2 Principles of Blood Collection...

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1 Preface iv PART ONE: The Principles of Hematology 1 Safety and Quality in the Hematology Laboratory An Overview of the Hematology Laboratory 1 The Study of Hematology 1 Functions of the Hematology Laboratory 1 Safety in the Hematology Laboratory 2 The Safety Oficer 2 Occupational Safety and Health Administration Acts and Standards 2 Avoiding Transmission of Infectious Diseases 3 Immune Status: Screening and Vaccination 5 Safe Work Practices and Protective Techniques for Infection Control 6 Safety Manual, Policies, and Practices 6 Standard Precautions 6 Handwashing 6 Personal Protective Equipment 7 Decontamination of Work Surfaces, Equipment, and Spills 8 General Infection Control Safety Practices 9 OSHA Medical Waste Standards 11 Quality Assessment in the Hematology Laboratory 12 Regulations and Organizations Impacting Quality 12 Components of Quality Assessment 12 Nonanalytical Factors in Quality Assessment 12 Quality Control in the Hematology Laboratory 16 Terms Used in Clinical QualityControl 16 Functions of a Quality Control Program 17 Using Statistical Analysis of Results in Quality Assessment 18 Other Statistical Applications in the Hematology Laboratory 20 2 Principles of Blood Collection Quality in Phlebotomy 25 Quality Assessment 25 Patient Care Partnership 25 The Phlebotomist as Laboratory Ambassador 26 Patients with Special Considerations 26 Pediatric Patients 26 Adolescent Patients 26 Geriatric Patients 26 Blood Collection Supplies and Equipment 26 Anticoagulants 26 Adverse Effects of Additives 27 Safe Blood Collection 27 Evacuated Blood Collection Tubes 29 Anticoagulants and Additives in Evacuated Blood Tubes Capillary Blood 31 Specimen Handling Requirements 32 CHAFTER HIGHLIGHTS 45 3 Molecular Genetics and Cellular Morphology Cellular Ultrastructure and Organization 50 Cellular Membranes 50 Cell Volume Homeostasis 52 Reactive and Neoplastic Growth Processes 53 Cytoplasmic Organelles and Metabolites 53 Cellular Inclusions and Metabolites 54 Nuclear Characteristics 54 Chromosomes 56 Activities of the Nucleus 58 The Foundations of Genetic Interactions 60 Genetic Alterations 61 Molecular Techniques in Hematology 63 Minimal Residual Disease 63 Hematopathology 67 Gene Rearranement Studies 69 CHAPTER HIGHLIGHTS 69 m REVIEW QUESTIONS 70 4 Hematopoiesis Hematopoiesis Defined 73 Origin of Blood Cells 73 Types of Human Stem Cells 73 Early Development of Blood Cells 73 Bone Marrow Sites and Function 75 Cellular Elements of Bone Marrow 76 Progenitor Blood Cells 76 Erythropoiesis 79 Granulopoiesis 79 Lymphopoiesis 79 Megakaryopoiesis 79 Other Cells Found in Bone Marrow 79 Interleukins 79 Hematopoietic Growth Factors 82 Examination of Maturing Blood Cells 83 General Cellular Characteristics 83 Nuclear Characteristics 83 Cytoplasmic Characteristics 85 Mature Blood Cells in Peripheral Blood 86 CHAPTER HIGHLIGHTS 86 m REVIEW QUESTIONS 87 BIBLIOGRAPHY 87 PART TWO: Erythrocytes 5 Erythrocyte Maturation, Physiology, and Lifecycle Erythropoiesis 90 Erythropoietin 90 General Characteristics of Maturation and Development 91 Developmental Stages 92 Reticulocytes 94

2 Contents vii Disorders Related to Erythrocyte Maturation and Production 97 Disorders of Eyhropoietin 97 Red Cell Increases 98 Dejkdive Nuchr Maturation 98 Characteristics and Biosynthesis of Hemoglobin 98 Genetic Inheritance of Hemoglobin 98 Chemical Composition and ConFguration of Hemoglobin 98 The Role of 2,3-Diphosphoglycerate 99 Oxygen Dissociation and Alterations 99 Carbon Dioxide Transport 100 Biosynthesis of Hemoglobin 101 Disorders Related to Hemoglobin Biosynthesis 104 Disorders of Heme (Porphyn'n) Synthesis 104 Disorders of Iron Metabolism 105 Disorders of Globulin Synthesis 108 On togeny of Hemoglobin 108 Variant Forms of Normal Hemoglobin 109 Abnormal Hemoglobin Molecules 110 Analysis of Hemoglobin I10 Membrane Characteristics and Metabolic Activities of Erythrocytes 111 Membrane Characteristics 112 Cytoplasmic Characteristics 113 Metabolic Activities 113 Catabolism of Erythrocytes 114 Measurement of Erythrocytes 116 Mean Corpuscular Volume 116 '. Mean Corpuscular Hemoglobin 117 Mean Corpuscular Hemoglobin Concentration 117 CHAPTER HIGHLIGHTS 118 CASE STUDIES 119 RWEW QUES~ONS 121 BIBL~OGRAPHY Erythrocyte Morphology and Inclusions Erythrocytes: Normal and Abnormal 126 Types of Variations in Erythrocyte Size 126 Kinds of Variations in Erythrocyte Shape 127 Alterations in Erythrocyte CoIor 134 Varieties of Erythrocyte Inclusions 135 Alterations in Erythrocyte Distribution 137 Parasitic Inclusions in Erythrocytes 137 Malaria 137 Other Parasitic Inclusions 141 CHAPTER HIGHLIGHIS 142. CASE SWDY 142 m REVIEW QUESTIONS 143 BIBLIOGRAPHY Classification and Laboratory Assessment of Anemias Causes of Anemia 145 Clinical Signs and Symptoms of Anemia 145 Classification of Anemias 145 Laboratory Assessment of Anemias 146 Quantitative Measurements $Anemia 147 Semiquantitative Grading of Erythrocyte Morphology 147 Supplementary Assessment of Anemias 148. CHAPTER HIGHLIGHTS 148 B REVIEW QUESTIONS 148 B~BLIOGI~APHY Acute and Chronic Blood Loss Anemias Acute Blood Loss Anemia 150 Etiology 150 Physiology 150 Laboratory Findings 150 Chronic Blood Loss Anemia 150 Etiology 150 CHAPTER HIGHLIGHTS 151 CASE STUDIES 151 I REVIEW QUES~ONS 153 BIBLIOGRAPHY Aplastic and Related Anemias.. Aplastic Anemia 154 Etiology 154 Pathophysiology 155 Clinical Features 158 Laboratory Findings 158 Treatment 158 Congenital Red Blood Cell-Related Disorders 159 Telomeres 159 Laboratory Findings in Bone Marrow Failure Syndromes 160 Pure Red Cell Aplasia la) Diamond-Blackfan Anemia 160 Fanconi Anemia 161 Transient Erythroblastopenia of Childhood 162 Congenital Dyserythropoietic Anemia 163 m CHAPTER HIGHLIGHTS 163 m CASE STUDIES 163 m REVIEW QUESTIONS 165 B~BL~OGRAPHY Iron Deficiency Anemia and Anemia of Chronic Inflammation ,. 166 Scope of the Problem 166 Iron Deficiency Anemia 166 Early Diagnosis 166 Etiology 166 Epidemiology 167 Physiology 168 Pathophysiology 169 Clinical Sips and Symptoms 170 Laboratory Characteristics 170 Anemia of hflammation or Anemia of chronic Disorders 173 Etiology 173 Pathophysiology 173 Laboratory Characteristics 174 Treaftnent 175 m C ~ EHIGHLIGHTS R 175 CASE STUDIES 176 R REVIEW QU~ONS 179 BIBLIOGRAPHY Megaloblastic Anemias..... Megaloblastic Anemias 18 1 Etiology 181 Epidemiology 182 Physiology 182 ~itaminb,, (Cobalamin) Transport 182 Vitamin Bin (Cobalamin) and Folic Acid Deeficiencies 183 Pathophysiology 184 Gastric Pathological Findings 184 Clinical Signs and Symptoms 186 Laboratory Findings 186 Treatment and Monitoring Therapy 188

3 viii Contents 12 Hemolytic Anemias Hemolytic Anemias 192 Inherited Hemolyhc Anemia 192 Acquired Hemolytic Anemia 197 Pathophysiolog 200 Diagnostic Tests 201 Paroxysmal Nocturnal Hemoglobinuria 201 Etiology 201 Epidemiology 202 Pathophysiology 202 Clinical Signs and Symptoms 202 Laboratory Findings 203 Treatment 203 Paroxysmal Cold Hemoglobinuria 203 m CHAPTER HIGHLIGHTS 203 m CASE STUDIES 204 REVIEW QUESTIONS 207 B~BLIOGRAPHY Hemoglobinopathies and Thalassemias.. Hemoglobin Defects 210 Demographics 21 0 Etiology 210 Sickle Cell Disease Etiology 212 Epidemioloey 212 Pathophysiology 212 Clinical Signs and Symptoms 213 General Signs and Symptoms 214 Laboratory Testing 214 Special Laboratory Testing 215 Management of Sickle Cell Disease 216 Sickle Cell Syndromes: Pathogenesis and New Approaches 2 18 Sickle P-Thalassemia 218 Sickle-C Disease 219 Sickle Cell Trait 219 Thalassemia 220 Demographics 220 Etiology 220 Pathophysiology 220 P-Thalassemia 220 a-thalassemia 223 Other Hernoglobinopathies 224 Hemoglobin C Disease 224 Hemoglobin SC Disease 224 Hemoglobin D Disease 224 Hemoglobin E Disease 224 Hemoglobin H Disease 225 Methemogiobinemia 225 Unstable Hemoglobins 225 Hereditary Persistance of Fetal Hemoglobin 225 CHAPTER HIGHLIGHTS 226 w CASE STUDIES 227 m REVIEW QUESTIONS 232 BIBLIOGWHY 233 Development and Prol$eration of Neutrophils, Eosinophils, and Basophils 236 Distribution of Neutrophils, Eosinophils, and Basophils 236 Normal Maturational Characteristics of Neutrophils, Eosinophils, and Basophils 237 Mature Fom 239 Granulation in Mature Forms 239 The Monocytic-Macrophage Series 240 Production and Development of Monocytes and Macrophages 240 Morphological Characteristics 241 Reference Ranges of Granulocytes and Monocytes 241 Functional Properties of Granulocytes and Monocytes 242 General Charactm'stics 243 The Role of Macrophages 243 Acute Inflammatory Response 243 Sepsis 245 Steps in Phagocytosis 245 Specialized Functions of Granulocytes 247 Assessment Methods 248 Total Leukocyte Count 248 Differential Blood Smear Evaluation 248 Absolute Cell Counts 248 Erythrocyte Sedimentation Rate 248 Assessment of Eosinophils and Basophils 249 Leukocyte Alkaline Phosphatase Test 249 Neutrophilic Function 249 Neutrophilic Hypersegmentation Index 249 CHAPTER HIGHLIGHTS 249 w CASE STUDY 250 REVIEW QUESTIONS 251 m BIBLIOGRAPHY Nonmalignant Disorders of Granulocytes and Monocytes Quantitative Disorders 254 Leukocytosis 254 Leukocytopenia 255 Morphological Abnormalities of Mature Granulocytes 256 Toxic Granulation 256 Dahle Bodies 256 Hypersegmentation 256 Pelger-HuZt Anomaly 256 May-Hedin Anomaly 257 Chkdiak-Higashi Syndrome 257 Alder-Reilly Inclusions 258 Ehrlichia 258 Abnormalities of Mature Granulocytes in Body Fluids 258 Qualitative Disorders 258 Defective Locomotion andchernotaxis 258 Defects in Microbicidal Activity 259 Other Fundional Anomalies of Neutrophils 259 Monocyte-Macrophage Disorders 259 Gaucker Disease 259 Niemann-Pick Disease 260 CHAPTER HIGHLIGHTS 260 m CASE STUDIES 260 m REVIEW QUESTIONS 264 PART THREE: Leukocytes 14 Leukocytes: The Granulocytic and Monocytic Series Introduction 235 The Granulocytic Series 235 Production of Neutrophils, Eosinophils, and Basophils 235 Sites of Development and Maturation Anatomical Origin and Development of Lymphocytes 266 Sites of Lymphocytic Development 266 Lymphocyte Physiology 267 Normal Reference Values 267 Determining Absolute Lymphocyte Values 268 Morphological Characteristics of Normal Lymphocytes 268 Maturational Stages 269 Specific Lymphocyte Morphological Variations Leukocytes: Lymphocytes and Plasma Cells

4 Contents ix Characteristics of Lymphocytes 273 Major Lymphocyte Categories and Functions 273 Monoclonal Antibodies 274 Major Lymphocyte Membrane Characteristics and Development 274 FURCC~O~U~ Testing of Lymphocytes 277 Plasma Cell Development and Maturation 277 Plasma Cell Development 277 Maturational Morphology 277 Plasmacytoid Lymphocytes 277 Plasma Cell Disorders 278 CHAPTER HIGHLIGHTS Leukocytes: Nonmalignant Lyrnphocytic Disorders Characteristics of Lymphocytes 281 Lymphocytosis 28 1 Disorders Associated with Lymphocytosis 282 Infectl'ous Mononucleosis 282 Cytomegalovirus Infection 286 Toxoplasmon's 287 Infectious Lymphocytosis 288 Bordetella pertussis (Haemophilus pertussis) Infection 289 Lymphocytopenia 289 Immune Disorders Associated with Lymphocytopenia 289 DiGeorge Syndrome 289 Acquired Immunodeficiency Syndrome(HN/ARS) 289 Systemic Lupus Erythematosus 293 B CHAPTER HIGHLIGHTS 294. CASE STUDIES 294 m REVIEW QUES~ONS 297 BIBLIOGRAPHY Characteristics of Leukemias, Lymphomas, and Myelomas Comparison of Leukemias, Lymphomas, and Myelomas 298 Forms of Leukemia 298 Classilications of Leukemias 299 French-Amm'can-British Classification 299 World Health Organization Classijication 299 Prognosis and Treatment 300 Factors Related to the Occurrence of Leukemia 300 Genetic and Immunological Factors 300 Occupational Exposure 302 Enwronmental Exposure 302 Chemical and Drug Exposure 302 Genetic Abnormalities and Associations 302 Viral Agents 303 Secondary Causes of Leukemias 303 Demographic Distribution of Leukemia and Lymphomas 304 Ethnic Origin and Race 304 Gender 305 rn CHAPTER HIGHLIGHTS 305 rn REVIEW QUESTIONS 306 rn BIBLIOGRAPHY Acute Leukemias Introduction 307 Epidemiology of Acute Leukemias 307 Prognosis of Acute Leukemias 308 French-American-British and World Health Organization Categories 308 French-American-British (FAB) Classification 308 World Health Organization (WHO) Organization Classfication 308 General Characteristics of Acute Myeloid Leukemias 309 Genetic Differences 309 Micro-RNAs 310 Acute Myeloid Leukemia 310 FABMO 311 Acute Myeloid Leukemia (FAB MI) 31 1 Acute Myeloid Leukemia (FAB M2) 312 Acute Promyelocytzc Leukemia (FAB M3) 312 Acute Myelomono~c Leukemia (FAB M4) 313 Acute Monocytic Leukemia (FAB M5) 314 Erythroleukemia (FAB M6) 315 Selected Examples of Unusual Forms 316 Acute megakatyoblastic leukemia FAB M7 316 Epidemiology of Acute Lymphoblastic Leukemia 316 Prognosis of Acute Lymphoblastic Leukemia 317 Classifications of Acute Lymphoblastic Leukemia 317 Characteristics of Acute Lymphoblastic Leukemia 317 Clinical Signs and Symptoms 31 7 Laboratory Data 317 Special Identification Techniques 318 Treatment 319 Mixed Lineage Leukemia 319 Cytogenetic Analysis 319 Cytogenetic Analysis in Acute Myeloid Leukemia 319 Cytogenetics in Acute Lymphoblastic Leukemia 320 Principles of Special Cytochemical Stains 320 Sudan Black B Stain 321 Myeloperoxidase Stain 326 Periodic Acid-Schiff Stain 322 Esterase Stains 323 Phosphatase Stains 324 Monoclonal Antibodies 325 lmmunophenotyping 325 Lymphoid 325 Other Surface Membrane Markers 326 Life-Threatening Emergencies 326 Infection 326 Bleeding 326 Leukemic Infiltration of Organs 326 MetabolicAbnormalities 326 Hyperleukocytosis 327 Treatment Options 327 Relapse 328 Stem Cell Transplant 328 Future Trends Vaccines 328 m CHAPTER HIGHLIGHTS 328 CASE STUDIES 329 REVIEW QUESTTONS 333 BIBLIOGRAPHY Lymphoid and Plasma Cell Neoplasms Mature B-Cell Neoplasms Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma 337 Epidemiology 337 Etiology 337 Cytogenetics 338 Molecular Genetics 339 Staging and Prognosis 339 Clinical Signs and Symptoms 340 Laboratory Data 341 Treatment Options 341 Minimal Residual Disease 342 Hairy Cell Leukemia 342 Hairy Cell Leukemia Variant 343 Prolymphocytic Leukemia 344

5 X Contents Multiple Myeloma (Plasma Cell Myeloma) 344 Epidemiology 344 Etiology 344 Clinical Signs and Symptoms 344 Laboratory Data 344 Treatment 345 Waldenstrom Primary Macroglobulinemia (Lymphoplasmacytic lymphoma) 346 Epidemiology 346 Etiology 346 Clinical Signs and Symptoms 346 Laboratory Data 346 Treatment 347 Lymphomas 347 Relationship Between Lymphomas and Leukemias 347 Characteristics 347 Categories 347 Pathophysiology 349 Prtrrursors of Hodgkin Disease and 8-Cell Lymphomas 350 Hodgkin Disease 350 Non-Hodgkin Lymphoma 351 Characteristics of Other Forms 352 Shry Syndrome 353 Mature T-cell and NK-Cell Neoplasms CHAPTER HIGHLIGHTS CASE STUDIES 354 REVIEW QUESTIONS 358 B~L~OGRAPHY 358 PART FOUR: Myeloproliferative Neoplasms 361 Myeloproliferative Neoplasms General Characteristics of Myeloproliferative Neoplasms 362 Relationship of the Myeloprolqerative Neoplasms 362 Common Disorders of Hemostasis and Coagulation 362 Prognosis and Treatment 363 Chronic Myelogenous Leukemia 363 Epidemiology 363 Pathophysiology 363 Cytogenetics 364 Genetic Alterations 364 Laboratory Data 365 Cytogenetic Studies 367 Prognosis and Treatment 367 Minimal Residual fisease 368 Leukemia-Specific Targets 369 Allogenkc Bone Marrow Transplantation 370 Polycythemia Vera, Essential Thrombocytosis (Essential Thrombocythemia), and Primary Myelofibrois 370 Polycythemia Vera 370 Epidemiology 370 Etiology 370 Pathophysiology 370 Karyotype 371 Clinical Signs and Symptoms 371 Luboratory Data 371 Abnormalities of Hemostasis and Coagulation 372 Other Laboratory Assays 372 Treatment 373 Prognosis and Complications 374 Primary Myelofibrosis 374 Epidemiology 374 Pathophysiology 374 Karyotype 375 Clinical Signs and Symptoms 375 Celluiar Alterations 375 Prognosis 376 Treatment 376 Essential Thrombocytosis/Essential Thrombocythemia 376 Diagnostic Characteristics 376 Epidemiology 377 Pathophysiology 377 Karyotype 377 Clinical Signs and Symptoms 377 Laboratory Findings 377 Relationship of Thrombocythemia and PV 377 Treatment CMER HIGHLIGHTS 378 CASE STUDIES REVIEW QUESTIONS BIBLIOGRAPHY Myelodysplastic Syndromes and Myelodysplastict Myeloproliferative Neoplasms Classification 386 Myelodysplastic Syndromes 386 Myelodysplastic/myeloproliferative neoplasms 386 Pathophysiology 387 Myelodysplastic Syndrome 387 Etiology 388 Epidemiology 389 Chromosomal Abnormalities 389 Clinical Signs and Symptoms 390 Laboratory Manifestations 390 Features of Selected Types of Myelodysplastic Syndromes 391 Myelodysplastic/Myeloproliferative Neoplasms 392 Chronic myelomonocytic leukemia 392 Other Classif;utions 393 Treatment Strategies 393 Relationship of Karyotype to Prognosis 394 CHAPTER HIGHLIGHTS 395 CASE STUDIES 396 REVIEW QUESTIONS 397 BIBLIOGRAPHY 398 PART FIVE: Principles and Disorders of Hemostasis and Thrombosis Principles of Hemostasis and Thrombosis Overview of Hemostasis a d Thrombosis 400 Blood Vasculature: Structure and function 400 Arteries and Veins 400 Arterioles and Venules 400 Capillaries 400 Vasculature Physiology 40 1 The Role of Vasoconstriction in Hemostasis 401 The Role of the Endothelium 401 Maintenance of Vascular Integrity 402 The Megakaryocytic CeU Series 403 General Characteristics of Megakaryocytic Development 403 Cellular Ultrastructure of a Mature Platelet 405 Platelet Kinetia, Life Span, and Normal Values 406 Platelet Function in Hemostasis 406 Overall Functions of Platelets 406 Platelet Adhesion 406 Platelet Aggregation 407 Platelet Plug Consolidation and Stabilization 408 Laboratory Assessment of Platelets 408

6 Contents xi Blood Coagulation Factors 410 Basic Concepts of Blood Coagulation 410 Common Characteristics of Coagulation Factors 410 Charactenenstics of Individual Factors 410 The Mechanism of Coagulation 413 Coagulation Pathways 413 Thrombin-Mediated Reactions 414 Fibrinolysis 414 Other Systems and Inhibitors 415 Laboratory Assessment of Blood Coagulation Factors 416 International Normalized Ratio 416 Specialized Assaysfor Coagulation Factors 417 Anticoagulants 417 New Thromboplastins 418 Assays for Fibrin Formation 419 Normal Protective Mechanisms Against Thrombosis 420 Normal Blood Flow 420 Removal of Activated Clotting Factors and Particulate Material 420 The Natural Anticoagulant Systems 420 Cellular Regulators 424 Modern View of Hemostasis 424 CHAPTER HIGHLIGHTS 424 REVIEW QUESTIONS 426 BLBLIOGRAPHY Disorders of Hemostasis and Thrombosis Vascular Disorders 43 1 Abnormal Platelet Morphology 432 Quantitative Platelet Disorders 432 Thromboqmpenia 432 Thrombocytosis 436 Qualitative Characteristics of Platelets: Thrombocytopathy 436 Types of Platelet Dysfunctions 437 Bleeding Disorders Related to Blood Clotting 439 Defective Production 440 Disorders of Destruction and Consumption 445 Disorders Related to Elevated Fibrin Split Products 449 The Hypercoagulable State 450 Primary States of Hypercoagulability 450 Secondary States of Hypercoagulability 450 Pregnancy-Associated Thrombosis 450 General Features 451 Impaired Fibrinolysis 454 Antithrombin 111 Deficiency 456 Laboratory Assessment of Hypercoagulable States 457 CHAPTER HIGHLIGHTS 458 CASE STUDIES 460 REVIEW QUESTIONS 462 BIBLIOGRAPHY 463 PART SIX: Fundamentals of Hematological Analysis Body Fluid Analysis Introduction 466 Cerebrospinal Fluid 466 Anatomy and Physiology 466 Production of Cerebrospinal Fluid 466 Specimen Collection: Lumbar Puncture 466 Laboratory Analysis 467 Pleural, Peritoneal, and Pericardial Fluids 473 Efisions: Transudates and Exudates 473 Pleural Fluid 473 Peritoneal Fluid 478 Pericardial Fluid 482 Seminal Fluid 484 Synovial Fluid 486 Anatomy and Physiology of Joints 486 Purpose of Arthrocentesis 486 Aspiration 487 Laboratory Assays 487 Body Fluid Slide Preparation 490 Staining of Body Fluid Sediment 490 Amniotic Fluid 490 CHAPTER HIGHLIGHTS 490 REVIEW QUES~ONS 493 B~BL~OGRAPHY Manual Procedures in Hematology..... Procedural Format 498 Coagulation Procedures 516 Specimen Quality 516 Special Collection Techniques 51 6 Anticoagulants 51 7 Specimen Handling 51 7 Specimen Preparation 517 General Sources of Error 51 7 Quality Control 518 REVIEW QUESTIONS Instrumentation in Hematology Instrumental Principles 527 The Electrical Impedance Principle 527 The Optical Detection Principle 527 Characteristics of Light Scatter 527 Radio Frequency 528 Fundamentals of Laser Technology 528 Principles of Flow Cytometty 529 The Basis of Cellular Identification 529 Whole Blood Cell Analysis 531 T ~ eofautomated s Cell Counting Instruments 532 General Histogram Characteristics 543 Analysis of Instrumental Data Output 543 The Erythrocyte Histogram 543 Quantitative Descriptors of Erythrocytes 543 The Leukocyte Histogram 544 Platelet Histograms 545 Derived Platelet Parameters 546 Laser Technology 547 Red Blood Cells/Platelets 547 Peroxidase 548 BasophiULobularity (Nuclear) Channel 549 Lymphocyte su6typing 549 Applications of Flow Cytometry 549 General Properties of Flow Cytometry 550 Hematological Applications 550 Clinical Applications of Flow Cytometry 550 Other Cellular Applications 551 Digital Microscopy 554 Artificial Neural Networks 554 Digital Cell Morphology 554 Instruments in Coagulation Studies 555 Electromechanical Methods 555 Photo-Optical Methods 555 Viscosity-based Detection System 558 Platelet Agglutination 559 Platelet Aggregation 559 New Automation 559 Summary 559 Instrumental Principles 559 Analysis of Elem'cal Impedance Instrumental Data Output 559

7 xii contents Laser Technology 560 Applications of Flow Cytometry 560 D English-Spanish Medical Phrases for the Instruments in Coagulation Studies Phlebotomist STUDIES 560 E MSDS Sheet CASE REVIEW QUESTIONS 569 B~BL~OGRAPHY 571 F Tube Guide APPENDICES G Frequently Used Abbreviations, A Answers to Review Questions Glossary 591 B The Basics of Medical Terminology Index 602 C SI Units