Anticoagulants, Antiplatelets, and Thrombolytics

Preface......Page 6
Contents......Page 10
Contributors......Page 12
1 Introduction......Page 13
2.1.2 Procedure......Page 14
2.2.1 Purpose and Rational......Page 15
2.2.3 Evaluation......Page 16
2.3.2 Procedure......Page 17
2.4.1 Purpose and Rational......Page 18
2.4.2 Procedure......Page 19
2.4.5 Modifications of the Method......Page 20
2.5.2 Procedure......Page 21
2.6.2 Procedure......Page 22
2.7.1 Purpose and Rational......Page 23
2.8.2 Procedure......Page 24
2.9.2 Procedure......Page 25
2.10.2 Procedure......Page 26
2.11.2 Procedure......Page 27
3 In Vitro Models of Thrombosis......Page 28
3.1.1 Purpose and Rational......Page 29
3.1.2 Procedure......Page 30
3.2.1 Purpose and Rational......Page 31
3.2.2 Procedure......Page 33
3.3.1 Purpose and Rational......Page 34
3.3.2 Procedure......Page 35
3.3.3 Evaluation......Page 36
References......Page 38
1 Introduction......Page 41
1.2 Models Based on Vessel Wall Damage......Page 43
1.3.3 Selection of Animal Model......Page 44
2.1.1 Purpose and Rationale......Page 45
2.1.2 Procedure......Page 53
2.1.3 Evaluation......Page 55
2.1.5 Modifications of the Method......Page 56
2.2.2 Procedure......Page 57
2.2.4 Critical Assessment of the Method......Page 58
2.2.5 Modifications of the Method......Page 59
2.3 Electrically Induced Thrombosis......Page 60
2.3.4 Critical Assessment of the Method......Page 64
2.4 Ferric Chloride (FeCl 3 )-Induced Thrombosis......Page 65
2.4.2 Procedure......Page 66
2.5 Thrombin-Induced Clot Formation in Rabbit Femoral or Canine Coronary Artery......Page 67
2.5.1 Purpose and Rationale......Page 68
2.6 Laser-Induced Thrombosis......Page 69
2.6.2 Procedure......Page 70
2.7.1 Purpose and Rationale......Page 71
2.8.1 Wire Coil-Induced Thrombosis......Page 72
2.8.2 Eversion Graft-Induced Thrombosis......Page 74
2.8.3 Arteriovenous (AV) Shunt Thrombosis......Page 76
2.8.4 Thread-Induced Venous Thrombosis......Page 77
2.8.5 Thrombus Formation on Superfused Tendon......Page 78
2.9.2 Procedure......Page 79
2.9.5 Modifications of the Method......Page 80
2.10.1 Purpose and Rationale......Page 81
2.12.1 Purpose and Rationale......Page 82
2.13.1 Purpose and Rationale......Page 83
2.14.2 Procedure......Page 84
2.14.4 Critical Assessment of the Method......Page 85
2.15.3 Evaluation......Page 86
2.16.2 Procedure......Page 87
3.1.1 Purpose and Rationale......Page 88
3.2.2 Procedure......Page 89
3.3.2 Procedure......Page 90
4.1 Purpose and Rationale......Page 91
4.1.1 Knock-out Mice......Page 94
5.2 Evaluation of Bleeding Tendency......Page 100
5.3 Selection of Models Based on Species-Dependent Pharmacology/ Physiology......Page 101
5.4 Selection of Models Based on Pharmacokinetics......Page 102
6 Clinical Relevance of Data Derived from Experimental Models......Page 104
References......Page 105
1 Introduction......Page 120
2 Heparin Versus LMWH......Page 123
3 Emerging Links Between Thrombosis and Inflammation: Potential Role of Heparin......Page 124
3.2 Heparin/LMWH and Inflammatory Bowel Diseases......Page 127
3.3 Heparin as an Anti-inflammatory Molecule: Potential Mechanisms......Page 128
4 Emerging Links Between Thrombosis and Cancer: Potential Role of Heparin......Page 129
4.2 Treatment of Venous thromboembolism in Cancer Patients......Page 131
4.4 Activation of Coagulation in Cancer......Page 133
4.5 Combination Anticoagulant and Antiplatelet Therapies in Cancer......Page 135
5 Heparin and Angiogenesis......Page 136
6 Conclusions......Page 137
References......Page 138
1.1 Antibody Generation......Page 144
1.3 Seroconversion......Page 145
2.1 Thrombocytopenia......Page 146
3.1 Antigen Assays......Page 147
3.2 Functional Assays......Page 149
3.3.2 HIT Positive Patients......Page 151
4 Clinical Management......Page 152
4.1 Direct Thrombin Inhibitors (DTIs)......Page 153
4.1.1 Argatroban......Page 154
4.1.2 Lepirudin......Page 155
4.2.1 Danaparoid......Page 156
4.3 Vitamin K Antagonists......Page 157
4.4.2 Multi-Targeted Treatment......Page 158
5 Regulatory Considerations......Page 159
6 Summary and Conclusions......Page 160
References......Page 161
1 Introduction......Page 168
2.2 Nematode Anticoagulant Proteins......Page 170
2.3 Anti-TF/VIIa......Page 172
2.4 TFPI......Page 173
3.1 Indirect FXa Inhibitors......Page 174
3.1.2 SSR126517E (Biotinylated Idraparinux)......Page 175
3.2.2 Apixaban......Page 176
3.2.3 Rivaroxaban (Bayer HealthCare AG and J&J/Scios, Inc.)......Page 177
3.2.5 DU-176b......Page 179
3.3 Selective, Direct FIXa and FXI Inhibitors......Page 180
4.1 Indirect Thrombin Inhibitors......Page 181
4.2 Direct Thrombin Inhibitors......Page 182
4.3.2 Dabigatran......Page 183
4.3.3 TGN-167......Page 184
5 Conclusions......Page 185
References......Page 186
1 Introduction......Page 191
1.1 Pharmacology of Warfarin......Page 192
1.2 Investigating Potential Alternatives to Warfarin......Page 193
1.3 Safer and More Efficacious Anticoagulation......Page 194
2 Clinical Pharmacology of Rivaroxaban......Page 195
2.1 Pharmacokinetics......Page 196
2.3 Toxicity and Adverse Effects......Page 197
3 Clinical Indications......Page 198
4 Post-operative Thromboprophylaxis......Page 199
5 Treatment of Venous Thrombosis......Page 203
6.1 Rivaroxaban in ACS......Page 204
7 Expert Opinion......Page 205
8 Conclusion......Page 207
References......Page 208
1 Introduction......Page 212
2.1 Heparin and Platelet GPIIa/IIIa Antagonists......Page 216
2.2.1 Limitations of Combined Therapy......Page 217
2.2.2 The CLARITY-TIMI Study......Page 218
2.2.4 The CHARISMA Study......Page 219
2.2.5 The CURE and PCI-CURE Studies......Page 220
2.2.6 The MATCH Study......Page 221
2.2.7 The CARESS Study......Page 222
2.2.8 Summary: Combination Aspirin and Clopidogrel Therapy......Page 223
3 Expert Opinion and Future Directions......Page 224
References......Page 225
1 Introduction......Page 229
2.2 Therapeutic Review......Page 231
3 Conclusion......Page 234
References......Page 235
1 Introduction......Page 237
2.2 Tea Extract......Page 239
2.4 Echistatin......Page 240
3.2 Diallyl Trisulfide......Page 241
4.1 Vitamin E......Page 242
5.1 Heparin......Page 243
5.2 Hirudin......Page 244
References......Page 245
1.1 Coagulation Activation in Cancer......Page 249
1.2 The Role of Tissue Factor in Cancer-Associated Coagulation Activation......Page 250
1.4 The Role of the Coagulation System in Blood-Borne Metastasis......Page 251
2.4 Evidence of Clotting Activation......Page 252
2.5 Quantitation of Pulmonary Tumor Nodules......Page 253
3.1 Effects of Heparins and Coumadin......Page 254
3.2 Anti-metastatic Effect of a Non-anticoagulant Low-Molecular Heparin (LMWH) Versus the Standard LMWH Enoxaparin......Page 255
3.3 The Effect of TF Inhibition on Experimental Metastasis......Page 258
3.4 Effect of Anti-platelet Agents on Experimental Metastasis......Page 261
5 Notes......Page 263
References......Page 265
1 Introduction......Page 268
2 Selectins and Anti-selectins......Page 269
2.1.1 Procedure......Page 270
3 Integrins......Page 271
3.1 Potent and Selective Small-Molecule Antagonists of 4 Integrins......Page 272
3.2.1. Leukocyte Integrin?4?1 as a PotentialTherapeutic Target......Page 273
3.3. ?2 Integrins......Page 274
3.4.2 Chronic Therapy with Platelet GPIIb/IIIa Antagonists......Page 275
4.1 Light Transmittance Aggregometry Assay......Page 276
4.4. SK-BR-3Cell-Vitronectin(?v?5-Mediated)Adhesion Assay......Page 277
5 Immunoglobulins......Page 278
5.3 Human Soluble (s)VCAM-1, ICAM-1, or PECAM Assay......Page 279
6 Conclusion......Page 280
References......Page 281
1 Introduction......Page 284
2 SNP Mapping......Page 286
2.1.1 Phase-I Metabolizing Enzymes......Page 288
2.2 Drug Transporter Gene Polymorphisms......Page 289
3 Pharmacogenomics of Warfarin Therapy......Page 290
4 Pharmacogenomics in CVD and Beyond......Page 292
5 Summary and Future Directions......Page 293
References......Page 294
1 Introduction......Page 297
2 Pathogenesis......Page 298
2.4 Reperfusion Injury and Nitric Oxide......Page 299
2.5 Role of Inflammatory Mediators......Page 300
3.3 Characteristics of Pain......Page 301
4 Management of Painful Episodes......Page 302
4.3 Hospitalization......Page 304
4.7 Rehabilitation and Psychological Considerations in the Management of SCD......Page 306
5.2 LMWH in Pregnancy and Sickle Cell Anemia......Page 308
Subject Index......Page 309
References......Page 310
SUBJECT INDEX......Page 314