CHAPTER 1 Origin and Development of Blood Cells 21
Blood Formation in the Fetus 21
Theories of Blood Formation 22
Fetal Hemoglobin 23
Fetal Myoglobin 25
Bone Marrow at Birth,Infancy,and Childhood 25
CHAPTER 2 Blood Changes During Growth-Postnatal Period,Infancy,and Childhood 27
Blood Changes in the Newborn Infant 27
Physiologic Anemia of the Newborn Infant 28
Bone Marrow Changes 28
Blood Volume 28
Hemoglobin Concentration 28
Erythrocyte Count 29
Hematocrit Percentage(Volume of Packed Red Cells) 29
Size of Red Cells(MCV)and Hemoglobin Concentration(MCHC) 30
Reticulocytes 30
Normoblasts 30
Platelets 30
White Blood Cells 30
Blood of Premature Infants 31
CHAPTER 3 Blood Dyscrasias in Relation to Maternal-Fetal Interaction 34
Hereditary Basis of Blood Diseases-Genetic and Environmental Influences 34
Blood Dyscrasias in Relation to Congenital Anomalies-General Principles 34
Hematologic Aspects of Maternal and Fetal Interaction-Placental Physiology and Defects 35
Fetal Hemorrhage Into the Maternal Circulation(Nonhemolytic Anemia of the New-born Infant) 35
Bleeding From the Placental Surface 37
Placental Transmission of Antibodies and Isoagglutinins 37
Placental Transmission of the L．E．Factor 38
Plasma Proteins in the Fetus and Newborn Infant 39
Immunologic Relationships 39
Transplacental Passage of Drugs Affecting Blood Elements in the Newborn Infant 40
CHAPTER 4 Erythrocytes-General Considerations 43
Properties of the Erythrocyte 43
Iron Content and Oxygen Capacity 44
Porphyrins and Blood Disorders 45
Rouleaux Formation and Sedimentation 45
Electrolyte Considerations 45
Erythrocyte Production 47
Normal Destruction of Erythrocytes 52
CHAPTER 5 Erythrocytes-Morphologic Abnormalities 59
General Considerations 59
Abnormalities in Size 59
Abnormalities in Shape 60
Miscellaneous Changes 62
CHAPTER 6 Blood Groups 66
Blood Group Factors 66
Definitions of Terms in Relation to Blood Groups 66
ABO Blood Group System 67
Rh-Hr Blood Group System 69
MN,Ss,and P Blood Group Systems 71
Rh Variants 72
CHAPTER 7 Transfusions in Pediatric Practice 75
Significant Factors in Transfusion Therapy 75
Indications for Transfusions 75
Blood Volume-plasma,Total Circulating Hemoglobin,and Erythrocyte Mass 76
Hemoglobin and Hematocrit Levels in Acute and Chronic Anemias 77
Choice and Dosage of Whole Blood,Packed Erythrocytes,and Plasma 77
Transfusions in Premature Infants 79
Limitations and Hazards of Transfusions 79
Transfusion Therapy in Hemorrhagic Disorders 83
Notes on Technique and Preservation of Blood 83
CHAPTER 8 Jaundice-Differential Diagnosis in the Neonatal Period 85
Jaundice in the Early Neonatal Period 86
Physiologic Jaundice(Icterus Neonatorum) 86
Hyperbilirubinemia of the Newborn Infant Unrelated to Isoimmunization 87
Relation of Vitamin K to Hyperbilirubinemia,Kernicterus,and Hemolytic Anemia 88
Hereditary Spherocytosis 88
Hereditary Nonspherocytic Hemolytic Disease 89
Elliptocytic(Ovalocytic)Hemolytic Anemia 89
Heinz-Body Anemia in the Newborn Infant 89
Acute Hemolytic Anemia Related to Naphthalene 89
Infections in Newborn Infants 90
Cytomegalic Inclusion Disease 90
Congenital Toxoplasmosis 90
Chronic Idiopathic Jaundice(Dubin-Johnson Type,Dubin-Sprinz Disease) 90
Jaundice in the Later Neonatal Period 91
Prolonged Obstructive Jaundice 91
Obstructive Jaundice Complicating Erythroblastosis-Inspissated Bile Syndrome 92
Inspissated Bile Syndrome of Unknown Etiology 93
Atresia of the Bile Ducts 94
Management of Prolonged Obstructive Jaundice 94
Galactosemia 95
Congenital Familial Nonhemolytic Jaundice With Kernicterus 95
Jaundice and Carotenemia 96
Jaundice Due to Pyloric Stenosis 96
Jaundice and Hypothyroidism 96
Hematomas 96
Miscellaneous 96
CHAPTER 9 Erythroblastosis Fetalis(Hemolytic Anemia of the Newborn Infant)-General Considerations 100
Definition 100
Pathogenesis 100
Clinical Features 101
Detection of Early Jaundice of the Newborn Infant 101
Kernicterus 102
Pathology 103
Maternal Antibodies-Pienatal Testing 104
Maternal Anti-Rh Titer 104
Effect of Previous Transfusions on the Mother 105
Immunization in the Rh-Positive Mother and Infant 105
Heterozygons and Homozygous Status of the Husband 105
Different Types of Antibodies 105
Transmission of Antibodies 106
Coombs Test(Antiglobulin Test) 106
Tests With Trypsinized Cells 107
Elution 107
Frequency of Blood Group Factors Causing Erythroblastosis 107
Prognostic Considerations and Family Patterns of Severity 108
Laboratory Findings-Blood 109
CHAPTER 10 Erythroblastosis Fetalis(Hemolytic Anemia of the Newborn Infant)-Treatment 114
Objectives of Treatment 114
Indications for Exchange Transfusions 115
Induction of Labor 119
Technique of Exchange Transfusions 120
Miscellaneous Treatment 124
Total Management of the Infant With Erythroblastosis 125
Treatment of the Infant in Cardiac Failure 127
Exchange Transfusion in Physiologic Hyperbilirubinemia of the Full-Term and Premature Infant 127
Exchange Transfusions as a Treatment of Poisonings 128
ABO Erythroblastosis 128
Clinical Features 129
Laboratory Findings-Blood 129
Relation of ABO Compatibility and Rh Immunization 131
Treatment 132
Differential Diagnosis 133
CHAPTER 11 Anemias-General Considerations 137
Classification 137
Orientation 138
Diagnosis 138
Principles of Treatment 155
Allergic Implications of Blood Disorders 155
CHAPTER 12 Iron-Deficiency Anemia 159
Etiology 159
Relation of Physiologic Anemia of the Newborn Infant to Iron-Deficiency Anemia 161
Clinical Features 162
Laboratory Data 163
Diagnosis 164
Treatment 165
Anemia of the Premature Infant 169
Management 170
Iron Transport-Serum Iron and Iron-Binding Capacity 171
Iron-Binding Capacity of Plasma in Various Clinical Conditions 172
Hemosiderosis and Hemochromatosis 174
Diagnostic Procedures 175
Treatment 175
Transient Dysproteinemia(Copper Deficiency in Infants) 175
Acute Iron Intoxication 176
Iron-Deficiency Anemia in Patients With Cyanotic Congenital Heart Disease 177
CHAPTER 13 Megaloblastic Anemia and Related Anemias 181
Megaloblastic Anemia of Infancy 182
Etiology 182
Clinical Features 183
Laboratory Findings 183
Treatment 183
Prognosis 184
Juvenile Pernicious Anemia 184
Etiology 184
Clinical Manifestations 185
Laboratory Findings 185
Diagnosis 186
Course and Prognosis 186
Treatment 186
Nutritional Megaloblastic Anemia 187
Miscellaneous Megaloblastic Anemias 187
Megaloblastic Anemia With Hermolytic Anemias 187
Megaloblastic Anemia With Hemochromatosis 188
Megaloblastic Anemia With Fish Tapeworm 188
Megaloblastic Anemia Caused by Anticonvulsant Therapy 188
Malabsorption Syndromes-Sprue(Tropical),Idiopathic Steatorrhea(Nontropical Sprue),and Celiac Disease 188
Normoblastic Macrocytic Anemias 189
CHAPTER 14 Hypoplastic and Aplastic Anemias 192
General Considerations 192
Classification 192
Hypoplastic Anemias 193
Idiopathic Hypoplastic Anemia-Pure Red Cell Anemia 193
Definition 193
Pathogenesis 194
Clinical Features 194
Laboratory Findings 195
Pathologic Findings 195
Diagnosis 195
Treatment 196
Acquired Hypoplastic Anemias 198
Anemia Due to Infections,Drugs,Chemicals,Toxins,and Autoimmune and Allergic States 198
Aplastic Crisis 198
Anemia Resulting from Suppressive Effect of Multiple Transfusions on Erythropoiesis 198
Miscellaneous 198
Aplastic Anemia(Bone Marrow Failure,Refractory Anemia) 199
Definition 199
Etiology 199
Idiopathic Aplastic Anemia 199
Congenital Aplastic Anemia With Multiple Congenital Anomalies(Fanconi Type) 200
Congenital Hypoplastic Anemia Without Associated Anomalies 201
Acquired(Secondary)Aplastic Anemias 201
Anemia Due to Antimicrobial and Other Chemotherapeutic Agents 201
Anemia Due to Industrial and Household Chemicals 201
Anemia Due to Irradiation 202
Miscellaneous Causes 202
Features Common to Idiopathic and Acquired Types of Aplastic Anemia 202
Pathology 202
Clinical Features 202
Laboratory Findings 203
Differential Diagnosis 203
Management 204
Course and Prognosis 206
CHAPTER 15 The Hemolytic Anemias 210
Definition-General Considerations of Pathogenesis 210
Classification 210
Principal Features of Increased Hemolysis 211
Evidence of Increased Marrow Activity 214
Additional Tests for Detecting Abnormal Hemolysis 215
Congenital Hemolytic Syndromes 218
Hereditary Spherocytosis(Congenital Hemolytic Jaundice,Congenital Hemolytic Anemia,Spherocytic Anemia,Chronic Acholuric Jaundice,Chronic Familial Jaundice) 219
Definition 219
Inheritance and Race 219
Etiology and Pathogenesis 219
Clinical Features 220
Growth 221
Laboratory Data 221
Hereditary Spherocytosis in the Newborn Period 222
Diagnosis 223
Treatment 223
Sporadic Congenital Spherocytosis Associated With Congenital Hypoplastic Throm-bocyopenia and Malformations 224
Hereditary Nonspherocytic Hemolytic Anemia(Atypical Familial Hemolytic Anamia,Congenital Nonspherocytie Anemia) 224
Hereditary Elliptocytosis With Hemolytic Anemia 225
Clinical and Blood Findings 226
Treatment 227
Hemolytic Anemia Due to Enzyme Deftciency Following Administration of Drugs and Other Agents 227
Nonhereditary Hemolytic Anemia-Paroxysmal Nocturnal Hemoglobinuria(Marchiafava-Micheli Syndrome) 228
Acquired Hemolytic Anemias 230
Autoimmune Hemolytic Anemia(Chronic Idiopathic Autoimmune Hemolytic Disease,Chronic Acquired Hemolytic Anemia) 231
Clinical Features 231
Blood Findings 231
Serologic Findings 232
Pathogenesis 232
Destruction of Sensitized Red Cells 233
Diagnosis 233
Treatment 233
Prognosis 234
Paroxysmal Cold Hemoglobinuria 235
Dysproteinemias 235
Acute Acquired Hemolytic Anemia(Lederer＇s Anemia) 235
Idiopathic Paroxysmal Myoglobinuria 236
March Hemoglobinuria 236
CHAPTER 16 The Hereditary Hemoglobinopathies 243
Methods for Determining the Hemoglobin Types 243
Designation of Hemoglobin Types 245
Electrophoretic Mobility of the Individual Hemoglobins 245
Fetal Hemoglobin 246
Hereditary Aspects 247
Relation of Genetic Composition to Clinical-Hematologic Variations 248
Target Cells 249
Syndromes Associated With the Abnormal Hemoglobins 250
Sickle Cell Disease 250
Sickling Phenomenon 250
Pathogenesis 252
Sickle Cell Trait 253
Incidence and Geographic Distribution 253
Clinical and Laboratory Features 253
Sickling and Malaria 253
Sickle Cell(Drepanocytic)Anemia 254
Pathology 254
Clinical Features 255
Skeletal Changes 257
Blood 258
Crises 259
Diagnosis 260
Treatment 261
Prognosis 262
Thalassamia(Cooley＇s Anemia,Mediterranean Anemia,Erythroblastic Anemia,Hereditary Leptocytosis) 262
Historical 262
Nomenclature 262
Race and Incidence 262
Genetic Transmission 263
Effect of the Gene for Thalassemia Upon Other Hemoglobins 263
Clinical Types 263
Fetal Hemoglobin in Patients With Thalassemia 265
Pathogenesis 265
Pathology 265
Clinical Features 266
Growth and Maturation 268
Skeletal Changes 268
Blood Picture 270
Hemosiderosis and Hemochromatosis 274
Red Cell Survival 274
Diagnosis 274
Course and Prognosis 276
Treatment 277
Homozygous Hemoglobin C Disease 279
Hemoglobin C Trait 279
Hemoglobin D 280
Hemoglobin E Disease 280
Hemoglobin G 281
Hemoglobin H 281
Hemoglobin I 282
Hemoglobin J 282
Hemoglobin M 283
Miscellaneous Abnormal Hemoglobins 283
Sickle Cell Variants 283
Sickle Cell-Thalassemia Disease(Microdrepanocytic Anemia) 283
Essential Features 284
Clinical Findings 285
Sickle Cell-Hemoglobin C Disease 285
Sickle Cell-Hereditary Spherocytosis 286
Sickle Cell-Hemoglobin D Disease 286
Thalassemia Variants 287
Thalassemia-Hemoglobin C Disease 287
Thalassemia-Hemoglobin E Disease 288
Thalassemia-Lepore Hemoglobin 289
CHAPTER 17 Polycythemia,Methemoglobinemia,Sulfhemoglobinemia,and Miscellaneous Anemias 299
Polyeythemia 299
Relative Polycythemia 299
Primary Polycythemia(Polycythemia Vera,Erythremia,Vaquez-Osier Disease) 300
Benign Familial Polycythemia 300
Secondary Polycythemia(Erythrocytosis,Erythrocythemia,Compensatory Polycythemia 300
Methemoglobinemia 301
Pathogenesis 301
Congenital(Familial)Methemoglobinemia 302
Congenital Methemoglobinemia Associated With Hemoglobin M 303
Drug-Induced Methemoglobinemia 303
Features Common to Methemoglobinemia 303
Diagnosis 303
Treatment 303
Methemoglobinemia in Young Infants 304
Sulfhemoglobinemia 304
Miscellaneous Anemias 305
Anemia of Chronic Renal Insufficiency 305
Pathogenesis 305
Laboratory Findings 305
Bone Marrow 306
Diagnosis 306
Treatment 306
Anemia of Infection 306
Pathogenesis 307
Blood Findings and Other Laboratory Data 307
Clinical Features 308
Treatment 308
Anemia of Acute Hemorrhage 308
Etiology 308
Blood Picture 308
Clinical Features 309
Treatment 309
Chronic Hemorrhagic Anemia 309
Etiology 309
Clinical and Laboratory Features 309
Treatment 310
Vitamin Deficiencies and Anemia 310
Anemia of Hypothyroidism 311
Blood Changes in Lead Poisoning 311
CHAPTER 18 Leukocytes-Cell Types 317
Growth and Multiplication 317
Chemotactic Factors 318
Functions-Phagocytosis and Antibody Formation 318
Erythrophagocytosis 319
L．E．Phenomenon 319
Life Span of Leukocytes 322
Leukoagglutinins 322
Types of White Cells 323
Granulocytic or Myeloid Series 323
Lymphocytes 331
Miscellaneous 334
Degenerative and Toxic Cytoplasmic Changes 337
Cell Stains 339
CHAPTER 19 Leukopenia and Leukopenic Syndromes 345
Pathogenesis 345
Causes 346
Treatment 351
CHAPTER 20 Leukocytosis,Leukemoid Reactions,and Lymphocytosis 354
Leukocytosis 354
Leukemoid Reactions 355
Lymphocytosis 356
Acute Infectious Lymphocytosis 357
Definition 357
Age 357
Etiology 357
Epidemiology 357
Pathology 357
Clinical Features 357
Incubation Period 358
Laboratory Findings 358
Differential Diagnosis 361
Treatment and Prognosis 363
Chronic Nonspecific Infectious Lymphocytosis(Low-Grade Fever Syndrome) 363
Clinical Picture 363
Blood 363
Differential Diagnosis 364
Treatment and Prognosis 365
CHAPTER 21 Infectious Mononucleosis 367
Definition 367
Historical 367
Pathology 367
Clinical Features 368
Laboratory Findings 371
Differential Diagnosis 375
Prognosis 375
Treatment 375
Recurrences 376
CHAPTER 22 Leukemia-General Aspects and Clinical Features 379
Classification of Leukemia in Childhood 379
Incidence,Age Distribution,Sex,and Frequency of Types 383
Etiology 384
Preleukemic Stage of Leukemia 387
Leukemia in the Newborn Period(Congenital Leukemia) 387
Spontaneous Remissions 388
Clinical Features 389
Differential Diagnosis 396
CHAPTER 23 Leukemia-Treatment 404
Treatment 404
Remissions-Criteria 413
Detailed Program of Treatment 413
Simplified Program of Treatment in Stem Cell(Lymphoblastic)Leukemia 418
Bone Marrow Transplantation 418
Laboratory Determinations 419
Treatment of Nervous System Involvement 419
Results of Treatment-Prognosis for Survival 419
CHAPTER 24 Leukemia-Allied Disorders 422
Infrequent Types of Leukemia 422
Bone Marrow Replacement and Leukoerythroblastosis 423
Myelofibrosis 423
Osteopetrosis(Marble-Bone Disease,Albers-Schonberg Disease) 424
Extramedullary Megakaryocytosis and Acute Megakaryocytic Leukemia 424
Thrombocythemia 425
Erythremic Myelosis(Di Guglielmo＇s Disease) 425
Chloroma and Chloroleukemia 426
Neoplasms of Lymphoid Tissue(Malignant Lymphomas) 426
CHAPTER 25 Disorders of the Spleen and the Reticuloendothelial System 436
Role of the Spleen in Blood Disorders 436
Structure of the Spleen 436
Normal Functions of the Spleen 436
Splenic Aspiration 438
Adrenalin Test in Diagnosis of Hypersplenic Syndromes 438
Indications for Splenectomy 438
Disorders of the Spleen 439
Splenomegaly 439
Hypersplenism 440
Congenital Absence of the Spleen 441
Primary Splenic Neutropenia 441
Felty＇s Syndrome 441
Primary Splenic Panhematopenia 441
Chronic Congestive Splenomegaly(Banti＇s Syndrome,Portal Hypertension,Splenic Anemia) 442
Etiology and Pathogenesis 442
Collateral Circulation 443
Pathology 443
Clinical Features 443
Laboratory Data 444
Diagnosis 444
Course and Prognosis 444
Treatment 444
Diseases of the Reticuloendothelial System 445
Gaucher＇s Disease 446
Pathology and Pathogenesis 446
Clinical Features 446
Blood 448
Heredity 448
Course and Treatment 448
Niemann-Pick Disease 448
Clinical Features 448
Pathology and Pathogenesis 449
Blood 449
Heredity 450
Treatment 450
Letterer-Siwe Disease,Hand-Schüller-Christian Disease,and Eosinophilic Granuloma 450
Letterer-Siwe Disease(Nonlipid Reticuloendotheliosis) 450
Pathology 450
Diagnosis 451
Blood 451
Treatment and Course 452
Hand-Schüller-Christian Disease 452
Clinical Features 452
Pathology 452
Diagnosis 453
Course 453
Treatment 453
Eosinophilic Granuloma 453
CHAPTER 26 Blood Coagulation 458
Normal Hemostatic Mechanisms 458
Disorders Due to a Deficiency of Factors Required for Thromboplastin Formation(Phase 1 of Coagulation) 464
General Consideration of the Hemophilias 464
Classic Hemophilia(Hemophilia A,AHG Defciency) 464
Hereditary Aspects 464
Clinical Aspects 465
Hemarthrosis 465
Management 466
Treatment of Bleeding 466
Treatment of Hemarthroses 469
Mild Hemophilia 470
Diagnosis 470
Roentgenographic Findings 470
Prognosis 471
Vascular Hemophilia(yon Willebrand＇s Disease,Pseudohemophilia B) 472
Plasma Thromboplastic Component Deficiency(Hemophilia B,Christmas Disease) 473
Clinical and Laboratory Features 473
Treatment 473
Plasma Thromboplastin Antecedent Defciency(Hemophilia C) 474
Clinical and Laboratory Features 474
Treatment 474
Disorders Due to a Deficiency of Factors Required for the Conversion of Prothrombin to Thrombin(Phase 2 of Coagulation) 474
General Considerations 474
Hypoprothrombinemia(Vitamin K and Prothrombin Deficiency) 475
Congenital Deficiencies 476
Idiopathic(Congenital)Hypoprothrombinemia 476
Labile Factor Deficiency(Factor Ⅴ Deficiency,Parahemophilia,Owren＇s Disease) 476
Stable Factor Deficiency(Factor Ⅶ Deficiency,Proconvertin Deficiency,Congenital Hypoproconvertinemia) 477
Hemorrhagic Disease of the Newborn Infant(Hypoprothrombinemia in the Newborn Infant) 477
Etiology-Prothrombin and Stable Factor Deficiency 477
Clinical and Laboratory Features 478
Differential Diagnosis 478
Treatment 479
Stuart-Prower Factor Deficiency 480
Multiple Defects 480
Capillary and Single Coagulation Factor Deficiency 480
Multiple Factor Deficiencies 481
Disorders Due to a Deficiency of Fibrinogen(Phase 3 of Coagulation) 481
Congenital Afibrinogenemia 481
Congenital Hypofibrinogenemia 481
Acquired Fibrinogen Deficiency 481
Hypofibrinogenemia in Patients With Congenital Heart Disease 481
Fibrinolysis(Fibrinolytic Purpura) 482
Laboratory Findings in Fibrinogen Deficiencies 482
Treatment of Fibrinogen Deficiencies 483
Circulating Anticoagulants 483
Summary of Replacement Therapy of the Coagulation Disorders 485
Epistaxis 486
Procedure for Screening Potential Bleeders 486
Laboratory Investigation of Coagulation Disorders 487
General Considerations 487