Hematology

1. Introduction - p. 350 2. Inherited Bone Marrow Failure Syndrome With Multi-Lineage Cytopenias - p. 350 3. Inherited Bone Marrow Failure Syndromes Predominantly with Anemia - p. 375 4. Inherited Bone Marrow Failure Syndromes with Predominantly Neutropenia - p. 386 5. Inherited Bone Marrow Failure Syndromes With Predominantly Thrombocytopenia - p. 393 6. Suggested Readings - p. 394 7. Chapter 31. Aplastic Anemia - p. 396 8. Chapter 32. Paroxysmal Nocturnal Hemoglobinuria - p. 416 9. Chapter 33. Acquired Disorders of Red Cell, White Cell, and Platelet Production - p. 431 10. Abstract - p. 431 11. Etiology and Classification - p. 431 12. Pathogenesis - p. 431 13. Primary Pure Red Cell Aplasia - p. 432 14. Secondary Forms of Pure Red Cell Aplasia - p. 432 15. Laboratory Evaluation - p. 434 16. Medical - p. 435 17. Hematopoietic Stem Cell Transplantation - p. 436 18. Secondary Forms of Neutropenias - p. 438 19. Laboratory Evaluation - p. 440 20. Nutritional Deficiencies - p. 448 21. Suggested Readings - p. 449 22. References - p. 449 23. Part V: Red Blood Cells - p. 449 24. Chapter 34. Pathobiology of the Human Erythrocyte and Its Hemoglobins - p. 451 25. Chapter 35. Approach to Anemia in the Adult and Child - p. 463 26. Chapter 36. Iron Homeostasis and Its Disorders - p. 473 27. Chapter 37. Disorders of Iron Homeostasis: Iron Deficiency and Overload - p. 483 28. Chapter 38. Anemia of Chronic Inflammation - p. 498 29. Chapter 39. Heme Biosynthesis and Its Disorders: Porphyrias and Sideroblastic Anemias - p. 507 30. Chapter 40. Megaloblastic Anemias - p. 524 31. Abstract - p. 524 32. Cobalamin - p. 524 33. Folates - p. 528 34. Intracellular One-Carbon Metabolism And Cobalamin–Folate Relationships - p. 531 35. Morphologic Expression Of Megaloblastosis - p. 533 36. Neurologic Dysfunction With Cobalamin Deficiency - p. 534 37. Other Effects Of Cobalamin And Folate Deficiency - p. 536 38. Spectrum Of Clinical Presentations With Cobalamin Deficiency - p. 536 39. Biochemical Indicators Of Evolving Deficiency - p. 536 40. Biochemical Evaluation Of Cobalamin And Folate Deficiencies - p. 537 41. Pathogenesis Of Cobalamin Deficiency - p. 540 42. Pathogenesis Of Folate Deficiency - p. 543 43. Megaloblastic Anemia Not Caused By Folate Or Cobalamin Deficiency - p. 547 44. Therapy - p. 547 45. Routine Supplementation Of Cobalamin And Folate - p. 551 46. Future Directions - p. 553 47. Suggested Readings - p. 553 48. References - p. 553 49. Chapter 41. Thalassemia Syndromes - p. 555 50. Abstract - p. 555 51. Definitions And Nomenclature - p. 555 52. Epidemiology - p. 555 53. Pathophysiology: General Principles - p. 555 54. BETA-Thalassemia Syndromes - p. 556 55. ALPHA-Thalassemia Syndromes - p. 579 56. Thalassemic Structural Variants - p. 583 57. Extraordinarily Unstable Hemoglobins - p. 584 58. References - p. 584 59. Suggested Readings - p. 584 60. Chapter 42. Pathobiology of Sickle Cell Disease - p. 585 61. Chapter 43. Clinical Aspects of Sickle Cell Disease - p. 599 62. Abstract - p. 599 63. Genetic Epidemiology of the Sickle Gene - p. 599 64. Variant Sickle Cell Syndromes - p. 599 65. Prevalence - p. 599 66. Clinical Laboratory Features and Diagnosis - p. 600 67. Clinical Presentation and Management - p. 602 68. Suggested Readings - p. 629 69. References - p. 629 70. Chapter 44. Hemoglobin Variants Associated With Hemolytic Anemia, Altered Oxygen Affinity, and Methemoglobinemias - p. 630 71. Chapter 45. Red Blood Cell Enzymopathies - p. 638 72. Chapter 46. Red Blood Cell Membrane Disorders - p. 650 73. Chapter 47. Autoimmune Hemolytic Anemia - p. 672 74. Chapter 48. Extrinsic Nonimmune Hemolytic Anemias - p. 688 75. Part VI: Non-Malignant Leukocytes - p. 696 76. Chapter 49. Neutrophilic Leukocytosis, Neutropenia, Monocytosis, and Monocytopenia - p. 698 77. Chapter 50. Lymphocytosis, Lymphocytopenia, Hypergammaglobulinemia, and Hypogammaglobulinemia - p. 708 78. Chapter 51. Disorders of Phagocyte Function - p. 717 79. Chapter 52. Congenital Disorders of Lymphocyte Function - p. 736 80. Chapter 53. Pediatric and Adult Histiocytic Disorders - p. 750 81. Chapter 54. Lysosomal Storage Diseases, Focusing On Gaucher Disease: Perspectives And Principles - p. 769 82. Chapter 55. Epstein-Barr Virus and Associated Lymphoproliferative Conditions - p. 782 83. Part VII: Hematologic Malignancies - p. 799 84. Chapter 56. Progress in the Classification of Hematopoietic and Lymphoid Neoplasms: Clinical Implications - p. 800 85. Chapter 57. Conventional and Molecular Cytogenomic Basis of Hematologic Malignancies - p. 813 86. Abstract - p. 813 87. Methods - p. 813 88. Myelodysplastic Syndromes - p. 833 89. Acute Myeloid Leukemia - p. 842 90. Acute Lymphoblastic Leukemia - p. 863 91. Chronic B-Cell Lymphocytic Leukemia (Chapter 76) - p. 871 92. Multiple Myeloma - p. 877 93. Lymphoma - p. 883 94. Hairy Cell Leukemia (Chapter 77) - p. 891 95. Allogeneic Hematopoietic Stem Cell Transplantation - p. 896 96. Future Directions - p. 897 97. References - p. 898 98. Chapter 58. Pharmacology and Molecular Mechanisms of Antineoplastic Agents for Hematologic Malignancies - p. 900 99. Abstract - p. 900 100. Tumor Cell Heterogeneity of Hematologic Malignancies - p. 900 101. Development of Chemotherapeutic Agents - p. 901 102. Traditional Cytotoxic Antineoplastic Agents Targeting the Cell Cycle and DNA - p. 902 103. Pharmacology of Traditional Chemotherapeutic Agents - p. 904 104. Pharmacology of Targeted Antineoplastic Agents - p. 912 105. Drug Resistance to Chemotherapeutic Agents or Multidrug Resistance - p. 931 106. Future Directions - p. 936 107. SUGGESTED READINGS - p. 936 108. Reference - p. 936 109. Chapter 59. Pathobiology of Acute Myeloid Leukemia - p. 937 110. Chapter 60. Clinical Manifestations and Treatment of Acute Myeloid Leukemia - p. 950 111. Chapter 61. Myelodysplastic Syndromes - p. 977 112. Abstract - p. 977 113. History - p. 977 114. Classification - p. 977 115. Epidemiology - p. 978 116. Pathobiology - p. 980 117. Germline Predisposition - p. 980 118. Clinical Manifestations - p. 985 119. Laboratory Manifestations - p. 986 120. Differential Diagnosis - p. 990 121. Prognosis - p. 991 122. Treatment of Patients with Myelodysplastic Syndromes - p. 993 123. Future Directions - p. 1000 124. Suggested Readings - p. 1000 125. References - p. 1000 126. Chapter 62. Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome in Adults - p. 1001 127. Chapter 63. Acute Myeloid Leukemia in Children - p. 1013 128. Chapter 64. Blastic Plasmacytoid Dendritic Cell Neoplasm - p. 1029 129. Chapter 65. Myelodysplastic Syndromes and Myeloproliferative Neoplasms in Children - p. 1036 130. Chapter 66. Pathobiology of Acute Lymphoblastic Leukemia - p. 1049 131. Chapter 67. Clinical Manifestations and Treatment of Childhood Acute Lymphoblastic Leukemia - p. 1066 132. Chapter 68. Acute Lymphoblastic Leukemia in Adults - p. 1078 133. Chapter 69. Chronic Myeloid Leukemia - p. 1103 134. Abstract - p. 1103 135. Introduction and Historical Perspective - p. 1103 136. Epidemiology - p. 1105 137. Molecular Biology - p. 1105 138. Cellular Biology - p. 1109 139. Transformation to Accelerated and Blast Phase - p. 1112 140. Molecular Basis of Tyrosine Kinase Inhibitor Resistance - p. 1112 141. Diagnosis and Initial Workup - p. 1115 142. Risk Stratification - p. 1116 143. Differential Diagnosis - p. 1118 144. Monitoring Response to Therapy - p. 1118 145. Therapy - p. 1120 146. Approach to the Newly Diagnosed Chronic Phase Patient - p. 1122 147. Approach to the Patient with Tyrosine Kinase Inhibitor Resistance - p. 1124 148. Treatment-Free Remission - p. 1125 149. Future Directions - p. 1126 150. Acknowledgments - p. 1127 151. Suggested Readings - p. 1127 152. References - p. 1127 153. Chapter 70. The Polycythemias - p. 1129 154. Abstract - p. 1129 155. Erythropoiesis - p. 1129 156. Erythropoietin, Oxygen Sensing, and Hypoxia-Inducible Factor - p. 1129 157. The Erythropoietin Receptor - p. 1131 158. The Renin–Angiotensin System and Hematopoiesis - p. 1131 159. Definition and Classification of Polycythemia - p. 1132 160. Relative Polycythemia - p. 1132 161. Absolute Polycythemias - p. 1133 162. Secondary Polycythemias - p. 1134 163. Polycythemia Vera - p. 1139 164. Clinical Manifestations - p. 1150 165. Laboratory Manifestations - p. 1154 166. Cytogenomic Abnormalities - p. 1156 167. Differential Diagnosis - p. 1158 168. Prognosis - p. 1159 169. Therapy - p. 1160 170. Future Directions - p. 1167 171. Suggested Readings - p. 1167 172. References - p. 1167 173. Chapter 71. Essential Thrombocythemia - p. 1169 174. Chapter 72. Primary Myelofibrosis and Chronic Neutrophilic Leukemia - p. 1193 175. Chapter 73. Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes - p. 1225 176. Chapter 74. Eosinophilia, Eosinophilic Neoplasms, and the Hypereosinophilic Syndromes - p. 1243 177. Chapter 75. Mast Cells and Mastocytosis - p. 1263 178. Chapter 76. Chronic Lymphocytic Leukemia - p. 1282 179. Chapter 77. Hairy Cell Leukemia - p. 1301 180. Chapter 78. The Pathologic Basis for the Classification of Non-Hodgkin and Hodgkin Lymphomas - p. 1314 181. Chapter 79. Origin of Hodgkin Lymphoma and Therapeutic Targets - p. 1331 182. Chapter 80. Hodgkin Lymphoma - p. 1339 183. Chapter81. Origin of Non-Hodgkin Lymphoma and Therapeutic Targets - p. 1352 184. Chapter 82. Clinical Manifestations, Staging, and Treatment of Follicular Lymphoma - p. 1367 185. Chapter 83. Marginal Zone Lymphomas (Extranodal/Malt, Splenic, and Nodal) - p. 1378 186. Chapter 84. Diffuse Large B-Cell Lymphoma of the Central Nervous System - p. 1390 187. Epidemiology - p. 1390 188. Pathogenesis - p. 1390 189. Clinical Presentation - p. 1394 190. Neuroimaging - p. 1394 191. Neuroimaging and Differential Diagnosis Prior to Biopsy - p. 1395 192. Tissue Diagnosis - p. 1396 193. Cerebrospinal Fluid Assessment for Diagnosis - p. 1396 194. Ophthalmology Exam and Vitreoretinal Specimen Testing for Diagnosis - p. 1397 195. Histology Characterization - p. 1398 196. Biomarkers for Diagnosis - p. 1399 197. Staging - p. 1400 198. Frontline Therapy and Response Assessment - p. 1401 199. Induction Therapy - p. 1401 200. Consolidation - p. 1402 201. Primary Central Nervous System Lymphoma in Older Adults - p. 1405 202. Induction in Older Adults—Should it Be REDUCED? - p. 1405 203. AUTOLOGOUS Hematopoietic Stem Cell Transplantation in Older Adults as Consolidation Therapy - p. 1406 204. Maintenance Therapy—Emerging Concept - p. 1406 205. Treatment of Primary Vitreoretinal Lymphoma - A Subset of Primary Central Nervous System Lymphoma - p. 1407 206. Real-World Treatment Patterns and Outcomes—Data from Population-Based Studies - p. 1407 207. Primary Central Nervous System Lymphoma in the Immunocompromised Host - p. 1408 208. Post-Transplant Lymphoproliferative Disease–Related Primary Central Nervous System Lymphoma - p. 1409 209. Autoimmune Disease–Related Primary Central Nervous System Lymphoma - p. 1409 210. Experimental Therapeutics in Primary Central Nervous System Lymphoma - p. 1409 211. NGR-Human Tumor Necrosis Factor With R-CHOP - p. 1409 212. Front-line Treatment Challenges and Controversies - p. 1410 213. Prognostic and Predictive Markers - p. 1412 214. Additional Prognostic and Predictive Markers - p. 1413 215. Relapsed and Refractory Disease - p. 1414 216. Non-Chemotherapeutic Targets and Agents - p. 1414 217. Prevention of Cns Relapse for Aggressive Systemic Lymphomas and Controversies - p. 1417 218. Perspective and Future Directions - p. 1417 219. Acknowledgments - p. 1417 220. Suggested Readings - p. 1417 221. References - p. 1417 222. Chapter 85. High-Grade B-Cell Lymphomas - p. 1420 223. Chapter 86. Mantle Cell Lymphoma - p. 1430 224. Chapter 87. Virus-Associated Lymphoma - p. 1439 225. Chapter 88. Malignant Lymphomas in Childhood - p. 1448 226. Chapter 89. T-Cell Lymphomas - p. 1462 227. Chapter 90. Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma - p. 1492 228. Chapter 91. Multiple Myeloma - p. 1506 229. Abstract - p. 1506 230. Screening, Epidemiology, and Risk Factors - p. 1506 231. Pathogenesis - p. 1506 232. Clinical Implications of Clonal Heterogeneity and Evolution - p. 1510222 233. Immune and Bone Marrow Microenvironment - p. 1510222 234. Clinical Manifestations - p. 1512 235. Genomic Biomarkers - p. 1524 236. Differential Diagnosis - p. 1524 237. Indications for Treatment - p. 1524 238. Treatment of Newly Diagnosed Myeloma - p. 1526 239. Relapsed Disease - p. 1533 240. Future Directions - p. 1538 241. Suggested Readings - p. 1538 242. References - p. 1538 243. Chapter 92. Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma - p. 1539 244. Chapter 93. Immunoglobulin Light-Chain Amyloidosis (Primary Amyloidosis) - p. 1553 245. Part VIII: Comprehensive Care of Patients with Hematologic Malignancies - p. 1566 246. Chapter 94. Key Considerations for Managing Infections in the Compromised Host - p. 1567 247. Chapter 95. Principles of Radiation Therapy for Hematologic Disease - p. 1583 248. Chapter 96. Grading and Toxicity Management after Immune Effector Therapy - p. 1594 249. Chapter 97. Identification and Management of Checkpoint Inhibition Toxicity - p. 1599 250. Chapter 98. Psychosocial Aspects Of Hematologic Disorders - p. 1605 251. Chapter 99. Pain Management and Antiemetic Therapy in Hematologic Disorders - p. 1616 252. Chapter 100. Palliative Care - p. 1631 253. Chapter 101. Therapy-Related Late Effects of Hematologic Malignancies - p. 1638 254. Part IX: Transplantation and Other Cell-Based Therapies - p. 1652 255. Chapter 102. Practical Aspects of Hematopoietic Stem Cell Harvesting and Mobilization - p. 1653 256. Chapter 103. Graft Engineering and Cell Processing - p. 1667 257. Chapter 104. Principles of Cell-Based Genetic Therapies - p. 1679 258. Chapter 105. Indications, Outcomes, and Donor Selection for Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies in Adults - p. 1689 259. Chapter 106. Unrelated Donor Hematopoietic Cell Transplantation - p. 1703 260. Chapter 107. Haploidentical Hematopoietic Stem Cell Transplantation - p. 1713 261. Abstract - p. 1713 262. Introduction - p. 1713 263. Historical Perspective - p. 1714 264. Immunological Considerations of Major Human Leukocyte Antigen Mismatched Grafts - p. 1714 265. Modern approaches to haploidentical transplantation (Fig. 107.3) - p. 1717 266. Comparative Outcomes Between Haploidentical and Other Donor Grafts - p. 1722 267. Potential Complications After Haploidentical Transplantation - p. 1725 268. Donor Selection for Haploidentical Transplantation (Table 107.4) - p. 1730 269. Conclusions and Future Directions - p. 1731 270. References - p. 1731 271. Suggested Readings - p. 1731 272. Chapter 108. Cord Blood Transplantation - p. 1732 273. Chapter 109. Graft-Versus-Host Disease and Graft-Versus-Leukemia Responses - p. 1749 274. Chapter 110. Supportive Care for the Transplant Patient - p. 1770 275. Part X: Transfusion Medicine - p. 1783 276. Chapter 111. Human Blood Group Antigens and Antibodies - p. 1785 277. Chapter 112. Principles of Red Blood Cell Transfusion - p. 1801 278. Chapter 113. Clinical Considerations in Platelet Transfusion Therapy - p. 1814 279. Chapter 114. Human Leukocyte Antigen and Human Neutrophil Antigen Systems - p. 1820 280. Chapter 115. Principles Of Plasma And Plasma Derivatives - p. 1837 281. Chapter 116. Hemapheresis - p. 1852 282. Chapter 117. Transfusion Reactions to Blood and Hematopoietic Stem Cell Therapy Products - p. 1864 283. Chapter 118. Transfusion-Transmitted Diseases - p. 1874 284. Chapter 119. Pediatric Transfusion Medicine - p. 1892 285. Chapter 120. Transfusion and Apheresis Support for Sickle Cell Disease Patients - p. 1900 286. Part XI: Hemostasis and Thrombosis - p. 1905 287. Chapter 121. Overview of Hemostasis and Thrombosis - p. 1906 288. Chapter 122. Blood Vessels - p. 1919 289. Chapter 123. Megakaryocyte And Platelet Structure - p. 1937 290. Chapter 124. Molecular Basis of Platelet Function - p. 1950 291. Chapter 125. Molecular Basis of Blood Coagulation - p. 1968 292. Chapter 126. Evaluation of the Patient With Suspected Bleeding Disorders - p. 1988 293. Chapter 127. Laboratory Evaluation of Hemostatic and Thrombotic Disorders - p. 1996 294. Chapter 128. Acquired Disorders of Platelet Function - p. 2007 295. Chapter 129. Diseases of Platelet Number: Immune Thrombocytopenia, Neonatal Alloimmune Thrombocytopenia, and Posttransfusion Purpura - p. 2020 296. Chapter 130. Thrombocytopenia Caused by Hypersplenism, Platelet Destruction, or Surgery/Hemodilution - p. 2033 297. Chapter 131. Heparin-Induced Thrombocytopenia - p. 2049 298. Chapter 132. Thrombotic Thrombocytopenic Purpura and the Hemolytic Uremic Syndromes - p. 2063 299. Chapter 133. Structure, Biology, and Genetics of von Willebrand Factor - p. 2081 300. Chapter 134. Hemophilia A and B - p. 2095 301. Abstract - p. 2095 302. Epidemiology - p. 2095 303. Factor VIII Biology: Genetics, Structure, Function, and Pathophysiology - p. 2096 304. Pathophysiology of Hemophilia A - p. 2098 305. Factor Ix Biology: Genetics, Structure, Function, and Pathophysiology - p. 2099 306. Clinical Features of Hemophilia - p. 2103 307. Clinical Management of Hemophilia - p. 2107 308. Inhibitors in Hemophilia B - p. 2120 309. Management of Inhibitors in Hemophilia B - p. 2121 310. Gene Therapy for Hemophilia - p. 2121 311. Hemophilia in the World—Economic Considerations - p. 2123 312. Acknowledgment - p. 2124 313. Suggested Readings - p. 2124 314. References - p. 2124 315. Chapter 135. Rare Coagulation Factor Deficiencies - p. 2125 316. Chapter 136. Transfusion Therapy for Coagulation Factor Deficiencies - p. 2144 317. Chapter 137. Disseminated Intravascular Coagulation - p. 2156 318. Chapter 138. Hypercoagulable States - p. 2167 319. Chapter 139. Antiphospholipid Syndrome - p. 2179 320. Chapter 140. Venous Thromboembolism - p. 2196 321. Chapter 141. Prevention and Treatment of Venous Thromboembolism in Pregnancy - p. 2205 322. Chapter 142. Atherothrombosis - p. 2212 323. Chapter 143. Antithrombotic Drugs - p. 2223 324. Chapter 144. Stroke - p. 2241 325. Chapter 145. Acute Coronary Syndromes - p. 2251 326. Chapter 146. Peripheral Artery Disease - p. 2261 327. Chapter 147. Atrial Fibrillation - p. 2270 328. Chapter 148. Bleeding And Clotting Disorders In Pediatrics - p. 2278 329. Part XII: Consultative Hematology - p. 2291 330. Chapter 149. Hematologic Changes in Pregnancy - p. 2292 331. Chapter 150. Hematologic Manifestations of End-Organ Failure - p. 2305 332. Chapter 151. Hematologic Manifestations of Solid Tumors - p. 2312 333. Chapter 152. Hematologic Manifestations of HIV/AIDS - p. 2319 334. Chapter 153. Hematologic Findings And Consequences Of Novel Coronavirus (SARS-COV-2) Infection - p. 2335 335. Chapter 154. Hematologic Aspects of Parasitic Diseases - p. 2342 336. Abstract - p. 2342 337. Malaria - p. 2342 338. Visceral Leishmaniasis - p. 2353 339. African Trypanosomiasis - p. 2356 340. American Trypanosomiasis - p. 2360 341. Babesiosis - p. 2363 342. Eosinophilia - p. 2365 343. Other Parasitic Diseases - p. 2366 344. Future Directions - p. 2367 345. Suggested Readings - p. 2367 346. References - p. 2367 347. Chapter 155. Hematologic Problems in the Surgical Patient: Bleeding and Thrombosis - p. 2369 348. Chapter 156. The Spleen and Its Disorders - p. 2378 349. Chapter 157. Aging and Hematologic Disorders - p. 2394 350. Chapter 158. Onco-Cardiology: Focus on Cardiac Complications of Hematologic Treatments - p. 2400 351. Chapter 159. Resources for the Hematologist: Interpretive Comments and Selected Reference Values for Neonatal, Pediatric, and Adult Populations - p. 2408.e3 352. Index - p. 2409 353. Confidence is ClinicalKey - p. 2476