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Main description:
An up-to-date overview of blood coagulation, hemostatis, and thrombosis, this volume also provides a state-of-the-art report of current anti-thrombotic and anti-coagulant strategies as well as a summary of current research interest in the area and potential future targets. It attempts to balance traditional pharmacology with the newer sciences of molecular biology and in so doing, sets a framework for future advances in the field. The book is a concise, current and useful reference for the basic researcher as well as the practicing physician working in the fields of cardiology, internal medicine or surgery.
Contents:
1: The Coagulation Pathway and Antithrombotic Strategies (With 7 Figures).- A. Introduction.- B. The Coagulation Pathway.- I. The Cascade/Waterfall Model.- II. The Revised Model.- III. Structure-Activity Relationships of Coagulation Proteases.- 1. Thrombin.- 2. Factor Xa.- 3. Factor VII/Tissue Factor Complex.- C. Physiological Regulators.- I. Antithrombin-III (ATIII) and Heparin Cofactor-II (HCII).- II. Tissue Factor Pathway Inhibitor.- III. Protein C/S-Thrombomodulin Complex.- D. Platelet and Cellular Contributions.- I. Cell Surface Dependence.- II. Platelet Participation.- III. Vascular Contributions.- E. Fibrinolysis.- F. Antithrombotic Strategies.- I. Coagulation Factor Inhibitors.- 1. Direct Thrombin Inhibitors.- 2. Thrombin Generation Inhibitors.- a) Factor Xa Inhibitors.- b) Inhibitors of Other Coagulation Factors.- II. Antiplatelet Agents.- 1. Platelet Adhesion and Activation Inhibitors.- 2. Fibrinogen Receptor Antagonists.- III. Thrombolytic Agents.- IV. Other Strategies.- G. Conclusion.- References.- 2: New Developments in the Molecular Biology of Coagulation and Fibrinolysis (With 7 Figures).- A. Introduction.- I. The Coagulation System.- II. The Plasminogen System.- III. Targeted Manipulation and Adenovirus-Mediated Transfer of Genes in Mice.- B. Embryonic Development and Reproduction.- I. Coagulation System.- 1. Tissue Factor and Factor VII.- 2. Thrombomodulin.- 3. Thrombin Receptor and Factor V.- 4. Fibrinogen.- II. Fibrinolytic System.- III. Integrated View of a Role for the Coagulation and Fibrinolytic System in Vascular Development.- C. Health and Survival.- I. Coagulation System.- II. Fibrinolytic System.- D. Hemostasis.- I. Coagulation System.- II. Fibrinolytic System.- E. Thrombosis and Thrombolysis.- I. Coagulation System.- II. Fibrinolytic System.- III. Fibrin Deposits and Pulmonary Plasma Clot Lysis in Transgenic Mice.- IV. Adenovirus-Mediated Transfer of t-PA or PAI-1.- F. Neointima Formation.- G. Atherosclerosis.- H. Tissue Remodeling Associated with Wound Healing.- I. Conclusions.- References.- 3: Epidemiology of Arterial and Venous Thrombosis (With 4 Figures).- A. Epidemiology: Its Potential and Its Limitations.- B. The Epidemiological Study of Arterial and Venous Thrombosis.- I. Arterial Thrombosis.- II. Venous Thrombosis.- C. Risk Factors for Arterial Thrombosis.- I. Fibrinogen.- II. Fetal-Infant Origins Hypothesis of Ischemic Heart Disease.- III. Insulin Resistance.- IV. Hyperhomocysteinemia.- D. Risk Factors for Venous Thrombosis.- E. Future Directions in Epidemiological Research.- I. Genetic Epidemiology.- II. Evidence Synthesis.- References.- 4: In Vivo Models of Thrombosis (With 5 Figures).- A. Introduction.- B. Vessel Wall Injury-Induced Model of Thrombosis.- I. Photochemical Reaction.- II. Laser.- III. Mechanically Induced Injury.- 1. Pinching or Crushing.- 2. Perfusion with Saline or Air.- 3. Endarterectomy and Balloon Angioplasty.- IV. Electrical Current-Induced Injury.- C. Stasis/Hypercoagulability-Induced Models of Thrombosis.- I. Wessler Test and Its Variants.- D. Foreign Surface-Induced Thrombosis.- I. Eversion Graft.- II. Wire Coils.- III. Preformed Thrombi.- IV. Hollenbach's Deep Venous Thrombosis Model.- V. A Novel Veno-Venous Shunt Model in Rabbit.- E. Transgenic Animal Models.- F. Conclusions.- References.- 5: Monitoring Antithrombotic Therapy.- A. Introduction.- I. Balancing Antithrombotic Efficacy Against the Risk of Bleeding.- B. Warfarin.- I. Mechanism of Action.- 1. Effect on Vitamin K-Dependent Clotting Factors.- 2. Kinetics of Vitamin K-Dependent Clotting Factors During Warfarin Therapy.- 3. Variation in Pharmacological Response.- II. Laboratory Monitoring.- 1. Prothrombin Time for Monitoring Warfarin Therapy.- 2. Standardisation of Thromboplastin Reagents.- 3. Choice of Thromboplastins for Clinical Monitoring.- III. Determinants of Bleeding Risk.- IV. Practical Aspects of Warfarin Dosing.- V. Maintenance Treatment.- 1. Anticoagulant Clinics.- 2. Computer-Assisted Monitoring and Patient Self-Monitoring.- VI. Alternative Methods of Monitoring Warfarin Therapy.- 1. Functional Prothrombin Assay.- 2. Prothrombin Fragment F1.2.- 3. Prothrombin-Proconvertin Ratio.- C. Heparin.- I. Heparin Structure.- II. Mechanism of Action.- III. Unfractionated Heparin.- 1. Pharmacokinetics.- 2. Laboratory Monitoring by the Activated Partial Thromboplastin Time (APTT).- 3. Heparin Resistance.- 4. Dose-Adjustment Nomograms.- 5. Subcutaneous Heparin Regimens.- 6. Determinants of Bleeding Risk.- 7. The Activated Clotting Time for Monitoring High Dose Heparin Therapy.- IV. Low Molecular Weight Heparin.- 1. Pharmacokinetics.- 2. Laboratory Monitoring by Chromogenic Anti-Factor Xa Assays.- 3. Clinical Efficacy and Bleeding Risks.- D. Direct-Acting Antithrombin Agents.- I. Role of Thrombin in Thrombogenesis.- II. Mechanism of Action and Clinical Studies.- III. Laboratory Monitoring.- E. Thrombolytic Agents.- I. Clinical Use.- II. Monitoring Thrombolytic Therapy.- F. Antiplatelet Agents.- I. Aspirin.- 1. Clinical Effects.- 2. Mechanism of Action.- 3. Laboratory Monitoring.- 4. Other Antiplatelet Agents.- G. Summary/Conclusion.- References.- 6: Use of Transgenic Mice in the Study of Thrombosis and Hemostasis (With 4 Figures).- A. Introduction.- B. Overview of Coagulation and Fibrinolysis.- C. Transgenic Technology.- I. Generation of Standard Transgenic Mice by Zygote Injection.- II. Generation of Knockout Mice.- D. Transgenic Mice Deficient in Coagulation Factors.- E. Transgenic Approaches to the Study of the Fibrinolytic System.- I. Plasminogen.- II. Plasminogen/Fibrinogen.- III. t-PA, u-PA and t-PA/u-PA.- IV. u-PAR and t-PA/u-PAR.- V. PAI-1.- F. Summary.- References.- 7: Current Antiplatelet Therapy (With 8 Figures).- A. Introduction.- B. Platelets: Physiological and Pathological Activities.- I. Physiological Activities.- II. Pathological Activities.- C. Current Antiplatelet Therapy.- I. Aspirin.- II. Dipyridamole.- III. Ticlopidine.- IV. Abciximab.- 1. Preclinical Development.- 2. Clinical Pharmacology.- 3. Additional Consequences.- a) Inhibition of Platelet Release.- b) Inhibition of Mac-1 Upregulation.- c) Inhibition of Platelet-Mediated Thrombin Generation.- d) Characterization of Abciximab Binding to ?v/?3.- 4. Clinical Experience.- a) Early Human Efficacy Studies.- b) The Phase III EPIC Trial.- c) The EPILOG Trial.- d) The CAPTURE Trial.- e) Clinical Summary of Abciximab.- D. Investigational Agents.- I. GPIIb/IIIa Antagonists.- II. Clopidogrel.- References.- 8: Platelet Membrane Receptors and Signalling Pathways: New Therapeutic Targets (With 7 Figures).- A. Introduction.- I. Platelet Activation.- II. Platelet Inhibition.- III. Regulation of Platelet Activation.- B. Signalling by Cell Surface Receptors.- I. G Protein-Coupled Receptor Signalling.- 1. Guanine Nucleotide Binding Proteins and Effector Regulation.- 2. The G Protein GTP/GDP Cycle and Effector Modulation.- 3. G Protein-Regulated Effectors.- a) Adenylyl Cyclase.- b) Phospholipase C.- c) Other ??-Regulated Effectors: src Family Kinases and PI 3-Kinase.- II. Tyrosine Kinase-Linked Receptors.- III. Ion Channels and Their Receptors.- C. Signal Enzymes and Mediators.- I. Phosphoinositide Metabolism.- II. Phospholipase A2.- III. PI 3-Kinase.- IV. Cyclic Nucleotides.- 1. cAMP.- 2. cGMP.- D. Platelet G Protein-Coupled Receptors.- I. Thrombin (PAR1).- 1. Thrombin Binding Sites.- 2. PAR1, A G Protein-Coupled Receptor for Thrombin.- 3. Other Protease-Activated Receptors (PARs).- 4. PAR1 and Human Platelet Activation.- II. Thromboxane A2 (TP Receptor).- III. ADP Receptors.- IV. 5-Hydroxytryptamine (5HT2A Receptor).- V. Vasopressin (V1 Receptor).- VI. Platelet Activating Factor (PAF).- VII. Adrenaline (?2-Adrenoceptor).- VIII. Prostacyclin (IP Receptor).- IX. Other Seven Transmembrane Receptors.- E. Tyrosine Kinase-Linked Receptors.- I. Collagen.- II. Fc?RUA.- III. Thrombopoietin.- F. Adhesion Receptors.- I. Integrins.- 1. GPIIb-IIIa.- 2. Other Platelet Integrins.- II. GP-IX-V (vWf Receptor).- III. PADGEM (P-Selectin).- IV. PECAM-1.- V. GPIV.- G. Clinical Settings for Antiplatelet Drugs.- I. The Platelet as a Target in Thrombotic Disease.- II. Overview of Currently Used Agents.- III. Possible Settings for New Antiplatelet Agents.- H. New Targets for Drug Development.- I. Receptors as Targets.- 1. ADP Receptors.- 2. Adhesion Receptors.- 3. Thrombin Receptor.- II. Signalling Pathways as Targets.- 1. Protein-Protein Interfaces.- 2. Enzyme Targets.- III. Development of New Drugs: Aspirin's Legacy.- References.- 9: Heparin and Other Indirect Antithrombin Agents (With 1 Figure).- A. Introduction.- I. Magnitude of the Problem of Intravascular Thrombosis and Thromboembolic Disease.- B. Unfractionated Heparin: The Prototypical Indirect Antithrombin.- I. History.- II. Source.- III. Structure.- IV. Mechanism of Action.- V. Pharmacokinetics.- 1. Administration.- a) Intravenous Route.- b) Subcutaneous Route.- c) Novel Methods of Administration.- 2. Distribution.- 3. Clearance.- 4. Effect of Physiological State.- 5. Drug Interactions.- VI. Clinical Indications.- 1. Venous Thrombosis and Thromboembolic Disease.- 2. Use of Heparin in Acute Coronary Syndromes.- 3. Heparin for Trousseau Syndrome: A Unique Therapy.- 4. Novel Uses of Heparin.- VII. Therapeutic Monitoring.- VIII. Toxicity.- IX. Antidotes: Reversal of Anticoagulant Effect.- C. Heparinoids and Related Anticoagulants.- I. Pentosans (Sulfonated Xylans).- 1. Source.- 2. Mechanism of Action.- 3. Administration.- 4. Clinical Uses.- 5. Toxicity.- 6. Clinical Relevance.- II. Dermatan Sulfate.- 1. Introduction.- 2. Source.- 3. Mechanism of Action.- 4. Pharmacokinetics.- 5. Clinical Use.- 6. Clinical Relevance.- III. Sulodexide.- 1. Introduction.- 2. Source.- 3. Mechanism of Action.- 4. Pharmacokinetics.- 5. Clinical Indications.- 6. Toxicity.- 7. Future.- IV. Danaparoid (Organan 10172).- 1. Introduction.- 2. Source.- 3. Mechanism of Action.- 4. Pharmacokinetics.- 5. Clinical Uses.- 6. Toxicity.- 7. Antidotes.- 8. Future.- V. Other Indirect Antithrombins.- D. Conclusion.- References.- 10: Low Molecular Weight Heparin.- A. Introduction.- B. Discovery and Development of Low Molecular Weight Heparins.- I. Properties of Unfractionated Heparin.- II. Antithrombotic Properties of Low Molecular Weight Heparin.- III. Advantages of Low Molecular Weight Heparin over Unfractionated Heparin.- C. Use of Low Molecular Weight Heparins.- I. Prevention of Venous Thromboembolism.- II. Orthopedic Surgery.- D. Trauma.- E. General Surgery.- I. Medical Patients.- II. Low Molecular Weight Heparinoid.- F. Treatment of Venous Thromboembolism.- G. Out-of-Hospital Treatment of Venous Thromboembolism with Low Molecular Weight Heparin.- H. Role of Low Molecular Weight Heparin in the Prevention and Treatment of Arterial Thrombosis.- I. Unstable Angina.- II. Thrombotic Stroke.- III. Peripheral Vascular Disease.- IV. Hemodialysis.- V. Other Vascular Problems.- I. Current Recommendations for the Use of Low Molecular Weight Heparin.- I. Prevention of Venous Thromboembolism.- II. Treatment of Venous Thromboembolism.- J. Summary and Conclusions.- References.- 11: Parenteral Direct Antithrombins (With 3 Figures).- A. Introduction.- B. Thrombin: Structure and Function.- C. Limitations of Current Antithrombotic Therapy.- D. Direct Thrombin Inhibitors.- I. Hirudin.- II. Other Direct Thrombin Inhibitors.- E. Potential Roles for Direct Thrombin Inhibition.- I. Acute Myocardial Infarction, Adjunct to.- Thrombolysis.- 1. Preclinical Studies.- 2. Phase II Clinical Trials.- 3. Phase III Clinical Trials.- 4. Further Acute Myocardial Infarction Studies.- II. Unstable Angina and Myocardial Infarction Without ST Elevation.- 1. Phase II Clinical Trials.- 2. Phase III Clinical Trials.- III. Adjunct to Percutaneous Revascularization.- 1. Preclinical Studies.- 2. Phase II Clinical Trials.- 3. Phase III Clinical Trials.- IV. Deep Venous Thrombosis.- V. Heparin-Induced Thrombocytopenia.- F. Rebound Phenomenon.- G. Summary and Future Directions.- References.- 12: Anticoagulant Therapy with Warfarin for Thrombotic Disorders (With 2 Figures).- A. Introduction.- B. Pathogenesis.- C. Pharmacology.- I. Mechanism of Action.- II. Assessment of Clinical Efficacy.- III. Optimal Therapeutic Regimens.- IV. Benefits of Monitoring.- D. Prevention and Management of Venous Thromboembolism.- I. Prevention of Venous Thrombosis Following Orthopedic Surgery.- II. Prevention of Stroke and Venous Thromboembolism in Acute Myocardial Infarction.- III. Treatment of Deep Venous Thrombosis.- E. Antithrombotic Therapy for Atrial Fibrillation.- F. Antithrombotic Therapy for Prosthetic Heart Valves.- G. Other Indications for Oral Anticoagulant Therapy.- H. Complications of Warfarin Therapy.- References.- 13: Oral Thrombin Inhibitors: Challenges and Progress (With 3 Figures).- A. Introduction.- I. Role of Thrombin in Hemostasis and Thrombosis.- II. Medical Need for Anticoagulant and Antithrombotic Drugs.- 1. Acute Anticoagulation.- 2. Chronic Anticoagulation with Warfarin.- B. Potential Advantages of Direct, Small Molecule Inhibitors.- C. Pharmacological and Pharmacokinetic Issues.- I. Safety.- II. Selectivity and Fibrinolytic Compromise.- III. Pharmacodynamics: Efficacy and Kinetics of Inhibition.- IV. The Rebound Phenomenon.- V. Oral Bioavailability and Pharmacokinetics.- D. Thrombin Inhibitors in Development.- I. Bivalent Direct Thrombin Inhibitors.- 1. Hirudin.- 2. Hirulog.- II. Reversible Inhibitors of Thrombin.- 1. Argatroban (Novastan).- 2. Napsagatran.- 3. Inogatran.- III. Covalent Inhibitors of Thrombin.- 1. Efegatran.- 2. Corvas: CVS 1123.- 3. DuPont Merck: DuP 714.- E. Summary and Conclusions.- References.- 14: Inhibitors of Factor Xa (With 6 Figures).- A. Introduction.- B. Rationale of Factor Xa Inhibitors.- C. Pharmacological Profile of Factor Xa Inhibitors.- I. ATIII-Dependent Inhibitors.- II. Direct Inhibitors.- 1. Naturally Occurring Inhibitors.- 2. Synthetic Small Molecule Inhibitors.- a) Peptidomimetics.- b) Benzamidine Derivatives.- c) Bisamidine Derivatives.- d) Argininal Derivatives.- e) Piperidinylpyridine Derivatives.- D. ATIII-Independent Inhibition of Factor Xa on Prothrombinase.- E. Comparative Antithrombotic Efficacy of Direct Factor Xa Inhibitors.- F. Summary and Conclusions.- References.- 15: Inhibitors of Tissue Factor/Factor Vila (With 4 Figures).- A. Introduction.- B. Role in Hemostasis.- C. Structural Biology of Tissue Factor and Factor Vila.- D. Endogenous Regulators of Tissue Factor.- I. Tissue Factor Pathway Inhibitor.- II. Antithrombin.- E. Pathophysiology of TF/VIIa.- F. Experimental Inhibitors of TF/VIIa.- I. Recombinant TFPI (rTFPI) and Truncated rTFPI.- II. Inactivated Factor Vila: FVIIai.- III. Recombinant Nematode Anticoagulant Peptide (rNAPc2).- IV. TF Antibodies.- G. Summary and Conclusions.- References.- 16: Natural Anticoagulants and Their Pathways (With 5 Figures).- A. Introduction.- I. The Protein C Activation Complex.- II. The APC Anticoagulant Complex.- III. Inhibition of the Anticoagulant Complex.- B. Modulation of the Protein C Pathway in Disease.- I. APC Resistance and Factor V Leiden.- C. Thrombomodulin as an Antithrombotic Agent.- D. Protein C as an Antithrombotic Agent.- I. Protein C and Arterial Thrombosis.- II. Reperfusion Injury.- E. Protein S as an Antithrombotic Agent.- F. Mutations to Modulate Natural Anticoagulant Responses.- I. Mutations in Protein C.- II. Mutations in Thrombin.- G. Inactive Coagulation Factors as Antithrombotics.- H. Summary.- References.
PRODUCT DETAILS
Publisher: Springer (Springer-Verlag Berlin and Heidelberg GmbH & Co. K)
Publication date: September, 2011
Pages: 485
Weight: 783g
Availability: Available
Subcategories: Cardiovascular Medicine, General Issues, Haematology, Pharmacology, Physiology
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