Clinical Hematology and Fundamentals of Hemostasis

Title Page
Copyright Page
Dedication
Acknowledgments
Preface
Special Collaborators
Contributors
Reviewers
Contents
Part 1: Introduction to Clinical Hematology
	Chapter 1: Morphology and Maturation of Human Blood Cells: Hematopoiesis
		Basic Morphology and Basic Concepts
		Morphology of Cells on the Normal Blood Smear
			Erythrocytes (Red Blood Cells)
			Platelets (Thrombocytes)
			Leukocytes (White Blood Cells)
		Hematopoiesis
			Description
			Origin of Hematopoiesis
		Erythropoiesis
			Pronormoblast (Rubriblast, Proerythroblast)
			Basophilic Normoblast (Prorubricyte, Basophilic Erythroblast)
			Polychromatophilic Normoblast (Rubricyte, Polychromatophilic Erythroblast)
			Orthochromatic Normoblast (Metarubricyte, Orthochromatic Erythroblast)
			Reticulocyte (Diffusely Basophilic Erythrocyte, Polychromatophilic Erythrocyte)
			Erythrocyte (Red Blood Cell, Discocyte)
		Myelopoiesis (Granulocytopoiesis)
			Morphological Changes
			Stages of Differentiation and Maturation
		Monopoiesis
			Monoblasts and Promonocytes
			Monocytes and Macrophages
		Lymphopoiesis
			Lymphoblasts and Prolymphocytes
			Lymphocytes
			Plasmablasts and Proplasmacytes
			Plasmacytes (Plasma Cells)
		Megakaryocytopoiesis
		Bone-Derived Cells
			Osteoblasts
			Osteoclasts
		Cell Line Ontogeny (Evolution)
			Multipotent Stem Cells—Colony-Forming Units (CFUs) (Hematopoietic Stem Cell)
		Trends in Therapeutic Manipulation of Hematopoiesis
			Recombinant Cytokines
			Clinical Trials of Recombinant Cytokines
			Clusters of Differentiation Nomenclature
			Clinical Applications of Cell Surface Markers
	Chapter 2: The Red Blood Cell: Structure and Function
		The Red Blood Cell Membrane
			Red Blood Cell Membrane Proteins
			Deformability
			Permeability
			Red Blood Cell Membrane Lipids
		Hemoglobin Structure and Function
			Hemoglobin Synthesis
			Hemoglobin Function
			Abnormal Hemoglobins of Clinical Importance
		Maintenance of Hemoglobin Function: Active Red Blood Cell Metabolic Pathways
		Erythrocyte Senescence and Hemolysis
			Extravascular Hemolysis
			Intravascular Hemolysis
	Chapter 3: Bone Marrow Structure and Function
		Bone Marrow Structure
			Erythropoiesis
			Granulopoiesis
			Megakaryopoiesis
			Lymphopoiesis
			Stem Cells
			Hematogones
			Marrow Stromal Cells
			Mast Cells
			Bone-Forming Cells
		Bone Marrow Function
		Indications for Bone Marrow Studies
		Obtaining and Preparing Bone Marrow for Hematologic Studies
			Equipment
			Aspiration
			Preparation of Bone Marrow Aspirate
			Histologic Marrow Particle Preparation
			Bone Marrow Core Biopsy
			Preparation of Trephine Biopsy
		Bone Marrow Examination
			Estimation of Bone Marrow Cellularity
			Bone Marrow Differential Count
			Bone Marrow and Peripheral Blood Interpretation Based on Cellularity and M:E Ratio Changes
			Bone Marrow Iron Stores
		Bone Marrow Report
	Chapter 4: Examination of the Peripheral Smear: Red Cell, White Cell, and Platelet Morphology
		Automation in the Hematology Laboratory
		Examination of the Peripheral Blood Smear
			Low-Power (10×) Scan
			High-Power (40×) Scan
			Oil Immersion (100×) Examination
		The Normal Red Blood Cell
		Assessment of Red Cell Abnormality
		Variations in Red Cell Distribution
			Normal Distribution
			Abnormal Distribution
		Variations in Red Cell Size
			Anisocytosis
			Normocytes
			Macrocytes
			Microcytes
		Hemoglobin Content—Red Cell Color Variations
			Normochromia
			Hypochromia
			Hyperchromia
			Polychromasia
		Variations in Red Cell Shape
			Poikilocytosis
			Target Cells (Codocytes)
			Spherocytes
			Stomatocytes
			Ovalocytes and Elliptocytes
			Sickle Cells (Drepanocytes)
			Fragmented Cells
			Burr Cells (Echinocytes)
			Acanthocytes (Thorn Cells, Spur Cells)
			Teardrop Cells (Dacrocytes)
		Red Cell Inclusions
			Howell–Jolly Bodies
			Basophilic Stippling
			Pappenheimer Bodies and Siderotic Granules
			Heinz Bodies
			Cabot Rings
			Hemoglobin C Crystals
			Hemoglobin SC Crystals
			Protozoan Inclusions
		Examination of Platelet Morphology
		Examination of White Blood Cell Morphology
			Immature White Blood Cells
			White Blood Cell Morphology
			WBC Cytoplasmic Inclusions
	Chapter 5: Quality Management in the Hematology Laboratory
		Quality Management
			Legal Implications
			Quality Management Plans
			Quality Approaches
			Quality System Essentials
		Quality Assurance and Quality Control
			Key Definitions
			General Quality Assurance Control Activity Guidelines
			Preanalytical, Analytical, and Postanalytical Factors in Testing
			Accuracy, Precision, and Error
			Method Validation
			CLIA Minimum Quality Control Requirements
			Levy–Jennings Graphs
			Westgard MultiRule Quality Control
			Peer Group Quality Control
		Hematology Laboratory Applications
			Quality Plan Example
			Method Validation Studies
			Quality Control
Part 2: Anemias
	Chapter 6: Anemia: Diagnosis and Clinical Considerations
		Causes, Considerations, and Compensatory Mechanisms
		Clinical Diagnosis of Anemia
		Classification of Anemia
		Laboratory Classification of Anemias
			Hemoglobin and Hematocrit Levels
			Morphological Classification of Anemias
			Other Laboratory Tests
		New RBC Parameters in Testing for Anemia
		Overview of the Treatment of Anemia
	Chapter 7: Iron Metabolism and Hypochromic Anemias
		Normal Iron Metabolism
			Distribution and Requirements
			Daily Iron Requirements
			Sources of Iron
			Iron Absorption and Transport
			Iron Regulation
			Iron Storage
		Laboratory Evaluation
			Serum Iron
			Total Iron-Binding Capacity
			Transferrin Saturation
			Ferritin
			Transferrin Receptor
			Free Erythrocyte Protoporphyrin and Zinc Protoporphyrin
			Bone Marrow Iron
			Reticulocyte Count and Reticulocyte Corpuscular Hemoglobin (CHr)
			Hepcidin
		Iron-Deficiency Anemia
			Etiology
			Pathophysiology
			Clinical Findings
			Laboratory Testing and Results
			Treatment
		Anemia of Chronic Inflammation
			Etiology
			Pathophysiology
			Clinical Findings
			Laboratory Testing and Results
			Treatment
		Sideroblastic Anemia
			Etiology
			Pathophysiology
			Clinical Findings
			Laboratory Testing and Results
			Treatment
		The Porphyrias
		Iron Overload and Hemochromatosis
			Etiology
			Pathophysiology
			Clinical Findings
			Laboratory Testing and Results
			Treatment
	Chapter 8: Megaloblastic Anemias and Other Macrocytic Anemias
		Etiology: Biochemical Aspects
		Clinical Manifestations
		Hematologic Features
			Ineffective Hematopoiesis
			Bone Marrow Morphology
			Peripheral Blood Morphology
		Etiology: B12 and Folic Acid Deficiency
			Vitamin B12 Deficiency
			Folic Acid Deficiency
		Laboratory Diagnosis of Megaloblastic Anemia
			Laboratory Tests for the Diagnosis of Vitamin B12 and Folic Acid Deficiencies
		Treatment
			Therapy for Vitamin B12 Deficiency
			Therapy for Folic Acid Deficiency
			Response to Therapy
		Macrocytic Nonmegaloblastic Anemias
		Vitamin-Independent Megaloblastic Changes
			Inherited
			Acquired
			Drug and Toxin Induced
	Chapter 9: Hemolytic Anemias: Intracorpuscular Defects: Hereditary Defects of the Red Cell Membrane
		Classification of Hemolytic Anemias
		Approach to Diagnosis of a Hemolytic State
			Tests Reflecting Increased Red Cell Destruction
			Tests Reflecting Increased Red Cell Production
			Establishing the Cause of Hemolysis
		Hereditary Defects of the Red Cell Membrane
			Red Cell Membrane Structure
			Classification of Hereditary Defects of the Red Cell Membrane
			Hereditary Spherocytosis
			Hereditary Elliptocytosis
		Disorders of Red Cell Hydration
			Hereditary Hydrocytosis and Hereditary Xerocytosis
	Chapter 10: Hemolytic Anemias: Intracorpuscular Defects: Hereditary Enzyme Deficiencies
		CHAPTER OUTLINE
		LEARNING OBJECTIVES
		Enzyme Deficiencies: Hexose Monophosphate Pathway
			Glucose-6-Phosphate Dehydrogenase Deficiency
				Mode of Inheritance
				TABLE 10-1 Distribution of Common G6PD Variants
				Pathogenesis
				FIGURE 10-1 Red cell metabolic pathways. The nucleated red cell dependsalmost exclusively on the breakdown of glucose for energy requirements. TheEmbden–Meyerhof (nonoxidative or anaerobic) pathway is responsible for most ofthe glucose utilization and generation of ATP. In addition, this pathway plays anessential role in maintaining pyridine nucleotides in a reduced state to supportmethemoglobin reduction (the methemoglobin reductase pathway) and 2,3-bisphosphoglycerate synthesis (the Luebering–Rapaport pathway). Thephosphogluconate pathway couples oxidative metabolism with pyridine nucleotideand glutathione reduction. It serves to protect red cells from environmentaloxidants.
				FIGURE 10-2 Reactions with erythrocytes to prevent accumulation of oxidants.
				BOX 10-1 Drugs and Chemicals Associated withHemolytic Anemia in G6PD Deficiency
		Enzyme Deficiencies: Glycolytic Pathway
			Pyruvate Kinase Deficiency (PKD)
			Other Enzyme Deficiencies of the Glycolytic Pathway
		Enzyme Deficiencies: Methemoglobin Reductase Pathway
			Methemoglobin Reductase Deficiency
			Methemoglobinemia
	Chapter 11: Hemolytic Anemias: Intracorpuscular Defects: The Hemoglobinopathies
		Review of Normal Hemoglobin Structure
		Overview of the Hemoglobinopathies
			Classification
			Nomenclature
			Laboratory Diagnosis
		Sickle Cell Anemia
			Historic Overview
			Definition
			Pathophysiology
			Clinical Findings
		Sickle Cell Trait
			Laboratory Testing and Results
		Laboratory Screening for Sickle Cell Disease
		Treatment
		Hemoglobin C Disease and Trait
		Hemoglobin D Disease and Trait
		Hemoglobin E Disease and Trait
		Hemoglobin OArab Disease and Trait
		Hemoglobin S With Other Abnormal Hemoglobins
			Hemoglobin SC Disease
			Hemoglobin SD Disease
			Hemoglobin SOArab and S-Oman Disease
			Hemoglobin S/β-Thalassemia Combination
			Laboratory Diagnosis of HbS With Other Abnormal Hemoglobins
		Unstable Hemoglobins
		Methemoglobinemia
	Chapter 12: Hemolytic Anemias: Intracorpuscular Defects: Thalassemia
		Genetics of Hemoglobin Synthesis
		Pathophysiology
		Thalassemia Syndromes
			A Broad Clinical Classification of Thalassemia Syndromes
			Beta Thalassemia
			Alpha Thalassemia
			Other Thalassemias and Thalassemia-Like Conditions
		Laboratory Diagnosis
			Routine Hematology Procedures
			Flow Cytometry
			Hemoglobin Electrophoresis
			High Performance Liquid Chromatography
			Hemoglobin Quantitation
			Routine Chemistry
			Differential Diagnosis of Microcytic, Hypochromic Anemia
		Treatment
			Blood Transfusion
			Other Treatments
			Curative Treatment
			Prevention
	Chapter 13: Rare Normocytic Normochromic Anemias: Aplastic Anemia and Related Disorders and Paroxysmal Nocturnal Hemoglobinuria
		Aplastic Anemia
			Pathogenesis
			Etiology
			Clinical Findings of Aplastic Anemia
			Laboratory Evaluation of Acquired Aplastic Anemia
			Treatment of Aplastic Anemia
			Congenital Aplastic Anemia
		Pure Red Cell Aplasia
			Acquired Pure Red Cell Aplasia
			Congenital Pure Red Cell Aplasia: Diamond-Blackfan Anemia
		Congenital Dyserythropoietic Anemias
		Paroxysmal Nocturnal Hemoglobinuria
			Pathogenesis
			Clinical Findings
			Laboratory Evaluation
			Treatment
		Relationships Among Conditions of Bone Marrow Hypoplasia
	Chapter 14: Hemolytic Anemias: Extracorpuscular Defects
		Immune Hemolytic Anemia
			Immune Hemolysis
			Classification of Immune Hemolytic Anemia
		Nonimmune Hemolytic Anemia
			Intracellular Infections
			Extracellular Infections
			Mechanical Etiologies
			Chemical and Physical Agents
			Acquired Membrane Disorders
	Chapter 15: Anemia Associated With Systemic Diseases
		Anemia of Chronic Kidney Disease
			Etiology and Pathophysiology
			Clinical Findings
			Laboratory Evaluation
			Treatment
		Anemia of Liver Disease
			Etiology and Pathophysiology
			Clinical Findings
			Laboratory Evaluation
			Treatment
		Anemia of Endocrine Disease/Disorders
			Diabetes
			Adrenal Insufficiency
			Thyroid Disease
			Hyperparathyroidism
			Hypogonadism
			Pituitary Dysfunction
		Myelophthisic Anemia
			Etiology and Pathophysiology
			Clinical Findings
			Laboratory Evaluation
			Treatment
		Anemia Associated With Viral Infections
			SARS-CoV-2 and COVID-19
			HIV and AIDS
		Anemia of Prematurity
			Etiology and Pathophysiology
			Clinical Findings
			Laboratory Evaluation
			Treatment
		Acknowledgment
Part 3: White Blood Cell Disorders
	Chapter 16: Benign White Blood Cell Disorders
		Neutrophils
			Neutrophil Function
			Disorders of Neutrophils
		Eosinophils
		Basophils
		Monocytes
		Lymphocytes
			Absolute Lymphocytosis: Reactive Versus Malignant Causes
			Lymphocytopenia
	Chapter 17: Introduction to Leukemia and the Acute Leukemias
		Overview of Leukemia
			Incidence and Prevalence
			Clinical Findings
			Historical Perspectives
			Etiology and Risk Factors
		Acute Leukemia
			Incidence
			Clinical Findings
			Evaluation of Morphology
		Acute Myeloid Leukemia
			FAB Classification
			WHO Classification
		Laboratory Testing of Acute Leukemia
			Specimens
			Cytochemistry
			Immunological Marker Studies
			Flow Cytometry
			Genetic Analysis
			Cytogenetics and FISH
			Molecular Studies
		Six Major Categories of the WHO Classification
			AML With Recurrent Genetic Abnormalities
			AML With Myelodysplasia-Related Changes
			Therapy-Related Myeloid Neoplasms
			Acute Myeloid Leukemia, Not Otherwise Specified
			Myeloid Sarcoma
			Myeloid Proliferations Related to Down Syndrome
		Acute Lymphoblastic Leukemia/Lymphoma (ALL/LBL)
			Review of Lymphocyte Ontogeny
			Clinical Findings
			Morphology
			Historical Classification: FAB Classification of ALL
			World Health Organization Classification of ALL
			T-Lymphoblastic Leukemia/Lymphoma (T-ALL/LBL)
			Burkitt’s Leukemia/Lymphoma (Mature B-CELL ALL)
			Childhood versus Adult ALL
			Acute Leukemias of Ambiguous Lineage
			Acute Leukemia of Ambiguous Lineage, Not Otherwise Specified
		Treatment of Acute Leukemia
	Chapter 18: Myeloproliferative Neoplasms I: Chronic Myelogenous Leukemia
		Chronic Myelogenous Leukemia
			Etiology
			Pathogenesis
			Clinical Findings
			Phases
			Laboratory Testing and Results
			Differential Diagnosis
			Prognosis
			Treatment
		Atypical Chronic Myelogenous Leukemia
		Chronic Neutrophilic Leukemia
		Chronic Eosinophilic Leukemia, Not Otherwise Specified
		Myeloproliferative Neoplasms, Unclassifiable
	Chapter 19: Myeloproliferative Neoplasms II: Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis
		Overview of Myeloproliferative Neoplasms
			History of the World Health Organization Classification
			Genetic Basis of Classical MPNs
			General Differentiation of MPNs
		Polycythemia Vera
			Definition
			Incidence
			Pathogenesis
			Clinical Findings
			Laboratory Testing and Results
			Differential Diagnosis
			Treatment
		Essential Thrombocythemia
			Definition
			Incidence
			Pathogenesis
			Clinical Findings
			Laboratory Testing and Results
			Differential Diagnosis
			Treatment
		Primary Myelofibrosis
			Definition
			Incidence
			Pathogenesis
			Clinical Findings
			Laboratory Testing and Results
			Differential Diagnosis
			Treatment
	Chapter 20: Myelodysplastic Syndromes
		Epidemiology, Etiology, and Pathogenesis
			MDS and Precursor States: Clonal Proliferative Diseases
			Genetic Anomalies
			Biological Characteristics of Disease Progression
			Ineffective Hematopoiesis
		Clinical Findings
		Prognosis
		Morphological Characteristics of Blood and Bone Marrow
			Definitions of Specific Morphological Characteristics
			Lineage Dysplasias
		Classification of MDS Subtypes
			MDS With Single Lineage Dysplasia
			MDS With Multilineage Dysplasia
			MDS With Ring Sideroblasts
			MDS With Isolated del(5q)
			MDS With Excess Blasts
			MDS, Unclassified
		Laboratory Testing and Results
			Bone Marrow Histology
			Flow Cytometry
			Cytogenetic and Molecular Abnormalities
		Therapy-Related Myelodysplastic Syndromes
		Myelodysplastic Syndromes in Children
		Diagnostic Challenges
			Reactive Causes of Dysplasia
			Cytogenetic and Molecular Findings Without Morphological Dysplasia
			MDS With Hypoplastic Marrow
		Treatment
			Supportive Care and Hematopoiesis-Improving Therapies
			Therapies Oriented Toward Improving Survival
		Myelodysplastic/Myeloproliferative Overlap Syndromes
	Chapter 21: Chronic Lymphocytic Leukemia and Related Lymphoproliferative Disorders
		Overview of Chronic Lymphocytic Leukemia
			Normal B-Cell Development
			Classification of Lymphoid Neoplasms
			Hematologic Abnormalities
			Epidemiology
		Etiology
		Pathophysiology
		Phenotypic Features and Methods for Studying Lymphocytes
		Clinical Findings
		Laboratory Testing and Results
		Genetic Abnormalities and Molecular Pathophysiology
		Clinical Course, Prognostic Factors, and Staging
		Treatment
		Differential Diagnosis
			CLL versus ALL
			B-Prolymphocytic Leukemia
			Small Lymphocytic Lymphoma
			Mantle Cell Lymphoma
			Small Cleaved-Cell Follicular Lymphoma
			Hairy Cell Leukemia
			Sézary Syndrome
			Adult T-Cell Leukemia/Lymphoma
			Chronic T-Cell Large Granular Lymphocytic Leukemia
			Reactive (Atypical) Lymphocytosis
			Plasma Cell Dyscrasias
	Chapter 22: The Lymphomas
		Hodgkin Lymphoma
			Epidemiology, Etiology, and Pathogenesis
			Pathology
			Clinical Findings
			Staging and Treatment
		Non-Hodgkin Lymphoma
			Epidemiology, Etiology, and Pathogenesis
			Pathology
			B-Cell Lymphomas
			T-Cell and Natural Killer (NK)-Cell Lymphomas
			Histiocytic and Dendritic Cell Tumors
			Diagnostic Evaluation of Lymphoid Neoplasia
			Treatment and Prognosis
		Acknowledgment
	Chapter 23: Multiple Myeloma and Related Plasma Cell Disorders
		Plasma Cell Development
		Immunoglobulin
			Structure and Function
			Abnormal Monoclonal Immunoglobulin Level Recognition and Measurement
			Laboratory Recognition and Measurement
		Monoclonal Gammopathy of Undetermined Significance
		Smoldering Myeloma
		Multiple Myeloma
			Epidemiology
			Etiology
			Pathophysiology
			Clinical Findings
			Laboratory Testing and Results
			Diagnostic Criteria
			Staging
			Treatment
		Variants of Plasma Cell Syndromes
			Solitary Plasmacytoma
			Plasma Cell Leukemia
			Nonsecretory Myeloma
			POEMS Syndrome
		Waldenström Macroglobulinemia
		Light-Chain Amyloidosis
		Light-Chain Deposition and Heavy-Chain Diseases
	Chapter 24: Lipid (Lysosomal) Storage Diseases and Histiocytosis
		Overview of Lipid Storage Diseases
		Gaucher’s Disease
			Historical Perspective
			Classification and Clinical Findings
			Laboratory Testing and Results
			Prognosis
			Treatment
		Niemann–Pick Disease
			Classification and Clinical Findings
			Laboratory Testing and Results
			Prognosis and Treatment
		Tay–Sachs Disease
			Clinical Findings
			Laboratory Testing and Results
			Prognosis and Treatment
		Mucopolysaccharidoses
			Classification
			Clinical Findings
			Laboratory Testing and Results
			Prognosis and Treatment
		Histiocytosis
			Sea-Blue Histiocyte Syndrome
			Langerhans Cell Histiocytosis
Part 4: Hemostasis and Introduction to Thrombosis
	Chapter 25: Hemostasis
		Platelets and the Hemostatic Mechanisms
			Stages of Hemostasis
			Vascular System
		Primary Hemostasis
			Platelet Structure
			Platelet Function and Platelet Plug Formation
		Secondary Hemostasis: Fibrin-Forming (Coagulation) System
			Classification of Coagulation Factors by Hemostatic Function
			Classification of Coagulation Factors by Physical Properties
			Blood Coagulation: The “Cascade” Theory
			Extrinsic Pathway (Factor VII)
			Intrinsic Pathway (Factors XII, XI, IX, and VIII)
			Common Pathway (Factors X, V, II, and I)
		Thrombin-Mediated Reactions in Hemostasis
			Thrombin-Mediated Platelet Aggregation
			Thrombin Formation: Role of Extrinsic Pathway
			Thrombin Formation: Role of Common Pathway
			Thrombin-Mediated Anticoagulant Activity
			Thrombin-Mediated Tissue Repair
		Fibrin-Lysing (Fibrinolytic) System
		Kinin System
		Complement System
		Laboratory Evaluation of Hemostasis
	Chapter 26: Disorders of Primary Hemostasis: Quantitative and Qualitative Platelet Disorders and Vascular Disorders
		CHAPTER OUTLINE
		LEARNING OBJECTIVES
		Laboratory Evaluation of Disorders of Primary Hemostasis
			TABLE 26-1 Classification of Bleeding Disorders by ScreeningTests
			BOX 26-1 Laboratory Tests to Assess Disorders ofPrimary Hemostasis
			ADVANCED CONTENT
		Quantitative Platelet Disorders: Thrombocytopenia
			CRITICAL THINKING QUESTION
			Deficient Platelet Production
				Thrombocytopenia Due to Ineffective Thrombopoiesis
				TABLE 26-2 Classification of Disorders CausingThrombocytopenia
				Congenital Thrombocytopenia
					TABLE 26-3 Congenital Disorders Associated With DecreasedPlatelet Production
			Abnormal Distribution of Platelets
			Increased Destruction of Platelets
				Immune-Mediated Thrombocytopenias
					TABLE 26-4 Comparison of Acute and Chronic ITP
				Immune Thrombocytopenic Purpura
					Childhood ITP
					Adult ITP
					Common Clinical Findings
						FIGURE 26-1 Oral cavity of a patient with idiopathic thrombocytopenic purpura(ITP).
						FIGURE 26-2 Petechial bleeding of the lower extremities in a patient with ITP.
						FIGURE 26-3 ITP, bone marrow aspirate. Note the increased number ofmegakaryocytes with normal cellularity (M/E 3:1).
					Laboratory Testing and Results
					Treatment
		Quantitative Platelet Disorders: Thrombocytosis
			Primary Thrombocytosis
			Reactive Thrombocytosis
		Qualitative Platelet Disorders
			Congenital Disorders of Platelet Function
			Acquired Qualitative Platelet Disorders
		Vascular Disorders
			Primary Purpura
			Secondary Purpura
			Vascular and Connective Tissue Disorders
	Chapter 27: Disorders of Secondary Hemostasis: Plasma Clotting Factors
		Plasma Clotting Factors, Associated Disorders, Laboratory Evaluation, and Treatment
			Fibrinogen (Factor I)
			Factor II (Prothrombin)
			Factor V (Proaccelerin; Labile Factor)
			Factor VII (Proconvertin; Stable Factor)
			Factor VIII (Antihemophilic Factor) and von Willebrand Factor
			Factor IX (Christmas Factor; Plasma Thromboplastin Component [PTC])
			Factor X (Stuart–Prower Factor)
			Factor XI (Plasma Thromboplastin Antecedent [PTA])
			Factor XII (Hageman Factor)
			Factor XIII (Fibrin-Stabilizing Factor)
			Prekallikrein (Fletcher Factor)
			High Molecular Weight Kininogen (Fitzgerald Factor; Flaujeac Factor; Williams–Fitzgerald–Flaujeac Factor)
		Circulating Anticoagulants/Acquired Inhibitors
			Specific Inhibitors
			Nonspecific Inhibitors: The Lupus Anticoagulant and Antiphospholipid Antibodies
	Chapter 28: Disseminated Intravascular Coagulation and Primary Fibrinolysis
		Components of the Fibrinolytic System
			Plasminogen
			Plasminogen Activators
			Plasminogen Activator Inhibitor-1
			Plasmin
			α2-Antiplasmin
			Thrombomodulin
			Thrombin-Activatable Fibrinolysis Inhibitor
			Fibrin and Fibrinogen
			CRITICAL THINKING QUESTION
		Congenital Abnormalities of the Fibrinolytic System
		Disseminated Intravascular Coagulation
			Triggering Mechanisms and Associated Clinical Disorders
			Clinical Presentation
			Laboratory Diagnosis
			Treatment
		Related Disorders
			TABLE 28-4 Laboratory Differentiation Between DIC andPrimary Fibrinolysis
		SUMMARY CHART
		CASE STUDY 28-1
		REVIEW QUESTIONS
		REFERENCES
	Chapter 29: Introduction to Thrombosis and Anticoagulant Therapy
		History
		Regulation of Coagulation and Fibrinolysis
			Role of Endothelium
			Platelets
			Procoagulant Factors and Thrombin Generation
			Natural Inhibitors of Coagulation Factors (Plasma Components)
			Fibrinolytic System
		Inherited Thrombophilia
			Activated Protein C Resistance
			Protein C Deficiency
			Protein S Deficiency
			Antithrombin Deficiency
			Prothrombin (F2) G20210A Mutation
			Hyperhomocysteinemia
			Tissue Factor Pathway Inhibitor Deficiency
			Factor XII Deficiency
			Dysfibrinogenemia
			Elevated Plasma Factor VIII Coagulant Activity
			Lipoprotein a and Thrombosis
			Other Coagulant Factors Associated With Thrombosis
		Acquired Thrombotic Disorders
			Lupus Anticoagulant/Antiphospholipid Syndrome
			Heparin-Induced Thrombocytopenia
		Other Acquired Conditions Associated With Thrombosis
			Thrombosis With Pregnancy and Use of Oral Contraceptives
			Thrombosis and Nephrotic Syndrome
			Cancer-Associated Thrombosis (CAT)
		Diagnostic Approach and Issues in Laboratory Testing
			BOX 29-1 Differential Diagnosis of HypercoagulableStates
			BOX 29-2 Risk Factors for VenousThromboembolism
			BOX 29-3 Evaluation of a Patient With SuspectedThrombophilia (Hereditary/Acquired)
			BOX 29-4 Suggested Evaluation Criteria for InheritedThrombophilia
			BOX 29-5 Testing for Inherited Thrombophilia
			BOX 29-6 Issues in Laboratory Testing in PatientsWith Thrombosis
			Complete History and Physical Examination
				TABLE 29-9 Coagulation Defects and Sites of Thrombosis
				D-Dimer Assay in the Diagnosis of Thromboembolism
				Testing During the Acute Event
			Conditions That Can Interfere With Test Results
			Testing in the Appropriate Clinical Setting
			Functional Assays
				Testing Considerations
		Anticoagulant Therapy
			Unfractionated Heparin Therapy
			Low Molecular Weight Heparin
			Vitamin K Antagonists
			Direct Oral Anticoagulants (DOACs)
				ADVANCED CONTENT
				Direct Thrombin Inhibitors (DTIs)
				ADVANCED CONTENT
			Antiplatelet Agents
			Thrombolytic Therapy
			SUMMARY CHART
			CASE STUDY 29-1
				PERTINENT HISTORY
				PERTINENT PHYSICAL FINDINGS
				LABORATORY FINDINGS
				QUESTIONS
				ANSWERS
			CASE STUDY 29-2
				PERTINENT HISTORY
				PERTINENT PHYSICAL FINDINGS
				LABORATORY FINDINGS
				QUESTIONS
				ANSWERS
			REVIEW QUESTIONS
Part 5: Select Laboratory Methods
	Chapter 30: Body Fluid Examination: Analysis of Serous, Cerebrospinal, and Synovial Fluids
		Types of Body Fluids and Anatomy
			Serous Fluids: Pericardial, Pleural, and Peritoneal
			Cerebrospinal Fluid
			Synovial Fluid
		Specimen Collection and Preparation
			Collection
			Preparation
			Laboratory Analysis and Clinical Correlations
		Cellular Components of Body Fluids
			Neutrophils
			Lymphocytes
			Macrophages
			Tissue Cells
			Eosinophils, Basophils, and Mast Cells
		Serous Fluids: Pleural, Pericardial, and Peritoneal
			Effusions: Transudates and Exudates
			Cellular Responses, Microorganisms, and Malignant Cells
		Types of Effusions, Laboratory Analysis, and Clinical Correlations
			Pleural and Pericardial Effusions
			Peritoneal Effusions
		Cerebrospinal Fluid (CSF)
			Specimen Collection and Processing
			Laboratory Analysis and Clinical Correlations
		Synovial Fluid
			Specimen Collection and Processing
			Laboratory Analysis and Clinical Correlations
			Crystal Analysis and Clinical Correlations
			Artifacts
		Acknowledgments
	Chapter 31: Hematology Methods
		Analytical Phases of Testing
		Specimen Collection
			Patient Identification
			Safety
			Verification of Laboratory Orders
			Method 31–1. Venipuncture
			Method 31–2. Capillary Blood Collection
			Labeling the Blood Specimen
		Specimen Accessioning
		Manual Cell Counts
			Method 31–3. Red Blood Cell Counts
			Method 31–4. White Blood Cell Counts
			Method 31–5. Platelet Counts
		Evaluation of the Peripheral Blood Smear
			Method 31–6. Slide Preparation and Wright Stain
			Alternate Staining Options
			Method 31–7. The White Blood Cell Differential
		Methods Used in Detection and Monitoring of Anemia
			Method 31–8. Hemoglobin Determination
			Method 31–9. Microhematocrit Determination
			Method 31–10. Red Blood Cell Indices
			Method 31–11. Reticulocyte Counts
			Method 31–11A. Reticulocyte Counts Using the Miller Disc
		Standard Methods for Specific Anemias
			Method 31–12. SickledexTM (aka sickle solubility testing)
			Method 31–13. Helena SPIFE® Alkaline Hemoglobin Electrophoresis
			Method 31–14. Helena SPIFE® Acid Hemoglobin Electrophoresis
			Method 31–15. Hemoglobin A2 Determination
			Method 31–16. Isoelectric Focusing
			Method 31–17. Hemoglobin F Acid Stain (Modified Kliehauer-Betke Test)
			Method 31–18. Screening Test for Glucose-6-Phosphate Dehydrogenase Deficiency
			Method 31–19. Staining for Heinz Bodies
			Method 31–20. Screening Method for Detection of Red Cell Pyruvate Kinase
			Nonspecific Tests of Inflammation
			Method 31–21. Westergren Erythrocyte Sedimentation Rate
			Method 31–22. Alifax® Erythrocyte Sedimentation Rate Analyzer
	Chapter 32: Principles of Automated Differential Analysis
		Specimen Evaluation by Cell Volume and VCS Technology: DxH Analyzer Series, Beckman Coulter®
			Red Cell Analysis
			Platelet Analysis
			Leukocyte Analysis
			Reticulocyte Analysis
			Nucleated Red Blood Cell Detection
			Abnormal Flags
			Body Fluid Analysis
			Additional Parameters
		Specimen Evaluation by Light Scattering and Cytochemical Analysis: ADVIA® Hematology Systems, Siemens Healthcare Diagnostics
			Red Cell Analysis
			Platelet Analysis
			Leukocyte Analysis
			Reticulocyte Analysis
			Nucleated Red Blood Cell Detection
			Abnormal Flags
			Cerebrospinal Fluid Analysis
		Specimen Evaluation With Hydrodynamic Focusing, RF/DC Technology, and Fluorescent Flow Cytometry: The Sysmex XN and XN-L Series Hematology Analyzers
			Red Cell Analysis
			Platelet Analysis
			Leukocyte Analysis
			Reticulocyte Analysis
			Nucleated Red Blood Cell Detection
			Abnormal Flags
			Body Fluid Analysis
		Specimen Evaluation by Multi-Angle Polarized Scatter (MAPSSTM) Technology: Abbott Alinity h-Series
			Red Cell Analysis
			Platelet Analysis
			Leukocyte Analysis
			Reticulocyte Analysis
			Nucleated Red Blood Cell Detection
			Abnormal Flags
			Body Fluid Analysis
			Additional Parameters
		Digital Morphology Analyzers: CellaVision Systems
		Quality Control and Quality Assurance Measures for Automated Complete Blood Count Instruments
			Quality Control Procedures
			Quality Assurance Measures
			Result Verification and Decision Rules
		Acknowledgments
	Chapter 33: Coagulation Methods
		Platelet Function Instrumentation and Tests
			Method 33–1: Bleeding Time
			Method 33–2: Closure Time—PFA-100® (Siemens)
			Method 33–3: Platelet Aggregation
		Coagulation Instrumentation
			General Types of Coagulation Instrumentation
			Methods of Endpoint Detection
			Complete Hemostasis Assessment
		Coagulation Screening Tests
			Method 33–4: Activated Partial Thromboplastin Time
			Method 33–5: One-Stage Prothrombin Time (Quick)
			Method 33–6: Thrombin Time
			Method 33–7: Mixing Studies—aPTT or PT 1:1: Mix
		Coagulation Factor Assays
			Method 33–8: One-Stage Quantitative Assay Method for Factors II, V, VII, and X
			Method 33–9: One-State Quantitative Assay Method for Factors VIII, IX, XI, and XII
			Method 33–10: Factor XIII Chromogenic Assay (Activity)
			Coagulation Inhibitors
		Tests to Monitor Anticoagulant Therapy
			Monitoring Anticoagulant Therapy With Coagulation Screening Assays
			Method 33–11: Anti-FXa Assay (Heparin Activity)
			Monitoring Direct Thrombin Inhibitors
		Tests to Measure Fibrin Formation
			Method 33–12: Reptilase Time
			Method 33–13: Fibrinogen Activity
		Tests for von Willebrand Disease
			Method 33–14: von Willebrand Factor Antigen
			Method 33–15: von Willebrand Factor Activity (vWF:RCo, Ristocetin Cofactor)
			von Willebrand Collagen Binding Activity
			von Willebrand Factor Multimer Analysis
			Molecular Analysis in vWD
		Tests to Assess Hereditary Thrombotic Risk
			Method 33–16: Activated Protein C Resistance/Factor V Leiden
		Antithrombin Assays
			Method 33–17: Antithrombin Functional Assay (Activity)— Chromogenic Substrate Assay
			Method 33–18: Antithrombin Immunological Assay (Antigen)—Microlatex Particle Immunological Assay
		Protein C Assays
			Method 33–19: Protein C Immunological Assay (Antigen)
			Method 33–20: Protein C Functional Assays (Activity)—Chromogenic Substrate Assay
			Method 33–21: Protein C Clot-Based Assay
		Protein S Assays
			Method 33–22: Protein S Functional Assay (Activity)— Clotting Assay
			Protein S Immunological Assay (Antigen)
		Prothrombin G20210A (Factor II) Mutation
		Tests for the Evaluation of Lupus Anticoagulants
		Confirmatory Tests for Lupus Anticoagulants
			Method 33–23: Platelet Neutralization Procedure
			Hexagonal Phospholipid Neutralization Assay
			Anti-Phospholipid Antibody Assays
		Tests for Fibrinolysis
			D-Dimer Quantitative Test
			Method 33–24: Euglobulin Lysis Time
			Method 33–25: Fibrin Degradation Products: Latex Aggulination Method
		Markers of Coagulation Activation and Thrombin Generation
	Chapter 34: Applications of Flow Cytometry to Hematopathology
		Basic Concepts of Flow Cytometry
			Threshold
			Photodetectors
			Amplification
			Fluorescence Compensation
		Flow Cytometric Analysis
			Sample Preparation
			Cytometer Operation
			Data Analysis
		Applications of Flow Cytometry
			Lymphocyte Subset Analysis and CD4 T-Cell Enumeration
			Leukemia and Lymphoma Immunophenotyping
			Leukemia and Lymphoma DNA Content Analysis
			Hematopoietic Progenitor Cell Enumeration
			Flow Crossmatching
			Detection of Paroxysmal Nocturnal Hemoglobinuria
			Residual White Blood Cell Enumeration
			Detection of Fetomaternal Hemorrhage
			Bead-Based Assays for Soluble Factors
	Chapter 35: Molecular Techniques in Hematopathology
		Structure of DNA and RNA
		Applications of DNA Technology in Laboratory Medicine
		Sample Sources for Molecular Procedures
		Nucleic Acid Extraction
			DNA Extraction From Cells or Tissue
			RNA Extraction
		Nucleic Acid Qualification
		Sequence-Specific DNA Fragmentation by Restriction Endonucleases
		Molecular Procedures
			Polymerase Chain Reaction (PCR)
			Reverse Transcription Polymerase Chain Reaction (RT-PCR)
			In Situ Hybridization to Tissue Immobilized on Glass Slides
			Fluorescence In Situ Hybridization
			DNA Sequencing
		Future Prospects of Molecular Assays
Answers to Chapter Critical Thinking Questions
Answers to Review Questions Chs 1-35
Glossary
Index
Hematologic Values