Preface; References; Contents; Contributors; Part I: Sickle Cell Disease; Chapter 1: Clinical Manifestations of Sickle Cell Disease Across the Lifespan; Introduction; Pathophysiology, Epidemiology, and Disease Modulators; Pathophysiology; Epidemiology; Genetic Modulators of Disease Severity; Prognosis; Treatment; Systemic Complications; Anemia; Painful Crises; Infections; Fever and Bacteremia; Infection Prevention; Specific Infections; Central Nervous System; Cardiovascular; Pulmonary; Renal; The Hepatobiliary and Gastrointestinal Systems; Bone Involvement

Ocular Manifestations Leg Ulcers; Thrombosis; Priapism; Treatment Toxicity; Other Major Life Events Complicated by SCD; Clinical Challenges; Newborn Screening: Identifying Patients for Early Clinical Care; Risk Stratification; Stigma and the Patient Experience; Knowledge Gaps; References; Chapter 2: Pathobiology of Sickle Cell Disease Vaso-occlusion and Targeted Therapies; Adhesion Pathways; Adhesive Interactions of Red Cells and Leukocytes with the Endothelium; Neutrophil-RBC Interactions; Therapeutic Interventions Targeting Adhesion Molecules; Inflammatory Pathways

Adenosine and Invariant Natural Killer T (iNKT) Cells Leukotrienes; Oxidative Stress and Impaired Nitric Oxide Biology; Role of Fetal Hemoglobin; Anti-sickling Agents; Chronic Pain in Sickle Cell Disease; Role of Activated Coagulation in SCD; Targeting Coagulation in SCD; Heparin; Direct Thrombin and Factor X Inhibitors; Vitamin K Antagonists; Role of Platelets in SCD; Antiplatelet Agents; Summary; References; Chapter 3: Current Non-HSCT Treatments for SCD; Disease-Modifying Therapies; Hydroxyurea; Blood Transfusions; Hematopoietic Stem Cell Transplantation

Supportive Therapies Analgesics; Non-opioid Analgesics; Opioid Analgesics; Other Adjuvant Therapies for Pain; Antibiotics and Immunizations; Penicillin Prophylaxis; Immunizations; Fluids; Evolving Therapies; Drugs Targeting Adhesion; GMI-1070; Crizanlizumab (SelG1); Drugs Targeting Hemoglobin Polymerization; GBT440; Other Mechanism-Based Therapies Under Investigation; References; Chapter 4: Risk-Based Therapies for Sickle Cell Disease; Introduction; Importance of Severity Prediction for Children with Sickle Cell Disease; Disease Severity Predictor or Association?

Historical Attempts to Identify Severity Predictors Risk Prediction in the Modern Era; Risk Stratification When Universal Newborn Screening, Penicillin Prophylaxis, and Routine TCD Screening Utilization Were Inconsistent or Unknown; Summary of the Predictive Value of the Three Most Commonly Studied Predictive Variables; HbF as a Predictor of SCA Complications; Alpha Globin Gene Number as a Predictor of SCA-Related Complications; Reticulocyte Count as a Predictor of SCA Severity; Where Do We Go from Here?; Conclusions; References