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Essentials in Hematology and Clinical Pathology
Ramadas Nayak, Sharada Rai, Astha Gupta
SECTION 1: DISORDERS OF RED CELLS
CHAPTER 1:
Introduction
DEFINITION
Functions of Blood Cells
HEMATOPOIESIS
Sites of Hematopoiesis
Terminology Used in Hematopoiesis
Normal Development of Blood Cells (Hematopoiesis)
Hematopoietic Stem Cells (HSC)
Progenitor Cells
Precursor Cells
Mature cells
Regulation of Hematopoiesis
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 2:
Classification of Anemia
RED CELL
Normal Parameters of Red Cell (Table 2.1)
ANEMIA
Definition of Anemia
Classification of Anemia
Clinical Features of Anemia
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 3:
Iron Deficiency Anemia
IRON METABOLISM
Distribution of Iron
Iron Absorption
Molecular Aspect of Iron Absorption (Fig. 3.1)
Transport of Iron
Iron Excretion
Regulation of Iron Balance
IRON DEFICIENCY ANEMIA
Etiology of Iron Deficiency Anemia (Table 3.3)
Pathogenesis of Iron Deficiency Anemia
Clinical Features
Physical Findings
Laboratory Findings
Peripheral Blood
Bone Marrow
Serum Iron Profile
Other Causes of Microcytic Hypochromic Anemia
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 4:
Megaloblastic Anemia
INTRODUCTION
DEFINITION
Cause of Megaloblastic Change and Macrocytic Red Cells
METABOLISM OF VITAMIN B12 AND FOLIC ACID
Vitamin B12 Metabolism
Absorption, Transport and Storage (Fig. 4.1)
Role of Vitamin B12
Folic Acid Metabolism
Role of Folic Acid (FA)
ETIOLOGY OF MEGALOBLASTIC ANEMIA
LABORATORY FINDINGS OF MEGALOBLASTIC ANEMIA
Peripheral Blood
Bone Marrow
Common Biochemical Tests for Vitamin B12 and Folic Acid Deficiency
ANEMIAS OF VITAMIN B12 DEFICIENCY
Causes of Vitamin B12 Deficiency (Table 4.2)
Decreased Intake
Impaired Absorption
Increased Demand
Pernicious Anemia
Definition
Incidence
Etiopathogenesis
Clinical Features (Fig. 4.9)
Laboratory Findings (Fig. 4.9)
Biochemical Parameters
ANEMIA OF FOLATE DEFICIENCY
Causes of Folic Acid Deficiency
Clinical Features
Laboratory Findings
Peripheral Blood
Bone Marrow
Biochemical Parameters
Specific Tests for Folic Acid Deficiency
NONMEGALOBLASTIC CAUSES OF MACROCYTIC ANEMIAS
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 5:
Introduction and Classification of Hemolytic Anemia
INTRODUCTION
Hemoglobin Structure
Acquired Chemically Modified Hemoglobin Derivatives
Defects in Hemoglobin
HEMOLYTIC ANEMIA
Definition
Mechanism and Consequences of Hemolysis
A. Features of Increased Red Cell Destruction
B. Features of Increased Red Cell Production
C. Damaged Red Cells
Clinical Features
Laboratory Findings in Hemolytic Anemias
Peripheral Blood
Bone Marrow
Extramedullary Hematopoiesis
Other Laboratory Findings
CLASSIFICATION OF HEMOLYTIC ANEMIAS
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 6:
Hemolytic Anemias due to Red Cell Membrane Disorders
INTRODUCTION
Structure of the Red Cell Membrane and Cytoskeleton (Fig. 6.1)
HEREDITARY SPHEROCYTOSIS
Definition
Etiopathogenesis
Mechanism of Hemolysis in HS (Fig. 6.2)
Clinical Features
Laboratory Findings
Peripheral Blood
Bone Marrow
Biochemical Findings
Osmotic Fragility Test
HEREDITARY ELLIPTOCYTOSIS
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 7:
Thalassemia Syndromes
INTRODUCTION
Definition
Classification
β-THALASSEMIA
Molecular Pathology
Clinical and Genetic Classification of β-thalassemia
Pathophysiology of β-thalassemia (Fig. 7.1)
A. Consequence of Defective or Absent β-chains
B. Consequences of Ineffective Erythropoiesis
C. Iron Overload and its Consequences
β-Thalassemia Major
Clinical Features
Laboratory Findings
Thalassemia Intermedia
Thalassemia Minor
Clinical Features
Laboratory Findings in Thalassemia Minor
α-THALASSEMIA
Molecular Pathology
Clinical Syndromes
Silent Carrier State
α-Thalassemia Trait
Hemoglobin H Disease
Hydrops Fetalis
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 8:
Sickle Cell Disease
INTRODUCTION
Classification of Sickle Cell Disease
Sickle Cell Anemia (SS)
Sickle Cell Trait (AS)
Other Sickling Syndromes (Compound Heterozygous)
SICKLE CELL ANEMIA
Definition
Etiopathogenesis
Molecular Basis of Sickling (Fig. 8.2)
Factors Affecting Sickling (Table 8.1)
Mechanism of Red Cell Damage
Pathogenesis of the Microvascular Occlusions
Clinical Features (Fig. 8.3)
A. Chronic Hemolytic Anemia
B. Crises
C. Infections
D. Chronic Organ Damage
Laboratory Findings in Sickle Cell Anemia
Peripheral Blood
Bone Marrow
Serum Findings
Urine Urobilinogen
Diagnostic/confirmatory Tests
Method
SICKLE CELL TRAIT
Pathogenesis
Clinical Features
Laboratory Findings
Peripheral Blood
Bone Marrow
Diagnostic Tests
OTHER SICKLING SYNDROMES
Hemoglobin Sβ Thalassemia
Hemoglobin SE Disease
Hemoglobin SD Disease
OTHER HEMOGLOBINOPATHIES
Hemoglobin D Punjab
Hemoglobin D Trait
Hemoglobin D Disease
Hemoglobin E
Hemoglobin E Trait
Hemoglobin E Disease
Hemoglobin C
Hemoglobin C Trait
Hemoglobin C Disease
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 9:
Hemolytic Anemias due to Red Cell Enzyme Deficiencies
METABOLIC PATHWAYS IN RED BLOOD CELLS
Hemolytic Disease due to Red Cell Enzyme Defects
GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY
Role of G6PD (Fig. 9.1)
Sequence of Events in G6PD Deficiency
Prevalence and Malaria
Genetics of G6PD
Clinical Presentation
Acute Hemolytic Anemia
Chronic Hemolytic Anemia (nonspherocytic)
Neonatal Hyperbilirubinemia
Favism
PYRUVATE KINASE DEFICIENCY
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 10:
Immunohemolytic Anemia
DEFINITION
CLASSIFICATION
ALLOIMMUNE HEMOLYTIC ANEMIA
Hemolytic Disease of the Newborn (HDN)
Rh Hemolytic Disease of newborn (Fig. 10.1)
ABO Hemolytic Disease of the Newborn
Hemolytic Transfusion Reactions (Chapter 60)
a. Immediate Hemolytic Transfusion Reaction
b. Delayed Hemolytic Transfusion Reaction
AUTOIMMUNE HEMOLYTIC ANEMIA
Warm Antibody Type
Etiology and Pathogenesis
Clinical Features
Laboratory Findings
Cold Agglutinin Type
Laboratory Findings
Cold Hemolysins Type (Donath-Landsteiner antibodies)
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 11:
Fragmentation Syndrome
INTRODUCTION
CLASSIFICATION
LABORATORY FINDINGS
March Hemoglobinuria
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 12:
Paroxysmal Nocturnal Hemoglobinuria
DEFINITION
ETIOLOGY AND PATHOGENESIS
CLINICAL FEATURES
LABORATORY FINDINGS
Peripheral Blood
Ham's Acidified Serum Test and Sucrose Hemolysis Test
Flow Cytometry
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 13:
Approach to Hemolytic Anemias
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 14:
Aplastic Anemia
DEFINITION
ETIOLOGY
Acquired
Inherited
PATHOGENESIS
CLINICAL FEATURES
LABORATORY FINDINGS
Peripheral Blood
Bone Marrow
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 15:
Pure Red Cell Aplasia
DEFINITION
ETIOLOGY
CLINICAL FEATURES
LABORATORY FINDINGS
Peripheral Blood
Bone Marrow
SUMMARY
SELF-ASSESSMENT EXERCISE
Multiple Choice Question
ANSWER
CHAPTER 16:
Miscellaneous RBC Disorders
ANEMIA OF CHRONIC DISEASE
Etiopathogenesis
Laboratory Findings
Peripheral Blood
Bone Marrow
Serum Iron
ANEMIA OF RENAL DISEASE
ANEMIA OF LIVER DISEASE
ANEMIAS OF BLOOD LOSS
Acute Blood Loss
Peripheral smear
Chronic Blood Loss
ANEMIA ASSOCIATED WITH MARROW INFILTRATION (MYELOPHTHISIC ANEMIA)
Etiology and Pathogenesis
SUMMARY
SELF-ASSESSMENT EXERCISE
Multiple Choice Questions
ANSWERS
CHAPTER 17:
Sideroblastic Anemia
INTRODUCTION
Definition
Classification
Types of Sideroblasts
HEREDITARY SIDEROBLASTIC ANEMIAS
Clinical Features
Laboratory Findings
Peripheral Blood
Bone Marrow
Other Findings
ACQUIRED IDIOPATHIC SIDEROBLASTIC ANEMIA
Secondary (drug-or toxin-induced) Sideroblastic Anemia
CONGENITAL DYSERYTHROPOIETIC ANEMIAS (CDA)
SUMMARY
SELF-ASSESSMENT EXERCISE
Multiple Choice Questions
ANSWERS
CHAPTER 18:
Polycythemia
INTRODUCTION
Definition
Classification
POLYCYTHEMIA VERA
Definition
Molecular Pathogenesis
Clinical Features
Laboratory Findings
Peripheral Blood
Bone Marrow
Bone Marrow Biopsy
Other Findings
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
SECTION 2: DISORDERS OF WHITE CELLS
CHAPTER 19:
Quantitative and Qualitative Disorders of White Blood Cells
INTRODUCTION
Types of Normal White Blood Cells (Fig. 19.1)
Neutrophils
Eosinophils
Basophils
Monocytes
Lymphocytes
Normal Differential Leukocyte Count (DLC)
CLASSIFICATION OF WBC DISORDERS
QUANTITATIVE DISORDERS OF LEUKOCYTES
Disorders of Neutrophils
Neutrophilia
Neutropenia (agranulocytosis)
Eosinophilia
Basophilia
Monocytosis (Table 19.8)
Lymphocytosis
Lymphocytopenia
CD4 and CD8 Lymphocytes
Decreased CD4
Plasma Cells
QUALITATIVE DISORDERS OF LEUKOCYTES
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 20:
Infectious Mononucleosis
DEFINITION
PATHOGENESIS
Productive Infection
Latent Infection
Molecular Basis of B Cell Proliferation
Immune Responses to EBV Infection
CLINICAL FEATURES
LABORATORY FINDINGS
Peripheral Smear
Serological Tests
Lymph Nodes
LESIONS ASSOCIATED WITH EBV INFECTION
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 21:
Introduction to Acute Leukemia
NEOPLASTIC PROLIFERATIONS OF WHITE CELLS
Myeloid Neoplasms
Lymphoid Neoplasms
Histiocytic and Dendritic Cell Neoplasms
ACUTE LEUKEMIA
Definition
Etiology and Pathogenesis
Risk Factors
Acquired Disorders
Classification
FAB Classification of Acute Leukemias
Revised WHO Classification (2008) of Acute Myelogenous Leukemia
Diagnosis of Acute Leukemia
Morphology of the Blasts
Cytochemistry
Immunophenotyping (Table 21.6)
Cytogenetics
Molecular Genetics
Clinical Presentation of Acute Leukemia
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 22:
Acute Lymphoblastic Leukemia
ACUTE LYMPHOBLASTIC LEUKEMIA
Definition
Molecular Pathogenesis
Classification of Acute Lymphoblastic Leukemia (see Tables 21.3 and 30.1) Clinical Features
Laboratory Findings
Peripheral Blood
Bone Marrow
Immunophenotyping
Biochemical Findings (Refer tumor lysis syndrome on page 166)
CSF Examination
Prognosis
ACUTE LYMPHOBLASTIC LYMPHOMA
Lymphnode
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 23:
Acute Myelogenous Leukemia and Related Neoplasm
ACUTE MYELOGENOUS LEUKEMIA
Definition
Molecular Pathogenesis
Clinical Features
Laboratory Findings
Peripheral Blood
Morphology of myeloblasts
Bone Marrow
Biochemical Findings (refer tumor lysis syndrome on page 166)
Positive FDP and Decreased Fibrinogen
Immunophenotyping
Cytogenetics
Prognosis
MYELOID SARCOMA
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 24:
Myelodysplastic Syndromes
DEFINITION
CLASSIFICATION
WHO Classification of Myelodysplastic Syndromes (Table 24.1)
ETIOLOGY AND MOLECULAR PATHOGENESIS
CLINICAL FEATURES
LABORATORY FINDINGS
Peripheral Smear
Bone Marrow
Morphological Features of Dysplasia (Table 24.2)
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 25:
Myeloproliferative Neoplasm
INTRODUCTION
Definition
Pathogenesis
ESSENTIAL THROMBOCYTHEMIA
Definition
Etiology
Clinical Features
Laboratory Findings
Peripheral Smear
Bone Marrow
Bone Marrow Biopsy
Extramedullary Hematopoiesis
Platelet Function
Course
PRIMARY MYELOFIBROSIS
Definition
Molecular Pathogenesis
Clinical Features
Laboratory Findings
Peripheral Smears
Bone Marrow
Bone Marrow Biopsy
Extramedullary Hematopoiesis
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 26:
Chronic Myelogenous Leukemia and Other Myeloid Neoplasms
CHRONIC MYELOGENOUS LEUKEMIA
Definition
Etiology and Pathogenesis
Molecular Pathogenesis (Figs 26.1 and 26.2)
Clinical Features
Physical Examination
Natural History of Chronic Myeloid Leukemia
Chronic/Stable/Indolent Phase (CP)
Laboratory Findingsc
Accelerated Phase (AP)
Blast Phase/crisis (BP)
Treatment
MYELODYSPLASTIC/MYELOPROLIFERATIVE NEOPLASMS
Chronic Myelomonocytic Leukemia (CMML)
Juvenile Myelomonocytic Leukemia (JMML)
Clinical features
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 27:
Chronic Lymphocytic Leukemia and Other Lymphoid Leukemias
CHRONIC LYMPHOCYTIC LEUKEMIA
Definition
Etiology and Pathogenesis
Cytogenetic Abnormalities
Clinical Features
Laboratory Findings
Peripheral Blood
Bone Marrow
Antiglobulin (Coombs) Test
Immunophenotype
Lymph Node
Course and Prognosis
Progression and Transformation of CLL
B cell Prolymphocytic Transformation
Transformation to Diffuse Large B cell Lymphoma (Richter syndrome)
PROLYMPHOCYTIC LEUKEMIA
B cell Prolymphocytic Leukemia
Definition
Clinical Features
Laboratory Findings
Prognosis
HAIRY CELL LEUKEMIA
Definition
Cell of Origin
Site Involved
Laboratory Findings
Peripheral Blood
Bone Marrow
Spleen
Immunophenotype and Molecular Characteristics
Clinical Features
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 28:
Plasma Cell Neoplasms
INTRODUCTION
Definition
Characteristics of Plasma Cell Neoplasms
PLASMA CELL MYELOMA
Definition
Etiology and Pathogenesis
Cell of Origin
Cytogenetic Abnormalities
Pathological Features
Laboratory Findings
Peripheral Blood
Bone Marrow
Serum Findings
Electrophoretic Studies on Serum and Urine
Morphology of Organs Involved
Clinical Manifestations
Due to Tumor Cells Causing Bony Lesions
Production of M Proteins (increased immunoglobulins)
Humoral Immune Deficiency
Renal Disease
Prognosis
Clinical Variants of Plasma Cell Myeloma
Asymptomatic (smoldering) plasma cell myeloma
Nonsecretory Myeloma
Plasma Cell Leukemia
PLASMACYTOMA
IMMUNOGLOBULIN DEPOSITION DISEASES
MONOCLONAL GAMMOPATHY OF UNCERTAIN SIGNIFICANCE
OSTEOSCLEROTIC MYELOMA
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 29:
Lymphopoietic System
INTRODUCTION
LYMPH NODES
Size and Shape
Capsule
Subcapsular Sinus
Parenchyma
Cortex
Medulla
DEVELOPMENT OF LYMPHOCYTES (LYMPHOPOIESIS)
Development of B Lymphocyte (Figs 29.1 and 29.2)
Stages
Development of T Lymphocyte (Fig. 29.2)
Stages
Natural Killer (NK) Cell
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 30:
Lymphoid Neoplasms
INTRODUCTION
Categorization of Lymphoid Neoplasms
CLASSIFICATION OF LYMPHOID NEOPLASMS
General Features of Lymphoid Neoplasms
PRECURSOR LYMPHOID NEOPLASMS
MATURE B CELL NEOPLASMS
Lymphoplasmacytic Lymphoma
Definition
Cell of Origin
Morphology
Spread
Immunophenotype
Molecular Genetics
Clinical Features
Prognosis
Marginal Zone Lymphoma
Definition
Cell of Origin
Morphology
Follicular Lymphoma
Definition
Cell of Origin
Morphology
Immunophenotype
Cytogenetics and Molecular Genetics
Clinical Features
Prognosis
Mantle Cell Lymphoma
Definition
Cell of Origin
Morphology
Immunophenotype
Cytogenetic Abnormalities and Molecular Genetics
Clinical Features
Prognosis
Diffuse Large B Cell Lymphoma (DLBCL)
Definition
Cell of Origin
Morphology
Immunophenotype
Cytogenetics and Molecular Profile
Etiology
Clinical Features
Prognosis
Burkitt Lymphoma
Definition
Cell of Origin
Clinical Variants
Morphology
Immunophenotype
Cytogenetic and Molecular Genetic Features (Fig. 30.4)
Prognosis
Plasma Cell Neoplasms are discussed in Chapter 28.
Composite Lymphoma
MATURE T CELL AND NK CELL NEOPLASMS
Peripheral T Cell Lymphoma, NOS
Definition
Cell of Origin
Morphology
Immunophenotype
Clinical Features
Prognosis
Anaplastic Large Cell Lymphoma
Definition
Cell of Origin
Morphology
Immunophenotype
Cytogenetic and Molecular Genetic Features
Clinical Features
Prognosis
Adult T Cell Leukemia/Lymphoma (ATLL)
Definition
Morphology
Clinical Features
Prognosis
Mycosis Fungoides
Definition
Age
Morphology
Immunophenotype
Sézary Syndrome
Definition
Morphology
Immunophenotype
Prognosis
Angioimmunoblastic T cell Lymphoma
Definition
Cell of Origin
Morphology
Immunophenotype
Prognosis
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 31:
Hodgkin Lymphoma
INTRODUCTION
Definition
Classification
Cell of Origin and Immunophenotype
Morphology of Neoplastic Cells
Reed-Sternberg (RS) Cells
Reed-Sternberg Cell Variants (Fig. 31.2)
General Morphological Features
Gross
Microscopy
CLASSICAL HODGKIN LYMPHOMA
Nodular Sclerosis Classical Hodgkin Lymphoma
Definition
Morphology
Immunophenotype
Prognosis
Mixed Cellularity Classical Hodgkin Lymphoma
Definition
Morphology
Immunophenotype
Prognosis
Lymphocyte-Rich Classical Hodgkin Lymphoma
Definition
Morphology
Immunophenotype
Prognosis
Lymphocyte-Depleted Classical Hodgkin Lymphoma
Definition
Morphology
Immunophenotype
Prognosis
NODULAR LYMPHOCYTE PREDOMINANT HODGKIN LYMPHOMA
Definition
Morphology
Sites Involved
Microscopy (Fig. 31.7)
Immunophenotype
Cell of Origin
Transformation
Prognosis
ETIOLOGY AND PATHOGENESIS OF HODGKIN LYMPHOMA
Pathogenesis (Fig. 31.8)
LABORATORY FINDINGS
Peripheral Blood
Biochemical Findings
Fine Needle Aspiration Cytology (FNAC)
Lymphnode Biopsy
CLINICAL FEATURES
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 32:
Langerhans Cell Histiocytosis
INTRODUCTION
DEFINITION
MORPHOLOGY
LABORATORY FINDINGS
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
SECTION 3: DISORDERS OF HEMOSTASIS
CHAPTER 33:
Normal Hemostasis and its Components
INTRODUCTION
Definition
PLATELETS
Morphology of Platelets
Role of Platelets in Hemostasis
BLOOD VESSEL WALL
Endothelial Cells
Vasoconstriction
COAGULATION SYSTEM
Traditional Coagulation Pathways (Fig. 33.2 and Table 33.1)
Extrinsic Pathway
Intrinsic Pathway
Common Pathway
Cell-based Coagulation
Steps
COAGULATION REGULATORY MECHANISM
FIBRINOLYTIC SYSTEM
NORMAL HEMOSTASIS
Primary Hemostatic Plug
Secondary Hemostatic Plug
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 34:
Bleeding Disorders: Vessel Wall Abnormalities
DISORDERS OF HEMOSTASIS
Classification of Hemostatic Disorders
Bleeding Disorders
Terminologies Used in Bleeding Disorders (Fig. 34.1)
Thrombotic Disorders
Classification of Thrombotic Disorders
BLEEDING DISORDERS CAUSED BY VESSEL WALL ABNORMALITIES
Classification
Acquired Disorders
Inherited Disorders
Hereditary Hemorrhagic Telangiectasia (Weber-Osler-Rendu syndrome)
Ehlers-Danlos Syndrome
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 35:
Bleeding Disorders: Abnormalities of Platelet
INTRODUCTION
Classification of Platelet Disorders
QUANTITATIVE PLATELET DISORDERS
Thrombocytopenia
Definition
Clinical Features of Thrombocytopenia
Causes of Thrombocytopenia
Idiopathic (Immune) Thrombocytopenic Purpura (ITP)
Types of ITP
Laboratory Findings
Spleen
Other Causes of Immune Mediated Thrombocytopenia
Nonimmune Thrombocytopenia: Thrombotic Microangiopathies
Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic-Uremic Syndrome (HUS)
Thrombocytosis
QUALITATIVE PLATELET DISORDERS
Hereditary Disorders of Platelet Function
Acquired Defects of Platelet Function
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 36:
Bleeding Disorders: Abnormalities of Coagulation Factors
INTRODUCTION
HEREDITARY DEFICIENCIES
Deficiencies of Factor VIII-vWF Complex
von Willebrand Disease (vWD)
Clinical Features
Laboratory Findings
Hemophilia
Hemophilia A (factor VIII deficiency)
Mode of Inheritance
Molecular Genetics
Clinical Features
Laboratory Findings
Complications of Hemophilia
Causes of Death
Treatment
Complications of Therapy
Hemophilia B (Christmas Disease, Factor IX Deficiency)
Clinical Features
Laboratory Findings
Other Hereditary Coagulation Disorders
ACQUIRED COAGULATION DISORDERS
Coagulation Factor Abnormalities
Inhibitors of Coagulation Factors
DISSEMINATED INTRAVASCULAR COAGULATION
Etiology and Pathogenesis (Fig. 36.2)
Mechanism of Thrombi/Clot Formation
Major Disorders Associated with DIC (Table 36.5)
Clinical Features
Laboratory Findings in DIC
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 37:
Thrombotic Disorders: Hypercoagulable States
INTRODUCTION
INHERITED HYPERCOAGULABLE STATES
Deficiency of Antithrombotic Factors
Antithrombin (AT) III Deficiency
Protein C Deficiency
Protein S Deficiency
Increased Prothrombotic Factors
Activated Protein C (APC) Resistance (Factor V Leiden)
Other Causes
ACQUIRED HYPERCOAGULABLE STATES
Antiphospholipid Antibody Syndrome (APLA/APS)
Types
Clinical Features
Laboratory Tests
Homocysteinemia
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
SECTION 4: CLINICAL PATHOLOGY
CHAPTER 38:
Anticoagulants and Collection of Blood
ANTICOAGULANTS
Calcium Chelating Agents
Uses
b. Oxalate
c. Sodium Citrate
Uses
d. Sodium Fluoride
Heparin
Disadvantages
Uses
STEPS IN HEMATOLOGICAL INVESTIGATION
Collection of Blood
Type of Blood Sample
1. Whole Blood
Uses
2. Serum
Uses
3. Plasma
Uses
Methods of Blood Collection
Complications Encountered During Blood Collection
Labeling
Laboratory Requisition Form
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 39:
Hematopoiesis
INTRODUCTION
ERYTHROPOIESIS
MYELOPOIESIS
Development of Eosinophils and Basophils
MEGAKARYOPOIESIS
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 40:
Hemoglobin Estimation
METHODS OF HEMOGLOBIN ESTIMATION
COLORIMETRIC METHODS
Visual Colorimetric Method
Sahli's Method or Acid Hematin Method
Alkaline Hematin Method
Photoelectric (Photocolorimetric) Method
Cyanmethemoglobin (Hemiglobincyanide; HiCN) Method
Automated Analyser (Cell Counter)
Hemo-cue Blood Hemoglobin System
Oxyhemoglobin Method
Haldane Method
OTHER METHODS
Physical Method
Chemical Methods
Gasometric Methods
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 41:
Cell Count
INTRODUCTION
RED BLOOD CELL COUNT
Manual Method
Equipment
Principle
RBC Diluting Fluids
Technique
Other Methods for RBC Count
Normal Range for RBC Count (Table 41.3)
Causes of Increased RBC Count
Causes of Decreased RBC Count
TOTAL WBC COUNT
Manual Method
Equipment
Principle
WBC Diluting Fluid
Technique
Sources of Error
Corrections of Total WBC Count for nRBC
Other Methods for WBC Count
Uses
Normal Range for WBC Count (Table 41.5)
Increased WBC Count
Decreased WBC Count
PLATELET COUNT
Manual Method
Equipment
Principle
Platelet Diluting Fluids
Technique
Sources of Error
Automated Analyser
Normal Range
Decreased Platelet Count
Increased Platelet Count
ABSOLUTE EOSINOPHIL COUNT
Manual Method
Equipment
Diluting Fluid
Technique
Normal Range of Eosinophil Count
Use
High AEC (Eosinophilia)
Automated Analyser/Cell Counters
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 42:
Peripheral Blood Smear Examination
INTRODUCTION
STAINS FOR BLOOD SMEAR
Romanowsky Stains
PREPARATION OF THE PERIPHERAL BLOOD SMEAR (FIGS 42.1A TO D)
Features of a Well-made Peripheral Smear
Sources of Error
FIXATION OF THE SMEAR
STAINING OF THE SMEAR
Procedure of Staining with Leishman Stain
Sources of Error
Procedure of Staining with Giemsa Stain
EXAMINATION OF A PERIPHERAL BLOOD SMEAR
RED BLOOD CELLS
WHITE BLOOD CELLS
Leukoerythroblastic Reaction or Blood Picture (Table 42.2)
PLATELETS
HEMOPARASITES
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 43:
Reticulocyte Count
METHODS OF RETICULOCYTE COUNT
Visual Method
Brilliant Cresyl Blue/New Methylene Blue Stain (Figs 43.1A and B)
Reticulocyte Count Correction for Anemia
Automated Method of Reticulocyte Count
SIGNIFICANCE OF RETICULOCYTE COUNT
Increased Reticulocyte Count
Causes
Reduced Reticulocyte Count
Causes
Other Uses of Supravital Stains
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 44:
Hematocrit, Red Cell Indices and ESR Estimation
HEMATOCRIT
Methods of Estimation of PCV
Wintrobe Method
Microhematocrit Method
Automated Analyser
Causes of Increased PCV (Table 18.1).
Rule of Three
RED CELL INDICES
Mean Corpuscular (cell) Volume (MCV)
Mean Corpuscular (cell) Hemoglobin (MCH)
Mean Corpuscular (cell) Hemoglobin Concentration (MCHC)
Red Cell Distribution Width (RDW)
Uses
ERYTHROCYTE SEDIMENTATION RATE
Factors Affecting ESR
Stages of ESR
Methods
Westergren Method
Disposable Methods
Wintrobe Method
Alternative Methods
Significance of ESR
Causes of Increased ESR (Table 44.3)
Causes of Decreased ESR
LE CELL TEST
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 45:
Bone Marrow Examination
INTRODUCTION
BONE MARROW ASPIRATION
Bone Marrow Needles
Parts of the Bone Marrow Needle
Sites for Bone Marrow Aspirate
Evaluation of Bone Marrow Aspirate
Indications for Bone Marrow Aspiration
Contraindications
Dry Tap
BONE MARROW TREPHINE BIOPSY
Sites of Trephine Biopsy
Indications for Trephine Biopsy
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 46:
Osmotic Fragility Test
INTRODUCTION
PRINCIPLE
PROCEDURE
INTERPRETATION
Use
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWER
CHAPTER 47:
Cytochemistry in Leukemia
DEFINITION
Main Uses of Cytochemistry
MYELOPEROXIDASE
Interpretation
SUDAN BLACK B
Interpretation
NONSPECIFIC ESTERASE
Interpretation
PERIODIC ACID SCHIFF REACTION
NEUTROPHIL ALKALINE PHOSPHATASE
NAP/LAP Score
Increased
Decreased
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 48:
Laboratory Evaluation of Hemostatic and Thrombotic Disorders
INTRODUCTION
TESTS FOR PLATELET COMPONENT
Platelet Count
Platelet Aggregation
Clot Retraction Test
Procedure
TESTS FOR PLATELET AND VASCULAR COMPONENT
Capillary Fragility Test (Hess test/tourniquet test)
Procedure
Bleeding Time (BT)
Methods
Template Method for BT
Normal Range: 2-9 Minutes
TESTS FOR COAGULATION COMPONENT
Coagulation or Clotting Time (Lee-White Method)
Procedure
Normal: 4-11 Minutes Disadvantages
Specimen Collection for Coagulation Studies
Quick's One Stage Prothrombin Time
Reagents Required
Procedure
Normal Range: 11-16 Seconds
Reporting of Prothrombin Time
Uses
Precautions
Activated Partial Thromboplastin Time (Partial Thromboplastin Time)
Reagents Required
Procedure
Normal Range: 30-40 Seconds
Uses
Interpretation
Thrombin Time (TT)
Reagents Required
Procedure
Use
TESTS FOR FIBRINOLYTIC ACTIVITY
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 49:
Flow Cytometry
INTRODUCTION
Specimen
Components of FCM (Fig. 49.1)
APPLICATIONS OF FLOW CYTOMETRY
SUMMARY
SELF-ASSESSMENT EXERCISE
Multiple Choice Question
ANSWER
CHAPTER 50:
Urine Analysis
INTRODUCTION
Collection of Urine Specimen
Preservation of Urine
Examination of Urine
PHYSICAL EXAMINATION
Volume
Polyuria
Nocturia
Oliguria
Anuria
Color (Table 50.2)
Chyluria
Lipiduria
Transparency and Turbidity
Odor (Table 50.3)
Reaction (pH)
Cause
Specific Gravity
Urinometer Method
Refractometer Method
Dipstick Method
Causes
Interpretation
CHEMICAL EXAMINATION
Proteinuria
Heat and Acetic Acid Test
Sulfosalicylic Acid Test
Heller's Test
Dipstick Method
Quantitative Estimation of Proteins in Urine
Causes of Proteinuria (albuminuria)
Reducing Substances in Urine
Benedict Qualitative test (semiquantitative)
Dipstick Method
Ketone Bodies
Rothera's Test
Gerhardt's Test (ferric chloride test)
Hart's Test
Dipstick Method
Bilirubin (bile pigment)
Fouchet's Test
Dipstick Method
Causes of Bilirubinuria
Urobilinogen
Ehrlich's Test
Dipstick Method
Causes of Increased Urobilinogen in Urine
Causes of Decreased/Absent Urobilinogen in Urine
Bile Salts
Hay's Sulfur Test
Tests for Blood in Urine
Benzidine Test
Orthotoluidine Test
Dipstick Method
Causes of Hematuria
Hemoglobinuria
Multistix Reagent Strips for Urine Testing
Automated Urinalysis
MICROSCOPIC EXAMINATION
Organized Deposit
Unorganized Sediments
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 51:
Body Fluids
INTRODUCTION
Specimen Collection
EXAMINATION OF BODY FLUIDS
Physical Examination
Chemical Examination
Microscopic Examination
Microbiological Examination
EXAMINATION OF SYNOVIAL FLUIDS
Physical Examination
Microscopic Examination
Chemical Examination
Microbiological Examination
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 52:
Cerebrospinal Fluid Examination
INTRODUCTION
Sites
Method of Collection
Indications for Lumbar Puncture
A. Diagnostic Indications
B. Therapeutic Indications
Contraindications for Lumbar Puncture
Complications of Lumbar Puncture
EXAMINATION OF CSF
Physical Examination
Microscopic Examination
Significance
Biochemical Evaluation
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 53:
Semen Analysis
INTRODUCTION
Indications for Semen Analysis
Collection of the Sample
DIFFERENT PROCEDURES OF SEMEN ANALYSIS
Standard Procedures
Physical Examination
Microscopic Examination
Tests for Antibody Coating of Spermatozoa
Optional Procedures
Indices of Multiple Sperm Defects
Panleukocyte (CD45) Immunocytochemical Staining
Interaction Between Spermatozoa and Cervical Mucus
Biochemical Assays for Accessory Sex Organ Function
Computer-aided Sperm Analysis
Research Procedures
CRYOPRESERVATION OF SPERMATOZOA
Indications for Cryopreservation
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 54:
Pregnancy Test
INTRODUCTION
Indications:
PREGNANCY TESTS
Immunological Tests for Pregnancy
Immunoassays without Radioisotopes
Immunoassays with Radioisotopes
Biologic Pregnancy Tests
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWER
CHAPTER 55:
Sputum Examination
INTRODUCTION
Sputum Collection
EXAMINATION OF SPUTUM
Physical Examination
Microscopic Examination
Cells
Other Structures
Parasites
Culture Study
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWER
CHAPTER 56:
Cytology
INTRODUCTION
Steps Involved in Processing of Cytological Smears
Specimen Collection
Fixation of Cytological Smears
Staining of Smears
Procedure for Pap Stain
CYTOLOGY OF FEMALE GENITAL TRACT
Lateral Vaginal Wall Smear
Uses of Vaginal Smear
Cervical Smear
CYTOLOGY OF OTHER SYSTEMS
Cytology of Respiratory Tract
Cytology of Gastrointestinal Tract
Cytology of Urinary Tract
BUCCAL SMEAR FOR BARR BODY
Leukocytes: Nuclear Sexing (Figs 56.5A and B)
FNAC APPEARANCE OF SOME COMMON LESIONS
Granulomatous (Tuberculous) Lymphadenitis (Fig. 56.6)
Pleomorphic Adenoma (Fig. 56.7)
Fibroadenoma Breast (Fig. 56.8)
Infiltrating Duct Carcinoma Breast (Fig. 56.9)
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 57:
Glucose Tolerance Test
ORAL GLUCOSE TOLERANCE TEST
Preparation of Individual
Procedure
Amount of Glucose to be Given in OGTT
Interpretation (Fig. 57.1)
Other Types of GTT
GLYCOSURIA
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 58:
Blood Group System
INTRODUCTION
ABO BLOOD GROUP SYSTEM
ABO Antigens
ABO Antibodies
Natural ABO Antibodies
Acquired ABO Antibodies
H Genes and H Antigens
Bombay Blood Group
ABO System and Disease
ABO Grouping Technique
Slide or Tile Technique
Tube Technique
Microplate Method
Microtyping System (Gel Card)
Rh BLOOD GROUP SYSTEM
Rh (D) System
Rh Antigen
Rh Antibodies
Clinical Significance
Rh (D) Typing Techniques
Slide or Tile Techniques
Tube Techniques
OTHER BLOOD GROUP SYSTEMS
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 59:
Antiglobulin Test
DIRECT ANTIGLOBULIN TEST
Materials Required
Technique (Fig. 59.1)
Interpretation
Uses of Direct Antiglobulin Test
INDIRECT ANTIGLOBULIN TEST
Materials Required
Technique (Fig. 59.1)
Interpretation
Uses of Indirect Antiglobulin Test
Controls for Antiglobulin Test
Gel Card Method (Figs 59.2A and B)
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 60:
Transfusion Medicine
BLOOD TRANSFUSION
Donor Selection
Collection of Blood
Predonation check-up
Compatibility Testing (Pretransfusion Testing)
Cross-matching (Tables 60.2 and 60.3)
Importance of cross-matching
Types
BLOOD COMPONENTS (FIG. 60.2)
Red Cells Concentrate or Packed Red Blood Cells (PRBCs)
Indications
Platelet Concentrate
Indications
Plasma
Fresh Frozen Plasma (FFP)
Indications
Cryoprecipitate AHF
Indication
Apheresis
Granulocyte Transfusion
TRANSFUSION REACTIONS
Noninfectious Complications
Immune Mediated (Immediate and Delayed) Reactions
Nonimmunological (Immediate and Delayed) Reactions
Infectious Complications
Exchange Transfusion
Indications
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 61:
Hematopoietic Stem Cell Transplantation
INTRODUCTION
Sources of Hematopoietic Stem Cells
Types of Hematopoietic Stem Cell Transplant
Indications for HSC transplantation (Table 61.1).
AUTOLOGOUS STEM CELL TRANSPLANT
Different steps of autologous stem cell transplantation (Fig. 61.1)
ALLOGENEIC STEM CELL TRANSPLANTATION
Different steps of allogeneic stem cell transplantation (Fig. 61.2)
COMPLICATIONS OF HSC TRANSPLANTATION
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 62:
Gastric Function Tests
TESTS FOR GASTRIC ACID SECRETION
Procedure
Stimulants Used for the Test
OTHER TESTS
Tests for Pepsin
Tests for Mucus
Test for Intrinsic Factor
Test for Blood
Test for Gastrin
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 63:
Liver Function Tests and Liver Biopsy
INTRODUCTION
Functions of Liver
LIVER FUNCTION TESTS
Tests for Excretory Functions
Bilirubin Metabolism
Causes of hyperbilirubinemia (Table 63.3).
Bromosulphthalein Excretion
Bile Acids (bile salts)
Tests of Liver Cell Injury
Enzymes that Detect Hepatocellular Injury
Serum aspartate transaminase (AST)
Serum alanine transaminase (ALT)
AST/ALT ratio
Enzymes that Detect Cholestasis
Tests of Metabolism and Biosynthesis
Plasma Protein Synthesis
Serum Ammonia
Serum Gamma Globulins (immunoglobulins)
Lipid and Lipoprotein Metabolism
Carbohydrate Metabolism
Immunologic Tests
Nonspecific Immunologic Reactions
Specific Antigens/Antibodies
Ancillary Diagnostic Tests
Alpha Fetoprotein
Ultrasonography
FNAC and/or Liver Biopsy
LIVER BIOPSY
Before the Biopsy
Needle
Procedure
Indications
Contraindications
Complications
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 64:
Renal Function Tests
TESTS FOR RENAL FUNCTION
Blood Chemistry
Renal Clearance Tests
Inulin Clearance Test
Creatinine Clearance
Urea Clearance Test
Concentration/Dilution Tests
Urine Specific Gravity
Concentration Test
Dilution Test
RENAL BIOPSY
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
CHAPTER 65:
Thyroid Function Tests
INTRODUCTION
Indications
Screening for Thyroid Dysfunction
Surveillance
Monitoring
THYROID FUNCTION TESTS (TABLE 65.1)
Serum Thyroid Hormones
Thyroid Stimulating Hormone/thyrotrophin (TSH)
Thyroid Hormone Levels
Thyrotrophin Releasing Hormone (TRH) Stimulation Test
Thyroglobulin (Tg)
Calcitonin Level
Thyroid Autoantibody Tests
Radioactive Iodine Uptake (RAIU)
Thyroid Scan
SUMMARY
SELF-ASSESSMENT EXERCISES
ANSWERS
Appendix
WHO CLASSIFICATION OF TUMORS OF HEMATOPOIETIC AND LYMPHOID TISSUES
Bibliography
INDEX
TOC
Index
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