Consultative hemostasis and thrombosis

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Consultative Hemostasis and Thrombosis
Dedication
Contributors
Preface
Contents
Part I : General Information
	1 The Consultative Process
		Abstract
		Keywords
		Extent of the Consultation
			Confirmatory Consultation
			Brief Consultation
			Comprehensive Consultation
			Urgent Consultation on a Catastrophically Ill Patient
			“Undiagnosing” Consultation
			Telemedicine Consultations
			Curbside Consultation
		Reason for Consultation
			Helping Another Physician
			Second Opinion Requested by the Primary Physician
			Second Opinion Requested by the Patient
			Second Opinion Sought by a Third-Party Payor
			Other Third Parties
			Disgruntled Patient or Family
			Inappropriate Consultations
		Consultant’s Point of View
		Duties of the Referring Physician and the Consultant
		Timing
		How to Do the Consultation
		Role of the Clinical Laboratory
		Recommendations
		Concerns
		Outcomes
			Total Agreement
			Supporting Consultation
			Finding Another Physician for the Patient
			Consultant Assumes Primary Care of the Patient
			Serious Troubles
			Redirecting the Thrust of a Workup
			Major Disagreements Between Physicians
			Duration of Consultation
			Noncompliant Patients
			End-of-Life Issues
			Family Members
			When a Diagnosis Is Not Forthcoming
		When Should a Consultant Request Consultation?
		References
	2 A Systematic Approach to the Bleeding Patient
		Abstract
		Key Words
		Introduction
		Clinical Evaluation
			Obtaining a Detailed History
				Have You Ever Experienced a Serious Hemorrhagic Complication During or After a Surgical Procedure?
				Have You Ever Experienced Excessive Vaginal Bleeding During Pregnancy or Immediately After Childbirth or Perineal Bleeding From an Episiotomy?
				Have You Experienced Persistent Menorrhagia in the Absence of Fibroids or Other Uterine Abnormalities?
				Do You Experience Brisk or Prolonged Bleeding After Epistaxis or Minor Cuts or Exaggerated Bruising After Minor Trauma?
				Have You Ever Developed Hemarthrosis, Retroperitoneal Hematoma, or Soft Tissue Hematoma in the Absence of Major Trauma?
				Have You Ever Experienced Spontaneous Bleeding, Poor Wound Healing, or Dehiscence of a Surgical Wound?
				Has Any Member of Your Family Experienced Severe Bleeding Complications, Perhaps Requiring Transfusion of Packed Red Blood Cells?
				Do You Have Any Known Medical Problems?
				Do You Take Any Prescription Medications, Over-the-Counter Medications, or Homeopathic Remedies on a Regular Basis?
				Have You Noticed Any Unusual Rashes or Easy Bruisability?
			Objective Findings on the Physical Examination
		Integrating Patient History and Physical Examination Findings With Laboratory Results
			Basic Laboratory Evaluation of Coagulation and Hemostasis
				Basic Laboratory Tests to Distinguish Between Platelet and Coagulation Defects
				Laboratory Assessment of the Procoagulant System
		Laboratory Monitoring of the Direct Oral Specific Anti–Factor Iia and Anti–Factor Xa Anticoagulants
		Tests for Lupus Anticoagulants
			Global Hemostatic Assessment Instruments
		Formulating Treatment Strategies for Managing Acute Hemorrhagic Episodes: How to Use Coagulation Laboratory Data
		References
PART II : Hemorrhagic Processes
	3 Hemophilia A and Hemophilia B
		Abstract
		Keywords
		Epidemiology and Genetics
			Carrier Testing
			Prenatal Diagnosis
			Postnatal Diagnosis
		Clinical Features of the Hemophilias
			Manifestations Early in Life
				Intraarticular Bleeding: Hemarthroses and Hemophilic Arthropathy
				Intramuscular Hemorrhage
				Hematuria/Hemospermia
				Intracranial Hemorrhage
				Gastrointestinal and Oropharyngeal Bleeding
				Pseudotumor Formation in Hemophilia
			Laboratory Characteristics
		Therapeutic Modalities for the Hemophilias
			Hemophilia Treatment Centers
			Clotting Factor Replacement Therapy With Coagulation Factor Concentrates
			Desmopressin
		Ancillary Treatments
			Antifibrinolytic Agents
			Fibrin Glues or Sealants and Hemostatic Preparations
			Dental Care
		The Aging Patient
		Treatment Complications
			Inhibitors
			Infectious Complications of Replacement Therapy in Hemophilia
		Gene Therapy
		References
	4 Less Common Congenital Disorders of Hemostasis
		Abstract
		Keywords
		Disorders of Fibrinogen
			Afibrinogenemia/Hypofibrinogenemia
				Pathogenesis and Genetics
				Clinical Manifestations
				Diagnosis
				Differential Diagnosis
				Treatment
			Dysfibrinogenemia
				Pathogenesis and Genetics
				Clinical Manifestations
				Diagnosis
				Differential Diagnosis
				Treatment
			Prothrombin Deficiency (Hypoprothrombinemia and Dysprothrombinemia)
				Pathogenesis and Genetics
				Clinical Manifestations
				Diagnosis
				Differential Diagnosis
				Treatment
			Factor V Deficiency
				Pathogenesis and Genetics
				Clinical Manifestations
				Diagnosis
				Differential Diagnosis
				Treatment
			Factor VII Deficiency
				Pathogenesis and Genetics
				Clinical Manifestations
				Diagnosis
				Differential Diagnosis
				Treatment
			Factor X Deficiency
				Pathogenesis and Genetics
				Clinical Manifestations
				Diagnosis
				Differential Diagnosis
				Treatment
			Factor XI Deficiency
				Pathogenesis and Genetics
				Clinical Manifestations
				Diagnosis
				Differential Diagnosis
				Treatment
			Deficiency of Contact Factors
				Factor XII Deficiency
					Pathogenesis and genetics.
					Clinical manifestations.
					Diagnosis.
					Differential diagnosis.
					Treatment.
				Prekallikrein Deficiency
				High-Molecular-Weight Kininogen Deficiency
				Factor XIII Deficiency
					Pathogenesis and genetics.
					Clinical manifestations.
					Diagnosis.
					Differential diagnosis.
					Treatment.
			Familial Combined Factor Deficiencies
				Combined Factor V/Factor VIII Deficiency (Type I)
					Pathogenesis and genetics.
					Diagnosis.
					Clinical manifestations.
					Treatment.
				Combined Factor II, VII, IX, and X and Protein C, S, and Z Deficiencies (Type III)
					Pathogenesis and genetics.
					Clinical manifestations.
					Diagnosis.
					Treatment.
					Differential diagnosis.
				Other Combined Familial Deficiencies
		α2-Plasmin Inhibitor Deficiency
			Pathogenesis and Genetics
			Clinical Manifestations
			Differential Diagnosis
			Diagnosis
			Treatment
		α1-Antitrypsin Pittsburgh (Antithrombin III Pittsburgh)
		East Texas Bleeding Disorder
			Pathogenesis and Genetics
			Clinical Manifestations
			Diagnosis
			Treatment
		Consultation Considerations
		Medical-Legal Issues
		Cost Containment Issues
		References
	5 Acquired Coagulation Disorders Caused by Inhibitors
		Abstract
		Keyword
		Introduction and Overview
		Laboratory Assessment of Inhibitors
		Acquired Hemophilia a (Acquired FVIII Inhibitors)
			Epidemiology and Associated Conditions
			Pathophysiology
			Clinical Presentation
			Diagnostic Confirmation
			Hemostatic Therapy
				Minor Bleeding
				Major Bleeding
					FVIII replacement.
					Bypassing therapy.
					Other therapies.
			Inhibitor Eradication
				Corticosteroids and Cyclophosphamide
				Rituximab
				Other Immunosuppressants
			Prognosis
			Special Considerations in Pregnancy-Related Acquired Hemophilia A
		Acquired Von Willebrand Syndrome
			Epidemiology and Associated Conditions
			Pathophysiology
			Clinical Presentation
			Diagnostic Confirmation
			Hemostatic Therapy
			Inhibitor Eradication
			Treatment of the Underlying Comorbidity
			Prognosis
		Other Coagulation Factor Inhibitors
			Factor II (Prothrombin) Inhibitors
				Hemostatic Therapy and Inhibitor Eradication
			Factor V Inhibitors
				Hemostatic Therapy and Inhibitor Eradication
			Factor VII Inhibitors
				Hemostatic Therapy and Inhibitor Eradication
			Factor IX Inhibitors
				Hemostatic Therapy and Inhibitor Eradication
			Factor X Inhibitors
				Hemostatic Therapy and Inhibitor Eradication
			Factor XI Inhibitors
				Hemostatic Therapy and Inhibitor Eradication
			Factor XIII Inhibitors
				Hemostatic Therapy and Inhibitor Eradication
			Fibrinogen Inhibitors
				Hemostatic Therapy and Inhibitor Eradication
		References
	6 von Willebrand Disease
		Abstract
		Keywords
		Introduction
		Historic Overview
		Physiology, Genetics, and Structure-Function Relationships
			Platelet-Related Functions of von Willebrand Factor
			Factor VIII–Related Functions of von Willebrand Factor
			von Willebrand Factor Levels in Health and Disease
		Clinical Presentation
		Diagnosis
			History and Physical Examination
			Bleeding Scores
			Laboratory Evaluation
				Diagnostic Assays for von Willebrand Disease
				Assays Used for the Classification of von Willebrand Disease
				Mild von Willebrand Disease Versus Low von Willebrand Factor—Diagnostic Levels for von Willebrand Disease
				Keys to Diagnosis
				Pitfalls of Diagnosis
		Classification
			Type 1
			Type 2
				Type 2A
				Type 2B
				Type 2M
				Type 2N
			Type 3
		Acquired von Willebrand Disease
		Treatment
			Treatment of Inherited von Willebrand Disease
				Desmopressin
				Replacement Therapy With von Willebrand Factor
				Antifibrinolytic Therapy
				Topical Agents
			Treatment of Acquired von Willebrand Disease
			Treatment of Heavy Menstrual Bleeding in Patients With von Willebrand Disease
			Treatment of von Willebrand Disease During Pregnancy
			Practical Considerations for Treatment of von Willebrand Disease
		References
	7 General Aspects of Thrombocytopenia, Platelet Transfusions, and Thrombopoietic Growth Factors
		Abstract
		Keywords
		Introduction
		Relation of Bleeding Risks to Platelet Count
		The Platelet Count and Surgical Risk
		The Biology of Platelet Production
		Causes of Thrombocytopenia
		Evaluation of the Thrombocytopenic Patient
			Medical History
			Symptoms and Signs of Thrombocytopenia
			Laboratory Investigations
		Treatment of Patients With Thrombocytopenia
			Treatments for Specific Causes of Thrombocytopenia
			Platelet Transfusion
				What Is the Transfusion Target for Bleeding Patients?
				What Is an Adequate Platelet Count for Procedures?
				When Should Prophylactic Platelet Transfusions Be Given?
				Which Platelet Product Should Be Used?
				What Dose of Platelets Should Be Given?
				What Are the Complications of Platelet Transfusion?
			Enhancement of Hemostatic Function
			Thrombopoietic Growth Factors
				Interleukin 11
				Recombinant Thrombopoietin and Thrombopoietin Receptor Agonists
				Low-Level Laser Light
		References
	8 Immune Thrombocytopenia
		Abstract
		Keywords
		Epidemiology
		Pathogenesis
		Clinical Presentation
			Thrombocytopenia
			Bleeding
			Fatigue
			Long-Term Outcomes
		Evaluation of a Patient With Suspected Immune Thrombocytopenia
		Differential Diagnosis of Immune Thrombocytopenia
			Nonimmune Thrombocytopenia
				Pseudothrombocytopenia
				Incidental Thrombocytopenia of Pregnancy (Gestational Thrombocytopenia)
				Hypersplenism
				Familial Thrombocytopenias
				Myelodysplastic Syndromes
			Secondary Immune Thrombocytopenia
				Drug-Induced Immune Thrombocytopenia
				Immune Thrombocytopenia Associated With Infections
				Immune Thrombocytopenia Associated With Other Autoimmune or Lymphoproliferative Disorders
				Acquired Pure Megakaryocytic Aplasia
		Management of Primary Immune Thrombocytopenia
			Initial Management of Adult Patients
				Observation
				Corticosteroids
				Intravenous Immunoglobulin
				Rh(D) Immune Globulin
			Second-Line Treatment
				Splenectomy
				Rituximab
				Thrombopoietin Receptor Agonists
			Other Therapies
				Danazol
				Cyclophosphamide
				Vinca Alkaloids
				Azathioprine
				Mycophenolate Mofetil
				Combination Therapy
				Removal of an Accessory Spleen
		Treatment of Critical Bleeding in Patients With Immune Thrombocytopenia
		Management of Immune Thrombocytopenia in Pregnancy
		References
	9 Congenital and Acquired Disorders of Platelet Function and Number
		Abstract:
		Key Words
		Introduction
		Historical Perspective
		Clinical Manifestations of Platelet-Related Bleeding and Tests of Platelet Function
			Does the Patient Have a Platelet-Related Bleeding Disorder?
		Differential Diagnosis of Platelet-Related Bleeding
			Is the Defect Acquired or Congenital?
		Acquired Platelet Disorders
			Medication-Related Platelet Dysfunction
			Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation
			Uremia
			Myeloproliferative Disorders
			Hypersplenism
		Congenital Platelet Disorders
			Congenital Platelet Disorders With a Normal Platelet Count
			Disorders With a Normal Platelet Count and Abnormal Aggregation
				Glanzmann Thrombasthenia
				Other Receptor Defects
				Hermansky–Pudlak Syndrome
				Chédiak–Higashi Syndrome
				Other Dense Granule Defects: Storage Pool Defect
				Defects of Intracellular Signaling Pathways
				Quebec Platelet Disorder
			Disorders With a Normal Platelet Count and Normal Pattern of Aggregation
				Scott Syndrome
			Disorders With Thrombocytopenia and Small Platelets
				Wiskott-Aldrich Syndrome/X-Linked Thrombocytopenia
			Disorders With Thrombocytopenia and Normal Platelet Size
				Familial Platelet Disorder/Acute Myeloid Leukemia
				Thrombocytopenia With Absent Radii
				Amegakaryocytic Thrombocytopenia With Radioulnar Synostosis
				Congenital Amegakaryocytic Thrombocytopenia
				Paris–Trousseau Thrombocytopenia
				ANKRD26 Thrombocytopenia
				ETV6 Thrombocytopenia
				Other Familial Thrombocytopenias
			Disorders With Thrombocytopenia and Large or Giant Platelets
				Glycoprotein Ib/IX/V Receptor Defects (Bernard-Soulier Syndrome, Mediterranean Macrothrombocytopenia, and Velocardiofacial [DiGeorge] Syndrome)
				Platelet-Type von Willebrand Disease (Gain-of-Function Mutation of Glycoprotein Ib/IX/V)
				MYH9-Related Thrombocytopenia (May-Hegglin, Sebastian, Fechtner, and Epstein Syndromes)
				GATA1-Related Thrombocytopenia
				Gray Platelet Syndrome
				White Platelet Syndrome
		Treatment of Platelet-Related Bleeding (General Guidelines)
		Conclusions
		References
	11 Hereditary Hemorrhagic Telangiectasia
		Abstract
		Keyword
		Historical Aspects
		Epidemiology
		Molecular Biology
		Pathogenesis
		Clinical Manifestations
			Epistaxis and Gastrointestinal Bleeding
			Visceral Organ Arteriovenous Malformations
				Liver Arteriovenous Malformations
				Pulmonary Arteriovenous Malformations
				Cerebral and Spinal Arteriovenous Malformations
		Diagnosis
		Management
			Screening for Visceral Arteriovenous Malformations
			Epistaxis
			Anemia
			Treatment of Arteriovenous Malformations
				Brain Arteriovenous Malformations
				Pulmonary Arteriovenous Malformations
				Liver Arteriovenous Malformations
		Hereditary Hemorrhagic Telangiectasia in the Pediatric Age Group
		Hereditary Hemorrhagic Telangiectasia and Pregnancy
		Hereditary Hemorrhagic Telangiectasia Centers of Excellence
		References
	12 Disseminated Intravascular Coagulation
		Abstract
		Key Words
		Historical Overview
		Physiology and Pathophysiology
		Causes of Disseminated Intravascular Coagulation
		Initiation of Disseminated Intravascular Coagulation
		Five Illustrative Causes of Disseminated Intravascular Coagulation
			Closed Head Injury
			Abdominal Aortic Aneurysm
			Placental Abnormalities
			Acute Promyelocytic Leukemia
			Acute Decompensated Disseminated Intravascular Coagulation With Dermal Necrosis Syndrome
		Diagnosis of Disseminated Intravascular Coagulation
		Differential Diagnosis of Disseminated Intravascular Coagulation
		Consequences of Disseminated Intravascular Coagulation
		Treatment of Patients With Disseminated Intravascular Coagulation
		Consultation Considerations
		Cost Containment Issues
		Medical-Legal Considerations
		References
	13 Crosstalk of Inflammation and Coagulation in Infectious Disease and Their Roles in Disseminated Intravascular Coagulation
		Abstract
		Keywords
		Introduction
		General Aspects of Primary Hemostasis, Coagulation, and Fibrinolysis
		Endothelial Activation and Its Effects on Coagulation During Inflammation
		Modulation of Inflammation by Coagulation in vivo
		Coagulation and Inflammatory Disorders Associated With Various Pathogens
			Inflammatory Networks in Gram-Negative Sepsis
			Early Events in Sepsis in Relation to Blood Coagulation: Lipopolysaccharide Studies
			Early and Late Effects Merge in Models of Sepsis and Disseminated Intravascular Coagulation
			Gram-Positive Bacterial Infections
			Viral Infections
			Viral Hemorrhagic Fevers
				Dengue Virus
				Hantavirus
				Ebola Virus
			Fungal and Parasitic Infections
		Treatment of Patients With Disseminated Intravascular Coagulation and Infection
		Plasma and Platelet Substitution Therapy
		Anticoagulant Therapy
		Restoration of Anticoagulant Pathways
		References
PART Ill : Thrombotic Processes
	14 Thrombophilia
		Abstract
		Keywords
		Introduction
		Should All Patients With Unprovoked Venous Thromboembolism Receive Lifelong Anticoagulation?
		Weighing Bleeding Risk
		Pursuit of Thrombophilia Testing May Divert Attention From More Important Clinical Risk Factors
		What Are the Pitfalls of Genetic Testing?
		When Is It Helpful to Test Unaffected Family Members for Genetic Mutations?
			Pregnancy
			Estrogen Use
			Major Surgery
			Airplane Flights
			Summary
		Testing Considerations for Particular Disorders
			Antithrombin III Deficiency
				Background
				Testing
				Acquired Antithrombin III Deficiencies
				Clinical Manifestations
			Protein C Deficiency
				Background
				Testing
				Acquired Protein C Deficiency
				Epidemiology and Clinical Manifestations
			Protein S Deficiency
				Background
				Testing
				Acquired Protein S Deficiency
				Epidemiology and Clinical Manifestations
			Factor V Leiden and Activated Protein C Resistance
				Background
				Testing
				Epidemiology and Clinical Manifestations
			Prothrombin Gene Mutation
				Background
				Testing
				Epidemiology and Clinical Manifestations
			Antiphospholipid Antibodies
				Background
				Testing
				Epidemiology and Clinical Manifestations
			Elevated Factor VIII Levels
				Background
				Testing
				Acquired Factor VIII Elevation
				Epidemiology and Clinical Manifestations
		Thrombophilia Testing of Null, Minimal, or Uncertain Value
		Searching for Occult Cancer With Unprovoked VTE
		Role of the Systems-Based Hematologist
		Conclusion
		References
	15 Pediatric Aspects of Thrombophilia
		Abstract
		Keywords
		Introduction
		Epidemiology
		Risk Factors
		Developmental Hemostasis
		Inherited Thrombophilia
		Clinical Features
			Extremity Deep Venous Thrombosis
			Pulmonary Embolism
			Cerebral Sinovenous Thrombosis
			Renal Vein Thrombosis
			Peripheral Arterial Thrombosis
			Acute Ischemic Stroke
		Diagnosis
		Treatment
			Observation
			Anticoagulation
			Thrombolysis
			Surgery
			Inferior Vena Caval Filters
			Antiplatelet Therapy
		Thromboprophylaxis
		Complications
		Summary
		References
	16 Prevention and Treatment of Venous Thromboembolism
		Abstract
		Key Words
		Epidemiology
		Pathogenesis of Venous Thrombosis
		Risk Factors for Venous Thromboembolism
		Venous Thromboembolism Prevention
		Diagnosis
			Cost-Effective Approach to Venous Thromboembolism Diagnosis
		Acute Treatment of Venous Thromboembolism
			Parenteral Direct Thrombin Inhibitors
			Initial Venous Thromboembolism Management—Inpatient Versus Outpatient
			Thrombolytic Therapy
			Surgical Embolectomy
			Inferior Vena Cava Interruption
				Oral Anticoagulants: Warfarin
				Oral Anticoagulation: Direct Oral Anticoagulants (See Chapter 37)
		Venous Thromboembolism in Pregnancy
		Central Venous Catheter– Associated Thrombosis
		Superficial Venous Thrombosis
		Clinical Course of Venous Thromboembolism
			Duration of Anticoagulation
			Complications of Anticoagulation
		References
	17 Venous Thromboses at Unusual Sites
		Abstract
		Keywords
		Historical Aspects
		Importance to The Patient and The Clinician
		Intra-Abdominal Thrombosis
			Mesenteric Vein Thrombosis
				Overview
				Causes
				Signs and Symptoms
				Diagnosis
				Treatment
			Splenic Vein Thrombosis
				Overview
				Causes
				Signs and Symptoms
				Diagnosis
				Treatment
			Portal Vein Thrombosis
				Overview
				Causes, Signs, and Symptoms
				Diagnosis
				Treatment
			Renal Vein Thrombosis
				Overview
				Causes
				Diagnosis
				Treatment
			Hepatic Vein Thrombosis
				Overview
				Causes
				Diagnosis
				Treatment
		Cerebral Venous Thrombosis
			Overview
			Causes
			Diagnosis
			Treatment
		Retinal Vein or Artery Thrombosis
			Overview
			Causes
			Treatment
		Upper Extremity Thrombosis
			Overview
			Causes
			Signs and Symptoms
			Diagnosis
			Treatment
		Lemierre Syndrome
			Overview
			Diagnosis
			Treatment
		Cutaneous Microvascular Thrombosis (Purpura Fulminans)
			Overview
			Causes
			Signs and Symptoms
			Diagnosis
			Treatment
		Ovarian Vein Thrombosis
			Overview
			Signs and Symptoms
			Diagnosis
			Treatment
		Thrombosis at Other Sites
			Adrenal Gland
			Pituitary Gland
			Placenta
		Consultation Considerations
		Laboratory Evaluation
		Cost Containment Issues
		References
	18 Postthrombotic Syndrome
		Abstract
		Keywords
		Synopsis
		Definition and Diagnosis of Postthrombotic Syndrome
			Distinguishing Postthrombotic Syndrome From Recurrence of Acute Ipsilateral Deep Vein Thrombosis
		Impact of Postthrombotic Syndrome on Quality of Life
		Economic Burden of Postthrombotic Syndrome
		Frequency of Postthrombotic Syndrome After Deep Vein Thrombosis
		Current Understanding of the Pathophysiology of Postthrombotic Syndrome
		Risk Factors for Postthrombotic Syndrome
		Therapeutic Management of Postthrombotic Syndrome
			Prevention of Postthrombotic Syndrome
			Prevention of Deep Vein Thrombosis in High-Risk Patients
			Prevention of Postthrombotic Syndrome After an Episode of Deep Vein Thrombosis
				Elastic Compression Stockings
				Pharmacologic Strategies
				Endovascular Strategies
		Treatment of Established Postthrombotic Syndrome
			Conservative Treatment
				Exercise Training
				Compression Therapy
				Pharmacologic Therapies
			Surgical Treatment
		Future Research
		References
	19 Thrombocytosis
		Abstract
		Keywords
		Introduction
		Spurious Thrombocytosis (Pseudothrombocytosis)
		Reactive Thrombocytosis
		Familial or Hereditary Thrombocytosis
		Essential Thrombocythemia
			Pathogenesis of Essential Thrombocythemia
			Criteria for the Diagnosis of Essential Thrombocythemia
			An Overview of Clinical Features of Essential Thrombocythemia
			Coagulation Laboratory Features of Essential Thrombocythemia: the Paradox of in Vivo Platelet Activation and Impaired Platelet Function
			Thrombohemorrhagic Complications of Essential Thrombocythemia
			Acquired Von Willebrand Syndrome in Essential Thrombocythemia
			Prognostic Indicators for Thrombosis and Hemorrhage in Essential Thrombocythemia
			Transformation of Essential Thrombocythemia to Acute Myeloid Leukemia and Other Malignancies
			Risk Assessment in Essential Thrombocythemia
			Treatment of Patients With Essential Thrombocythemia
				Hydroxyurea Therapy
				Anagrelide Therapy
				Recombinant Interferon-α
				Alkylating Agents and Radioactive Phosphorus
				Aspirin
				Plateletpheresis
				Ruxolitinib
			Pregnancy and Essential Thrombocythemia
		References
	20 Antiphospholipid Syndrome
		Abstract
		Keywords
		Introduction
		Epidemiology
			Normal Individuals
			Normal Pregnancy
			Patients With Autoimmune Disorders (Non-Antiphospholipid Syndrome)
			Patients With Thromboembolic Disorders
			Patients With Pregnancy Morbidity
		Immunology and Pathophysiology of Antiphospholipid Antibodies
			Autoantibody Subsets
				Anti-β2-Glycoprotein I Antibodies
				Anti-Prothrombin Antibodies
				Cofactor-Independent Antibodies
			Pathophysiologic Mechanisms
				Disruption of the Annexin A5 Anticoagulant Shield
				Endothelial Cell Activation
				Complement Activation
				Neutrophil Extracellular Traps
				Platelet Activation
				Inhibition of Natural Anticoagulant and Fibrinolytic Pathways
				Effects on the Placenta and Placentation
				Role of a “Second-Hit” in Thrombotic Events in Antiphospholipid Syndrome
		Antiphospholipid Antibodies: Detection in the Clinical Laboratory
			Who Should Be Tested for Antiphospholipid Antibodies?
			Anticardiolipin Antibodies
			Anti-β2GPI Antibodies
			Lupus Anticoagulant
			Antiphospholipid Antibody “Profile”
			Noncriteria Laboratory Tests for Antiphospholipid Syndrome
		Antiphospholipid Syndrome: Clinical Manifestations
			Venous Thromboembolism
			Arterial Thromboembolism
			Pregnancy Morbidity
			Other Clinical Manifestations of Antiphospholipid Syndrome
				Dermatologic Manifestations
				Nonthromboembolic Neurologic Manifestations
				Cardiac Valve Disease
				Renal Manifestations
				Hematologic Manifestations
			Catastrophic Antiphospholipid Syndrome
		Antiphospholipid Antibodies and Antiphospholipid Syndrome: Therapeutic Management
			Individuals With Elevated Antiphospholipid Antibody Levels but No History of Thromboembolism
				Asymptomatic Individuals
				Patients With Systemic Lupus Erythematosus
				Patients With Obstetric Antiphospholipid Syndrome
			Patients With Venous Thromboembolism
			Patients With Arterial Thromboembolism
			Patients With Pregnancy Morbidity
				The Pregnant Individual With Antiphospholipid Antibodies but No Prior Manifestations of Antiphospholipid Syndrome
				The Pregnant Patient With a History of Obstetric Antiphospholipid Syndrome
				The Pregnant Patient With a History of Thrombotic Antiphospholipid Syndrome
			Patients With Catastrophic Antiphospholipid Syndrome
		References
	21 Antiplatelet Therapy in Cardiovascular Medicine
		Abstract
		Keywords
		Coronary Atherosclerotic Disease
			Epidemiology
			Vascular Atherogenesis
			Arterial Thrombogenesis
			Platelet Deposition
			Activation of Coagulation Factors
			Platelet-Directed Therapies
				Aspirin
					Pharmacodynamics.
					Pharmacokinetics.
					Adverse effects.
					Primary prevention.
					Secondary prevention of vascular events.
					Aspirin dosing.
					Coronary artery bypass.
					Percutaneous coronary intervention.
				Platelet P2Y12 Receptor Antagonists
					Clopidogrel
						Pharmacodynamics.
						Pharmacokinetics.
						Safety.
					Clinical experience
						Vascular disease.
				Coronary Artery Stenting
					Acute coronary syndromes.
					Acute coronary syndromes: prepercutaneous coronary intervention treatment, duration of therapy, and clinical benefit.
					Clopidogrel response variability.
					Prasugrel
						Pharmacodynamics.
						Pharmacokinetics.
						Safety.
						Clinical experience
							Acute coronary syndromes.
						Ticagrelor
							Pharmacodynamics.
						Pharmacokinetics.
						Safety.
						Clinical experience
							Acute coronary syndromes.
						Cangrelor
							Pharmacodynamics.
							Pharmacokinetics.
							Clinical experience and safety.
					On-treatment platelet reactivity testing.
					Methods to assess platelet responsiveness to P2Y12-directed pharmacotherapy.
					High on-treatment platelet reactivity and events after percutaneous coronary intervention.
					Pharmacogenomics and P2Y12 inhibitor therapy.
					Protease-activated receptor 1 antagonist.
					GPIIb/IIIa antagonists.
					Intravenous platelet glycoprotein IIb/IIIa receptor antagonists.
					Abciximab
						Pharmacodynamics.
						Pharmacokinetics.
						Clinical experience.
					Tirofiban
						Pharmacodynamics.
						Clinical experience.
					Eptifibatide
						Pharmacodynamics.
						Pharmacokinetics.
						Clinical experience.
						Agent-specific characteristics.
						Current recommendations.
		References
	22 Nonarteriosclerotic Disorders of the Arterial System
		Abstract
		Key Words
		Pathophysiology of Arterial Thrombosis
		Atherosclerosis, Atrial Fibrillation, and Other Cardioembolic Sources
		Nonarteriosclerotic Arterial Occlusive Disease
			Evaluation
			Treatment
		Thrombophilia in Arterial Disease
			Factor V Leiden
				Risk Factor for Arterial Thromboembolism
				Clinical Consequences
			Prothrombin 20210 Mutation
				Risk Factor for Arterial Thromboembolism
				Clinical Consequences
			Protein C, Protein S, or Antithrombin III Deficiency
				Risk Factor for Arterial Thromboembolism
				Clinical Consequences
			Hyperhomocysteinemia, Homocystinuria, Methylenetetrahydrofolate Reductase Polymorphisms
				Risk Factor for Arterial Thromboembolism
				Clinical Consequences
			Antiphospholipid Syndrome
				Risk Factor for Arterial Thromboembolism
				Clinical Consequences
			Fibrinogen Abnormalities
				Fibrinogen Plasma Level and Polymorphisms
					Risk factor for arterial thromboembolism.
					Clinical consequences.
				Dysfibrinogenemia and Afibrinogenemia
			Elevation of Factor VIII and Von Willebrand Factor
				Risk Factor for Arterial Thromboembolism
				Clinical Consequences
			Abnormalities in the Fibrinolytic Pathway (Abnormal Levels and Polymorphisms of Plasminogen Activator Inhibitor 1, Tissue Plasminogen Activator, and Thrombin-Activatable Fibrinolysis Inhibitor)
				Risk Factors for Arterial Thromboembolism
					Plasminogen.
					Tissue plasminogen activator.
					Plasminogen activator inhibitor 1.
					Thrombin-activatable fibrinolysis inhibitor.
			Myeloproliferative Disorders
			Lipoprotein (a) Elevation
			Other Disorders
		Anatomic Abnormalities
			Popliteal Artery Entrapment Syndrome
				Key Details
				When to Consider It
				How to Diagnose It
			Thoracic Outlet Syndrome
				Key Details
				When to Consider It
				How to Diagnose It
		Abnormalities of the Vascular Wall
			Nonvasculitic Abnormalities of the Vascular Wall
				Dissections
					Key details.
				Fibromuscular Dysplasia
					Key details.
					When to consider it.
					How to diagnose it.
				Vascular Ehlers–Danlos Syndrome (EDS)
					Key details.
					When to consider it.
					How to diagnose it.
				Segmental Arterial Mediolysis (SAM)
					Key details.
					When to consider it.
					How to diagnose it.
				Cystic Adventitial Disease
					Key details.
					When to consider it.
					How to diagnose it.
				Endofibrosis
					Key details.
					When to consider it.
					How to diagnose it.
				Vasospasm
			Vasculitis
		Drugs and Medications
			Cocaine and Other Illicit Drugs
			Other Drugs
		Patient Education
		References
	23 Thrombosis and Cancer
		Abstract
		Keywords
		Introduction
		Epidemiology
			Idiopathic Venous Thromboembolism and Occult Cancer
			Venous Thromboembolism as a Complication of Cancer
			Venous Thromboembolism and Cancer Treatments
			Clinical Impact of Cancer-Associated Venous Thromboembolism
		Prediction of the Risk of Cancer-Associated Thrombosis
			Incidental Venous Thromboembolism in Cancer Patients
			Biomarkers
			Risk Assessment Tools
		Pathogenesis of Venous Thromboembolism in Cancer
			Virchow Triad
			Tumor Procoagulants
			Cancer and Inflammation
			Cancer and Platelets
		Guidelines on the Prevention and Treatment of Cancer- Associated Thrombosis
		Venous Thromboembolism Prophylaxis in Patients With Cancer
			Surgical Patients
			Hospitalized Medical Patients
			Cancer Patients in the Outpatient Setting
		Catheter-Associated Venous Thromboembolism
		Treatment of Cancer- Associated Thrombosis
			Direct Oral Anticoagulants for Treatment of Cancer-Associated Venous Thromboembolism
			Inferior Vena Cava Filters
		Anticoagulation Therapy and Survival in Cancer
		Summary and Conclusions
		References
	24 Thrombotic Thrombocytopenic Purpura and Related Thrombotic Microangiopathies
		Abstract
		Keywords
		Introduction
		Historical Review
		Clinical Manifestations
		Laboratory Findings
		Types of Thrombotic Thrombocytopenic Purpura
		Causes and Pathophysiology of Thrombotic Thrombocytopenic Purpura
		Von Willebrand Factor, ADAMTS13, and Thrombotic Thrombocytopenic Purpura
			ADAMTS13 Assays
		Other Observations
		Other Thrombotic Microangiopathies
		Differential Diagnosis of Thrombotic Thrombocytopenic Purpura
		Distinction Between Thrombotic Thrombocytopenic Purpura and Hemolytic-Uremic Syndrome
			2011 Hemolytic-Uremic Syndrome Outbreak in Europe
		Treatment of Patients With Thrombotic Thrombocytopenic Purpura
		Treatment of Patients With Other Types of Thrombotic Microangiopathy
		New Approaches to Therapy
		Medical-Legal Implications
		Consultative Considerations
		References
	25 Complement-Mediated Coagulation Disorders
		Abstract
		Keywords
		Introduction
		Brief Historic Perspective
		Complement for the Clinician
			Membrane-Bound Complement Regulators
			Soluble Complement Regulators
			Activation of the Classical Pathway
			Activation of the Alternative Pathway of Complement
			Activation of the Lectin Pathway of Complement
		Complement and Thrombosis
		Paroxysmal Nocturnal Hemoglobinuria
			Definition
			Pathophysiology
			Diagnosis
				What Tests Should Be Ordered?
				Clinical Manifestations
			Treatment
		Atypical Hemolytic Uremic Syndrome
			Definition
			Pathophysiology
			Diagnosis
				What Tests Should Be Ordered?
				Clinical Manifestations
			Treatment
		Other Complement-Related Anemias
			HELLP Syndrome
			Transplant-Associated Thrombotic Microangiopathy
			Cold Agglutinin Disease
		Novel Complement Inhibitors
		Conclusion and Future Perspectives
		References
	26 Heparin-Induced Thrombocytopenia
		Abstract:
		Key Words
		Historical Overview
		Terminology
		Definition
		Pathogenesis
		Frequency
			Platelet Count Monitoring for Heparin-Induced Thrombocytopenia
		Clinical Features
			Temporal Profile
			Severity of Thrombocytopenia
			Venous Thrombosis
			Arterial Thrombosis
			Limb Ischemic Syndromes
			Microvascular Thrombotic Complications of Warfarin Therapy
			Heparin-Induced Skin Lesions
			Neurologic Syndromes
			Cardiac Syndromes
			Outpatient Presentation of Heparin-Induced Thrombocytopenia (Delayed-Onset HIT)
			Spontaneous Heparin-Induced Thrombocytopenia Syndrome
			Heparin-Induced Thrombocytopenia in Children
		Differential Diagnosis
			Overdiagnosis of Heparin-Induced Thrombocytopenia
		Clinical Scoring Systems
		Laboratory Testing
			Platelet Activation Assays
				Washed Platelet Activation Assays
				Platelet Aggregation Assays That Use Platelet-Rich Plasma
			Platelet Factor 4–Dependent Immunoassays
				Solid-Phase Enzyme Immunoassays
				Rapid Immunoassays: Instrumentation Based
				Rapid Immunoassays: Particle Gel Immunoassay
			Rapid Immunoassays: Lateral Flow Immunoassay
			Interpreting Heparin-Induced Thrombocytopenia Test Results: Iceberg Model and Enzyme-Immunoassay Optical Densities
		Clinical-Treatment Interface: Delayed-Onset Heparin-Induced Thrombocytopenia and Treatment Implications
		Treatment of Patients With Thrombosis Associated With Heparin-Induced Thrombocytopenia
			Lepirudin
			Argatroban
			Bivalirudin
			Direct Thrombin Inhibitor–Warfarin Overlap
			Danaparoid
			Fondaparinux
			Choice of a Nonheparin Anticoagulant: Direct Thrombin Inhibitor Versus Indirect Factor Xa Inhibitor
			Direct Oral Anticoagulants
			Adjunctive Treatments
		Caveats in the Management of Heparin-Induced Thrombocytopenia
		Treatment of Patients With Isolated Heparin-Induced Thrombocytopenia
		Reexposure to Heparin After Previous Heparin-Induced Thrombocytopenia
		Specialized Clinical Situations
			Cardiac Surgery
			Percutaneous Coronary Intervention
			Hemodialysis
		Prevention of Heparin-Induced Thrombocytopenia
		References
PART IV : Therapeutic Agents
	27 Parenteral Antithrombotic Agents
		Abstract
		Keywords
		Introduction
		Parenteral Antithrombotic Agents
			Heparin
				Mechanism and Pharmacology
				Administration and Monitoring
				Heparin Resistance
				Indications and Clinical Use
				Adverse Effects
				Reversal of Effect
			Low-Molecular-Weight Heparin
				Mechanism and Pharmacology
				Administration and Monitoring
				Indications and Clinical Use
				Adverse Effects
				Reversal of Effect
			Pentasaccharides
				Mechanism and Pharmacology
				Administration and Monitoring
				Indications and Clinical Use
				Adverse Effects
				Reversal of Effect
			Bivalirudin
				Mechanism and Pharmacology
				Administration and Monitoring
				Indications and Clinical Use
				Adverse Effects
				Reversal of Effect
			Argatroban
				Mechanism and Pharmacology
				Administration and Monitoring
				Indications and Clinical Use
				Adverse Effects
				Reversal of Effect
			Danaparoid
				Mechanism and Pharmacology
				Administration and Monitoring
				Indications and Clinical Use
				Adverse Effects
				Reversal of Effect
			Novel Parenteral Antithrombotic Strategies
				FXI-ASO (ISIS 416858)
		Summary
		References
	28 Blood Component and Pharmacologic Therapy for Hemostatic Disorders
		Abstract
		Keywords
		Synopsis
		Introduction and Historical Overview
		Traditional Blood Components
			Red Blood Cells
			Platelets
			Fresh Frozen Plasma
			Cryoprecipitate
		Adverse Effects of Blood Transfusion Therapy
			Commercial Plasma Fractions
		Recombinantly Derived Plasma Coagulation Proteins
			Recombinant Factor VIIa
				Background
				Mechanism of Action
				Dose and Administration
				Indications
				Toxicity
		Pharmaceutical Agents
			Desmopressin
				Background
				Mechanisms of Action and Tachyphylaxis
				Dose and Administration
				Indications
					Hemophilia and von Willebrand disease.
					Congenital platelet defects.
					Acquired platelet dysfunction.
					Obstetrics/gynecology.
				Toxicity
			Lysine Analogue Antifibrinolytic Agents
				Background
				Dose and Administration
				Indications
				Thrombocytopenic Patients
				Cardiac Surgery
				Orthopedic Surgery
				Orthotopic Liver Transplantation
				Trauma
				Obstetric and Gynecologic Indications
				Neurosurgery
				Other Uses
				Topical Antifibrinolytic Therapy
				Toxicity
			Aprotinin
			Vitamin K
				Background
				Mechanism of Action, Dose, and Administration
				Dose and Administration
				Indications
				Toxicity
		Other Agents
			Estrogens
			Protamine
		Management of Patients Who Refuse Transfusion or Are “Untransfusable”
		Summary
		References
	29 Therapeutic Apheresis—Applications for Hemorrhagic and Thrombotic Disorders
		Abstract
		Keywords
		Overview and Technical Considerations
		Clinical Considerations
			Targets and Goals for Therapy
			Indications for Therapeutic Apheresis
			Therapeutic Apheresis Procedural Considerations: Replacement Fluids, Venous Access and Extracorporeal Anticoagulation
				Replacement Fluids
				Venous Access
				Extracorporeal Anticoagulation
			Procedural Adverse Events
		Hemorrhagic Indications
			Posttransfusion Purpura
			Coagulation Factor Inhibitors
			Myeloproliferative Neoplasms and Acquired von Willebrand Disease
			Multiple Factor Deficiencies due to Sepsis-Associated Multiorgan Dysfunction and Acute Liver Failure
			Pulmonary-Renal Syndromes With Bleeding as a Complication
			Removal of Anticoagulant Substances
			Immune Thrombocytopenic Purpura
		Thrombotic Indications
			Thrombotic Thrombocytopenic Purpura
			Hemolytic Uremic Syndrome
			Thrombotic Microangiopathy
			Catastrophic Antiphospholipid Syndrome
			Heparin-Induced Thrombocytopenia
			Polycythemia Vera and Essential Thrombocytosis
		Conclusion
		References
	30 Use of Vena Cava Filters and Venous Access Devices
		Abstract
		Keywords
		Vena Cava Filters
			Introduction
			Historical Perspective
			Currently Available Vena Cava Filters
				Permanent Filters
				Optional Filters
			Technical Aspects
			Studies on Efficacy of Inferior Vena Cava Filters
			Adverse Outcomes After Filter Placement
				Permanent Filters
				Optional (Retrievable) Filters
			What Is the Safety and Efficacy of Vena Cava Filters in Alternative Insertion Sites (Suprarenal Inferior Vena Cava and Superior Vena Cava)?
			Should Patients With Permanent Vena Cava Filters Receive Prophylactic Anticoagulation?
			Can Patients With Vena Cava Filters Undergo Magnetic Resonance Imaging?
			Potential Indications for Inferior Vena Cava Filter Placement
				Contraindication to Anticoagulation
				Failure of Anticoagulant Therapy
				Pulmonary Thromboendarterectomy
				Trauma
				Free-Floating Venous Thrombus
				During Thrombolysis for Proximal Deep Venous Thrombosis
				Unsubstantiated Indications
					Patients With Cancer
					High-Risk Orthopedic Patients
					Bariatric Surgery
					Other Indications
			Appropriate Preventive Health Care and Follow-Up for Patients With Vena Cava Filters
			Areas of Future Research
			Conclusions
		Thrombosis Related to Venous Access Devices
			Introduction
			Pathogenesis and Epidemiology
			Clinical Presentation, Diagnosis, and Management
				Catheter Occlusion
				Occlusive Venous Thrombosis
				Superior Vena Cava Occlusion
				Right Atrial Thrombi
			Prevention of Venous Access Device–Related Thrombosis
			Vascular Access for Hemodialysis
		References
PART V : Issues Specific to Women
	31 Thrombotic Risk of Contraceptives and Other Hormonal Therapies
		Abstract
		Keywords
		Basic Science
		Hormonal Contraceptive Use and Thrombosis
			Venous Thromboembolism
			Myocardial Infarction
			Stroke
		Hormonal Contraception and Thrombophilia
			Counseling Thrombophilic Women in Hormonal Contraception Use
		Hormone Replacement Therapy and Thrombosis
		Hormone Replacement Therapy and Cardiovascular Disease
		Hormone Replacement Therapy and Stroke
		Hormone Replacement Therapy and Venous Thromboembolic Disease
		Selective Estrogen Receptor Modulators, Aromatase Inhibitors, and Thrombosis
			Aromatase Inhibitors
		Estrogen Therapy in Transgender Females
		Summary
		References
	32 Bleeding and the Management of Hemorrhagic Disorders in Pregnancy
		Abstract
		Keywords
		Introduction
		Normal Placentation
		Placental Separation and Expulsion
		Involution of the Uterus
		Obstetric Bleeding
		Miscarriage
		Ectopic Pregnancy
		Bleeding After the First Trimester of Pregnancy
		Postpartum Hemorrhage
			Risk Factors for Postpartum Hemorrhage
				Preexisting Anemia
				Thrombocytopenia
			Obstetric Management of Postpartum Hemorrhage
				Hematologic Management of Massive Postpartum Hemorrhage
			Other Hemostatic Agents
				Laboratory Testing in Management of Postpartum Hemorrhage
		Pregnancy and Childbirth in Women With Bleeding Disorders
			Management of Pregnancy and Childbirth in Women With Bleeding Disorders
		Summary
		References
	33 Thrombophilia in Pregnancy
		Abstract
		Key Words
		Introduction
		Anticoagulant Therapy During Pregnancy
			Heparin and Heparinoid Compounds
			Vitamin K Antagonists
			Parenteral Direct Thrombin Inhibitors
			Oral Direct Thrombin and Factor Xa Inhibitors (Direct Oral Anticoagulants [DOACs])
			Aspirin
			Thrombolytic Therapy
		Acute Venous Thromboembolism During Pregnancy
			Diagnosis of Venous Thromboembolism During Pregnancy
				Diagnosis of Deep Vein Thrombosis
				Diagnosis of Pulmonary Embolism
			Treatment of Venous Thromboembolism During Pregnancy
			Prevention of Pregnancy-Associated Venous Thromboembolism
				Prevention of Venous Thromboembolism in Pregnant Women With Thrombophilia and No History of Venous Thrombosis
				Prevention of Venous Thromboembolism in Pregnant Women With Prior Deep Vein Thrombosis or Pulmonary Embolism
				Prevention of Venous Thromboembolism During the Postpartum Period
		Prevention of Placenta-Mediated Pregnancy Complications
			Thrombophilia and Placenta-Mediated Pregnancy Complications
			Placenta-Mediated Pregnancy Complications in Women With Antiphospholipid Syndrome
			Placenta-Mediated Pregnancy Complications in Women Without Antiphospholipid Antibodies or Known Inherited Thrombophilias
			Placenta-Mediated Pregnancy Complications in Women With Inherited Thrombophilias
		Peripartum Anticoagulant Management
		Screening for Thrombophilia
		References
PART VI : Special Issues
	34 Surgery and Hemostasis
		Abstract
		Keywords
		Surgery for Patients With Congenital Hemostatic Defects
		Effects of Surgery on Hemostasis
			Thrombotic Signals as a Result of Surgery
			Prophylaxis Against Thrombosis
			Cardiopulmonary Bypass Surgery
			Orthotopic Liver Transplantation
		Preoperative Hemostatic Testing
			Screening for Hemostatic Defects
			Screening for Thrombotic Disorders
		Invasive Procedures in Patients With Abnormal Coagulation Tests
		Massive Transfusion Protocols in Trauma
		Consultation on Patients With Intraoperative or Postoperative Hemorrhage
			Closing Comments and Opinions
		References
	35 Anticoagulation in the Perioperative Period
		Abstract
		Key Words
		General Approach
		Thrombosis Risk by Reason for Antithrombotic Therapy
			Venous Disease
			Arterial Disease
				Myocardial Infarction and Stroke
				Atrial Fibrillation
				Mechanical Prosthetic Valves
		Bleeding Risk
		Recommended Approaches Listed by Antithrombotic Agents
			Antiplatelet Agents
				Aspirin
				P2Y12 Inhibitors
				Vorapaxar
		Anticoagulants
			Heparins
			Warfarin
			Continuing Warfarin
			Bridging
			Simple Warfarin Interruption
			Direct Oral Anticoagulants
		Special Situations
			Common Procedures
				Gastrointestinal Procedures
				Cardiac Device Surgery
				Percutaneous Coronary Interventions
		Neuraxial Anesthesia
		Drug Eluting Stents
		Antithrombotic Reversal for Emergency Surgery
			Antiplatelet Agents
			Warfarin
			Heparin
			Direct Oral Anticoagulants
		Summary
		References
	36 Understanding and Managing the Coagulopathy of Liver Disease
		Abstract
		Keywords
		Introduction
		Hemostatic Alterations in Different Types of Liver Disease
			Acute Liver Failure
			Cholestatic Liver Disease
			Nonalcoholic Fatty Liver Disease
		Difficulty in Interpreting Hemostasis Test Results in Patients With Liver Disease
		(Mis)Use of the International Normalized Ratio in Liver Disease
		The Concept of Rebalanced Hemostasis in Liver Disease
		Prevention and Treatment of Bleeding Complications (Boxes 36.1 and 36.2)
			Prophylactic Preprocedural Correction of a Prolonged International Normalized Ratio Is Not Indicated
			Prophylactic Preprocedural Correction of Moderate Thrombocytopenia Is Not Indicated
			How to Change Clinical Practice?
			Wait-and-See: A Rational Approach to Procedural Hemostasis Management
			Treatment of Spontaneous Bleeding
			Variceal Bleeding
			Role of Infection and Renal Failure
		Thrombotic Complications and Treatment (Boxes 36.3 & 36.4)
			Venous Thrombosis
			Arterial Thrombosis
			Portal Vein Thrombosis
			Hepatic Artery Thrombosis Following Liver Transplantation
		Hemostatic Management During Liver Transplantation
		Conclusion
		References
	37 Outpatient Oral Anticoagulant Therapy
		Abstract
		Key Words
		Vitamin K Antagonists
			Mechanism of Action
			Pharmacokinetics and Pharmacodynamics
			Warfarin and Drug Interactions
			Therapeutic Range and Monitoring
			Practical Aspects of Warfarin Management
				Initiation and Maintenance Dosing
				Management of Nontherapeutic International Normalized Ratios
				Management of Oral Anticoagulation During Invasive Procedures
				Diagnostic Evaluation of Bleeding
				Predicting and Managing the Risks of Oral Anticoagulant Therapy
				Anticoagulation Management Services
				Patient Self-Testing and Patient Self-Management
		Target-Specific, Direct Oral Anticoagulants
			Limitations of Warfarin
			Direct Factor IIa Inhibitors
				Dabigatran
			Direct Factor Xa Inhibitors
				Rivaroxaban
				Apixaban
				Edoxaban
				Betrixaban
			Practical Management of the Direct Oral Anticoagulants
				Selecting Patients for Direct, Target- or Factor-Specific Oral Anticoagulants Therapy (Atrial Fibrillation and Venous Thromboembolism)
				Initiation of Direct, Target- or Factor-Specific Oral Anticoagulants Therapy (Atrial Fibrillation and Venous Thromboembolism)
				Care Transitions and Patient Follow-Up Strategies
				Monitoring or Measuring Direct, Target- or Factor-Specific Oral Anticoagulants Activity
				Managing Drug–Drug Interactions
				Managing Invasive Procedures
				Managing Bleeding or Urgent Surgery
				Managing Transitions Between Classes of Anticoagulants
			Limitations of the Direct Oral Anticoagulants
			Implications for Clinical Practice
		References
	38 Hematologic Interventions for Acute Central Nervous System Disease
		Abstract
		Keywords
		Introduction
		Acute Ischemic Stroke
			Antithrombotic Therapy
				Antiplatelet Agents
				Anticoagulant Agents
			Bleeding Risk Associated With Parenteral Anticoagulation
			Effect in Subgroups
				Large Vessel Atherosclerotic Stenosis/Occlusion
				Cardioembolism
				Hypercoagulable States
			Thrombolytic Therapy
			Mechanical Thrombectomy
				Consultation Strategies
		Cerebral Venous Thrombosis
			Consultation Strategies
		Overview of Central Nervous System Bleeding
		Spontaneous Intracerebral Hemorrhage
			Consultation Strategies
		Treatment
			Hyperacute Hemostatic Therapy
			Reversal Strategies With Particular Coagulation Abnormalities
				Oral Vitamin K Antagonists
				Oral Direct Thrombin Inhibitors
			Direct Oral Anticoagulants
			Oral Antiplatelet Agents
		Parenteral Anticoagulants
			Unfractionated Heparin, Low-Molecular-Weight Heparins, and Heparinoids
				Intravenous Direct Thrombin Inhibitors
			Thrombolytic Agents
				GPIIb/IIIa Inhibitors
				Other Agents With Antithrombotic Effects
				Systemic Disorders Associated With Bleeding
		Aneurysmal Subarachnoid Hemorrhage
			Procoagulant Therapy to Prevent Early Rebleeding
			Treatment of Vasospasm and Delayed Cerebral Ischemia
		Traumatic Brain Injury
			Traumatic Brain Injury–Related Coagulopathy
			Hematologic Interventions for Traumatic Brain Injury
		Correction of Coagulation Test Results Before Neurosurgical Procedures
		Restarting or Initating Antithrombotic Therapy After Central Nervous System Hemorrhage
			Antithrombotic Therapy in Patients After Intracerebral Hemorrhage
				Consultation Strategies
			Antithrombotic Therapy in Patients After Hemorrhagic Conversion of Ischemic Stroke
			Antithrombotic Therapy in Patients After Subdural Hematoma
		References
	40 Hemorrhage Control and Thrombosis Following Severe Injury
		Abstract
		Keywords
		Introduction
		Massive Transfusion and the Coagulopathy of Trauma
			Pathogenesis
			Clinical Presentation
		Treatment of Postinjury Coagulopathy
			Pharmaceutical Treatment of Postinjury Coagulopathy (Recombinant Factor VIIa, Fibrinogen, Prothrombin Complex Concentrates, Tranexamic Acid)
			Patients With Congenital Bleeding Diatheses
			Patients With Acquired Bleeding Diatheses and Comorbid Conditions
		Thrombocytopenia
		Thrombosis in Trauma Patients
		Thrombocytosis in Trauma Patients
		Summary
		References
	41 Hemostatic Aspects of Sickle Cell Disease
		Abstract
		Keywords
		Historical Perspective
		Pathogenesis of Sickle Cell Disease
			The Red Blood Cell and Hemoglobin S Polymerization
			Leukocytes
			Platelets
			Endothelium
			Inflammation
			Hemostatic Changes
				Pathogenesis
		Clinical Considerations
			The Role of Hemostatic Abnormalities in Vaso-Occlusion
			Thrombophilic Deoxyribonucleic Acid Mutations
			Red Blood Cell Transfusion
			Hydroxyurea Therapy
		Acute Chest Syndrome
			Etiology and Pathophysiology
			Clinical Management
		Pulmonary Hypertension in Sickle Cell Disease
			Pathophysiology
			Clinical Management
		Stroke
		New Drugs in Sickle Cell Disease
		References
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	W
	X
	Z