Anemia of Chronic Disease

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ISBN: 9780824759728 | 0824759729
Cover: Hardcover
Copyright: 3/1/2005

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This book summarizes the most current research on the anemia of chronic disease and identifies effective diagnostic strategies for this common clinical condition-covering key topics related to the design and selection of therapeutic options including the treatment of the underlying disease, the biology of erythropoietin and the regulation of erythropoiesis, the disturbance of iron homeostasis, and the complex nature of the systemic inflammatory response.

Contributors

xiii

Introduction: Anemia of Chronic Disease: The Enigma and the Challenge

Chaim Hershko, Victor R. Gordeuk and Günter Weiss

xvii

PART I: BASICS

1. Regulation of Iron Metabolism

(60)

Kostas Pantopoulos

Biology of Iron

(2)

Iron's Toxicity

(2)

Iron Distribution in the Body

(1)

Biomedical Aspects of Iron Metabolism

(3)

Mechanisms for Dietary Iron Absorption and Erythroid Iron Utilization

(5)

Regulation of Dietary Iron Absorption and Erythroid Iron Utilization

(4)

Cellular Iron Uptake

(5)

Intracellular Iron Storage

(2)

Posttranscriptional Regulation of Cellular Iron Metabolism by the IRE/IRP System

(4)

Iron Regulatory Proteins, IRP1, and IRP2

(5)

Other Regulatory Mechanisms

(1)

Conclusions

(27)

2. Erythropoietin and Erythropoiesis

(26)

Eric Metzen and Wolfgang Jelkmann

Introduction

(1)

Chemical Structure of EPO

(2)

Sites and Control of EPO Production

(4)

Assay of Circulating Epo and Interpretation of Results

(1)

Action of EPO on Hemopoietic Cells

(3)

Pathophysiological Aspects

(15)

3. Sepsis and Systemic Inflammatory Response Syndrome

(18)

Herbert Tilg

Introduction

(1)

Definitions

(1)

Pathogenesis

(8)

Epidemiology

(1)

Categorical Definitions and Patient Risk

(1)

New Concepts in the Treatment of Sepsis

(1)

Conclusions

100

(5)

PART II: PATHOPHYSIOLOGY

4. Disturbances of Iron Homeostasis

105

(22)

Victoriano Mulero and Jeremy H. Brock

Normal Iron Metabolism

105

(6)

The Imbalance of Iron Homeostasis During Inflammation

111

(5)

Disturbance of Iron Trafficking in Macrophages Infected with Intracellular Pathogens

116

(11)

5. Inhibition of Erythropoiesis by Inflammatory Cytokines

127

(18)

Robert T. Means, Jr.

Introduction

127

(3)

Inhibition of Erythroid Progenitors by Specific Cytokines

130

(5)

Effects of Erythropoietin and Other Colony Stimulating Factors on Cytokine Inhibition of Erythropoiesis

135

(1)

Implications for Therapy

136

(9)

6. Endogenous Erythropoietin in the Anemia of Chronic Disorders

145

(56)

Yves Beguin

Introduction

145

(3)

Effects of Cytokines on Erythropoietin Production

148

(2)

Interpretation of Serum EPO Levels

150

(6)

Serum Erythropoietin in Anemia of Chronic Disorders

156

(5)

Serum Erythropoietin in Cancer

161

(6)

Serum Erythropoietin and Chemotherapy

167

(6)

Serum Erythropoietin as Predictor of Response to rHuEPO

173

(28)

7. Erythrophagocytosis and Decreased Erythrocyte Survival

201

(28)

J.J.M. Marx

Introduction

201

(1)

The Physiology of Erythrocyte Aging

202

(2)

Methods for Estimation of Erythrocyte Life Span

204

(1)

Causes of Decreased Erythrocyte Survival and Life Span

205

(1)

Effect of Inflammation on Erythrocyte Survival

206

(1)

Uptake of Effete Erythrocytes by the Macrophage System

207

(2)

Erythrocyte Destruction and Release of Iron from Hemoglobin and Macrophages

209

(4)

Major Proteins Involved in Iron Release from Hemoglobin and Macrophages

213

(6)

Iron Release from Macrophages in Inflammation

219

(10)

8. New Regulator Molecules in Anemia of Chronic Diseases

229

(26)

Olivier Loréal and Pierre Brissot

Introduction

229

(1)

Hepcidin: A Key Molecule in Iron Metabolism

230

(3)

Hepcidin: A Key Molecule in Anemia of Chronic Diseases

233

(1)

Hepcidin Expression Regulators

234

(6)

Molecular Function of Hepcidin

240

(4)

Conclusions

244

(11)

PART III: ACD RATIONALE: IS ANEMIA PART OF THE BODY'S PHYSIOLOGICIAL RESPONSE TO INFLAMMATION?

9. Iron Withholding as a Defense Strategy

255

(26)

Eugene D. Weinberg

Introduction

255

(1)

Historical Development of the Concept of Iron Withholding Defense

256

(4)

Components of Iron Withholding Defense

260

(5)

Invader Factors Associated with Iron Withholding Defense

265

(5)

Host Factors Associated with Impaired Iron Withholding Defense

270

(4)

Ecological Aspects of Iron Withholding Defense

274

(7)

10. Iron, Iron Genes, and the Immune System

281

(54)

C.S. Cardoso, G. Weiss and M. De Sousa

Introduction

281

(1)

Iron Homeostasis: A Brief Summary

282

(25)

Interplay Between Iron Metabolism and Cytokine Activities

307

(5)

Conclusion

312

(23)

PART IV: DIAGNOSIS OF ACD

11. Clinical Approach to the Patient with Anemia of Chronic Disease

335

(14)

Victor R. Gordeuk

Introduction

335

(1)

Chronic Inflammatory Process

336

(2)

Hypoproliferative Anemia of Normocytic or Microcytic, Morphology

338

(1)

Absence of Other Causes of a Hypoproliferative Anemia

339

(1)

Changes in Iron Metabolism

340

(1)

Diagnosis of Iron Deficiency in the Setting of Inflammation

341

(3)

Hepcidin

344

(1)

Conclusion

344

(1)

Appendix

345

(4)

12. Usefulness of Old and New Diagnostic Tests in ACD

349

(16)

Kari Punnonen and Allan Rajamaki

Distinguishing the Anemia of Chronic Disease from Other Forms of Anemia

349

(2)

Red Blood Cell Morphology and Traditional Classification of Anemias on the Basis of Mean Corpuscular Volume

351

(1)

The Traditional Markers of Iron Status Including Ferritin, Transferrin, and Serum Iron in Diagnosis of ACD

352

(3)

Soluble Transferrin Receptor and TfR-F Index in the Differential Diagnosis of IDA and ACD

355

(3)

Analysis of Hemoglobin Synthesis and Red Blood Cells

358

(1)

Novel Markers of Iron Turnover

359

(1)

Summary

360

(5)

PART V: THERAPY

13. Treatment of ACD: An Introduction

365

(2)

Günter Weiss

14. Human Recombinant Erythropoietin

367

(14)

Hanspreet Kaur, Alan Lichtin, and Deepjot Singh

Introduction

367

(1)

Mechanism of Action

368

(1)

Serum Erythropoietin Levels as Guidelines for Therapy

369

(1)

Erythropoietin Therapy for HIV Infection/HIV Treatment Related Anemia

370

(2)

Erythropoietin Therapy of Anemia in Patients with Rheumatoid Arthritis

372

(1)

Treatment of Anemia in Inflammatory Bowel Disease

373

(1)

Erythropoietin in Patients with Malignancy or Chemotherapy

373

(1)

Side Effects

374

(2)

Summary

376

(5)

15. Iron Therapy and the Anemia of Chronic Disease

381

(16)

Victor R. Gordeuk

Introduction

381

(1)

Ineffectiveness and Potential Harm of Routine Iron Therapy in the Anemia of Chronic Disease

382

(1)

Iron Deficiency

383

(5)

Iron Therapy for Patients with Combined Iron Deficiency and the Anemia of Chronic Disease

388

(5)

Iron Therapy in Anemia of Chronic Disease Patients Receiving Erythropoietin

393

(4)

16. Blood Transfusions

397

(40)

Eleftherios C. Vamvakas

RBC Transfusion Therapy in Chronic Anemia

399

(3)

Established Noninfectious Risks of ABT

402

(5)

Infectious Risks of ABT

407

(10)

Purported Noninfectious Risks of ABT

417

(9)

Summary

426

(11)

17. Iron and Erythropoietin

437

(52)

Lawrence T. Goodnough

Introduction

437

(1)

Prevalence of Anemia of Chronic Disease

438

(1)

Anemia and Adverse Outcomes

438

(5)

Management of Anemia

443

(1)

Erythropoietin, Iron, and Erythropoiesis

443

(2)

Erythropoietin Response to Anemia

445

(2)

Iron-Restricted Erythropoiesis

447

(7)

Laboratory Evaluation of Iron Metabolism

454

(6)

Iron Therapy Strategies

460

(1)

Current Issues in Erythropoietin Therapy

461

(5)

Conclusion

466

(23)

PART VI: CONTROVERSIES IN ACD THERAPY

18. Positive Effects of Correction of Anemia in Malignant Diseases

489

(70)

Gudrun Pohl and Heinz Ludwig

Introduction

489

(9)

Indications for Anemia Treatment

498

(1)

Treatment Options

499

(10)

Positive Effects of Correction of ACD

509

(26)

Conclusion

535

(24)

19. Putative Negative Effects of the Correction of Anemia in ACD

559

(34)

Günter Weiss

Introduction: ACD as a Defense Strategy of the Body

559

(4)

Severe ACD Is Associated with a Poor Prognosis: Does this Imply that Anemia Correction May Be Beneficial?

563

(3)

Potential Hazards of Specific Therapeutic Regimen

566

(10)

General Consideration Concerning Anemia Correction in ACD

576

(17)

PART VII: SPECIFIC CONDITIONS OF ACD

20. Anemia of Chronic Disease in Hematologic Disorders and Oncology

593

(14)

Robert T. Means and Gordon D. McLaren

Frequency of Anemia of Chronic Disease in Hematologic and Oncologic Disorders

593

(2)

Pathogenesis of ACD in Hematologic and Oncologic Disorders

595

(2)

Diagnosis of ACD in Cancer Patients

597

(1)

Treatment

598

(9)

21. Anemia in Cancer Patients Undergoing Surgery

607

(8)

D. Öfner

Introduction

607

(1)

Patients and Methods

608

(1)

Results and Discussion

608

(7)

22. Iron Status, Anemia of Chronic Disease, and Infection

615

(18)

Johan R. Boelaert

Tuberculosis

616

(4)

HIV Infection

620

(3)

HIV/Tuberculosis Coinfection

623

(1)

Hepcidin as Key Mediator of Infection-Related Anemia of Chronic Disease

624

(9)

23. ACD in Inflammatory Rheumatic Diseases

633

(26)

J.P. Kaltwasser and U. Arndt

Introduction and Pathogenesis

633

(3)

Incidence of Anemia

636

(1)

Differential Diagnosis of Anemia

636

(1)

Laboratory Diagnosis

637

(3)

Clinical Impact of ACD in Rheumatic Disorders

640

(1)

Treatment of ACD

641

(6)

Summary and Possible Therapeutic Future Options

647

(12)

24. Anemia in Intensive Care Patients

659

(12)

Albert van de Wiel

Introduction

659

(1)

Mechanisms

660

(4)

Therapy

664

(1)

Summary

665

(6)

25. Anemia in Renal Disease

671

(56)

Jorge Luis Ajuria, Paul L. Kimmel, and Robert S. Siegel

Introduction

671

(2)

Epidemiology of Renal Disease in the United States

673

(1)

Anemia and Chronic Renal Disease

674

(1)

Pathophysiology

675

(1)

Erythropoietin and the Kidney

675

(2)

Erythropoietin Production in Renal Disease

677

(1)

Erythropoietin Production in Acute Renal Failure

678

(1)

Uremia and Erythropoiesis

679

(1)

Erythropoiesis in Uremia

680

(1)

Erythropoiesis and Inflammation

681

(1)

Renal Failure and Myelofibrosis

682

(1)

Shortened Erythrocyte Life Span

683

(2)

Membrane Alterations in Uremic Erythrocytes

685

(3)

Abnormal Hemostasis

688

(2)

Trends in rHuEPO Therapy

690

(1)

Management of Anemia

691

(3)

Clinical Sequelae of Anemia in Chronic Renal Disease

694

(1)

Clinical Benefits of rHuEPO Therapy

695

(2)

Conclusion

697

(30)

26. Anemia of Chronic Disease in Inflammatory Bowel Diseases

727

(18)

Christoph Gasche

Importance of ACD in IBD

727

(1)

Specific Pathogenesis of Anemia in IBD

728

(3)

Current Therapy

731

(3)

Unanswered Issues

734

(11)

Index

745

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Anemia of Chronic Disease

Summary

Table of Contents

Supplemental Materials