Clinical Laboratory Hematology, 4th Edition By Shirlyn Mckenzie, Kristin Landis-Piwoward, Lynne Williams (eBook PDF)

Document Content and Description Below

Clinical Laboratory Hematology Contents Foreword Preface Organization Suitable for all Levels of Learning Unique Pedagogical Features Appendices A Complete Teaching and Learning Package Revie... wers Contributors Credits Section One Introduction to Hematology Chapter 1 Introduction Objectives—Level I and Level II Chapter Outline Key Terms Background Basics Overview Introduction Composition of Blood Reference Intervals for Blood Cell Concentration Hemostasis Checkpoint 1.1 Blood Component Therapy Investigation of a Hematologic Problem The Value of Laboratory Testing Checkpoint 1.2 Summary Review Questions Level I and Level II References Chapter 2 Cellular Homeostasis Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I and Level II Overview Introduction Review of Cell Structure Cell Membrane Lipids Proteins Carbohydrates Cytoplasm Checkpoint 2.1 Nucleus Nuclear Envelope Chromatin Nucleoli Checkpoint 2.2 Review of the Flow of Genetic Information DNA Replication DNA Repair Mutations and Polymorphisms Transcription RNA Processing Checkpoint 2.3 Control of Gene Expression Translation Protein Folding Post-translational Modifications Protein Degradation Tissue Homeostasis: Proliferation, Differentiation, and Apoptosis Proliferation: The Cell Cycle Phases Molecular Regulation Cyclins and Cyclin-Dependent Kinases Regulation of Cdk Activity Checkpoints Checkpoint 2.4 Differentiation Epigenetics Methylation Histone Modifications Translational Regulation Apoptosis Necrosis versus Apoptosis Molecular Regulation Caspases Bcl-2 Proteins Apoptosis and the Hematopoietic System Checkpoint 2.5 Abnormal Tissue Homeostasis and Cancer Summary Review Questions Level I Level II References Section Two The Hematopoietic System Chapter 3 Structure and Function of Hematopoietic Organs Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I and Level II Overview Introduction Development of Hematopoiesis Hematopoietic Tissue Bone Marrow Vasculature Stroma Hematopoietic Cells Checkpoint 3.1 Blood Cell Egress Checkpoint 3.2 Extramedullary Hematopoiesis Thymus Spleen Architecture Blood Flow Function Checkpoint 3.3 Hypersplenism Checkpoint 3.4 Splenectomy Lymph Nodes Mucosa-Associated Lymphoid Tissue (MALT) Lymphadenopathy Summary Review Questions Level I Level II References Chapter 4 Hematopoiesis Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I and Level II Overview Introduction Hematopoiesis Hematopoietic Precursor Cells Stem Cells Stem Cell Phenotype The Stem Cell Compartment Stem Cell Niches Progenitor Cells Maturing Cells Checkpoint 4.1 Revised Hematopoietic Precursor Cell Model Checkpoint 4.2 Cytokines and the Control of Hematopoiesis Growth Factor Functions Characteristics of Growth Factors Early-Acting (Multilineage) Growth Factors Stem Cell Factor (SCF) and Flt3 Ligand (FL) Interleukin 3 and GM-CSF (CSF2) Interleukin 6 and Interleukin 11 Later-Acting (Lineage-Restricted) Growth Factors Indirect-Acting Growth Factors Lineage-Specific Cytokine Regulation Erythropoiesis Granulopoiesis and Monopoiesis Megakaryocytopoiesis/Thrombopoiesis Lymphopoiesis Checkpoint 4.3 Negative Regulators of Hematopoiesis Cytokine Receptors, Signaling Pathways, and Transcription Factors Cytokine Receptors Receptors With Intrinsic Tyrosine Kinase Domains Hematopoietic Growth Factor Receptor Superfamily Receptor Functional Domains Signaling Pathways Checkpoint 4.4 Transcription Factors Clinical Use of Hematopoietic Growth Factors Hematopoietic Microenvironment Components of the Hematopoietic Microenvironment Cellular Components Extracellular Matrix Hematopoietic Microenvironment Niches Adhesion to the Microenvironment Stem Cell Niche Lymphoid Niches Erythroid Niches Megakaryocytic Niches Summary Review Questions Level I Level II References Chapter 5 The Erythrocyte Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Erythropoiesis and Red Blood Cell Maturation Erythroid Progenitor Cells Erythroid-Maturing Cells Checkpoint 5.1 Characteristics of Cell Maturation Pronormoblast Cytoplasm Nucleus Basophilic Normoblast Cytoplasm Nucleus Polychromatophilic Normoblast Cytoplasm Nucleus Orthochromic Normoblast Cytoplasm Nucleus Reticulocyte Checkpoint 5.2 Erythrocyte Erythroblastic Islands Erythrocyte Membrane Membrane Composition Lipid Composition Checkpoint 5.3 Protein Composition Checkpoint 5.4 Membrane Permeability Checkpoint 5.5 Erythrocyte Metabolism Glycolytic Pathway Hexose Monophosphate (HMP) Shunt Methemoglobin Reductase Pathway Checkpoint 5.6 Rapoport-Luebering Shunt Checkpoint 5.7 Erythrocyte Kinetics Erythrocyte Concentration Checkpoint 5.8 Regulation of Erythrocyte Production Checkpoint 5.9 Erythrocyte Destruction Checkpoint 5.10 Summary Review Questions Level I Level II Disclaimer References Chapter 6 Hemoglobin Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Hemoglobin Structure Checkpoint 6.1 Hemoglobin Synthesis Heme Globin Chain Synthesis Checkpoint 6.2 Regulation of Hemoglobin Synthesis Ontogeny of Hemoglobin Embryonic Hemoglobins Fetal Hemoglobin Adult Hemoglobins Checkpoint 6.3 Glycosylated Hemoglobin Checkpoint 6.4 Hemoglobin Function Oxygen Transport The Allosteric Property of Hemoglobin Adjustments in Hemoglobin–Oxygen Affinity Checkpoint 6.5 Carbon Dioxide Transport Plasma Transport Carbonic Acid Hemoglobin Binding Nitric Oxide and Hemoglobin Artificial Oxygen Carriers Hemoglobin Catabolism Extravascular Destruction Intravascular Destruction Checkpoint 6.6 Acquired Nonfunctional Hemoglobins Methemoglobin Sulfhemoglobin Carboxyhemoglobin Checkpoint 6.7 Summary Review Questions Level I Level II References Chapter 7 Granulocytes and Monocytes Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Granulopoiesis and Monocytopoiesis Leukocyte Concentration in the Peripheral Blood Leukocyte Surface Markers Leukocyte Function Neutrophils Differentiation, Maturation, and Morphology Myeloblast Promyelocyte Myelocyte Metamyelocyte Band Neutrophil Segmented Neutrophil Checkpoint 7.1 Distribution, Concentration, and Kinetics Bone Marrow Peripheral Blood Tissues Neutrophil Kinetics Checkpoint 7.2 Function Adherence Migration Checkpoint 7.3 Microbial Killing: Intracellular Degranulation Oxygen-Dependent Killing Oxygen-Independent Killing Microbial Killing: Neutrophil Extracellular Traps (NETs) Other Functions Checkpoint 7.4 Eosinophils Differentiation, Maturation, and Morphology Eosinophilic Myelocyte to Mature Eosinophil Eosinophilic Granules Distribution, Concentration, and Kinetics Function Basophils Differentiation, Maturation, and Morphology Basophilic Myelocyte to Mature Basophil Mast Cell Distribution, Concentration, and Kinetics Function Checkpoint 7.5 Monocytes Differentiation, Maturation, and Morphology Monoblast Promonocyte Monocyte Macrophage Distribution, Concentration, and Kinetics Function Bacterial Killing Cellular Scavenging Adaptive Immune Response Checkpoint 7.6 Summary Review Questions Level I Level II References Chapter 8 Lymphocytes Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Lymphopoiesis Ontogeny of Lymphopoiesis Transcriptional Regulation of Lymphopoiesis Cytokines in Lymphopoiesis Antigen-Dependent and -Independent Lymphopoiesis Mature Lymphocytes Checkpoint 8.1 Lineage Differentiation B Lymphocytes B Lymphocyte Membrane Markers B Lymphocyte Antigen Receptor (BCR) Immunoglobulin Gene Rearrangement B Lymphocyte Developmental Stages Pro-B to Pre-B Cells Immature to Naive Mature B Cells Checkpoint 8.2 Final Maturation to Effector B Cells B Cell Subclasses Checkpoint 8.3 T Lymphocytes Major Histocompatibility Complex T Lymphocyte Membrane Markers T Lymphocyte Antigen Receptor T Lymphocyte Developmental Stages Pro-T to Pre-T Cell to Double Positive Thymocyte Positive and Negative Selection Double positive to Single Positive Thymocytes to Mature T Lymphocytes T Lymphocyte Subclasses Natural Killer Cells Natural Killer T (NKT) Cells Lymphocyte Identification and Morphology Checkpoint 8.4 Morphologic Classification of Immature Lymphocytes Lymphoblast Prolymphocyte Lymphocyte Morphology of Activated Lymphocytes Reactive Lymphocyte Immunoblast Checkpoint 8.5 Plasmacytoid Lymphocyte Plasma Cells Memory Cells Checkpoint 8.6 Lymphocyte Distribution, Concentration, and Kinetics Checkpoint 8.7 Lymphocyte Function B Lymphocytes (Humoral Immunity) Effector Cell Development Immunoglobulin Pathologies Checkpoint 8.8 T Lymphocytes (Cell-Mediated Immunity) Antigen-Presenting Cells CD4+ T Cells CD8+ T Cells Memory T Cells Natural Killer Cells Adhesion Molecules of the Adaptive Immune Response Aging and Lymphocyte Function Lymphocyte Metabolism Summary Review Questions Level I Level II References Chapter 9 The Platelet Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Megakaryocytes Megakaryopoiesis Megakaryocyte Progenitor Cell Compartment Regulation of Megakaryocyte Production Humoral Regulation Checkpoint 9.1 Megakaryocyte Microenvironment Stages of Megakaryocyte Development Endomitosis Cytoplasmic Maturation Checkpoint 9.2 Thrombopoiesis Peripheral Blood Platelets Platelet Morphology Quantitative Platelet Evaluation Platelet Count Platelet Indices Reticulated Platelets Checkpoint 9.3 Platelet Function Hemostasis Immune Response Checkpoint 9.4 Summary Review Questions Level I Level II References Chapter 10 The Complete Blood Count and Peripheral Blood Smear Evaluation Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Pre-Examination Phase of the CBC Checkpoint 10.1 Examination Phase of the CBC Automated Results Leukocyte Count, Erythrocyte Count, Platelet Count, Hematocrit, and Hemoglobin Checkpoint 10.2 Erythrocyte Indices Mean Cell Volume Mean Cell Hemoglobin Mean Cell Hemoglobin Concentration Red Cell Distribution Width Reticulocyte Count Platelet Indices Mean Platelet Volume Platelet Distribution Width Reticulated Platelets WBC Differential Checkpoint 10.3 The Peripheral Blood Smear Low-Power Magnification High-Power Magnification White Blood Cells and Platelets Erythrocyte Morphology Anisocytosis Checkpoint 10.4 Microcytes Macrocytes Checkpoint 10.5 Poikilocytosis Acanthocytes Codocytes Dacryocytes Drepanocytes (Sickle Cells) Echinocytes Elliptocytes Keratocytes Knizocytes Leptocytes Schistocytes Spherocytes Stomatocytes Checkpoint 10.6 Variation in Hemoglobin (Color) Hypochromic Cells Polychromatophilic Erythrocytes Checkpoint 10.7 Erythrocyte Inclusions Basophilic Stippling Cabot Rings Howell-Jolly Bodies Heinz Bodies Iron Inclusions Checkpoint 10.8 Clinical Laboratory Professional’s Review of CBC Data Post-Examination Phase of the CBC Physiologic Variation in Hematologic Parameters CBC Variations in Newborns and Children Checkpoint 10.9 CBC Variations Between Ethnic Groups and Sexes, in Elderly People, and by Geographic Location Summary Review Questions Level I Level II References Section Three The Anemias Chapter 11 Introduction to Anemia Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction How Anemia Develops Interpretation of Abnormal Hemoglobin Concentrations Adaptations to Anemia Increase in Oxygenated Blood Flow Increase in Oxygen Utilization by Tissue Diagnosis of Anemia History Clinical Presentation Laboratory Evaluation Erythrocyte Count, Hematocrit, and Hemoglobin Erythrocyte Indices Checkpoint 11.1 Reticulocyte Count Checkpoint 11.2 Quantitation of Reticulocyte Immaturity Blood Smear Examination Leukocyte and Platelet Abnormalities Tests for Erythrocyte Destruction Bone Marrow Erythrocyte Survival Studies Differential Diagnosis of Anemia Based on Laboratory Tests Checkpoint 11.3 Classification of Anemias Morphologic Classification Microcytic, Hypochromic Anemia Macrocytic Anemia Normocytic, Normochromic Anemia Functional Classification Proliferation Defects Maturation Defects Survival Defects Sites of Destruction in Hemolytic Anemia Source of Defect in Hemolytic Anemias Intrinsic Defects Extrinsic Defects Classification Using the Red Cell Distribution Width Checkpoint 11.4 Laboratory Testing Schemas for Anemia Diagnosis Summary Review Questions Level I Level II References Chapter 12 Anemias of Disordered Regulation of Iron Metabolism and Heme Synthesis Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Iron Metabolism Distribution Absorption Enterocyte Uptake of Dietary Iron Export of Iron from Enterocyte to Plasma Absorption versus Storage Transport Iron Concentration in the Blood Cellular Uptake of Iron Storage Ferritin Hemosiderin Physiological Regulation of Iron Balance Systemic Iron Balance Increased Hepcidin Expression Hepcidin Inhibition Hypoxia Infection and Inflammation Intracellular Iron Balance Checkpoint 12.1 Iron Metabolism in the Mitochondria Iron Requirements Factors That Increase Fe Requirements Menstruation Pregnancy Infancy/Childhood Laboratory Assessment of Iron Iron Studies Checkpoint 12.2 Complete Blood Count (CBC) Hepcidin Ferrokinetics Iron-Deficiency Anemia Historical Aspects Etiology Checkpoint 12.3 Pathophysiology Clinical Presentation Laboratory Evaluation Peripheral Blood Iron Studies Erythrocyte Protoporphyrin (EP) Studies Bone Marrow Therapy Anemia of Chronic Disease Etiology Pathophysiology Clinical Presentation Laboratory Evaluation Peripheral Blood Checkpoint 12.4 Bone Marrow Therapy Iron Refractory Iron-Deficiency Anemia (Irida) Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Functional Iron Deficiency (FID) Etiology Laboratory Evaluation Therapy Anemias Associated with Abnormal Heme Synthesis Sideroblastic Anemias Etiology Pathophysiology Hereditary Sideroblastic Anemia Acquired Sideroblastic Anemia Lead Poisoning Alcoholism Associated with Malignancy Clinical Presentation Laboratory Evaluation Peripheral Blood Bone Marrow Molecular Studies Therapy Hemochromatosis Hereditary Hemochromatosis Etiology and Pathophysiology Clinical Presentation Laboratory Evaluation Secondary Hemochromatosis Treatment Checkpoint 12.5 Porphyrias Etiology Pathophysiology Congenital Erythropoietic Porphyria Erythropoietic Protoporphyria Clinical Presentation Laboratory Evaluation Congenital Erythropoietic Porphyria Erythropoietic Protoporphyria Prognosis and Therapy Summary Review Questions Level I Level II References Chapter 13 Hemoglobinopathies: Qualitative Defects Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Structural Hemoglobin Variants Identification of Hemoglobin Variants Methods of Analysis Checkpoint 13.1 Nomenclature Checkpoint 13.2 Pathophysiology Altered Solubility Altered Function Altered Stability Checkpoint 13.3 Sickle Cell Anemia Pathophysiology Solubility and Polymerization of Hemoglobin S Irreversibly Sickled Cells Red Blood Cell (RBC) Destruction Vaso-Occlusion Clinical Presentation Anemia Vaso-Occlusive Crisis Bacterial Infection Checkpoint 13.4 Acute Splenic Sequestration Acute Chest Syndrome Iron Overload Laboratory Evaluation Peripheral Blood Bone Marrow Hemoglobin Electrophoresis Solubility Test Sickling Test Other Diagnostic Tests Other Laboratory Findings Therapy Checkpoint 13.5 Sickle Cell Trait Other Sickling Disorders Checkpoint 13.6 Hemoglobin C Disease Hemoglobin S/C Disease Checkpoint 13.7 Hemoglobin D Checkpoint 13.8 Hemoglobin E Checkpoint 13.9 Unstable Hemoglobin Variants Pathophysiology Clinical Presentation Laboratory Evaluation Peripheral Blood Other Laboratory Findings Checkpoint 13.10 Therapy Hemoglobin Variants With Altered Oxygen Affinity Hemoglobin Variants with Increased Oxygen Affinity Hemoglobin Variants with Decreased Oxygen Affinity Methemoglobinemias Checkpoint 13.11 Summary Review Questions Level I Level II References Chapter 14 Thalassemia Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Thalassemia versus Hemoglobinopathy Checkpoint 14.1 Types of Thalassemia Genetic Defects in Thalassemia Checkpoint 14.2 Pathophysiology Clinical Presentation Checkpoint 14.3 Laboratory Evaluation Treatment Curative Therapy Maintenance Therapy Transfusion-Dependent Thalassemia Non-Transfusion-Dependent Thalassemia α-Thalassemia General Considerations Etiology Affected Alleles Affected Individuals Genotypes α-Thalassemia Major (α0/α0 or α-thal-1/α-thal-1); Hydrops Fetalis Pathophysiology Clinical Presentation Laboratory Evaluation Checkpoint 14.4 Hemoglobin H Disease (α0/α+ or α-thal-1/α-thal-2 Pathophysiology Checkpoint 14.5 Clinical Presentation Laboratory Evaluation Treatment and Prognosis α-Thalassemia Minor (α+/α+ or α-thal-2/α-thal-2; α0/α or α-thal-1/normal) Pathophysiology Clinical Presentation Laboratory Evaluation Treatment and Prognosis Silent Carrier (α+/α or α-thal-2/normal) Pathophysiology/Clinical Presentation/Laboratory Evaluation Treatment and Prognosis β-Thalassemia General Considerations Genetics Affected Individuals β-Thalassemia Major (β0/β0, β0/β+, β+/β+) Pathophysiology Checkpoint 14.6 Clinical Presentation Laboratory Evaluation Treatment Prognosis β-Thalassemia Minor (β0/β or β+/β) Pathophysiology Clinical Presentation Laboratory Evaluation Checkpoint 14.7 Treatment and Prognosis β-Thalassemia Intermedia (β+/β+, β0/β+, β0/β) Clinical Presentation Laboratory Evaluation Treatment and Prognosis β-Thalassemia Minima (βSC/β) Other Thalassemias and Thalassemia-Like Conditions δβ-Thalassemia γδβ-Thalassemia Hemoglobin Constant Spring Clinical Presentation Laboratory Evaluation Checkpoint 14.8 Hereditary Persistence of Fetal Hemoglobin (HPFH) Genetics Variants Homozygotes Heterozygotes Hemoglobin Lepore Genetics Pathophysiology Laboratory Evaluation Combination Disorders Checkpoint 14.9 Differential Diagnosis of Thalassemia Checkpoint 14.10 Summary Review Questions Level I Level II References Chapter 15 Megaloblastic and Nonmegaloblastic Macrocytic Anemias Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Megaloblastic Anemia Checkpoint 15.1 Clinical Presentation Checkpoint 15.2 Laboratory Evaluation Peripheral Blood Checkpoint 15.3 Bone Marrow Other Laboratory Findings Checkpoint 15.4 Folate Structure and Function Metabolism Requirements Checkpoint 15.5 Pathophysiology of Folate Deficiency Causes of Folate Deficiency Inadequate Diet Increased Requirement Malabsorption Drug Inhibition Checkpoint 15.6 Laboratory Evaluation of Folate Deficiency Cobalamin (Vitamin B12) Structure and Function Checkpoint 15.7 Metabolism Absorption Transport Requirements Checkpoint 15.8 Pathophysiology of Cobalamin Deficiency Impaired DNA Synthesis Defective Fatty Acid Degradation Checkpoint 15.9 Causes of Cobalamin Deficiency Pernicious Anemia Other Causes of Malabsorption Nutritional Deficiency Other Causes Checkpoint 15.10 Laboratory Evaluation of Cobalamin Deficiency Gastric Analysis CobaSorb Test Checkpoint 15.11 Therapy Other Megaloblastic Anemias Drugs Enzyme Deficiencies Congenital Deficiencies Orotic Aciduria Congenital Dyserythropoietic Anemia Other Hematopoietic Diseases Checkpoint 15.12 Macrocytic Anemia Without Megaloblastosis Alcoholism Liver Disease Checkpoint 15.13 Stimulated Erythropoiesis Hypothyroidism Checkpoint 15.14 Summary Review Questions Level I Level II References Chapter 16 Hypoproliferative Anemias Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Aplastic Anemia Checkpoint 16.1 Epidemiology Pathophysiology Classification and Etiology Acquired Forms of Aplastic Anemia Idiopathic Drugs And Chemical Agents Ionizing Radiation Infectious Agents Metabolic Association with Clonal Disorders Inherited Aplastic Anemia Fanconi Anemia Other Causes of Inherited Aplastic Anemia Clinical Presentation Laboratory Evaluation Peripheral Blood Bone Marrow Other Laboratory Findings Prognosis and Therapy Differentiation of Aplastic Anemia from other Causes of Pancytopenia Myelophthisic Anemia Myelodysplastic Syndromes Congenital Dyserythropoietic Anemia Hypersplenism Other Checkpoint 16.2 Pure Red Cell Aplasia Acute Acquired Pure Red Cell Aplasia Chronic Acquired Pure Red Cell Aplasia Diamond-Blackfan Syndrome Other Hypoproliferative Anemias Renal Disease Pathophysiology Laboratory Evaluation Therapy Endocrine Abnormalities Summary Review Questions Level I Level II References Chapter 17 Hemolytic Anemia: Membrane Defects Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Skeletal Protein Abnormalities Vertical Interactions Horizontal Interactions Lipid Composition Abnormalities Hereditary Spherocytosis Pathophysiology Clinical Presentation Laboratory Evaluation Checkpoint 17.1 Osmotic Fragility Test Autohemolysis Test Antihuman Globulin Test Checkpoint 17.2 Identification of Deficient/Defective Membrane Protein Therapy Hereditary Elliptocytosis Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Checkpoint 17.3 Hereditary Pyropoikilocytosis (HPP) Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Checkpoint 17.4 Hereditary Stomatocytosis Syndromes Pathophysiology Laboratory Evaluation Checkpoint 17.5 Therapy Checkpoint 17.6 Abnormal Membrane Lipid Composition: Acanthocytosis Spur Cell Anemia Abetalipoproteinemia (Hereditary Acanthocytosis) Lecithin-Cholesterol Acyl Transferase (LCAT) Deficiency Rare Forms Checkpoint 17.7 Paroxysmal Nocturnal Hemoglobinuria (PNH) Pathophysiology Clinical Presentation Laboratory Evaluation Checkpoint 17.8 Therapy Summary Review Questions Level I Level II References Chapter 18 Hemolytic Anemia: Enzyme Deficiencies Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I and Level II Overview Introduction Hexose Monophosphate Shunt Glycolytic Pathway Clinical and Laboratory Evaluation in Erythrocyte Enzyme Deficiencies Diagnosis Checkpoint 18.1 Glucose-6-Phosphate Dehydrogenase Deficiency Etiology Checkpoint 18.2 Pathophysiology Checkpoint 18.3 G6PD Variants Females with G6PD Deficiency Clinical Presentation Acute Acquired Hemolytic Anemia Hereditary Nonspherocytic Hemolytic Anemia Neonatal Hyperbilirubinemia Laboratory Evaluation Qualitative Fluorescent Spot Test Dye Reduction Test Ascorbate Cyanide Test Cytochemical Staining Quantitation of G6PD Molecular Methods Differential Diagnosis Therapy Other Defects and Deficiencies of the Hmp Shunt and Gsh Metabolism Pyruvate Kinase (Pk) Deficiency Etiology Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Checkpoint 18.4 Other Enzyme Deficiencies in the Glycolytic Pathway Abnormal Erythrocyte Nucleotide Metabolism Summary Review Questions Level I Level II References Chapter 19 Hemolytic Anemia: Immune Anemias Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Classification Of Immune Hemolytic Anemias Checkpoint 19.1 Sites And Factors That Affect Hemolysis Checkpoint 19.2 Mechanisms Of Hemolysis IgG-Mediated Hemolysis Complement-Mediated Hemolysis IgM-Mediated Hemolysis Checkpoint 19.3 Laboratory Identification of Sensitized Red Cells Direct Antiglobulin Test Indirect Antiglobulin Test Checkpoint 19.4 Negative DAT in AIHA Positive DAT in Normal Individuals Autoimmune Hemolytic Anemias (AIHA) Warm Autoimmune Hemolytic Anemia Pathophysiology Clinical Presentation Checkpoint 19.5 Laboratory Evaluation Differential Diagnosis Checkpoint 19.6 Therapy Cold Autoimmune Hemolytic Anemia Pathophysiology Clinical Presentation Checkpoint 19.7 Laboratory Evaluation Checkpoint 19.8 Differentiation of CAS Agglutinins from Benign Cold Agglutinins Checkpoint 19.9 Therapy Paroxysmal Cold Hemoglobinuria Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Checkpoint 19.10 Mixed-Type AIHA Drug-Induced Hemolytic Anemias Mechanism of In Vivo Action for Drug-Dependent Antibodies Mechanism of In Vivo Action for Drug-Independent Antibodies Checkpoint 19.11 Alloimmune Hemolytic Anemia Hemolytic Transfusion Reactions Pathophysiology Clinical Presentation Checkpoint 19.12 Laboratory Evaluation Checkpoint 19.13 Therapy Hemolytic Disease of the Fetus and Newborn (HDFN) Pathophysiology Sensitization Prenatal Period Postnatal Period Clinical Presentation Checkpoint 19.14 Laboratory Evaluation Rh Incompatibility ABO Incompatibility Checkpoint 19.15 Therapy Rh Immune Globulin (RhIG) Summary Review Questions Level I Level II References Chapter 20 Hemolytic Anemia: Nonimmune Defects Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Hemolytic Anemia Caused by Physical Injury to the Erythrocyte Thrombotic Microangiopathic Anemia (TMA) Checkpoint 20.1 Hemolytic Uremic Syndrome Shiga Toxin–Producing E. Coli Hemolytic Uremic Syndrome (Stec-Hus) Secondary HUS Atypical HUS Checkpoint 20.2 Pathophysiology Checkpoint 20.3 Clinical Presentation Laboratory Evaluation Checkpoint 20.4 Therapy Thrombotic Thrombocytopenic Purpura Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Checkpoint 20.5 Disseminated Intravascular Coagulation Checkpoint 20.6 HELLP Syndrome Malignant Hypertension Other Conditions Associated with MAHA Other Erythrocyte Physical Trauma Resulting in Hemolytic Anemia Traumatic Cardiac Hemolytic Anemia Thermal Injury Exercise-Induced Hemoglobinuria Hemolytic Anemias Caused by Antagonists in The Blood Infectious Agents Malarial Parasites Babesiosis Checkpoint 20.7 Bartonellosis Clostridium perfringens Animal Venoms Chemicals and Drugs Summary Review Questions Level I Level II References Section Four Nonmalignant Disorders of Leukocytes Chapter 21 Nonmalignant Disorders of Leukocytes: Granulocytes and Monocytes Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Checkpoint 21.1 Neutrophil Disorders Quantitative Disorders Neutrophilia Immediate Neutrophilia Acute Neutrophilia Chronic Neutrophilia Conditions Associated with Neutrophilia Bacterial Infection Tissue Destruction/Injury, Inflammation, and Metabolic Alterations Leukemoid Reaction Checkpoint 21.2 Leukoerythroblastic Reaction Stimulated Bone Marrow States Physiologic Leukocytosis Checkpoint 21.3 Neutropenia Decreased Bone Marrow Production Stem Cell Disorders Megaloblastic Anemia Chemicals/Drugs Congenital Neutropenia Increased Cell Loss Immune Neutropenia Hypersplenism Pseudo-Neutropenia False Neutropenia Checkpoint 21.4 Qualitative or Morphologic Abnormalities Nuclear Abnormalities Pelger-Huët Anomaly Hypersegmentation Pyknotic Nucleus Checkpoint 21.5 Cytoplasmic Abnormalities Döhle Bodies Toxic Granules Cytoplasmic Vacuoles Intracellular Organisms Inherited Functional Abnormalities Alder-Reilly Anomaly Chédiak-Higashi Syndrome May-Hegglin Anomaly Chronic Granulomatous Disease Myeloperoxidase Deficiency Leukocyte Adhesion Deficiency Checkpoint 21.6 Eosinophil Disorders Nonclonal (Reactive) Hypereosinophilia Clonal (Neoplastic) Hypereosinophilia Idiopathic Hypereosinophilia Basophil and Mast Cell Disorders Checkpoint 21.7 Monocyte/Macrophage Disorders Quantitative Disorders Qualitative Disorders Gaucher Disease Niemann-Pick Disease Miscellaneous Lysosomal Storage Disorders Histiocytoses Summary Review Questions Level I Level II References Chapter 22 Nonmalignant Lymphocyte Disorders Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Lymphocytosis Infectious Mononucleosis EBV Pathophysiology Clinical Presentation Laboratory Evaluation Peripheral Blood Bone Marrow Serologic Tests Therapy Checkpoint 22.1 Toxoplasmosis Cytomegalovirus Clinical Presentation Laboratory Evaluation Bordetella Pertussis Reactive Lymphocytosis Plasmacytosis Persistent Polyclonal B-Cell Lymphocytosis Lymphocytopenia Lymphocyte Sequestration and Destruction Checkpoint 22.2 Immune Deficiency Disorders Acquired Immunodeficiency Syndrome Clinical Presentation Surveillance Hiv Case Definition Pathophysiology Laboratory Evaluation Disease Monitoring Therapy Checkpoint 22.3 Other Acquired Immune Deficiency Disorders Congenital Immune Deficiency Disorders Severe Combined Immunodeficiency Syndrome Sex-Linked SCID Checkpoint 22.4 Autosomal SCID Wiskott-Aldrich Syndrome Checkpoint 22.5 DiGeorge Syndrome Sex-Linked Agammaglobulinemia Ataxia-Telangiectasia Hyper IgE Syndrome Summary Review Questions Level I Level II References Section Five Neoplastic Hematologic Disorders Chapter 23 Introduction to Hematopoietic Neoplasms Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Pathophysiology Cancer Stem Cells Checkpoint 23.1 Checkpoint 23.2 Molecular Basis of Cancer Oncogenes Tumor Suppressor Genes Epigenetics DNA Methylation Histone Deacetylation MicroRNAs Checkpoint 23.3 Cell Cycle Checkpoints and Cancer Checkpoint 23.4 Apoptosis and Cancer Leukemogenesis Genetic Susceptibility Somatic Mutation Viral Infection Immunologic Dysfunction Miscellaneous Factors Checkpoint 23.5 Epidemiology Clinical Presentation Laboratory Evaluation Checkpoint 23.6 Hematopoietic Neoplasm Classification Laboratory Procedures for Diagnosing and Classifying Neoplasms Cytochemical Analysis Immunologic Analysis Genetic Analysis Cytogenetics Molecular Analysis Checkpoint 23.7 Prognosis and Treatment of Neoplastic Disorders Prognosis Treatment Chemotherapy Molecular-Targeted Therapy Epigenetic Therapy Bone Marrow Transplant Stem Cell Transplants Hematopoietic Growth Factors Complications of Treatment Summary Review Questions Level I Level II References Chapter 24 Myeloproliferative Neoplasms Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Classification Pathophysiology General Features Checkpoint 24.1 Chronic Myeloid Leukemia (CML) Etiology and Pathophysiology Disease Progression and Additional Chromosome/Molecular Mutations Philadelphia (Ph) Chromosome in Acute Leukemias Checkpoint 24.2 Clinical Presentation Laboratory Evaluation Peripheral Blood Bone Marrow Checkpoint 24.3 Terminal Phase Therapy Imatinib HSC Transplantation Differential Diagnosis Checkpoint 24.4 Chronic Neutrophilic Leukemia (CNL) Etiology and Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Differential Diagnosis Checkpoint 24.5 Essential Thrombocythemia (Et) Etiology and Pathophysiology JAK2(V617F) MPL Mutations Calreticulin (CALR) Mutations Clinical Presentation Laboratory Evaluation Peripheral Blood Bone Marrow Tests of Hemostasis Molecular Genetics Other Laboratory Evaluation Prognosis and Therapy Chemotherapy Molecular Targets Differential Diagnosis Checkpoint 24.6 Polycythemia Vera (PV) Classification Etiology and Pathophysiology JAK2 Other Mutations Epigenetics Genes and Presentation of Phenotype Clinical Presentation Laboratory Evaluation Peripheral Blood Bone Marrow Other Laboratory Evaluation Molecular Genetics Prognosis and Therapy Phlebotomy Chemotherapy Molecular Targets Differential Diagnosis Secondary Polycythemia Tissue Hypoxia Inappropriate Increase in Erythropoietin Familial Polycythemia Neonatal Polycythemia Checkpoint 24.7 Relative Polycythemia Laboratory Differentiation of Polycythemia Checkpoint 24.8 Erythropoietin Measurement Genetic Studies Bone Marrow Changes Primary Myelofibrosis (Pmf) Etiology and Pathophysiology Cytokine Involvement Gene Mutations Checkpoint 24.9 Clinical Presentation Laboratory Evaluation Peripheral Blood Checkpoint 24.10 Bone Marrow Molecular Genetics Prognosis and Therapy Differential Diagnosis Myeloproliferative Neoplasm, Unclassifiable (Mpn, U) Clonal Hypereosinophilia Myeloid and Lymphoid Neoplasms Associated with Eosinophilia and PDGFRA, PDGFRB, or FGFR1 Mutations Myeloid and Lymphoid Neoplasms with PDGFRA Rearrangement Clinical Presentation Laboratory Evaluation Therapy Myeloid Neoplasms with PDGFRB Rearrangement Clinical Presentation Laboratory Evaluation Therapy Myeloid and Lymphoid Neoplasms with FGFR1 Abnormalities Clinical Presentation Laboratory Evaluation Therapy Chronic Eosinophilic Leukemia, Not Otherwise Specified (CEL-NOS) Clinical Presentation Laboratory Evaluation Therapy Differential Diagnosis Idiopathic Hypereosinophilic Syndrome (I-HES) Mast Cell Disease (Mastocytosis) Summary Review Questions Level I Level II References Chapter 25 Myelodysplastic Syndromes Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Pathophysiology Checkpoint 25.1 Cytogenetics, Epigenetics, and Single Gene Mutations Abnormal Karyotypes −5 and del(5q) −7 and del(7q) +8 del(20q) −Y Complex Karyotype Epigenetic Changes Oncogenes and Tumor Suppressor Genes Proliferation Abnormalities Checkpoint 25.2 Incidence Clinical Presentation Laboratory Evaluation Peripheral Blood Erythrocytes Leukocytes Platelets Micromegakaryocytes Checkpoint 25.3 Bone Marrow Dyserythropoiesis Dysgranulopoiesis Dysmegakaryopoiesis Molecular Diagnostics Additional Laboratory Evaluation Checkpoint 25.4 Blast and Precursor Cell Classification Myeloblasts Promyelocytes Ring Sideroblasts Checkpoint 25.5 Immunological Identification of Blasts Classification Description of MDS Subgroups MDS with Single Lineage Dysplasia (MDS-SLD) MDS with Ring Sideroblasts (MDS-RS) MDS with Multilineage Dysplasia (MDS-MLD) MDS with Excess Blasts (MDS-EB) MDS with Isolated del(5q) MDS, Unclassifiable (MDS-U) Refractory Cytopenia of Childhood Checkpoint 25.6 Variables of MDS Subgroups Hypoplastic MDS MDS with Fibrosis Therapy-Related Myelodysplasia Differential Diagnosis Prognosis Therapy Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPNS) Chronic Myelomonocytic Leukemia (CMML) Atypical Chronic Myeloid Leukemia (aCML, BCR/ABL1−) Checkpoint 25.7 Juvenile Myelomonocytic Leukemia MDS/MPN with Ring Sideroblasts and Thrombocytosis (MDS/MPN-RS-T) Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable (MDS/MPN, U) Summary Review Questions Level I Level II Case Study References Chapter 26 Acute Myeloid Leukemias Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Etiology And Pathophysiology Laboratory Evaluation Peripheral Blood Bone Marrow Checkpoint 26.1 Other Laboratory Evaluation Classification Identification of Cell Lineage Cytochemistry Immunophenotyping Cytogenetic Analyses Checkpoint 26.2 WHO Classification of AML AML with Recurrent Genetic Abnormalities AML with T(8;21)(Q22;Q22.1); RUNX1-RUNX1T1 AML with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11 AML with t(9;11)(p21.3;q23.3); MLLT3-KMT2A Checkpoint 26.3 AML with PML-RARA Hypergranular APL Microgranular APL Variant Diagnostic Gene Rearrangement Checkpoint 26.4 AML with T(6;9)(P23;Q34.1); DEK-NUP214 AML with INV(3)(Q21.3;Q26.2) or T(3;3)(Q21.3;Q26.2); GATA2, MECOM AML with t(1;22)(p13.3;q13.32); RBM15-MKL1 AML with Mutated NPM1 AML with Biallelic Mutations of CEBPA Provisional Subclasses and Miscellaneous Mutations AML With BCR-ABL1 AML with Mutated RUNX1 FLT3 and AML Checkpoint 26.5 Therapy-Related Myeloid Neoplasms AML with Myelodysplasia-Related Changes AMLs Not Otherwise Specified AML with Minimal Differentiation AML without Maturation Checkpoint 26.6 AML with Maturation Checkpoint 26.7 Acute Myelomonocytic Leukemia (AMML) Acute Monoblastic Leukemia and Acute Monocytic Leukemia (AMOL) Pure Erythroid Leukemia (PEL) Checkpoint 26.8 Acute Megakaryoblastic Leukemia (AMKL) Acute Basophilic Leukemia (ABL) Acute Panmyelosis with Myelofibrosis Myeloid Sarcoma Myeloid Proliferations Related to Down Syndrome Therapy Checkpoint 26.9 Summary Review Questions Level I Level II References Chapter 27 Precursor Lymphoid Neoplasms Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Etiology and Pathophysiology Clinical Presentation Checkpoint 27.1 Laboratory Evaluation Peripheral Blood Bone Marrow Tissue Involvement Other Laboratory Evaluation Checkpoint 27.2 Identification of Cell Lineage Morphology and Cytochemistry Terminal Deoxynucleotidyl Transferase (TdT) Immunophenotyping Checkpoint 27.3 Cytogenetic Analysis Molecular Analysis Who Classification B Lymphoblastic Leukemia/Lymphoma Immunophenotyping Cytogenetics and Pathogenesis Prognosis T Lymphoblastic Leukemia/Lymphoma Immunophenotyping Checkpoint 27.4 Cytogenetics and Pathogenesis Prognosis Checkpoint 27.5 Acute Leukemias of Ambiguous Lineage Acute Undifferentiated Leukemia Acute Leukemias with Lineage Heterogeneity Checkpoint 27.6 Natural Killer Cell Lymphoblastic Leukemia/Lymphoma Therapy Summary Review Questions Level I Level II References Chapter 28 Mature Lymphoid Neoplasms Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Etiology and Pathophysiology Acquired Genetic Factors Inherited Genetic Factors Environmental Factors Checkpoint 28.1 Diagnosis and Who Classification Laboratory Evaluation Prognosis Therapy Staging Checkpoint 28.2 Mature B Cell Neoplasms Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Peripheral Blood Immunophenotyping Lymph Node Biopsy Molecular Prognostics Cytogenetics and Prognosis Transformation Therapy B Cell Prolymphocytic Leukemia Peripheral Blood Immunophenotyping Hairy Cell Leukemia Peripheral Blood Bone Marrow Tissue Involvement Checkpoint 28.3 Follicular Lymphoma Lymph Node Biopsy Immunophenotyping and Cytogenetics Prognosis and Treatment Mantle Cell Lymphoma (MCL) Peripheral Blood Lymph Node Biopsy Immunophenotyping and Cytogenetics Prognosis Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue Lymph Node Biopsy Immunophenotyping Treatment Lymphoplasmacytic Lymphoma Lymph Node Biopsy Molecular Evaluation Treatment Diffuse Large B Cell Lymphoma Genomic Profiling and Immunohistochemistry Molecular Prognostics Burkitt Lymphoma Lymph Node Biopsy Immunophenotyping and Molecular Evaluation Plasma Cell Neoplasms Plasma Cell Myeloma Cytogenetics Peripheral Blood and Bone Marrow Monoclonal Gammopathy of Undetermined Significance (MGUS) Plasmacytoma Mature T and NK Cell Neoplasms Nodal T and NK Cell Lymphomas Peripheral T Cell Lymphoma, Not Otherwise Specified (NOS) Angioimmunoblastic T Cell Lymphoma (AITL) Anaplastic Large Cell Lymphoma (ALCL) Extranodal T and NK Cell Lymphomas Hepatosplenic T Cell Lymphoma (HSTCL) Extranodal NK/T Cell Lymphoma, Nasal Type Subcutaneous Panniculitis-Like T Cell Lymphoma Enteropathy-Associated T Cell Lymphoma (EATL) Leukemic T and NK Cell Lymphomas T Cell Prolymphocytic Leukemia (T-PLL) T Cell Large Granular Lymphocytic (T-LGL) Leukemia Adult T Cell Leukemia/Lymphoma (ATLL) Sézary Syndrome Hodgkin Lymphoma (HL) Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) Classical Hodgkin Lymphoma (CHL) Checkpoint 28.4 Checkpoint 28.5 Summary Review Questions Level I Level II References Chapter 29 Hematopoietic Stem Cell Transplantation Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Origin and Differentiation of Hematopoietic Stem Cells Sources of Hematopoietic Stem Cells and Types of Stem Cell Transplants Allogeneic Stem Cell Transplantation Autologous Stem Cell Transplantation Checkpoint 29.1 Umbilical Cord Blood Stem Cell Transplantation Checkpoint 29.2 Collection and Processing of Hematopoietic Stem Cells Bone Marrow Peripheral Blood Umbilical Cord Blood Purging Cryopreservation and Storage of Hematopoietic Stem Cells Infusion of Hematopoietic Stem Cells Quantitation of Hematopoietic Stem Cells Determination of Mononuclear Cell Count CD34 Enumeration by Flow Cytometry Cell Culture for Colony Forming Units Checkpoint 29.3 Collection Target for Stem Cells Hematopoietic Engraftment Evidence of Initial Engraftment Evidence of Long-Term Engraftment Checkpoint 29.4 Role of the Clinical Laboratory Professional in Stem Cell Transplantation Graft-Versus-Host Disease and Graft-Versus-Leukemia Effect Complications Associated with Stem Cell Transplantation Early Complications Graft Failure Graft-versus-Host Disease (GVHD) Passenger Lymphocyte Syndrome (PLS) Peritransplant Infections Recurrence of Malignant Disease Other Complications Late Complications Checkpoint 29.5 Increased Availability and Success of Stem Cell Transplantation Gene Therapy Summary Review Questions Level I Level II References Section Six Body Fluids Chapter 30 Morphologic Analysis of Body Fluids in the Hematology Laboratory Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Types of Body Fluids Serous Fluids Cerebrospinal Fluid Checkpoint 30.1 Synovial Fluid Bronchoalveolar Lavage (BAL) Hematologic Analysis of Body Fluids Specimen Collection and Handling Physical Characteristics Cell Counting Manual Cell Counts Automated Cell Counts Cell Count Reference Intervals and Correlation with Disease Cerebrospinal Fluid Serous Fluids: Pleural, Peritoneal, Pericardial Synovial Fluids Bronchoalveolar Lavage Nucleated Cell Differential Cytocentrifuge Slide Preparation Manual Slide Preparation Cell Types and Microscopic Findings Common to All Fluids Morphologic Findings Resulting from Artifact Nonspecific Reactive Changes Microorganisms Malignant Cells in Body Fluids Checkpoint 30.2 Microscopic Findings in Specific Fluids Serous: Pleural, Peritoneal, Pericardial Checkpoint 30.3 Cerebrospinal Fluid Checkpoint 30.4 Joint Fluid Checkpoint 30.5 Analysis of Other Fluids BAL Fluid Amniotic Fluid Lamellar Body Counts Semen Analysis Physical and Chemical Properties Volume and Appearance Liquefaction Viscosity pH Microscopic Analysis Motility Vitality Sperm Count Morphology Summary Review Questions Level I Level II References Section Seven Hemostasis Chapter 31 Primary Hemostasis Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Role of the Vascular System Structure of Blood Vessels Functions of Blood Vessels in Hemostasis Checkpoint 31.1 Functions of Endothelial Cells Checkpoint 31.2 Platelets in Hemostasis Platelet Structure Peripheral Zone Glycocalyx Plasma Membrane Membrane Receptors GPIb/IX GPIIb/IIIa Collagen Receptors Platelet Alloantigens Checkpoint 31.3 Structural Zone Microtubules Microfilaments and Intermediate Filaments Organelle Zone Dense Granules α-Granules Lysosomes and Peroxisomes Platelet Metabolic Activity Membrane Systems Open Canalicular System (OCS) Dense Tubular System (DTS) Platelet Functions Maintenance of Vascular Integrity Formation of the Primary Hemostatic Plug Platelet Adhesion Checkpoint 31.4 Platelet Activation Platelet Agonists Platelet Shape Change Platelet Secretion (Release) Roles of the Granule Contents Platelet Aggregation Checkpoint 31.5 Biochemistry of Platelet Activation G Proteins Phospholipase C and the Phosphoinositide Pathway Role of Ca++ Arachidonate Pathway Cyclic AMP (cAMP) Pathway Platelet Plug Checkpoint 31.6 Platelets and Secondary Hemostasis Physiologic Controls of Platelet Activation and Aggregation Summary Review Questions Level I Level II References Chapter 32 Secondary Hemostasis and Fibrinolysis Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction The Coagulation Mechanism Checkpoint 32.1 Procoagulant Factors Properties of the Blood Coagulation Factors Prothrombin Group Fibrinogen Group Contact Group Mechanism of Action Cofactors Substrate Enzymes Vitamin K–Dependent Coagulation Proteins Function of Vitamin K Acarboxy Proteins Checkpoint 32.2 Structure of the Blood Coagulation Proteins Catalytic Domain Non-catalytic Domains Checkpoint 32.3 Coagulation Cascade Complex Formation on Phospholipid Surfaces The Intrinsic Pathway Contact Factors Factor XII (FXII) Prekallikrein (PK) High-Molecular-Weight Kininogen (HK) Factor XI (FXI) Other Factors in the Intrinsic Pathway Factor IX (FIX) Factor VIII (FVIII) von Willebrand Factor (VWF) Checkpoint 32.4 The Extrinsic Pathway Tissue Factor (TF) Factor VII (FVII) Checkpoint 32.5 The Common Pathway Factor X Activation Thrombin Generation Factor X (FX) Factor V (FV) Prothrombin (FII) Roles of Thrombin Formation of Fibrin Fibrinogen Release of Fibrinopeptides (FP) A and B Assembly of Fibrin Polymers Fibrin Stabilization Factor XIII (FXIII) Checkpoint 32.6 Fibrinolytic System Components of the Fibrinolytic System Checkpoint 32.7 Plasminogen (PLG) and Plasmin (PLN) Activators of Fibrinolysis Contact Pathway Plasminogen Activators Physiologic Plasminogen (PLG) Activators Tissue-Type Plasminogen Activator (tPA) Urinary-Type Plasminogen Activator (uPA) Exogenous Activators Fibrin Degradation Fibrinogen Degradation Products (FDPS) Fibrin Degradation Products (FDPS) Systemic Effects of Plasmin Checkpoint 32.8 Inhibitors of Fibrinolysis Plasminogen Activator Inhibitors (PAIS) Plasminogen Activator Inhibitor-1 (PAI-1) Plasminogen Activator Inhibitor-2 (PAI-2) Activated Protein C Inhibitor (PAI-3) Lipoprotein Receptor-Related Protein (LRP) Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) α2-Antiplasmin (AP) α2-Macroglobulin (α2-M) Control of Hemostasis Blood Flow Liver Clearance Positive Feedback Amplification Negative Feedback Inhibition Biochemical Inhibitors Antithrombin (AT) Heparin Cofactor II (HCII) Protein C (PC) and Protein S (PS) Thrombomodulin Endothelial Protein C Receptor (EPCR) Tissue Factor Pathway Inhibitor (TFPI) Protease Nexin-1 (PN1) α2-Macroglobulin α1-Antitrypsin (α1-Protease Inhibitor [α1-PI]) C1-Esterase Inhibitor (C1-INH) Protein Z (PZ) and Protein Z–Dependent Protease Inhibitor (ZPI) Checkpoint 32.9 Physiologic Hemostasis The Tissue Factor Pathway Initiation Propagation Termination Basal Coagulation Hemostasis in the Newborn Summary Review Questions Level I Level II References Chapter 33 Disorders of Primary Hemostasis Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Diagnosis of Bleeding Disorders Clinical Manifestations of Primary Hemostasis Bleeding Disorders Clinical Manifestations of Secondary Hemostasis Bleeding Disorders Nonspecific Bleeding Evaluation of a Patient with Abnormal Bleeding Laboratory Evaluation of Abnormal Bleeding Checkpoint 33.1 Hereditary Vascular System Disorders Acquired Vascular System Disorders Purpura Resulting from Decreased Connective Tissue Senile Purpura Cushing Syndrome and Glucocorticoid Therapy Scurvy Purpura Associated with Dysproteinemias Paraproteins Amyloidosis Purpura Resulting from Vasculitis Miscellaneous Causes of Purpura Mechanical Purpura Artificially Induced Purpura Easy Bruising Syndrome Purpura Fulminans Checkpoint 33.2 Quantitative Platelet Disorders Thrombocytopenia Increased Destruction Immune-Mediated Destruction Autoimmune Thrombocytopenia ITP in Childhood ITP in Adults Alloimmune Thrombocytopenias Post-Transfusion Purpura Drug-Induced Thrombocytopenia Miscellaneous Thrombocytopenias Checkpoint 33.3 Nonimmune Destruction Decreased Production Megakaryocyte Hypoplasia Syndromes Decreased Megakaryocyte Proliferation Aplastic Anemia Replacement of Normal Marrow Ineffective Thrombopoiesis Hereditary Thrombocytopenia Checkpoint 33.4 Abnormal Distribution of Platelets Increased Splenic Sequestration Dilutional Thrombocytopenia Hypothermia Conditions with Multiple Mechanisms of Thrombocytopenia Thrombocytosis Primary Thrombocytosis Secondary (Reactive) Thrombocytosis and Transient Thrombocytosis Checkpoint 33.5 Artifacts in the Quantitative Measurement of Platelets Qualitative (Functional) Platelet Disorders Hereditary Disorders of Platelet Function Disorders of Platelet Adhesion Bernard-Soulier Syndrome Von Willebrand Disease Defects of Collagen Receptors Disorders of Platelet Aggregation Disorders of Platelet Secretion, Granule Abnormalities, and Signal Transduction Deficiences of Dense Granules (δ-StoragePool Disease/δSPD) Gray Platelet Syndrome (GPS) Quebec Platelet Disorder Abnormalities of the Platelet Secretory Mechanism Defective Thromboxane A2(TXA2) Synthesis Signal Transduction Defects Disorders of Platelet Procoagulant Activity Checkpoint 33.6 Acquired Disorders of Platelet Function Chronic Renal Failure Hematologic Disorders Drugs Aspirin Checkpoint 33.7 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Alcohol Antibiotics Cardiopulmonary Bypass Surgery Summary Review Questions Level I Level II References Chapter 34 Disorders of Secondary Hemostasis Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Bleeding Characteristics Laboratory Evaluation Hereditary Disorders of Secondary Hemostasis Autosomal Dominant Inheritance – von Willebrand Disease von Willebrand Factor Inheritance Characteristics of VWD Classification Clinical Presentation Laboratory Evaluation of VWD Screening Tests Diagnostic Tests Specialized Diagnostic Testing Checkpoint 34.1 Related Clinical Syndromes Prenatal Diagnosis Therapy for VWD Checkpoint 34.2 X-Linked Recessive Disorders Historical Background Inheritance Characteristics Factor VIII Mutations Factor IX Mutations Pathophysiology of Bleeding in the Hemophilias Checkpoint 34.3 Clinical Presentation Severe Hemophilia Moderate and Mild Hemophilia Laboratory Evaluation of the Hemophilias Checkpoint 34.4 Carrier Detection and Prenatal Diagnosis Therapy for Hemophilia Factor Replacement Therapy Gene Therapy Inhibitors Autosomal Recessive Disorders Coagulation Factor Disorders with Bleeding Symptoms Fibrinogen (Factor I) Deficiency Hypofibrinogenemia and Afibrinogenemia Dysfibrinogenemia Checkpoint 34.5 Prothrombin (Factor II) Deficiency Factor V (FV) Deficiency Factor VII (FVII) Deficiency Checkpoint 34.6 Factor X (FX) Deficiency Factor XI (FXI) Deficiency Factor XIII (FXIII) Deficiency Combined Factor V and Factor VIII Deficiency (F5F8D) Combined Deficiencies of Vitamin K-Dependent Coagulation Factors Checkpoint 34.7 Coagulation Factor Deficiencies without Clinical Bleeding Disorders of Fibrinolytic Protein Inhibitors with Bleeding Symptoms Acquired Disorders of Hemostasis Associated with Bleeding Disseminated Intravascular Coagulation Primary Fibrinogenolysis Liver Disease Vitamin K Deficiency Acquired Pathologic Inhibitors Inhibitors of Single Factors Clinical Presentation Laboratory Evaluation Therapy for Factors VIII and IX Inhibitors Lupus Anticoagulant Common Bleeding Disorders in the Neonate Summary Review Questions Level I Level II References Chapter 35 Thrombophilia Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Thrombus Formation Arterial Thrombi Mechanism of Formation Risk Factors Laboratory Evaluation Venous Thrombi Risk Factors Laboratory Evaluation Checkpoint 35.1 Microparticles in Arterial and Venous Thrombosis Thrombophilia Hereditary Thrombophilia Antithrombin (AT) Deficiency Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Protein C Deficiency Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Protein S Deficiency Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Checkpoint 35.2 Activated Protein C Resistance Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Prothrombin Gene Mutation G20210A Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Checkpoint 35.3 Other Potential Genetic Risk Factors Heparin Cofactor II Deficiency Tissue Factor Pathway Inhibitor Variant ABO Blood Group Hyperhomocysteinemia (HC) Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Fibrinogen Disorders Pathophysiology Clinical Presentation Laboratory Evaluation Elevated Factor VIII and VWF Elevated Levels of Other Coagulation Factors Factor XII and Thromboembolic Disease Fibrinolytic System Disorders Plasminogen Deficiency Tissue Plasminogen Activator (tPA) and Plasminogen Activator Inhibitor (PAI) Checkpoint 35.4 Acquired Thrombohemorrhagic Conditions Acquired Fibrinolytic Defects Antiphospholipid (aPL) Antibodies/Antiphospholipid Syndrome (APS) Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Heparin-Induced Thrombocytopenia (HIT) Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Checkpoint 35.5 Thrombotic Microangiopathies (TMA) Thrombotic Thrombocytopenic Purpura (TTP) Pathophysiology Clinical Presentation and Treatment Laboratory Evaluation Hemolytic Uremic Syndrome Pathophysiology Clinical Presentation Therapy Disseminated Intravascular Coagulation (DIC) Incidence Etiology Pathophysiology Clinical Presentation Laboratory Evaluation Therapy Checkpoint 35.6 Malignancy Pregnancy and Oral Contraceptives (OCs) Postoperative State and Trauma Hematologic Disorders Laboratory Testing in Patients with Suspected Thrombosis Checkpoint 35.7 Anticoagulant Therapy Heparin Mechanism of Action Dosage Considerations Laboratory Monitoring Complications Oral Anticoagulants Mechanism of Action Dosage Considerations Laboratory Monitoring Complications New Oral Anticoagulants (NOAC)/Direct Oral Anticoagulants (DOAC) Thrombolytic Therapy Mechanism of Action Therapeutic Agents Laboratory Monitoring Complications Antiplatelet Therapy Aspirin Other NSAIDS ADP Receptor Antagonists Dipyridamole Intravenous Antiplatelet Agents Checkpoint 35.8 Summary Review Questions Level I Level II References Chapter 36 Hemostasis: Laboratory Testing and Instrumentation Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Specimen Collection and Processing Specimen Collection Specimen Processing Platelet-Poor Plasma (PPP) Platelet-Rich Plasma (PRP) Citrated Whole Blood Checkpoint 36.1 Laboratory Investigation of Primary Hemostasis Bleeding Time Platelet Function Analyzers PFA-100®, 200® (Siemens Healthcare, Inc.) VerifyNow Accumetrics Assay System (Accriva Diagnostics) Platelet Aggregometry Platelet-Rich Plasma Light Transmission Aggregometry Whole Blood (WB) Aggregation Multiplate® Platelet Function Analyzer Additional Tests Evaluating Platelets Flow Cytometry Clot Retraction Checkpoint 36.2 Laboratory Investigation of Secondary Hemostasis Screening Tests Prothrombin Time (PT) Activated Partial Thromboplastin Time (APTT) Checkpoint 36.3 Thrombin Time (TT) Quantitative Fibrinogen Assay Tests to Identify a Specific Factor Deficiency Mixing Studies Checkpoint 36.4 Specific Coagulation Factors Checkpoint 36.5 Reptilase Time (RT) Prekallikrein (Screening Test) Factor XIII Laboratory Tests for von Willebrand Factor (VWF) VWF Activity by Ristocetin Cofactor (VWF:RCo) Assay VWF Activity Using Ristocetin Independent Methods VWF Antigen Assay (VWF:Ag) VWF Multimer Analysis Collagen-Binding Assays for VWD A Disintegrin and Metalloprotease with a Thrombospondin type 1 motif, member 13 (ADAMTS-13) Identification of Inhibitors Lupus Anticoagulants/Antiphospholipid Antibodies Dilute Russell Viper Venom Time (dRVVT) Test Hexagonal Phospholipids Specific Factor Inhibitor Assay (Nijmegen-Bethesda Assay) Checkpoint 36.6 Laboratory Investigation of the Fibrinolytic System D-Dimer Fibrin Degradation Products Euglobulin Clot Lysis α2-Antiplasmin Activity Laboratory Investigation of Hemostasis (Primary, Secondary, or Fibrinolytic Pathway) Using Global Assays Thromboelastography (TEG) ROTEM® (TEM) Calibrated Automated Thrombogram (CAT) Laboratory Investigation of Hereditary and Acquired Thrombophilias (Hypercoagulable States) Antithrombin (AT) Protein C Protein S Activated Protein C Resistance (APCR) Prothrombin G20210A Checkpoint 36.7 Checkpoint 36.8 Additional Testing for Thrombosis Plasminogen Plasmin–Antiplasmin (PAP) Complex Plasminogen Activator Inhibitor (PAI-1) Tissue Plasminogen Activator (tPA) Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) Checkpoint 36.9 Molecular Markers of Hemostatic Activation Laboratory Evaluation: Assessment for Pharmaceutical Intervention of Hemostasis Oral Vitamin K Antagonist Therapy and the Prothrombin Time–INR Value Direct Oral Anticoagulants (DOACs) Non-Parenteral Anticoagulation Heparin Therapy Monitoring Activated Partial Thromboplastin Time Thrombin Time Anti-Xa Assay Checkpoint 36.10 Direct Thrombin Inhibitor (DTI) Therapy Monitoring Anticoagulant Reversal Therapeutic Alterations in Fibrinolytic Pathway Hemostasis Instrumentation Evolution of Hemostasis Testing Automated Hemostasis Analyzer Methodologies Electromechanical Clot Detection Systems Optical/Photometric/Turbidimetric Clot Detection Systems Chromogenic Detection Methods Immunologic Detection Methods Selecting a Hemostasis Analyzer Point-of-Care Hemostasis Instrumentation Summary Review Questions Level I Level II References Section Eight Hematology Procedures Chapter 37 Hematology Procedures Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Laboratory Testing Regulations Specimen Collection: Phlebotomy Anticoagulants Checkpoint 37.1 Equipment Specimen Collection Tubes Needles Tube Holders Syringe Tourniquet Lancets Other Equipment Venipuncture Capillary Puncture Phlebotomy Safety Checkpoint 37.2 Microscopy: The Microscope Bright-Field Microscopy Principles of the Compound Microscope Checkpoint 37.3 Lens Aberrations Infinity Optical System Phase-Contrast Microscopy Koehler Illumination Preventative Maintenance Checkpoint 37.4 Peripheral Blood Smear Preparation Manual Method Automated Method Checkpoint 37.5 Peripheral Blood Smear Staining Checkpoint 37.6 Checkpoint 37.7 Peripheral Blood Smear Examination Checkpoint 37.8 Cell Enumeration by Hemacytometer Manual Leukocyte Count Manual Erythrocyte Count Manual Platelet Count Checkpoint 37.9 Hemoglobin Concentration Hematocrit Erythrocyte Indices Checkpoint 37.10 Erythrocyte Sedimentation Rate (ESR) Reticulocyte Count Checkpoint 37.11 Solubility Test for Hemoglobin S Hemoglobin Electrophoresis Checkpoint 37.12 Quantitation of Hemoglobin A2 Acid Elution for Hemoglobin F Quantitation of Hemoglobin F Alkali Denaturation Other Methods Checkpoint 37.13 Heat Denaturation Test for Unstable Hemoglobin Heinz Body Stain Osmotic Fragility Test Checkpoint 37.14 Donath-Landsteiner Test for Paroxysmal Cold Hemoglobinuria (PCH) Erythropoietin Soluble Transferrin Receptor Checkpoint 37.15 Cytochemical Stains Myeloperoxidase Sudan Black B Chloroacetate Esterase α-Naphthyl Esterase (Nonspecific Esterase) Periodic Acid-Schiff Leukocyte Alkaline Phosphatase Checkpoint 37.16 Acid Phosphatase and Tartrate-Resistant Acid Phosphatase (TRAP) Checkpoint 37.17 Terminal Deoxynucleotidyl Transferase Checkpoint 37.18 Toluidine Blue Reticulin Stain and Masson’s Trichrome Stain Summary Review Questions Level I Level II References Chapter 38 Bone Marrow Examination Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Indications for Bone Marrow Evaluation Bone Marrow Procedure Checkpoint 38.1 Bone Marrow Processing for Examination Bone Marrow Aspirate Bone Marrow Core Biopsy Morphologic Interpretation of Bone Marrow Bone Marrow Aspirate Bone Marrow Differential Count Myeloid to Erythroid Ratio Checkpoint 38.2 Bone Marrow Touch Imprints Bone Marrow Clot and Particle Preparation, Sections, and Core Biopsy Bone Marrow Cellularity Benign Lymphoid Aggregates versus Malignant Lymphoma Bone Marrow Iron Stores Prussian Blue Stain for Iron Use of Bone Marrow Iron Evaluation Checkpoint 38.3 Special Studies on Bone Marrow Flow Cytometry Cytogenetics Molecular Genetics Cytochemical Stains Bone Marrow Report Summary Review Questions Level I Level II References Chapter 39 Automation in Hematology Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Automated Blood Cell–Counting Instruments Checkpoint 39.1 Impedance Instruments Coulter® LH Series Checkpoint 39.2 Checkpoint 39.3 Beckman-Coulter Unicel® DxH 800 Checkpoint 39.4 Sysmex XE-Series™ Checkpoint 39.5 Sysmex XN-Series™ Checkpoint 39.6 Abbott CELL-DYN Sapphire® Checkpoint 39.7 The Immuno T-cell (CD3/4/8) The ImmunoTM (CD61) Light-Scattering Instruments Siemens Healthcare ADVIA 120 Checkpoint 39.8 Siemens Healthcare ADVIA 2120 Automated Digital Cell Morphology Instrument CellaVision® DM96 System Summary Review Questions Level I Level II References Chapter 40 Flow Cytometry Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Principles of Flow Cytometry Isolation of Single Particles Light Scattering Checkpoint 40.1 Detection of Fluorochromes Data Analysis Checkpoint 40.2 Immunophenotyping by Flow Cytometry Checkpoint 40.3 Specimen Requirements and Preparation for Immunophenotyping Isolation of Cells by Gating Checkpoint 40.4 Fluorescence Activated Cell Sorting (FACS) Diagnosis and Classification of Mature Lymphoid Neoplasms Diagnosis and Classification of Acute Leukemia Acute Lymphoblastic Leukemia/Lymphoma Checkpoint 40.5 Acute Myeloid Leukemia Acute Leukemia of Ambiguous Lineage Diagnosis of Myelodysplastic Syndrome (MDS) Detection of Minimal Residual Disease (MRD) by Flow Cytometry Diagnosis and Surveillance of Immunodeficiency Disorders Diagnosis and Surveillance of HIV Checkpoint 40.6 Findings in Primary Immunodeficiency Disorders Flow Cytometry in Systemic Autoimmune Disease CD34 Enumeration Paroxysmal Nocturnal Hemoglobinuria (PNH) Hereditary Spherocytosis (HS) DNA Analysis Proliferation Ploidy Clinical Applications of DNA Analysis Summary Review Questions Level I Level II References Chapter 41 Chromosome Analysis of Hematopoietic and Lymphoid Disorders Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I Level II Overview Introduction Chromosome Structure and Morphology Mitosis Cytogenetic Procedures Specimen Preparation Harvest Procedure and Banding Chromosome Analysis Checkpoint 41.1 Chromosome Abnormalities Numerical Aberrations Structural Aberrations Polymorphic Variation Cytogenetic Nomenclature Cytogenetic Analysis of Hematopoietic and Lymphoid Disorders Checkpoint 41.2 Processing Specimens Chronic Myelogenous Leukemia Myeloproliferative Neoplasms Other Than CML Acute Myeloid Leukemia Checkpoint 41.3 Myelodysplastic Syndromes Checkpoint 41.4 Acute Lymphoblastic Leukemia/Lymphoma Checkpoint 41.5 Lymphoma and Lymphoproliferative Disorders Bone Marrow Transplantation Molecular Cytogenetics Summary Review Questions Level I Level II References Chapter 42 Molecular Analysis of Hematologic Diseases Objectives—Level II Chapter Outline Key Terms Background Basics Level II Overview Introduction Checkpoint 42.1 Overview of Molecular Technologies Nucleic Acid Extraction Nucleic Acid Amplification Polymerase Chain Reaction Real-Time Polymerase Chain Reaction (qPCR) Reverse Transcriptase PCR (RT-PCR) Multiplex PCR Other Amplification Techniques Hybridization Techniques Fluorescent in Situ Hybridization (FISH) Southern Blot Allele-Specific Oligonucleotides (ASO) Microarray Technology Bead Array Technology Direct DNA Sequence Analysis Chain Termination Sequencing Next-Generation Sequencing Clinical Applications of Molecular Diagnostics in Hematopathology Checkpoint 42.2 Erythrocyte Disorders Fanconi Anemia (FA) Hemochromatosis Hereditary Persistence of Fetal Hemoglobin (HPFH) Thalassemia Hemoglobinopathies Polycythemia Vera Leukocyte Disorders Myeloproliferative Neoplasms (MPNs) BCR/ABL1 (22q11.23/9q34.1) CALR (19p13.2) JAK2 (9p24) MPL (1p34) Myelodysplastic Syndrome (MDS) Acute Myeloid Leukemia (AML) ASXL1 (20q11) CEBPα (19q13.1) KIT (4q12) DNMT3A (2p23) FLT3 (13q12) IDH1/IDH2 (2q33.3/15q26.1) MLL (11q23) NPM1 (5q35.1) KRAS, NRAS (12p12.1, 1p13.2) RUNX1/RUNX1T1 (21q22.3/8q22) TET2 (4q24) TP53 (4q24) Acute Lymphoblastic Leukemia (ALL) BCR/ABL1 (22q11.23/9q34.1) ETV6/RUNX1 (12p13/21q22.3) MLL (11q23) PAX5 (9p13) IKZF1 (7p12.2) EBF1 (5q33.3) Chronic Lymphocytic Leukemia (CLL) del (13q14) TP53 (17p13.1) NOTCH1 (9q34.3) ATM (11q22–q23) SF3B1 (2q33.1) Lymphoma IGH/BCL2 CCND1/IGH MYC/IGH Checkpoint 42.3 Infectious Diseases Clinical Applications of Molecular Diagnostics in Hemostasis CYP2C9 VKORC1 Factor V Leiden (FVL) Prothrombin G20210A Hemophilia A Hemophilia B Methylenetetrahydrofolate Reductase (MTHFR) von Willebrand Disease (VWD) Checkpoint 42.4 Summary Review Questions Level II References Section Nine Quality Assessment Chapter 43 Quality Assessment in the Hematology Laboratory Objectives—Level I Objectives—Level II Chapter Outline Key Terms Background Basics Level I and Level II Overview Test Coding and Reimbursement Quality Assessment Basic Components Pre-Examination Component Examination Component Post-Examination Component Checkpoint 43.1 Healthcare Quality Improvement Safe Effective Efficient Timely Patient-Centered Equity Checkpoint 43.2 Proficiency Testing Checkpoint 43.3 Competency Testing Checkpoint 43.4 Method Evaluation/Instrument Comparison Selection Analytical Reliability Checkpoint 43.5 Linearity and Reportable Range Determinations Reference Interval Determination Checkpoint 43.6 Laboratory Safety Universal Precautions Occupational Health and Safety Administration (OSHA) Standards Safety Data Sheets Checkpoint 43.7 Quality Control Control Materials Establishing Quality Control (QC) Limits Checkpoint 43.8 Interpreting Quality Control Charts Westgard Rules Evaluation of Quality Control Charts Using the Westgard Multirule Approach Checkpoint 43.9 Bull’s Testing Algorithm (Moving Averages) Monitoring Quality Control with Patient Specimens Individual Quality Control Plan Checkpoint 43.10 Review of Patient Results Hematology Detection of Abnormal Test Results Checkpoint 43.11 Use of Delta Checks Correction for Interfering Substances Hemostasis Overanticoagulation/Under-anticoagulation Checkpoint 43.12 Interfering Substances Use of Delta Checks Summary Review Questions Level I Level II References Appendices Appendix A Appendix B Hematopoietic and Lymphoid Neoplasms: Immunophenotypic and Genetic Features Appendix C 2017 WHO Classification of Hematologic, Lymphopoietic, Histiocytic/Dendritic Neoplasms Appendix D Hematology Procedures Procedure 37-1 Koehler Illumination Procedure 37-2 Peripheral Blood Smear Preparation Procedure 37-3 Peripheral Blood Smear Staining Procedure 37-4 Peripheral Blood Smear Examination Principle Sample Reagents and Equipment Quality Control Procedure Reference Interval Comments Procedure 37-5 Manual Leukocyte Count Principle Reagents and Equipment Quality Control Sample Procedure Calculations Comments Procedure 37-6 Manual Platelet Count Principle Reagents and Equipment Quality Control Sample Procedure Calculations Reference Intervals Comments Procedure 37-7 Hemoglobin Concentration Determination Principle Reagents and Equipment Quality Control Sample Procedure Interpretation of Results Reference Intervals Comments Procedure 37-8 Microhematocrit Determination Principle Reagents and Equipment Quality Control Sample Procedure Reference Intervals Comments Procedure 37-9 Erythrocyte Sedimentation Rate Principle Reagents and Equipment Quality Control Sample Procedure Reference Interval Comments Procedure 37-10 Reticulocyte Count Principle Reagents and Equipment Quality Control Sample Procedure Calculations Example: Example: Reference Interval Comments Procedure 37-11 Solubility Test for Hemoglobin S Principle Reagents and Equipment Quality Control Sample Procedure Results Comments Procedure 37-12 Osmotic Fragility Test Principle Reagents and Equipment Quality Control Sample Procedure Preparation of the NaCl Solutions for Osmotic Fragility Test Calculations Construction of Erythrocyte Fragility Graph Reference Interval Comments Appendix E Answers to Review Questions Chapter 1 Chapter 2 Level I Level II Chapter 3 Level I Level II Chapter 4 Level I Level II Chapter 5 Level I Level II Chapter 6 Level I Level II Chapter 7 Level I Level II Chapter 8 Level I Level II Chapter 9 Level I Level II Chapter 10 Level I Level II Chapter 11 Level I Level II Chapter 12 Level I Level II Chapter 13 Level I Level II Chapter 14 Level I Level II Chapter 15 Level I Level II Chapter 16 Level I Level II Chapter 17 Level I Level II Chapter 18 Level I Level II Chapter 19 Level I Level II Chapter 20 Level I Level II Chapter 21 Level I Level II Chapter 22 Level I Level II Chapter 23 Level I Level II Chapter 24 Level I Level II Chapter 25 Level I Level II Chapter 26 Level I Level II Chapter 27 Level I Level II Chapter 28 Level I Level II Chapter 29 Level I Level II Chapter 30 Level I Level II Chapter 31 Level I Level II Chapter 32 Level I Level II Chapter 33 Level I Level II Chapter 34 Level I Level II Chapter 35 Level I Level II Chapter 36 Level I Level II Chapter 37 Level I Level II Chapter 38 Level I Level II Chapter 39 Level I Level II Chapter 40 Level I Level II Chapter 41 Level I Level II Chapter 42 Level II Chapter 43 Level I Level II Appendix F Answers to Checkpoints Chapter 1 Checkpoint 1-1 Answer Checkpoint 1-2 Answer Chapter 2 Checkpoint 2-1 Answer Checkpoint 2-2 Answer Checkpoint 2-3 Answer Checkpoint 2-4 Answer Checkpoint 2-5 Answer Chapter 3 Checkpoint 3-1 Answer Checkpoint 3-2 Answer Checkpoint 3-3 Answer Checkpoint 3-4 Answer Chapter 4 Checkpoint 4-1 Answer Checkpoint 4-2 Answer Checkpoint 4-3 Answer Checkpoint 4-4 Answer Chapter 5 Checkpoint 5-1 Answer Checkpoint 5-2 Answer Checkpoint 5-3 Answer Checkpoint 5-4 Answer Checkpoint 5-5 Answer Checkpoint 5-6 Answer Checkpoint 5-7 Answer Checkpoint 5-8 Answer Checkpoint 5-9 Answer Checkpoint 5-10 Answer Chapter 6 Checkpoint 6-1 Answer Checkpoint 6-2 Answer Checkpoint 6-3 Answer Checkpoint 6-4 Answer Checkpoint 6-5 Answer Checkpoint 6-6 Answer Checkpoint 6-7 Answer Chapter 7 Checkpoint 7-1 Answer Checkpoint 7-2 Answer Checkpoint 7-3 Answer Checkpoint 7-4 Answer Checkpoint 7-5 Answer Checkpoint 7-6 Answer Chapter 8 Checkpoint 8-1 Answer Checkpoint 8-2 Answer Checkpoint 8-3 Answer Checkpoint 8-4 Answer Checkpoint 8-5 Answer Checkpoint 8-6 Answer Checkpoint 8-7 Answer Checkpoint 8-8 Answer Chapter 9 Checkpoint 9-1 Answer Checkpoint 9-2 Answer Checkpoint 9-3 Answer Checkpoint 9-4 Answer Chapter 10 Checkpoint 10-1 Answer Checkpoint 10-2 Answer Checkpoint 10-3 Answer Checkpoint 10-4 Answer Checkpoint 10-5 Answer Checkpoint 10-6 Answer Checkpoint 10-7 Answer Checkpoint 10-8 Answer Checkpoint 10-9 Answer Chapter 11 Checkpoint 11-1 Answer Checkpoint 11-2 Answer Checkpoint 11-3 Answer Checkpoint 11-4 Answer Chapter 12 Checkpoint 12-1 Answer Checkpoint 12-2 Answer Checkpoint 12-3 Answer Checkpoint 12-4 Answer Checkpoint 12-5 Answer Chapter 13 Checkpoint 13-1 Answer Checkpoint 13-2 Answer Checkpoint 13-3 Answer Checkpoint 13-4 Answer Checkpoint 13-5 Answer Checkpoint 13-6 Answer Checkpoint 13-7 Answer Checkpoint 13-8 Answer Checkpoint 13-9 Answer Checkpoint 13-10 Answer Checkpoint 13-11 Answer Chapter 14 Checkpoint 14-1 Answer Checkpoint 14-2 Answer Checkpoint 14-3 Answer Checkpoint 14-4 Answer Checkpoint 14-5 Answer Checkpoint 14-6 Answer Checkpoint 14-7 Answer Checkpoint 14-8 Answer Checkpoint 14-9 Answer Checkpoint 14-10 Answer Chapter 15 Checkpoint 15-1 Answer Checkpoint 15-2 Answer Checkpoint 15-3 Answer Checkpoint 15-4 Answer Checkpoint 15-5 Answer Checkpoint 15-6 Answer Checkpoint 15-7 Answer Checkpoint 15-8 Answer Checkpoint 15-9 Answer Checkpoint 15-10 Answer Checkpoint 15-11 Answer Checkpoint 15-12 Answer Checkpoint 15-13 Answer Checkpoint 15-14 Answer Chapter 16 Checkpoint 16-1 Answer Checkpoint 16-2 Answer Chapter 17 Checkpoint 17-1 Answer Checkpoint 17-2 Answer Checkpoint 17-3 Answer Checkpoint 17-4 Answer Checkpoint 17-5 Answer Checkpoint 17-6 Answer Checkpoint 17-7 Answer Checkpoint 17-8 Answer Chapter 18 Checkpoint 18-1 Answer Checkpoint 18-2 Answer Checkpoint 18-3 Answer Checkpoint 18-4 Answer Chapter 19 Checkpoint 19-1 Answer Checkpoint 19-2 Answer Checkpoint 19-3 Answer Checkpoint 19-4 Answer Checkpoint 19-5 Answer Checkpoint 19-6 Answer Checkpoint 19-7 Answer Checkpoint 19-8 Answer Checkpoint 19-9 Answer Checkpoint 19-10 Answer Checkpoint 19-11 Answer Checkpoint 19-12 Answer Checkpoint 19-13 Answer Checkpoint 19-14 Answer Checkpoint 19-15 Answer Chapter 20 Checkpoint 20-1 Answer Checkpoint 20-2 Answer Checkpoint 20-3 Answer Checkpoint 20-4 Answer Checkpoint 20-5 Answer Checkpoint 20-6 Answer Checkpoint 20-7 Answer Chapter 21 Checkpoint 21-1 Answer Checkpoint 21-2 Answer Checkpoint 21-3 Answer Checkpoint 21-4 Answer Checkpoint 21-5 Answer Checkpoint 21-6 Answer Checkpoint 21-7 Answer Chapter 22 Checkpoint 22-1 Answer Checkpoint 22-2 Answer Checkpoint 22-3 Answer Checkpoint 22-4 Answer Checkpoint 22-5 Answer Chapter 23 Checkpoint 23-1 Answer Checkpoint 23-2 Answer Checkpoint 23-3 Answer Checkpoint 23-4 Answer Checkpoint 23-5 Answer Checkpoint 23-6 Answer Checkpoint 23-7 Answer Chapter 24 Checkpoint 24-1 Answer Checkpoint 24-2 Answer Checkpoint 24-3 Answer Checkpoint 24-4 Answer Checkpoint 24-5 Answer Checkpoint 24-6 Answer Checkpoint 24-7 Answer Checkpoint 24-8 Answer Checkpoint 24-9 Answer Checkpoint 24-10 Answer Chapter 25 Checkpoint 25-1 Answer Checkpoint 25-2 Answer Checkpoint 25-3 Answer Checkpoint 25-4 Answer Checkpoint 25-5 Answer Checkpoint 25-6 Answer Checkpoint 25-7 Answer Chapter 26 Checkpoint 26-1 Answer Checkpoint 26-2 Answer Checkpoint 26-3 Answer Checkpoint 26-4 Answer Checkpoint 26-5 Answer Checkpoint 26-6 Answer Checkpoint 26-7 Answer Checkpoint 26-8 Answer Checkpoint 26-9 Answer Chapter 27 Checkpoint 27-1 Answer Checkpoint 27-2 Answer Checkpoint 27-3 Answer Checkpoint 27-4 Answer Checkpoint 27-5 Answer Checkpoint 27-6 Answer Chapter 28 Checkpoint 28-1 Answer Checkpoint 28-2 Answer Checkpoint 28-3 Answer Checkpoint 28-4 Answer Checkpoint 28-5 Answer Chapter 29 Checkpoint 29-1 Answer Checkpoint 29-2 Answer Checkpoint 29-3 Answer Checkpoint 29-4 Answer Checkpoint 29-5 Answer Chapter 30 Checkpoint 30-1 Answer Checkpoint 30-2 Answer Checkpoint 30-3 Answer Checkpoint 30-4 Answer Checkpoint 30-5 Answer Chapter 31 Checkpoint 31-1 Answer Checkpoint 31-2 Answer Checkpoint 31-3 Answer Checkpoint 31-4 Answer Checkpoint 31-5 Answer Checkpoint 31-6 Answer Chapter 32 Checkpoint 32-1 Answer Checkpoint 32-2 Answer Checkpoint 32-3 Answer Checkpoint 32-4 Answer Checkpoint 32-5 Answer Checkpoint 32-6 Answer Checkpoint 32-7 Answer Checkpoint 32-8 Answer Checkpoint 32-9 Answer Chapter 33 Checkpoint 33-1 Answer Checkpoint 33-2 Answer Checkpoint 33-3 Answer Checkpoint 33-4 Answer Checkpoint 33-5 Answer Checkpoint 33-6 Answer Checkpoint 33-7 Answer Chapter 34 Checkpoint 34-1 Answer Checkpoint 34-2 Answer Checkpoint 34-3 Answer Checkpoint 34-4 Answer Checkpoint 34-5 Answer Checkpoint 34-6 Answer Checkpoint 34-7 Answer Chapter 35 Checkpoint 35-1 Answer Checkpoint 35-2 Answer Checkpoint 35-3 Answer Checkpoint 35-4 Answer Checkpoint 35-5 Answer Checkpoint 35-6 Answer Checkpoint 35-7 Answer Checkpoint 35-8 Answer Chapter 36 Checkpoint 36-1 Answer Checkpoint 36-2 Answer Checkpoint 36-3 Answer Checkpoint 36-4 Answer Checkpoint 36-5 Answer Checkpoint 36-6 Answer Checkpoint 36-7 Answer Checkpoint 36-8 Answer Checkpoint 36-9 Answer Checkpoint 36-10 Answer Chapter 37 Checkpoint 37-1 Answer Checkpoint 37-2 Answer Checkpoint 37-3 Answer Checkpoint 37-4 Answer Checkpoint 37-5 Answer Checkpoint 37-6 Answer Checkpoint 37-7 Answer Checkpoint 37-8 Answer Checkpoint 37-9 Answer Checkpoint 37-10 Answer Checkpoint 37-11 Answer Checkpoint 37-12 Answer Checkpoint 37-13 Answer Checkpoint 37-14 Answer Checkpoint 37-15 Answer Checkpoint 37-16 Answer Checkpoint 37-17 Answer Checkpoint 37-18 Answer Chapter 38 Checkpoint 38-1 Answer Checkpoint 38-2 Answer Checkpoint 38-3 Answer Chapter 39 Checkpoint 39-1 Answer Checkpoint 39-2 Answer Checkpoint 39-3 Answer Checkpoint 39-4 Answer Checkpoint 39-5 Answer Checkpoint 39-6 Answer Checkpoint 39-7 Answer Checkpoint 39-8 Answer Chapter 40 Checkpoint 40-1 Answer Checkpoint 40-2 Answer Checkpoint 40-3 Answer Checkpoint 40-4 Answer Checkpoint 40-5 Answer Checkpoint 40-6 Answer Chapter 41 Checkpoint 41-1 Answer Checkpoint 41-2 Answer Checkpoint 41-3 Answer Checkpoint 41-4 Answer Checkpoint 41-5 Answer Chapter 42 Checkpoint 42-1 Answer Checkpoint 42-2 Answer Checkpoint 42-3 Answer Checkpoint 42-4 Answer Chapter 43 Checkpoint 43-1 Answer Checkpoint 43-2 Answer Checkpoint 43-3 Answer Checkpoint 43-4 Answer Checkpoint 43-5 Answer Checkpoint 43-6 Answer Checkpoint 43-7 Answer Checkpoint 43-8 Answer Checkpoint 43-9 Answer Checkpoint 43-10 Answer Checkpoint 43-11 Answer Checkpoint 43-12 Answer Appendix G Answers to Case Study Questions Chapter 1 Question Explanation Question Explanation Chapter 3 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 5 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 6 Question Explanation Question Explanation Question Explanation Question Explanation Chapter 7 Question Explanation Question Explanation Question Explanation Question Explanation Chapter 8 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 9 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 10 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 11 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 12 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 13 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 14 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 15 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 16 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 17 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 18 Question Explanation Question Explanation Question Explanation Chapter 19 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 20 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 21 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 22 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 23 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 24 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 25 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 26 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 27 Question Explanation Question Explanation Question Explanation Question Explanation Chapter 28 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 29 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 30 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 31 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 32 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 33 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 34 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 35 Question Explanation Question Explanation Question Explanation Chapter 38 Question Explanation Question Explanation Question Explanation Chapter 40 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 41 Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Question Explanation Chapter 42 Question Explanation Question Explanation Glossary Index [Show More]

Last updated: 1 year ago

Preview 1 out of 600 pages