Non-Neoplastic Hematologic Disorders: A Quick Review of Modern Diagnostic and Therapeutic Approaches

Preface
Contents
Contributors
Part I: Benign Disorders of White Blood Cells
	1: Benign Neutrophilic Disorders
		Introduction
		Pathogenesis
		Diagnosis
			Neutrophilia
			Neutropenia
		Differential Diagnosis
			Neutrophilia
			Neutropenia
		Prognosis
		Treatment
		Promising Clinical Study
		References
	2: Benign Eosinophil Disorders
		Introduction
		Pathogenesis
		Diagnosis
		Differential Diagnosis
		Treatment
		Prognosis
		References
	3: Benign Monocytic Disorders
		Introduction
		Pathogenesis
		Diagnosis
		Differential Diagnosis
		Prognosis
		Treatment
		Promising Clinical Studies
		References
	4: Benign Basophil and Mast Cell Disorders
		Basophils
			Introduction
			Pathophysiology
			Diagnosis
			Differential Diagnosis
			Treatment
		Mast Cells
			Introduction
			Pathophysiology
			Diagnosis
			Differential Diagnosis
			Prognosis
			Treatment
			Promising Clinical Studies
		References
	5: Benign Lymphocytic Disorders
		Introduction
		Pathogenesis
		Diagnosis
			Peripheral Blood Smear Review
			Flow Cytometry
			Cytogenetic and Molecular Tests
		Differential Diagnoses
			Benign Lymphocytosis
			Malignant Lymphocytosis
			Lymphocytopenia
		Prognosis
		Treatment
		Promising Clinical Studies
		References
	6: Primary and Secondary Immunodeficiency
		Introduction
		Pathogenesis
		Diagnosis
		Differential Diagnosis
		Prognosis
		Treatment
			Prophylactic Antimicrobial Therapy
			Immunoglobulin Therapy
			HSCT
		Promising Clinical Studies
		References
	7: Benign Histiocytic and Dendritic Cell Disorders
		Introduction
		Pathogenesis
		Diagnosis
		Differential Diagnoses
		Treatment
		Prognosis
		Hemophagocytic Lymphohistiocytosis
			Introduction
			Diagnosis
			Treatment
			Prognosis
			Promising Clinical Studies
		References
Part II: Disorders of Red Blood Cells
	8: Iron Deficiency Anemia
		Introduction
		Pathogenesis
			Development of Iron Deficiency and Iron Deficiency Anemia
		Diagnosis
			Clinical Presentation
		Laboratory Findings
		Prognosis
		Treatment
		Nutritional Intake
		Oral Iron Therapy
		Parental Iron Therapy
		Red Blood Cell Transfusion
		Promising Clinical Studies
		References
	9: Anemia of Inflammation
		Introduction (Definition, Epidemiology, Etiology, Novel Findings)
		Pathophysiology
		Diagnosis
		Differential Diagnosis
		Prognosis
		Treatment
		Promising Clinical Studies
		References
	10: Megaloblastic Anemia
		Introduction
		Etiology
			Folic Acid (FA) Deficiency
			Cyanocobalamin (Vitamin B12)
			Drugs
			Copper Deficiency
		Pathogenesis
		Diagnosis
		Differential Diagnosis
		Prognosis
		Treatment
		Promising Clinical Studies
		References
	11: Sideroblastic Anemia
		Introduction
		Pathogenesis
			cSA
			Acquired Sideroblastic Anemia (aSA)
		Diagnosis
		Differential Diagnosis
		Prognosis
		Treatment
		Promising Clinical Studies
		References
	12: Hemoglobin Disorders
		Thalassemia
			Introduction
			Pathogenesis
				α-thalassemia
				β-Thalassemia
		Sickle Cell Hemoglobinopathy
			Introduction
			Pathogenesis
			Diagnosis
			Treatment
		Other Hemoglobin Disorders
		Promising Clinical Studies
		References
	13: Red Blood Cell Enzymopathies
		Introduction
		Pathogenesis
		Diagnosis
		Major Differential Diagnosis
		Prognosis
		Treatment
		Promising Clinical Studies
		References
	14: Red Blood Cell Membrane Disorders
		Introduction
		Hereditary Spherocytosis
			Introduction and Epidemiology
			Pathophysiology
		Clinical Presentation
			Evaluation
			Management
		Hereditary Stomatocytosis
			Introduction
			Pathogenesis
			Clinical Features
			Diagnosis
			Treatment
		Hereditary Xerocytosis
			Introduction
			Pathophysiology
			Clinical Features
			Diagnosis
		Treatment
		Hereditary Elliptocytosis (HE)
			Epidemiology
			Pathophysiology
			Evaluation
			Differential Diagnosis
			Treatment
		Promising Clinical Trials
		References
	15: Congenital Dyserythropoietic Anemias
		Introduction
		Pathogenesis
			CDA Type I
			CDA Type II
			CDA Type III
			CDA IV
			Another CDA Variant
		Diagnosis
		Differential Diagnosis
		Prognosis
		Treatment
		Promising Clinical Studies
		References
	16: Autoimmune Hemolytic Anemia
		Introduction
		Pathogenesis (Table 16.2)
		Diagnosis
			Clinical Features
			Primary Evaluation
				Hemolysis Screen
				Specific Tests (Fig. 16.1)
				Detection of Underlying Disorders
		Major Differential Diagnosis
			DAT Positive
			DAT Negative
		Prognosis
		Treatment
			General Management
			wAIHA (Fig. 16.2)
			Salvage Therapy for Severe Hemolysis Associated with wAIHA
		Promising Clinical Studies
		References
	17: Cryopathic Hemolytic Anemias
		Introduction
		Pathogenesis
			Cold Agglutinins and “I” antigen
			Cold Hemolysin and “P” antigen
		Diagnosis
		Major Differential Diagnosis
		Prognosis
		Treatment
		Promising Clinical Studies
		References
	18: Methemoglobinemia
		Introduction
		Pathogenesis
		Diagnosis
		Differential Diagnosis
		Prognosis
		Treatment
		Promising Clinical Studies (Potential Clinical Trials, Targeted Therapy, Gene Therapy)
		References
	19: Extrinsic Non-immune Hemolysis
		Introduction
		Pathogenesis
		Diagnosis
		Major Differential Diagnosis
			Hemolysis Secondary to Drugs or Toxins
			Wilson Disease (WD)
			Infections
			Thrombotic Microangiopathies
				Thrombotic Thrombocytopenic Purpura (TTP)
				Disseminated Intravascular Coagulopathy (DIC)
				Hemolytic Uremic Syndrome (HUS)
				Tumor-Related TMA
			Intravascular Devices
			Hemolysis Associated with Liver Disease
			Hypersplenism
			Toxins Caused by Insect, Snake, or Spider Bites
			Pregnancy Associated Hemolysis
		Treatment
		Promising Clinical Study
		References
	20: Pure Red Cell Aplasia
		Introduction
		Pathogenesis
		Diagnosis
		Differential Diagnoses
			Congenital PRCA
			Acquired PRCA
		Treatment
		Promising Clinical Studies
		References
	21: Aplastic Anemia
		Introduction
		Pathogenesis
		Diagnosis
		Major Differential Diagnosis
		Prognosis
		Treatment
		Promising Clinical Studies
		References
	22: Porphyrias
		Introduction [1]
		Pathogenesis [2, 3]
		Diagnosis [4, 5]
			Clinical Manifestations of Disease
			Laboratory Diagnosis
		Screening
		Confirmation
		Major Differential Diagnosis
		Prognosis
		Treatment
		Promising Clinical Studies [6]
		References
	23: Hereditary and Acquired Iron Overload Disorder
		Introduction
		Pathogenesis, Diagnosis, and Treatment
		Hereditary Hemochromatosis
		HFE Hemochromatosis
		Clinical Presentation
		Diagnosis
		Treatment
		Prognosis
		Juvenile Hemochromatosis
		TFR2 Hemochromatosis
		Ferroportin Disease
		Congenital Aceruloplasminemia
		Congenital Atransferrinemia
		Acquired Iron Overload Disorder
		Treatment
		Promising Clinical Studies
		References
	24: Polycythemia/Erythrocytosis
		Introduction
		Pathogenesis
		Diagnosis
		Differential Diagnosis
			Primary Polycythemia
				Hereditary
				Acquired
			Secondary Polycythemias
				Hereditary
				Acquired
		Treatment
		Prognosis
		Promising Clinical Studies
		References
Part III: Disorders of Platelets
	25: Congenital Platelet Disorders
		Introduction
		Pathogenesis
		Pathogenesis and Clinical Presentations
		Congenital Thrombocytopenia
			Macrothrombocytopenia
			Thrombocytopenia with Normal Platelet Size
			Microthrombocytopenia
		Congenital Thrombocytopathies
			Defective Platelet Adhesion Function
			Defective Platelet Activation Function (ADP Receptor Defects)
			Defective Platelet Aggregation Function
			Defective Platelet Secretion Function (Storage Pool Disease)
			Defective Platelet Procoagulant Function
		Diagnosis
		Treatment
		Further Reading
	26: Acquired Platelet Defects
		Introduction
		Etiology and Pathogenesis
		Systemic Disorders
			Renal Failure
			Liver Disease
		Hematological Disorders
			Paraproteinemia
			Myeloproliferative Disorders (MPDs)
		Myelodysplasia
		Drug-Related Platelet Dysfunction
			Drugs Used for Their Direct Antiplatelet Effect
			Drugs with Antiplatelet Effect as an Adverse Effect
		Quantitative Platelet Defects
		Diagnosis
		Major Differential Diagnosis
		Prognosis
		Treatment
		References
	27: Heparin-Induced Thrombocytopenia (HIT)
		Introduction
			Variants of HIT
		Pathogenesis
		Clinical Features
			Thrombocytopenia
		Diagnosis
		Differential Diagnosis
		Treatment
			Parenteral Anticoagulants
			Oral Anticoagulation
			Other Treatments
			Cardiovascular Surgery
			Duration of Anticoagulation
			Reexposure to Heparin
		References
	28: Thrombotic Thrombocytopenic Purpura/Hemolytic-Uremic Syndrome/Atypical Hemolytic-Uremic Syndrome
		Thrombotic Thrombocytopenic Purpura
			Introduction
			Clinical Findings
			Pathogenesis
			Diagnosis
			Major Differential Diagnosis
			Specific Subtypes of TTP Cases
				Obstetric TTP
				Idiopathic TTP Associated with Other Autoimmune Conditions
				HIV Associated TTP
				Cancer and Organ Transplantation Associated TTP
			Prognosis
			Treatment
			Promising Clinical Studies
			Hemolytic-Uremic Syndrome
		Typical Hemolytic-Uremic Syndrome
			Introduction
			Etiology
			Diagnosis
			Prognosis
			Treatment
		Atypical Hemolytic-Uremic Syndrome
			Introduction
			Etiology
			Novel Findings
			Pathogenesis
			Diagnosis
			Prognosis
			Treatment
			Response Assessment
			Discontinuation of Therapy
		References
Part IV: Bleeding Disorders
	29: Hemophilia A and B
		Introduction
		Pathogenesis
		Diagnosis
		Differential Diagnosis
		Prognosis
		Treatment
		Promising Clinical Studies
		References
	30: Von Willebrand Disease
		Introduction
		Pathogenesis
		Diagnosis
		Major Differential Diagnosis of Each vWD Subtype
		Prognosis
		Treatment[4]
		References
	31: Rare Familial Deficiencies of Coagulation Factors II, V, VII, X, XI, and XIII
		Introduction
		Epidemiology
		Pathogenesis
		Diagnosis
			Morphology/Histopathology/Cytology
			Key Laboratory Findings
			Laboratory Diagnosis
			Molecular Diagnosis
			Global Hemostasis Tests
		Major Differential Diagnosis
			Acquired Coagulation Disorders
			Von Willebrand Disease
			Hemophilia A and B
		Prognosis
		Treatment
			Antifibrinolytics
		Promising Clinical Studies
		References
	32: Congenital Afibrinogenemia, Hypofibrinogenemia, Dysfibrinogenemia
		Introduction
		Pathogenesis
		Clinical Features
		Diagnosis
		Differential Diagnosis
		Management
			Principles of Treatment
			Spontaneous or Posttraumatic Bleeding
			Dental Extraction
			Elective Surgery
			Menorrhagia
			Pregnancy
			Prophylaxis
		Managing Patients with Dysfibrinogenemia
			Managing Thrombosis in Hypofibrinogenemia/Dysfibrinogenemia
		Prognosis
			Prenatal Diagnosis
		References
	33: Acquired Inhibitors of Coagulation Factors
		Introduction
		Pathogenesis
		Clinical Features
		Diagnostic Workup
			Antibody Titration
		Differential Diagnosis
			Agents to Arrest the Bleeding
			Removal of the Factor VIII Inhibitor
			Elimination of the Antibody with Immunosuppressive Agents
		Prognosis
		Promising Clinical Studies
		Board Questions
		Caveats
		References
	34: Disseminated Intravascular Coagulation
		Introduction
		Pathogenesis
		Clinical Manifestations
		Laboratory Investigations
		Treatment Strategies
		Questions
		References
	35: Liver Disease and Coagulopathy
		Introduction
		Pathogenesis
			Primary Hemostasis
			Coagulation System
			Fibrinolysis
		Diagnosis
			Major Differential Diagnosis
		Treatment
			Prevention of Bleeding
				Vitamin K
				FFP
				Platelet Transfusion
				Thrombopoietin-Receptor Agonists
				Spleen-Directed Therapies
				Management of Bleeding in Chronic Liver Disease
		Board Question
		References
	36: Therapeutic Principles of Bleeding Disorders
		Introduction
		Pathogenesis
		Diagnosis
		Major Differential Diagnosis
		Prognosis
		Treatment
			Blood Products
			Antifibrinolytics and Vitamin K
			Stopping Anticoagulation
		Promising Clinical Studies
		Caveats
		Board Questions
			Question 1
			Question 2
			Question 3
		References
Part V: Clotting Disorders
	37: Familial Thrombophilia
		Introduction
		Pathogenesis
			Factor V Leiden Deficiency
			Prothrombin Gene Mutation
			Protein C Deficiency
			Protein S Deficiency
			Antithrombin Deficiency
		Diagnosis
		Prognosis
		Treatment
		Promising Clinical Studies
		Caveats
		Board Question
		References
	38: Antiphospholipid Syndrome
		Introduction
			Etiology and Pathogenesis
		Diagnosis
			Laboratory Workup
				Major Differential Diagnosis (Table 38.2)
			Other Conditions with Positive Antiphospholipid Antibodies
		Prognosis
		Treatment (Fig. 38.1)
			Acute Thrombosis
			Long-Term Thrombosis Prevention
		Promising Clinical Studies
		Caveats
		Board Questions (Multiple Choice)
		References
	39: Principles of Antithrombotic and Fibrinolytic Therapy
		Introduction
		Pathophysiology
		Diagnosis
		Treatment
			Acute Therapy of VTE
			Duration of Anticoagulant Therapy
		Special Site of VTE
			Superficial Thrombophlebitis
			Upper-Extremity DVT
			Visceral Thrombosis
			Cerebral Sinovenous Thrombosis (CSVT)
			Retinal Vein Thrombosis
		Perioperative Management of Antithrombotic Therapy
		Prevention of VTE in Hospitalized or Surgical Patients
		Pregnancy and Estrogen Exposure
		Antiphospholipid Syndrome
		Cancer-Associated Thrombosis (CAT)
		Heparin-Induced Thrombocytopenia
		Acute Coronary Syndrome and Ischemic Stroke
		Anticoagulants
		Board Review Questions
		Reference
Part VI: Transfusion Medicine
	40: Principles and Clinical Applications of Human Blood Groups and Human Leukocyte Antigen System
		Human Blood Groups
		Clinical Applications
		Human Leukocyte Antigen System Introduction
		Methods for HLA Typing (Antigen or Allele)
			Serology
			Molecular
		Methods to Identify HLA Antibodies
			Cell-Based Assays
			Solid-Phase Assays
		Clinical Applications
			Role of HLA in Transfusion
				FNHTR
				TRALI
			Role of HLA Typing in Transplant
		References
	41: Red Cell Transfusion
		Introduction
		Pre-transfusion Testing
		Component Manufacturing
		Blood Product Modification
		Transfusion Guidelines for RBCs
		Post-transfusion Complications
		References
	42: Platelet Transfusions
		Introduction
		Platelet Component Types
		Platelet Specifics
		Platelet Transfusion Guidelines
			Indications
			Contraindications
		Response to Platelet Transfusion and Platelet Refractoriness
		Transfusion Infectious Risks and Platelet Modifications
		Adverse Effects of Platelet Transfusion
		References
	43: Plasma Product Transfusion: Fresh Frozen Plasma, Cryoprecipitate, Intravenous Immunoglobulin, and Albumin
		Introduction
		Fresh Frozen Plasma (FFP)
		Cryoprecipitate
		Intravenous Immune Globulin (IVIG)
		Albumin Infusion
		References
	44: Recombinant Human Plasma Proteins in Clinical Practice
		Introduction
		Clinical Indications and Applications of Available Recombinant Proteins
			Factor VIII and Factor IX
			Von Willebrand Factor (VWF)
			Factor VIIa
			Factor XIII
			Antithrombin (AT)
			C1-Esterase Inhibitor (C1INH)
			Factor X
			Alpha-1 Antitrypsin (AAT)
		Promising Clinical Studies
		References
	45: Basics of Therapeutic Apheresis
		Introduction (Definition, Epidemiology, Etiology, Novel Findings)
		Therapeutic Plasma Exchange
		Red Blood Cell Exchange
		Cellular Reductions
		Leukapheresis
		Low-Density Lipoprotein Apheresis
		Extracorporeal Photopheresis
		Apheresis Considerations
			“One Compartment Model”
			Replacement Fluid and Fluid Balance
			Clinical Decision Making
			Medications
			Vascular Access
			Citrate Toxicity, Hypocalcemia, and Electrolyte Abnormalities
		Differences Between Apheresis and Hemodialysis
		References
	46: Therapeutic Plasma Exchange
		Introduction
		Indications
		One-Compartment Model
		Exchange Volume and Prediction of Substance Removal
		Care of the Patient Undergoing Therapeutic Plasma Exchange
			Fluid Replacement
			Anticoagulation
			Vascular Access
			Medications and Drug Removal by Therapeutic Plasma Exchange
				ACE-Inhibitors
				Therapeutic Drug Removal
			Hypocalcemia and Therapeutic Plasma Exchange
			Risks Associated with Therapeutic Plasma Exchange
		References
Part VII: Miscellaneous Disorders
	47: Lipid Storage Diseases
		Etiology and Pathogenesis
		Diagnosis: General Approach
		Differential Diagnosis
		Treatment and Prognosis
		Promising Clinical studies
		References
	48: Benign Lymphadenopathy
		Introduction
			Reactive Follicular Hyperplasia
				Introduction
				Pathogenesis
				Diagnosis
				Major Differential Diagnosis
				Prognosis
				Treatment
				Caveats
			Progressive Transformation of Germinal Center (PTGC)
				Introduction
				Pathogenesis
				Diagnosis
				Major Differential Diagnosis
				Prognosis
				Treatment
				Caveats
			Histiocytic Necrotizing Lymphadenitis (Kikuchi–Fujimoto Disease)
				Introduction
				Pathogenesis
				Diagnosis
				Major Differential Diagnosis
				Prognosis
				Treatment
				Caveats
			Dermatopathic Lymphadenitis
				Introduction
				Pathogenesis
				Diagnosis
				Major Differential Diagnosis
				Prognosis
				Treatment
				Caveats
			SLE Lymphadenitis
				Introduction
				Pathogenesis
				Diagnosis
				Major Differential Diagnosis
				Prognosis
				Treatment
				Caveats
			Kimura Disease
				Introduction
				Pathogenesis
				Diagnosis
				Major Differential Diagnoses
				Prognosis
				Treatment
				Promising Clinical Studies
				Caveats
			Castleman Disease (CD)
				Introduction
				Pathogenesis
				Diagnosis
				Major Differential Diagnosis
				Prognosis
				Treatment
				Promising Clinical Studies
				Caveats
			Rosai–Dorfman Disease (RDD)
				Introduction
				Pathogenesis
				Diagnosis
				Major Differential Diagnosis
				Prognosis
				Treatment
				Promising Clinical Studies
				Caveats
			Rheumatoid Arthritis-Related Lymphadenopathy
				Introduction
				Pathogenesis
				Diagnosis
				Major Differential Diagnoses
				Prognosis
				Treatment
			Sarcoid Lymphadenopathy
				Introduction
				Pathogenesis
				Diagnosis
				Major Differential Diagnosis
				Treatment
				Promising Clinical Studies
				Caveats
			HIV-Associated Lymphadenopathy
				Introduction
				Pathogenesis
				Diagnosis
				Major Differential Diagnosis
				Prognosis
				Treatment
			IgG4-Related Lymphadenopathy
				Introduction
				Pathogenesis
				Diagnosis
				Major Differential Diagnosis
				Prognosis
				Treatment
		References
	49: Hypersplenism and Hyposplenism
		Hypersplenism
			Introduction
			Pathogenesis
			Diagnosis
			Major Differential Diagnosis
			Prognosis
			Treatment
			Promising Clinical Studies
			Caveats
		Hyposplenism
			Introduction
			Pathogenesis
			Diagnosis
			Major Differential Diagnosis
			Prognosis
			Treatment
			Promising Clinical Studies
			Caveats
		References
	50: Common Infections in Patients with Hematologic Neoplasms and Hematopoietic Stem Cell Transplant
		Introduction
		Pathogenesis
			Microorganisms
			Underlying Malignancy
			Cytoreduction and Immunotherapy
			Normal Flora
			Pathogens from Donor Cells
		Diagnosis
		Differential Diagnosis
		Prognosis
		Treatment
		Promising Clinical Studies
		References
	51: Microorganism-Induced Benign Hematologic Conditions
		Human Parvovirus B19 (B19V)
			Introduction
			Pathogenesis
			Diagnosis
			Prognosis
			Treatment
			Promising Clinical Studies
			Caveats
		Epstein–Barr Virus (EBV)
			Introduction
			Pathogenesis
			Diagnosis
			Prognosis
			Treatment
			Promising Clinical Studies
			Caveats
		Human Herpes Virus 8 (HHV8)
			Introduction
			Pathogenesis
			Diagnosis
			Prognosis
			Treatment
			Promising Clinical Studies
			Caveats
		Hepatitis C Virus (HCV)
			Introduction
			Pathogenesis
			Diagnosis
			Prognosis
			Treatment
			Promising Clinical Studies
			Caveats
		Intraerythrocytic Parasites
			Babesia Species
				Introduction
				Pathogenesis
				Diagnosis
				Prognosis
				Treatment
				Promising Clinical Studies: Caveats
			Plasmodium Species
				Introduction
				Pathogenesis
				Diagnosis
				Prognosis
				Treatment
				Promising Clinical Trials
				Caveats
		References
Index