Immune Hematology

230 Pages·2018·3.72 MB·English

by  Jenny M. Despotovic

Immune
Hematology
Diagnosis and Management of
Autoimmune Cytopenias
Jenny M. Despotovic
Editor
123
Immune Hematology
Jenny M. Despotovic
Editor
Immune Hematology
Diagnosis and Management of Autoimmune
Cytopenias
Editor
Jenny M. Despotovic
Baylor College of Medicine
Texas Children's Hospital
Houston, TX
USA
ISBN 978-3-319-73268-8 ISBN 978-3-319-73269-5 (eBook)
https://doi.org/10.1007/978-3-319-73269-5
Library of Congress Control Number: 2018939554
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Preface
The autoimmune cytopenias are a fascinating and clinically challenging group of
disorders characterized by the development of autoantibodies against self-antigens
on the surface of hematopoietic cells. The pathophysiology of these disorders is
complex and incompletely understood but is generally related to loss of self-
tolerance due to immune dysregulation. These disorders can be primary or second-
ary to underlying systemic autoimmunity or immune deficiency. The diagnosis of
these disorders can be challenging and varies significantly according to disease and
underlying pathology. While antibody testing is a cornerstone of diagnosis in some
autoimmune cytopenias, it offers low sensitivity and specificity for others.
This book offers an extensive overview of immune thrombocytopenia (ITP),
autoimmune hemolytic anemia (AIHA), Evans syndrome, thrombotic thrombocyto-
penic purpura (TTP), and autoimmune neutropenia (AIN). Each section contains
chapters covering historical background, pathophysiology, differential diagnosis,
diagnostic workup, and management, offering a much more in-depth review of
these disorders than is available in most hematology or immunology textbooks.
Readers will find many useful figures, tables, and diagnostic algorithms to comple-
ment the text.
The first part covers ITP, a condition in which autoantibodies are generated
against platelet antigens resulting in peripheral destruction of circulating platelets
and often profound thrombocytopenia. The trigger of the development of platelet
antibodies is often not identified but is typically thought to result from an environ-
mental stimulus such as infection. The pathophysiology of this disorder is complex
and involves the generation of antiplatelet antibodies, T-cell imbalance with a shift
in the T-cell profile favoring decreased self-tolerance, and abnormal production of
platelets. There are a variety of treatments available for both acute control of bleed-
ing symptoms and long-term management and each will be comprehensively
reviewed in Part I.
Part II covers AIHA and Evans syndrome. Autoimmune hemolytic anemia is a
rare but potentially life-threatening disorder resulting from antibodies against
endogenous erythrocytes and often severe hemolytic anemia. The complications of
hemolytic anemia can be devastating and this part highlights the importance of early
v
vi Preface
diagnosis and prompt treatment of the various forms of AIHA. As each type of
AIHA has a different pathophysiology, each requires a different management strat-
egy. Evans syndrome is historically defined as the combination of AIHA and ITP
but currently encompasses any two (or more) autoimmune cytopenias occurring
simultaneously or separately. The antibodies which cause the cytopenias are not
cross-reacting but discrete antibodies, and therefore highlight a more generalized
immune dysregulation which typically becomes a chronic disease with a number of
important complications often requiring immunomodulatory therapy.
Thrombotic thrombocytopenic purpura (TTP) is the focus of Part III. This is a
fascinating autoimmune cytopenia caused by autoantibodies against a disintegrin
and metalloproteinase with a thrombospondin type 1 motif, member 13
(ADAMTS13), resulting in microangiopathic hemolytic anemia and often severe
thrombocytopenia due to consumptive coagulopathy. Prior to the use of plasma
exchange, this disorder was almost universally fatal. Experts in this field provide
the latest information available on the pathophysiology and treatment of TTP in
this part.
Finally, Part IV covers autoimmune neutropenia (AIN), a common cause of
severe neutropenia in childhood with a typically benign clinical course. Given the
extensive differential diagnosis of severe neutropenia, the authors of this part pro-
vide critical information on the typical presentation and biology driving AIN, as
well as approach to workup and treatment, if needed.
Within this book, readers are offered an in-depth and comprehensive review of
the autoimmune cytopenias. Any hematologist, immunologist, general practitioner,
or trainee wanting better understanding of these entities from a historical and patho-
logical perspective, or requiring relevant and up-to-date information regarding diag-
nosis and management of the immune hematologic disorders, will benefit from
these expert contents.
Houston, TX Jenny M. Despotovic
Contents
Part I Immune Thrombocytopenia (ITP)
1 Background of Immune Thrombocytopenia . . . . . . . . . . . . . . . . . . . . 3
Kristina M. Haley
2 Pathophysiology of Immune Thrombocytopenia . . . . . . . . . . . . . . . . . 17
Taylor Olmsted Kim
3 Presentation and Evaluation of Immune Thrombocytopenia . . . . . . . 35
Vicky R. Breakey
4 The Treatment of Immune Thrombocytopenia . . . . . . . . . . . . . . . . . . 45
Kandace L. Gollomp and Michele P. Lambert
Part II Autoimmune Hemolytic Anemia (AIHA)
5 Background, Presentation and Pathophysiology
of Autoimmune Hemolytic Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Shawki Qasim
6 Treatment of Autoimmune Hemolytic Anemia . . . . . . . . . . . . . . . . . . 103
Omar Niss and Russell E. Ware
7 Evans Syndrome: Background, Clinical Presentation,
Pathophysiology, and Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Amanda B. Grimes
Part III Thrombotic Thrombocytopenic Purpura (TTP)
8 Background and Presentation of Thrombotic Thrombocytopenic
Purpura . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Clay Cohen
9 Pathophysiology of Thrombotic Thrombocytopenic Purpura . . . . . . 171
Sarah E. Sartain
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viii Contents
10 Evaluation and Treatment of Thrombotic
Thrombocytopenic Purpura . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
Satheesh Chonat
Part IV Autoimmune Neutropenia (AIN)
11 Background and Pathophysiology of Autoimmune Neutropenia . . . . 207
Jacquelyn M. Powers
12 Evaluation and Management of Autoimmune Neutropenia . . . . . . . . 213
Alicia K. Chang
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
Contributors
Vicky  R.  Breakey, MD, MEd, FRCPC (Peds) Department of Pediatrics,
McMaster University, Hamilton, ON, Canada
Alicia K. Chang, MD Section of Hematology-Oncology, Department of Pediatrics,
Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA
Satheesh Chonat, MD Pediatric Hematology, Department of Pediatrics, Emory
University School of Medicine and Aflac Cancer and Blood Disorders Center,
Children’s Healthcare of Atlanta, Atlanta, GA, USA
Clay Cohen, MD Department of Pediatric Hematology and Oncology, Baylor
College of Medicine, Houston, TX, USA
Kandace L. Gollomp, MD Division of Hematology, The Children’s Hospital of
Philadelphia, Philadelphia, PA, USA
Amanda B. Grimes, MD Baylor College of Medicine, Texas Children’s Hospital,
Houston, TX, USA
Kristina M. Haley, DO, MCR Pediatric Hematology/Oncology, Department of
Pediatrics, Oregon Health and Science University, Portland, OR, USA
Michele P. Lambert, MD Division of Hematology, The Children’s Hospital of
Philadelphia, Philadelphia, PA, USA
Omar Niss, MD Division of Hematology, Department of Pediatrics, Cincinnati
Children’s Hospital Medical Center and University of Cincinnati College of
Medicine, Cincinnati, OH, USA
Taylor Olmsted Kim, MD Section of Hematology/Oncology, Department of
Pediatrics, Texas Children’s Cancer and Hematology Centers, Baylor College of
Medicine, Houston, TX, USA
Jacquelyn M. Powers, MD, MS Pediatric Hematology/Oncology, Baylor College
of Medicine, Texas Children’s Cancer and Hematology Center, Houston, TX, USA
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x Contributors
Shawki Qasim, MD Baylor College of Medicine, Texas Children’s Hospital,
Houston, TX, USA
Sarah E. Sartain, MD Baylor College of Medicine, Texas Children’s Hospital,
Houston, TX, USA
Russell E. Ware, MD, PhD Division of Hematology, Department of Pediatrics,
Cincinnati Children’s Hospital Medical Center and University of Cincinnati College
of Medicine, Cincinnati, OH, USA