دانلود کتاب Consultative hemostasis and thrombosis

فهرست مطالب :

Copyright Page 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