Thomas Kühne
Immune Thrombocytopenia (ITP) (eBook, PDF)
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Thomas Kühne
Immune Thrombocytopenia (ITP) (eBook, PDF)
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The material of ITP became more and more complex and substantial in recent years. The current edition was updated in a difficult time reflected by the COVID-19 pandemic with many obstacles and adversities. Therefore all authors worked hard on this edition and contributed to the successful completion of this book. It would be a desirable conclusion if this new edition would contribute to optimal ITP patient care and management.
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The material of ITP became more and more complex and substantial in recent years. The current edition was updated in a difficult time reflected by the COVID-19 pandemic with many obstacles and adversities. Therefore all authors worked hard on this edition and contributed to the successful completion of this book. It would be a desirable conclusion if this new edition would contribute to optimal ITP patient care and management.
Produktdetails
- Produktdetails
- Verlag: UNI-MED Verlag AG
- Seitenzahl: 203
- Erscheinungstermin: 13. Mai 2022
- Englisch
- ISBN-13: 9783837456240
- Artikelnr.: 64078148
- Verlag: UNI-MED Verlag AG
- Seitenzahl: 203
- Erscheinungstermin: 13. Mai 2022
- Englisch
- ISBN-13: 9783837456240
- Artikelnr.: 64078148
1.Introduction18 2.History of ITP21 2.1.Introduction: What is thrombocytopenic bleeding?21 2.2.History of bleeding22 2.3.History of the pathogenesis of ITP23 2.4.History of management of patients with ITP23 2.5.The therapeutic translation of IVIg to other autoimmune disorders with similar pathophysiology as in ITP25 2.6.Stimulation of platelet production by megakaryocytes26 2.7.Recent development of clinical research of ITP and new aspects of platelets themselves27 3.Basic immunology of ITP30 3.1.T cell and cytokine abnormalities in ITP30 3.2.B cell abnormalities31 3.3.Dendritic Cells (DC) in ITP31 3.4.Environmental factors in ITP32 3.5.Alternative modes of thrombocytopenia in ITP33 3.6.Conclusions33 4.Megakaryopoiesis in ITP36 4.1.Overview of normal thrombopoiesis36 4.2.Thrombopoiesis in ITP: evidence for accelerated platelet destruction38 4.3.Thrombopoiesis in ITP: evidence for impaired platelet production39 4.4.Megakaryopoiesis in ITP: evidence for direct roles of megakaryocytes40 5.Genetics of ITP45 5.1.Challenges in defining a genetic etiology of ITP45 5.2.Germline single-nucleotide variant (SNV) candidate gene approach45 5.3.Familial ITP45 5.4.Genome-wide association studies (GWAS)46 5.5.Future Directions47 6.Differential diagnosis of ITP: Inherited Thrombocytopenias48 6.1.Inherited Thrombocytopenias48 6.1.1.Clinical and laboratory peculiarities of inherited thrombocytopenias48 6.1.2.When to suspect inherited thrombocytopenias54 6.2.Differential diagnosis between ITP and inherited thrombocytopenias55 6.3.How to confirm the suspicion of inherited thrombocytopenia57 7.Secondary ITP59 7.1.Definition and limitation59 7.2.Etiology59 7.3.Diagnostic workflow60 7.4.Genetic panel62 7.5.Adult versus children62 7.6.Conclusions64 8.Standardization of definitions, terminology and outcome criteria: a common language in ITP67 8.1.Criteria adopted by the IWG to harmonize terminology and definitions in ITP68 8.2.Primary and secondary ITP and diagnostic platelet count threshold68 8.3.Definition of the different phases and severity of the disease69 8.4.Therapeutic goals70 8.5.Definition of response71 8.6.Refractory ITP: definition, therapeutic goals and response assessment73 8.7.Clinical trial-adapted criteria for eligibility and outcome assessment75 8.8.Application of 2009 IWG proposals in real-word and need for revision75 8.9.Conclusions75 9.Decision making in the management of children with ITP80 9.1.A preference-sensitive decision80 9.2.Shared decision making81 9.3.Conclusion81 10.ITP in childhood: a problem-oriented review of the management84 10.1.Clinical presentation and diagnosis85 10.2.Prevention from and therapy of bleeding87 10.3.Non-intervention88 10.4.Intervention88 10.5.Splenectomy90 10.6.Conclusions90 11.ITP in adulthood93 11.1.Treatment of adult ITP94 11.1.1.General rules94 11.1.2.First-line therapy (initial treatment for newly diagnosed patients)94 11.1.3.Second-line therapy95 11.1.4.Other second-line therapies97 11.1.5.Patients failing multiple therapies99 11.1.6.New second- or third- or later-line therapies in the management of adults with ITP100 11.2.Conclusion101 12.Management of ITP in the elderly105 12.1.Diagnosis of ITP in the elderly105 12.2.Treating ITP in the elderly105 12.2.1.Intravenous immunoglobulins (IVIg)106 12.2.2.Corticosteroids106 12.2.3.Managing treatment failure and corticosteroid dependency106 12.2.4.Thrombopoietin receptor agonists106 12.2.5.Rituximab107 12.2.6.Fostamatinib108 12.2.7.Splenectomy108 12.2.8.Other medications108 12.2.9.Investigational therapies108 13.Chronic refractory ITP110 13.1.Practical Considerations of Refractory ITP110 13.2.Infection-related thrombocytopenia113 13.3.Drug-induced thrombocytopenia115 13.4.Secondary ITP115 13.5.Therapeutic approach116 13.5.1.General approach to refractory ITP117 13.5.1.1.Observation117 13.5.1.2.Standard therapy117 13.5.1.3.Therapy for refractory disease117 13.6.Outcomes and sequelae121 13.7.Summary122 14.Immune thrombocytopenia in pregnancy127 14.1.The differential diagnosis of thrombocytopenia during pregnancy127 14.2.ITP in pregnancy128 14.3.Conclusion130 15.Drugs in ITP: mechanisms of action133 15.1.Steroids133 15.2.Intravenous immunoglobulin (IVIg)134 15.3.Anti-D134 15.4.Rituximab (anti-CD20)135 15.5.Drugs that stimulate platelet production136 15.6.Conclusion137 16.Mechanism of action of high dose intravenous immunoglobulin in ITP141 16.1.Introduction141 16.2.Mononuclear phagocyte system (MPS) blockade142 16.3.Anti-idiotype antibodies144 16.4.IgG Fc region sialylation and the inhibitory Fc receptor (FcgRIIB)145 16.5.Cytokine modulation146 16.6.Neonatal Fc receptor (FcRn)147 16.7.Dendritic cells (DCs) and immunomodulation148 16.8.Current and emerging IVIg alternatives and mimetics for use in ITP149 16.9.Other mechanisms and conclusions151 17.Immune thrombocytopenia – the patients' perspective158 17.1.Patients “hate steroids”158 17.2.Rituximab159 17.3.Patients try to avoid splenectomy159 17.4.Patients and Thrombopoetin-Receptor Agonists (TRAs)159 17.5.Other therapies160 17.6.The quagmire of modern medicine160 17.7.What patients really want162 17.8.Conclusions162 18.Quality of Life as a treatment endpoint for patients with ITP164 18.1.Introduction164 18.2.Assessment of Health Related Quality of Life in ITP164 18.2.1.HRQoL in Adults164 18.2.2.HRQoL in Children165 18.3.ITP symptoms in HRQoL165 18.3.1.Bleeding and Bruising166 18.3.2.Fatigue167 18.4.Impact of treatments on HRQoL167 18.4.1.First-line agents167 18.4.2.Second-line therapies168 18.5.Conclusion169 19.Fatigue as a treatment end point in ITP172 19.1.How do we define fatigue172 19.2.How can we assess fatigue172 19.3.How much of a problem is fatigue in ITP173 19.4.Why does fatigue develop in ITP176 19.5.Cytokines and Immune dysregulation177 19.6.How do we manage the ITP patient with fatigue179 19.7.Improving the Standard of Care180 19.8.Conclusion181 20.Guidelines for using ITP management guidelines186 20.1.Guidelines for management of ITP187 20.2.Pros and cons of guidelines187 20.3.Evidence based vs. patient centered management188 21.State of the Art and future Considerations of ITP190 21.1.Heterogeneity of ITP190 21.2.Unknown etiology of ITP192 21.3.Immunomodulation in inflammatory and autoimmune disorders192 21.4.Platelet stimulation by thrombopoietin receptor agonists (TPO-RA) of megakaryopoiesis193 21.5.Future progress and the question of adequate management of ITP194 22.List of abbreviations201 Index203
1.Introduction182.History of ITP212.1.Introduction: What is thrombocytopenic bleeding?212.2.History of bleeding222.3.History of the pathogenesis of ITP232.4.History of management of patients with ITP232.5.The therapeutic translation of IVIg to other autoimmune disorders with similarpathophysiology as in ITP252.6.Stimulation of platelet production by megakaryocytes262.7.Recent development of clinical research of ITP and new aspects of platelets themselves273.Basic immunology of ITP303.1.T cell and cytokine abnormalities in ITP303.2.B cell abnormalities313.3.Dendritic Cells (DC) in ITP313.4.Environmental factors in ITP323.5.Alternative modes of thrombocytopenia in ITP333.6.Conclusions334.Megakaryopoiesis in ITP364.1.Overview of normal thrombopoiesis364.2.Thrombopoiesis in ITP: evidence for accelerated platelet destruction384.3.Thrombopoiesis in ITP: evidence for impaired platelet production394.4.Megakaryopoiesis in ITP: evidence for direct roles of megakaryocytes405.Genetics of ITP455.1.Challenges in defining a genetic etiology of ITP455.2.Germline single-nucleotide variant (SNV) candidate gene approach455.3.Familial ITP455.4.Genome-wide association studies (GWAS)465.5.Future Directions476.Differential diagnosis of ITP: Inherited Thrombocytopenias486.1.Inherited Thrombocytopenias486.1.1.Clinical and laboratory peculiarities of inherited thrombocytopenias486.1.2.When to suspect inherited thrombocytopenias546.2.Differential diagnosis between ITP and inherited thrombocytopenias556.3.How to confirm the suspicion of inherited thrombocytopenia577.Secondary ITP597.1.Definition and limitation597.2.Etiology597.3.Diagnostic workflow607.4.Genetic panel627.5.Adult versus children627.6.Conclusions648.Standardization of definitions, terminology and outcome criteria: a common language in ITP678.1.Criteria adopted by the IWG to harmonize terminology and definitions in ITP688.2.Primary and secondary ITP and diagnostic platelet count threshold688.3.Definition of the different phases and severity of the disease698.4.Therapeutic goals708.5.Definition of response718.6.Refractory ITP: definition, therapeutic goals and response assessment738.7.Clinical trial-adapted criteria for eligibility and outcome assessment758.8.Application of 2009 IWG proposals in real-word and need for revision758.9.Conclusions759.Decision making in the management of children with ITP809.1.A preference-sensitive decision809.2.Shared decision making819.3.Conclusion8110.ITP in childhood: a problem-oriented review of the management8410.1.Clinical presentation and diagnosis8510.2.Prevention from and therapy of bleeding8710.3.Non-intervention8810.4.Intervention8810.5.Splenectomy9010.6.Conclusions9011.ITP in adulthood9311.1.Treatment of adult ITP9411.1.1.General rules9411.1.2.First-line therapy (initial treatment for newly diagnosed patients)9411.1.3.Second-line therapy9511.1.4.Other second-line therapies9711.1.5.Patients failing multiple therapies9911.1.6.New second- or third- or later-line therapies in the management of adults with ITP10011.2.Conclusion10112.Management of ITP in the elderly10512.1.Diagnosis of ITP in the elderly10512.2.Treating ITP in the elderly10512.2.1.Intravenous immunoglobulins (IVIg)10612.2.2.Corticosteroids10612.2.3.Managing treatment failure and corticosteroid dependency10612.2.4.Thrombopoietin receptor agonists10612.2.5.Rituximab10712.2.6.Fostamatinib10812.2.7.Splenectomy10812.2.8.Other medications10812.2.9.Investigational therapies10813.Chronic refractory ITP11013.1.Practical Considerations of Refractory ITP11013.2.Infection-related thrombocytopenia11313.3.Drug-induced thrombocytopenia11513.4.Secondary ITP11513.5.Therapeutic approach11613.5.1.General approach to refractory ITP11713.5.1.1.Observation11713.5.1.2.Standard therapy11713.5.1.3.Therapy for refractory disease11713.6.Outcomes and sequelae12113.7.Summary12214.Immune thrombocytopenia in pregnancy12714.1
1.Introduction18 2.History of ITP21 2.1.Introduction: What is thrombocytopenic bleeding?21 2.2.History of bleeding22 2.3.History of the pathogenesis of ITP23 2.4.History of management of patients with ITP23 2.5.The therapeutic translation of IVIg to other autoimmune disorders with similar pathophysiology as in ITP25 2.6.Stimulation of platelet production by megakaryocytes26 2.7.Recent development of clinical research of ITP and new aspects of platelets themselves27 3.Basic immunology of ITP30 3.1.T cell and cytokine abnormalities in ITP30 3.2.B cell abnormalities31 3.3.Dendritic Cells (DC) in ITP31 3.4.Environmental factors in ITP32 3.5.Alternative modes of thrombocytopenia in ITP33 3.6.Conclusions33 4.Megakaryopoiesis in ITP36 4.1.Overview of normal thrombopoiesis36 4.2.Thrombopoiesis in ITP: evidence for accelerated platelet destruction38 4.3.Thrombopoiesis in ITP: evidence for impaired platelet production39 4.4.Megakaryopoiesis in ITP: evidence for direct roles of megakaryocytes40 5.Genetics of ITP45 5.1.Challenges in defining a genetic etiology of ITP45 5.2.Germline single-nucleotide variant (SNV) candidate gene approach45 5.3.Familial ITP45 5.4.Genome-wide association studies (GWAS)46 5.5.Future Directions47 6.Differential diagnosis of ITP: Inherited Thrombocytopenias48 6.1.Inherited Thrombocytopenias48 6.1.1.Clinical and laboratory peculiarities of inherited thrombocytopenias48 6.1.2.When to suspect inherited thrombocytopenias54 6.2.Differential diagnosis between ITP and inherited thrombocytopenias55 6.3.How to confirm the suspicion of inherited thrombocytopenia57 7.Secondary ITP59 7.1.Definition and limitation59 7.2.Etiology59 7.3.Diagnostic workflow60 7.4.Genetic panel62 7.5.Adult versus children62 7.6.Conclusions64 8.Standardization of definitions, terminology and outcome criteria: a common language in ITP67 8.1.Criteria adopted by the IWG to harmonize terminology and definitions in ITP68 8.2.Primary and secondary ITP and diagnostic platelet count threshold68 8.3.Definition of the different phases and severity of the disease69 8.4.Therapeutic goals70 8.5.Definition of response71 8.6.Refractory ITP: definition, therapeutic goals and response assessment73 8.7.Clinical trial-adapted criteria for eligibility and outcome assessment75 8.8.Application of 2009 IWG proposals in real-word and need for revision75 8.9.Conclusions75 9.Decision making in the management of children with ITP80 9.1.A preference-sensitive decision80 9.2.Shared decision making81 9.3.Conclusion81 10.ITP in childhood: a problem-oriented review of the management84 10.1.Clinical presentation and diagnosis85 10.2.Prevention from and therapy of bleeding87 10.3.Non-intervention88 10.4.Intervention88 10.5.Splenectomy90 10.6.Conclusions90 11.ITP in adulthood93 11.1.Treatment of adult ITP94 11.1.1.General rules94 11.1.2.First-line therapy (initial treatment for newly diagnosed patients)94 11.1.3.Second-line therapy95 11.1.4.Other second-line therapies97 11.1.5.Patients failing multiple therapies99 11.1.6.New second- or third- or later-line therapies in the management of adults with ITP100 11.2.Conclusion101 12.Management of ITP in the elderly105 12.1.Diagnosis of ITP in the elderly105 12.2.Treating ITP in the elderly105 12.2.1.Intravenous immunoglobulins (IVIg)106 12.2.2.Corticosteroids106 12.2.3.Managing treatment failure and corticosteroid dependency106 12.2.4.Thrombopoietin receptor agonists106 12.2.5.Rituximab107 12.2.6.Fostamatinib108 12.2.7.Splenectomy108 12.2.8.Other medications108 12.2.9.Investigational therapies108 13.Chronic refractory ITP110 13.1.Practical Considerations of Refractory ITP110 13.2.Infection-related thrombocytopenia113 13.3.Drug-induced thrombocytopenia115 13.4.Secondary ITP115 13.5.Therapeutic approach116 13.5.1.General approach to refractory ITP117 13.5.1.1.Observation117 13.5.1.2.Standard therapy117 13.5.1.3.Therapy for refractory disease117 13.6.Outcomes and sequelae121 13.7.Summary122 14.Immune thrombocytopenia in pregnancy127 14.1.The differential diagnosis of thrombocytopenia during pregnancy127 14.2.ITP in pregnancy128 14.3.Conclusion130 15.Drugs in ITP: mechanisms of action133 15.1.Steroids133 15.2.Intravenous immunoglobulin (IVIg)134 15.3.Anti-D134 15.4.Rituximab (anti-CD20)135 15.5.Drugs that stimulate platelet production136 15.6.Conclusion137 16.Mechanism of action of high dose intravenous immunoglobulin in ITP141 16.1.Introduction141 16.2.Mononuclear phagocyte system (MPS) blockade142 16.3.Anti-idiotype antibodies144 16.4.IgG Fc region sialylation and the inhibitory Fc receptor (FcgRIIB)145 16.5.Cytokine modulation146 16.6.Neonatal Fc receptor (FcRn)147 16.7.Dendritic cells (DCs) and immunomodulation148 16.8.Current and emerging IVIg alternatives and mimetics for use in ITP149 16.9.Other mechanisms and conclusions151 17.Immune thrombocytopenia – the patients' perspective158 17.1.Patients “hate steroids”158 17.2.Rituximab159 17.3.Patients try to avoid splenectomy159 17.4.Patients and Thrombopoetin-Receptor Agonists (TRAs)159 17.5.Other therapies160 17.6.The quagmire of modern medicine160 17.7.What patients really want162 17.8.Conclusions162 18.Quality of Life as a treatment endpoint for patients with ITP164 18.1.Introduction164 18.2.Assessment of Health Related Quality of Life in ITP164 18.2.1.HRQoL in Adults164 18.2.2.HRQoL in Children165 18.3.ITP symptoms in HRQoL165 18.3.1.Bleeding and Bruising166 18.3.2.Fatigue167 18.4.Impact of treatments on HRQoL167 18.4.1.First-line agents167 18.4.2.Second-line therapies168 18.5.Conclusion169 19.Fatigue as a treatment end point in ITP172 19.1.How do we define fatigue172 19.2.How can we assess fatigue172 19.3.How much of a problem is fatigue in ITP173 19.4.Why does fatigue develop in ITP176 19.5.Cytokines and Immune dysregulation177 19.6.How do we manage the ITP patient with fatigue179 19.7.Improving the Standard of Care180 19.8.Conclusion181 20.Guidelines for using ITP management guidelines186 20.1.Guidelines for management of ITP187 20.2.Pros and cons of guidelines187 20.3.Evidence based vs. patient centered management188 21.State of the Art and future Considerations of ITP190 21.1.Heterogeneity of ITP190 21.2.Unknown etiology of ITP192 21.3.Immunomodulation in inflammatory and autoimmune disorders192 21.4.Platelet stimulation by thrombopoietin receptor agonists (TPO-RA) of megakaryopoiesis193 21.5.Future progress and the question of adequate management of ITP194 22.List of abbreviations201 Index203
1.Introduction182.History of ITP212.1.Introduction: What is thrombocytopenic bleeding?212.2.History of bleeding222.3.History of the pathogenesis of ITP232.4.History of management of patients with ITP232.5.The therapeutic translation of IVIg to other autoimmune disorders with similarpathophysiology as in ITP252.6.Stimulation of platelet production by megakaryocytes262.7.Recent development of clinical research of ITP and new aspects of platelets themselves273.Basic immunology of ITP303.1.T cell and cytokine abnormalities in ITP303.2.B cell abnormalities313.3.Dendritic Cells (DC) in ITP313.4.Environmental factors in ITP323.5.Alternative modes of thrombocytopenia in ITP333.6.Conclusions334.Megakaryopoiesis in ITP364.1.Overview of normal thrombopoiesis364.2.Thrombopoiesis in ITP: evidence for accelerated platelet destruction384.3.Thrombopoiesis in ITP: evidence for impaired platelet production394.4.Megakaryopoiesis in ITP: evidence for direct roles of megakaryocytes405.Genetics of ITP455.1.Challenges in defining a genetic etiology of ITP455.2.Germline single-nucleotide variant (SNV) candidate gene approach455.3.Familial ITP455.4.Genome-wide association studies (GWAS)465.5.Future Directions476.Differential diagnosis of ITP: Inherited Thrombocytopenias486.1.Inherited Thrombocytopenias486.1.1.Clinical and laboratory peculiarities of inherited thrombocytopenias486.1.2.When to suspect inherited thrombocytopenias546.2.Differential diagnosis between ITP and inherited thrombocytopenias556.3.How to confirm the suspicion of inherited thrombocytopenia577.Secondary ITP597.1.Definition and limitation597.2.Etiology597.3.Diagnostic workflow607.4.Genetic panel627.5.Adult versus children627.6.Conclusions648.Standardization of definitions, terminology and outcome criteria: a common language in ITP678.1.Criteria adopted by the IWG to harmonize terminology and definitions in ITP688.2.Primary and secondary ITP and diagnostic platelet count threshold688.3.Definition of the different phases and severity of the disease698.4.Therapeutic goals708.5.Definition of response718.6.Refractory ITP: definition, therapeutic goals and response assessment738.7.Clinical trial-adapted criteria for eligibility and outcome assessment758.8.Application of 2009 IWG proposals in real-word and need for revision758.9.Conclusions759.Decision making in the management of children with ITP809.1.A preference-sensitive decision809.2.Shared decision making819.3.Conclusion8110.ITP in childhood: a problem-oriented review of the management8410.1.Clinical presentation and diagnosis8510.2.Prevention from and therapy of bleeding8710.3.Non-intervention8810.4.Intervention8810.5.Splenectomy9010.6.Conclusions9011.ITP in adulthood9311.1.Treatment of adult ITP9411.1.1.General rules9411.1.2.First-line therapy (initial treatment for newly diagnosed patients)9411.1.3.Second-line therapy9511.1.4.Other second-line therapies9711.1.5.Patients failing multiple therapies9911.1.6.New second- or third- or later-line therapies in the management of adults with ITP10011.2.Conclusion10112.Management of ITP in the elderly10512.1.Diagnosis of ITP in the elderly10512.2.Treating ITP in the elderly10512.2.1.Intravenous immunoglobulins (IVIg)10612.2.2.Corticosteroids10612.2.3.Managing treatment failure and corticosteroid dependency10612.2.4.Thrombopoietin receptor agonists10612.2.5.Rituximab10712.2.6.Fostamatinib10812.2.7.Splenectomy10812.2.8.Other medications10812.2.9.Investigational therapies10813.Chronic refractory ITP11013.1.Practical Considerations of Refractory ITP11013.2.Infection-related thrombocytopenia11313.3.Drug-induced thrombocytopenia11513.4.Secondary ITP11513.5.Therapeutic approach11613.5.1.General approach to refractory ITP11713.5.1.1.Observation11713.5.1.2.Standard therapy11713.5.1.3.Therapy for refractory disease11713.6.Outcomes and sequelae12113.7.Summary12214.Immune thrombocytopenia in pregnancy12714.1