Iron in Clinical Practice

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

Assessment of Hepatic Iron Overload 143

Bibliography 144

23 Impact of Iron Overload on the Endocrine System 147
Amy Morrison and Miles Levy

Introduction 147

Diabetes Mellitus 147

Reproductive Endocrinology 148

Growth and Bone Health 150

Adrenal Function 150

Summary 151

Bibliography 152

24 Iron Overload and the Musculoskeletal System 153
Kassim Javaid

Introduction 153

Osteoporosis and Fracture Risk 153

Osteoarthritis 154

Calcium Pyrophosphate Deposition Disease 155

Management of Iron Overload in the Joints 155

Bibliography 156

Part 3c Assessment and Management of Iron Overload 157

25 Assessment of Iron Overload 159
Subarna Chakravorty

Introduction 159

Awareness of Potential Causes 159

Assessment of Transfusional Iron Overload 159

Role of Serum Ferritin and Iron Studies in Assessing Iron Overload 160

Imaging in Iron Overload 161

Monitoring Requirements for At-risk Patients 162

Bibliography 163

26 Management of Iron Overload 165
Nandini Sadasivam

Introduction 165

Iron Chelation Therapy 165

Indications for Iron Chelation Therapy 165

Administration of Iron Chelation Therapy 166

Combination Chelation Therapy 166

When to Start Iron Chelation Therapy 168

Practical Tips for Clinicians 168

Desferrioxamine 168

Deferasirox 169

Deferiprone 169

Calculation of ROIL Adults 169

Calculation of ROIL in Paediatric 169

Practical Prescribing Tips 170

Dose Adjustments for Comorbidities 171

Renal Disease 171

Desferrioxamine 171

Deferasirox 171

Established Dialysis 171

Liver Disease 171

Deferasirox 171

Pregnancy 171

Emerging Novel Therapies 171

Bibliography 172

Index 173

Learn the tools for addressing a widespread public health issue with this practical guide.

Iron deficiency and iron overload are among the most common health conditions encountered in the course of clinical practice, with the potential to produce a range of morbidities and increase overall mortality. However, these conditions are often under-recognized, resulting in unnecessary disease and loss of well-being. There is an urgent need to raise awareness among clinicians of the causes, effects and management of iron imbalance.

Iron in Clinical Practice meets this need with a brisk, practical guide to recognizing and treating both iron deficiency and iron overload in clinical settings. Edited by two Oxford haematologists and leading specialists in iron management, it covers major areas of medicine and surgery impacted by these disorders. The result is an essential resource for both beginning and experienced clinicians. Iron in Clinical Practice readers will find:

• Introductory chapters outlining the role of iron in the body, its utilization and mechanisms of trafficking and distribution, and how these are impacted by disease.
• Coverage of a range of clinical settings across medicine, surgery and primary care.
• Illustrations, tables, and graphs throughout.

Iron in Clinical Practice is ideal for all health care practitioners of any specialty.

Sue Pavord, MD, is a Consultant Haematologist at Oxford University Hospitals NHS FT, UK, and Associate Senior Lecturer in Medicine at the University of Oxford. She specialises in all aspects of medical haematology and has established services for iron deficiency management in different clinical settings, and has led national guidelines in this area. She is President of the British Society for Haematology 2024-2026.

Noemi Roy, MD, is Consultant Haematologist at Oxford University Hospitals NHS FT, UK, and an Honorary Senior Clinical Lecturer at the University of Oxford. She specialises in red cell disorders and iron overload. She has been a key player in patient and public engagement in the field and is co-founder of the Congenital Anaemia Network.