List of Contributors xiii Preface xvii About the Companion Website xix Part 1 Introduction to Iron 1 1 An Introduction to Iron in the Body 3 Sue Pavord and Noemi Roy Introduction 3 Iron in the Body 3 Essential Functions of Iron in the Body 6 Iron Deficiency 6 Iron Overload 6 Bibliography 9 2 Regulation of Iron Trafficking in the Body 11 Megan Teh and Hal Drakesmith Introduction 11 Hepcidin and Systemic Iron Homeostasis 11 Regulation of Hepcidin 12 Sensing Iron Concentrations 12 Erythropoietic Demand 14 Inflammation 14 Cellular Iron Homeostasis: Ferritin and Transferrin Receptor 14 Assessing Iron Status - How the Markers Used Relate to Underlying Biology 15 Bibliography 16 3 Iron and Immunity 17 Fabiana Busti and Domenico Girelli Introduction 17 The Battle for Iron and the Concept of ''Nutritional Immunity'' 17 Therapeutic Interventions Harnessing Nutritional Immunity 18 Iron Status and Susceptibility to Infections 19 Iron Deficiency and Health of Populations 19 Iron Overload and Risk of Infection 20 Iron Status and Response to Vaccines 20 Bibliography 22 Part 2 Iron Deficiency 23 Part 2a Assessment and Management of Iron Deficiency 25 4 Impact of Iron Deficiency on the Individual 27 Patrick Kyei-Mensah Introduction 27 Symptoms and Signs of Iron Deficiency 28 Impact of Iron Deficiency on Specific At-risk Groups 28 Pregnancy, Parturition and Lactation 30 Paediatric Population 30 Non-pregnant Premenopausal Women 31 Individuals from Resource-poor Settings 31 Other Clinical Situations Associated with Iron Deficiency 31 Gastrointestinal Bleeding 31 Heart Failure 31 Chronic Obstructive Airway Disease 32 Renal Disease 32 Conclusion 32 Bibliography 32 5 Assessment of Iron Deficiency 33 Hanke L. Matlung and Dorine W. Swinkels Introduction 33 Definitions 33 Ferritin Thresholds 33 Inflammation and Liver Disease 36 Additional Biomarkers 36 Red Cell Indices 36 Hepcidin Levels 37 Conclusion 38 Bibliography 38 6 Available Treatments for Iron Deficiency 39 Paolo Polzella Introduction 39 Oral Iron Supplementation 39 Administration of Oral Iron 39 Intravenous Iron Therapy 40 Potential Adverse Effects of Intravenous Iron 41 Individualising Treatment 42 Bibliography 43 Part 2b Causes, Impact, Management and Prevention of Iron Deficiency in Clinical Specialties 45 7 Iron Deficiency in Primary Care 47 David McCartney Introduction 47 Presentation of Iron Deficiency in Primary Care 47 The Main Causes of Iron Deficiency in Primary Care 48 Pre-menopausal Women 48 Post-menopausal Women and Men 49 Older Adults 49 The Diagnosis of Iron Deficiency in Primary Care 49 Haemoglobin 49 Iron Studies 49 Further Investigations 50 Treatment of Iron Deficiency in Primary Care 50 Dietary Advice and Prevention of Future Iron Deficiency 51 Bibliography 51 8 Iron Deficiency in the Preoperative Patient 53 Caroline R. Evans Introduction 53 Haemoglobin Thresholds 53 Causes of Iron Deficiency in the Surgical Setting 54 Laboratory Tests 54 Management of Preoperative Iron Deficiency 55 Iron Treatment 55 Postoperative Management 56 Conclusion 56 Bibliography 56 9 Iron Deficiency in Gastroenterology 57 Mohmmed Tauseef Sharip and Nurulamin M. Noor Introduction 57 Gastrointestinal Causes of Iron Deficiency 57 Assessment of Iron Deficiency in Patients with Gastrointestinal Disease 59 Specific Gastrointestinal Investigations 59 Angiodysplasia 62 Treatment of Iron Deficiency in Patients with Gastrointestinal Disease 62 Bibliography 64 10 Iron Deficiency in Renal Medicine 65 Philip A. Kalra Introduction 65 Types of Iron Used in Nephrology and Safety Considerations 65 Iron Use in Haemodialysis Patients 66 Iron Use in Non-Dialysis-Dependent Chronic Kidney Disease 68 Iron Use in Peritoneal Dialysis 68 Bibliography 69 11 Iron Deficiency in Cardiology 71 Samira Lakhal-Littleton Introduction 71 Causes of Iron Deficiency in Heart Failure 71 Impact of Iron Deficiency in Heart Failure 72 Management of Iron Deficiency in Heart Failure 72 Diagnostic and Management Uncertainties in Individuals with Cardiac Disease 73 Current Definitions of Iron Deficiency 73 Current Iron Replacement Therapies 74 Bibliography 75 12 Iron Deficiency in Neurology 77 Carmen Jacob and Ian Galea Introduction 77 Iron Utilisation in the Central Nervous System 77 Iron and Neurocognitive Development 79 Neurological Associations in Iron Deficiency 79 Recommendations for Management of Iron Deficiency with Neurological Symptoms 80 Conclusion 80 Bibliography 80 13 Iron Deficiency in Obstetrics 83 Sue Pavord Introduction 83 The Maternal Effects of Iron Deficiency 83 Fetal Effects of Iron Deficiency 85 Defining Anaemia in Pregnancy 85 How Is Iron Deficiency Diagnosed in Pregnancy? 86 Indications for Intravenous Iron 86 Management of Postpartum Anaemia 87 Bibliography 87 14 Iron Deficiency in Gynaecology 89 Imo J. Akpan Introduction 89 Causes of Heavy Menstrual Bleeding 89 Definition of Heavy Menstrual Bleeding 89 Prevention of Iron Deficiency in Gynaecology 89 Investigation of Heavy Menstrual Bleeding 90 Management of Heavy Menstrual Bleeding 91 Hormonal Preparations 91 Anticoagulation Modification 91 Haemostatic Agents 92 Surgical Management 92 Iron Deficiency and Iron Deficiency Anaemia in Gynaecology 92 Impact of Iron Deficiency in Gynaecology 92 Management of Iron Deficiency in Women with Gynaecological Bleeding 94 Oral Iron Supplementation 94 Parenteral Iron Supplementation 95 Blood Transfusion 95 Bibliography 95 15 Iron Deficiency in Orthopaedics 97 Antony Palmer Introduction 97 Diagnosis 97 Aetiology of Iron Deficiency 98 Preoperative Treatment of Iron Deficiency Anaemia 98 Patient Outcomes 98 Iron Deficiency Without Anaemia 100 Bibliography 100 16 Iron Deficiency in Intensive Care 101 Akshay Shah Introduction 101 Iron Homeostasis in Critical Illness 101 Diagnosing Iron Deficiency in Critical Illness 103 Clinical Implications of Iron Deficiency in Intensive Care Unit 103 Patient Blood Management in Intensive Care 104 Intravenous Iron in Intensive Care 104 Concomitant Therapies for Anaemia Management in Intensive Care 104 Bibliography 105 17 Iron Deficiency in Medical Oncology 107 Sue Pavord Introduction 107 Causes of Anaemia in Patients with Cancer 107 Diagnosis of Iron Deficiency in Patients with Cancer 108 Management of Anaemia in Patients with Cancer 108 Erythropoiesis Stimulating Agents 108 Blood Transfusion in Oncology 109 Prevention of Anaemia in Patients with Cancer 109 Implementation of Local Policy 109 Novel Anti-anaemia Agents 110 Conclusion 110 Bibliography 111 Part 3 Iron Overload 113 Part 3a Causes of Iron Overload 115 18 Transfusional Iron Overload 117 Samah Babiker and John Porter Introduction 117 The Causes of Iron Overload and Influencing Factors 117 Pathophysiology and Effects of Transfusional Iron Loading on Body Iron Distribution 117 Rates of Transfusional Iron Overloading and Distribution in Different Diseases 119 Consequences of Transfusional Iron Overload 119 Prevention of Transfusional Iron Overload 121 Bibliography 121 19 Haemochromatosis 123 Graca Porto Introduction 123 Pathogenesis 123 Frequency and Penetrance of HFE-Related Haemochromatosis 124 Diagnosis 125 Treatment and Prevention 127 Bibliography 127 20 Ineffective Erythropoiesis 129 Noémi Roy Introduction 129 Erythropoiesis 129 The Role of Erythropoietin and Iron 130 Ferrokinetic Studies 131 Erythroferrone 131 Bibliography 132 Part 3b Effects of Iron Overload on Body Organs 133 21 Iron Overload in the Heart 135 Malcolm Walker Iron and the Heart 135 Cardiac Iron Regulation 135 Iron Overload 135 Clinical Presentations and Their Management 136 Ventricular Dysfunction and Heart Failure 136 Arrhythmia 137 Assessment of Cardiac Iron 137 Magnetic Resonance Imaging 137 Other Heart Tests 138 Long-Term Management and Prevention 138 Bibliography 140 22 Iron Overload and the Liver 141 Emma Saunsbury and Jeremy Cobbold Introduction 141 Histological Patterns of Hepatic Iron Overload 141 Pathophysiology of Hepatic Damage Secondary to Iron Overload 141.