Hematology: Basic Principles and Practice (7th Edition)

Description

Get the expert guidance you need to offer your patients the best possible outcomes with Hematology: Basic Principles and Practice, 7th Edition. This thoroughly up-to-date text contains both unparalleled scientific content and must-know clinical guidance, so you can enhance your problem-solving skills and make optimal use of the newest diagnostic techniques and therapeutic options in this fast-changing field.

Table of Contents

1. Contributors
2. Preface
3. Virtual Microscope Slide List
4. Part I Molecular and Cellular Basis of Hematology
5. 1 Anatomy and Physiology of the Gene
6. The Genetic View of the Biosphere: The Central Dogma of Molecular Biology
7. Anatomy and Physiology of Genes
8. Storage and Transmission of Genetic Information
9. Expression of Genetic Information Through the Genetic Code and Protein Synthesis
10. mRNA Metabolism
11. Gene Regulation
12. Epigenetic Regulation of Gene Expression
13. Enhancers, Promoters, and Silencers
14. Transcription Factors
15. Regulation of mRNA Splicing, Stability, and Translation (Posttranscriptional Regulation)
16. Small Interfering RNA and Micro RNA
17. Additional Structural Features of Genomic DNA
18. Key Methods for Gene Analysis
19. Use of Transgenic and Knockout Mice to Define Gene Function
20. DNA-Based Therapies
21. Future Directions
22. Suggested Readings
23. 2 Epigenetics and Epigenomics
24. Functional Chromatin Domains
25. DNA Methylation
26. Histones and Histone Variants
27. Covalent Histone Modifications
28. Transcription Factors
29. Chromatin Remodelers
30. Experimental Approaches in Epigenetics
31. Mechanisms of Disease
32. Epigenetic Therapies
33. Future Directions
34. Suggested Readings
35. 3 Genomic Approaches to Hematology
36. Principles of Genomic Approaches
37. Next-Generation Sequencing Technology
38. DNA-Level Characterization
39. Sequencing Approaches to Epigenomics
40. RNA-Level Characterization
41. Single-Cell RNA and DNA Sequencing
42. Protein-Level Characterization
43. Metabolite-Level Characterization
44. Functional Genomics
45. Pharmacogenomics
46. Clinical Use of Genomics
47. Future Directions
48. Suggested Readings
49. 4 Regulation of Gene Expression, Transcription, Splicing, and RNA Metabolism
50. Introduction to Gene Regulation in Hematology
51. How Genes Are Organized in DNA
52. Transcription of Genes
53. RNA Splicing
54. Nuclear Export of RNA
55. RNA Metabolism
56. Micro-RNA
57. Summary
58. Suggested Readings
59. 5 Protein Synthesis, Processing, and Trafficking
60. Protein Synthesis
61. Regulation of mRNA Translation
62. Protein Folding
63. Protein Modifications
64. Protein Degradation
65. Sorting From the Cytosol Into Other Compartments
66. Cotranslational Protein Translocation Into the Endoplasmic Reticulum
67. Protein Trafficking Within the Secretory Pathway
68. Processing of Proteins in the Endoplasmic Reticulum
69. Intragolgi Transport and Protein Processing
70. Sorting Events at the Trans-Golgi Network
71. Endocytic Traffic
72. Specificity of Vesicular Targeting
73. Conclusions
74. Suggested Readings
75. References
76. 6 Protein Architecture
77. Amino Acids and the Peptide Bond
78. Future Directions
79. References
80. 7 Signaling Transduction and Metabolomics
81. Signaling Transduction
82. Metabolomics and Control of Hematopoietic Cell Metabolism
83. Summary and Perspectives
84. Suggested Readings
85. 8 Pharmacogenomics and Hematologic Diseases
86. Variation in the Human Genome
87. Single-Nucleotide Polymorphisms
88. Single-Nucleotide Polymorphisms and Phenotypes
89. Haplotypes, Linkage Disequilibrium, and Hapmap
90. Structural Genomic Variants
91. Somatic Genomic Variants
92. Catalogues of Genomic Variants, Genotyping Platforms, and Genome-Wide Association Studies
93. Genetic Variations Influencing Drug Response: Pharmacogenetics–Pharmacogenomics–Pharmacoepigenomics
94. Optimization of Drug Therapy
95. Genetic Variations That Influence Drug Disposition
96. Drug Transporters
97. Genetic Variations Influencing Drug Targets
98. Adverse Drug Effects Presenting as Hematologic Disorders
99. Drug Development
100. Future Directions
101. References
102. Part II Cellular Basis of Hematology
103. 9 Hematopoietic Stem Cell Biology
104. Embryonic Origin of Hematopoietic Stem Cells
105. Definition and Characterization of Hematopoietic Stem Cells
106. Regulation of Hematopoietic Stem Cell Fate
107. Intrinsic Pathways
108. Hematopoietic Stem Cell Metabolism
109. Novel Growth Factors for Hematopoietic Stem Cells and Clinical Testing
110. Generating Hematopoietic Stem Cells From Pluripotent Stem Cells and by Reprogramming of Somatic Cells
111. Hematopoietic Stem Cell Regeneration
112. Hematopoietic Stem Cells and Malignancy
113. Suggested Readings
114. References
115. 10 Stem Cell Model of Hematologic Diseases
116. Cell of Origin Studies in Hematologic Malignancies
117. Acute Myeloid Leukemia
118. Myelodysplastic Syndromes
119. Myeloproliferative Neoplasms
120. Acute Lymphoblastic Leukemia
121. Mature B-Cell Malignancies
122. Chronic Lymphocytic Leukemia
123. Hairy Cell Leukemia
124. Diffuse Large B-Cell Lymphoma
125. Follicular Lymphoma
126. Conclusion
127. References
128. 11 Hematopoietic Microenvironment
129. Evolution of the Niche Concept
130. Hematopoietic Microenvironment During Development
131. Adult Bone Marrow Microenvironment
132. Extrinsic Regulation of the Hematopoietic Stem Cell Niche
133. Lymphoid Niches
134. Erythroid Niches
135. Megakaryocytic Niches
136. Human Bone Marrow Microenvironment
137. Hematopoietic Microenvironment in Acute Leukemia and Myelodysplasia
138. Future Directions
139. References
140. 12 Cell Adhesion
141. Adhesion Molecules
142. Extracellular Matrix Proteins
143. Integrins
144. Immunoglobulin-Like Receptors
145. Other Adhesion Receptors That Mediate Protein–Protein Interactions
146. Lectin Adhesion Receptors
147. Ligand Binding Versus Cell Adhesion
148. Regulation of Adhesion Receptors
149. Regulation of Synthesis
150. Regulation of Surface Expression
151. Regulation of Binding Affinity
152. Cell Signalling Through Adhesion Molecules
153. Cooperative Interactions Between Signaling and Adhesion Molecules
154. Altered Expression of Adhesion Molecules
155. Suggested Readings
156. 13 Chemokines and Hematopoietic Cell Trafficking
157. Chemokines in Control of Leukocyte Trafficking
158. Leukocyte Entry Into Tissues
159. Leukocyte Migration Within Tissues
160. Leukocyte Exit From Tissues
161. Summary
162. Suggested Readings
163. References
164. 14 Interactions Between Hematopoietic Stem and Progenitor Cells and the Bone Marrow
165. Hematopoietic Stem and Progenitor Cell Homing
166. Hematopoietic Stem and Progenitor Cell Mobilization: A Dynamic Multifaceted Process
167. Concluding Remarks
168. References
169. 15 Vascular Growth in Health and Disease
170. Hemostatic, Hematopoietic, and Vascular Systems as a Functional Continuum
171. Constituents of the Vascular System
172. Processes Involved in Blood Vessel Formation
173. Mechanisms Triggering Angiogenesis
174. Therapeutic Implications of Angiogenesis in Hematology
175. Summary
176. References
177. 16 Cytokine/Receptor Families and Signal Transduction
178. Cytokine/Receptor Families and Signal Transduction
179. Models of Ligand-Receptor Binding and Activation
180. Cytokine-Receptor Intracellular Signaling in the Context of in Vivo
181. References
182. 17 Control of Cell Division
183. The Cell Division Cycle
184. Signaling
185. Cyclins and Cdks
186. CDK Inhibitors
187. Transcriptional Regulation: MYC, RB-E2F, DREAM, and MMB-FOXM1
188. Ubiquitination
189. DNA Replication
190. Mitosis
191. Cell Cycle Checkpoints
192. Special Hematology Cell Cycle Features
193. References
194. 18 Cell Death
195. Physiologic Cell Turnover
196. Executioners of Apoptosis
197. Activation of Procaspases
198. Discs, Apoptosomes, Inflammasomes, and Piddosomes
199. Nonapoptotic Roles for Caspases
200. Inhibitors of Apoptosis Proteins
201. Core Apoptosis Pathways
202. BCL-2 Family Proteins and the Intrinsic Pathway of Apoptosis
203. BCL-2 Family Protein and the Endoplasmic Reticulum Gateway to Apoptosis
204. Nonapoptotic Roles for BCL-2 Family Proteins
205. Death Receptor Signaling and the Extrinsic Pathway of Apoptosis
206. Cell Survival/Death Pathways and Adaptive Responses to Stress
207. Clinical Applications
208. Summary
209. References
210. Part III Immunologic Basis of Hematology
211. 19 Overview and Compartmentalization of the Immune System
212. The Innate Immune System
213. Immune Deficiency Conditions Caused by Mutations in the Innate Immune System
214. Innate Immunity and Tissue Homeostasis
215. Adaptive Immune Response
216. Cells of the Innate and Adaptive Immune Systems
217. Anatomy of the Immune System
218. Encounters With Antigen: the Inflammatory Response
219. Systemwide Surveillance: the Role of Lymphatic Circulation
220. Secondary Lymphoid Tissue: Common and Unique Anatomy and Functions
221. Suggested Readings
222. References
223. 20 B-Cell Development
224. Stages of B-Cell Development
225. B Lineage Specification and Commitment
226. Immunoglobulin Gene Rearrangement and Expression
227. The Pro-B- and Pre-B-Cell Checkpoints
228. The Hematopoietic Microenvironment
229. Fetal B-Cell Development
230. Secondary Lymphoid Compartments
231. Effects of Aging on B-Cell Development and Function
232. References
233. 21 T-Cell Immunity
234. Introduction
235. T-Cell Activation
236. T-Cell Development
237. T-Cell Function
238. Maturation of T Cell–Mediated Immunity
239. Inhibition of T Cell–Mediated Immunity
240. Therapeutic Manipulation of T Cell–Mediated Immunity
241. Suggested Readings
242. 22 Natural Killer Cell Immunity
243. Fundamental Biology
244. Natural Killer Cell Development
245. Natural Killer Cell Receptors
246. Adaptive Immune Properties of Natural Killer Cells
247. The Role of Natural Killer Cells in Human Disease
248. The Therapeutic Potential of Natural Killer Cells
249. Future Directions
250. Suggested Readings
251. References
252. 23 Dendritic Cell Biology
253. Dendritic Cell Subsets and Development
254. The Concept of Maturation
255. Antigen Acquisition and Dendritic Cell Activation
256. Antigen Processing
257. T-Cell Activation
258. B-Cell Activation
259. Natural Killer Cell Activation
260. Activation of Other Elements of the Immune System
261. Tolerance and Autoimmunity
262. Subversion of Dendritic Cell Function by Pathogens and Tumors
263. Future Directions
264. Suggested Readings
265. References
266. 24 Complement and Immunoglobulin Biology Leading to Clinical Translation
267. The Complement System: an Overview
268. Immunoglobulins
269. Therapeutic Use of Immunoglobulin
270. Drugs Targeting the Complement System
271. Suggested Readings
272. References
273. 25 Tolerance and Autoimmunity
274. Self-Reactive Lymphocytes: Origin and Control
275. Breakdown of Self-Tolerance in Autoimmune Diseases
276. Implications and Therapy
277. References
278. Part IV Disorders of Hematopoietic Cell Development
279. 26 Biology of Erythropoiesis, Erythroid Differentiation, and Maturation
280. Erythroid Progenitor Cell Compartment
281. Erythroid Morphologically Recognizable Precursor Cell Compartment
282. Erythropoietin and EPOR
283. Signal Transduction by EPOR
284. Alterations in EPOR and Its Signaling in Disorders of Erythropoiesis
285. Hematopoietic Microenvironment
286. Ontogeny of Erythropoiesis
287. Transcription Factors in Erythropoiesis
288. Transcriptional and Posttranscriptional Impairment in Disorders of Erythropoiesis
289. Cellular Dynamics in Erythropoiesis
290. Suggested Readings
291. References
292. 27 Granulocytopoiesis and Monocytopoiesis
293. Granulocytopoiesis
294. Control of Granulopoiesis
295. Role of Developmentally Important Neutrophil-Specific Genes in Disease
296. Eosinophil Production
297. Basophil and Mast Cell Production
298. Monocytopoiesis
299. Suggested Readings
300. References
301. 28 Thrombocytopoiesis
302. Megakaryocyte Biology
303. Cytokine Regulation of Thrombocytopoiesis
304. Endomitosis
305. Transcriptional Control of Megakaryocytopoiesis
306. Micrornas in Megakaryocytopoiesis
307. Future Directions
308. References
309. 29 Inherited Bone Marrow Failure Syndromes
310. Introduction
311. Inherited Bone Marrow Failure Syndrome With Pancytopenia
312. Inherited Bone Marrow Failure Syndromes With Predominantly Anemia
313. Inherited Bone Marrow Failure Syndromes With Predominantly Neutropenia
314. Inherited Bone Marrow Failure Syndromes With Predominantly Thrombocytopenia
315. Suggested Readings
316. 30 Aplastic Anemia
317. History
318. Classification
319. Epidemiology
320. Etiology and Pathogenesis
321. Pathophysiologic Pathways Leading to Aplastic Anemia
322. Typical and Atypical Presentations
323. Clinical Associations
324. Laboratory Evaluation
325. Diagnosis of Aplastic Anemia
326. Bone Marrow
327. Differential Diagnosis of Pancytopenia
328. Treatment
329. Prognosis
330. Suggested Readings
331. References
332. 31 Paroxysmal Nocturnal Hemoglobinuria
333. Pathophysiology
334. Clinical Features
335. Clonality and Bone Marrow Failure
336. Natural History
337. Laboratory Evaluation
338. Diagnosis
339. Therapy
340. Approach to Treatment
341. References
342. 32 Acquired Disorders of Red Cell, White Cell, and Platelet Production
343. Acquired Pure Red Cell Aplasia
344. Etiology and Classification
345. Primary Pure Red Cell Aplasia
346. Secondary Forms of Pure Red Cell Aplasia
347. Laboratory Evaluation
348. Differential Diagnosis
349. Therapy
350. Prognosis
351. Acquired White Blood Cell Production Disorders
352. Classification of Acquired Neutropenias
353. Secondary Forms of Neutropenias
354. Laboratory Evaluation
355. Differential Diagnosis
356. Therapy
357. Large Granular Lymphocyte Leukemia
358. Pathogenesis
359. Clinical Presentation and Physical Features
360. Laboratory Diagnosis
361. Differential Diagnosis
362. Therapy
363. Prognosis
364. Acquired Platelet Production Disorder
365. Selective Megakaryocyte Aplasia
366. Infection
367. Chemotherapy and Irradiation
368. Nutritional Deficiencies
369. Marrow Infiltration
370. Ethanol-Related Disorders
371. Other Drug-Related Disorders
372. Suggested Readings
373. References
374. Part V Red Blood Cells
375. 33 Pathobiology of the Human Erythrocyte and Its Hemoglobins
376. Essential Features of Red Blood Cell Homeostasis
377. Major Features of the Red Blood Cell Membrane
378. Enzymes of Red Blood Cell Intermediary
379. Red Blood Cell Senescence and Destruction
380. Hemoglobin Synthesis, Structure, and Function
381. Nosology of Hemoglobinopathies
382. Suggested Readings
383. 34 Approach to Anemia in the Adult and Child
384. Overview of Erthropoiesis
385. Definition of Anemia
386. Mechanisms of Anemia
387. Comparison of Etiologies of Anemia in Adults and Children
388. Systemic Approach to Anemia
389. Future Directions
390. References
391. 35 Pathophysiology of Iron Homeostasis
392. Regulation of Cellular and Systemic Iron Homeostasis
393. Use of Iron for Erythropoiesis
394. Recycling of Erythrocyte Iron by Macrophages
395. Liver Regulation of Systemic Iron Homeostasis and Iron Storage
396. Intestinal Iron Absorption
397. Future Directions
398. References
399. 36 Disorders of Iron Homeostasis
400. Laboratory Evaluation of Iron Status
401. Iron Deficiency
402. Iron Overload
403. References
404. 37 Anemia of Chronic Diseases
405. Description and Epidemiology
406. Etiology and Pathogenesis
407. Biology and Molecular Aspects
408. Diagnosis
409. Treatment
410. Summary and Future Directions
411. References
412. 38 Heme Biosynthesis and Its Disorders
413. Heme Biosynthesis
414. Porphyrias
415. Sideroblastic Anemias
416. Sideroblastic Anemia and Porphyrinuria Caused by Drugs
417. Presentations Associated With Sideroblastic Anemia or Porphyrinuria
418. Suggested Readings
419. References
420. 39 Megaloblastic Anemias
421. Cobalamin
422. Folates
423. Intracellular One-Carbon Metabolism and Cobalamin–Folate Relationships
424. Morphologic Expression of Megaloblastosis
425. Neurologic Dysfunction with Cobalamin Deficiency
426. Other Effects of Cobalamin and Folate Deficiency
427. Spectrum of Clinical Presentations with Cobalamin Deficiency
428. Biochemical Indicators of Evolving Deficiency
429. Biochemical Evaluation of Cobalamin and Folate Deficiencies
430. Pathogenesis of Cobalamin Deficiency
431. Pathogenesis of Folate Deficiency
432. Megaloblastic Anemia Not Caused by Folate or Cobalamin Deficiency
433. Clinical Presentations and Evaluation for Folate and Cobalamin Deficiency
434. Approach to Diagnosis and Therapy of Megaloblastosis
435. Therapy
436. Routine Supplementation of Cobalamin and Folate
437. Hyperhomocysteinemia
438. Folate Fortification of Food and the Risk for Cancer
439. Future Directions
440. Suggested Readings
441. References
442. 40 Thalassemia Syndromes
443. Definitions and Nomenclature
444. Etiology, Epidemiology, and Pathophysiology
445. Pathophysiology: General Principles
446. β-Thalassemia Syndromes
447. Pathophysiology: Recent Findings
448. α-Thalassemia Syndromes
449. Thalassemic Structural Variants
450. Extraordinarily Unstable Hemoglobins
451. Suggested Readings
452. References
453. 41 Pathobiology of Sickle Cell Disease
454. Early Years of Sickle Cell Disease Research
455. Genetic Considerations
456. Abnormal Molecular Behaviors of Sickle Hemoglobin
457. Abnormalities of Sickle Red Blood Cells
458. The Role of Red Blood Cells in Disease Pathogenesis
459. Unique Systems Biology of Sickle Cell Anemia
460. Inflammation
461. Basis of Phenotypic Diversity
462. References
463. 42 Sickle Cell Disease
464. Prevalence
465. Diagnosis
466. Clinical Presentation and Management
467. Variant Sickle Cell Syndromes
468. Suggested Readings
469. References
470. 43 Hemoglobin Variants Associated With Hemolytic Anemia, Altered Oxygen Affinity, and Methemoglobinemias
471. Unstable Hemoglobins
472. Hemoglobins With Increased Oxygen Affinity
473. Hemoglobins With Decreased Oxygen Affinity
474. Suggested Readings
475. 44 Red Blood Cell Enzymopathies
476. Metabolic Pathways
477. Enzymopathies Associated With Hemolytic Anemia
478. Other Enzymopathies of the Glutathione Pathway
479. Other Enzymopathies of the Glycolytic Pathway
480. Other Enzymopathies
481. Enzymopathies Associated With Polycythemia
482. Enzymopathies Associated With Methemoglobinemia
483. Suggested Readings
484. 45 Red Blood Cell Membrane Disorders
485. Vertical and Horizontal Interactions of Membrane Proteins and Disorders of Red Blood Cell Shape
486. Differential Diagnosis
487. Therapy and Prognosis
488. Hereditary Elliptocytosis and Related Disorders
489. Red Blood Cell Membrane Disorders Manifested by Target Cell Formation
490. Red Cell Membrane Variants and Infectious Disease
491. Suggested Readings
492. 46 Autoimmune Hemolytic Anemia
493. History
494. Epidemiology
495. Pathobiology
496. Etiology and Pathophysiology
497. Symptoms, Clinical Findings, and Risks
498. Laboratory Diagnosis of Autoimmune Hemolytic Anemia
499. Immunologic Phenomena Associated With Autoimmune Hemolytic Anemia
500. Secondary Autoimmune Hemolytic Anemia
501. Differential Diagnosis
502. Treatment
503. Future Directions
504. References
505. 47 Extrinsic Nonimmune Hemolytic Anemias
506. Fragmentation Hemolysis: Microangiopathy
507. Other Forms of Mechanical Damage to Red Blood Cells
508. Drug-Induced Oxidative Hemolysis
509. Miscellaneous, Poorly Characterized Causes of Extrinsic Hemolytic Anemias
510. References
511. Part VI Non-Malignant Leukocytes
512. 48 Neutrophilic Leukocytosis, Neutropenia, Monocytosis, and Monocytopenia
513. Neutrophilic Leukocytosis (Neutrophilia)
514. Neutropenia (and Agranulocytosis)
515. Monocytosis
516. Monocytopenia
517. Suggested Readings
518. 49 Lymphocytosis, Lymphocytopenia, Hypergammaglobulinemia, and Hypogammaglobulinemia
519. Quantitative Disorders of Lymphocytes
520. Quantitative Disorders of Immunoglobulins
521. References
522. 50 Disorders of Phagocyte Function
523. Approach to Diagnosis of Phagocyte Function Disorders
524. Disorders of the Respiratory Burst Pathway
525. Disorders of Phagocyte Adhesion and Chemotaxis
526. Defects in the Structure and Function of Lysosomal Granules
527. Miscellaneous Inherited and Acquired Disorders of Phagocyte Function
528. References
529. 51 Congenital Disorders of Lymphocyte Function
530. Defects of Thymus Organogenesis
531. Severe Combined Immune Deficiency Due to Early Defects in T Lymphocyte Development
532. Other Combined Immunodeficiencies
533. Combined Immunodeficiencies With Osseous Dysplasia
534. Other Combined Immunodeficiencies
535. Disorders With T Cell-Mediated Immune Dysregulation
536. Defects of Cell-Mediated Cytotoxicity
537. Defects of B-Cell Development and Function
538. B-Cell–Intrinsic Defects of Class-Switch Recombination
539. Suggested Readings
540. References
541. 52 Histiocytic Disorders
542. Langerhans Cell Histiocytosis
543. Juvenile Xanthogranulomatous Disease
544. Erdheim–Chester Disease
545. Hemophagocytic Lymphohistiocytosis
546. Macrophage Activation Syndrome
547. Sinus Histiocytosis With Massive Lymphadenopathy or Rosai–Dorfman Disease
548. Suggested Readings
549. 53 Lysosomal Storage Diseases
550. Pathobiology of Lysosomal Storage Diseases
551. Genetics and Diagnosis of Lysosomal Storage Diseases
552. Therapy of Lysosomal Storage Diseases: An Overview
553. Hematologic Manifestations of Lysosomal Storage Diseases
554. Conclusions and Future Directions
555. References
556. 54 Infectious Mononucleosis and Other Epstein-Barr Virus–Associated Diseases
557. Biology of Epstein-Barr Virus
558. Primary Epstein-Barr Virus Infection
559. Latent Epstein-Barr Virus Infection
560. Immune Response to Epstein-Barr Virus
561. Epstein-Barr Virus Vaccine Development
562. Infectious Mononucleosis
563. Other Epstein-Barr Virus Associated Diseases
564. Future Directions
565. References
566. Part VII Hematologic Malignancies
567. 55 Progress in the Classification of Hematopoietic and Lymphoid Neoplasms
568. Progress in the Diagnosis and Classification of Myeloid Neoplasms
569. Evolving Concepts in Classification of Lymphoid Neoplasms
570. Dendritic Cell and Histiocytic Neoplasms: Principal Considerations for Diagnosis and Treatment
571. References
572. 56 Conventional and Molecular Cytogenomic Basis of Hematologic Malignancies
573. Methods
574. Early Mutations in Leukemogenesis and Age-Related Clonal Hematopoiesis
575. Chronic Myeloproliferative Neoplasms
576. Myelodysplastic Syndromes
577. Acute Myeloid Leukemia
578. Acute Lymphoblastic Leukemia
579. B-Cell Chronic Lymphocytic Leukemia
580. Multiple Myeloma
581. Lymphoma
582. Hairy Cell Leukemia
583. T-Cell Lymphoproliferative Neoplasms
584. Allogeneic Hematopoietic Cell Transplantation
585. Future Directions
586. References
587. 57 Pharmacology and Molecular Mechanisms of Antineoplastic Agents for Hematologic Malignancies
588. Tumor Cell Heterogeneity of Hematologic Malignancies
589. Development of Chemotherapeutic Agents
590. Traditional Cytotoxic Antineoplastic Agents Targeting the Cell Cycle and DNA
591. Pharmacology of Traditional Chemotherapeutic Agents
592. Pharmacology of Targeted Antineoplastic Agents
593. Drug Resistance to Chemotherapeutic Agents or Multidrug Resistance
594. Future Directions
595. Mechlorethamine (Mustargen)
596. Topoisomerase II Inhibitors
597. Topoisomerase I Inhibitors
598. Histone Deacetylase Inhibitors
599. Tyrosine Kinase Inhibitors
600. Janus Kinase Inhibitors
601. References
602. 58 Pathobiology of Acute Myeloid Leukemia
603. Phenotype of Acute Myeloid Leukemia
604. Etiology of Acute Myeloid Leukemia
605. Genetic and Epigenetic Alterations in Acute Myeloid Leukemia
606. Biology of Acute Myeloid Leukemia
607. Future Directions
608. Suggested Readings
609. 59 Clinical Manifestations and Treatment of Acute Myeloid Leukemia
610. Introduction
611. Epidemiology
612. Pathobiology
613. Clinical and Laboratory Manifestations
614. Diagnosis and Classification
615. Prognosis
616. Therapy: Frontline
617. Acute Promyelocytic Leukemia
618. Additional Issues in Acute Myeloid Leukemia
619. Future Directions
620. References
621. 60 Myelodysplastic Syndromes
622. History
623. Classification
624. Epidemiology and Etiology
625. Pathobiology
626. Clinical Features of Myelodysplastic Syndrome
627. Diagnostic Systems and Clinical Syndromes
628. Treatment of Patients With Myelodysplastic Syndromes
629. Future Directions
630. Suggested Readings
631. References
632. 61 Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome in Adults
633. Acute Myeloid Leukemia
634. Transplantation for Myelodysplastic Syndrome
635. Future Directions
636. Suggested Readings
637. References
638. 62 Acute Myeloid Leukemia in Children
639. Epidemiology
640. Pathobiology
641. Clinical and Laboratory Manifestations and Diagnosis
642. Therapy
643. Supportive Care
644. Future Directions
645. Conclusion
646. Suggested Readings
647. 63 Myelodysplastic Syndromes and Myeloproliferative Neoplasms in Children
648. Myelodysplastic Syndromes
649. Myeloproliferative Neoplasms
650. Other Myeloproliferative Neoplasms
651. Future Directions
652. Suggested Readings
653. References
654. 64 Pathobiology of Acute Lymphoblastic Leukemia
655. Clonal Origin of Leukemic Lymphoid Cells
656. Lineage-Specific Features of Leukemic Lymphoblasts
657. Genetic Basis of Acute Lymphoblastic Leukemia
658. Chemotherapy Resistance Mechanisms and Novel Therapeutic Targets
659. Future Directions
660. Suggested Readings
661. References
662. 65 Clinical Manifestations and Treatment of Childhood Acute Lymphoblastic Leukemia
663. Introduction
664. Epidemiology
665. Pathobiology
666. Clinical Manifestations
667. Differential Diagnosis
668. Prognosis
669. Therapy, Including Stem Cell Transplantation
670. Acute Lymphoblastic Leukemia Relapse
671. Supportive Care
672. Late Effects of Treatment
673. Future Directions
674. References
675. 66 Acute Lymphoblastic Leukemia in Adults
676. Epidemiology
677. Etiology
678. Clinical Manifestations
679. Clinical and Laboratory Evaluation
680. Approach to Diagnosis
681. Morphology
682. Cytochemistry
683. Immunophenotype
684. Cytogenetics and Molecular Genetics
685. Differential Diagnosis
686. Prognosis
687. Minimal Residual Disease
688. Treatment of Acute Lymphoblastic Leukemia
689. Remission Induction
690. Postremission Therapy
691. Central Nervous System Disease: Prophylaxis and Treatment
692. Maintenance Therapy
693. Allogeneic Stem Cell Transplant in First Complete Remission
694. Therapy for Specific Disease Subsets
695. Burkitt Lymphoma/Leukemia
696. Adolescents and Young Adults With Acute Lymphoblastic Leukemia: the Intersection Between Pediatric and Adult Care
697. Older Adults With Acute Lymphoblastic Leukemia
698. Relapsed Acute Lymphoblastic Leukemia
699. Novel Therapies
700. Survivorship
701. Future Directions
702. Suggested Readings
703. References
704. 67 Chronic Myeloid Leukemia
705. Etiology/Epidemiology/Genetics
706. Pathophysiology
707. Clinical Features
708. Prognosis
709. Therapy
710. Treatment of CML Patients With Advanced Disease
711. References
712. 68 The Polycythemias
713. Erythropoiesis
714. Erythropoietin, Oxygen Sensing, and Hypoxia-Inducible Factor
715. The Erythropoietin Receptor
716. The Renin–Angiotensin System and Hematopoiesis
717. Definition and Classification of Polycythemia
718. Relative Polycythemia
719. Absolute Polycythemias
720. Secondary Polycythemias
721. Polycythemia Vera
722. Clinical Manifestations
723. Laboratory Manifestations
724. Cytogenetic Abnormalities
725. Differential Diagnosis
726. Prognosis
727. Therapy
728. Future Directions
729. References
730. 69 Essential Thrombocythemia
731. Epidemiology
732. Pathobiology
733. Clinical Manifestations
734. Laboratory Manifestations
735. Differential Diagnosis
736. Prognosis
737. Therapy
738. Future Directions
739. References
740. 70 Primary Myelofibrosis
741. Epidemiology
742. Clinical Manifestations
743. Laboratory Manifestations
744. Differential Diagnosis
745. Prognosis
746. Future Directions
747. References
748. 71 Eosinophilia, Eosinophil-Associated Diseases, Eosinophilic Leukemias, and the Hypereosinophilic Syndromes
749. Epidemiology
750. Morphology and Phenotype of Eosinophils
751. Origin, Differentiation, Recruitment, and Activation of Eosinophils
752. Monitoring of Eosinophil Numbers and Activity in Health and Disease
753. Etiology and Pathobiology of He
754. Definition and Classification of HE and HES
755. Clinical Manifestations of HES in Various Organ Systems and Differential Diagnosis
756. Treatment Algorithm, Treatment Options and Prognosis
757. Summary and Future Perspectives
758. References
759. 72 Mast Cells and Mastocytosis
760. Introduction
761. Origin and Development of Mast Cells
762. Mast Cell Activation and Function
763. Tools to Study Human Mast Cells
764. Epidemiology and Classification of Mastocytosis
765. Treatment
766. Future Directions
767. References
768. 73 The Pathologic Basis for the Classification of Non-Hodgkin and Hodgkin Lymphomas
769. Introduction and Historical Background
770. Mature B-Cell Neoplasms
771. T and Natural Killer-Cell Lymphomas
772. References
773. 74 Origin of Hodgkin Lymphoma
774. Introduction
775. Classification of Hodgkin Lymphoma
776. Future Directions
777. References
778. 75 Hodgkin Lymphoma
779. Epidemiology and Etiology
780. Pathobiology of Hodgkin Lymphoma
781. Diagnosis and Staging
782. Clinical Features
783. Prognostic Factors, Risk Stratification, and Treatment Groups
784. Treatment of Early-Stage Hodgkin Lymphoma
785. Treatment of Advanced-Stage Hodgkin Lymphoma
786. Relapsed and Refractory Hodgkin Lymphoma
787. Novel Agents
788. Special Considerations
789. Long-Term Complications of Treatment in Hodgkin Lymphoma
790. Conclusion
791. References
792. 76 Origin of Non-Hodgkin Lymphoma
793. Overview of B-Cell Lymphomas
794. Diffuse Large B-Cell Lymphoma
795. Gene Expression Profiles Define Diffuse Large B-Cell Lymphoma Subtypes
796. Burkitt Lymphoma
797. Follicular Lymphoma
798. Mantle Cell Lymphoma
799. Other Non-Hodgkin Lymphomas
800. Future Directions
801. Suggested Readings
802. 77 Chronic Lymphocytic Leukemia
803. Epidemiology
804. Familial Chronic Lymphocytic Leukemia
805. Pathobiology
806. B-Cell Receptor Pathway and Its Role in Pathogenesis
807. Clinical Manifestations
808. Diagnosis and Laboratory Manifestations
809. Laboratory Manifestations
810. Prognosis
811. Treatment
812. Treatment of Patients With Relapsed Chronic Lymphocytic Leukemia
813. Special Clinical Scenarios in Chronic Lymphocytic Leukemia
814. Infections in Patients With Chronic Lymphocytic Leukemia
815. Autoimmune Complications of Chronic Lymphocytic Leukemia
816. Future Directions
817. Financial Support
818. Suggested Readings
819. 78 Hairy Cell Leukemia
820. Introduction
821. Epidemiology
822. Etiology and Cell of Origin
823. Clinical Presentation and Diagnosis
824. Differential Diagnosis
825. Treatment
826. Future Directions
827. References
828. 79 Marginal Zone Lymphomas (Extranodal/Malt, Splenic, and Nodal)
829. Initial Evaluation of Marginal Zone Lymphoma
830. Staging of Marginal Zone Lymphoma
831. Extranodal Marginal Zone Lymphoma of MALT Type
832. Splenic Marginal Zone Lymphoma
833. Nodal Marginal Zone Lymphoma
834. Suggested Readings
835. References
836. 80 Clinical Manifestations, Staging, and Treatment of Follicular Lymphoma
837. Epidemiology
838. Pathogenesis
839. Clinical Presentation
840. Diagnosis of Follicular Lymphoma
841. Staging
842. Natural History
843. Treatment of Follicular Lymphoma
844. When to Institute Therapy
845. Treatment Approaches
846. Treatment of Relapsed Indolent Lymphoma
847. Suggested Readings
848. References
849. 81 Mantle Cell Lymphoma
850. Introduction
851. Epidemiology
852. Pathobiology
853. Clinical Manifestations
854. Laboratory Manifestations
855. Diagnosis
856. Therapy
857. Prognosis
858. Future Directions
859. Suggested Readings
860. References
861. 82 Diagnosis and Treatment of Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma
862. Diffuse Large B-Cell Lymphoma
863. Primary Central Nervous System Lymphoma
864. Burkitt Lymphoma
865. Salvage Therapy
866. Future Directions
867. References
868. 83 Virus-Associated Lymphoma
869. Epstein-Barr Virus
870. Kaposi Sarcoma–Associated Herpesvirus
871. Human T-Lymphotropic Virus-1
872. HIV-Associated Lymphomas
873. AIDS Primary Central Nervous System Lymphoma
874. Hepatitis C Virus
875. Future Directions
876. Suggested Readings
877. References
878. 84 Malignant Lymphomas in Childhood
879. Non-Hodgkin Lymphoma
880. Hodgkin Lymphoma
881. Rare Subtypes of Lymphoma
882. Future Directions
883. Suggested Readings
884. References
885. 85 T-Cell Lymphomas
886. The Peripheral T-Cell Lymphomas (Noncutaneous)
887. Future Directions
888. Cutaneous T-Cell Lymphomas
889. Future Directions
890. Suggested Readings
891. 86 Plasma Cell Neoplasms
892. Epidemiology
893. Historical Aspects
894. Pathobiology
895. Genomics
896. Microenvironment and Signaling
897. Cytokines
898. Immune Environment
899. Clinical Manifestations
900. Laboratory Manifestations
901. International Staging System
902. Differential Diagnosis
903. Treatment
904. Treatment of Newly Diagnosed Myeloma
905. Autologous Stem Cell Transplant
906. Relapsed Disease
907. Future Directions
908. Suggested Readings
909. References
910. 87 Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma
911. Epidemiology
912. Pathogenesis
913. Mutation in MYD88
914. CXCR4 WHIM Mutations
915. Impact of WM Genomics on Clinical Presentation
916. Marrow Microenvironment
917. Clinical Features
918. Morbidity Mediated by the Effects of IgM
919. Laboratory Findings
920. Marrow Findings
921. Immunologic Abnormalities
922. Serum Viscosity
923. Imaging
924. Lymph Node Biopsy
925. Treatment
926. Suggested Readings
927. References
928. 88 Immunoglobulin Light Chain Amyloidosis (Primary Amyloidosis)
929. Epidemiology
930. Pathobiology of the Disease
931. Clinical Manifestations
932. Laboratory Manifestations
933. Differential Diagnosis
934. Prognosis
935. Therapy
936. Conclusions
937. Future Directions and Summary
938. Suggested Readings
939. Part VIII Comprehensive Care of Patients with Hematologic Malignancies
940. 89 Clinical Approach to Infections in the Compromised Host
941. Hematologic Conditions Predisposing to Infection
942. Infection Management in the Hematopoietic Stem Cell Transplant Recipient: a Model of Severe Immune Deficiency
943. References
944. 90 Psychosocial Aspects of Hematologic Disorders
945. Accompanying Trends in Psychosocial Issues
946. Clinical Course of Hematologic Malignancies
947. Decision for Hematopoietic Stem Cell Transplantation
948. Factors That Influence Psychosocial Adjustment
949. Differentiating Psychiatric Complications From Expected Psychologic Response
950. Screening for Psychologic Distress
951. Management of Psychosocial Problems
952. Future Directions
953. Suggested Readings
954. References
955. 91 Pain Management and Antiemetic Therapy in Hematologic Disorders
956. Taxonomy of Pain
957. Evaluation of the Pain Complaint
958. Therapy Directed at the Underlying Etiology
959. Nonpharmacologic Methods of Pain Management
960. Pharmacotherapy
961. Specific Clinical Problems
962. Pathophysiology of Nausea and Vomiting
963. Patient Assessment
964. Therapy
965. Conclusion
966. References
967. 92 Palliative Care
968. Pediatric Palliative Care: Specific Issues
969. Communication
970. Caregivers
971. Relief of Suffering
972. Psychologic Concerns
973. Management Concerns During the Last Days of Life
974. Hospice Programs
975. Bereavement
976. Self-Care for Clinicians
977. Conclusion and Future Directions
978. References
979. 93 Late Complications of Hematologic Diseases and Their Therapies
980. Cardiovascular Disease
981. Pulmonary Effects
982. Endocrinologic Effects
983. Pregnancy Outcomes
984. Musculoskeletal Effects
985. Neurocognitive Effects
986. Other Toxicities
987. Potential Late Effects by Diagnosis
988. Providing Clinical Care to Survivors
989. Future Directions
990. Suggested Readings
991. References
992. Part IX Cell-Based Therapies
993. 94 Overview and Historical Perspective of Current Cell-Based Therapies
994. References
995. 95 Practical Aspects of Hematologic Stem Cell Harvesting and Mobilization
996. Selection and Evaluation of the Stem Cell Donor
997. Collection of Bone Marrow for Transplantation
998. Collection of Umbilical Cord Blood Stem Cells for Transplantation
999. Collection of Peripheral Blood Stem Cells for Transplantation
1000. Quality Control of HSC Products
1001. Suggested Readings
1002. References
1003. 96 Investigational New Drug–Enabling Processes for Cell-Based Therapies
1004. Overview of the Cell Therapy Product
1005. The Regulation of Cell Therapy Products
1006. The Investigational New Drug Process
1007. When Is a Cell Therapy Product Ready to Be Tested in a Clinical Trial?
1008. Conclusions
1009. Suggested Readings
1010. References
1011. 97 Graft Engineering and Cell Processing
1012. Regulatory Issues With Cell Processing
1013. Professional Standards
1014. Manipulation of Hematopoietic Stem Cell Transplantation Products
1015. Evaluation of Manipulated Grafts
1016. Cellular Therapy Products
1017. Future Directions
1018. Suggested Readings
1019. 98 Principles of Cell-Based Genetic Therapies
1020. Hematologic Diseases, Cellular Targets, and the Basis for Genetic Therapies
1021. Vector Systems
1022. Experience in Hematologic Clinical Trials to Date
1023. Insertional Mutagenesis
1024. Recent Modifications of Vector Systems Based on Clinical Experience
1025. Future Directions
1026. Acknowledgements
1027. Suggested Readings
1028. References
1029. 99 Mesenchymal Stromal Cells
1030. Endogenous Mesenchymal Stem Cells
1031. Bone Marrow Mesenchymal Stem Cell Manufacture and Phenotype
1032. Immune Profile of Mesenchymal Stem Cells
1033. Mesenchymal Stromal Cell Immune Plasticity in Response to Inflammatory Cues
1034. Mesenchymal Stromal Cell Immune Privilege: a Controversial Issue
1035. Mesenchymal Stromal Cells for the Prevention and Treatment of Steroid-Refractory Acute Graft-Versus Host Disease
1036. Mesenchymal Stromal Cells to Promote Hematopoietic Stem Cell Engraftment in Preclinical Models of Stem Cell Transplantation
1037. Clinical Trials of Mesenchymal Stromal Cells to Promote Hematopoietic Stem Cell Engraftment
1038. Safety Profile of Adoptively Transferred Mesenchymal Stromal Cells
1039. Regulatory Oversight of Mesenchymal Stromal Cells Development and Marketing Approval
1040. Future Directions
1041. References
1042. 100 T-Cell Therapy of Hematologic Diseases
1043. Introduction
1044. Types of Cellular Immunotherapy
1045. Genetic Modification of T Cells
1046. Future Applications and Implementation of Cell Therapies for Cancer
1047. References
1048. 101 Natural Killer Cell–Based Therapies
1049. Introduction
1050. Natural Killer Cell Biology
1051. Clinical Applications of Natural Killer Cells
1052. Future Directions
1053. Conclusion
1054. References
1055. 102 Immune Checkpoint Blockade in Hematologic Malignancies
1056. Introduction
1057. Cytotoxic T Lymphocyte-Associated Antigen 4
1058. Programmed Cell Death Protein 1
1059. Checkpoint Blockade Therapies After Hematopoietic Stem Cell Transplantation
1060. Lessons From CTLA-4 and PD-1 Blockade
1061. Future Directions
1062. Conclusion
1063. References
1064. Part X Transplantation
1065. 103 Overview and Choice of Donor of Hematopoietic Stem Cell Transplantation
1066. Allogeneic Transplantation
1067. Source of Hematopoietic Stem Cells
1068. Conditioning Regimens
1069. Complications After Stem Cell Transplantation
1070. Future Directions
1071. References
1072. 104 Indications and Outcomes of Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies in Adults
1073. Background
1074. Patient Population
1075. Conditioning Regimens
1076. Graft Sources
1077. Alternative Donor Transplants—Cord Blood and Haploidentical Grafts
1078. Graft Versus Malignancy Effects
1079. Prognostic Factors
1080. Clinical Research in Allogeneic Transplantation
1081. Long-Term Survival After Allogeneic Transplantation
1082. Disease-Specific Indications for Allogeneic Transplantation
1083. References
1084. 105 Unrelated Donor Hematopoietic Cell Transplantation
1085. Donor Identification and Likelihood of Transplantation
1086. Donor Evaluation and Selection
1087. Process of Identifying a Suitable Unrelated Donor
1088. Human Leukocyte Antigen Typing Methods
1089. Assessment of the Vector of Mismatching
1090. Assessment of Human Leukocyte Antigen Haplotypes
1091. Clinical Importance of Donor HLA Matching in Cases of Unrelated Donor HCT
1092. Human Leukocyte Antigen−Matched Unrelated Donor Hematopoietic Cell Transplantation
1093. Single-Locus Mismatched Unrelated Hematopoietic Cell Transplantation
1094. The Level of HLA Expression
1095. Beyond Classic HLA: Major Histocompatibility Complex Resident Variation
1096. Future Directions
1097. Suggested Readings
1098. References
1099. 106 Haploidentical Hematopoietic Cell Transplantation
1100. Definitions: What Is an HLA Haplotype, and Who Is an HLA-Haploidentical Donor?
1101. Why HLA-Haploidentical Bone Marrow Transplant? (see Box 106.1)
1102. Immunologic Considerations in HLA-Haploidentical HSCT
1103. Complications of HLA-Haploidentical SCT
1104. Modern Approaches to HLA-Haploidentical SCT
1105. Practical Considerations in HLA-Haploidentical Stem Cell Transplant
1106. Conclusions
1107. Suggested Readings
1108. References
1109. 107 Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies
1110. Single Unit Cord Blood Transplantation
1111. Double-Unit Cord Blood Transplantation
1112. Cord Blood Unit Selection
1113. Double-Unit Versus Single-Unit Cord Blood Transplantation
1114. Novel Strategies to Enhance Engraftment
1115. Adoptive Immunotherapy
1116. Future Directions
1117. Suggested Readings
1118. References
1119. 108 Graft-Versus-Host Disease and Graft-Versus-Leukemia Responses
1120. Graft-Versus-Host Disease: Clinical and Pathologic Aspects
1121. Pathophysiology of Acute Graft-Versus-Host Disease
1122. Biomarkers of Acute Graft-Versus-Host Disease
1123. Chronic Graft-Versus-Host Disease
1124. Chronic Graft-Versus-Host Disease: Pathophysiology
1125. Biomarkers of Acute Graft-Versus-Host Disease
1126. Therapy for Chronic Graft-Versus-Host Disease
1127. Graft-Versus-Leukemia Responses
1128. Future Directions
1129. Suggested Readings
1130. References
1131. 109 Complications After Hematopoietic Cell Transplantation
1132. Infections
1133. Early Noninfectious Complications
1134. Late Noninfectious Complications
1135. Graft-Versus-Host Disease
1136. Future Directions
1137. Suggested Readings
1138. References
1139. Part XI Transfusion Medicine
1140. 110 Human Blood Group Antigens and Antibodies
1141. Erythrocyte Blood Group Antigens
1142. References
1143. 111 Principles of Red Blood Cell Transfusion
1144. Red Blood Cell Components
1145. Appropriate Transfusion Practice in Various Clinical Settings
1146. Red Blood Cell Preservation and Storage
1147. Biochemical Changes Associated With Red Blood Cell Storage
1148. Red Cell Alloimmunization
1149. Alternatives to Allogeneic Red Cell Transfusions
1150. Blood Substitutes
1151. Red Blood Cell Substitutes
1152. Suggested Readings
1153. 112 Clinical Considerations in Platelet Transfusion Therapy
1154. Platelet Collection and Manufacturing
1155. Prophylactic Platelet Transfusion
1156. Adverse Effects of Platelet Transfusion
1157. Platelet Refractoriness
1158. References
1159. 113 Human Leukocyte Antigen and Human Neutrophil Antigen Systems
1160. Genetics, Structure, and Function of Human Leukocyte Antigen Molecules
1161. Organization of the Human Leukocyte Antigen Genes
1162. Inheritance and Linkage Disequilibrium
1163. Structure of the Human Leukocyte Antigen Class I and II
1164. Expression of Human Leukocyte Antigen Molecules
1165. Human Leukocyte Antigen Polymorphism and Its Clinical Significance
1166. Nonclassic MHC and MHC Class I Chain-Related Molecules
1167. Non-Human Leukocyte Antigen Polymorphism and Its Clinical Significance
1168. Human Leukocyte Antigen Nomenclature
1169. Immunologically Defined Human Leukocyte Antigen Nomenclature
1170. Sequence-Defined Allelic Nomenclature
1171. Human Leukocyte Antigen Typing in Clinical Hematology and Determination of Compatibility HLA Typing
1172. Testing for Allosensitization and Determination of Compatible Recipient-Donor Pairs
1173. The Human Leukocyte Antigen Molecules as Antigens and HLA Alloimmunization
1174. Human Leukocyte Antigen as a Functional Mediator of Graft-Versus-Host Disease and/or Graft-Versus-Neoplasia Effect
1175. Graft-Versus-Host Disease
1176. Graft-Versus-Neoplasia Effect
1177. Human Leukocyte Antigen and T Cell-Directed Immunization
1178. Monitoring Immune Responses With Tetrameric Human Leukocyte Antigen-Peptide Complexes
1179. Human Leukocyte Antigen Summary
1180. Human Neutrophil Antigens and Their Clinical Significance
1181. The HNA-1 Antigen System
1182. The HNA-2 Antigen System
1183. HNA-3 Antigen Systems
1184. HNA-4 and HNA-5 Antigen Systems
1185. Clinical Significance of Antibodies to Neutrophil Antigens
1186. Autoimmune Neutropenia of Childhood
1187. Transfusion Reactions
1188. Neutrophil Antigens Summary
1189. Suggested Readings
1190. References
1191. 114 Principles of Neutrophil (Granulocyte) Transfusions
1192. Therapeutic GTX for Neutropenic Infections: Historical Experience
1193. Therapeutic GTX for Neutropenic Infections: Modern Experience
1194. Therapeutic GTX in Infants and Children
1195. Prophylactic Granulocyte Transfusions in Neutropenic Patients
1196. Alternative or Additive Measures to Granulocyte Transfusions
1197. Author’s Approach to Therapeutic GTX
1198. References
1199. 115 Transfusion of Plasma and Plasma Derivatives
1200. Plasma Products
1201. Cryoprecipitate
1202. Albumin
1203. Intravenous Immunoglobulin
1204. Hyperimmune Immunoglobulin Products
1205. Suggested Readings
1206. 116 Preparation of Plasma-Derived and Recombinant Human Plasma Proteins
1207. Plasma Fractionation
1208. Product Safety
1209. Plasma Products
1210. Coagulation Factor Concentrates
1211. Other Coagulation and Anticoagulant Concentrates
1212. Plasma Proteinase Inhibitors
1213. Future Directions
1214. Suggested Readings
1215. 117 Transfusion Therapy for Coagulation Factor Deficiencies
1216. Hemophilia A and B
1217. Transfusion Therapy for Hemophilia A and B
1218. Treatment of Hemophilia
1219. Inhibitors of Factor VIII and Factor IX
1220. von Willebrand Disease
1221. Acquired Factor VIII and von Willebrand Factor Deficiency
1222. Other Coagulation Protein Deficiencies
1223. Other Plasma-Derived Protein Concentrates
1224. Future Directions
1225. Suggested Readings
1226. References
1227. 118 Hemapheresis
1228. Principles of Apheresis
1229. Technology and Techniques
1230. Therapeutic Plasmapheresis
1231. Replacement Fluids for Plasma Exchange
1232. Hematopoeitic Stem Cell Collection
1233. Complications of Therapeutic Apheresis
1234. Pediatric Hemapheresis
1235. Pediatric Apheresis
1236. References
1237. 119 Transfusion Reactions to Blood and Cell Therapy Products
1238. Hemolytic Transfusion Reactions
1239. Acute Intravascular Hemolytic Transfusion Reactions
1240. Acute Extravascular Hemolytic Transfusion Reaction
1241. Delayed Hemolytic Reactions
1242. Febrile Nonhemolytic Transfusion Reactions
1243. Allergic Transfusion Reactions
1244. Hypotensive Transfusion Reaction
1245. Infectious Complications of Transfusion
1246. Transfusion-Related Acute Lung Injury
1247. Transfusion-Associated Circulatory Overload
1248. Suggested Readings
1249. 120 Transfusion-Transmitted Diseases
1250. Hepatitis Viruses
1251. Retroviral Infection
1252. Human Herpesvirus Infections
1253. Epstein-Barr Virus (HHV-4)
1254. Parvovirus
1255. West Nile Virus
1256. Dengue Viruses
1257. Chikungunya Virus
1258. Zika Virus
1259. Pandemic Influenza A
1260. Bacterial Contamination
1261. Spirochete Infections
1262. Parasitic Infections
1263. Transmissible Spongiform Encephalopathies
1264. Future Directions
1265. Suggested Readings
1266. References
1267. 121 Pediatric Transfusion Medicine
1268. Pediatric Blood Banking
1269. Technical Considerations/Mechanical Devices
1270. Transfusion Medicine: General Indications and Dosing
1271. Transfusion Medicine: Indications in Unique Pediatric Populations
1272. References
1273. Part XII Hemostasis and Thrombosis
1274. 122 Overview of Hemostasis and Thrombosis
1275. Hemostatic System
1276. Disorders of Hemostasis or Thrombosis
1277. Treatment of Disorders of Hemostasis and Thrombosis
1278. References
1279. 123 The Blood Vessel Wall
1280. Structure of the Vessel Wall
1281. Vascular Development and Differentiation
1282. Physiologic Functions of the Endothelium
1283. Suggested Readings
1284. References
1285. 124 Megakaryocyte and Platelet Structure
1286. Megakaryocyte Development
1287. Regulation of Megakaryocyte Development
1288. Platelet Formation
1289. Platelets
1290. References
1291. 125 Molecular Basis of Platelet Function
1292. Molecular Basis of Platelet Adhesion
1293. Molecular Basis of Platelet Activation
1294. Molecular Basis of Platelet Aggregation
1295. Molecular Basis of Inherited Platelet Disorders
1296. Suggested Readings
1297. References
1298. 126 Molecular Basis of Blood Coagulation
1299. Inventory: Procoagulant, Anticoagulant, and Fibrinolytic Proteins, Inhibitors and Receptors
1300. Connectivity and Dynamics in Hemostasis
1301. Future Directions
1302. Acknowledgements
1303. Suggested Readings
1304. References
1305. 127 Regulatory Mechanisms in Hemostasis
1306. Main Points
1307. Key Events in Blood Coagulation
1308. The Anticoagulant Intravascular Space
1309. The Procoagulant Extravascular Space
1310. The Regulators of Coagulation
1311. References
1312. 128 Clinical Approach to the Patient With Bleeding or Bruising
1313. Epidemiology
1314. Pathobiology
1315. Clinical Manifestations
1316. Laboratory Manifestations
1317. Differential Diagnosis of Bruising and Bleeding
1318. Prognosis
1319. Therapy
1320. Future Directions
1321. References
1322. 129 Laboratory Evaluation of Hemostatic and Thrombotic Disorders
1323. Laboratory Evaluation of Coagulation Proteins
1324. Screening for Coagulation Protein Defects: Activated Partial Thromboplastin Time, Prothrombin Time and Thrombin Clotting Time
1325. Evaluation of Specific Coagulation Protein Defects
1326. Practical Approach to Laboratory Testing of Coagulation Proteins
1327. Laboratory Evaluation of Platelets and Von Willebrand Factor
1328. Laboratory Evaluation of Fibrinolysis
1329. Other Activities for Hemostasis Laboratories
1330. Acknowledgments
1331. References
1332. 130 Acquired Disorders of Platelet Function
1333. Drugs, Foods, and Additives That Affect Platelet Function
1334. Antiplatelet Drugs
1335. Clonal Disorders
1336. Leukemias and Myelodysplastic Syndromes
1337. Solid Tumors
1338. Systemic Metabolic Disorders
1339. Platelet Dysfunction Related With Extracorporeal Circuits
1340. Miscellaneous
1341. Antiplatelet Antibodies
1342. Scurvy
1343. Acquired Platelet Dysfunction With Eosinophilia
1344. Suggested Readings
1345. References
1346. 131 Diseases of Platelet Number
1347. Immune Thrombocytopenia
1348. Neonatal Alloimmune Thrombocytopenia
1349. Posttransfusion Purpura
1350. References
1351. 132 Thrombocytopenia Caused by Platelet Destruction, Hypersplenism, or Hemodilution
1352. Approach to Patients With Thrombocytopenia
1353. Anatomy and Physiology
1354. Pathologic Platelet Sequestration: Hypersplenism
1355. Drug-Induced Thrombocytopenic Syndromes
1356. Drug-Induced Immune Thrombocytopenia
1357. Gold-Induced Thrombocytopenia
1358. Drug-Induced Autoimmune Thrombocytopenia
1359. Drug-Induced Immune Thrombocytopenia of Rapid Onset
1360. Thrombocytopenia Caused by Glycoprotein IIb/IIIa Receptor Antagonists
1361. Miscellaneous Drug-Induced Thrombocytopenic Syndromes
1362. Other Causes of Destructive Thrombocytopenia
1363. Thrombocytopenia Associated With Cardiovascular Disease
1364. Hemodilution and Platelet Consumption After Surgery
1365. References
1366. 133 Heparin-Induced Thrombocytopenia
1367. Epidemiology
1368. Pathobiology
1369. Clinical and Laboratory Manifestations
1370. Differential Diagnosis
1371. Clinical Scoring Systems
1372. Laboratory Diagnosis
1373. Prognosis
1374. Therapy
1375. Platelet Count Monitoring for Heparin-Induced Thrombocytopenia
1376. Anticoagulation and Previous Heparin-Induced Thrombocytopenia
1377. References
1378. 134 Thrombotic Thrombocytopenic Purpura and the Hemolytic Uremic Syndromes
1379. Differential Diagnosis
1380. Thrombotic Thrombocytopenic Purpura
1381. Shiga Toxin Hemolytic Uremic Syndrome
1382. Atypical Hemolytic Uremic Syndrome
1383. Other Thrombotic Microangiopathic Disorders
1384. Future Directions
1385. Suggested Readings
1386. 135 Hemophilia A and B
1387. Epidemiology
1388. Factor VIII Biology: Genetics, Structure, Function, and Pathophysiology
1389. Pathophysiology of Hemophilia A
1390. Factor IX Biology: Genetics, Structure, Function, and Pathophysiology
1391. Clinical Features of Hemophilia
1392. Clinical Management of Hemophilia
1393. Future Directions
1394. References
1395. 136 Inhibitors in Hemophilias
1396. Hemophilia A
1397. Hemophilia B
1398. Factor VII Deficiency
1399. Suggested Readings
1400. References
1401. 137 Rare Coagulation Factor Deficiencies
1402. Introduction
1403. Fibrinogen Deficiency(OMIM 202400)
1404. Dysfibrinogenemia (OMIM 134820 Aα-Chain, 134830 Bβ-Chain, and 134850 γ-Chain)
1405. Prothrombin Deficiency (OMIM 176930)
1406. Factor V Deficiency (OMIM 227400)
1407. Factor VII Deficiency (OMIM 227500)
1408. Factor X Deficiency (OMIM 227600)
1409. Factor XI Deficiency (OMIM 264900)
1410. Deficiencies of Factor XII, Prekallikrein or High-Molecular-Weight Kininogen
1411. Factor XIII Deficiency (OMIM 134570 [A Subunit] and 134580 [B Subunit])
1412. Congenital Deficiencies Involving Multiple Coagulation Factors
1413. References
1414. 138 Structure, Biology, and Genetics of von Willebrand Factor
1415. Functions of von Willebrand Factor
1416. Basal von Willebrand Factor Levels
1417. von Willebrand Factor Gene
1418. Domain Structure
1419. Biosynthesis
1420. Storage and Secretion
1421. ADAMTS13
1422. Clearance
1423. ABO Blood Groups
1424. Areas of Ongoing Investigation
1425. von Willebrand Disease
1426. Suggested Readings
1427. 139 Disseminated Intravascular Coagulation
1428. Epidemiology
1429. Pathobiology
1430. Clinical Manifestations
1431. Laboratory Manifestations
1432. Differential Diagnosis
1433. Therapy
1434. References
1435. 140 Hypercoagulable States
1436. Inherited Hypercoagulable States
1437. Acquired Hypercoagulable States
1438. Combined Inherited and Acquired Hypercoagulable States
1439. Clinical Evaluation of Patients With Hypercoagulable States
1440. Thrombophilia Screening
1441. Laboratory Evaluation of Thrombophilia
1442. Management of Thrombosis in Patients With Hypercoagulable States
1443. Conclusions and Future Directions
1444. References
1445. 141 The Antiphospholipid Syndrome
1446. Definition of Antiphospholipid Syndrome
1447. Antigenic Specificities of Antiphospholipid Antibodies
1448. Pathogenic Effects of Antiphospholipid Antibodies
1449. Antiphospholipid Assays
1450. Clinical Manifestations of the Antiphospholipid Syndrome
1451. Treatment of Patients With Antiphospholipid Syndrome
1452. Nonanticoagulant Treatments Under Study for Antiphospholipid Syndrome
1453. Suggested Readings
1454. 142 Venous Thromboembolism
1455. Pathogenesis of Venous Thromboembolism and Clinical Risk Factors
1456. Thrombogenic Factors
1457. Protective Mechanisms
1458. Hypercoagulable States
1459. Natural History of Venous Thromboembolism
1460. Prognosis of Venous Thromboembolism
1461. Long-Term Complications of Venous Thromboembolism
1462. Diagnosis of Venous Thromboembolism
1463. Objective Diagnostic Tests for Deep Venous Thrombosis
1464. Diagnostic Strategies for Acute Deep Venous Thrombosis
1465. Pulmonary Embolism
1466. Objective Diagnostic Tests for Pulmonary Embolism
1467. Diagnosis of Acute Recurrent Venous Thromboembolism
1468. Prophylaxis of Venous Thromboembolism
1469. Treatment of Venous Thromboembolism
1470. Venous Thrombosis in Pregnancy
1471. Cancer-Associated Venous Thrombosis
1472. Suggested Readings
1473. 143 Mechanical Interventions in Arterial and Venous Thrombosis
1474. Overview of Catheter-Based Thrombolytic Interventions
1475. Conclusion
1476. References
1477. 144 Atherothrombosis
1478. Pathobiology
1479. Lipoprotein Homeostasis and the “Cholesterol Hypothesis”
1480. Foam Cell Formation and the Fatty Streak
1481. Lesion Evolution: Remodeling and the Vulnerable Plaque
1482. Plaque Rupture and Acute Arterial Thrombosis
1483. Hyperlipidemia, Atherosclerosis, and a Systemic Prothrombotic State
1484. Cross-Talk Between Coagulation and Inflammation Systems Impact Atherogenesis
1485. Plaque Regression
1486. Additional Future Directions
1487. References
1488. 145 Stroke
1489. Definition
1490. Epidemiology
1491. Pathobiology
1492. Clinical Manifestations
1493. Investigations
1494. Therapy
1495. Prognosis
1496. Future Directions
1497. Suggested Readings
1498. 146 Acute Coronary Syndromes
1499. Classification
1500. Pathophysiology
1501. Antithrombotic Management
1502. Reperfusion Therapy for ST-Segment Elevation Myocardial Infarction
1503. Antiplatelet Therapy
1504. Anticoagulant Therapy
1505. Conclusions and Future Directions
1506. Suggested Readings
1507. References
1508. 147 Atrial Fibrillation
1509. Epidemiology
1510. Pathobiology
1511. Clinical Manifestations
1512. Diagnosis and Differentials
1513. Heart Rate and Rhythm Control
1514. Prevention of Stroke and Thromboembolism
1515. Anticoagulant-Related Bleeding
1516. Future Directions
1517. References
1518. 148 Peripheral Artery Disease
1519. Epidemiology
1520. Pathobiology
1521. Clinical Manifestations
1522. Diagnosis
1523. Prognosis
1524. Therapy
1525. Future Directions
1526. Suggested Readings
1527. References
1528. 149 Antithrombotic Drugs
1529. Antiplatelet Drugs
1530. Anticoagulants
1531. Oral Anticoagulants
1532. Fibrinolytic Drugs
1533. Conclusions and Future Directions
1534. References
1535. 150 Disorders of Coagulation in the Neonate
1536. Developmental Hemostasis
1537. Neonatal Hemorrhagic Disorders
1538. Evaluation of the Bleeding Neonate
1539. Neonatal Thromboembolic Disorders
1540. Suggested Readings
1541. References
1542. Part XIII Consultative Hematology
1543. 151 Hematologic Changes in Pregnancy
1544. Anemia in Pregnancy
1545. Hemoglobinopathies and Pregnancy
1546. Other Hemolytic Anemias
1547. Thrombocytopenia
1548. Leukemia and Lymphoma
1549. Bleeding Disorders
1550. Hemophilias
1551. Venous Thromboembolic Disease and Pregnancy
1552. Prophylactic Anticoagulation During Pregnancy
1553. Thrombophilia and Pregnancy
1554. Future Directions
1555. Suggested Readings
1556. References
1557. 152 Hematologic Manifestations of Childhood Illness
1558. Infectious Disease
1559. Collagen Vascular Disease and Acute Vasculitis
1560. Cardiopulmonary Disease
1561. Hematologic Manifestations of Childhood Gastrointestinal Disease
1562. Endocrine Disease
1563. Anorexia Nervosa
1564. Thromboembolic Complications in Childhood Illness
1565. Hematologic Complications of Solid Organ Transplant in Children
1566. Hematologic Aspects of Poisoning
1567. Hematologic Aspects of Metabolic Diseases
1568. Splenomegaly in Children
1569. Suggested Readings
1570. References
1571. 153 Hematologic Manifestations of Liver Disease
1572. Red Blood Cell Abnormalities
1573. White Blood Cell Abnormalities
1574. Platelet Abnormalities
1575. Coagulation and Liver Disease
1576. Treatment of Liver Disease–Related Bleeding
1577. Hypercoagulability and Thrombosis in Patients With Liver Disease
1578. Future Directions
1579. Suggested Readings
1580. 154 Hematologic Manifestations of Renal Disease
1581. Anemia
1582. Uremic Bleeding
1583. Thrombosis
1584. Hemolytic Uremic Syndrome
1585. Hematologic Abnormalities in the Renal Transplant Patient
1586. References
1587. 155 Hematologic Manifestations of Malignancy
1588. Erythrocytes
1589. Platelets
1590. Leukocytes
1591. Bone Marrow Metastases
1592. Thrombosis and Cancer
1593. Future Directions
1594. Suggested Readings
1595. 156 Integrative Therapies in Patients With Hematologic Diseases
1596. Integrative Therapy Domains and Their Use
1597. Research Techniques of Integrative Therapies
1598. Review of Results of Integrative Therapies in Hematology/Oncology Patients
1599. Individual Integrative Therapy Modalities
1600. References
1601. 157 Hematologic Manifestations of HIV/AIDS
1602. Definition and Epidemiology of HIV Infection
1603. Transmission of HIV-1
1604. Etiology and Pathogensis
1605. Clinical Course of HIV-1 Infection
1606. Hematologic and Bone Marrow Abnormalities in HIV-1 Infection
1607. Leukopenia and Neutropenia: Incidence and Pathogenesis
1608. Thrombocytopenia in HIV Infection
1609. Thrombotic Microangiopathy and Thrombotic Thrombocytopenic Purpura
1610. Thromboembolic Disease
1611. References
1612. 158 Hematologic Aspects of Parasitic Diseases
1613. Malaria
1614. Visceral Leishmaniasis
1615. African Trypanosomiasis
1616. American Trypanosomiasis
1617. Babesiosis
1618. Eosinophilia
1619. Other Parasitic Diseases
1620. Future Directions
1621. Suggested Readings
1622. References
1623. 159 Hematologic Problems in the Surgical Patient
1624. Preoperative Evaluation of Hemostatic Risk
1625. Hemostatic Agents
1626. Management of Patients With Hemostatic Abnormalities
1627. Intraoperative and Postoperative Bleeding
1628. Perioperative Anticoagulation Management
1629. Perioperative Thromboprophylaxis
1630. Summary
1631. Suggested Readings
1632. References
1633. 160 The Spleen and Its Disorders
1634. Normal Splenic Anatomy and Function
1635. Examination of the Spleen
1636. Imaging of the Spleen
1637. Tests of Splenic Function
1638. Asplenia and Hyposplenia
1639. Acquired Hyposplenism
1640. Splenomegaly and Hypersplenism
1641. Splenectomy
1642. Conclusions and Future Directions
1643. References
1644. 161 Hematology in Aging
1645. Epidemiology
1646. Pathobiology
1647. Clinical Manifestations
1648. Laboratory Manifestations
1649. Differential Diagnosis
1650. Prognosis
1651. Therapy
1652. Future Directions
1653. References
1654. 162 Resources for the Hematologist
1655. Appendix Contents
1656. Interpretive Comments
1657. Selected Reference Values
1658. Index

Author Biography

Leslie Silberstein

Affiliations and Expertise
Director, Transfusion Medicine Professor of Pathology Boston Children’s Hospital Harvard Medical School Boston, MA

John Anastasi

Affiliations and Expertise