Immune Hematology: Diagnosis and Management of Autoimmune Cytopenias [Team-IRA]

This text provides a concise yet comprehensive overview of the most common autoimmune cytopenias affecting adults and children. The book is divided into four sections, each of which focuses on a major autoimmune cytopenia. The first section features background, pathophysiology, presentation, evaluation, and treatment strategies for immune thrombocytopenia (ITP), the most common cause of antibody-mediated platelet destruction. The second section reviews common forms and treatment strategies for autoimmune hemolytic anemia (AIHA), including a chapter dedicated specifically to Evans Syndrome. The third section comprehensively reviews the pathophysiology, diagnosis and current management approaches to thrombotic thrombocytopenic purpura (TTP), a potentially life-threatening autoimmune syndrome. The book concludes with a final section on autoimmune neutropenia. Each section includes a review of common underlying systemic autoimmune conditions and immune deficiency syndromes that can accompany or cause autoimmune cytopenias. Written by experts in each content area, Immune Hematology: Diagnosis and Management of Autoimmune Cytopenias is a valuable resource for clinicians and professionals who treat patients afflicted with autoimmune cytopenias, including primary care providers, hematologist/oncologists, immunologists, among others. Preface Contents Contributors Part I: Immune Thrombocytopenia (ITP) Chapter 1: Background of Immune Thrombocytopenia Introduction Historical Perspective Terminology Presentation Primary ITP and Secondary ITP Differential Diagnosis Conclusion References Chapter 2: Pathophysiology of Immune Thrombocytopenia Platelet Autoantibodies Balance of Platelet Destruction and Production Abnormal Megakaryocyte Morphology Antibody Destruction of Megakaryocytes Inadequate Thrombopoietin Levels T Cell-Mediated ITP T Cell-Propagated Autoantibody Production Helper T Cell Responses Role of Th17 Cells Regulatory T cells B Cell-Mediated ITP B-Regulatory Cells Myeloid-Derived Suppressor Cells Genetic Studies Secondary ITP Helicobacter pylori-Related ITP CMV-Related ITP Varicella Zoster-Related ITP Hepatitis C-Related ITP HIV-Related ITP Malignancy-Related ITP Other Autoimmune Disorders Evans Syndrome Autoimmune Lymphoproliferative Syndrome (ALPS) References Chapter 3: Presentation and Evaluation of Immune Thrombocytopenia Introduction Clinical Presentation History Physical Examination Bleeding Assessment Initial Diagnostic Investigations Diagnostic Approach Additional Testing for Suspected ITP The Role of Bone Marrow Testing Platelet Antibody Testing Screening Tests for Associated Conditions Infectious Triggers for ITP: Hepatitis C, HIV, and H. pylori Autoimmune Conditions Immunodeficiencies Summary References Chapter 4: The Treatment of Immune Thrombocytopenia Introduction General Treatment Considerations Who Should Be Treated? First-Line Management Corticosteroids Mechanism of Action Steroid Treatment Recommendations Intravenous Immunoglobulin Mechanism of Action IVIG Treatment Recommendations Anti-D Immunoglobulin Mechanism of Action Anti-D Treatment Recommendations Second-Line Therapy Splenectomy Mechanism of Action Splenectomy Treatment Recommendations Rituximab Mechanism of Action Rituximab Treatment Recommendations Thrombopoietin Receptor Agonists (TPO-RAs) Mechanism of Action TPO-RA Adverse Effects Treatment Recommendations Use of TPO-RAs in Pediatric ITP Use of TPO-RAs in Newly Diagnosed ITP Management of Life-Threatening Bleeding Other Agents Antimetabolites Novel Therapies References Part II: Autoimmune Hemolytic Anemia (AIHA) Chapter 5: Background, Presentation and Pathophysiology of Autoimmune Hemolytic Anemia History of Immune Hemolysis Definitions and Classification Warm AIHA Pathophysiology Clinical Features Cold AIHA (Cold Agglutinin Disease) Pathophysiology Clinical Features Paroxysmal Cold Hemoglobinuria Pathophysiology Clinical Features Mixed AIHA References Chapter 6: Treatment of Autoimmune Hemolytic Anemia Introduction Diagnosis and Classification Etiology Frontline Treatment Blood Transfusions Corticosteroids Second-Line Treatments Rituximab Splenectomy Immunosuppressive Therapies Additional Treatment Options Acute Temporizing Therapy Third-Line Therapies “Last-Resort” Options Emerging Novel Therapies Treatment of Secondary AIHA Evans Syndrome ALPS Other Primary Immune Deficiencies Systemic Lupus Erythematosus Cold AIHA Conclusions References Chapter 7: Evans Syndrome: Background, Clinical Presentation, Pathophysiology, and Management Introduction Background History Definitions/Terminology Clinical Presentation Epidemiology Clinical Features Etiology ALPS CVID Systemic Autoimmunity Pathophysiology Evans Syndrome ALPS CVID Systemic Autoimmunity Novel and Miscellaneous Disorders of Immune Dysregulation Management General Principles Primary Evans Syndrome Secondary Evans Syndrome Conclusion References Part III: Thrombotic Thrombocytopenic Purpura (TTP) Chapter 8: Background and Presentation of Thrombotic Thrombocytopenic Purpura Historical Perspective Incidence Differential Diagnosis Shiga Toxin-Mediated Hemolytic-Uremic Syndrome Complement-Mediated TMA Drug-Mediated TMA Disorders of Vitamin B12 Metabolism Coagulation-Mediated TMA Clinical Presentation Initial Evaluation/Workup Conclusion References Chapter 9: Pathophysiology of Thrombotic Thrombocytopenic Purpura Introduction Normal Pathophysiology of VWF and ADAMTS13 VWF ADAMTS13 Pathogenesis of TTP Endothelial Injury, Microvascular Thrombosis, and Organ Dysfunction Hematologic Findings Antibodies in Acquired TTP Other Etiologies of Acquired TTP Newer Concepts in the Pathogenesis of TTP: The Alternative Complement Pathway The Alternative Complement Pathway (Fig. 9.3) AP Activation on ULVWF Strings and the Implications in TTP Clinical Evidence of AP Activation in TTP Conclusion References Chapter 10: Evaluation and Treatment of Thrombotic Thrombocytopenic Purpura Clinical Presentation Laboratory Diagnosis Initial Management of Acquired TTP Plasma Therapy Corticosteroids Rituximab Monitoring After Initial Management of Acquired TTP Risk Factors and Prevention of Relapse Management of Refractory/Relapsing Acquired TTP Immunomodulatory Agents Cyclosporine A Vincristine Cyclophosphamide Mycophenolate Mofetil Bortezomib Splenectomy Newer Agents N-acetylcysteine Targeted Therapy in TTP Recombinant ADAMTS13 Long-Term Outcomes Conclusion References Part IV: Autoimmune Neutropenia (AIN) Chapter 11: Background and Pathophysiology of Autoimmune Neutropenia Overview of Neutropenia Epidemiology of Autoimmune Neutropenia Pathophysiology of Immune Neutropenia Neonatal Immune Neutropenia Primary Autoimmune Neutropenia Secondary Autoimmune Neutropenia References Chapter 12: Evaluation and Management of Autoimmune Neutropenia Evaluation and Workup Differential Diagnosis of Isolated Childhood Neutropenia Cyclic Neutropenia Severe Congenital Neutropenia (SCN) Neutropenia Secondary to Drug Administration and Nutrient Deficiencies AIN Associated With Other Autoimmune Diseases Diagnosis Neutrophil Antibody Detection Methods Human Neutrophil Alloantigens HNA-1 HNA-2 HNA-3 HNA-4a and HNA-5a Treatment Conclusions References Index