| Preface |
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xi | |
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1 Molecular Biology of the Cell |
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1 | (26) |
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Compartmentalization of the Cell |
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1 | (2) |
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1 | (2) |
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Gene Transcription and Messenger RNA Translation: The Production and Journey of mRNA |
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3 | (3) |
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DNA Mutations can Alter Protein Synthesis by a Number of Mechanisms |
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6 | (1) |
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Transcriptional Control of Gene Expression |
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6 | (8) |
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Cis-Elements and Transcription Factors |
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8 | (1) |
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Chromatin and Epigenetic Control of Gene Expression |
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9 | (5) |
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Transcription Factors, Control of Gene Expression, and Lineage Commitment |
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14 | (2) |
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16 | (1) |
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Regulatory Noncoding RNAs |
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16 | (1) |
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DNA Replication and Telomeres |
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16 | (1) |
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Mutations and How They Result in Disease |
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17 | (2) |
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19 | (1) |
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20 | (1) |
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21 | (1) |
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21 | (1) |
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Link Between Metabolism and Gene Expression |
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22 | (4) |
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Removal Of Circulating and Cellular Debris by Lysosomes |
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26 | (1) |
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26 | (1) |
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27 | (10) |
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27 | (1) |
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Road Maps of Hematopoiesis |
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27 | (5) |
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Cellular Pathways as HSCs Differentiate Into Terminally Mature Cells |
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27 | (5) |
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Transcriptional Control of Hematopoiesis |
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32 | (1) |
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33 | (4) |
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3 Growth Factor Signaling |
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37 | (10) |
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Signaling at Different Stages of Hematopoiesis |
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37 | (1) |
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38 | (1) |
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Signaling Pathways Downstream of Receptors |
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39 | (7) |
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39 | (1) |
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Cytokine Signaling Pathways |
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40 | (1) |
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The RASIMAP Kinase Pathway |
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41 | (1) |
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Phosphatidylinositol 3-Kinase Pathway |
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41 | (1) |
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41 | (5) |
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Mutations in Signaling Components Leading to Clonal Hematologic Disorders |
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46 | (1) |
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4 Erythropoiesis and Examination of the Peripheral Blood and Bone Marrow |
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47 | (6) |
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47 | (2) |
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Examination of Peripheral Blood and the Bone Marrow |
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49 | (1) |
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Erythroid Cells in the Bone Marrow and Peripheral Blood |
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49 | (4) |
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53 | (16) |
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53 | (2) |
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55 | (1) |
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55 | (1) |
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55 | (1) |
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55 | (7) |
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Blood and Bone Marrow Appearances |
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56 | (1) |
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Causes of Iron Deficiency |
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57 | (5) |
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Iron-Refractory Iron-Deficiency Anemia (IRIDA) |
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62 | (1) |
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62 | (5) |
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Congenital Sideroblastic Anemia |
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63 | (4) |
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67 | (1) |
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67 | (1) |
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Differential Diagnosis of Hypochromic Microcytic Anemias |
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68 | (1) |
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6 The Porphyrias and Iron Overload |
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69 | (7) |
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Congenital Erythropoietic Porphyria |
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69 | (2) |
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Congenital Erythropoietic Protoporphyria |
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71 | (1) |
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71 | (5) |
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71 | (3) |
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Rare Causes of Iron Overload |
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74 | (1) |
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Hereditary Hyperferritinemia with Autosomal Dominant Congenital Cataract Syndrome |
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74 | (2) |
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76 | (13) |
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77 | (4) |
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Blood Count and Blood Film Appearances |
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79 | (2) |
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81 | (1) |
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Causes of Megaloblastic Anemia |
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81 | (8) |
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81 | (3) |
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84 | (1) |
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Abnormalities of Vitamin β12 or Folate Metabolism |
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84 | (2) |
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86 | (3) |
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89 | (17) |
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Hereditary Hemolytic Anemia |
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91 | (8) |
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91 | (1) |
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Red Cell Blood Group Antigens |
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91 | (1) |
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92 | (1) |
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Hereditary Elliptocytosis |
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92 | (2) |
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Normal Red Cell Metabolism |
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94 | (2) |
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Hemolytic Anemias Associated with Inherited Defects of Enzymes |
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96 | (3) |
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Acquired Hemolytic Anemia |
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99 | (7) |
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Autoimmune Hemolytic Anemias |
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99 | (2) |
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101 | (1) |
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Drug-Induced Immune Hemolytic Anemia |
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101 | (1) |
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Isoimmune Hemolytic Anemia |
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101 | (1) |
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Red Cell Fragmentation Syndromes |
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101 | (1) |
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Secondary Hemolytic Anemias |
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102 | (1) |
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Paroxysmal Nocturnal Hemoglobinuria |
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103 | (1) |
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104 | (2) |
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9 Genetic Disorders of Hemoglobin |
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106 | (24) |
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106 | (12) |
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108 | (7) |
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β-Thalassemia Intermedia (Nontransfusion-Dependent Thalassemia) |
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115 | (2) |
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117 | (1) |
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β-Thalassemia with A Dominant Phenotype |
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117 | (1) |
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118 | (1) |
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118 | (4) |
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X-linked α-Thalassemia and Mental Retardation Syndrome |
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119 | (3) |
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Structural Hemoglobin Variants |
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122 | (8) |
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122 | (6) |
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Other Structural Hemoglobin Defects |
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128 | (1) |
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128 | (1) |
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129 | (1) |
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10 Benign Disorders of Phagocytes |
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130 | (25) |
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Granulopoiesis and Monocyte Production |
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130 | (1) |
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131 | (2) |
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Mononuclear Phagocytic System |
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133 | (1) |
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Reticuloendothelial System |
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133 | (4) |
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Hereditary Variation in White Cell Morphology |
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137 | (3) |
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137 | (1) |
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138 | (1) |
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Chediak--Higashi Syndrome |
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139 | (1) |
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Alder (Alder--Reilly) Anomaly |
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139 | (1) |
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Myeloperoxidase Deficiency |
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139 | (1) |
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Neutrophil-Specific Granule Deficiency |
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139 | (1) |
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Mucopolysaccharidoses VI and VII |
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139 | (1) |
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Dorfman--Chanarin Syndrome |
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140 | (1) |
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Lysinuric Protein Intolerance |
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140 | (1) |
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Disorders of Phagocytic Function |
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140 | (2) |
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Chronic Granulomatous Disease |
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140 | (1) |
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Papillon--Lefevre Syndrome |
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141 | (1) |
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141 | (1) |
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Leukocyte Adhesion Deficiency |
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141 | (1) |
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142 | (1) |
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142 | (3) |
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Neutrophil Leukocytosis (Neutrophilia) |
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142 | (1) |
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143 | (1) |
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Eosinophil Leukocytosis (Eosinophilic) |
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143 | (1) |
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Monocytosis and Basophil Leukocytosis |
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143 | (1) |
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144 | (1) |
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Leukoerythroblastic Reaction |
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145 | (1) |
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146 | (3) |
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Severe Congenital Neutropenia |
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146 | (2) |
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Idiopathic Cytopenias of Undetermined Significance |
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148 | (1) |
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149 | (1) |
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149 | (1) |
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Lysosomal Storage Diseases |
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150 | (5) |
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150 | (1) |
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151 | (2) |
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Sea-Blue Histiocyte Syndrome |
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153 | (2) |
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11 Benign Disorders of Lymphocytes and Plasma Cells |
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155 | (30) |
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155 | (2) |
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156 | (1) |
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Chimeric Antigen Receptor Cells |
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157 | (1) |
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157 | (3) |
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160 | (2) |
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Lymphocyte Proliferation and Differentiation |
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162 | (2) |
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Somatic Hypermutation In Normal B Cells |
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164 | (1) |
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164 | (1) |
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165 | (1) |
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165 | (2) |
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165 | (2) |
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167 | (1) |
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168 | (1) |
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Sinus Histiocytosis with Massive Lymphadenopathy (Rosai--Dorfman Disease) |
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168 | (1) |
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Primary Immunodeficiency Disorders |
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168 | (17) |
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Acquired Immunodeficiency Syndrome |
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170 | (10) |
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Autoimmune Lymphoproliferative Syndrome |
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180 | (5) |
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12 Aplastic and Dyserythropoietic Anemias |
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185 | (13) |
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185 | (8) |
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185 | (1) |
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Inherited Aplastic Anemia |
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186 | (5) |
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191 | (2) |
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193 | (2) |
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193 | (2) |
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Congenital Dyserythropoietic Anemias |
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195 | (3) |
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13 The Hematologic Neoplasms: Laboratory Techniques and Acute Myeloid Leukemia |
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198 | (43) |
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198 | (10) |
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198 | (1) |
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Flow Cytometric Immunophenotyping |
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199 | (2) |
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201 | (1) |
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Fluorescence in Situ Hybridization |
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201 | (1) |
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Molecular Genetic Analysis |
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201 | (7) |
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208 | (33) |
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212 | (1) |
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212 | (2) |
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214 | (1) |
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214 | (11) |
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Classification of Myeloid Neoplasms with Germline Predisposition |
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225 | (4) |
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Acute Leukemias of Ambiguous Lineage |
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229 | (1) |
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Specific Diagnostic Aspects in AMI |
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229 | (12) |
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14 Acute Lymphoblastic Leukemia |
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241 | (15) |
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241 | (1) |
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B-Lymphoblastic Leukemia/Lymphoma, BCR-ABLI -Like |
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241 | (1) |
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B-All with Intrachromosomal Amplification of Chromosome 21 |
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242 | (1) |
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T-Lymphoblastic Leukemia/Lymphoma |
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242 | (1) |
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Early T-Cell Precursor All |
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242 | (1) |
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Acute Natural Killer Cell Leukemia |
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242 | (1) |
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242 | (2) |
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244 | (2) |
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246 | (1) |
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247 | (1) |
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Fluorescence in Situ Hybridization |
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248 | (1) |
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248 | (2) |
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248 | (1) |
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248 | (2) |
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250 | (6) |
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250 | (2) |
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252 | (4) |
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15 Myelodysplastic Syndromes |
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256 | (15) |
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256 | (7) |
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256 | (7) |
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Cytogenetic Abnormalities |
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263 | (1) |
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263 | (5) |
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266 | (1) |
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266 | (1) |
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266 | (2) |
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268 | (1) |
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268 | (1) |
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Molecular Genetics During Follow-Up |
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268 | (1) |
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268 | (1) |
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Clonal Hematopoiesis of Indeterminate Potential |
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269 | (2) |
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16 Myeloproliferative Neoplasms |
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271 | (31) |
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Chronic Myeloid Leukemia, BCR-ABLI+ |
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271 | (6) |
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272 | (1) |
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273 | (3) |
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276 | (1) |
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Chronic Neutrophilic Leukemia |
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277 | (1) |
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The Nonleukemic Myeloproliferative Diseases |
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277 | (18) |
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279 | (3) |
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282 | (1) |
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Essential Thrombocythemia |
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283 | (5) |
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288 | (7) |
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Leukemic Transformation of Polycythemia Vera and Myelofibrosis |
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295 | (5) |
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Chronic Eosinophilic Leukemia, Not Otherwise Specified |
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300 | (1) |
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Myeloproliferative Disorder Unclassifiable |
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300 | (2) |
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17 Mastocytosis, Myeloid/Lymphoid Neoplasms with Eosinophilia and Specific Cytogenetic Rearrangements, Myelodysplastic/Myeloproliferative Neoplasms |
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302 | (15) |
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302 | (7) |
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303 | (6) |
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309 | (1) |
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309 | (1) |
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Myeloid/Lymphoid Neoplasms with Eosinophilic and Abnormalities of PDGFRA, PDGFRB or FGFRI, or with PCM1-JAK2 |
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309 | (3) |
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Chronic Myelomonocytic Leukemia |
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311 | (1) |
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Atypical Chronic Myeloid Leukemia, BCR-ABLI |
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312 | (1) |
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Myelodysplastic/Myeloproliferative Neoplasms With Ring Sideroblasts and Thrombocytosis |
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312 | (2) |
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Juvenile Myelomonocytic Leukemia |
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314 | (3) |
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314 | (1) |
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315 | (2) |
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18 Chronic Lymphocytic Leukemia and Other Mature B-and T-Cell Leukemias |
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317 | (18) |
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317 | (11) |
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Chronic Lymphocytic Leukemia |
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317 | (8) |
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B-Cell Prolymphocytic Leukemia |
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325 | (2) |
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327 | (1) |
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328 | (7) |
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T-Cell Prolymphocytic Leukemia |
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328 | (2) |
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T-Cell Large Granular Lymphocytic Leukemia |
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330 | (3) |
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Adult T-Cell Leukemia/Lymphoma |
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333 | (1) |
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Aggressive NK-Cell Leukemia |
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333 | (2) |
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19 Small B-Cell Lymphomas |
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335 | (26) |
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336 | (1) |
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336 | (1) |
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Genetic and Molecular Abnormalities |
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337 | (1) |
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Clinical Features and Diagnosis |
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337 | (4) |
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341 | (1) |
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342 | (3) |
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Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia |
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345 | (1) |
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Monoclonal Gammopathy of Undetermined Significance IgM+ |
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346 | (1) |
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346 | (2) |
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Splenic Marginal Zone Lymphoma |
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348 | (1) |
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Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue (Malt Lymphoma) |
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349 | (2) |
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Nodal Marginal Zone B-Cell Lymphoma |
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351 | (1) |
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352 | (4) |
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Other Subtypes of Follicular Lymphomas |
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355 | (1) |
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356 | (5) |
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20 Aggressive Mature B-Cell Neoplasms |
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361 | (15) |
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Diffuse Large B-Cell Lymphoma, Nos |
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361 | (4) |
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T-Cell/Histiocytic-Rich Large B-Cell Lymphoma |
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365 | (1) |
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Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type |
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365 | (1) |
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Lymphomatoid Granulomatosis |
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365 | (1) |
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Primary Mediastinal (Thymic) Large B-Cell Lymphoma |
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365 | (1) |
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Intravascular Large B-Cell Lymphoma |
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366 | (1) |
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ALK-Positive Diffuse Large B-Cell Lymphoma |
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366 | (4) |
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370 | (1) |
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Primary Effusion Lymphoma and Other HHV8-Related Disorders |
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370 | (1) |
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371 | (1) |
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High Grade B-Cell Lymphoma |
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372 | (4) |
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21 Myeloma and Related Neoplasms |
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376 | (23) |
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Multiple (Plasma Cell) Myeloma |
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376 | (7) |
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383 | (1) |
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383 | (1) |
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Smoldering (Asymptomatic) Myeloma |
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383 | (1) |
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383 | (1) |
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Solitary Plasmacytoma of Bone |
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383 | (1) |
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Extraosseous (Extramedullar) Plasmacytoma |
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383 | (1) |
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384 | (1) |
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Other Causes of Serum M-Proteins |
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384 | (5) |
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Monoclonal Gammopathy of Uncertain Significance |
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387 | (2) |
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389 | (1) |
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389 | (10) |
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392 | (1) |
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392 | (2) |
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Reactive Systemic (AA) Amyloidosis |
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394 | (1) |
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Light Chain Deposition Disease |
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394 | (5) |
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22 Peripheralt-and NK-Cell Neoplasms |
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399 | (19) |
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Mature T- and NK-Cell Neoplasms |
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399 | (1) |
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Epstein-Barr Virus Positive T-Cell Lymphoproliferative Diseases of Childhood |
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399 | (1) |
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Chronic Active EBV Infection: Hydroa Vacciniforme-Like Lymphoproliferative Disorder |
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399 | (1) |
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Systemic EBV+ T-Cell Lymphoma Of Childhood |
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400 | (1) |
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Extranodal NK-/T-Cell Lymphoma, Nasal Type |
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400 | (1) |
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Enteropathy-Associated T-Cell Lymphoma |
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401 | (1) |
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Hepatosplenic T-Cell Lymphoma |
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402 | (2) |
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Primary Cutaneous T-Cell Lymphomas |
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404 | (1) |
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Subcutaneous Panniculitis-Like T-Cell Lymphoma |
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404 | (1) |
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405 | (2) |
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Folliculotrophic Mycosis Fungoides (Mycosis Fungoides-Associated Follicular Mucinosis) |
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406 | (1) |
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406 | (1) |
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Granulomatous Slack Skin Disease |
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406 | (1) |
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407 | (1) |
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Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders |
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408 | (2) |
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409 | (1) |
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Primary Cutaneous Anaplastic Large Cell Lymphoma |
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409 | (1) |
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Primary Cutaneous γδT-Cell Lymphoma |
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410 | (1) |
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Primary Cutaneous Aggressive Epidermotrophic CD8+ T-Cell Lymphoma (Provisional Category) |
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410 | (1) |
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Primary Cutaneous Small/Medium CD4+ T-Cell Lymphoproliferative Disorder (Provisional Category) |
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411 | (1) |
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Peripheral T-Cell Lymphoma, Not Otherwise Specified |
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411 | (1) |
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Angioimmunoblastic T-Cell Lymphoma |
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412 | (1) |
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Anaplastic Large Cell Lymphoma, ALK Positive |
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413 | (1) |
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Anaplastic Large Cell Lymphoma, ALK Negative |
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414 | (4) |
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418 | (16) |
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Presentation and Evolution |
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418 | (1) |
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418 | (3) |
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Hodgkin Reed-Stemberg Cell |
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419 | (2) |
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Classification of Hodgkin Lymphoma |
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421 | (3) |
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Nodular Sclerosing Hodgkin Lymphoma |
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421 | (1) |
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Mixed Cellularity Hodgkin Lymphoma |
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422 | (1) |
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Lymphocyte-Rich Classic Hodgkin Lymphoma |
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422 | (1) |
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Lymphocyte-Depleted Hodgkin Lymphoma |
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423 | (1) |
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Nodular Lymphocyte-Predominant Hodgkin Lymphoma |
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423 | (1) |
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424 | (8) |
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427 | (5) |
|
|
|
432 | (2) |
|
|
|
434 | (17) |
|
Hemophagocytic Lymphohistiocytosis (Hemophagocytic Syndrome) |
|
|
434 | (1) |
|
|
|
435 | (1) |
|
|
|
435 | (4) |
|
Histiocytic and Dendritic Cell Neoplasms |
|
|
439 | (1) |
|
|
|
439 | (1) |
|
Langerhans Cell Histiocytosis |
|
|
439 | (5) |
|
|
|
444 | (1) |
|
Indeterminate Dendritic Cell Tumor |
|
|
444 | (1) |
|
Interdigitating Dendritic Cell Sarcoma |
|
|
444 | (2) |
|
Follicular Dendritic Cell Sarcoma |
|
|
446 | (1) |
|
Fibroblastic Reticular Cell Tumor |
|
|
447 | (1) |
|
Disseminated Juvenile Xanthogranuloma |
|
|
447 | (1) |
|
|
|
447 | (1) |
|
Blastic Plasmacytoid Dendritic Cell Neoplasm |
|
|
448 | (3) |
|
25 Stem Cell Transplantation |
|
|
451 | (17) |
|
Human Leukocyte Antigen System |
|
|
451 | (1) |
|
Human Leukocyte Antigen Nomenclature |
|
|
451 | (1) |
|
Typing of Human Leukocyte Antigens |
|
|
452 | (1) |
|
Other Human Leukocyte Antigens |
|
|
452 | (1) |
|
Stem Cell Transplantation |
|
|
452 | (16) |
|
Nonmyeloablative (Reduced Intensity) Transplants |
|
|
453 | (2) |
|
|
|
455 | (2) |
|
Complications of Stem Cell Transplants |
|
|
457 | (2) |
|
Graft-Versus-Host Disease |
|
|
459 | (4) |
|
Post-Transplant Lymphoproliferative Disorders |
|
|
463 | (5) |
|
26 Normal Hemostasis, Platelet Production and Function |
|
|
468 | (11) |
|
|
|
470 | (1) |
|
Regulation of Coagulation |
|
|
470 | (2) |
|
Megakaryocyte and Platelet Production |
|
|
472 | (3) |
|
Platelet and Von Willebrand Factor Function |
|
|
475 | (4) |
|
27 Vascular and Platelet Bleeding Disorders |
|
|
479 | (15) |
|
Vascular Bleeding Disorders |
|
|
479 | (1) |
|
Hereditary Hemorrhagic Telangiectasia (Osler--Weber--Rendu Syndrome) |
|
|
479 | (1) |
|
|
|
479 | (1) |
|
|
|
479 | (1) |
|
|
|
479 | (1) |
|
Purpura Associated with Protein Deposition |
|
|
479 | (1) |
|
Immune-Mediated Vessel Wall Purpuras |
|
|
480 | (1) |
|
Platelet Bleeding Disorders |
|
|
480 | (14) |
|
|
|
480 | (7) |
|
Disorders of Platelet Function |
|
|
487 | (7) |
|
28 Inherited and Acquired Coagulation Disorders |
|
|
494 | (16) |
|
Hereditary Coagulation Disorders |
|
|
494 | (10) |
|
|
|
494 | (9) |
|
|
|
503 | (1) |
|
Other Hereditary Coagulation Disorders |
|
|
503 | (1) |
|
Acquired Coagulation Disorders |
|
|
504 | (6) |
|
|
|
504 | (1) |
|
Overdosage with Anticoagulants |
|
|
505 | (1) |
|
Disseminated Intravascular Coagulation |
|
|
505 | (2) |
|
Acquired Coagulation Factor Inhibitor |
|
|
507 | (2) |
|
Thromboelastometry and Throrvboelastography |
|
|
509 | (1) |
|
29 Thrombosis and Antithrombotic Therapy |
|
|
510 | (18) |
|
|
|
510 | (1) |
|
|
|
510 | (5) |
|
|
|
510 | (5) |
|
Acquired Risk Factors For Venous Thrombosis |
|
|
515 | (1) |
|
Antiphospholipid Syndrome |
|
|
515 | (1) |
|
Diagnosis of Venous Thrombosis |
|
|
515 | (1) |
|
Clinical Probability Assessment |
|
|
515 | (1) |
|
Diagnosis of Pulmonary Embolus |
|
|
516 | (3) |
|
|
|
516 | (3) |
|
|
|
519 | (1) |
|
|
|
519 | (1) |
|
|
|
519 | (1) |
|
|
|
519 | (1) |
|
Glycoprotein IIB/IIIA Inhibitors |
|
|
519 | (1) |
|
|
|
520 | (1) |
|
|
|
520 | (3) |
|
|
|
520 | (2) |
|
|
|
522 | (1) |
|
Indirect Factor Xa Inhibitors |
|
|
523 | (1) |
|
Direct Factor Xa Inhibitors |
|
|
523 | (1) |
|
Direct Thrombin Inhibitors |
|
|
523 | (1) |
|
|
|
523 | (4) |
|
|
|
527 | (1) |
|
30 Hematologic Aspects of Systemic Diseases |
|
|
528 | (20) |
|
Anemia of Chronic Disorders |
|
|
528 | (1) |
|
Malignant Diseases (Other than Leukemias, Lymphomas, Histiocytic and Myeloproliferative Disorders) |
|
|
529 | (1) |
|
Rheumatoid Arthritis and Other Connective Tissue Diseases |
|
|
530 | (3) |
|
|
|
533 | (1) |
|
|
|
533 | (5) |
|
|
|
538 | (1) |
|
|
|
539 | (3) |
|
|
|
539 | (2) |
|
|
|
541 | (1) |
|
Parasitic Infections Diagnosed In Blood |
|
|
542 | (1) |
|
Marrow Involvement In Other Infections |
|
|
542 | (1) |
|
Granulomatous Inflammation |
|
|
542 | (1) |
|
|
|
542 | (1) |
|
|
|
543 | (1) |
|
Osteopetrosis (Albers--Schonberg or Marble Bone Disease) |
|
|
543 | (1) |
|
|
|
544 | (1) |
|
|
|
544 | (3) |
|
|
|
547 | (1) |
|
|
|
548 | (8) |
|
|
|
548 | (4) |
|
Effects of Malaria on Various Organs |
|
|
549 | (1) |
|
Comparative Methods For Malaria Diagnosis |
|
|
549 | (3) |
|
Resistance to Antimalarial Therapy |
|
|
552 | (1) |
|
|
|
552 | (1) |
|
|
|
552 | (1) |
|
|
|
553 | (1) |
|
|
|
553 | (1) |
|
|
|
554 | (1) |
|
|
|
554 | (1) |
|
|
|
555 | (1) |
|
|
|
556 | (11) |
|
|
|
556 | (1) |
|
|
|
557 | (1) |
|
|
|
557 | (1) |
|
|
|
558 | (1) |
|
Blood Grouping and Cross-Matching |
|
|
559 | (1) |
|
|
|
559 | (1) |
|
Clinical Blood Transfusion |
|
|
560 | (1) |
|
Complications of Blood Transfusion |
|
|
560 | (4) |
|
|
|
561 | (2) |
|
|
|
563 | (1) |
|
Transfusion-Related Acute Lung Injury |
|
|
563 | (1) |
|
Graft-Versus-Host Disease |
|
|
563 | (1) |
|
|
|
564 | (3) |
|
|
|
564 | (1) |
|
|
|
564 | (1) |
|
|
|
565 | (1) |
|
|
|
565 | (2) |
| Appendix: 2016 World Health Organization Classification of Lymphoid and Myeloid Neoplasms |
|
567 | (4) |
| Index |
|
571 | |
