry | 47 | ||
| Principle | 47 | ||
| Nephelometer | 47 | ||
| Turbidimetry | 48 | ||
| Refractometry | 48 | ||
| Osmometry | 48 | ||
| Principle of Freezing-Point Osmometry | 48 | ||
| Freezing-Point Osmometer | 48 | ||
| Flow Cytometry | 48 | ||
| Instrument Components | 48 | ||
| Electrochemistry | 49 | ||
| Potentiometry | 49 | ||
| Reference Electrodes | 50 | ||
| Ion-Selective Electrode | 50 | ||
| pH Electrode | 50 | ||
| pCO2 Electrode | 50 | ||
| Coulometry | 50 | ||
| Amperometry | 50 | ||
| pO2 Gas-Sensing Electrode | 50 | ||
| Voltammetry | 50 | ||
| Conductance | 51 | ||
| Impedance | 51 | ||
| Electrophoresis and Densitometry | 51 | ||
| Isoelectric Focusing | 51 | ||
| Chromatography | 51 | ||
| Gas Chromatography | 52 | ||
| Liquid Chromatography | 53 | ||
| Mass Spectrometry | 54 | ||
| Atomic Weights (amu and Da) | 54 | ||
| Example 4-5. | 54 | ||
| Solution | 54 | ||
| Mass/Charge Ratio | 54 | ||
| Example 4-6. | 54 | ||
| Basic Components | 54 | ||
| Ion Source Unit | 54 | ||
| Mass Spectrometer Analyzer Unit | 55 | ||
| Ion Detector | 56 | ||
| Scintillation Counter | 56 | ||
| Capillary Electrophoresis | 57 | ||
| Nuclear Magnetic Resonance Spectroscopy | 57 | ||
| General Analytic Methods and Issues | 57 | ||
| Chemicals | 57 | ||
| Water | 58 | ||
| Types of Water Purity | 58 | ||
| Purification | 58 | ||
| Monitoring Water Purity | 58 | ||
| Once Your System Has Been Installed | 59 | ||
| Measurement of Mass | 59 | ||
| Types of Balances | 59 | ||
| Unequal-Arm Substitution Balances | 59 | ||
| Magnetic Force Restoration Balance | 59 | ||
| Top-Loading Balances | 59 | ||
| Electronic Balances | 59 | ||
| Calibration | 59 | ||
| Handling Weights Used for Testing Accuracy | 59 | ||
| Environmental Concerns for Best Weighing Accuracy | 59 | ||
| Balance Specifications | 60 | ||
| Laboratory Glassware and Plasticware | 60 | ||
| Types of Glassware | 60 | ||
| Types of Plasticware | 60 | ||
| Volumetric Laboratoryware | 60 | ||
| Pipets | 60 | ||
| Class A Designation | 60 | ||
| Types of Pipets | 60 | ||
| Micropipets | 60 | ||
| Pipet Calibration | 61 | ||
| Volumetric Flasks | 61 | ||
| Calibration of Volumetric Glassware | 61 | ||
| Thermometry | 61 | ||
| Types of Thermometers | 61 | ||
| Special Applications of Temperature-Sensing Devices | 61 | ||
| Mercury-Free Laboratories | 61 | ||
| Thermometer Calibration | 61 | ||
| Water Baths | 62 | ||
| Maintenance | 62 | ||
| Quality Control | 62 | ||
| Heating Blocks, Dry-Bath Incubators, and Ovens | 62 | ||
| Mixing | 62 | ||
| Single-Tube Mixers | 62 | ||
| Multiple-Tube Mixers | 62 | ||
| Aqueous Solution | 62 | ||
| Molarity | 62 | ||
| Example 4-7. | 62 | ||
| PART 2 Clinical Chemistry | 167 | ||
| CHAPTER 14 Evaluation of Renal Function, Water, Electrolytes, and Acid-Base Balance | 169 | ||
| Key Points | 169 | ||
| Volume and Osmolality of Body Fluid | 170 | ||
| Measurement of Body Fluid Volumes | 170 | ||
| Body Fluid Volumes | 170 | ||
| Composition of the Body Fluid | 171 | ||
| Extracellular Composition | 171 | ||
| Intracellular Composition | 171 | ||
| Measurement of Plasma Osmolality | 171 | ||
| Effect of Hyperglycemia on Serum Na | 172 | ||
| Tonicity | 172 | ||
| Osmolality and Specific Gravity | 172 | ||
| Regulation of Extracellular Volume | 172 | ||
| Nonrenal Control of Water and Electrolyte Balance | 173 | ||
| Measurement of Renal Function | 174 | ||
| Concept of Clearance | 174 | ||
| Quick Formulas for the Calculation of Clearance | 174 | ||
| Conversion of Clearance in L/Week to mL/Minute | 174 | ||
| Measurement of Glomerular Filtration Rate | 174 | ||
| Measurement of GFR With Exogenous Substances | 174 | ||
| Measurement of GFR With Endogenous Substances | 174 | ||
| Creatinine as a Measure of Renal Function | 174 | ||
| Creatinine Measurement | 175 | ||
| Cimetidine-Enhanced Creatinine Clearance | 175 | ||
| Formulas to Estimate Creatinine Clearance as an Estimate of GFR | 175 | ||
| Urea as Measure of Renal Function | 176 | ||
| Measurement of Urea | 176 | ||
| Other Measures of GFR | 177 | ||
| Cystatin C | 177 | ||
| β-2-Microglobulin | 177 | ||
| β Trace Protein | 177 | ||
| Tryptophan Glycoconjugate | 177 | ||
| Urea Clearance and Urea/Creatinine Ratio in Serum | 177 | ||
| Glomerular Filtration Rate, Renal Plasma Flow, and Filtration Fraction | 178 | ||
| Fractional Excretion | 178 | ||
| Renal Failure Index | 178 | ||
| Fractional Reabsorption | 178 | ||
| Free Water Clearance and Negative Free Water Clearance | 178 | ||
| Biomarkers of Acute Kidney Injury | 178 | ||
| Kidney Injury Molecule-1 | 179 | ||
| Neutrophil Gelatinase–Associated Lipocalin | 179 | ||
| Interleukin-18 | 179 | ||
| Fatty Acid–Binding Protein | 179 | ||
| Disorders of Potassium | 180 | ||
| Control of Transcellular Flux of Potassium | 180 | ||
| Control of Renal Excretion of Potassium | 180 | ||
| Plasma Renin Activity, Plasma Aldosterone Concentration, and Abnormalities in Potassium Metabolism | 181 | ||
| Causes and Pathogenesis of Hypokalemia | 181 | ||
| Differential Diagnosis of Hypokalemia | 182 | ||
| Causes and Pathogenesis of Hyperkalemia | 182 | ||
| Differential Diagnosis of Hyperkalemia | 183 | ||
| Disorders of Water, Sodium, and Antidiuretic Hormone Metabolism | 183 | ||
| Regulation of Thirst and ADH Release | 183 | ||
| urine Concentration and Dilution | 184 | ||
| Polyuria | 185 | ||
| Osmotic Diuresis | 185 | ||
| Water Diuresis | 185 | ||
| Causes and Pathogenesis of Hyponatremia (Table 14-8) | 185 | ||
| Causes and Pathogenesis of Hypernatremia | 186 | ||
| Acid-Base Disorders | 187 | ||
| Bicarbonate and Carbon Dioxide Buffer System | 187 | ||
| Definitions of Acid and Base | 187 | ||
| Whole Body Acid-Base Balance | 187 | ||
| Net Acid Production | 187 | ||
| Net Acid Excretion | 188 | ||
| Metabolic Acidosis | 188 | ||
| Classification | 188 | ||
| Renal Acidosis | 188 | ||
| Organic Acidosis | 188 | ||
| Lactic Acidosis. | 188 | ||
| d-Lactic Acidosis. | 189 | ||
| Ketoacidosis. | 189 | ||
| Serum Anion Gap | 189 | ||
| Differential Diagnosis | 190 | ||
| Compensation of Metabolic Acidosis | 190 | ||
| Metabolic Alkalosis | 190 | ||
| Causes and Pathogenesis | 190 | ||
| Compensation of Metabolic Alkalosis | 191 | ||
| Respiratory Acidosis | 191 | ||
| PART 3 Urine and Other Body Fluids | 443 | ||
| CHAPTER 28 Basic Examination of urine | 445 | ||
| Key Points | 445 | ||
| urine Formation | 446 | ||
| Components of Basic (Routine) urinalysis | 446 | ||
| Specimen Evaluation | 446 | ||
| Gross/Physical Examination | 446 | ||
| Appearance | 446 | ||
| Color | 446 | ||
| Red urine. | 447 | ||
| Yellow-Brown or Green-Brown urine. | 447 | ||
| Orange-Red or Orange-Brown urine. | 447 | ||
| Dark Brown or Black urine. | 447 | ||
| Clarity (Character) | 447 | ||
| Chyluria. | 447 | ||
| Lipiduria. | 447 | ||
| Odor | 448 | ||
| urine Volume | 448 | ||
| Increases in urine Volume | 448 | ||
| Defective Hormonal Regulation of Volume Homeostasis. | 448 | ||
| Defective Renal Salt/Water Absorption. | 448 | ||
| Osmotic Diuresis. | 448 | ||
| Decreases in urine Volume | 448 | ||
| Prerenal. | 448 | ||
| Postrenal. | 449 | ||
| Renal Parenchymal Disease. | 449 | ||
| Specific Gravity and Osmolality | 449 | ||
| Specific Gravity | 449 | ||
| Methods. | 449 | ||
| Reagent Strip. | 449 | ||
| Refractometer. | 449 | ||
| PART 4 Hematology, Coagulation, and Transfusion Medicine | 507 | ||
| CHAPTER 30 Basic Examination of Blood and Bone Marrow | 509 | ||
| Key Points | 509 | ||
| Hematology Principles and Procedures | 510 | ||
| Hemoglobin | 510 | ||
| Hemoglobin Derivatives | 510 | ||
| Hemiglobin (Methemoglobin) | 510 | ||
| Sulfhemoglobin | 510 | ||
| Carboxyhemoglobin | 511 | ||
| Measurement of Hb Concentration | 511 | ||
| Hemiglobincyanide Method | 511 | ||
| Principle. | 511 | ||
| Reagent. | 511 | ||
| Method. | 511 | ||
| Errors in Hemoglobinometry | 512 | ||
| Errors Inherent in the Sample. | 512 | ||
| Errors Inherent in the Method. | 512 | ||
| Errors Inherent in the Equipment. | 512 | ||
| Operator’s Errors. | 512 | ||
| Spectrophotometric Identification of Hemoglobins | 512 | ||
| Hematocrit (Packed Cell Volume) | 512 | ||
| Gross Examination | 512 | ||
| Hematocrit Measurement by Micromethod | 512 | ||
| Equipment | 512 | ||
| Procedure | 512 | ||
| Interpretation of Results | 512 | ||
| 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 | 513 | ||
| Erythrocyte Counts: Manual | 513 | ||
| Semiautomated Methods | 513 | ||
| Reticulocyte Count: Manual | 514 | ||
| Principle | 514 | ||
| Reagent. | 514 | ||
| Controls. | 514 | ||
| Procedure | 514 | ||
| Reference Values | 514 | ||
| Interpretation | 514 | ||
| Sources of Variation | 514 | ||
| Leukocyte Counts: Manual | 514 | ||
| Specimen Collection | 514 | ||
| Hemocytometer Method | 514 | ||
| Counting Chamber. | 514 | ||
| Diluting Fluid. | 514 | ||
| Procedure. | 514 | ||
| Sources of Error. | 515 | ||
| Errors Due to the Nature of the Sample. | 515 | ||
| Operator’s Errors. | 515 | ||
| Errors Due to Equipment. | 515 | ||
| Inherent or Field Errors. | 515 | ||
| Nucleated Red Blood Cells. | 515 | ||
| Example. | 515 | ||
| Reference Value. | 515 | ||
| Platelet Counts | 515 | ||
| Hemocytometer Method—Phase-Contrast Microscope | 515 | ||
| Specimen. | 515 | ||
| Diluent Solution. | 515 | ||
| Procedure | 515 | ||
| Calculation. | 515 | ||
| Sources of Error. | 516 | ||
| Falsely Elevated Counts. | 516 | ||
| Falsely Low Counts. | 516 | ||
| Variation In Automated Platelet Count | 516 | ||
| Reticulated Platelets | 516 | ||
| Electronic Counting | 516 | ||
| Instrument Technology | 516 | ||
| Electrical Impedance | 516 | ||
| Radiofrequency Conductivity | 517 | ||
| Light Scattering | 517 | ||
| Cytochemistry | 517 | ||
| Reporting/Flagging | 517 | ||
| Sources of Error | 517 | ||
| Automated Reticulocyte Counting | 517 | ||
| Physiologic Variation | 518 | ||
| Physiologic Variation in Erythrocytes | 518 | ||
| Physiologic Variation in Leukocytes | 519 | ||
| Physiologic Variation in Platelets | 519 | ||
| Erythrocyte Sedimentation Rate | 519 | ||
| Plasma Factors | 520 | ||
| Red Cell Factors | 520 | ||
| Stages in the ESR | 520 | ||
| Methods | 520 | ||
| Westergren Method | 520 | ||
| Equipment. | 520 | ||
| Reagent. | 521 | ||
| Procedure | 521 | ||
| Modified Westergren Method | 521 | ||
| Sources of Error | 521 | ||
| Alternative Methods and Technologies to Measure ESR | 521 | ||
| Application | 521 | ||
| Blood Film Examination | 522 | ||
| Examination of Wet Preparations | 522 | ||
| Making and Staining Blood Films | 522 | ||
| Wedge Method | 522 | ||
| Cover Glass Method | 522 | ||
| Spinner Method | 522 | ||
| Blood Stains | 522 | ||
| Wright’s Stain | 522 | ||
| Procedure | 522 | ||
| Staining Problems | 523 | ||
| Excessively Blue Stain. | 523 | ||
| Excessively Pink Stain. | 523 | ||
| Other Staining Problems. | 523 | ||
| Other Stains | 523 | ||
| Reference Method | 523 | ||
| Automated Slide Stainer | 523 | ||
| Erythrocytes | 523 | ||
| Color | 523 | ||
| Hemoglobin Content | 523 | ||
| Polychromatophilia | 523 | ||
| Size | 524 | ||
| 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 | 528 | ||
| Lymphocyte | 529 | ||
| Artifacts | 529 | ||
| Broken Cells | 529 | ||
| Degenerative Changes | 529 | ||
| Contracted Cells | 530 | ||
| Endothelial Cells | 530 | ||
| Radial Segmentation of the Nuclei | 530 | ||
| Vacuolation | 530 | ||
| “Pseudophagocytosis” | 530 | ||
| Sources of Error in the Differential Leukocyte Count | 530 | ||
| Automated Differential Leukocyte Counting | 531 | ||
| Digital Image Processing | 531 | ||
| Platelets on Peripheral Blood Smear Examination | 531 | ||
| Bone Marrow Examination | 531 | ||
| Preparation of the Aspirate and Biopsy Section | 532 | ||
| Marrow Films | 532 | ||
| Direct Films | 532 | ||
| Imprints | 532 | ||
| Crush Preparations | 532 | ||
| Special Studies | 532 | ||
| Histologic Sections | 532 | ||
| Staining Marrow Preparations | 532 | ||
| Romanowsky’s Stain | 532 | ||
| Perls’ Test for Iron | 532 | ||
| Procedure | 532 | ||
| Interpretation | 532 | ||
| Sections | 533 | ||
| Examination of Marrow | 533 | ||
| Peripheral Blood | 533 | ||
| Cellularity of the Marrow | 533 | ||
| Distribution of Cells | 533 | ||
| Maturation | 534 | ||
| Presence of Rare Cell Types or Abnormal Cells | 534 | ||
| Evaluation of the Biopsy Specimen | 535 | ||
| Interpretation | 535 | ||
| Indications for Marrow Study | 535 | ||
| Selected References | 535 | ||
| References | e57 | ||
| References | 535 | ||
| CHAPTER 31 Hematopoiesis | 536 | ||
| Key Points | 536 | ||
| Stem Cells | 536 | ||
| Hematopoietic Stem Cells and Progenitors | 537 | ||
| Hematopoietic Growth Factors | 537 | ||
| Hematopoietic Tissues | 539 | ||
| Embryonic and Fetal Hematopoiesis | 539 | ||
| Postnatal Hematopoiesis | 539 | ||
| Erythrocyte Production | 539 | ||
| Normoblastic Maturation | 539 | ||
| Megaloblastic Maturation | 540 | ||
| Regulation of Erythrocyte Production | 540 | ||
| Synthesis of Hemoglobin | 541 | ||
| Heme Synthesis | 541 | ||
| Globin Synthesis | 541 | ||
| Structure and Function of Hemoglobin | 541 | ||
| Erythrocyte Destruction | 541 | ||
| Degradation of Hemoglobin | 543 | ||
| Erythrokinetics | 543 | ||
| Measurements of Total Production of Erythrocytes or Hemoglobin | 543 | ||
| Measurements of Total Destruction of Erythrocytes or Hemoglobin | 543 | ||
| Measurements of Effective Production of Erythrocytes | 544 | ||
| Reticulocyte Count | 544 | ||
| Measurements of Effective Survival of Erythrocytes in Blood | 544 | ||
| Summary | 544 | ||
| The Porphyrias | 544 | ||
| Physiology | 544 | ||
| Clinical Porphyrias and Their Biochemical Basis | 544 | ||
| Neurovisceral Symptoms in Isolation | 544 | ||
| Acute Intermittent Porphyria (AIP) | 544 | ||
| Aminolevulinic Acid Dehydratase Deficiency Porphyria (ADP) | 545 | ||
| Neurovisceral Symptoms Plus Photosensitivity | 545 | ||
| Variegate Porphyria (VP) | 545 | ||
| Hereditary Coproporphyria (HCP) | 546 | ||
| Photosensitivity Plus Hemolytic Anemia | 546 | ||
| Porphyria Cutanea Tarda (PCT) | 546 | ||
| Congenital Erythropoietic Porphyria (CEP) | 546 | ||
| Hepatoerythropoietic Porphyria (HEP) | 546 | ||
| Photosensitivity in Isolation | 546 | ||
| Erythropoietic Protoporphyria (EPP) | 546 | ||
| Analytic Techniques | 546 | ||
| Neutrophils | 547 | ||
| Morphology of Neutrophil Precursors | 547 | ||
| Distribution and Kinetics | 548 | ||
| Function | 548 | ||
| Eosinophils | 548 | ||
| Morphology of Eosinophil Precursors | 548 | ||
| Distribution and Kinetics | 549 | ||
| Function | 549 | ||
| Basophils and Mast Cells | 549 | ||
| Morphology | 549 | ||
| Distribution and Kinetics | 550 | ||
| Function | 550 | ||
| Monocytes and Macrophages | 550 | ||
| Morphology | 550 | ||
| Distribution and Kinetics | 551 | ||
| Function | 551 | ||
| Megakaryocytes | 551 | ||
| Morphology | 551 | ||
| Megakaryocytes in Blood | 552 | ||
| Distribution and Kinetics | 552 | ||
| Function | 552 | ||
| Lymphocytes | 552 | ||
| Primary Lymphoid Tissue | 552 | ||
| B Cell Development: Bone Marrow (Table 31-8) | 552 | ||
| T Cell Development: Thymus (Table 31-9) | 554 | ||
| Natural Killer Cells: Bone Marrow | 555 | ||
| Secondary Lymphoid Tissue | 555 | ||
| Lymphocyte Function and Physiology | 555 | ||
| Selected References | 556 | ||
| References | e59 | ||
| References | 556 | ||
| CHAPTER 32 Erythrocytic Disorders | 557 | ||
| Key Points | 557 | ||
| Anemias | 557 | ||
| General Manifestations | 557 | ||
| Impaired Production—Iron Deficiency Anemia | 558 | ||
| Iron Metabolism | 558 | ||
| Iron Deficiency Anemia | 559 | ||
| Clinical Features | 559 | ||
| Laboratory Features | 559 | ||
| Blood. | 559 | ||
| Marrow. | 559 | ||
| Serum Iron. | 560 | ||
| Serum (Total) Iron-Binding Capacity. | 560 | ||
| Percent Saturation of TIBC. | 560 | ||
| Serum Ferritin. | 560 | ||
| Erythrocyte Porphyrins. | 560 | ||
| Serum Transferrin Receptors. | 560 | ||
| Serum Transferrin Receptor–to–Serum Ferritin Ratio. | 560 | ||
| Reticulocyte Hemoglobin Content. | 560 | ||
| Hepcidin Level. | 560 | ||
| Differential Diagnosis | 560 | ||
| Management | 561 | ||
| Impaired Production—Megaloblastic Anemia | 561 | ||
| Macrocytosis With Normoblastic Marrow | 561 | ||
| Megaloblastic Anemia | 561 | ||
| Blood | 561 | ||
| Marrow. | 561 | ||
| Erythrokinetics. | 561 | ||
| Cobalamin (Vitamin B12) Metabolism | 562 | ||
| Cobalamin Deficiency | 562 | ||
| Inadequate Intake | 562 | ||
| Defective Production of Intrinsic Factor | 562 | ||
| Pernicious Anemia | 562 | ||
| Clinical Features | 562 | ||
| Gastric Findings | 562 | ||
| Immune Abnormalities | 562 | ||
| Pernicious Anemia in Children | 563 | ||
| Gastrectomy | 563 | ||
| Defective Absorption of Cobalamin | 563 | ||
| Malabsorption Syndromes. | 563 | ||
| Lack of Availability of Cobalamin. | 563 | ||
| Diagnosis of Cobalamin Deficiency | 563 | ||
| Therapeutic Trial. | 563 | ||
| Serum Cobalamin Assay. | 563 | ||
| Methylmalonic Acid and Homocysteine Assays. | 563 | ||
| Deoxyuridine Suppression Test. | 563 | ||
| Detecting the Cause of Cobalamin Deficiency | 563 | ||
| Folic Acid Metabolism | 564 | ||
| The Folate–Cobalamin Relationship | 564 | ||
| Folic Acid Deficiency | 564 | ||
| Inadequate Intake of Folate | 564 | ||
| Evolution of Laboratory Abnormalities. | 564 | ||
| Nutritional Folate Deficiency. | 564 | ||
| Liver Disease. | 564 | ||
| Defective Absorption of Folate | 564 | ||
| Increased Requirement for Folate | 565 | ||
| Inadequate Utilization of Folate | 565 | ||
| Diagnosis of Folate Deficiency | 565 | ||
| Serum and Red Cell Folate. | 565 | ||
| urinary Formiminoglutamic Acid | 565 | ||
| Deoxyuridine Suppression Test. | 565 | ||
| Plasma Homocysteine Assay. | 565 | ||
| Acute Megaloblastic Anemia | 565 | ||
| Therapy for Megaloblastic Anemia | 565 | ||
| Other Defects of Nucleoprotein Synthesis | 565 | ||
| Congenital Defects | 565 | ||
| Synthetic Inhibitors | 565 | ||
| Refractory Anemias | 566 | ||
| Impaired Production—Other | 566 | ||
| Anemia of Chronic Disease | 566 | ||
| Anemia of Renal Insufficiency | 566 | ||
| Anemia in Liver Disease | 566 | ||
| Anemia in Endocrine Disease | 566 | ||
| Anemia Associated With Bone Marrow Infiltration (Myelophthisic Anemia) | 567 | ||
| Aplastic Anemia | 567 | ||
| Clinical Features | 567 | ||
| Etiology | 567 | ||
| Pathogenesis | 567 | ||
| Prognosis | 567 | ||
| Management | 567 | ||
| Idiopathic Aplastic Anemia | 568 | ||
| Blood | 568 | ||
| Bone Marrow. | 568 | ||
| Erythrokinetics. | 568 | ||
| Aplastic Anemia Associated With Chemical or Physical Agents | 568 | ||
| Toxic Aplastic Anemias. | 568 | ||
| Ionizing Radiation. | 568 | ||
| Hypersensitive Aplastic Anemias. | 568 | ||
| Aplastic Anemia Associated With Other Disease | 568 | ||
| Infection. | 568 | ||
| Paroxysmal Nocturnal Hemoglobinuria. | 568 | ||
| Pregnancy. | 569 | ||
| Thymoma. | 569 | ||
| Immunologic Diseases. | 569 | ||
| Inherited Aplastic Anemia | 569 | ||
| Fanconi’s Anemia. | 569 | ||
| Other Inherited Aplastic Anemias. | 569 | ||
| Pure Red Cell Aplasia | 569 | ||
| Transitory Arrest of Erythropoiesis (Transient Aplastic Crises) | 569 | ||
| Transient Erythroblastopenia of Childhood | 569 | ||
| Congenital Red Cell Aplasia (Diamond-Blackfan Anemia; Congenital Hypoplastic Anemia) | 569 | ||
| Acquired Pure Red Cell Aplasia | 570 | ||
| Sideroblastic Anemia | 570 | ||
| Hereditary Sideroblastic Anemias | 570 | ||
| Acquired Sideroblastic Anemias | 570 | ||
| Refractory Anemia With Ring Sideroblasts. | 570 | ||
| Secondary (Drug- or Toxin-Induced) Sideroblastic Anemia | 570 | ||
| Refractory Anemia | 570 | ||
| Congenital Dyserythropoietic Anemias | 570 | ||
| Blood Loss Anemia | 571 | ||
| Acute Posthemorrhagic Anemia | 571 | ||
| Chronic Posthemorrhagic Anemia | 571 | ||
| Hemolysis—General | 571 | ||
| Erythrocyte Survival Studies | 571 | ||
| Hemoglobin Destruction | 571 | ||
| Blood Film | 572 | ||
| Bone Marrow | 572 | ||
| Hemolysis—Membrane Disorders | 572 | ||
| Hereditary Spherocytosis | 572 | ||
| Osmotic Fragility Test | 573 | ||
| Autohemolysis Test | 573 | ||
| Hereditary Elliptocytosis | 573 | ||
| Common HE | 573 | ||
| Hereditary Pyropoikilocytosis | 573 | ||
| Spherocytic HE | 574 | ||
| Southeast Asian Ovalocytosis | 574 | ||
| Hereditary Stomatocytosis (Hereditary Hydrocytosis) | 574 | ||
| Paroxysmal Nocturnal Hemoglobinuria | 574 | ||
| Sucrose Hemolysis Test | 574 | ||
| Acidified Serum Test (Ham Test) | 574 | ||
| Hemolysis—Hemoglobin Disorders | 575 | ||
| Normal Hemoglobins | 575 | ||
| Hb A (α2β2) | 575 | ||
| Hb F (α2γ2) | 575 | ||
| Hb A2 (α2δ2) | 575 | ||
| Embryonic Hemoglobins. | 575 | ||
| The Globin Gene Clusters. | 575 | ||
| Glycosylated Hemoglobins. | 575 | ||
| Laboratory Investigation of Hemoglobinopathies and Thalassemias | 576 | ||
| Cation-Exchange HPLC. | 576 | ||
| Hemoglobin Electrophoresis and Isoelectric Focusing. | 576 | ||
| Alkali Denaturation Test for Hb F. | 576 | ||
| Acid Elution Slide Test for F Cells. | 576 | ||
| Hb A2 Quantitation. | 576 | ||
| Sickling Test—Metabisulfite Slide Test. | 576 | ||
| Sickle Solubility Test. | 576 | ||
| DNA Analysis (Old, 2001). | 577 | ||
| Structural Hemoglobin Variants | 577 | ||
| Abnormal Hemoglobin Syndromes | 577 | ||
| Sickling Disorders | 580 | ||
| Sickle Cell Trait (Hb AS) | 580 | ||
| Sickle Cell Disease (Hb SS) | 580 | ||
| Complications. | 580 | ||
| Diagnosis. | 582 | ||
| Hemoglobin SC Disease | 582 | ||
| Hb S/β-Thalassemia | 582 | ||
| Hb SS/α-Thalassemia | 582 | ||
| Hemoglobin SD Disease | 582 | ||
| (Hb S/D–Los Angeles). | 582 | ||
| Hb S/O Arab. | 582 | ||
| Other Common β-Chain Variants | 582 | ||
| Hb C Trait (β6 glu→lys). | 582 | ||
| Hb C Disease. | 583 | ||
| Hb C/β+-Thalassemia. | 583 | ||
| Hb C/β0-thalassemia. | 583 | ||
| Hb E (β 26 glu→lys). | 583 | ||
| Hb E Trait (Hb AE). | 583 | ||
| Hemoglobin E Disease. | 583 | ||
| Hb E/β-Thalassemia. | 583 | ||
| Hb D Los Angeles (Punjab) (β121 glu→gln). | 583 | ||
| Common α-Chain Variants | 583 | ||
| Hb G Philadelphia (α 68asn→lys). | 583 | ||
| Disorders of Hemoglobin Function and Stability | 584 | ||
| Hemoglobins Associated With High Oxygen Affinity and Polycythemia | 584 | ||
| Hemoglobins Associated With Low Oxygen Affinity | 584 | ||
| M Hemoglobins: Pseudocyanosis | 584 | ||
| Unstable Hemoglobins (Bunn, 1998) | 584 | ||
| Heat Instability Test. | 584 | ||
| Isopropanol Precipitation Test. | 584 | ||
| Thalassemias | 584 | ||
| Molecular Defects | 585 | ||
| β-Thalassemias | 585 | ||
| Homozygous β-Thalassemia (Thalassemia Major; Cooley’s Anemia) | 585 | ||
| Heterozygous β-Thalassemia (β-Thalassemia Trait; Thalassemia Minor; Cooley’s Trait) | 586 | ||
| δβ0-Thalassemia | 587 | ||
| δβ+-Thalassemia: Lepore Hemoglobins | 587 | ||
| Hereditary Persistence of Fetal Hemoglobin | 587 | ||
| Deletional Pancellular HPFH. | 587 | ||
| Hb Kenya. | 587 | ||
| Nondeletional Pancellular HPFH. | 587 | ||
| α-Thalassemias | 587 | ||
| α-Thalassemia Syndromes | 588 | ||
| Hemoglobin Bart’s Hydrops Fetalis (−−/−−). | 588 | ||
| Hemoglobin H Disease (−α/−−). | 588 | ||
| Hemoglobin H Preparation. | 588 | ||
| α-Thalassemia Trait: Heterozygous α°-Thalassemia (−−/αα) or Homozygous α+-Thalassemia (−α/−α). | 588 | ||
| Silent Carrier α-Thalassemia (Heterozygous α+-Thalassemia) (αα/−α). | 589 | ||
| Hemoglobin Constant Spring (αCSα/). | 589 | ||
| Screening and Prenatal Diagnosis of Hemoglobin Disorders | 589 | ||
| Hemolysis—Metabolic Disorders | 589 | ||
| Erythrocyte Metabolism | 589 | ||
| Glucose-6-Phosphate Dehydrogenase Deficiency | 589 | ||
| Heinz Bodies | 590 | ||
| Ascorbate Cyanide Test | 591 | ||
| Fluorescent Spot Test | 591 | ||
| Quantitative Assay of G6PD. | 591 | ||
| Pyruvate Kinase (PK) Deficiency | 591 | ||
| Fluorescent Spot Test. | 591 | ||
| Quantitative Assay of PK. | 591 | ||
| Other Glycolytic Enzyme Deficiencies | 591 | ||
| Pyrimidine-5′-Nucleotidase Deficiency | 592 | ||
| Hemolysis—Acquired; Extrinsic | 592 | ||
| Chemical Agents | 592 | ||
| Agents Hemolytic to Normal Cells | 592 | ||
| Agents Hemolytic to Abnormal Cells | 592 | ||
| Physical Agents | 592 | ||
| Heat | 592 | ||
| Traumatic Hemolysis | 592 | ||
| Macroangiopathic Hemolytic Anemia (Cardiac Valvular Disease and Prostheses). | 592 | ||
| Thrombotic Microangiopathy (Microangiopathic Hemolytic Anemia). | 592 | ||
| Hemolytic-Uremic Syndrome | 593 | ||
| Thrombotic Thrombocytopenic Purpura (TTP) | 593 | ||
| Preeclampsia/Eclampsia | 593 | ||
| Infectious Agents | 593 | ||
| Immune Hemolytic Anemias | 593 | ||
| Autoimmune Hemolytic Anemia | 593 | ||
| Etiology and Pathophysiology. | 594 | ||
| AIHA Associated With Warm Antibody. | 594 | ||
| AIHA Associated With Cold Antibody. | 595 | ||
| Cold Agglutinin Disease | 595 | ||
| Paroxysmal Cold Hemoglobinuria | 595 | ||
| AIHA Associated With Warm and Cold Antibodies | 595 | ||
| Alloimmune Hemolytic Disease of the Newborn | 595 | ||
| Drug-Induced Immune Hemolytic Anemia | 596 | ||
| Formation of Ternary Complexes (Neoantigen Formation). | 596 | ||
| Adsorption of Drug to Red Cell Membrane. | 596 | ||
| Induction of Autoantibody by Drugs. | 596 | ||
| Nonimmunologic Adsorption of Immunoglobulins to Red Cell Membrane. | 596 | ||
| Laboratory Diagnosis of Anemia | 596 | ||
| Macrocytic Anemia (Increased MCV) | 597 | ||
| Megaloblastic Marrow | 597 | ||
| Nonmegaloblastic Marrow | 597 | ||
| Microcytic and Hypochromic Anemias (Decreased MCV and MCH) | 597 | ||
| Normocytic and Normochromic Anemias (Normal MCV) | 597 | ||
| Optimal Marrow Response: Reticulocyte Production Index Greater Than Two | 597 | ||
| Direct Antiglobulin (Coombs’) Test. | 598 | ||
| Inadequate Marrow Response: Reticulocyte Production Index Less Than Two | 598 | ||
| Polycythemia | 598 | ||
| Relative Polycythemia | 598 | ||
| Absolute Polycythemia | 598 | ||
| Appropriately Increased Erythropoietin Production Due to Hypoxia | 598 | ||
| Arterial Oxygen Unsaturation | 599 | ||
| High Oxygen Affinity Hemoglobinopathy | 599 | ||
| Inappropriate Erythropoietin Production | 599 | ||
| Neoplasms | 599 | ||
| Renal Disorders | 599 | ||
| Familial Polycythemia | 599 | ||
| Polycythemia Vera | 599 | ||
| Measurement of Erythrocyte and Plasma Volume | 599 | ||
| Erythrocyte Volume | 599 | ||
| Plasma Volume | 599 | ||
| Interpretation | 599 | ||
| Selected References | 600 | ||
| References | e60 | ||
| References | 600 | ||
| CHAPTER 33 Leukocytic Disorders | 601 | ||
| Key Points | 602 | ||
| Leukocytes | 602 | ||
| Nonneoplastic Disorders | 603 | ||
| Granulocytic and Monocytic Disorders | 603 | ||
| Neutrophilia | 603 | ||
| Mechanisms | 603 | ||
| Determinants | 604 | ||
| Neutropenia | 604 | ||
| Morphologic Alterations in Neutrophils | 606 | ||
| Toxic Granulation | 606 | ||
| Döhle Inclusion Bodies | 606 | ||
| May-Hegglin Anomaly | 606 | ||
| Alder-Reilly Anomaly | 606 | ||
| Pelger-Huët Anomaly | 607 | ||
| Chédiak-Higashi Syndrome | 607 | ||
| Functional Disorders of Neutrophils | 607 | ||
| Eosinophilia | 608 | ||
| Basophilia | 609 | ||
| Monocytosis | 610 | ||
| Monocytopenia | 610 | ||
| Lymphocytic and Plasmacytic Disorders | 610 | ||
| Lymphocytes in Normal Individuals | 610 | ||
| Lymphocytosis | 610 | ||
| Acute Infectious Lymphocytosis | 610 | ||
| Pertussis | 611 | ||
| Chronic Lymphocytosis/Persistent Polyclonal B Cell Lymphocytosis | 611 | ||
| Retrovirus-Associated Diseases and Conditions | 611 | ||
| Infectious Mononucleosis and Epstein-Barr Virus Infection | 611 | ||
| Etiology and Pathophysiology. | 611 | ||
| Clinical Features. | 612 | ||
| Complications. | 612 | ||
| Hematologic Features. | 613 | ||
| Serologic Findings in Immunocompetent Patients | 613 | ||
| Heterophil Antibody. | 613 | ||
| Differential Diagnosis. | 613 | ||
| Course. | 613 | ||
| Cytomegalovirus Infection | 613 | ||
| Toxoplasmosis | 613 | ||
| Autoimmune Lymphoproliferative Syndrome | 614 | ||
| Other Nonneoplastic Causes of Lymphadenopathy | 614 | ||
| Lymphocytopenia | 614 | ||
| Acquired Immunodeficiency Syndrome | 614 | ||
| Etiology. | 614 | ||
| Hematologic Features. | 614 | ||
| Functional Disorders of Lymphocytes | 614 | ||
| Plasmacytosis | 615 | ||
| Leukemoid Reactions | 615 | ||
| Neutrophilic Leukemoid Reactions | 615 | ||
| Eosinophilic Leukemoid Reactions | 615 | ||
| Erythroblastosis and Leukoerythroblastosis | 615 | ||
| Lymphocytic Leukemoid Reactions | 615 | ||
| Neoplastic Disorders Primarily Involving Leukocytes | 615 | ||
| Overview of Hematopoietic Neoplasms | 615 | ||
| Chronic Myeloproliferative Disorders | 616 | ||
| Chronic Myelogenous Leukemia | 616 | ||
| Clinical Features | 616 | ||
| Laboratory Features | 616 | ||
| Blood. | 616 | ||
| Marrow. | 616 | ||
| Neutrophil Alkaline Phosphatase. | 616 | ||
| Cytogenetic Abnormalities. | 616 | ||
| Other Findings. | 616 | ||
| Course | 616 | ||
| Chronic Neutrophilic Leukemia | 617 | ||
| Polycythemia Vera | 617 | ||
| Clinical Features | 618 | ||
| Laboratory Features | 618 | ||
| Blood. | 618 | ||
| Marrow. | 618 | ||
| Diagnosis | 618 | ||
| Primary Myelofibrosis | 618 | ||
| Biology | 619 | ||
| Course | 619 | ||
| Essential Thrombocythemia | 619 | ||
| Clinical Features | 619 | ||
| Laboratory Features | 619 | ||
| Blood. | 619 | ||
| Marrow. | 619 | ||
| Diagnosis | 619 | ||
| Genetics | 619 | ||
| Chronic Myeloproliferative Disease, Unclassifiable | 620 | ||
| Chronic Eosinophilic Leukemia, Not Otherwise Specified, and Idiopathic Hypereosinophilic Syndrome | 620 | ||
| Mastocytosis | 620 | ||
| Myeloproliferative Neoplasm, Unclassifiable | 621 | ||
| Myeloid and Lymphoid Neoplasms with Eosinophilia and Abnormalities of PDGFRA, PDGFRB, or FGFR1 | 621 | ||
| Myelodysplastic and Myelodysplastic/Myeloproliferative Neoplasms | 621 | ||
| Types of Abnormal Cellular Maturation | 621 | ||
| Myelodysplastic/Myeloproliferative Neoplasms | 622 | ||
| Chronic Myelomonocytic Leukemia | 622 | ||
| Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative | 622 | ||
| Juvenile Myelomonocytic Leukemia | 623 | ||
| Myelodysplastic/Myeloproliferative Disease, Unclassifiable | 623 | ||
| Refractory Anemia with Ring Sideroblasts Associated With Marked Thrombocytosis | 623 | ||
| Myelodysplastic Syndromes | 623 | ||
| Refractory Cytopenia with Unilineage Dysplasia | 623 | ||
| Refractory Anemia | 623 | ||
| Refractory Neutropenia | 624 | ||
| Refractory Thrombocytopenia | 624 | ||
| Refractory Anemia with Ring Sideroblasts | 624 | ||
| Refractory Cytopenia with Multilineage Dysplasia | 624 | ||
| Refractory Anemia with Excess Blasts | 624 | ||
| Myelodysplastic Syndrome with Isolated del(5q) | 624 | ||
| Myelodysplastic Syndrome, Unclassified | 624 | ||
| Childhood Myelodysplastic Syndrome; Refractory Cytopenia of Childhood | 624 | ||
| Acute Myeloid Leukemia | 625 | ||
| Acute Leukemia with Recurrent Genetic Abnormalities | 626 | ||
| AML with Balanced Translocations/Inversions | 626 | ||
| AML with t(8;21)(q22;q22), RUNX1-RUNX1T1. | 626 | ||
| AML with inv(16)(p13q22) or t(16;16)(p13.1;q22), CBFβ/MYH11. | 627 | ||
| Acute Promyelocytic Leukemia with t(15;17)(q22;q12), PML/RARα, and Variants. | 627 | ||
| AML with t(9;11)(p22;q23); MLLT3-MLL. | 627 | ||
| AML with t(6;9)(p23;q34); DEK-NUP214. | 627 | ||
| AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1. | 627 | ||
| AML (Megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1. | 627 | ||
| AML with Gene Mutations | 628 | ||
| AML with NPM1 Mutation. | 628 | ||
| AML with CEBPA. | 628 | ||
| Acute Myeloid Leukemia with Myelodysplasia-Related Changes | 628 | ||
| Therapy-Related Myeloid Neoplasms | 628 | ||
| Acute Myeloid Leukemia, Not Otherwise Specified | 628 | ||
| Acute Myeloblastic Leukemia, Minimally Differentiated | 628 | ||
| Acute Myeloblastic Leukemia without Maturation (M1) | 629 | ||
| Acute Myeloblastic Leukemia with Maturation | 629 | ||
| Acute Myelomonocytic Leukemia | 629 | ||
| Acute Monoblastic and Acute Monocytic Leukemia | 629 | ||
| Erythroleukemia | 629 | ||
| Acute Megakaryoblastic Leukemia | 630 | ||
| Acute Basophilic Leukemia | 630 | ||
| Acute Panmyelosis with Myelofibrosis | 630 | ||
| Myeloid Sarcoma | 630 | ||
| Myeloid Proliferations Related to Down Syndrome | 631 | ||
| Transient Abnormal Myelopoiesis | 631 | ||
| Myeloid Leukemia Associated with Down Syndrome | 631 | ||
| Blastic Plasmacytoid Dendritic Cell Neoplasm | 631 | ||
| Acute Leukemias of Ambiguous Lineage | 631 | ||
| Undifferentiated Acute Leukemia | 631 | ||
| Mixed Phenotype Acute Leukemia with t(9;22)(q34;q11.2); BCR-ABL1 | 631 | ||
| Mixed Phenotype Acute Leukemia with t(v;11q23); MLL Rearranged | 631 | ||
| Mixed Phenotype Acute Leukemia, B/Myeloid, NOS | 632 | ||
| Mixed Phenotype Acute Leukemia, T/Myeloid, NOS | 632 | ||
| Mixed Phenotype Acute Leukemia, NOS—Other Rare Types | 632 | ||
| Natural Killer Cell Lymphoblastic Leukemia/Lymphoma | 632 | ||
| Precursor Lympoid Neoplasms | 632 | ||
| B Lymphoblastic Leukemia/Lymphoma | 632 | ||
| Clinical Features | 632 | ||
| Marrow | 632 | ||
| Cytogenetics | 632 | ||
| B Lymphoblastic Leukemia/Lymphoma with t(9;22)(q34;q11.2); BCR-ABL1 | 632 | ||
| B Lymphoblastic Leukemia/Lymphoma with t(v;11q23); MLL Rearranged | 632 | ||
| B Lymphoblastic Leukemia/Lymphoma with t(12;21)(p12;q22); TEL-AML1 (ETV6-RUNX1) | 633 | ||
| B Lymphoblastic Leukemia/Lymphoma with t(1;19)(q23;p13.3); E2A-PBX1 (TCF3-PBX1) | 633 | ||
| B Lymphoblastic Leukemia/Lymphoma with t(5;14)(q31;q32); IL3-IGH | 633 | ||
| B Lymphoblastic Leukemia/Lymphoma with Hyperdiploidy | 633 | ||
| B Lymphoblastic Leukemia/Lymphoma with Hypodiploidy | 633 | ||
| B Lymphoblastic Leukemia/Lymphoma, Not Otherwise Specified (Refers to All Other B-ALL) | 633 | ||
| Precursor T Lymphoblastic Leukemia/Lymphoblastic Lymphoma | 633 | ||
| Morphology. | 633 | ||
| Genetics. | 633 | ||
| Mature B Cell Neoplasms | 633 | ||
| Monoclonal B Cell Lymphocytosis | 633 | ||
| Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma | 633 | ||
| B Cell Prolymphocytic Leukemia | 635 | ||
| Splenic Marginal Zone Lymphoma | 636 | ||
| Hairy Cell Leukemia | 636 | ||
| Splenic B Cell Lymphoma/Leukemia, Unclassifiable | 637 | ||
| Splenic Diffuse Red Pulp Small B Cell Lymphoma | 637 | ||
| Hairy Cell Leukemia Variant | 637 | ||
| Lymphoplasmacytic Lymphoma | 637 | ||
| Heavy Chain Diseases | 638 | ||
| γ Heavy Chain Disease | 638 | ||
| α Heavy Chain Disease | 638 | ||
| µ Heavy Chain Disease | 638 | ||
| Plasma Cell Neoplasms | 638 | ||
| Monoclonal Gammopathy of Undetermined Significance | 638 | ||
| Plasma Cell Myeloma | 638 | ||
| Clinical Variants | 639 | ||
| Asymptomatic (Smoldering) Myeloma. | 639 | ||
| Nonsecretory Myeloma. | 639 | ||
| Plasma Cell Leukemia. | 639 | ||
| Solitary Plasmacytoma of Bone. | 639 | ||
| Extraosseous Plasmacytoma. | 639 | ||
| Monoclonal Immunoglobulin Deposition Diseases | 639 | ||
| Primary Amyloidosis | 639 | ||
| Monoclonal Light and Heavy Chain Deposition Diseases | 639 | ||
| Osteosclerotic Myeloma | 639 | ||
| Extranodal Marginal Zone B Cell Lymphoma of Mucosa-Associated Lymphoid Tissue | 640 | ||
| Nodal Marginal Zone Lymphoma | 640 | ||
| Pediatric Nodal Marginal Zone Lymphoma | 640 | ||
| Follicular Lymphoma | 640 | ||
| Primary Cutaneous Follicle Center Lymphoma | 641 | ||
| Mantle Cell Lymphoma | 641 | ||
| Diffuse Large B Cell Lymphoma, NOS | 642 | ||
| T Cell/Histiocyte-Rich Large B Cell Lymphoma | 642 | ||
| Primary DLBCL of the CNS | 642 | ||
| Primary Cutaneous DLBCL, Leg Type | 642 | ||
| EBV-Positive DLBCL of the Elderly | 643 | ||
| DLBCL Associated with Inflammation | 643 | ||
| Lymphomatoid Granulomatosis | 643 | ||
| Primary Mediastinal (Thymic) Large B Cell Lymphoma | 643 | ||
| Intravascular Large B Cell Lymphoma | 643 | ||
| ALK-Positive Large B Cell Lymphoma | 643 | ||
| Plasmablastic Lymphoma | 643 | ||
| Large B Cell Lymphoma Arising in HHV8-Associated Multicentric Castleman’s Disease | 643 | ||
| Primary Effusion Lymphoma | 643 | ||
| Burkitt Lymphoma | 644 | ||
| B Cell Lymphoma, Unclassifiable, with Features Intermediate Between DLBCL and Burkitt Lymphoma | 644 | ||
| B Cell Lymphoma, Unclassifiable, with Features Intermediate Between DLBCL and Classical Hodgkin Lymphoma | 644 | ||
| Mature T Cell And Natural Killer Cell Neoplasms | 645 | ||
| T-Prolymphocytic Leukemia | 645 | ||
| Large Granular Lymphocyte Leukemia | 645 | ||
| Chronic Lymphoproliferative Disorders of NK Cells | 645 | ||
| Aggressive NK Cell Leukemia | 645 | ||
| EBV-Positive T Cell Lymlphoproliferative Disorders of Childhood | 647 | ||
| Adult T Cell Leukemia-Lymphoma | 647 | ||
| Extranodal NK/T Cell Lymphoma, Nasal Type | 647 | ||
| Enteropathy-Associated T Cell Lymphoma | 647 | ||
| Hepatosplenic T Cell Lymphoma | 648 | ||
| Subcutaneous Panniculitis-like T Cell Lymphoma | 648 | ||
| Mycosis Fungoides and Sézary Syndrome | 648 | ||
| Primary Cutaneous CD30-Positive T Cell Lymphoproliferative Disorder | 649 | ||
| Primary Cutaneous γδ T Cell Lymphoma | 649 | ||
| Angioimmunoblastic T Cell Lymphoma | 649 | ||
| Peripheral T/NK Cell Lymphoma, Unspecified | 650 | ||
| Anaplastic Large Cell Lymphoma | 650 | ||
| Hodgkin Lymphoma | 650 | ||
| Classical Hodgkin Lymphoma | 651 | ||
| Nodular Sclerosis | 651 | ||
| Mixed Cellularity | 652 | ||
| Lymphocyte Depletion | 652 | ||
| Nodular Lymphocyte Predominant HL | 652 | ||
| Nodular Lymphocyte-Rich Classical HL | 652 | ||
| Immunodeficiency-Associated Lymphoproliferative Disorders | 652 | ||
| HIV-Associated Lymphomas | 653 | ||
| Posttransplant Lymphoproliferative Disorders | 653 | ||
| Histiocytic and Dendritic Cell Neoplasms | 653 | ||
| Hemophagocytic Syndromes | 653 | ||
| Langerhans Histiocytosis | 653 | ||
| Interdigitating Dendritic Cell Sarcoma/Tumor | 654 | ||
| Follicular Dendritic Cell Sarcoma/Tumor | 654 | ||
| Dendritic Cell Sarcoma, Not Otherwise Specified | 654 | ||
| Selected References | 654 | ||
| References | e63 | ||
| References | 655 | ||
| CHAPTER 34 The Flow Cytometric Evaluation of Hematopoietic Neoplasia | 656 | ||
| Key Points | 656 | ||
| Technical Considerations | 656 | ||
| Instrumentation | 656 | ||
| Reagents | 657 | ||
| Panel Design | 658 | ||
| Specimen Handling and Sample Preparation | 659 | ||
| Data Acquisition | 660 | ||
| Interpretive Considerations | 660 | ||
| Normal Patterns of Antigen Expression | 660 | ||
| Abnormal Patterns of Antigenic Expression in Hematopoietic Neoplasia | 660 | ||
| Acute Leukemia | 660 | ||
| Diagnosis and Classification | 660 | ||
| Prognostic Factors | 664 | ||
| Therapeutic Targets | 664 | ||
| Residual Disease Monitoring in Acute Leukemia | 664 | ||
| Lymphoma | 665 | ||
| Diagnosis and Classification | 665 | ||
| Prognostic Factors | 669 | ||
| Therapeutic Targets | 669 | ||
| Minimal Residual Disease Detection | 669 | ||
| Plasma Cell Neoplasms | 671 | ||
| Myelodysplastic Syndromes and Myeloproliferative Disorders | 671 | ||
| Paroxysmal Nocturnal Hemoglobinuria | 672 | ||
| Summary | 672 | ||
| Selected References | 673 | ||
| References | e69 | ||
| References | 673 | ||
| CHAPTER 35 Immunohematology | 674 | ||
| Key Points | 675 | ||
| Basic Immunohematologic Concepts | 675 | ||
| Blood Group Antigens | 675 | ||
| Immunogenicity | 675 | ||
| Chemical Characteristics | 676 | ||
| Antigen Density | 676 | ||
| Blood Group Antibodies | 676 | ||
| Immunoglobulins and Antigen Binding | 676 | ||
| Blood Group Alloantibodies and Autoantibodies | 677 | ||
| The Complement System and Blood Banking | 677 | ||
| Role of Complement in Erythrocyte Destruction | 677 | ||
| Intravascular Hemolysis | 677 | ||
| Extravascular Hemolysis | 677 | ||
| Erythrocyte Antigens and Antibodies | 678 | ||
| ABO and H Blood Group Systems (ISBT no. 001 and 018) | 678 | ||
| Null and Weak Phenotypes | 679 | ||
| Biochemistry | 680 | ||
| Molecular Biology | 681 | ||
| ABO Antibodies | 682 | ||
| Less Common ABO Antibodies | 682 | ||
| Anti-A1. | 682 | ||
| Anti-H. | 682 | ||
| Biological Role | 682 | ||
| MNS Blood Group System (ISBT no. 002) | 682 | ||
| Null Phenotypes | 683 | ||
| Biochemistry | 683 | ||
| Molecular Biology | 684 | ||
| MNSs Antibodies | 684 | ||
| Anti-M and -N | 684 | ||
| Anti-S, -s, and -U | 684 | ||
| Biological Role | 684 | ||
| P Blood Group System (ISBT no. 003 and 028) | 684 | ||
| Null/Weak Phenotypes | 684 | ||
| Biochemistry | 684 | ||
| Molecular Biology | 685 | ||
| P Blood Group Antibodies | 686 | ||
| Anti-P1 | 686 | ||
| Alloanti-PP1Pk | 687 | ||
| Alloanti-P | 687 | ||
| Auto-Anti-P (Donath-Landsteiner) | 687 | ||
| Biological Role | 687 | ||
| Rh and RHAG Blood Group Systems (ISBT no. 004 and 030) | 687 | ||
| Theories of Rh Inheritance and Classification System | 687 | ||
| Biochemistry | 687 | ||
| Molecular Biology | 688 | ||
| D Antigen | 688 | ||
| Weak D Antigen | 690 | ||
| Partial D Antigen | 690 | ||
| Rh-Negative Phenotype | 690 | ||
| C/c, E/e, and Compound Rh Antigens | 691 | ||
| G Antigen | 691 | ||
| Weak and Deletion C/c and E/e Phenotypes | 691 | ||
| RHAG Alloantigens | 691 | ||
| Rhnull Phenotype | 691 | ||
| Rhmod Phenotype | 691 | ||
| Rh Antibodies | 691 | ||
| Biological Role | 691 | ||
| Lutheran Blood Group System (ISBT no. 005) | 692 | ||
| Null/Weak Phenotypes | 692 | ||
| Biochemistry | 692 | ||
| Molecular Biology | 693 | ||
| Lutheran Antibodies | 693 | ||
| Biological Role | 693 | ||
| Kell and KX Blood Group Systems (ISBT no. 006 and 019) | 693 | ||
| Null and Weak Phenotypes | 693 | ||
| Biochemistry | 695 | ||
| Molecular Biology | 695 | ||
| Kell Antibodies | 695 | ||
| Biological Role | 696 | ||
| Lewis Blood Group System (ISBT no. 007) | 696 | ||
| Biochemistry | 696 | ||
| Molecular Biology | 696 | ||
| Lewis Antibodies | 697 | ||
| Biological Role | 697 | ||
| Duffy Blood Group System (ISBT no. 008) | 697 | ||
| Biochemistry | 697 | ||
| Molecular Biology | 698 | ||
| Duffy Antibodies | 698 | ||
| Biological Role | 698 | ||
| Kidd Blood Group System (ISBT no. 009) | 699 | ||
| Null Phenotypes | 699 | ||
| Biochemistry | 699 | ||
| Molecular Biology | 699 | ||
| Kidd Antibodies | 700 | ||
| Biological Role | 700 | ||
| Diego Blood Group System (ISBT no. 010) | 700 | ||
| Biochemistry | 700 | ||
| Molecular Biology | 700 | ||
| Diego Antibodies | 701 | ||
| Biological Role | 701 | ||
| Cartwright Blood Group System (ISBT no. 011) | 701 | ||
| PART 5 Hemostasis and Thrombosis | 783 | ||
| CHAPTER 39 Coagulation and Fibrinolysis | 785 | ||
| Key Points | 785 | ||
| Overview of Coagulation and Fibrinolysis | 785 | ||
| Physiologic Hemostasis | 786 | ||
| Endothelium and Platelets | 786 | ||
| Coagulation Protein System | 787 | ||
| Characterization of Coagulation Proteins | 787 | ||
| Physiologic Protein Assemblies | 787 | ||
| The Formation of Fibrin and the Fibrinolytic System | 788 | ||
| The Anticoagulation Protein Systems (Fig. 39-5) | 788 | ||
| Protein C/Protein S System | 789 | ||
| Antithrombin | 789 | ||
| Tissue Factor Pathway Inhibitor | 790 | ||
| Current Hypothesis for Initiation of the Hemostatic System | 790 | ||
| Clinical Laboratory Hemostasis | 790 | ||
| Physiologic Hemostasis Versus Clinical Assays | 790 | ||
| Screening Tests for Coagulation Disorders | 791 | ||
| Activated Partial Thromboplastin Time (Fig. 39-7, A) | 791 | ||
| Prothrombin Time (Fig. 39-7, B) | 791 | ||
| Thrombin Time (Fig. 39-7, C) | 791 | ||
| Assays Used in Clinical Coagulation Testing | 792 | ||
| Practical Approach to Patients with Coagulation Disorders | 793 | ||
| Hereditary Coagulation Protein Defects | 794 | ||
| Deficiency of Factor VIII (Hemophilia A) or Factor IX (Hemophilia B) | 794 | ||
| Evaluation of Carriers | 795 | ||
| Treatment of Hemophilia | 795 | ||
| Complications of Treatment | 795 | ||
| Hereditary Deficiencies of Other Coagulation Factors | 795 | ||
| Disorders With Prolonged APTT and Normal PT | 796 | ||
| Factor XI | 796 | ||
| FXII, Prekallikrein, and High Molecular Weight Kininogen | 797 | ||
| Disorders With Prolonged APTT and PT | 797 | ||
| Disorders of Fibrinogen | 797 | ||
| FII Deficiency | 797 | ||
| FV Deficiency | 797 | ||
| FX Deficiency | 797 | ||
| Combined Deficiency of FV and FVIII | 797 | ||
| Combined Deficiency of Vitamin K–Dependent Clotting Factors | 798 | ||
| Disorders With Normal APTT and Prolonged PT | 798 | ||
| FVII Deficiency | 798 | ||
| Disorders With Normal APTT and PT | 798 | ||
| FXIII Deficiency | 798 | ||
| Hereditary Hemorrhagic Disorders of Fibrinolysis | 798 | ||
| Acquired Coagulation Disorders | 798 | ||
| Thrombotic Disorders and Disseminated Intravascular Coagulation | 798 | ||
| Liver Disease | 799 | ||
| Vitamin K Deficiency | 799 | ||
| Massive Transfusion | 799 | ||
| Acquired Coagulation Protein Inhibitors and Lupus Anticoagulant | 799 | ||
| Selected References | 800 | ||
| References | e86 | ||
| References | 800 | ||
| CHAPTER 40 Blood Platelets and von Willebrand Disease | 801 | ||
| Key Points | 801 | ||
| Normal Platelet Biology | 801 | ||
| Platelet Structure | 801 | ||
| Platelet Membrane Glycoproteins and Phospholipids | 802 | ||
| Role Of Platelets In Hemostasis And Platelet Activation Mechanisms | 802 | ||
| Platelet Activation and Signaling Events | 803 | ||
| Platelet Coagulant Activity | 805 | ||
| Laboratory Evaluation of Platelet Function Disorders | 805 | ||
| Initial Laboratory Evaluation | 805 | ||
| Screening Studies of Platelet Function | 805 | ||
| Platelet Aggregation and Secretion Studies | 806 | ||
| Evaluation of Platelet Function Using Flow Cytometry | 808 | ||
| Quantitative Platelet Disorders | 809 | ||
| Thrombocytopenia | 809 | ||
| Congenital Thrombocytopenia | 809 | ||
| Immune Thrombocytopenic Purpura | 809 | ||
| Drug-Induced Thrombocytopenia | 811 | ||
| Heparin-Induced Thrombocytopenia | 811 | ||
| Thrombotic Thrombocytopenic Purpura | 811 | ||
| Thrombocytosis | 811 | ||
| Inherited Disorders of Platelet Function | 811 | ||
| Overview | 811 | ||
| Disorders Of Platelet Adhesion | 812 | ||
| Bernard-Soulier Syndrome | 812 | ||
| von Willebrand Disease | 813 | ||
| Disorders of Platelet Aggregation | 813 | ||
| Glanzmann Thrombasthenia | 813 | ||
| Disorders of Platelet Granules, Secretion, And Signal Transduction | 813 | ||
| Deficiency of Granule Stores | 813 | ||
| δ-Storage Pool Deficiency | 813 | ||
| Gray Platelet Syndrome | 814 | ||
| Quebec Platelet Disorder | 814 | ||
| Defects in Receptors, G-Proteins, and Platelet Signal Transduction | 814 | ||
| Defects in Cytoskeletal Assembly | 815 | ||
| Disorders of Platelet Procoagulant Activities | 815 | ||
| Transcription Factor Mutations and Associated Platelet Dysfunction | 815 | ||
| RUNX1/CBFA2 (Familial Platelet Disorder With Predisposition to Acute Myelogenous Leukemia) | 815 | ||
| GATA-1 | 815 | ||
| Relative Frequencies of Various Inherited Platelet Defects | 815 | ||
| Evaluation of Patients with Suspected Platelet Disorders | 815 | ||
| Therapy for Congenital Platelet Function Defects | 816 | ||
| Von Willebrand Factor and Von Willebrand Disease | 816 | ||
| von Willebrand Factor Biology | 816 | ||
| von Willebrand Disease and Its Subtypes | 817 | ||
| Laboratory Tests of von Willebrand Factor | 818 | ||
| Acquired von Willebrand Disease | 819 | ||
| Acquired Disorders Affecting Platelet Function | 819 | ||
| Myeloproliferative Disorders | 819 | ||
| Acute Leukemias and Myelodysplastic Syndromes | 819 | ||
| Dysproteinemias | 820 | ||
| Uremia | 820 | ||
| Acquired Storage Pool Disease | 820 | ||
| Antiplatelet Antibodies and Platelet Function | 821 | ||
| Drugs That Inhibit Platelet Function | 821 | ||
| Selected References | 821 | ||
| References | e89 | ||
| References | 822 | ||
| CHAPTER 41 Laboratory Approach to Thrombotic Risk | 823 | ||
| Key Points | 823 | ||
| Physiologic Anticoagulant Pathways | 823 | ||
| Thrombophilic Proteins or Factors | 824 | ||
| Antithrombin | 824 | ||
| Protein C | 825 | ||
| Protein S | 826 | ||
| Activated Protein C Resistance and Factor VLeiden | 826 | ||
| Prothrombin 20210 | 826 | ||
| Elevated Coagulation Factor Levels | 826 | ||
| Dysfibrinogenemia | 827 | ||
| Hypofibrinolytic Mechanisms | 827 | ||
| Other Possible Defects | 827 | ||
| Acquired Hypercoagulable States | 827 | ||
| Antiphospholipid Syndrome and Lupus Anticoagulant | 828 | ||
| Hyperhomocysteinemia | 828 | ||
| General Aspects of the Laboratory Evaluation for Thrombotic Risk | 828 | ||
| Selected References | 829 | ||
| References | e94 | ||
| References | 829 | ||
| CHAPTER 42 Antithrombotic Therapy | 831 | ||
| Key Points | 831 | ||
| Preanalytic Variables and Controls | 831 | ||
| Vitamin K Antagonists | 831 | ||
| Heparin | 834 | ||
| Low-Molecular-Weight Heparin | 835 | ||
| Fondaparinux | 835 | ||
| Heparin-Induced Thrombocytopenia | 836 | ||
| Monitoring of Heparin Therapy during Procedures | 839 | ||
| Direct Thrombin Inhibitors | 840 | ||
| New Oral Anticoagulants | 840 | ||
| Antiplatelet Therapy | 840 | ||
| Appendix: Clinical and Laboratory Standards Institute Preanalytic Guidelines (CLSI, 2008) | 842 | ||
| Storage of Specimens | 842 | ||
| Quality Control | 842 | ||
| Selected References | 842 | ||
| References | e96 | ||
| References | 842 | ||
| PART 6 Immunology and Immunopathology | 843 | ||
| CHAPTER 43 Overview of the Immune System and Immunologic Disorders | 845 | ||
| Key Points | 845 | ||
| Lymphoid Cells | 845 | ||
| T Lymphocytes | 845 | ||
| B Lymphocytes | 846 | ||
| Antigen-Presenting Cells | 846 | ||
| Natural Killer Cells | 846 | ||
| Nonlymphoid Cells | 846 | ||
| Neutrophils and Eosinophils | 846 | ||
| Basophils and Mast Cells | 846 | ||
| Humoral Factors | 846 | ||
| Immunoglobulins | 846 | ||
| Complement | 847 | ||
| Cytokines | 847 | ||
| Histocompatibility Antigens | 847 | ||
| Mechanisms of Immunologic Injury | 848 | ||
| Laboratory Applications of Immunologic Assessment | 848 | ||
| Therapeutics in Immunology | 849 | ||
| Selected References | 850 | ||
| References | e98 | ||
| References | 850 | ||
| CHAPTER 44 Immunoassays and Immunochemistry | 851 | ||
| Immunoassays and Immunochemistry | 851 | ||
| General Characteristics of Antigen–Antibody Reaction | 851 | ||
| Characteristics of Antigens | 852 | ||
| Characteristics of Antibodies | 852 | ||
| Polyclonal Antibodies | 852 | ||
| Monoclonal Antibodies | 852 | ||
| Antibody Production by Recombinant Technology | 852 | ||
| Kinetics of Antigen–Antibody Reaction | 852 | ||
| Overview of General Principles of Immunoassays | 853 | ||
| Classes of Immunoassays | 853 | ||
| Conjugation Chemistry | 853 | ||
| Characteristics of the Solid Phase | 853 | ||
| Precipitin and Nephelometric Immunoassays | 854 | ||
| Background and Principles of Precipitin Reaction | 854 | ||
| Nephelometric Immunoassays | 855 | ||
| Particle Immunoassay | 855 | ||
| Principle of Particle Agglutination | 855 | ||
| Hemagglutination | 855 | ||
| Gelatin Particle Agglutination | 857 | ||
| Latex Agglutination | 857 | ||
| Latex Turbidimetric Assay | 857 | ||
| Particle-Counting Immunoassay | 857 | ||
| Other Particle lmmunoassays | 857 | ||
| Summary | 857 | ||
| Radioimmunoassay | 859 | ||
| Background | 859 | ||
| Assay Principles and Methods | 859 | ||
| Summary | 861 | ||
| Enzyme Immunoassay | 861 | ||
| Background and Classification | 861 | ||
| Heterogeneous Enzyme Immunoassays | 861 | ||
| Colorimetric Enzyme Immunoassay | 862 | ||
| Fluorescent Enzyme Immunoassay | 862 | ||
| Chemiluminescent Enzyme Immunoassay | 863 | ||
| Homogeneous Enzyme Immunoassays | 863 | ||
| Background | 863 | ||
| Enzyme-Multiplied Immunoassay Technique | 864 | ||
| Substrate-Labeled Fluorescent Immunoassay | 864 | ||
| Apoenzyme Reactivation lmmunoassay | 864 | ||
| Enzyme Inhibitory Homogeneous Immunoassay | 865 | ||
| Cloned Enzyme Donor Immunoassay | 866 | ||
| Summary | 867 | ||
| Fluorescent Immunoassay | 867 | ||
| Background and Classification | 867 | ||
| Heterogeneous Fluorescent Immunoassay | 867 | ||
| Fluoroimmunometric Method | 867 | ||
| Radial Partition Immunofluorometric Assay | 868 | ||
| Time-Resolved Fluoroimmunoassay | 868 | ||
| Homogeneous Fluorescent Immunoassay | 868 | ||
| Fluorescence Polarization Assay | 868 | ||
| Fluorescence Excitation Transfer Immunoassay | 869 | ||
| Fluorescent Protection Immunoassay | 869 | ||
| Chemiluminescent Immunoassay | 869 | ||
| Background | 869 | ||
| Chemiluminescent Immunoassay Using Acridinium Esters as Labels | 869 | ||
| Electrochemiluminescent Immunoassay | 869 | ||
| Instrument Automation and Modulation of Assay Systems | 870 | ||
| Homogeneous Assay Systems | 870 | ||
| Heterogeneous Immunoassay Systems | 870 | ||
| Practical Flow of the Immunoassay in the Analytic System | 870 | ||
| Instrumentation and Key Points for the Heterogeneous Immunoassay | 870 | ||
| Reaction Cuvette | 870 | ||
| Sampling and Fluid Delivery Type | 871 | ||
| Carryover | 871 | ||
| Bound/Fixed Separation and Washing Systems | 871 | ||
| New Systems For The Next Generation (Modular Systems) | 871 | ||
| Rapid and Simple Test Devices for Point-of-Care Testing | 872 | ||
| Background | 872 | ||
| Flow-Through Assay Devices (Immunofiltration Assay Devices) | 872 | ||
| Dipping Strip | 872 | ||
| Immunochromatographic Devices | 872 | ||
| Summary | 873 | ||
| Simultaneous Multiple Immunoassays | 873 | ||
| Background | 873 | ||
| Microspot Assay | 874 | ||
| Multianalyte Microarray Immunoassay | 875 | ||
| Flow Cytometric Immunoassay | 875 | ||
| Microchannel Assay Using Compact Disk | 875 | ||
| Summary | 875 | ||
| Selected References | 876 | ||
| References | e99 | ||
| References | 876 | ||
| CHAPTER 45 Laboratory Evaluation of the Cellular Immune System | 877 | ||
| Key Points | 877 | ||
| General Principles of Cellular Immunology | 878 | ||
| Lymphocyte Activation and Proliferation | 878 | ||
| Unraveling the Biochemical Pathways of Lymphocyte Activation | 879 | ||
| Antigen-Induced Activation of T Lymphocytes | 879 | ||
| T Cell Recognition, Activation, and Signal Transduction | 879 | ||
| Signal Transduction Following Antigen-Specific Stimulation | 879 | ||
| T Cell Responses | 879 | ||
| B Cell Responses in Cellular Immunity | 881 | ||
| Flow and Image Cytometry in Evaluation of Cellular Immunity | 881 | ||
| The Flow Cytometer and Other Tools | 882 | ||
| The Light Source and Signal Processing | 882 | ||
| The Flow Cell | 882 | ||
| Colors and More Colors: Applications of Fluorochromes | 883 | ||
| Gating and Data Analysis | 884 | ||
| Immunophenotypic Analysis | 884 | ||
| DNA Analysis | 885 | ||
| General Aspects | 885 | ||
| Sample Preparation | 885 | ||
| DNA Studies of Interest in Cellular Immunology | 886 | ||
| Quantitative Flow Cytometry | 887 | ||
| Clinical Significance of Cellular Immune Testing | 887 | ||
| Clinical Interpretation of Cellular Immune Testing | 887 | ||
| Age and the Immune Response | 888 | ||
| Malnutrition and the Immune Response | 888 | ||
| Cancer and the Immune Response | 888 | ||
| Methodologic Approach to Cellular Immune Testing | 888 | ||
| Stages of Study: The Screening Stage | 889 | ||
| Stages of Study: The Confirming Stage | 889 | ||
| General Aspects | 889 | ||
| Thymic Presence | 890 | ||
| Skin Testing | 890 | ||
| Stages of Study: Analytic Immune Studies | 890 | ||
| Laboratory Evaluation of Lymphocyte Function | 891 | ||
| Lymphocyte Transformation Assays | 891 | ||
| Principles of Lymphocyte Transformation | 891 | ||
| Mitogen-Induced Blastogenesis | 891 | ||
| Mixed Lymphocyte Culture | 892 | ||
| Cytotoxicity Assays | 893 | ||
| Cytotoxic T Cell (CTL) Assays | 893 | ||
| Natural Killer Cell–Mediated Cytotoxicity | 895 | ||
| Microlymphocytotoxicity Assay | 895 | ||
| Laboratory Evaluation of Granulocyte and Monocyte Function | 895 | ||
| Assays of Neutrophilic Activation | 895 | ||
| Assays of Phagocytosis and Endocytosis | 896 | ||
| Assays of Enzymatic Activity and Intracellular Killing | 896 | ||
| Assays of Opsonization | 897 | ||
| Assays of Membrane Permeability | 897 | ||
| Quality Control and Quality Assurance in the Cellular Laboratory | 897 | ||
| Selected References | 898 | ||
| References | e101 | ||
| References | 898 | ||
| CHAPTER 46 Laboratory Evaluation of Immunoglobulin Function and Humoral Immunity | 899 | ||
| Key Points | 899 | ||
| Structural Properties of Antibodies | 899 | ||
| Antibody Molecules | 899 | ||
| Antibody–Antigen Interaction | 901 | ||
| The Genetic Basis of Antibody Diversity | 902 | ||
| General Properties of Immunoglobulins | 902 | ||
| Immunoglobulin M | 902 | ||
| Immunoglobulin G | 903 | ||
| Immunoglobulin A | 904 | ||
| Immunoglobulin D | 906 | ||
| Immunoglobulin E | 906 | ||
| Summary | 906 | ||
| Clinical Significance of Immunoglobulins | 906 | ||
| Disease Pathogenesis | 906 | ||
| Hyperimmunoglobulinemia | 906 | ||
| Serum Immunoglobulin Levels | 906 | ||
| Polyclonal Immunoglobulins | 907 | ||
| Monoclonal Immunoglobulins | 907 | ||
| Cryoglobulins | 908 | ||
| Disease Diagnosis | 908 | ||
| Immunofixation | 908 | ||
| Immunoglobulin Free Light Chain Analysis | 909 | ||
| Cryoglobulin Testing | 910 | ||
| Oligoclonal Immunoglobulin Bands in Cerebrospinal Fluid | 910 | ||
| Problems in Detecting Monoclonal Bands | 911 | ||
| Disease Prevention and Therapy | 912 | ||
| Selected References | 912 | ||
| References | e107 | ||
| References | 913 | ||
| CHAPTER 47 Mediators of Inflammation: | 914 | ||
| Key Points | 914 | ||
| Structure and Function of the Complement System | 914 | ||
| Nomenclature | 915 | ||
| C3: Central Molecule of Complement Activation Pathways | 916 | ||
| The Classical Pathway | 916 | ||
| The Alternative Pathway | 917 | ||
| The Mannan-Binding Lectin Pathway | 917 | ||
| Terminal Complement Components | 917 | ||
| Anaphylatoxins | 917 | ||
| Regulation of Complement Activation | 918 | ||
| Fluid-Phase Regulators | 918 | ||
| Cell-Associated Regulatory Proteins | 919 | ||
| Complement Receptors | 919 | ||
| Complement Biosynthesis | 920 | ||
| Complement Genetics | 920 | ||
| Complement and Acquired Immunity | 920 | ||
| Genetic Complement Deficiencies | 920 | ||
| Assessment of Complement Activity in Disease | 922 | ||
| Complement in Disease States | 923 | ||
| Rheumatologic Diseases | 923 | ||
| Hereditary Angioedema | 923 | ||
| Infectious Diseases | 923 | ||
| Renal Diseases | 924 | ||
| Ophthalmologic Diseases | 924 | ||
| Dermatologic Diseases | 924 | ||
| Hematologic Diseases | 924 | ||
| Neurologic Diseases | 924 | ||
| Cardiovascular Diseases | 925 | ||
| Biocompatibility | 925 | ||
| Organ Transplantation | 925 | ||
| Clinically Useful Complement Inhibitors | 925 | ||
| Assays of Complement | 926 | ||
| General Principles | 926 | ||
| Functional Evaluation of the Classical Pathway | 926 | ||
| Functional Evaluation of the Alternative Pathway | 927 | ||
| Functional Assay of C1-Inhibitor and Factor H | 927 | ||
| Complement Levels by Antigenic Assays | 927 | ||
| Kinins and the Kinin-Generating System | 927 | ||
| Cytokines | 927 | ||
| Cell Adhesion Molecules | 929 | ||
| Integrins | 929 | ||
| Selectins | 930 | ||
| Leukocyte Extravasation | 930 | ||
| Perspectives | 932 | ||
| Selected References | 932 | ||
| References | e108 | ||
| References | 932 | ||
| CHAPTER 48 Human Leukocyte Antigen: | 933 | ||
| Key Points | 933 | ||
| Genetics of the Major Histocompatibility Complex | 934 | ||
| Basic Genetics | 934 | ||
| Composition of The MHC | 935 | ||
| Localization of MHC Genes | 935 | ||
| Inheritance | 936 | ||
| Linkage Disequilibrium | 936 | ||
| Ethnic Variation | 936 | ||
| Class I Molecules—HLA-A, HLA-B, HLA-C Subregions | 937 | ||
| Structure of Class I Molecules | 937 | ||
| Organization of Class I Genes | 937 | ||
| Regulation of Class I Gene Expression | 937 | ||
| Function of Class I Molecules | 938 | ||
| Other Class I Genes | 938 | ||
| HLA-G | 938 | ||
| HLA-E | 939 | ||
| HLA-F | 939 | ||
| Class II Molecules—HLA-DR, HLA-DQ, HLA-DP Subregions | 939 | ||
| Structure of Class Ii Molecules | 939 | ||
| Organization of Class Ii Genes | 939 | ||
| DR Subregion | 939 | ||
| DQ Subregion | 940 | ||
| DP Subregion | 940 | ||
| Linkage Disequilibrium of Genes in the Class Ii Region | 940 | ||
| Regulation of Class II Gene Expression | 940 | ||
| Function of Class Ii Molecules | 940 | ||
| Other Class Ii Genes | 941 | ||
| Characteristics of Antigenic Fragments Bound by MHC Class I and Class II Molecules | 941 | ||
| Recognition of Foreign MHC Molecules | 941 | ||
| Tandem Repeats and Single Nucleotide Polymorphisms in the MHC | 941 | ||
| Minor Histocompatibility Molecules | 941 | ||
| HLA Nomenclature | 942 | ||
| Serologic and Cellular Specificities | 942 | ||
| Dna-Based Allele Designations | 942 | ||
| Techniques for Identifying HLA Polymorphism | 943 | ||
| Dna-Based Typing of Class I and Class Ii Alleles | 943 | ||
| Preparation and Amplification of DNA | 943 | ||
| Sequence-Specific Priming | 943 | ||
| Sequence-Specific Oligonucleotide Hybridization | 943 | ||
| Sequence-Specific Conformational Polymorphism or Heteroduplex Analysis | 943 | ||
| Nucleic Acid Sequencing | 944 | ||
| Resolution of DNA-Based Typing | 944 | ||
| Serologic Detection of Class I and Class Ii Molecules | 944 | ||
| Lymphocyte Preparation | 944 | ||
| Lymphocyte Microcytotoxicity Assay | 944 | ||
| HLA Typing Sera Trays | 945 | ||
| Cross-Reactivity | 945 | ||
| Cellular Detection of Class Ii Molecules | 945 | ||
| Tissue/Organ Transplantation | 945 | ||
| Genetic Basis of Transplantation | 945 | ||
| Histocompatibility Matching | 946 | ||
| HLA Matching | 946 | ||
| HLA-Specific Antibody Detection in Recipient Serum | 947 | ||
| Serum Screening (PRA) | 947 | ||
| Donor-Specific Crossmatch | 949 | ||
| Antibody Detection Techniques | 951 | ||
| Direct Complement-Dependent Cytotoxicity | 951 | ||
| Indirect Crossmatch Techniques | 951 | ||
| Autoantibodies | 951 | ||
| B Cell Antibodies | 951 | ||
| Selection of Recipient Serum Samples for Donor Crossmatch | 951 | ||
| Renal Transplantation | 951 | ||
| Nonrenal Organ Transplantation | 952 | ||
| Allogeneic Hematopoietic Progenitor Cell Transplantation | 952 | ||
| HLA Typing for Progenitor Cell Transplantation | 952 | ||
| Summary | 953 | ||
| Selected References | 953 | ||
| References | e114 | ||
| References | 953 | ||
| CHAPTER 49 The Major Histocompatibility Complex and Disease | 954 | ||
| Key Points | 954 | ||
| Overview of the Human Major Histocompatibility Complex DNA Sequence | 955 | ||
| Genes in the Central or Class III Region | 955 | ||
| Tumor Necrosis Factor and Lymphotoxin α and β Genes | 955 | ||
| Heat-Shock Protein 70 Genes | 956 | ||
| C2, C4, and Cfb Genes and Typing | 956 | ||
| Disease Associations with C2, C4, and CFB Genes | 957 | ||
| Complotypes | 957 | ||
| Extended Haplotypes | 957 | ||
| MHC Disease Associations | 957 | ||
| MHC Monogenic Disease Associations | 959 | ||
| Hereditary Hemochromatosis and the HFE Gene | 959 | ||
| Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency | 959 | ||
| Polygenic Diseases with MHC Associations | 960 | ||
| Abacavir Hypersensitivity | 960 | ||
| Ankylosing Spondylitis | 960 | ||
| Celiac Disease | 960 | ||
| Narcolepsy | 960 | ||
| Rheumatoid Arthritis | 960 | ||
| Type 1 Diabetes | 960 | ||
| Methods of Detecting Association or Linkage of Disease with Genetic Markers | 961 | ||
| Genetic Polymorphism | 961 | ||
| Gene and Phenotype Frequencies | 961 | ||
| Strength of Association | 961 | ||
| Analysis of Mode of Inheritance Based on Sibling Pairs | 961 | ||
| Analysis of Mode of Inheritance Based on Population Studies | 961 | ||
| Lod Score Method | 962 | ||
| Summary | 962 | ||
| Selected References | 962 | ||
| References | e117 | ||
| References | 962 | ||
| CHAPTER 50 Immunodeficiency Disorders | 963 | ||
| Key Points | 963 | ||
| Clinical Signs and Symptoms of Immunodeficiency | 964 | ||
| Evaluation of the Immune System | 964 | ||
| First-Level Investigations | 965 | ||
| Clinical History, Physical Examination, and Initial Blood Count | 965 | ||
| Immunoglobulins | 966 | ||
| Radiologic Imaging | 966 | ||
| Pulmonary Functions | 967 | ||
| Second-Level Investigations | 967 | ||
| Antibody Production | 967 | ||
| IgG Subclasses | 967 | ||
| T Cell Immunity | 967 | ||
| T Cell Functional Assessment | 967 | ||
| Polymorphonuclear Killing Assays | 968 | ||
| Complement Evaluation | 968 | ||
| Third-Level Investigations | 968 | ||
| Enzyme Measurements for Metabolic Defects | 968 | ||
| Natural Killer Cell Assays | 969 | ||
| Additional Phagocyte Analyses | 969 | ||
| Cytokines and Cytokine Receptors | 969 | ||
| Additional Cell Surface Markers | 969 | ||
| MHC Class I and II Molecules | 969 | ||
| Treatment by Targeting Cell Surface Receptors | 970 | ||
| Using Novel Immunogens to Assess Antibody Production | 970 | ||
| Molecular Genetics and Prenatal Diagnosis | 970 | ||
| Novel Approaches to Treating Immunodeficiency Disorders | 971 | ||
| Summary | 972 | ||
| Selected references | 972 | ||
| References | e120 | ||
| References | 972 | ||
| CHAPTER 51 Clinical and Laboratory Evaluation of Systemic Rheumatic Diseases | 973 | ||
| Key Points | 973 | ||
| Overview and Classification of Systemic Rheumatic Diseases | 973 | ||
| Systemic Lupus Erythematosus and Related Lupus-like Disorders | 974 | ||
| Etiologic Factors in Systemic Lupus Erythematosus | 974 | ||
| What are the Diagnostic Criteria for Systemic Lupus Erythematosus? | 974 | ||
| What are “Lupus-Like” Syndromes and Diseases? | 974 | ||
| Autoantibody Profile in Systemic Lupus Erythematosus | 974 | ||
| Antibodies to Native DNA or Double-Stranded DNA | 975 | ||
| Antibodies to Sm and Nuclear Ribonucleoprotein | 975 | ||
| Antibodies to SS-A/Ro and SS-B/La | 976 | ||
| Clinical Subsets of Systemic Lupus Erythematosus Associated With Antibodies to SS-A/Ro | 976 | ||
| Anti-Ku and Anti-Ki Antibodies | 976 | ||
| Antibodies to P Ribosomal Proteins | 976 | ||
| Proliferating Cell Nuclear Antigen Multiprotein Complex | 977 | ||
| Antiphospholipid Antibodies in Systemic Lupus Erythematosus | 977 | ||
| Chronic Discoid Lupus and Other Cutaneous Variants | 977 | ||
| Drug-Induced Lupus Erythematosus, Antihistone and Antichromatin Antibodies | 977 | ||
| Sjögren’s Syndrome | 977 | ||
| Scleroderma | 980 | ||
| Antibodies to Centromere Antigens | 980 | ||
| Antibodies to Scl-70 (DNA Topoisomerase I) | 980 | ||
| Antibodies to RNA Polymerases | 980 | ||
| Autoantibodies to the Nucleolar Antigen Fibrillarin (U3-snRNP) | 980 | ||
| Antibodies Targeting the Nucleolar Organizing Region | 980 | ||
| Rheumatoid Arthritis | 980 | ||
| Rheumatoid Factor | 982 | ||
| Antikeratin Antibody | 983 | ||
| Antiperinuclear Factor | 983 | ||
| Anti-Cyclic Citrullinated Peptide | 983 | ||
| Anti-RA33 | 983 | ||
| Polymyositis and Dermatomyositis | 983 | ||
| Concept of Overlap Syndromes | 984 | ||
| Mixed Connective Tissue Disease | 984 | ||
| Molecular Biology and Functions of Certain Nuclear and Intracellular Autoantigens | 984 | ||
| Profiles of Autoantibodies in Various Systemic Rheumatic Diseases | 984 | ||
| Decision Chart for the Diagnostic Workup of Autoimmune Diseases | 984 | ||
| Diagnostic Methods in Autoantibody Detection | 985 | ||
| Variations in Methods Used for Detection of Autoantibodies to Nuclear and Intracellular Antigens | 989 | ||
| Enzyme-Linked Immunosorbent Assays | 990 | ||
| Immunoblotting | 990 | ||
| Selected References | 990 | ||
| References | e122 | ||
| References | 990 | ||
| CHAPTER 52 Vasculitis | 991 | ||
| Key Points | 991 | ||
| Classification | 992 | ||
| Pathogenesis of Vasculitis | 992 | ||
| Perspective on Use of Clinical Laboratory Tests | 993 | ||
| Routine Tests | 993 | ||
| Special Tests | 993 | ||
| Test Patterns In Vasculitis | 993 | ||
| CBC | 993 | ||
| ESR/CRP | 994 | ||
| urinalysis | 994 | ||
| Viral Disease | 994 | ||
| Connective Tissue Disease | 994 | ||
| Antineutrophil Cytoplasmic Antibody | 994 | ||
| Detection Methods | 994 | ||
| Antigenic Specificity | 994 | ||
| Disease Associations | 995 | ||
| Vasculitis | 995 | ||
| Inflammatory Disease of Gastrointestinal and Hepatobiliary Tracts | 996 | ||
| Other Diseases | 996 | ||
| Test Interpretation | 996 | ||
| Synopses of Major Idiopathic Vasculitic Syndromes | 996 | ||
| Polyarteritis Nodosa | 996 | ||
| Epidemiology | 996 | ||
| Clinical Features | 996 | ||
| Clinical Laboratory Findings | 996 | ||
| Diagnosis | 996 | ||
| PART 7 Medical Microbiology | 1035 | ||
| CHAPTER 55 Viral Infections | 1037 | ||
| Key Points | 1037 | ||
| Overview | 1038 | ||
| Viral Culture | 1039 | ||
| Specimen Collection | 1040 | ||
| Equipment and Supplies | 1040 | ||
| Viral Antigen Detection | 1040 | ||
| Molecular Detection | 1041 | ||
| Viral Serology | 1042 | ||
| Clinical Viral Infectious Syndromes | 1042 | ||
| Herpetic Mucocutaneous Infections | 1042 | ||
| Specimen Collection and Handling Guidelines | 1042 | ||
| Cell Culture Isolation of Herpes Simplex Virus | 1043 | ||
| Nucleic Acid–Based Detection of Herpes Simplex Virus | 1043 | ||
| Direct Detection of Herpes Simplex Virus | 1044 | ||
| Serologic Diagnosis | 1044 | ||
| Viral Respiratory Tract Infections | 1044 | ||
| Influenza | 1044 | ||
| Bronchiolitis and RSV | 1046 | ||
| Croup | 1046 | ||
| Metapneumovirus | 1046 | ||
| Other Viral Respiratory Tract Infections | 1047 | ||
| Specimen Collection | 1048 | ||
| Virus Antigen Assays | 1048 | ||
| Virus Isolation | 1048 | ||
| Molecular Detection Methods | 1048 | ||
| Infectious Mononucleosis and Related Infections | 1048 | ||
| Diagnosis of Infectious Mononucleosis | 1049 | ||
| Heterophile-Negative Infectious Mononucleosis | 1049 | ||
| Chronic Fatigue Syndrome | 1050 | ||
| Congenital and Perinatal Viral Infections | 1050 | ||
| Cytomegalovirus | 1050 | ||
| Rubella | 1052 | ||
| Herpes Simplex Virus | 1052 | ||
| Human Immunodeficiency Virus, Parvovirus, Enterovirus, Hepatitis B Virus, and Varicella Infections | 1052 | ||
| Viral Meningitis and Encephalitis | 1053 | ||
| Laboratory Diagnosis | 1054 | ||
| Viral Exanthems and Common Cutaneous Infections | 1055 | ||
| Viral Gastroenteritis | 1056 | ||
| Laboratory Diagnosis | 1057 | ||
| Viral Infection in Immunocompromised Host | 1057 | ||
| Viral Hepatitis | 1058 | ||
| Acquired Immunodeficiency Syndrome | 1060 | ||
| Virus-Associated Neoplasia | 1061 | ||
| Selected References | 1063 | ||
| References | e132 | ||
| Websites and E-Mail Addresses | 1064 | ||
| References | 1064 | ||
| CHAPTER 56 Chlamydial, Rickettsial, and Mycoplasmal Infections | 1065 | ||
| Key Points | 1065 | ||
| Chlamydial Infections | 1065 | ||
| Structure | 1066 | ||
| Replication | 1066 | ||
| Chlamydia trachomatis | 1066 | ||
| Epidemiology, Pathology, and Clinical Manifestations | 1066 | ||
| Chlamydophila (Formerly Chlamydia Psittaci) | 1067 | ||
| Epidemiology | 1067 | ||
| Pathogenesis and Pathology | 1067 | ||
| Clinical Manifestations | 1067 | ||
| Chlamydophila (Formerly Chlamydia Pneumoniae) | 1067 | ||
| Epidemiology | 1068 | ||
| Pathogenesis | 1068 | ||
| Clinical Manifestations | 1068 | ||
| Laboratory Diagnosis | 1068 | ||
| Chlamydia trachomatis | 1068 | ||
| Cell Culture | 1068 | ||
| Nonculture Direct Detection Methods | 1068 | ||
| Direct Fluorescent Antibody Tests. | 1068 | ||
| Enzyme Immunoassays. | 1068 | ||
| Nucleic Acid Hybridization Tests. | 1069 | ||
| Nucleic Acid Amplification. | 1069 | ||
| Verification of Nonculture Tests | 1069 | ||
| Serologic Tests | 1069 | ||
| Chlamydophila psittaci | 1069 | ||
| Chlamydophila pneumoniae | 1069 | ||
| Treatment | 1070 | ||
| Rickettsial Infections | 1070 | ||
| Infections Caused By Organisms of the Genus Rickettsia | 1070 | ||
| Structure and Function | 1070 | ||
| Rocky Mountain Spotted Fever | 1070 | ||
| African Tick Bite Fever, Boutonneuse Fever, and Other Spotted Fevers | 1070 | ||
| Rickettsialpox | 1072 | ||
| Flea-borne Spotted Fever | 1072 | ||
| Murine Typhus and Louse-borne Typhus | 1072 | ||
| Rickettsiae as Agents of Bioterrorism | 1072 | ||
| Laboratory Diagnosis | 1072 | ||
| Treatment | 1073 | ||
| Scrub Typhus Caused by Orientia Tsutsugamushi | 1073 | ||
| Infections Caused by Organisms of the Genera Ehrlichia and Anaplasma | 1073 | ||
| Structure and Function | 1073 | ||
| Human Monocytotropic Ehrlichiosis | 1073 | ||
| Human Infection with Ehrlichia ewingii | 1074 | ||
| Human Granulocytotropic Anaplasmosis | 1074 | ||
| Laboratory Diagnosis | 1074 | ||
| Treatment | 1074 | ||
| Infections Caused by Coxiella burnetii | 1074 | ||
| Structure and Function | 1074 | ||
| Q Fever | 1075 | ||
| Laboratory Diagnosis | 1075 | ||
| Treatment | 1075 | ||
| Infections Caused by Organisms of the Genus Bartonella | 1075 | ||
| Structure and Function | 1075 | ||
| Cat Scratch Disease, Bacillary Angiomatosis, and Bacillary Peliosis | 1075 | ||
| Trench Fever and Bacillary Angiomatosis | 1076 | ||
| Oroya Fever and Verruga Peruana | 1076 | ||
| Laboratory Diagnosis | 1076 | ||
| Treatment | 1076 | ||
| Mycoplasmal Infections | 1076 | ||
| Mycoplasma Pneumoniae | 1076 | ||
| Epidemiology | 1076 | ||
| Pathogenesis and Pathology | 1076 | ||
| PART 8 Molecular Pathology | 1253 | ||
| CHAPTER 64 Introduction to Molecular Pathology | 1255 | ||
| Key Points | 1255 | ||
| The Molecular Biology Revolution and Its Impact on the Practice of Pathology | 1255 | ||
| Discussion of Diagnostic Molecular Pathology | 1255 | ||
| Application of Molecular Pathology to Detection of Cancer | 1256 | ||
| Implications of Molecular Diagnostics on the Practice of Pathology and Medicine | 1256 | ||
| Redefining Disease | 1256 | ||
| Use of Molecular Biology in the Treatment of Disease | 1257 | ||
| Data Analysis | 1257 | ||
| Quality Assurance | 1257 | ||
| Caveats | 1257 | ||
| Selected References | 1257 | ||
| References | e164 | ||
| References | 1257 | ||
| CHAPTER 65 Molecular Diagnostics: | 1258 | ||
| Key Points | 1258 | ||
| Nucleic Acid Biochemistry and Biology | 1258 | ||
| Molecular Composition and Structure | 1258 | ||
| Nucleic Acid–Associated Enzymes | 1260 | ||
| Replication of DNA | 1260 | ||
| Transcription of DNA to RNA | 1261 | ||
| Posttranscriptional Modification | 1261 | ||
| Translation of RNA to Protein | 1261 | ||
| Transcriptional Control | 1261 | ||
| Gene Regulation Mediated by Small RNA | 1262 | ||
| Epigenetics and Gene Regulation | 1262 | ||
| Mechanisms of DNA Repair | 1262 | ||
| DNA Mutations | 1263 | ||
| Nucleic Acid Analyses | 1263 | ||
| Electrophoretic Separation | 1264 | ||
| Nucleic Acid Hybridization | 1264 | ||
| Hybridization Assays: Basic Components | 1264 | ||
| Probe | 1265 | ||
| Sample | 1266 | ||
| Controlled Conditions Permissive for Complementary Base Pairing | 1266 | ||
| Detection of Hybrids | 1266 | ||
| Hybridization Assay Formats | 1266 | ||
| Liquid or Solution Phase Hybridization | 1267 | ||
| Solid-Support Hybridization | 1267 | ||
| Dot/Blot Hybridization | 1267 | ||
| Southern and Northern Hybridizations | 1267 | ||
| Microarray Hybridization (“DNA Chip Technology”) | 1267 | ||
| In Situ Hybridization | 1268 | ||
| Amplification Methods | 1268 | ||
| Polymorphism Detection Assays | 1268 | ||
| DNA Sequencing | 1268 | ||
| Relationship to Laboratory Evaluation of Disease | 1269 | ||
| Molecular Diagnosis | 1269 | ||
| Beyond Diagnosis | 1270 | ||
| Selected References | 1270 | ||
| References | e165 | ||
| References | 1270 | ||
| CHAPTER 66 Polymerase Chain Reaction and Other Nucleic Acid Amplification Technology | 1271 | ||
| Key Points | 1271 | ||
| Target Amplification Methods | 1271 | ||
| Polymerase Chain Reaction | 1271 | ||
| Reverse-Transcriptase Polymerase Chain Reaction | 1272 | ||
| Nested Polymerase Chain Reaction | 1272 | ||
| Multiplex Polymerase Chain Reaction | 1273 | ||
| End-Point Quantitative Polymerase Chain Reaction | 1273 | ||
| Real-Time (Homogeneous, Kinetic) Polymerase Chain Reaction | 1274 | ||
| Rapid-Cycle Polymerase Chain Reaction | 1276 | ||
| Digital Polymerase Chain Reaction | 1276 | ||
| Transcription-Based Amplification | 1276 | ||
| Strand-Displacement Amplification | 1277 | ||
| Loop-Mediated Amplification | 1278 | ||
| Helicase-Dependent Amplification | 1278 | ||
| Probe Amplification Methods | 1279 | ||
| Cleavase/Invader Technology | 1279 | ||
| Signal Amplification Methods | 1280 | ||
| Branched DNA | 1280 | ||
| Hybrid Capture Assays | 1281 | ||
| Whole Genome Amplification | 1281 | ||
| Summary | 1281 | ||
| Selected References | 1281 | ||
| References | e166 | ||
| References | 1281 | ||
| CHAPTER 67 Hybridization Array Technologies | 1282 | ||
| Key Points | 1282 | ||
| Array Technologies | 1282 | ||
| Macroarrays | 1283 | ||
| Microarrays | 1283 | ||
| Microarray Substrates | 1283 | ||
| Microarray Fabrication | 1283 | ||
| Delivery Technologies | 1284 | ||
| In Situ Synthesis | 1284 | ||
| Oligonucleotide Microarrays | 1284 | ||
| cDNA Microarrays | 1285 | ||
| Sequencing Arrays | 1285 | ||
| Hybridization, Detection, and Image Analysis | 1285 | ||
| Bioinformatics | 1286 | ||
| Intellectual Property Issues | 1288 | ||
| Clinical Applications of Array Technology | 1288 | ||
| Array Technology in the Clinical Laboratory | 1288 | ||
| Array Technology in Clinical Disease | 1289 | ||
| Limitations | 1289 | ||
| Selected References | 1289 | ||
| References | e167 | ||
| References | 1289 | ||
| CHAPTER 68 Applications of Cytogenetics in Modern Pathology | 1290 | ||
| Key Points | 1290 | ||
| Definitions | 1290 | ||
| Cytogenetics | 1291 | ||
| Chromosomes | 1291 | ||
| Chromosome Structure | 1291 | ||
| Cell Culture | 1292 | ||
| Specimens | 1292 | ||
| Cell Culture Technique | 1292 | ||
| Staining | 1292 | ||
| Karyotype Analysis | 1293 | ||
| Computer-Assisted Imaging | 1294 | ||
| Fluorescence In Situ Hybridization | 1294 | ||
| Technique | 1295 | ||
| Multicolor Fluorescence In Situ Hybridization | 1297 | ||
| Microarray Technology | 1297 | ||
| Chromosome Abnormalities | 1298 | ||
| Numerical Abnormalities | 1298 | ||
| Euploidy | 1298 | ||
| Aneuploidy | 1298 | ||
| Structural Chromosome Abnormalities | 1299 | ||
| Conclusions | 1301 | ||
| Nomenclature | 1301 | ||
| Clinical | 1304 | ||
| Clinical Applications | 1304 | ||
| Prenatal Cytogenetics | 1304 | ||
| Postnatal | 1304 | ||
| Childhood and Adult | 1305 | ||
| Cancer Genetics | 1305 | ||
| Cytogenetic Disorders | 1306 | ||
| Chromosomal Aneuploidy Syndromes | 1306 | ||
| Autosomal Aneuploidies | 1306 | ||
| Sex Chromosome Aneuploidies | 1308 | ||
| Other Sex Chromosome Abnormalities | 1309 | ||
| Structural Chromosome Anomalies | 1309 | ||
| Microdeletion Syndromes and Contiguous Gene Syndromes | 1309 | ||
| Other Cytogenetic Phenomena | 1311 | ||
| Fragile X Syndrome | 1311 | ||
| Breakage Syndromes | 1311 | ||
| Summary | 1311 | ||
| Selected References | 1312 | ||
| References | e170 | ||
| Further Reading | 1313 | ||
| References | 1313 | ||
| CHAPTER 69 Establishing a Molecular Diagnostics Laboratory | 1314 | ||
| Special Considerations for Molecular Diagnostics Laboratories | 1314 | ||
| Infectious Disease | 1314 | ||
| Cancer | 1314 | ||
| Inherited Disorders | 1315 | ||
| Regulation and Regulatory Agencies | 1315 | ||
| Clinical Laboratory Improvement Acts 1988, 2003 | 1315 | ||
| Genetic Information Nondiscrimination Act | 1316 | ||
| Food and Drug Administration | 1316 | ||
| Analyte-Specific Reagents | 1316 | ||
| In Vitro Multivariate Index Assay or IVDMIA Draft Guidance | 1317 | ||
| Laboratory Design and Requirements | 1317 | ||
| Laboratory Design | 1317 | ||
| Practices to Aid in Contamination Control | 1318 | ||
| Equipment | 1318 | ||
| Personnel | 1318 | ||
| Laboratory Director | 1319 | ||
| Technical Supervisor | 1319 | ||
| Medical Technologists and Molecular Biology Technicians | 1319 | ||
| Certification of Personnel in Molecular Diagnostics | 1319 | ||
| Financial Management | 1320 | ||
| Reimbursement for Molecular Diagnostics Tests | 1320 | ||
| Patent Issues | 1320 | ||
| Laboratory Information System | 1321 | ||
| Test Management | 1321 | ||
| Menu/Selection | 1321 | ||
| Methods | 1322 | ||
| Clinical Test Formats | 1322 | ||
| Automated Platforms for Molecular Testing | 1322 | ||
| Quality Assurance and Quality Control of the Testing Process | 1322 | ||
| Quality Assurance | 1322 | ||
| Assay Design and Development | 1323 | ||
| New Test Verification/Validation | 1324 | ||
| Analytical Verification | 1327 | ||
| Clinical Verification | 1328 | ||
| Quality Control of the Testing Process | 1329 | ||
| Quality Control of Equipment | 1329 | ||
| Conclusions | 1329 | ||
| Selected References | 1329 | ||
| References | e171 | ||
| References | 1329 | ||
| CHAPTER 70 Molecular Diagnosis of Genetic Diseases | 1330 | ||
| Key Points | 1330 | ||
| Choice of Techniques | 1331 | ||
| Choice of Applications | 1333 | ||
| Special Concepts Unique to Molecular Genetic Disorders | 1334 | ||
| Molecular Heterogeneity | 1334 | ||
| Variable Penetrance and Expressivity | 1334 | ||
| Uniparental Disomy | 1334 | ||
| Imprinting | 1334 | ||
| Anticipation | 1335 | ||
| Epigenetic Influences and Nonmendelian Inheritance | 1335 | ||
| Allele Frequencies and Mass Population Screening | 1335 | ||
| Predictive Genetic Testing | 1335 | ||
| Specific Disease Examples | 1335 | ||
| Cystic Fibrosis | 1335 | ||
| Duchenne Muscular Dystrophy | 1336 | ||
| Sickle Cell Anemia and Other Hemoglobinopathies | 1337 | ||
| Hereditary Thrombophilias | 1337 | ||
| Trinucleotide Repeat Expansion Disorders | 1338 | ||
| Fragile XA and Fragile XE Syndromes | 1339 | ||
| Neurodegenerative Disorders: Huntington Disease, X-linked Spinal and Bulbar Muscular Atrophy, Spinocerebellar Ataxias, and Dentatorubral-Pallidoluysian Atrophy | 1339 | ||
| Myotonic Dystrophy | 1339 | ||
| Friedreich Ataxia | 1341 | ||
| Laboratory Testing for Trinucleotide Repeat Disorders | 1341 | ||
| Prader-Willi and Angelman Syndromes | 1341 | ||
| Familial Cancers | 1341 | ||
| Tumor Suppressor Genes: Retinoblastoma as a Paradigm | 1343 | ||
| Oncogenes: Multiple Endocrine Neoplasia Type 2 as a Paradigm | 1343 | ||
| Hereditary Breast–Ovarian Cancer | 1343 | ||
| The Hereditary Colorectal Cancer Syndromes | 1343 | ||
| Hereditary Nonpolyposis Colorectal Cancer | 1344 | ||
| Familial Adenomatous Polyposis and Attenuated Familial Adenomatous Polyposis | 1344 | ||
| MYH-Associated Polyposis | 1344 | ||
| Laboratory Testing for Familial Cancer Mutations | 1344 | ||
| Hemochromatosis | 1345 | ||
| Spinal Muscular Atrophy | 1345 | ||
| Mitochondrial DNA Disorders | 1345 | ||
| Other Targets of Molecular Genetic Testing and Screening | 1346 | ||
| Future Directions | 1346 | ||
| Selected References | 1347 | ||
| References | e172 | ||
| References | 1347 | ||
| CHAPTER 71 Identity Analysis: | 1348 | ||
| Key Points | 1348 | ||
| Historical Background | 1348 | ||
| Advantages of DNA | 1349 | ||
| Choosing Genetic Markers | 1349 | ||
| Samples and Specimen Collection | 1349 | ||
| DNA Extraction and Quantification | 1350 | ||
| Test Methods and Marker Systems | 1350 | ||
| Short Tandem Repeats | 1350 | ||
| X and Y Chromosome Markers | 1350 | ||
| Mitochondrial DNA Sequencing | 1352 | ||
| Other Systems | 1352 | ||
| Analysis and Use of Test Data | 1352 | ||
| DNA in the Crime Laboratory | 1352 | ||
| DNA in the Pathology Laboratory | 1352 | ||
| Exclusion of Parentage | 1353 | ||
| Probability of Exclusion | 1354 | ||
| Cumulative Probability of Exclusion | 1354 | ||
| Inclusion of Parentage | 1355 | ||
| Paternity Index Calculation | 1355 | ||
| Likelihood of Parentage | 1355 | ||
| Estimating Parentage with an Absent Parent | 1356 | ||
| Reconstruction of Families | 1356 | ||
| Software Systems | 1357 | ||
| Quality Assurance Standards | 1357 | ||
| Conclusion | 1358 | ||
| Acknowledgment | 1358 | ||
| Selected References | 1358 | ||
| References | e174 | ||
| References | 1358 | ||
| CHAPTER 72 Pharmacogenomics and Personalized Medicine | 1359 | ||
| Key Points | 1359 | ||
| Overview | 1359 | ||
| Basic Concepts | 1359 | ||
| Drug-Metabolizing Enzyme Pharmacogenomics | 1360 | ||
| Phase I Enzymes | 1360 | ||
| Phase II Enzymes | 1361 | ||
| uridine Diphosphate Glucuronosyltransferases | 1361 | ||
| Sulfotransferases | 1361 | ||
| Glutathione S-Transferases | 1361 | ||
| N-Acetyltransferase | 1366 | ||
| Thiopurine S-Methyltransferase | 1366 | ||
| Drug-Transporter Pharmacogenomics | 1367 | ||
| ABCB1, ABCC1/2, and ABCG2 Efflux Transporters | 1367 | ||
| ABCB1 | 1367 | ||
| ABCC1 and ABCC2 | 1368 | ||
| ABCG2 | 1369 | ||
| OATP, OCT, and OAT Uptake Transporters | 1369 | ||
| Organic Anion Transporting Polypeptides | 1369 | ||
| Organic Cation Transporter | 1369 | ||
| Organic Anion Transporter | 1369 | ||
| Drug Target Pharmacogenomics | 1371 | ||
| DNA Repair Genes | 1371 | ||
| Thymidylate Synthase | 1374 | ||
| Epidermal Growth Factor Receptor | 1374 | ||
| K-ras Mutation | 1376 | ||
| Pharmacogenomics in Cancer Chemotherapy | 1376 | ||
| 5-Fluorouracil | 1376 | ||
| Irinotecan | 1377 | ||
| Tamoxifen | 1378 | ||
| Platinum Agents | 1379 | ||
| Antibody Therapy | 1380 | ||
| Pharmacogenomics in Other Diseases | 1380 | ||
| Diabetes | 1380 | ||
| Human Immunodeficiency Virus | 1380 | ||
| Osteoporosis | 1381 | ||
| Psychiatric and Cognitive Disorders | 1381 | ||
| Epigenomics | 1381 | ||
| Conclusions | 1382 | ||
| Selected References | 1382 | ||
| References | e175 | ||
| References | 1382 | ||
| PART 9 Clinical Pathology of Cancer | 1383 | ||
| CHAPTER 73 Diagnosis and Management of Cancer Using Serologic and Tissue Tumor Markers | 1385 | ||
| Key Points | 1385 | ||
| Serum Markers as an Effective Tool for Diagnosis and Monitoring of Cancer | 1386 | ||
| Functional Classification of Tumor Markers | 1386 | ||
| Oncoproteins Are Markers for Cell Proliferation | 1387 | ||
| Tumor Suppressors/Cell Differentiation | 1387 | ||
| Adhesion Molecules and Metastasis | 1387 | ||
| Other Markers | 1387 | ||
| Monoclonal-Antibody-Defined Tumor Markers | 1388 | ||
| Clinical Applications | 1388 | ||
| Screening | 1388 | ||
| Diagnosis | 1388 | ||
| Prognosis: Recurrence, Metastasis, and Survival | 1388 | ||
| Monitoring Treatment Response | 1389 | ||
| Recommendations for Ordering Tumor Marker Tests | 1389 | ||
| Individual Tumor Markers | 1392 | ||
| α-Fetoprotein | 1392 | ||
| Angiogenic Factors | 1392 | ||
| β2-Microglobulin | 1392 | ||
| Carcinoembryonic Antigen | 1392 | ||
| CA 15-3 and CA 27.29 | 1393 | ||
| CA 19-9, CA 50, and CA 19-5 | 1393 | ||
| CA 125 | 1393 | ||
| CA 72-4 | 1393 | ||
| Calcitonin | 1393 | ||
| Chromogranin A | 1393 | ||
| Cytokeratin 19 Fragment | 1393 | ||
| Human Chorionic Gonadotropin | 1394 | ||
| HER2/neu (c-erbB-2) Oncoprotein | 1394 | ||
| p53 | 1394 | ||
| Parathyroid Hormone-Related Peptide | 1394 | ||
| Serum and urine Markers for Prostate Cancer | 1394 | ||
| Serum Prostate-Specific Antigen | 1394 | ||
| Methods to Improve the Performance of Serum PSA Measurement for the Early Detection of Prostate Cancer | 1395 | ||
| Free PSA, Complex PSA, and Percentage of Free PSA | 1395 | ||
| Principles of Measurement. | 1396 | ||
| PSA Doubling Time, Velocity, and Density | 1396 | ||
| urine Markers | 1397 | ||
| urine Prostate Cancer Antigen 3 | 1397 | ||
| urine Hypermethylated Glutathione S-Transferase pi 1 Gene | 1397 | ||
| urine Fusion Gene Variants | 1397 | ||
| Fecal Occult Blood Testing and Mutant Protein Markers in Stool | 1397 | ||
| Circulating Tumor Cells in Peripheral Blood | 1398 | ||
| Conclusions and Directions for the Future | 1398 | ||
| Serum Genomics and Proteomics as Potential Biomarkers for Cancer | 1398 | ||
| Circulating Nucleic Acids in the Detection of Cancer | 1398 | ||
| Serum Proteomics in the Detection of Cancer | 1398 | ||
| Selected References | 1399 | ||
| References | e180 | ||
| References | 1399 | ||
| CHAPTER 74 Oncoproteins and Early Tumor Detection | 1400 | ||
| Key Points | 1400 | ||
| Overview | 1400 | ||
| Cell Biology and Mitogenesis | 1401 | ||
| Signal Transduction Pathways | 1401 | ||
| Oncoproteins in Tumor Detection | 1402 | ||
| Growth Factors | 1402 | ||
| Transforming Growth Factors α and β | 1402 | ||
| Platelet-Derived Growth Factor | 1403 | ||
| Basic Fibroblast Growth Factor | 1403 | ||
| Epidermal Growth Factor and Hepatocyte Growth Factor | 1404 | ||
| Growth Factor Receptors | 1404 | ||
| Epidermal Growth Factor Receptor | 1405 | ||
| HER2/neu Receptor | 1405 | ||
| HER2/neu Detects Pulmonary Neoplasms | 1405 | ||
| HER2/neu in the Detection of Hepatocellular Carcinomas | 1405 | ||
| p185erbB-2 ECD in Other Tumors | 1405 | ||
| G-Proteins | 1405 | ||
| ras-p21 Protein | 1405 | ||
| ras-p21 in Lung Cancer | 1406 | ||
| ras-p21 in Angiosarcoma | 1406 | ||
| ras-p21 in Pancreatic Cancer | 1406 | ||
| Cytosolic Mitogenic Kinases | 1406 | ||
| raf | 1406 | ||
| Nuclear Oncoproteins | 1407 | ||
| p53 and c-myc Proteins | 1407 | ||
| Detection of Malignancies by Assaying for p53 Protein | 1407 | ||
| Hepatocellular Carcinoma | 1407 | ||
| Breast and Lung Cancers | 1407 | ||
| Colon Cancer | 1407 | ||
| Bladder Cancer | 1407 | ||
| Circulating Anti-p53 Antibodies in Tumor Detection | 1407 | ||
| Antibodies to p53 Are Present in the Sera of Many Patients with Epithelial Cell Tumors and Lymphomas | 1407 | ||
| Anti-p53 in Ovarian Cancer | 1407 | ||
| Anti-p53 in Hepatocellular Carcinoma | 1407 | ||
| Anti-p53 in Oral and Esophageal Cancers | 1407 | ||
| Anti-p53 in Lung Cancers | 1408 | ||
| Anti-p53 Predicts Cancer Occurrence in Patients with Asbestos Exposure | 1408 | ||
| Anti-p53 in Colorectal Cancer | 1408 | ||
| myc Oncogene–Encoded Protein in Tumor Detection | 1408 | ||
| Serum Anti–c-myc Protein Antibodies in Tumor Detection in Breast Cancer, Ovarian Cancer, Leukemias, and Lymphomas | 1408 | ||
| Combined Oncogene Marker Proteins for Detection of Colorectal Cancer | 1408 | ||
| Nuclear Matrix Proteins—Detection of Bladder Cancer | 1408 | ||
| NMP-22 Is an Excellent Biomarker for Bladder and Urothelial Cancers | 1408 | ||
| Bladder Tumor Antigen | 1409 | ||
| Use of Multiple Oncoprotein Markers in the Diagnosis of Cancer | 1409 | ||
| Multiple Oncoprotein Assay in Patients at Risk for Tumor Development in Patients with Pneumoconiosis | 1409 | ||
| Oncoprotein Arrays Likewise Hold Promise in Detecting Antioncoprotein Antibodies in Sera | 1409 | ||
| Proteomic Approaches to Early Detection of Cancer in Serum | 1409 | ||
| Application of the Proteomic Approach to the Diagnosis of Cancers | 1410 | ||
| Ovarian Cancer | 1410 | ||
| Prostate Cancer | 1410 | ||
| Proteomics Show Promise in Early Tumor Detection | 1410 | ||
| Protein Arrays for Specific Types of Cancer | 1410 | ||
| Squamous Cell Carcinomas of the Head and Neck | 1410 | ||
| Breast Cancer | 1410 | ||
| Lung Cancer | 1410 | ||
| Detection of Oncogenes in Serum and Other Body Fluids | 1410 | ||
| Cell-Free Nucleic Acid Testing in Cancer | 1410 | ||
| Gene Mutations | 1410 | ||
| Microsatellite Alterations | 1411 | ||
| Promoter Hypermethylation | 1411 | ||
| Gene Arrays Detecting Oncoprotein Abnormalities | 1411 | ||
| Cell DNA Testing for Cancer Using Fluorescence In Situ Hybridization | 1411 | ||
| Diagnostic Efficacy of Serum Oncoproteins | 1412 | ||
| How Specific Is Oncoprotein Expression for Different Cancer Types? | 1412 | ||
| Sensitivities of Oncoprotein Expression | 1412 | ||
| Origins of Malignancies | 1412 | ||
| Tumor Size and Oncoprotein Levels | 1412 | ||
| Evaluation and Conclusions | 1414 | ||
| Selected References | 1414 | ||
| References | e183 | ||
| References | 1414 | ||
| CHAPTER 75 Molecular Diagnosis of Hematopoietic Neoplasms | 1415 | ||
| Key Points | 1415 | ||
| Role of Clinical Molecular Diagnostics in Hematologic Cancers | 1416 | ||
| Molecular Diagnosis of Acute Leukemias | 1416 | ||
| Gene Fusion Concept in Leukemia and the Basis for Reverse-Transcription Polymerase Chain Reaction Analysis | 1416 | ||
| Acute Myeloid Leukemias | 1417 | ||
| Acute Promyelocytic Leukemia: t(15;17)/PML-RARA Abnormality | 1418 | ||
| Core Binding Factor–Related Acute Myeloid Leukemias: t(8;21)/RUNX1-RUNX1T1 and Inv(16) or t(16;16)/CBFB-MYH11 Abnormalities | 1420 | ||
| Acute Myeloid Leukemias with FLT3, NPM1, and CEBPA Gene Mutations | 1421 | ||
| FLT3 Mutations in AML | 1421 | ||
| NPM1 Mutations in Acute Myeloid Leukemia | 1421 | ||
| CEBPA Mutations in Acute Myeloid Leukemia | 1422 | ||
| Other Gene Mutations in Acute Myeloid Leukemias | 1422 | ||
| Acute Lymphoblastic Leukemia/Lymphoma, B and T Cell Lineage | 1422 | ||
| B Cell Lymphoblastic Leukemia/Lymphoma (Precursor B Cell Acute Lymphoblastic Leukemia) | 1422 | ||
| Major Translocation Fusion Gene Abnormalities in B Cell ALL | 1423 | ||
| Prenatal Origins of Childhood Leukemias | 1425 | ||
| T Cell Lymphoblastic Leukemia/Lymphoma | 1426 | ||
| Molecular Diagnosis of Myeloproliferative Neoplasms | 1426 | ||
| Chronic Myelogenous Leukemia, BCR-ABL1 Positive | 1426 | ||
| Ph-Negative Myeloproliferative Neoplasms: Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis—JAK2 and MPL Gene Mutations | 1428 | ||
| Mastocytosis and the KIT D816V Gene Mutation | 1429 | ||
| Neoplastic Disorders Associated with Eosinophilia | 1429 | ||
| Molecular Diagnosis of Non-Hodgkin Lymphomas | 1430 | ||
| Rationale for Molecular Genetic Analysis in the Lymphoid Disorders | 1430 | ||
| Antigen Receptor Gene Rearrangements for Clonality Determination | 1430 | ||
| Mechanism of Antigen Receptor Gene Rearrangements | 1430 | ||
| Techniques to Detect Antigen Receptor Gene Rearrangements: Southern Blot Hybridization | 1432 | ||
| Techniques to Detect Antigen Receptor Gene Rearrangements: Polymerase Chain Reaction | 1432 | ||
| Advantages and Shortcomings Southern Blot Hybridization and Polymerase Chain Reaction for Lymphoid Clonality Assessment | 1433 | ||
| Molecular Detection and Significance of Common Lymphoma-Associated Chromosomal Translocations | 1434 | ||
| t(14;18)/BCL2-IGH@ Abnormality in Follicular and Diffuse Large B Cell Lymphomas | 1434 | ||
| t(11;14)/CCND1-IGH@ Abnormality in Mantle Cell Lymphoma | 1435 | ||
| MALT1, BCL10, and FOXP1 Gene Abnormalities in Extranodal Marginal Zone B Cell Lymphomas | 1435 | ||
| Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Molecular and Cytogenetic Prognostic Markers | 1436 | ||
| Diffuse Large B Cell Lymphomas: Role of BCL6 and MYC Gene Abnormalities and Classification Based on Gene Expression Profiling | 1436 | ||
| MYC Gene Translocations in Burkitt Lymphomas and “High-Grade” B Cell Lymphomas, Unclassifiable | 1437 | ||
| ALK Gene Abnormalities in Anaplastic Large Cell Lymphomas | 1438 | ||
| TCL1A Gene Abnormalities in T Cell Prolymphocytic Leukemia | 1438 | ||
| Emerging Technologies Impacting Molecular Diagnosis and Prognosis Prediction in Hematolymphoid Neoplasia | 1439 | ||
| Selected References | 1440 | ||
| References | e186 | ||
| References | 1440 | ||
| CHAPTER 76 Molecular Genetic Pathology of Solid Tumors | 1441 | ||
| Key Points | 1441 | ||
| Molecular Genetic Pathology of Specific Solid Tumors by Major Organ | 1442 | ||
| Brain Tumor | 1442 | ||
| Glioblastoma Multiforme | 1442 | ||
| Oligodendroglioma | 1445 | ||
| Breast Cancer | 1446 | ||
| Sporadic, Nonhereditary Breast Cancer | 1446 | ||
| Hereditary Breast Cancer | 1448 | ||
| Thyroid Cancer | 1448 | ||
| Papillary Thyroid Carcinoma | 1448 | ||
| Follicular Carcinoma | 1448 | ||
| Medullary Carcinoma | 1449 | ||
| Lung Cancer | 1449 | ||
| Hepatocellular Carcinoma | 1450 | ||
| Gastric Cancer | 1450 | ||
| Colorectal Cancer | 1451 | ||
| Pancreatic Cancer (Non-neuroendocrine Tumor) | 1452 | ||
| Kidney Tumor | 1453 | ||
| Renal Cell Carcinoma: Clear Cell Carcinoma | 1453 | ||
| Translocation-Associated RCC | 1453 | ||
| Gene Expression Profiling by Affymetrix in RCC | 1454 | ||
| Bladder Cancer | 1454 | ||
| Prostate Cancer | 1454 | ||
| Cervical Cancer | 1455 | ||
| Ovarian Cancer | 1455 | ||
| Histologic Subtypes of Serous Carcinoma | 1456 | ||
| Molecular Classification of Ovarian Cancer | 1456 | ||
| Clear Cell Ovarian Carcinoma | 1456 | ||
| BRCA1 and BRCA2 in Ovarian Cancer | 1456 | ||
| Melanoma | 1456 | ||
| Molecular Genetic Pathology of Sarcoma | 1457 | ||
| Sarcomas with Fusion Genes | 1457 | ||
| Fusion Genes Involving TET Genes | 1457 | ||
| Ewing’s Sarcoma/Primitive Peripheral Neuroectodermal Tumor | 1457 | ||
| Fusion Genes Involving Receptor Tyrosine Kinase Genes | 1457 | ||
| Fusion Genes Involving Chromatin Remodeling Genes | 1457 | ||
| Fusion Genes Involving Growth Factors | 1457 | ||
| Other Types of Fusion Genes | 1458 | ||
| Sarcomas with Oncogenic Mutations | 1458 | ||
| KIT and PDGFRA in Gastrointestinal Stromal Tumor | 1458 | ||
| Sarcomas with Variable Complex Genetic Alterations with No Specific Pattern | 1458 | ||
| Cancers of Unknown Origin | 1458 | ||
| Molecular Genetic Pathology of Syndromatic Cancers | 1459 | ||
| Hereditary Colonic Cancer Syndrome | 1459 | ||
| Familial Adenomatous Polyposis Syndrome | 1459 | ||
| Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) | 1459 | ||
| Familial Juvenile Polyposis Syndrome | 1459 | ||
| Peutz-Jeghers Syndrome | 1460 | ||
| Multiple Endocrine Neoplasia | 1460 | ||
| Selected References | 1461 | ||
| References | e194 | ||
| References | 1462 | ||
| CHAPTER 77 High-Throughput Genomic and Proteomic Technologies in the Post-genomic Era | 1463 | ||
| Key Points | 1463 | ||
| Overview | 1463 | ||
| The Human Genome Project | 1464 | ||
| Public Sequencing Effort (Hierarchical Shotgun Sequencing) | 1464 | ||
| Private Sequencing Effort (Whole-Genome Shotgun Sequencing) | 1465 | ||
| Finishing the Sequence of the Human Genome | 1465 | ||
| High-Throughput Technologies | 1466 | ||
| Genomic | 1466 | ||
| Serial Analysis of Gene Expression | 1466 | ||
| Microarray | 1466 | ||
| Real Competitive Polymerase Chain Reaction | 1468 | ||
| Proteomic | 1470 | ||
| Mass Spectrometry | 1470 | ||
| Protein Arrays | 1471 | ||
| Molecular Markers for the Diagnosis of Human Neoplasia | 1471 | ||
| Genomic | 1471 | ||
| Proteomic | 1471 | ||
| Diagnostic Cancer Applications | 1472 | ||
| Small, Round Blue Cell Tumors | 1472 | ||
| Barrett’s Esophagus | 1473 | ||
| Thyroid | 1473 | ||
| Distinguishing Follicular Thyroid Carcinoma from Adenoma | 1473 | ||
| Adenocarcinoma | 1473 | ||
| Pancreatic Cancer | 1473 | ||
| Other | 1473 | ||
| Prognostic Molecular Markers of Disease | 1474 | ||
| Genomic | 1474 | ||
| Diffuse Large B-Cell Lymphoma | 1474 | ||
| Follicular Lymphoma | 1474 | ||
| Acute Myeloid Leukemia | 1475 | ||
| Breast Cancer | 1475 | ||
| Integrating Genomics and Proteomics | 1476 | ||
| Pitfalls of Molecular Markers for Both Prognostics and Diagnostics | 1476 | ||
| Microarray Data Sets | 1476 | ||
| “Overfitting” the Predictor | 1476 | ||
| The “Bystander” Effect | 1476 | ||
| Limitations of Proteomic Techniques | 1476 | ||
| Conclusions and Future Challenges | 1477 | ||
| Selected References | 1477 | ||
| References | e199 | ||
| References | 1477 | ||
| Appendixes\r | 1479 | ||
| APPENDIX 1 Physiologic Solutions, Buffers, Acid-Base Indicators, Standard Reference Materials, and Temperature Conversions | 1481 | ||
| Physiologic Solutions | 1481 | ||
| Buffers* | 1481 | ||
| Example 1 | 1481 | ||
| Example 2 | 1481 | ||
| Sorensen’s Phosphate Buffers | 1482 | ||
| Tris(hydroxymethyl)aminomethane Buffer* | 1482 | ||
| Acid-Base Indicators* | 1482 | ||
| Standard Reference Materials | 1484 | ||
| Temperature Conversion | 1484 | ||
| Selected References | 1484 | ||
| APPENDIX 2 Desirable Weights, Body Surface Area, and Body Mass Index | 1485 | ||
| APPENDIX 3 Approximations of Total Blood Volume | 1489 | ||
| Adults | 1489 | ||
| Children | 1489 | ||
| Selected References | 1489 | ||
| APPENDIX 4 Periodic Table of the Elements | 1490 | ||
| References | 1490 | ||
| APPENDIX 5 SI Units | 1491 | ||
| References | 1508 | ||
| APPENDIX 6 Common Chimeric Genes Identified in Human Malignancies | 1509 | ||
| References | 1511 | ||
| APPENDIX 7 Disease/Organ Panels | 1513 | ||
| AMA Designated Disease/Organ Panels | 1514 | ||
| References | 1514 | ||
| Index | 1515 | ||
| A | 1515 | ||
| B | 1518 | ||
| C | 1519 | ||
| D | 1522 | ||
| E | 1523 | ||
| F | 1524 | ||
| G | 1525 | ||
| H | 1526 | ||
| I | 1528 | ||
| J | 1529 | ||
| K | 1529 | ||
| L | 1530 | ||
| M | 1531 | ||
| N | 1533 | ||
| O | 1534 | ||
| P | 1534 | ||
| Q | 1537 | ||
| R | 1537 | ||
| S | 1538 | ||
| T | 1540 | ||
| U | 1542 | ||
| V | 1542 | ||
| W | 1542 | ||
| X | 1543 | ||
| Y | 1543 | ||
| Z | 1543 | ||
| Inside back cover\r | ibc1 |