Index

A aIIbb3, 60, 62, 69, 70, 73, 74, 79, 80 AA. See (AA) AJW202, 293 AA metabolism, 139 Akt-1, 345 a2b1, 69, 70, 318–323 Akt-2, 345 ABCB1 gene, 176 ALX-0081, 296 Abciximab, 206–208, 497, 500, 501, 504–505, ALX-0681, 298 509, 513, 514, 525 Anagrelide, 227, 229 approval, 206 Ankle brachial indexes (ABIs), 549, 587, EPIC trial, 207 595–597 EPILOG study, 207 framingham risk score, 551 EPISTENT study, 207 screening, 550 binding, 207 sensitivity, 551 thrombocytopenia, 206 specificity, 551 in unstable angina, 208 vascular risk, 550 ABIs. See Ankle brachial indexes (ABIs) Antagomirs, 439 Acetylsalicylic acid (), 137–158 Antibodies, 317 ACS. See Acute coronary syndromes (ACS) Anticoagulants, 525, 537 Acute coronary syndromes (ACS), 288 Anticoagulation, 533, 534 Acute ischemic stroke, 143, 149–150 Antioxidant, 233 Acute myocardial infarction, 142, 143, 149, Antiplatelet agents, 263, 553 153, 157 Antithrombotic Trialist’s ADAMTS-13, 93 Collaboration, 553 Adenosine diphosphate (ADP), 37, 88, 96, aspirin, 553 166, 473 clopidogrel, 553 Adenosine triphosphate (ATP), 37 dipyridamole, 553 Adhesion, 90, 112–118, 125 meta-analysis, 560 Adhesion molecules infiltration, 264 , 553 Adiponectin, 315 risk reduction, 553 ADP. See Adenosine diphosphate (ADP) ticlopidine, 553 ADP inhibitors (or P2Y12 blockers), 497–499, vascular events, 553 501–505, 507–509, 513, 514 Antiplatelet therapy, 472 ADP- antagonists, 169 Apixaban, 535, 539 Adverse effects, 153–156 Aptamers, 299–301 Aegyptin, 327 Arachidonic acid (AA), 474

P. Gresele et al. (eds.), Antiplatelet Agents, Handbook of Experimental 607 Pharmacology 210, DOI 10.1007/978-3-642-29423-5, # Springer-Verlag Berlin Heidelberg 2012 608 Index

ARC1779, 299–300 TXS signaling, 279 ARC15105, 300 Cardiovascular death, 248 AR-C69931MX, 456 Carotid endarterectomy (ACE) inhibition, Aspirin, 474, 496, 498–499, 501–502, 143, 156 504–507, 511–514, 520, 522, Carotid stenosis, 523 527, 531, 533–537, 539, CCBs. See Calcium channel blockers 553–556, 567–603 (CCBs) AAA trial, 554 CD36, 46 antiplatelet prophylaxis, 273 CD39, 75, 100 aspirininsensitive agonists, 273 CD40L, 97 aspirin resistance, 397, 411, 413, 414, CD39/NTPDaseI 417, 426 ecto-nucleotidase, 381 CLIPS, 554 hydrolyzes ATP and ADP, 381 COX1, 553 CEACAM1. See Carcinoembryonic antigen- FDA, 556 related cell adhesion molecule 1 meta-analysis, 556 (CEACAM1) Physicians’ Health Study, 553 , 146 POPADAD, 554 CHD. See Coronary heart disease (CHD) resistance, 144–148, 535–536 Chemokines, 455 (Tx) A2, 553 ADP co-stimulation, 455 Aspirin/dipyridamole, 529 MDC, 455 Atherogenesis, 119, 121–126 SDF-1, 455 Atherosclerotic plaques, 263 TARC, 455 Atopaxar, 252–256 Cilostazol, 227, 230–234, 537–538 ATP. See Adenosine triphosphate (ATP) CLEC-2, 32 Atrial fibrillation, 525 Clopidogrel, 168, 170, 171, 456, 476–487, Atrial septal aneurysm, 536 497–500, 502–505, 507–509, 511–514, 523–525, 528, 530, 531, 534, 535, 567, 586–590 B resistance, 421, 422 Bernard–Soulier Syndrome (BSS), 29, 292 Coagulation, 101 Biomarkers, 257, 439 extrinsic pathway of coagulation, 101 Blood–brain barrier, 521 fibrin, 89 Blood pressure control, 156 intrinsic pathway of coagulation, 101 BSS. See Bernard–Soulier Syndrome (BSS) Coagulation factor XII, 28 Btk, 345 Collagen, 26, 91, 345 Buffered aspirin, 155 a2b1, 91 GPVI, 91 Collagen receptors, 29–33, 313 C glycoprotein VI (GPVI), 30 Calcium channel blockers (CCBs), 174 GPVI deficiency, 30 CalDAG-GEFI, 351 GPVI/FcRg, 32 Calin, 326 I-domain, 31 Cancer, 572, 573, 577, 578, 581, 583, Compliance, 145, 147, 475 598, 600–603 Coronary heart disease (CHD), 569, 576–578, Cangrelor, 168, 184, 185 583, 586, 587, 590–593, 595, Carcinoembryonic antigen-related cell 597–599, 602 adhesion molecule 1 (CEACAM1), COX-1. See -1 (COX-1) 77, 78 COX-2. See Cyclooxygenase-2 (COX-2) Carcinogenesis, 279 Cryptogenic stroke, 536 pharmacological inhibition, 280 Crystal structure, 319 TP receptors, 280 cSrc, 351 Index 609

Cyclic adenosine 3´-5´-monophosphate Enteric-coated, 140, 155 (cAMP), 226–234 Enteric-coated preparations, 140 Cyclic guanosine 3´-5´-monophosphate EP2. See E receptor 2 (EP2) (cGMP), 226–228, 230, 233, 234 EP4. See receptor 4 (EP4) Cyclooxygenase-1 (COX-1), 97, 137–158, 473 Eph kinase receptors, 44 Cyclooxygenase-2 (COX-2), 138–141, 146, Eph kinases, 98 153, 156 Eph kinases and ephrins , 138, 139, 141, 156–158 EphA4, 74 CYP1A2, 175 EphB1, 74 CYP3A4/5, 175 Ephrin B1, 74 CYP2B6, 175 Eptifibatide, 497, 500, 504, 505, 509, 513, 514 CYP2C9, 175 in dosing, 209 CYP2C19, 175 in renal failure, 208 CYP2C19*2, 175, 176 in stent placement, 209 CYP2C19*17, 176 ERp57 CYP isoforms, 477 disulfide isomerase, 373 Cytochrome P452, 477 GPVI activation, 373 Cytokines, 120, 122, 124–125 Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), 228 ESAM. See Endothelial cell-specific adhesion D molecule (ESAM) 82D6A3, 295 ESRS. See Essen stroke risk score (ESRS) Dense tubular system, 88 Essen stroke risk score (ESRS), 532 Diabetes, 579, 590, 592–595, 597–599, 602 EXP3179, 318 Diabetes mellitus, 477 Extracranial hemorrhages, 151, 154 Diabetic patients, 273 , 146, 157 Dipyridamole, 227, 230–234, 522–523, F 529–531 Factor XI (FXI), 104 Dipyridamole associated headache, 530 Factor XII (FXII), 103 Disease models, 440 Fc receptor (FcR) g-chain, 94 Drug development, 357 FcRg chain, 314 Dual, 262 Fibrin, 34 Dual COXIB/TP antagonists, 270–272 Fibrinogen, 34 Dual TXS inhibitor/TP antagonist, 268 Fibronectin, 34 peripheral artery disease, 269 , 157 picotamide, 269 Function, 320–321 ridogrel, 268 Functional genomics ulcerative colitis, 269 animal models, 370, 380–387 DZ-697b, 318 knockout mice, 378, 381–388 zebrafish, 379, 381, 387, 388 E Future perspectives, 279–280 FV, 103 E5555, 240 FXI. See Factor XI (FXI) Elinogrel, 168, 186 FXII. See Factor XII (FXII) Endothelial cell-specific adhesion molecule Fyn, 351 (ESAM), 99 Endothelium dysfunction activation of COXs, 267 adhesion proteins, 267 G hypertrophy, 267 GAF domains, 227, 230 nitric oxide, 267 gas6. See Growth arrest-specific gene 6 (gas6) production of , 267 Gastrointestinal (GI) toxicity, 142, 154 610 Index

G6B G protein-coupled receptors (GPCRs), 344 G6b-B isoform, 372 A2 adrenergic, 72 ITAM, 372 IP, 62, 67, 77 Gene association studies PAR1/3/4, 61, 63, 65, 71–72, 80 modifiers for platelet aggregation, 380 P2Y1, 61, 63, 71, 80 SNPs, 377, 380 P2Y12, 61, 64, 66, 67, 71, 80 Gene therapy, 441–442 TP, 61, 62 Genome-wide association study G-proteins, 242 platelet count and volume, 379, 380 G12/13, 68, 73 GI toxicity. See Gastrointestinal (GI) toxicity Gi (Gi1,Gi2,Gi3,Gz), 63 Glanzmann thrombasthenia (GT) syndrome, Gq, 61, 63–68, 71–73 36, 202 Gs, 63, 66, 77 Glycocalyx, 99 GPV, 324 Glycoprotein Iba (GPIba), 61, 69, 90, 93, GPVI. See Glycoprotein VI (GPVI) 343, 345 GPVI–collagen interactions, 313 Glycoprotein Ib (GPIb) receptor antagonists, GPVI-depleted mice, 316 301–304 a-Granules, 88 Glycoprotein IIb, 525 d-Granules, 88 Glycoprotein IIb/IIIa (GP IIb/IIIa), 201–208, GRAVITAS, 484 459, 460 Growth arrest-specific gene 6 (gas6), 44, 98 binding sites, 203 protein S, 381 biosynthesis, 202 receptor, 381–383 fibrinogen binding, 203 Tyro3, Axl, or Mer, 381–383 binding, 201, 203 Gsalpha/RGS2 platelet aggregation, 201 adenylyl cyclase, 376 structure, 201 cAMP, 374, 376 Glycoprotein VI (GPVI), 61, 69, 70, 75, 76, 78, G protein-coupled receptor, 376 79, 90, 94, 313, 341 platelet inhibition-aggregation test, 376 GP61, 323 GT. See Glanzmann thrombasthenia (GT) GPCRs. See G protein-coupled receptors GUSTO moderate or severe bleeding, 248 (GPCRs) GPG-292, 303–304 GPIba. See Glycoprotein Iba (GPIba) H GPIb-IX-V complex, 290 h6B4-Fab, 301–303 GPIba,28 Heat-shock protein 47 (Hsp47), 324 GP IIb/IIIa. See Glycoprotein IIb/IIIa Hematopoiesis, 438 (GP IIb/IIIa) Hematopoietic progenitor kinase 1-interacting GP IIb/IIIa inhibitors, 201–208, 497, 499–501, protein of 55 (HIP-55) 504–505, 509–514, 525, 531 actin-binding adaptor, 373 available antagonists, 204–205 thrombin, 373 bleeding association, 213 Heparin, 525 bleeding end points, selected major clinical Heritability, 404, 405, 408, 410, 411, 416, trials, 213 417, 419 bleeding risk, 212 12-HETE, 451 comparison to bivalirudin, 215 20-diHETE, 451 future indications, 217 Higher doses, , 271 risk factors, 213 High platelet reactivity (HPR), 172, 177 use in European Society of Cardiology Himbacine derivative, 243 Guidelines, 215 HIP-55. See Hematopoietic progenitor kinase use with percutaneous coronary 1-interacting protein of 55 (HIP-55) intervention, 214 HPR. See High platelet reactivity (HPR) GPIs, 459, 460 Hydroxyeicosatetraenoic acid GPIV or CD36, 323 (12-HETE), 450 Index 611

I Inter-individual variability, 145, 148, 158, 487 , 146, 157 Intermittent claudication, 229, 231, 232 aIIbb3 Intracranial dissections, 537 fibrin, 104 Intracranial hemorrhage, 154–156, 247 IIb/IIIa inhibitors, 525 Intracranial stenosis, 533 Immune response, 453 Ischemic stroke, 275 antigen presenting cells, 453 PERFORM, 275 CD40-CD40L, 453 TP receptor inhibition, 275 immunoglobulins, 453 Ischemic stroke or tRansient ischemic toll-like receptor, 453 Attack, 275 Immunoreceptor tyrosine-based activation Isoprostanes, 272 motif (ITAM), 30, 49, 341 ITAM. See Immunoreceptor tyrosine-based Immunoreceptor tyrosine-based inhibition activation motif (ITAM) motif (ITIM), 356 ITIM. See Immunoreceptor tyrosine-based Impedance aggregometry, 474 inhibition motif (ITIM) Indobufen, 157, 534 Inflammation, 118–125 Inflammatory disorders, 448 J allergic rhinitis, 448 JAQ1, 317 asthma, 448 J-LANCELOT ACS, 253 atherosclerosis, 448 J-LANCELOT CAD, 253 chronic obstructive pulmonary disease (COPD), 448 eczema, 448 K immune responses (pathogens), 448 Kinases, 345 inflammatory bowel disease (IBD), 448 rheumatoid arthritis (RA), 448 Inflammatory mediators, 450 L Inflammatory processes, 448 Laboratory monitoring, 471–489 adaptive immune response, 449 Laboratory tests, 473–474 chronic inflammation and tissue LAIR-1. See Leukocyte Associated Ig-ike remodelling, 449 Receptor-1 (LAIR-1) innate immune response, 449 Laminin, 34, 315 leukocyte recruitment, 449 LANCELOT, 253 platelet chemotaxis and migration, 449 LAPP. See Leech antiplatelet protein (LAPP) Inherited platelet disorders Leech antiplatelet protein (LAPP), 327 Bernard–Soulier syndrome, 374 Leptin bleeding disorder, 374 cardiovascular, 383 defects in GPVI, TXA2R, and P2Y12, 374 leptin receptor deficient db/db mice, 383 Glanzmann thrombastenia, 374 obese, 383 Inhibitors of a2b1, 321–322 Lesions, 266 Inhibitors of GPVI, 316–317 Leukocyte Associated Ig-ike Receptor-1 Inhibitors of TXS, 267 (LAIR-1), 326 , 268 Leukocyte recruitment, 449 , 268 adhesion molecules, 449 Innate immune cells, 117, 125 endothelium, endothelial cells, 449 Inside-out (I-O), 341 eosinophils, 449 Integrin a2b1, 318 integrins, 450 Integrins, 33–37 lymphocytes, 449 a2b1, 90, 94, 95 monocytes, 449 a5b1, 91 neutrophils, 449 a6b1, 91 platelet-leukocyte complexes, 449 aIIbb3, 90 P-selectin, 450 612 Index

Leukocyte recruitment (cont.) PKCbeta, 385 PSGL-1, 450 PKCdelta, 385 , 451 PKCtheta, 385 Light transmission aggregometry (LTA), Rac1, 385, 386 174, 473 Rap1b, 385, 386 Linker for activation of T cells (LAT), 351–352 Mouse models, platelet receptor function LNAs. See Locked nucleic acids (LNAs) defects Locked nucleic acids (LNAs), 439 a2A-AR, 384 Lotrafiban, 531 activation, 383, 384 Lowest effective dose, 142–144, 158 CalDAG-GEFI, 384 LTA. See Light transmission aggregometry CD150, 384 (LTA) CIB1, 384 Lyn, 352 Kindlin-3/FERMT3, 384 TSSC6, 384 Mouse models, secretion defects M Chediak–Higashi syndrome, 386 MACE. See Major adverse cardiovascular endobrevin or VAMP8, 386 events (MACE) Hermansky–Pudlack syndrome, 386 Major adverse cardiovascular events ILK, 386 (MACE), 253 RanBP10, 386 Matrix metalloproteinase-9 (MMP-9), 233 MPV. See Mean platelet volume (MPV) MDR 1. See Multidrug resistance protein 1 Multidrug resistance protein 1 (MDR 1), 176 (MDR 1) Multiple electrode aggregometry (MEA), 174 MEA. See Multiple electrode aggregometry Myocardial infarction (MI), 240, 568, (MEA) 571–576, 579, 581, 582, 584–588, Mean platelet volume (MPV), 397–406, 409, 590–592, 595, 603 425, 426 Megakaryocyte COX-1 and COX-2, 141 Megakaryocytes, 4 N endomitosis, 6 Nanobodies, 296 extracellular matrices, 9 , 146, 156, 157 osteoblastic niche, 9 NF-kB. See Nuclear factor kappa-light-chain- vascular niche, 10 enhancer of activated B cells migrate, 6 (NF-kB) multivesicular bodies (MVBs), 8 Nitric oxide (NO), 64, 100, 226, 230 thrombopoietin, 5 Nonprostaglandin effects, 144 Megakaryocytopoiesis, 438 Nonresponsiveness, 145 Metabolism, 175 Non-thienopyridines, 168 MI. See Myocardial infarction (MI) Nonvalvular atrial fibrillation, 152 Mice, 316 NO synthase, 100 MicroRNA (miRNA) biogenesis, 436 NSTE-ACS, 246–248, 253, 258 Migration, 451, 452 Nuclear factor kappa-light-chain-enhancer chemokines, 452 of activated B cells (NF-kB), 233, chemotaxis, 452 458, 459 Milrinone, 227, 229, 232 miRNA biogenesis. See MicroRNA (miRNA) biogenesis O Monocyte chemotactic protein-1 (MCP-1), 233 Omeprazole, 479 Mouse models, intracellular signaling On-treatment platelet reactivity, 148 AKT1, 385 Oral bioavailability, 140 JNK1, 385 Oral GP IIb/IIIa inhibitors, 211 PI3K, 385 clinical failure, 211 PKC, 385 meta-analysis, 211 PKCalpha deficient mice, 385 Outside-in (O-I), 341 Index 613

P phosphodiesterase 2, 227–230 PACAP. See Pituitary adenylate cyclase- phosphodiesterase 3, 227–232, 234 activating polypeptide (PACAP) phosphodiesterase 5, 227, 230, 233, 234 PAD. See Peripheral artery disease (PAD) Picotamide, 557 PAR-1. See Protease-activated receptor 1 ADEP trial, 557 (PAR-1) DAVID trial, 557 PAR-4. See Protease-activated receptor 4 receptors, 557 (PAR-4) TxA2 synthase, 557 Paraoxonase-1, 176 PI-3K, 362 PAR-1 inhibitors, 241–242 PI-3Ka, 352 Patent foramen ovale (PFO), 536 PI-3Kb, 352–353 PDEs. See Phosphodiesterases (PDEs) PI-3Kd, 353 PEAR1. See Platelet endothelial aggregation PI-3Kg, 353 receptor-1 (PEAR1) Pituitary adenylate cyclase-activating PECAM-1. See Platelet endothelial cell polypeptide (PACAP), 50 adhesion molecule-1 (PECAM-1) bleeding tendency, 375 Peptic ulcer, 155 cAMP, 374–376 Peptidomimetics, 243 thrombocytopenia, 375 PERFORM design, 278–279 VPAC1, 374–376 dose, 278 PKC. See Protein kinase C (PKC) follow-up, 278 PKCa, 353 risk-factor control, 279 PKCb, 353 superiority goal, 278 PKCd, 354 PERFORM trial, 276 PKCy, 353 antiproliferative properties, 277 Placebo-controlled aspirin trials, 142, 150 antivasoconstrictive effect, 277 Placebo-controlled randomized trials, 142, 157 platelet function, 276 Plaque rupture, 112–119, 122, 124 stages of disease, 277 Platelet, 10, 288, 438 Peripheral artery disease (PAD), 548 actin, 15 aging, 548 delivery vehicles, 440–441 asymptomatic, 548 dense-granules, 18 claudication, 548 DTS, 14 critical limb ischemia, 548 a-granules, 17 myocardial infarction, 548 lysosomes, 19 prevalence, 548 membrane, 12 stroke, 548 microparticles, 440 vascular death, 548 microtubule, 16 Peripheral vascular disease, 231 mitochondria, 18 Peroxisome proliferator activated receptor OCS, 13 (PPAR), 458 peroxisomes, 19 PFA-100, 474 reactivity, 438, 439 PFO. See Patent foramen ovale (PFO) release, 10 PGE2. See (PGE2) spectrin, 15 PGH2/TXA2, 273 stored, 442 PGI2. See (PGI2) Platelet activation PGSL-1, 457, 458 by ADP, 71 Pharmacodynamic (PD) interaction, 146 by collagen, 60, 61, 69–70, 76 Phosphatidylserine, 102 by epinephrine, 72 Phosphodiesterases (PDEs), 226, 230–234, 460 outside-in signaling, 73, 74 cilostazol, 461 by thrombin, 71–73 PDE2, 461 by TxA2, 72–73 PDE3, 461 Platelet agonists PDE5, 461 ADP, 70–73 614 Index

Platelet agonists (cont.) Prostaglandin E receptor 4 (EP4), 40 collagen, 69–70 Prostaglandin H-synthase (PGHS)-1 epinephrin, 72 and-2, 138 thrombin, 71–72 receptor IP, 99 TxA2, 72–73 Protease-activated receptor 1 (PAR-1), 29, Platelet and endothelial cell adhesion 97, 240 molecule, 98 Protease-activated receptor 4 (PAR-4), 97, 242 Platelet count, 397–406, 424 Protein kinase A (PKA), 229 Platelet COX-1 activity, 141, 142, 144, Protein kinase C (PKC), 267, 359 146–148, 157 Protein tyrosine phosphatase, 32 Platelet endothelial aggregation receptor-1 Proteomics (PEAR1), 47 two-dimensional difference gel Platelet endothelial cell adhesion molecule-1 electrophoresis, 371 (PECAM-1), 49, 77, 78 Proton pump inhibitors, 173 Platelet function, 449 P-selectin, 29, 48, 95, 455–458 dichotomy, 449 bimosiamose, 457 pro-inflammatory, 449 quinoline salicylic acids, 457 pro-thrombotic, 449 RB40.34, 457 Platelet inhibition and patient outcomes P-selectin glycoprotein ligand-1(PSGL-1), 48 (PLATO), 503, 504, 508 PSGL-1. See P-selectin glycoprotein ligand-1 , 111–126, 552 (PSGL-1) mean platelet volume, 553 Pulmonary embolism, 152 P selectin, 553 Purinergic receptors, 454

soluble CD40 ligand, 553 P2X1, 454, 455 urinary excretion of 11-deydro-TxB2, 552 P2Y1, 454–456 Platelet turnover, 476 P2Y12, 454–456 Platelet type III collagen binding protein P2X1,37 (TIIICBP), 325 P2Y1, 37, 96 ® Platelet VASP , 476 P2Y12, 37, 96, 166, 473 Plateletworks, 474 P2Y1-specific antagonists, 455 PLATO. See Platelet inhibition and patient P2Y1, 455, 456 outcomes (PLATO) P2Y12-specific antagonists, 455 PLCb, 354 PLCg2, 354 p38-MAPK, 352, 362 Q Polyphosphates, 103 QTc prolongation, 255–256 Poor responders, 483 PPAR. See Peroxisome proliferator activated receptor (PPAR) R Prasugrel, 168, 180, 181, 497, 502–504, Rap1b, 355 507–511, 513, 514 Reactive oxidant species (ROS), 263 Preeclampsia, 153 Receptors, 263 Primary prevention, 151, 154, 156, 158, Recombinant tissue plasminogen activator, 521 565–603 Renal function, 156 Prodrugs, 167 Repair processes, 452 Proplatelet, 7, 11 growth factors, 452 actin, 7 matrix metalloproteinases, 452 microtubules, 7 tissue remodelling, 452 Prostacyclin (PGI2), 62, 99, 267, 268, RGS proteins 273, 274, 277 RGS10, 76, 77 Prostacyclin receptor, 41–42 RGS18, 76, 77 Prostaglandin E2 (PGE2), 40 Risk factors, 552 Prostaglandin E receptor 2 (EP2), 40 age, 552 Index 615

cigarette smoking, 552 ticlopidine, 558 diabetes mellitus, 552 Thrombin, 240, 345, 352 Rivaroxaban, 539 Thrombin receptor, 39–40 , 146 PAR-1, 43 PAR-4, 43 S Thromboelastography, 474 SAPAT. See Swedish angina pectoris aspirin Thrombosis, 111–125 trial (SAPAT) Thrombotic risk, 316 Sarpogrelate, 538–539 Thrombotic thrombocytopenic purpura SCH530348, 240 (TTP), 291 Secondary prevention, 151 Thromboxane (TX), 138, 139, 262 Secondary stroke prevention, 521–527 Thromboxane A2 (TXA2), 37, 95–97, 138–142, Second messengers, 226 144, 145, 148, 150, 156, 158, 269, Sema4D, 75 274, 345, 473 Semaphorin 4D, 98 Thromboxane metabolite, 141, 157 Serine protease inhibitors (SERPINS), 103 (TP), 263, 266 SERPINS. See Serine protease inhibitors aspirin-insensitive TP agonists, 264 (SERPINS) posttranscriptional modifications, 264 Serum TXB2, 141, 145, 147, 148, 157 signaling, 263 Sildenafil, 227, 230 upregulation, 263 SLP76, 355 TIAs. See Transient ischaemic attacks (TIAs) Snake venoms, 316 Ticagrelor, 168, 182, 497, 502–504, 508, 511, Soluble dimeric GPVI-Fc, 318 513, 514 Statins, 174 Ticlopidine, 168, 169, 531 Stroke, 230, 231, 233, 234, 240, 288, 568, 572, TIMI major or minor bleeding, 245 573, 575–578, 580–582, 584–588, Tirofiban, 209–210, 497, 501, 504, 509, 513, 514 590–592, 594–599, 603 in ST-segment elevation myocardial Subendothelial extracellular matrix, 29 infarction, 210 Sulfinpyrazone, 157 Tissue damage, 452 Surface-connected open canalicular system, 88 cationic proteins (PCPs), 452 Surgical blood loss, 242 free radicals, 452 Swedish angina pectoris aspirin trial platelet basic proteins (PBPs), 452 (SAPAT), 498 reactive oxygen species (ROS), 452 Syk, 355–356, 358–359 TLT-1. See TREM-like transcript-1 (TLT-1) TMEM16F. See Transmembrane protein 16F (TMEM16F) T TP. See Thromboxane receptor (TP) Tadalafil, 227, 230 TP antagonists, 271, 274 Tailored antiplatelet treatment, 486 endothelial dysfunction, 275 Tailoring antiplatelet therapy, 148 inflammation, 275 Targeted Platelet Inhibition to Clarify the pharmacokinetics and Optimal Strategy to Medically pharmacodynamics, 271 Manage Acute Coronary Syndromes platelet aggregation, 271 (TRILOGY ACS), 504, 510 TAIPAD study, 272 Template bleeding time, 242 terutroban, 271 Terutroban, 538 TRA•CER, 247 Tetraspanins, 45 Traditional nonsteroidal antiinflammatory Therapeutic window, 481 drugs (NSAIDs), 146, 156, 157 Thienopyridines, 167–169, 558 Transient ischaemic attacks (TIAs), 571–573, ADP receptors, 558 581, 584, 585, 587, 588, CAPRIE, 558 594–596, 599 CHARISMA, 559 Transmembrane protein 16F (TMEM16F), 102 clopidogrel, 558 TRA-PCI, 245 616 Index

Treatment failure, 145 Vav1/3, 356 TREM-like transcript-1 (TLT-1), 47 VerifyNow-aspirin, 474 Triflusal, 157, 530 Vitronectin, 34 TRITON-TIMI 38, 241 von Willebrand disease (vWD), 292 TTP. See Thrombotic thrombocytopenic von Willebrand factor (vWF), 28, 60–62, 69, purpura (TTP) 70, 74, 90, 93, 288, 343 TX. See Thromboxane (TX) A1-domain, 93 TXA2. See Thromboxane A2 (TXA2) Vorapaxar, 244–245, 539 TXA2/prostaglandin H2 receptor, 37 VPAC1. See Vasoactive intestinal peptide/ TX generation, 272 pituitary adenylate cyclase- monocytes, 272 activating peptide receptor 1 platelet COX-2, 272 (VPAC1) Tyrosine kinase receptors, 44 vWD. See von Willebrand disease (vWD) vWF. See von Willebrand factor (vWF) VWF–GPIb interaction, 288, 293, 304 U Ulcer bleeding, 155 Unstable angina, 142, 143, 150, 154, 157 W Upper GI complications, 155 Walking distances, 232 Urinary 11-dehydro-TXB2, 147 Warfarin, 534, 535, 539

V Vardenafil, 227, 230 Z Variability, 395–426 Zebrafish models Vascular disorders, 142–144 BAMBI, 387 Vascular prostacyclin (PGI2), 139, 157 DCBLD2, 387 Vasoactive intestinal peptide/pituitary ESAM, 387 adenylate cyclase-activating peptide LRRC32, 387 receptor 1 (VPAC1), 50 MLCK, 387