Platelets in Hematologic and Cardiovascular Disorders: a Clinical Handbook Edited by Paolo Gresele, Valentin Fuster, Jose A

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Cambridge University Press 978-0-521-88115-9 - Platelets in Hematologic and Cardiovascular Disorders: A Clinical Handbook Edited by Paolo Gresele, Valentin Fuster, Jose A. Lopez, Clive P. Page and Jos Vermylen Index More information

INDEX

1,4,5-IP3, 41, 171 α-Storage Pool Deficiency, 61, 209 1,4,5-triphospahte (IP3), 93, 246 A156 V mutation, 55, 202 6B4, 351 abciximab, 2, 81, 87, 125, 229, 243, 345, 392, 419 14–3-3ξ, 23, 152 for arterial thrombosis treatment and prevention, 112, 266 17β-estradiol (17β-E2, 100nM), 61, 209 bleeding complications, 379 for patients with STEMI, 428 α-actinin, 4, 129 vs. placebo, 428 α granules, 1, 93, 125, 247 pharmacokinetics, 419 contents release by, 15, 149 recanalization with, 447 defects recommended for PCI treatment, 422 α-Storage Pool Deficiency, 61–62, 209 to reduce reocclusion after angioplasty, 466 Jacobsen Syndrome (JS), 63, 211 and surgery, 86, 237 Medich platelet disorder, 63, 211 thrombocytopenia from, 380 Paris Trousseau Syndrome (PTS), 63, 211 Abciximab Before Direct Angioplasty and Stenting in MI Quebec platelet disorder (QPD), 62, 210 Regarding Acute and Long-Term Follow-Up (ADMIRAL) White Platelet Syndrome (WPS), 63, 211 trial, 428 and inflammation, 326 Abciximab Emergent Stroke Treatment Trial (AbESTT), 447 sCD40L and, 56, 204 Abciximab Emergent Stroke Treatment Trial-II (AbESTT-II), α,δ-storage pool deficiency, 63, 211 447

α2 integrin (GPIa), 29, 163 abdominal vein thrombosis (AVT), 47, 190

α2A-adrenergic receptor, 66, 214 ABO blood group α2-adrenergic receptors, 58, 206 compatibility, 93, 247

α2β1 integrin, 28–29, 163 for infant and platelet donor, 93, 246 platelet receptors for, 341 ACCP Consensus Conference on Antithrombotic Therapy, 465 polymorphisms, 29, 163 ACCP Consensus Conference, recommendation on aspirin

GPIa (α2 integrin), 29, 163 use, 464 signaling, 29, 162 acenocoumarol structure, 28, 162 and uncontrolled bleeding, 23, 152 α-granule proteins, 85, 235 acetylsalicylic acid (ASA). See aspirin

αIIb β3 blockers acid phosphatases and bleeding, 81, 230 in lysomes, 3, 125–127 and iatrogenic platelet disorders, 81, 229 acidosis, in trauma patients, and platelet dysfunction, 98, 252 laboratory monitoring, 81, 230 acquired coagulation factor deﬁciency, 23, 151

αIIbβ3, 85, 234 acquired von Willebrand syndrome (AVWS), 53, 191 αIIbβ3 antagonists actin, 9, 137 monitoring, 392 assembly, 15, 149 variation in response to, 392 actin binding protein, 24, 152 αIIbβ3 integrin, 9, 161 actin cytoskeleton, 4, 128

afﬁnity regulation, 26, 157 and GqG13, 43, 172 clinical relevance and future directions, 27, 161 actin ﬁlaments epitopes location for conformation-dependent mAbs, 26, 159 distribution, 11, 139 ligand-binding site location, 26, 158 actin toxins, 11, 139 polymorphisms, 11, 161 activated partial thromboplastin time (APTT), structure, 25–26, 157 21, 150

483

© Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-88115-9 - Platelets in Hematologic and Cardiovascular Disorders: A Clinical Handbook Edited by Paolo Gresele, Valentin Fuster, Jose A. Lopez, Clive P. Page and Jos Vermylen Index More information

Index

activated platelets adiponectin, 61, 208 and arterial thrombosis, 109, 262 adipose tissue αIIbβ3 in, 26, 157 and leptin, 60, 208 complex formation with monocytes, 81, 231 ADP. See adenosine 5-diphosphate (ADP)

ex vivo flow cytometry for assessing, 8, 135 ADP-receptor (P2Y12) antagonists, 115, 269 flow cytometry detection, 8, 135 afibrinogenemia, 68, 215 inflammatory molecules produced by, 107, 270 aggregometer structure, 13–15, 150 for quantifying platelet function in whole blood sample, 7, 132 granule secretion, 15, 149 AGI-1067, 302 shape change, 14, 147 aging, and atherosclerosis, 293 active bleeding, therapeutic platelet transfusions, 99, 251–254 air travel-related, venous thromboembolism (VTE) Acute Catheterization and Urgent Intervention Strategy preventing, 478 (ACUITY) trial, 425, 427 airway obstruction, PDHRF and, 326 acute coronary syndrome (ACS), 3, 126, 279 airway remodeling clopidogrel for patients with, 414 chronic inflammation in bronchial asthma in, 330 plaque rupture in, 68, 216 Akt acute lymphoblastic leukemia and Gas6 activities, 54, 194 abnormal platelet function in, 85, 234 Akt1, 43, 175 acute myelogenous leukemia Akt2, 43, 172–175 δ-SPD and development, 60, 208 Alberio, L., 86, 236 ADAMTS13 albinism deficiency, 175 oculocutaneous, 25, 208 inherited deficiency, 165 alcohol abuse, 21, 150 adducin, 5, 130 allergen, platelet response to, 331 adenosine, 326 allergic asthma, 330 adenosine 5-diphosphate (ADP), 40, 60, 84, 175, allergic dermatites, 333 207, 234 allergic inflammation in dense granules, 2, 93, 126, 248 platelet chemotaxis in, 328 enzymatic degradation, 92, 244 alloimmune thrombocytopenia (AIT) monitoring stimulated responses, 397 fetal and neonatal, 43, 169–172 and platelet activation, 93, 246 clinical presentation, 41, 170 and platelet aggregation, 1–5, 129, 131 diagnosis, 41, 171 and platelet function, 97, 251 intracranial haemorrhage (ICH), 41, 171 platelet receptors for, 341 long-term effects of antenatal management, 43, 175 receptor antagonists, 343–345, 429 management strategies, 43, 174 release from platelet granules, 282 overall approach to therapy, 43, 173 succinate and, 64, 212 pathogenesis, 41, 169 adenosine 5-triphosphate (ATP), 60, 207 predictors of disease, 41, 171 in dense granules, 2, 126 screening programs, 43, 172–175 increased, in cystic fibrosis, 332 alloimmune thrombocytopenia (AIT), 24, 155 measurement of secretion, 11, 140 alloimmunized platelet refractoriness, 93, 247

PGE2 and, 62, 210 management, 94, 248 and proplatelet elongation, 10, 139 prevention, 93, 247 adenosine receptors, 343 alpha-thrombin-induced serotonin adenylate cyclase, 343 LDL and, 57, 204 adhesion molecules American Association of Blood Banks, 87, 243 from activated platelets, 106, 255 American College of Cardiology/American Heart Association adhesion proteins guidelines for NSTE ACS treatment, 415 hereditary defects, 67, 215 PCI guidelines, 398 as platelet-derived mediators, 108, 255 American College of Chest Physicians, 477 platelet receptor abnormalities, 57, 204 American Heart Association (AHA) Guidelines for Primary

α2-adrenergic receptors, 58, 206 Prevention of Cardiovascular Disease and Stroke, 409 Glanzmann’s thrombasthenia (GT), 203 AMG531

GPIa/IIa (α2/β1) abnormalities, 56, 204 for refractory ITP,29, 163 GPVI abnormalities, 57, 204 amine-polystyrene particles, 63, 212

P2Y1 receptor abnormalities, 57, 204 amino acids

thromboxane A2 receptor defects, 58, 205 residues for ligand binding, 26, 158 von Willebrand disease (VWD), 56, 202 aminooxidases, 109, 265

484

Index

aminophospholipid translocase, 83, 233 resistance, 411 Amotosalen HCl dipyridamole, 346 adding to platelet transfusions, 244 experimental anagrelide, 353 collagen receptors, 351 Anand, S.S., 375 COX inhibitors, 351 Ancylostoma caninum, 374 GPIb-vWf interaction, 350 Andonegui, G., 63, 211 P-selectin, 351 Andre, P., 81, 230 serotonin, 351 anemia future research, 381, 429 in childhood, 29, 163 glycoprotein IIb/IIIa inhibitors, 261, 418–429 from erythropoietin deficiency, 83, 232 hemorrhagic complications vs. anticoagulants, 378 angiogenesis and hemostatic abnormalities, 99, 254 platelet regulation of, 251, 308 impact on limb ischemia, 462 regulators of, 2, 125 irreversible, 345 angioplasty, reocclusion after, abciximab to reduce rate, 466 monitoring, 392 angiopoietin-1, 2, 313, 315 future research, 400 angiotensin converting enzyme (ACE), 99, 251–254 laboratory, 386 angiotensin-converting enzyme inhibitors (ACEI) summary and future of, 399 interaction between aspirin and, 380 nonhemorrhagic complications, 379 ankle brachial index (ABI), 458 vs. oral anticoagulants ankle pressure index, 458 in atrial fibrillation, 376–378 antibiotics for heart failure treatment, 376 prophylactic after splenectomy in children, 30, 165 in percutaneous endovascular revascularization, 465 antibodies pharmacogenomic factors in resistance to, 353 to Human Leukocyte Antigens (HLA) Class I, 93, 247 as potential cancer growth inhibitors, 312 loss over time, 95, 248 to prevent arterial thrombosis, 471 anticoagulant factors, 108, 261 for preventing cardiovascular events, 460 anticoagulants resistance, 155 for arterial thrombosis treatment and prevention, 112, 267 in stroke prevention, 438 for atrial fibrillation with other risk factors, 451 for stroke treatment and secondary prevention in CHF management, 115, 268 aspirin, 280 haemorrhagic complications vs. antiplatelet therapies, 378 clopidogrel, 323 intracranial haemorrhage (ICH) and, 378 dipyridamole, 445 for myocardial infarction prevention, 109, 265 future research, 453 oral therapy, 373 glycoprotein IIb/IIIa receptor antagonists, 329 vs. antiplatelet therapies, 376 ticlopidine, 444 in CAD treatment, 374 warfarin, 448 overtreatment with, and haematomas, 15, 149 thienopyridines, 412–418 and platelet count, 1, 124 antiplatelet effects, 412 role in preventing stroke in atrial fibrillation, 376 See also clopidogrel; ticlopidine for systolic dysfunction, 115, 269 for thrombosis prophylaxis, 109, 265 anti-D thromboxane pathway inhibitors, 347 for ITP,159 and warfarin, 374 in children, 30, 164 Antiplatelet Trialists’ Collaboration, 460, 462, 464, 473, 479 limitations, 27, 160 antithrombin, 109, 265 antigen, binding to IgE, 328 antithrombin III (ATIII) anti-LIBS (ligand-induced binding site) antibodies, 26, 158 levels in diabetes mellitus-type II, 286 antiphospholipid antibodies (APLA), 156 antithrombotic therapy

antiphospholipid syndrome, 109, 264 αIIbβ3 integrin as target of, 27, 161 antiplatelet therapies, 407 for atrial fibrillation, 381 ADP receptor antagonists, 343–345 with direct thrombin inhibitors (DTI), 372 and arterial bypass surgery, 464–465 future research, 357 aspirin, 342, 370 for peripheral vascular surgery, 465 in atrial fibrillation, 411 tissue factor and factor VIIa as targets, 374 clinical efficacy in cardiology, 407 with pentasaccharides and factor Xa inhibitors, 370–372 dose, 409 with unfractionated heparin and Low Molecular Weight mechanism of action, 407 Heparins, 125 pharmacokinetics, 407 Antithrombotic Trialists’ Collaboration, 309, 410, 461, 471

485

Index

anuria aryl sulfatase in HUS, 45, 176 in lysomes, 3, 125–127 aortic stenosis (AS) BK ASA (acetylsalicylic acid). See aspirin AVWS and, 85, 235 ASCET (ASpirin non-responsiveness and Clopidogrel Endpoint apheresis platelets, 86, 242 Trial) trial, 396 apixaban, 373 Ashcoff, K., 12 APLA. See antiphospholipid antibodies (APLA) ASPECT (Antithrombotics in the Secondary Prevention of Events aplastic anemia in Coronary Thrombosis), 112, 267 from clopidogrel, 380 aspirin, 342 from ticlopidine, 380 and allergic asthmatics, 332 ApoE-/- mouse, 293 anticancer activity, clinical trials, 316 for investigating platelet adhesion in atherosclerotic lesion anti-inflammatory effects, 115, 268 development, 295 for arterial thrombosis treatment and prevention, 109, apoptosis, 13, 142 265, 367 apoptosis inhibitory proteins, 13, 147 for atrial fibrillation, 411, 439 aprotinin, 99, 253, 350 or warfarin vs. placebo, 450 arachidonate benefits of, 342

TxA2 from, 46, 186 and bleeding time, 3, 128 arachidonate metabolites, 59–60, 207 for carotid artery stenosis, 438 arachidonic acid (AA), 5, 79, 84, 107, 131, 228, 234, 255, 327 clinical efﬁcacy in cardiology, 407 impaired liberation from membrane phospholipids, 64, 212 primary prevention, 156 metabolism, 97, 251 secondary prevention in CAD, 409 in diabetic patients, 285 clopidogrel in combination with, 80, 229, 378, 442 and platelet aggregation, 4, 129 vs. clopidogrel, 414 in prostaglandin synthesis, 342 for PAD, 461 arachidonic acid metabolism, 62, 210 for coronary artery disease, 374 arachidonic acid-induced platelet thromboembolism, 67, 215 dipyridamole use with, 347 Arg/Gln substitution, 27, 160 dose, 409 argatroban, 350, 372 effect on thromboprophylaxis, 309 Arixtra Study in Percutaneous Coronary Intervention: a effectiveness of, 352 Randomized Evaluation (ASPIRE) Pilot Trial, 371 gastric bleeding from, 342 Arp 2/3 complex of proteins, 15, 149 guidelines for cessation prior to surgery, 86, 236 arterial bypass surgery and iatrogenic platelet disorders, 227 and antiplatelet therapies, 464–465 impact on platelets, 86, 236 arterial circulation interaction with angiotensin-converting enzyme inhibitors walking distance and impaired, 463 (ACEI), 380 arterial stents laboratory monitoring, 79, 228 combination clopidogrel/aspirin therapy after, 444 low-dose ticlopidine after, 445 for cardiovascular disease, 462 arterial thrombi, 108, 261 vs. high-dose, after angioplasty, 466 and activated platelets, 109, 262 measuring platelet responses to, 390 antiplatelet therapies, 367, 471 mechanism of action, 407 clinical presentation, 113, 261–267 monitoring, 393 consequences of, 108, 261 nonhemorrhagic complications, 379 future research, 289 NSAID drug interaction with, 353 leptin and, 66, 213 for peripheral arterial disease, 460 risk factors for, 109, 262 pharmacokinetics, 407 treatment and prevention, 113, 265–267 vs. placebo, for preventing stroke, 452 anticoagulation, 112, 267 as platelet inhibitor, 87, 243, 288, 472 aspirin, 109, 265, 367 and postoperative bleeding, 476 cilostazol, 111, 266 and priming activity, 70 dipyridamole, 111, 266 resistance, 4, 79, 129, 228, 342, 394, 411 glycoprotein IIb/IIIa inhibitors, 112, 266 identifying with PFA-100, 395 thienopyridines, 110, 265 role in thromboprophylaxis, 310 arterial wall tissue factor side effects, 378 role of, 81, 229 and stroke artherosclerosis optimal dose for secondary stroke prevention, 441 mouse model, 67, 215 prevention, 438

486

Index

risk, 408 autoerythrocyte sensitization syndrome, 148 treatment and secondary prevention, 280 autoimmune lymphoproliferative syndrome, 29, 164 with thienopyridines for peripheral endovascular autoimmune platelet dysfunction procedures, 466 and platelet function disorders, 85, 236 and thrombopoietin, 58, 207 automated analysis

thromboxane A2 (TxA2) measurement for monitoring platelet size and appearance, 24, 156 therapy, 391 Axl receptor ticlopidine with, 413 for Gas6, 53, 194 variation in response to, 392 azathioprine and warfarin, 374 for ITP,28, 162 for noncardioembolic stroke, 448 AZD 6140, 302, 344, 398, 429 for PAD, 461 ximelagatran and, 373 β-thromboglobulin (βTG), 2, 126

aspirin effect, 69, 226 β1 integrin aspirin therapy cytoplasmic domain of, 28, 162 in low-risk ET, 54, 194 gene encoding, 28, 162 assassin bug, 351 β-galactosidase Assessment of best Loading Dose of clopidogrel to Blunt platelet in lysomes, 3, 127 activation, Inﬂammation and Ongoing Necrosis β-glucuronidase (ALBION) study, 416 in lysomes, 3, 127 Assessment of Safety and Efﬁcacy of New Thrombolytic Regimen β-lactam antibiotics, and iatrogenic platelet disorders, 82, 231 (ASSENT)-3 trial, 428 β-thromboglobulin (βTG) asthma, 159 measurement of plasma levels, 11, 139

clinical studies, 330 PGE2 and, 62, 210 experimental animal studies, 329 β-tubulin isoform serotonin and, 325 absence of, 4, 128 atherosclerosis, 99, 251–254, 279, 293 bacterial sepsis assessment of burden and risk, 293 as splenectomy risk, 27, 161 biological markers to predict presence, 293 bacterial testing, for platelet transfusions, 87, 243 clinical manifestations, 301 Bak alloantigen, 27, 160 future research, 302 barbourin, 346 and inflammatory cells accumulation, 294 Basel Stent Kosten-Effekivitats Trial–Late Thrombotic Events hypochlorite-modified proteins in plaques, 57, 204 (BASKET-LATE) study, 417 and peripheral arterial disease (PAD), 458 basic fibroblast growth factor (bFGF), 109, 262 platelet adhesion Bcl-2, 13, 136 and lesion formation initiation, 295 Bcl-3 protein, 299

transition from loose to ﬁrm, 296 Bcl-xL, 13, 130 risk factors for, 279 Becker, R.P.,8, 134 second-hand smoke and, 22, 264 Behnke, O., 8, 12, 134, 140 atopic dermatitis, 333 beraprost, 349, 463 atorvastatin Bernard–Soulier syndrome (BSS), 2, 21, 22, 28–29, 38, 85, 108, clopidogrel interaction with, 353, 417 126, 150, 163, 166, 236, 255 ATP. See also adenosine 5-triphosphate (ATP) molecular defects, 55, 202 atrial ﬁbrillation, 114, 267 possibility for platelet study, 7, 132 antiplatelet therapies vs. oral anticoagulants, 376–378 Bessis, M., 8, 134 antithrombotic therapy for, 115, 269 betahexosaminidase aspirin for, 411, 439 in lysomes, 3, 127 and cerebral ischemic events, 288 BgII restriction fragment length polymorphism (BglII), 29, 163 clopidogrel in, 418 Bigalke, B., 302 and other risk factors bilirubin anticoagulants for, 451 impact on platelet transfusion outcome, 95, 250 pathogenesis of thromboembolic events in, 376 Billroth, T., 311 treatment with warfarin or aspirin vs. placebo, 450 bioprosthetic valves Atrial Fibrillation Clopidogrel Trial with Irbesartan for stroke risk and, 451 Prevention of Vascular Events (ACTIVE-W) trial, 418 thromboembolism from, 114, 267 Aurora-B/AIM-1, 7, 133 biotynilated idraparinux (SSR126517), 371 autoantibodies, interference with platelet surface function, bivalirudin, 350, 372, 427 85, 236 with GP IIb/IIIa inhibitor, 425

487

Index

bleeding and fetoneonatal alloimmune thrombocytopenia (FNAIT), anticoagulants vs. antiplatelet therapies, 378 29, 163 aspirin and, 408 Bresalier, R., 452 clopidogrel with aspirin and, 378 bronchial asthma essential thrombocythemia (ET) and, 53, 191 chronic inflammation and airway remodelling, 330 gastrointestinal, aspirin and, 378 BT. See bleeding time (BT) GP IIb/IIIa inhibitors dose and, 426 buffy coat method of platelet preparation, 86, 242 with oral anticoagulation, 465 PFA-100 for evaluating interoperative risk, 7, 133 CAD. See coronary artery disease (CAD) postoperative, aspirin and, 476 cafe-au-lait´ spots therapeutic platelet transfusions, 99, 251–254 in Fanconi’s anemia, 107, 255 warfarin and, 377 calcium bleeding disorder deficient homeostasis, 285 impaired epinephrine-induced aggregation and, 45, 186 in dense granules, 2, 126 inspection for subcutaneous, 13, 147 rise in intracellular, 14, 148 prolonged in EP3 knockout mice, 67, 214 calcium-calmodulin, 15, 149 bleeding patient calmodulin, 24, 152 differential diagnosis, 21, 150 cAMP focused medical history and general physical exam, 15, 149 agents acting on, 348 initial urgent measures, 13, 147 cAMP synthesis bleeding time, 3, 127 epinephrine to inhibit, 45, 186 cardio-pulmonary bypass procedure and, 98, 252 suppression of, 41, 169 and hematocrit, 99, 253 cancer PFA-100 versus, 7, 133 role of screening, 316 and platelet count, 93, 245 thrombin impact on dormancy, 317 bleeding time (BT) and thrombosis, 227 limitations for screening, 69, 226 historical perspective, 311 as platelet function test, 386 laboratory findings in hypercoagulation, 311 blood platelet role in metastasis, 312 platelet biogenesis in, 12, 140 thrombin role, 313 shed vs. venous tissue factor role, 313 platelet number and MMP-2 content, 68, 216 tumor cell adhesion, 312 blood coagulation cascade, 54, 194 cancer cells blood coagulation factors, 23, 152 release of MMP-2 and platelet aggregation, 56, 202 blood loss cangrelor, 302, 344, 398, 429 estimating extent, 13, 147 capillary bleeding blood sampling, 1, 124 petechiae from, 14, 147 preventing artefactual in vitro platelet activation, 9, 137 CAPRIE trial, 396 blood thrombogenicity, and glycemic control, 285 carboxylate-polystypartirene particles, 63, 212 blood transfusion cardiac valves and bleeding, 23–24, 152 replacement and stroke risk, 451 blood vessel injury thromboembolism from, 450 platelet reponse to, 54, 201 cardiopulmonary bypass procedures blood-borne metastasis, 312 and platelet activation, 98, 252 BM-567, 348 cardiovascular death BM-573, 348 risk in PAD patients, 458 Boersma, E., 425 cardiovascular disease, 99, 251–254 Bolzano variant, 55, 202 antiplatelet therapies to prevent, 460 Bombeli, T., 295 and cigarette smoking, 109, 264 bone marrow endothelial dysfunction and, 98, 252 platelet biogenesis in, 12, 140 low-dose aspirin for, 462 suppression by clopidogrel, 380 cardiovascular morbidity and mortality ticlopidine side effects on, 413 particulate impact on, 63, 212 bone marrow examination carotid artery stenosis, aspirin for, 438 for thrombocytosis evaluation, 53, 192 carotid endarterectomy, 437 Born, GVR, 4, 128 aspirin for stroke prevention after, 441 Boston Area Anticoagulation Trial for Atrial Fibrillation, 449 carotid stenting, abciximab for, 447 Br polymorphism caspases, 13, 147

488

Index

catalase, 3, 126 chronic thromoctopenia catecholamines prophylactic platelet transfusions for, 96, 250 in dense granules, 2, 126 cilostazol, 116, 270, 349, 463 cathepsin and abnormal platelet function testing, 82, 231 in lysomes, 3, 127 for arterial thrombosis treatment and prevention, cathepsin G, 299 110–111, 266 leukocyte-derived, 114, 267 as platelet inhibitor, 87, 243 CBFA2 transcription factor circulating agonists and familial thrombocytopenia-leukemia, 39, 167 and platelet activation, 282 CCI (corrected count increments), 93, 246 cirrhosis, 83, 232 CD36 receptor, 21, 29, 150, 163 claudication and antiplatelet drugs, 462 polymorphisms, 30, 164 clinical resistance, 352 CD40 ligand (CD40L), 82, 112, 231, 266, 324 Clinical Trial of Reviparin and Metabolic Modulation in Acute elevated serum levels and risk for coronary event, 298 Myocardial Infarction Treatment Evaluation (CREATE), and leukocyte functioning, 114, 267 370 release from activated platelets, 298 clonal thrombocytosis (CT), 45, 186 CD62P. See P-selectin (CD62P) vs. reactive, 53, 191 CD84, 47, 189 clopidogrel, 79, 86, 115, 228, 236, 269, 343, 413, 473 celecoxib, 452 for ACS patients, 374 cellular cross talk with endothelial cells, leukocytes, platelets, for acute coronary syndrome patients, 414 106, 255 vs. aspirin, for PAD, 461 platelet-endothelial interaction, 106, 255 with aspirin, 378, 442 cell adhesion, 110–111, 266 in atrial fibrillation, 418 signaling, thrombosis, and inflammation, 111, 266 for cerebrovascular disease, 323 platelet-leukocyte cross talk, 61, 268 guidelines for cessation prior to surgery, 86, 236 adhesion, 112, 267 inadequate response to, 353 signaling, thrombosis, and inflammation, 113, 267 interaction with atorvastatin, 417 cephalosporins, bleeding and abnormal platelet function interindividual variability in response to, 417 from, 82, 231 ischemic event prevention, 414 cerebrovascular diseases. See also stroke laboratory monitoring of efficacy and resistance, 80, aspirin for, 280 229 atherosclerosis and, 279 measuring platelet responses to, 390 ischemic, 288 metabolism of, 344 limitation of mechanical interventions, 437 in patients with ST-elevation MI (STEMI), 417 uniqueness of, 437 pharmacodynamics, 413 CHADS-2 clinical rule, 61, 268 pharmacokinetics, 413 chamber-based thrombosis platelet inhibition, 396 clinical presentation, 114, 267 as platelet inhibitor, 87, 243 risk factors for, 114, 267 and priming activity, 70, 227 treatment and prevention, 115, 269 resistance, 397, 417 CHARISMA (Clopidogrel for High Atherothrombotic Risk and risks of, 379 Ischemic Stabilization, Management, and Avoidance) side effects, 380 study, 80, 229, 396, 443 vs. ticlopidine, for stent placement, 419 Chediak–Higashi syndrome (CHS), 61, 209 variation in response to, 392 chemokine receptors, 325 Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic chemokines, 53, 192, 227 carotid Stenosis (CARESS) trial, 444 as immune function regulators, 107, 255 Clopidogrel and Aspirin in the Management of Peripheral as primer, 59–60, 208 Endovascular Revascularization (CAMPER) study, 466 Chimeric 7E3 Antiplatelet Therapy in Unstable angina Refractory Clopidogrel and Metoprolol in MI (COMMIT) trial, 418 to standard treatment (CAPTURE) trial, 422 Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)–TIMI Chimowitz, M., 449 28 trial, 417 Chinese Acute Stroke Trial (CAST), 439 Clopidogrel Aspirin Stent International Cooperative Study cholesterol ester transfer protein (CETP) inhibitor, 109, 264 (CLASSICS), 415 chronic contact dermatitis, 333 Clopidogrel for High Atherothrombotic Risk and Ischemic chronic critical limb ischaemia, 458 Stabilization, Management, and Avoidance chronic myelogenous leukemia (CML) (CHARISMA) trial, 414 abnormal platelet function in, 85, 234 Clopidogrel for the Reduction of Events During Observation chronic obstructive pulmonary disease (COPD), 332 (CREDO) trial, 416, 444

489

Index

Clopidogrel in Unstable Angina to Prevent Recurrent Events congenital platelet disorders (CURE) trial, 410, 442 α-granule defects, 61 clopidogrel resistance, 5, 129 α-storage pool deficiency, 59, 61, 207, 209 Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events Jacobsen syndrome (JS), 63, 211 (CAPRIE) study, 110, 266, 414, 442 Medich platelet disorder, 63, 211 CLOSURE trial, 453 Paris Trousseau syndrome (PTS), 63, 211 clot formation, collecting data on, 391 Quebec platelet disorder (QPD), 62, 210 clot signature analyzer, 69, 227 White platelet syndrome (WPS), 63, 211 clot time, 69, 227 α,δ-storage pool deficiency, 63, 211 clotting factors Chediak–Higashi syndrome (CHS), 209 degradation of, 23, 152 hereditary thrombocytopenia, 209 neutralization by autoantibodies, 24, 152 Hermansky–Pudlak syndrome (HPS), 208 coagulation adhesive protein hereditary defects, 67, 215 future research, 87, 244 basics, 54, 201 influence on platelets, 79, 228 classification, 54, 201 overview, 82, 232 future research, 69, 216 platelet procoagulant activity, 82–87, 244 membrane phospholipids abnormalities α-granule proteins, 85, 235 Scott syndrome, 66, 213 defects, 85, 236 Stromorken syndrome, 66, 214 effect of antagonists on, 87, 243 Montreal platelet syndrome, 67, 215 heterogeneity of platelets, 86, 236 platelet receptor abnormalities for adhesive proteins, 55, 201 microvesicles, 84, 234 Bernard–Soulier syndrome (BSS), 201 phosphatidylserine (PS) exposure, 83, 233 Glanzmann’s thrombasthenia (GT), 203

tissue factor, 86, 243 GPIa/IIa (α2/β1) abnormalities, 56, 204 platelets’ effect on, 22, 232 GPVI abnormalities, 57, 204 platelet products enhancing TF synthesis, 79, 228 von Willebrand disease (VWD), 56, 202 vascular endothelium and, 92, 244 platelet receptor abnormalities for soluble agonists, 57, 204

coagulation cascade α2-adrenergic receptors, 58, 206

activation, 283 P2Y1 receptor abnormalities, 57, 204

pathway, 374 thromboxane A2 receptor defects, 58, 205 coagulation factors prevalence and diagnostic evaluation, 68, 215 acquired deﬁciency, 23, 151 primary secretion defects, 67, 214 as platelet-derived mediators, 108, 261 signal-transduction pathways abnormalities, 64, 212 coagulation-type bleeding disorder, arachidonic acid (AA) impaired liberation from membrane 21, 150 phospholipids, 63, 212 COAT platelets, 86, 237 cyclooxygenase defects, 64, 212 coated platelets, 86, 236 GTP-binding proteins abnormalities, 65, 212 coﬁlin, 43, 173 phospholipase C activation defects, 65, 213 collagen, 86, 236, 308 thromboxane synthetase, 64, 212

α2β1 integrin as cell surface receptor for, 28, 161 treatment of inherited disorders, 68, 216 binding sites, 30, 164 congenital thrombocytopenias in infants, 100, 254 PECAM-1 braking effect on signaling, 47, 187 congenital thrombocytosis, 186 and platelet activation in vivo, 39, 167 congestive heart failure (CHF), 114, 267 platelet adhesion to, 21, 150 contact dermatitis, 333 and platelet aggregation, 5, 131 Controlled Abciximab and Device Investigation to Lower Late platelet receptors for, 341 Angioplasty Complication (CADILLAC), 428 platelet reponse to, 29, 162 COPD (chronic obstructive pulmonary disease), 332 response to, 60, 207 cordocentesis, 173 Collagen/ADP (CADP) CT, 395 coronary artery bypass surgery (CABG) Collagen/Epinephrine (CEPI) CT, 395 platelet transfusion impact, 99, 253 Combination Hemotherapy and Mortality Prevention (CHAMP) coronary artery disease (CAD) trial, 375 atherosclerosis and, 279 combined antiplatelet/anticoagulant treatment role, 374 coagulation cascade activation, 283 Comparison of Measurements of Platelet aggregation with diabetes as risk factor, 285 Aggrastat, Reopro, and Eptiﬁbatide (COMPARE) trial, endothelial dysfunction, 279 422 oral anticoagulants in treatment, 374 Cone and Plate(let) Analyzer, 8, 134 platelet activation and aggregation process, 280–283 congenital disorders platelet derived microparticles, 284 and bleeding, 13–15, 150 platelet glycoprotein polymorphisms, 284

490

Index

coronary heart disease, Framingham Heart Study Prediction vascular endothelial growth factor (VEGF), Score for, 109, 262 58, 205 coronary thrombosis cytokines and cytokine-like factors larger platelets and, 3, 127 as platelet-derived mediators, 108, 255 corrected count increments (CCI), 93, 246 cytoplasm, 7, 133 corticosteriods cytoplasmatic mediators, 327 for chronic ITP,28, 161 cytoskeleton Coumadin, 316 of resting platelet, 3, 127 Coumadin Aspirin Reinfarction Study (CARS) cytosolic free calcium, 282 trial, 375 cytosolic free concentration COX isoforms in activated platelets, 42, 171 inhibition, 115, 269 COX-1, 342 dabigatran etexilate, 373 aspirin inhibition of, 393 Dale, G.L., 86, 242 COX-2, 342 danaparoid, 475 COX-2 inhibitors and NSAIDs danazol effect on stroke risk, 452 for ITP,27, 161 COX-2 selective inhibitors, 115, 269 for refractory ITP,28, 162 COX-2 speciﬁc inhibitors, 81, 230 DAVID study, 461 C-reactive protein, 112, 266 Day, S.M., 81, 229 C-reactive protein level (CRP), 53, 192 dazoxiben, 347 and PAD, 287 DDAVP (L-deamino-8-o-arginine vasopressin), and risk of stroke, 288 83, 233 CREST study (Clopidogrel Resistance and Stent Thrombosis D-dimer assay, 107, 270 Study), 398 DeBruyn, P.P., 8, 134 critical limb ischaemia deep vein thrombosis (DVT), 116, 270, 367, 471 chronic, 458 Defreyn, G., 64, 212 prostaglandins for, 463 demarcation membrane system (DMS), 7, 133 Crohn’s disease, 333 dendritic cells CT. See clonal thrombocytosis (CT) platelet interaction with, 328 C-terminal side dense granules, 1, 2, 93, 125, 126, 246 of αIIb and β3 chains, 25, 157 absence of, 85, 236 CTX family, 47, 189 contents release by, 15, 149 CURE trial, 396, 414 sCD40L and, 56, 204 CXC chemokines dense tubular system (DTS), 3, 127 and coronary artery disease, 69, 226 depression cyclins, 7, 133 ITP and, 26, 157 cyclooxygenase serotonin and, 351 aspirin inhibition of, 342, 343 desmopressin defects, 64, 212 for inherited platelet disorders, 68, 216 cyclopentyltriazolopyrimidines, 429 dexamethasone cyclophosphamide for ITP,26, 27, 158, 160 for refractory ITP,28, 162 dextran, anticoagulant activity of, 85, 235 cyclosporine diabetes mellitus, 100, 254 impact on platelet transfusion outcome, 95, 250 and cardiovascular risk, 109, 264 for refractory ITP,29, 162 as risk factor for CAD, 285 “cysteine switch” motif (PRCGXPD), 55, 202 diacylglycerol, 41, 171 cystic ﬁbrosis, 332 dialysis, 83, 232 Cyt P450 enzymes diclofenac, and vascular events, 452 and clopidogrel conversion, 353 diesel exhaust particles cytochalasin, 11, 139 impact on platelet activation, 68, 215 Cytochrome P450 DiGeorge syndrome, 37, 166 individual variability of activity, 397 DiGeorge/velocardiofacial syndrome, 55, 202 cytokines, 53, 192 dilutional thrombocytopenia and trauma, 98, 252 as primer, 25, 208 dipyridamole, 346, 473 chemokines, 59–60, 208 for arterial thrombosis treatment and prevention, 110, 266 human studies, 69, 226 for cerebrovascular disease, 445 leptin, 60, 208 effect on thromboprophylaxis, 309 thrombopoietin (TPO), 58, 206 relationship with cilostazol, 349

491

Index

dipyrimadole dysfunctional state in vascular inflammation, 109, 265 with aspirin, 396 functions, 109, 264 direct thrombin inhibitors (DTI) platelet adhesion to, 294 antithrombotic therapy with, 372 platelets and, 315 disintegrins, 345 secretion of chemokines, 294 disseminated intravascular coagulation, 23, 83, 152, 233 endothelial differentiation gene (Edg)-1, 315 trauma and, 97, 251 endothelial NOS (eNOS), 96, 109, 250, 265 Do Tirofiban and ReoPro Give Similar Efficacy Trial (TARGET), endothelium 422 circulating cells adhesion to activated, 324 Dohle-like bodies, 37, 166 prothombotic shear-dependent factors release by, 108, 261 drug-induced thrombocytopenia, 41, 167 See also vascular endothelium from heparin, 41, 168 endothelium-derived relaxing factor (EDRF), 92, 95, drug interaction 244, 250 and pharmacodynamic resistance, 352, 353 endotoxin drugs in vitro effects on platelets, 63, 211 affecting platelet function, 13, 130 Enhanced Suppression of the Platelet IIb/IIIa Receptor with DTI. See direct thrombin inhibitors (DTI) Integrilin Therapy (ESPRIT) trial, 422 Duke bleeding time, 3, 127 enoxaparin, 370 Dutch Bypass Oral anticoagulants or aspirin study, 464 Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial DVT risk in hospitalized medical patients, 271 Infarction Treatment-Thrombolysis In Myocardial dynactin, 10, 139 Infarction study 25 (ExTRACT-TIMI 25), 370 dynein, 4, 10, 11, 128, 139 enteric coating of aspirin, 342 dysfibrinogenemia, 68, 215 enteric-coated aspirin dysmegakaryocytopoiesis, 106, 255 pharmacokinetic resistance with, 352 eph receptor tyrosine kinases, 47, 190 ecchymosis, 14, 148 ephrins, 47, 189 Echis carinatus, 346 epidermal growth factor (EGF), 109, 262, 315 echistatin, 346 platelet release of, 330 Eckert, B., 447 epinephrine, 45, 186 EDRF,13, 147. See endothelium-derived relaxing factor (EDRF) defective platelet response to, 58, 206 nitric oxide (NO) mice studies EDTA in vivo effect, 66, 213 and low platelet count, 1, 124 myeloproliferative disorders and, 84, 234 Efficacy and Safety of Subcutaneous Enoxaparin versus and platelet aggregation, 5, 131 intravenous unfractionated heparin, in Non-Q-wave as primer, 61, 209 Coronary Events (ESSENCE) trial, 370 succinate and, 64, 212 EGF. See epidermal growth factor (EGF) and variable bleeding tendency, 69, 227 Ehlers–Danlos syndrome, 21, 150 epistaxis, 14, 147 eicosanoids epithelial neutrophil activating protein-78 (ENA-78; CXCL5), as platelet-derived mediators, 109, 263 108, 255 elastin epoprostenol gelatinase A ability to hydroyize, 56, 202 and abnormal platelet function testing, 82, 231 electrospray, 13, 141 Epstein Syndrome, 108, 255 ELISA Epstein, E., 47, 187 plasma sample storage, 13, 140 eptifibatide, 81, 229, 346, 392, 419 Eltrombopag for arterial thrombosis treatment and prevention, 112, 266 for refractory ITP,29, 163 bleeding complications, 379 emergency treatment pharmacokinetics, 419 for ITP,26, 159 recommended for PCI treatment, 422 ENA-78, 60, 207 thrombocytopenia from, 380 end-binding protein three (EB3), 10, 138 erythrocytes endogenous protein synthesis in arterial thrombosis, 108, 261 and α granules, 1, 125 erythroid-megakaryocytic progenitor, 5, 132 endomitosis, 5, 6, 131, 132 erythromelalgia, 47, 189 endoperoxide analog U46619 erythropoietin succinate and, 64, 212 anemia from deficiency, 82, 232 endothelial cells E-selectin (CD62E), 110, 266, 296, 324 cellular cross talk with platelets and leukocytes, 106, 255 ESPRIT study, 445

492

Index

estrogens factor Xa inhibitors as primer, 61, 209 antithrombotic therapy with, 370–372 ET. See essential thrombocythemia (ET) oral direct, 373 eukaryotic cells factor Xa phospholipids in, 83, 232 unfractionated heparin (UFH) and, 367 European Atrial Fibrillation Trial (EAFT), 376, 450 factor XI, 54, 194 European Stroke Prevention Study-1 (ESPS-1), 445 platelet binding sites for, 23, 152 European Stroke Prevention Study-2 (ESPS-2), 445 factor XII Evaluation in PTCA to Improve Long-Term Outcome with deﬁciency, 22, 150 Abciximab GP IIb/IIIa Blockade (EPILOG), familial hypercholesterolemia (FH) 419 and premature coronary artery disease, 69, 216 Evaluation of 7E3 for the Prevention of Ischemic Complications familial thrombocytopenia-leukemia, 39, 167 (EPIC) trial, 419 FAMOUS trial, 317 Evaluation of Platelet Inhibition in STENTing (EPISTENT) Fanconi’s anemia, 29, 106, 163, 255 trial, 419 fatigue Evans syndrome, 39, 166 ITP and, 26, 157 exercise Fechtner Syndrome, 108, 255 MPV (mean platelet volume) and, 3, 126 Ferroni, P., 287 exosomes fetal alloimmune thrombocytopenia (AIT), 43, vs. microvesicles, 84, 234 169–172 extended stored platelets fetal blood sampling (FBS), 43, 172, 173 for transfusions, 92, 244 fetoneonatal alloimmune thrombocytopenia (FNAIT), Extension stage for hemostatic plug, 25, 37, 166, 187 99, 254 adenosine 5-diphosphate (ADP), 43, 175 Br polymorphism amd, 29, 163 epinephrine, 45, 186 Pen/Yuk and, 27, 160 G protein-mediated signaling, 41, 167 ﬁbrin clots

Gq and activation of phospholipase Cb, 41, 171 and platelet procoagulant activity, 84, 234

Gq G13 and actin cytoskeleton, 43, 169–172 and thrombin generation, 86, 236 platelet activation in vivo, 41, 171 ﬁbrin meshwork, 472

signaling through Gi family members, 43, 175 ﬁbrin monomer thrombin, 45, 176 and platelet-tumor cell adhesion, 312

thromboxane A2 (TxA2), 46, 186 ﬁbrinogen, 82, 97, 108, 231, 251, 261

extracellular matrix (ECM), platelets and composition of, αIIbβ3 integrin as receptor, 24, 156 330 anti-PlA antibodies inhibiting binding, 27, 159

extreme thrombocytosis binding to αIIbβ3, 282 platelet count, 46, 186 binding to GP IIb/IIIa, 95, 248 extrinsic tenase, 83, 232 binding, 46, 187 deficiency, 22, 151 Fabre, J.E., 67, 214 delivery to α granules, 2, 125 Facilitated Intervention with Enhanced Reperfusion Speed to increased production of, 112, 266 Stop Events (FINESSE) study, 429 inherited disorders, 68, 215 factor IIa. See thrombin and leukocyte recruitment, 300 factor IXa. 54, 201 levels in diabetes mellitus-type II, 286 factor V, 54, 85, 201, 235 MMP-2 and, 56, 203 deficiency, 22, 151 surface level of, 86, 242 Leiden mutation, 85, 235 fibrinogen receptor, 345 plasma vs., platelet, 85, 235 fibrinolysis factor V Leiden, 310 in Quebec platelet syndrome, 86, 236 factor Va, 54, 201 vascular endothelium and, 92, 244 factor VII fibrinolytic inhibitors deficiency, 21, 150 for inherited platelet disorders, 68, 216 levels in diabetes mellitus-type II, 286 fibrinolytic Factor VIIa, 80, 229 abciximab with, 428 Factor VIII fibrinopeptide A (FPA) as platelet primer, 54, 194 in diabetic patients, 286 factor VIIIa, 54, 79, 194, 228 fibrin-specific thrombolytic agents, 24, 152 factor X fibroblast growth factor (FGF) levels in diabetes mellitus-type II, 286 platelet release of, 313

493

Index

ﬁbronectin, 345 gelsolin, 14, 148 α granules release of, 93, 247 gene expression, 13, 141 surface level of, 86, 242 gene therapy, 355 Fifth Organization to Assess Strategies in Acute Ischemic Gent, M., 444, 475 Syndromes (OASIS-5) trial, 371 ghrelin, 61, 208

filamin, 4, 15, 129, 149 Gi family, 41, 169 filamin- GPIbα connection, 4, 129 signaling through members, 43, 173 filamin-1, 24, 152 Giesen, P.L.,79, 228 filopodia, 14, 15, 148, 149, 324 Girolami, B., 463 Fitzgerald, D.J., 302 Glanzmann’s thrombasthenia (GT), 24, 56, 126, 156, 203 flippase, 83, 233 global platelet function floppase, 83, 233 bleeding time, 3, 127 flow cytometric analysis of platelets, 391 rapid platelet function assay, 4, 128 flow cytometry, 8, 134 Global Use of Strategies to Open Coronary Arteries (GUSTO) advantages/limitations, 9, 138 study group, 378

for determining αIIbβ3 receptor occupancy, 392 Global Use of Strategies to Open Occluded Coronary Arteries monoclonal antibodies, 8, 135 (GUSTO) IIb trial, 372 platelet markers for detection, 13, 136 Global Utilization of Streptokinase and tPA for Occluded fluorescein isothiocyanate (FITC), 8, 134 Coronary Arteries (GUSTO) IV-ACS trial, 423 fluoxetine glucocorticoids and abnormal platelet function testing, 82, 231 for ITP,26, 158 foam cells, 300 glycated LDL, in hyperglycaemia, 286 fondaparinux, 370 glycemic control foods and platelet function in vitro, 82, 231 and blood thrombogenicity, 285 foreign substances glycoprotein (GP) Ib/IX/V complex, 21–24, 150, 156, 324 as primer, 63, 212 and adhesion, 94, 248 Forer, A., 12, 140 platelet deficiency, 54, 201 Fragmin during Instability in Coronary Artery Disease (FRISC) polymorphisms of, 24, 156 trial, 368 signaling and functions, 23–24, 155 Fragmin in unstable coronary artery disease study (FRIC) trial, 368 structure, 22–23, 152 Framingham Heart Study Prediction Score, for coronary heart glycoprotein (GP) Ibα, 282 disease, 109, 262 glycoprotein (GP) IIb/IIIa complex Framingham study, 287 and thrombus growth, 95, 248 free fatty acids glycoprotein (GP) polymorphisms, 284 insulin and release of, 285 glycoprotein Ib FXI MMP-2 and, 56, 203 activation by thrombin, 83, 232 glycoprotein IIb/IIIa antagonists, 261 as block for fibrinogen binding, 261 λ granules, 327 effort to develop orally active, 346

G13 glycoprotein IIb/IIIa inhibitors, 418–429 and actin cytoskeleton, 43, 169–172 See also abciximab; eptifibatide; tirofiban Gabbeta, J., 64, 212 for arterial thrombosis treatment and prevention, 112, 266 Galt, S.W., 55, 202 benefit in patients undergoing PCI, 422 gamma irradiation, for platelet transfusions, 92, 244 clinical studies, 419 gangrene dosing and relationship with bleeding, 426 purpura fulminans and, 15, 149 in NSTE ACS, 422–426 Gas-6. See growth-arrest specific gene 6 (Gas-6) patient subgroups with enhanced benefits, 423 Gasic, G., 312 upstream vs. periprocedural administration, 425 gastric acid production, aspirin and, 110, 265 vs. other antithrombotic agents, 426–429 gastric ulcer, healing, 316 overdosing, 426 gastrointestinal system in patients with STEMI, 428–429 bleeding, aspirin and, 79, 228, 378 pharmacodynamics, 419 side effects from clopidogrel, 380 pharmacokinetics, 419 GATA1 and secondary stroke prevention, 447 syndromes of abnormalities, 39, 167 for stroke treatment and secondary prevention, 329 gelatinase A (MMP-2) glycoprotein V (GPV), 11, 139 as platelet primer, 55, 202 glycyl-L-prolyl-L-arginyl-L-prolin (GPRP), 10, 138 and VEGF release, 58, 206 Goedel, A., 47, 187

494

Index

GOLD (AU-assessing Ultegra), 393 Gross, P.L.,80, 229 Gorelick, P., 444 growth factors GP Ia/IIa (a2/β1) as platelet-derived mediators, 108, 261 abnormalities, 56, 204 growth-arrest speciﬁc gene 6 (Gas-6), 47, 190 GP Ibα, 82, 84, 231, 234 human studies, 68, 215 GP IIb/IIIa, 108, 261 mice studies

GP IIb/IIIa (αIIb/β3) in vivo effect, 64, 212 abnormalities, 56, 203 as platelet primer, 53, 193 GPCRs, 40, 167 growth-regulating oncogene-α (Gro-α; CXCL1), 108, 255

GPIa (α2 integrin), 29, 163 Gro-α gene, 313 GPIa/IIa (α2/β1) abnormalities, 56, 204 GTP-binding proteins GPIb α, 22, 151 low molecular weight in Rho family, 43, 173 binding, and atherogenesis, 296 GTP-binding proteins abnormalities, 65, 212 GPIb α gene guanidinosuccinic acid (GSA) defects, 55, 202 accumulation of, 83, 232 GPIb β, 22, 151 guanine nucleotide exchange factor (GEF), 43, 173 amino acids, 22, 151 guanosine 5-diphosphate (GDP), 41, 165–167 GPIb/IX/V complex guanosine 5-triphosphate (GTP), 41, 165–167 time dependence of platelet surface expression, guanylyl cyclase, 82, 231 9, 138 Gurbel, P.A.,398 GPIbβ gene GUSTO-V trial, 428 defects, 55, 202 GPIIb (αIIb integrin), 27, 161 H. pylori GPIIb/IIIa receptor antagonists, 116, 269 testing for, 25, 156 GPIIb-IIIa complex and thrombocytopenia, 25–26, 157 MoAbs and, 9, 136 hematoma, 15, 149

GPIIIa (β3 integrin), 27, 159 hemophilia, 22, 150 GPIIIb, 29, 163 acquired A, 24, 152 GPIV, 29, 163, 324 and subcutaneous hematomas, 15, 149 GPIX, 22, 151 hemorrhage. See bleeding; intracranial haemorrhage amino acids, 23, 151 (ICH) GPIX gene Hemoscope TEG, 391 defects, 55, 202 Haemostasis Analysis System (HAS), 391 GPVI, 21, 22, 23, 30, 39, 150, 151, 164, 167 hairy cell leukemia, 84, 234 abnormalities, 56, 204 Haller, C.J., 8, 135 adhesion initiation by, 110, 265 Hansson, L., 438 collagen and clustering of, 39, 167 Hass, W., 444 platelet surface expression, 302 Hayden, M., 408 polymorphisms, 30, 164 HDL-cholesterol

Gq as atherosclerotic biological marker, 293 and actin cytoskeleton, 43, 169–172 Heart failure Long-term Antithrombotic Study (HELAS) study, and activation of phospholipase Cβ, 41, 171 376

Gq-linked receptor P2Y1, 343 heat shock proteins graft material and oxidative stress, 99, 254 for peripheral bypass, 464 hematocrit graft-versus-host disease (GVHD) and bleeding time, 99, 253 impact on platelet transfusion outcome, 95, 250 hemodialysis, 83, 232 preventing, 92, 244 hemolysis gram-negative bacteria intravascular (IVH), 27, 160 lipopolysaccharides (LPS) release from, 63, 211 hemolytic uremic syndrome (HUS), 37, 43, 165, 175 granules, 1, 124 hemophilias, 79, 83, 228, 232 contents release by, 15, 149 hemorrhages, intracranial (ICH) mechanism of movement, 11, 139 in AIT, 41, 171 mediators released, 325 in utero, 41, 171 secretion, 15, 149 hemorrhagic stroke, 437 granulophysin, 60, 207 hemostasis gray platelet syndrome, 3, 61, 108, 126, 209, 255 abnormalities in cancer, 311 green ﬂuorescent protein (GFP) technology, 9, 138 blood-borne TF role in, 81, 229

495

Index

hemostasis (Contd.) human immunodeficiency virus (HIV) low-dose and frequent transfusions, 97, 251 and ITP,29, 163 platelet-endothelial interaction in, 94, 248 serological evaluation for, 24, 156 hemostatic plugs, 79, 227 and thrombocytopenia, 25, 157 See also coagulation Human Leukocyte Antigens (HLA), Class I hemostatic system antibodies to, 93, 247 platelets in, 93, 245 human platelet antigen HPA 1 a hemotopoietic stem cells and FNAIT, 99, 254 megakaryocytes derived from, 5, 131 human umbilical vein endothelial cells (HUVECs) Henoch Schonlein¨ purpura, 15, 149 platelet adhesion to, 295 heparanase, 327 hydroxychloroquine, 473 heparin, 350, 1, 124 hydroxyeicosatetraenoic acid (12-HETE), 327 with GP IIb/IIIa inhibitor, 425 hydroxyurea inhibition of metastasis, 312 and leukemia, 54, 194 to reduce DVT incidence, 272 hydroxyurea, 353 heparin-induced thrombocytopenia (HIT), 41, 168 from acquired von Willebrand syndrome, 84, 234 heparinoids hypercholesterolemia, 100, 254 for arterial thrombosis treatment and prevention, 112, 267 familial (FH) and premature coronary artery disease, and DVT risk, 271 69, 216 hepatitis C hypercoagulability in cancer, 311 serological evaluation for, 24, 156 laboratory findings, 311 and thrombocytopenia, 25, 157 hyperfibrinogenemia, in cancer patients, 311 hepatocyte growth factor (HGF), 315 hyperglycaemia hepatocytes, 22–23, 151 glycated LDL in, 286 herbal medications and nuclear factor kappa B (NF-κB), 285 and platelet function in vitro, 82, 231 hyperhomocysteinemia, 109, 265 hereditary thrombocytopenia, 61, 209 hyperpigmentation, in Fanconi’s anemia, 107, 255 Hermansky–Pudlak syndrome (HPS), 60, 208 hypertension, 99, 109, 254, 262 heterogeneity of platelets, 86, 236 Hypertension Optimal Treatment (HOT) trial, 408 HGF (hepatocyte growth factor), 315 hypobaric hypoxia high molecular weight kininogen, 22, 151 and haemostasis, 478 high-density lipoprotein cholesterol (HDL) hypochlorite-modified proteins and thrombus formation, 109, 264 in atherosclerotic plaques, 57, 204 Hippocrates, 342 hypochlorous acid (HOCl-LDL) hirudin, 1, 124, 372 LDL oxidized by, 57, 204 hirulog, 372 hypodysfibrinogenemia, 68, 215 histamine hypofibrinogenemia, 68, 215 δ granule storage of, 326 hyposplenism, 46, 187 as primer, 61, 209 hypotension HIV. See Human Immunodeficiency Virus (HIV) and need for fluid replacement, 13, 147 Ho, D., 447 hypothermia in trauma patients HOCl-LDL. See hypochlorous acid (HOCl- LDL) and platelet dysfunction, 98, 252 Hoffman, R., 447 Hzf (hematopoietic zinc finger protein) homocysteinemia, as atherosclerotic biological marker, 293 zinc and, 63, 211 hormone replacement therapy (HRT) and coronary events in postmenopausal women, 69, 227 ibuprofen hormones, 53, 192 and vascular events, 452 human studies, 69, 227 ICAM-2, 324 mice studies ICH. See intracranial haemorrhage (ICH) in vivo effect, 66, 213 Ichor full blood counter, 390 as primer, 61–62, 209 idraparinux sodium, 371 epinephrine, 61, 209 IgE in platelet chemotaxis in allergic inflammation, 328 estrogens, 61, 209 IL-8 (interleukin-8), 60, 207 histamine, 61, 209 iloprost, 349 HPA-2 polymorphism, 24, 155 immune defence mechanisms, platelet role in, 334 Huang, E.M., 64, 212 immune function human fibroblast collagenase (MMP- 1) chemokines as regulators, 107, 255 as platelet primer, 55, 202 platelets role in, 341

496

Index

immune thrombocytopenic purpura (ITP), 37, 155–165 chronic disorders additional clinical features, 26, 157 future research, 334 in childhood, 37, 163–165 dermatologic diseases, 333 differential diagnosis, 29, 163 inflammatory bowel disease (IBD), 333 management at presentation, 30, 164 molecules produced by activated platelets, 107, 270 managing acute after first week, 30, 164 platelet chemotaxis in allergic, 328 managing chronic after 6–12 months, 30, 165 platelet-derived mediators, 22, 264 chronic, 28, 161 adhesion proteins, 108, 255 chronic refractory, 28, 162 chemokines, 107, 255 immunosuppression, 28, 162 coagulation factors, 108, 261 investigational approaches, 29, 162 cytokines and cytokine-like factors, 108, 255 clinical management eicosanoids and lipid mediators, 109, 262 emergent treatment, 9, 159–161 growth factors, 108, 261 initial treatment, 26, 158 proteases, 109, 264 differential diagnosis, 24, 156 platelet-endothelial interaction in, 95, 250 epidemiology and presentation, 24, 155 role of platelets, 106, 255 initial evaluation, 21–24, 156 processes, 323 pathogenesis and laboratory diagnosis, 25–26, 157 rheumatoid arthritis, 334 immunoglobulin-type receptors, 324 inflammatory cells immunology platelets as, 323–329

α2β1 integrin, 28–29, 163 mediators released, 325 polymorphisms, 29, 163 receptors involved, 324 signaling, 29, 162 structural characteristics, 323 structure, 28, 162 inherited thrombocytopenias

αIIbβ3 integrin, 9, 159–161 children with, 29, 163 afﬁnity regulation, 26, 157 myelodysplasia, 40, 167 clinical relevance and future directions, 27, 161 inherited thrombocytopenias, 41, 165–167 epitopes location for conformation-dependent mAbs, initiation stage of platelet activation, 37, 39, 165, 166 26, 159 insulin ligand-binding site location, 26, 158 and platelet reactivity, 285 polymorphisms, 11, 161 and release of free fatty acids, 285 structure, 25–26, 157 insulin-like growth factor (IGF), 315 CD36 receptor, 29, 163 platelet release of, 330 polymorphisms, 30, 164 integrin, 111, 266, 345 future research, 31, 165 and platelet adhesion, 297 glycoprotein (GP) Ib/IX/V complex and platelet-EC adhesion, 110, 265 polymorphisms of, 24, 156 signaling, 46, 187 signaling and functions, 23–24, 152 integrin receptors, 21, 150

structure, 22–23, 151 integrin αIIbβ3, 392 GPVI, 30, 164 and platelet adhesion, 297

polymorphisms, 30, 164 integrin αIIbβ3 antagonists, 81, 229 impact cone and plate(let) analyzer, 69, 227, 390 and bleeding, 81, 230 impedance (whole blood) platelet aggregometry, 6, 132 laboratory monitoring, 81, 230

impedance whole blood aggregometry (WBA), 388 integrin αvβ3, and platelet adhesion, 297 Imperiale, T.F.,475 interferon alpha, 54, 194 inducible NOS (iNOS), 96, 250 interferon-γ infants CD40L and, 114, 267 congenital thrombocytopenias, 100, 254 interleukin (IL)-1, 327 Fanconi’s anemia, 106, 255 and reactive thrombocytosis, 46, 187 response to transfusions, 93, 245 interleukin (IL)-1β Thrombocytopenia with Absent Radii (TAR syndrome), release from activated platelets, 298 106, 255 interleukin (IL)-4 Wiskott–Aldrich syndrome in, 107, 255 and reactive thrombocytosis, 46, 187 X-linked congenital thrombocytopenias, 107, 255 interleukin (IL)-6 infection and reactive thrombocytosis, 46, 187 and reactive thrombocytosis, 46, 186 interleukin-1β, 112, 266 inﬂammation CD40L and, 114, 267 anti-inﬂammatory effects of platelet inhibition, 9, 270 International Stroke Trial (IST), 439

497

Index

intracellular adhesion molecule-2 (ICAM-2), 82, 231 platelet activation under controlled shear conditions, 7, 133 Intracoronary Stenting and Antithrombotic Regimen platelet function under ﬂow, 8, 134 Rapid Early Action for Coronary Treatment (ISAR-REACT 2) VerifyNow, 6, 132 trial, 425, 427 platelet morphology tests, 125–127 intracranial haemorrhage (ICH) platelet count, 1, 125 in AIT, 41, 171 platelet size and appearance, 126 anticoagulation therapy and, 378 quantifying platelet pathophysiology, 140 prevention in ITP treatment, 30, 164 soluble platelet activation markers spontaneous fetal, 43 glycoprotein V (GPV), 139 from warfarin, 449 granular contents, 11, 139 intravascular hemolysis (IVH), 27, 160 platelet adhesion assay, 9–11, 140 intravenous immunoglobulin (IVIG) sP-selectin, 11, 139 for ITP,27, 160 study techniques, 13, 141 intrinsic tenase, 83, 232 urinary markers

ions, 53, 191 TxA2 metabolites, 12, 140

zinc as primer, 62, 211 TxB234.110, 12, 140 ISAR-Abciximab a Superior Way to Eliminate Elevated Lages, B., 60, 208 Thrombotic Risk in Diabetics (SWEET) trial, 426 lamellipodia, 14, 148, 324 isbogrel, 347 laminin

ischemic cerebrovascular diseases, 288 α2β1 integrin as cell surface receptor for, 28, 161 ischemic events and tumor cell adhesion, 313 clopidogrel for preventing, 414 latrunculin, 11, 139 ischemic stroke, 367 LDL-cholesterol, as atherosclerotic biological marker, 293 isoprostanes, 97, 251 Lee, D., 447 ITGA2B promoter, 357 leg arteries, disease in, 458 Ivy bleeding time, 127 lepirudin, 372 leptin Jacobsen Syndrome (JS), 63, 108, 211, 255 mice studies and in vivo effect, 66, 213 JAK2V617F molecular marker, 37–48, 190 as primer, 60, 208 essential vs. reactive thrombocytosis, 53, 192 Leu57Phe mutation, 55, 202 and ET, 53, 194 leucine-rich glycoproteins, 324 junctional adhesion molecule-(JAM)-1, 324 leukemia junctional adhesion molecule–C (JAM-C or JAM-3), acute myelogenous 82, 231 d-SPD and development, 60, 208 and platelet function disorders, 84, 234 Kawasaki disease transient megakaryocytic, 41, 169 and reactive thrombocytosis, 46, 186 leukemia inhibitory factor (LIF), 13, 141 Kearney, P.,452 leukemic transformation kidney disease, platelet function disorders and, 82, 232 risk in thrombocythemia, 53, 193

kinesin, 4, 11, 128, 139 leukocyte integrin αMβ2 kinetic platelet aggregometer, 400 afﬁnity state change, 82, 231 kininogen, 82, 231 leukocytes high molecular weight, 112, 151, 224, 267 as risk factor for thrombosis in ET, 53, 194 and leukocyte recruitment, 300 in arterial thrombosis, 108, 261 kit ligand (KL), 13, 142 binding to activated platelets, 112, 267 Kozak (-5T/C) polymorphism, 24, 156 cellular cross talk with platelets and endothelial cells, 106, 255 laboratory method for platelet assessment enhancement of TF production, 81, 230 blood sampling, 1, 124 and platelet adhesion, 295 ﬂow cytometric assessment, 8, 134 platelet aggregation with, 159 future research, 13, 142 platelet interaction with, 308, 328 global platelet function PMP enhancement of adhesion, 284 bleeding time, 3, 127 polymorphonuclear, in ischemic stroke, 288 rapid platelet function assay, 4, 128 recruitment of, 324 platelet aggregation tests leukoreduction, 87, 94, 243, 248 agonist-induced, 5, 129 Libman–Sacks endocarditis, 115, 269 impedance (whole blood) platelet aggregometry, 132 life span of platelets optical (turbidometric) platelet aggregometry, 4, 128 in ITP,26, 157

498

Index

ligand-binding site Ma, H., 67, 214 location of, 26, 157 macothrombocytopenias, 108, 255 light transmission aggregometry (LTA), 387 macromolecular ligand fibrinogen limitations, 388, 395 binding site for, 26, 158 limb ischaemia, 108, 261 macrophage inflammatory peptide (MIP-1; CCL3), 108, 255 antiplatelet treatment impact on, 462 macrophage-derived chemokine (MDC), 59, 207 Lindblad, B., 441 macrophages Lindmarker, P.,317 monocyte differentiation into, 298 lipid mediators macrothrombocytopenias, 2, 21, 28–29, 126, 150, 163 as platelet-derived mediators, 109, 262 congenital, 4, 128 lipid rafts, 82, 227–232 MAIPA (monoclonal antibody immobilization of platelet lipopolysaccharides (LPS) glycoprotein assay), 43, 171 mice studies and in vivo effect, 67, 215 malignancy. See cancer as primer, 63, 211 MALT trial, 317 lipoprotein Marcus, A.J., 81, 230 as atherosclerotic biological marker, 293 marginal band of microtubules, 3, 128 liver disease Martens, L., 48, 191 platelet function disorders from, 83, Mas, J., 451 232 mast cells liver regeneration degranulation, 328 serotonin and, 2, 126 and matrix degeneration by proteases from, 299 LMWHs. See low-molecular-weight heparin (LMWH) mast cell growth factor, 13, 141 lotrafiban, 346, 447 MATCH study, 396, 443 low molecular weight GTP-binding proteins Matetzsky, S., 397 in Rho family, 43 matrix metalloproteinase-2 (MMP-2), platelet secretion of, 298 low-density lipoproteins (LDL), 57, 204 matrix metalloproteinases (MMP), 109, 264, 327, 330 elevated, and CAD, 109, 262 CD40L and release, 298 as platelet primer, 57, 204 human studies low-molecular-weight heparin (LMWH), 350 on cardiovascular disorders, 68, 215 for anticoagulation, 367 mice studies and in vivo effect, 65, 212 aspirin compared to, 475 as platelet primer, 55, 202 for thromboprophylaxis, 471 zinc and, 63, 211 and VTE risk reduction, 479 matrix-assisted laser-desorption ionization (MALDI), 13, 141 vs. warfarin, for prophylaxis of VTE, 309 May-Hegglin anomaly, 11, 108, 139, 255 LPA. See lysophosphatidic acid (LPA) May-Hegglin inherited thrombocytopenia (MYH9-RD), 29, 37, LRR sequence 163, 166 extracellular, 22, 150 MCP-3 (monocyte chemoattractant protein), 60, 207 L-selectin, 324 mean fluorescent intensity, 8, 135 LTA (light transmission aggregometry), 387 mean platelet volume (MPV), 2, 126 limitations, 388, 395 and acute cardiac events, 3, 127 lumiaggregometry, 60, 208 exercise and, 3, 126 lung cancer patients high levels as risk for coronary atherosclerosis, 3, 126 unfractionated and LMWH for, 317 mediators lungs platelet release of, 325 megakaryocytes in, 12, 140 Medical Research Council (MRC), 473 platelet biogenesis in, 12, 140 Medich platelet disorder, 63, 211 lupus. See systemic lupus erythematosus (SLE) megakaryoblastic leukemia lupus anticoagulant, 24, 152 dysfunctional platelets in, 84, 234 Lyman, S., 27, 161 megakaryocyte growth and development factor (MGDF), 354 lymphoblastic leukemia, acute megakaryocyte progenitors abnormal platelet function in, 84, 234 and endomitosis, 6, 132 lymphoid progenitor megakaryocytes, 323 from hematopoietic stem cells, 5, 131 classification schemes, 6, 132 lysis cytoplasm conversion, 8, 135 collecting data on, 391 development and platelet formation, 5–13, 147 lysophosphatidic acid (LPA), 58, 204, 315 apoptosis and platelet biogenesis, 13, 142 lysosomal membrane protein CD63, 2, 126 commitment to megakaryocyte lineage, 5, 131 lysosomes, 3, 126, 327 cytoplasmic maturation, 7, 133

499

Index

megakaryocytes (Contd.) molecular typing cytoskeletal machine of platelet production, 9–11, 140 for compatible donors for platelet transfusion, 94, 248 endomitosis, 6, 132 molecules platelet formation, 7, 133 in granules, 1, 124 platelet formation in vivo, 11, 140 monoclonal antibodies (MoAbs), 8, 135 regulation, 13, 140 monoclonal antibody immobilization of platelet glycoprotein features of mature, 7, 133 assay (MAIPA), 42, 171 fragments, 12, 140 monocyte chemotactic protein-3 (MCP-3; CCL7), 108, 255 future research, 15, 150 monocytes, 294 in lungs, 12, 140 and atherosclerotic lesion development, 298 in TAR syndrome, 106, 255 complex formation with activated platelets, 81, 230

membrane glycoprotein αIIβ3,2,125 in ischemic stroke, 288 membrane phospholipids abnormalities platelet activation and regulation of transformation, 298 Scott syndrome, 66, 213 monomeric G proteins, 41, 169 Stromorken syndrome, 66, 214 Montreal platelet syndrome, 67, 215 membrane skeleton Montrucchio, G., 63, 211 of resting platelet, 323 Moroi, M., 24, 156 membrane systems, 3, 127 morphology tests for platelets, 3, 125–127 meningococcaemia platelet count, 1, 125 purpura fulminans and, 15, 149 platelet size and appearance, 2, 126 menses mortality rate danazol to stop temporarily, 11, 161 of alloimmune thrombocytopenia (AIT), 41, 171 Mer receptor mouse for Gas6, 53, 194 advantages for human biology study, 64, 212 mesenchymal cells MPL (MPLW515L/K), 48, 190 thrombin as growth factor, 313 Mpl polymorphisms metal ion-dependent adhesion site (MIDAS), 25, 157 and variation in normal platelet counts, 45, 186 metargidin, 299 mRNA metastasis, platelet role in, 312 platelet translation into protein, 299 methylprednisolone in platelets, 341 for ITP,26, 158 mucosal bleeding, 15, 149 MGDF (megakaryocyte growth and development factor), 354 multimerin, 62, 210 microarray technology, 13, 141 and platelet factor V, 85, 235 microparticles multiple myeloma activated platelet release of, 108, 261 and platelet function disorders, 85, 235 leukocyte-derived, 300 Multiple Platelet Function Analyzer (Multiplate), 390 platelet-derived, and atherosclerosis, 284 Multiple Risk Factor Interventional Trial (MRFIT), 287 microtubules multivesicular bodies direct visualization of dynamics, 9, 138 and formation of platelet α-granules, 2, 125 marginal band of, 3, 128 mycophenylate mofetil and proplatelet formation, 9, 137 for refractory ITP,29, 162 secondary function, 11, 139 myelodysplasia, 24, 39, 156, 167 microvascular symptoms myelodysplastic syndrome, 53, 192 in essential thrombocythemia, 47, 189 myelogenous leukemia microvesicles acute generation of, 84, 234 d-SPD and development, 60, 208 tissue-factor bearing, 82, 231 chronic MIP-1 (macrophage inﬂammatory protein), 60, 207 abnormal platelet function in, 84, 234 mitochondria myeloid progenitor, 5, 131 in platelets, 3, 126 myeloproliferative disorders, 2, 126 mitosis promoting factor (MPF), 7, 132 and platelet function disorders, 83, 233 mitral stenosis, 116, 269 MYH9 gene, 108, 255 mitral valve prolapse MYH9-RD (myosin heavy chain 9 related disorders), embolism prophylaxis in, 116, 269 37, 166 Mitsui, T., 66, 213 myocardial infarction, 3, 108, 127, 261 MLL transcription factor anticoagulants for preventing, 109, 265 and familial thrombocytopenia-leukemia, 39, 167 risk in PAD patients, 458 Mohr, J., 448 myosin light chain kinase, 43, 172

500

Index

myosin light chain phosphorylation oral anticoagulants epinephrine and, 61 vs. antiplatelet therapies in atrial ﬁbrillation, 376–378 nadroparin, 317 for heart failure treatment, 376 Nak epitope on CD36, 29, 164 bleeding with, 465 Nak phenotype orboﬁban, 346 racial difference, 30, 164 organelles, 3, 11, 126, 139 NAP-2, 60, 207 mechanism of movement, 11, 139 naproxen Organization to Assess Strategies for Ischemic Syndromes and vascular events, 452 (OASIS) pilot trial, 375 National Cholesterol Education Project Adult Treatment orthopedic surgery Panel III (NCEP ATP-III), 109, 263 as risk factor for acute VTE, 473 National Institute of Health (NIH) stroke scale, 447 warfarin vs. LMWH for VTE prophylaxis, 309 nematode anticoagulant peptide (NAPc2), 374 osteoporosis neonatal thrombocytopenias as corticosteriods side effect in children, 30, 164 alloimmune (AIT), 43, 169–172 otamixaban, 371 neonatal thrombocytopenias, 41, 169 outpatients, prophylactic high-dose platelet transfusions for, 97, neuronal NOS (nNOS), 96, 250 251 neutropenia, 413 outside-in signaling, 46, 187 as antiplatelet therapy side effect, 380 oxidative stress, 99, 253 from clopidogrel, 380 ozagrel, 347 as ticlopidine side effect, 461

neutrophil activating peptide-2 (NAP-2; CXCL-7), P2TPLC receptor, 343

108, 255 P2x1 receptors neutrophil priming, 53, 191 and responses to ADP,45, 176

Newman, P.J.,27, 159 P2Y1 receptor abnormalities, 57, 204

Niemetz, J., 81, 230 P2Y1 receptors nitric oxide (NO; EDRF), 92, 95, 244, 250 and responses to ADP,45, 176

bioavailability, 279 P2Y12 inhibitor, 398

decreased availability of biologically active and PAD, P2Y12 receptors, 343, 417, 473 458 abnormalities, 57, 204 effect on platelet function, 96, 250 inhibition and thienopyridine resistance, 396 from endothelium, 109, 264 and responses to ADP,45, 175 loss of function, 98, 252 P2C1 receptor, 343 nitric oxide-donating aspirin (NO-aspirin), 351 paclitaxel-eluting stent, 417 nitroaspirin, 463 PAD. See peripheral artery disease (PAD) nocodazole, 9, 137 PAF. See platelet-activating factor (PAF) noncompliance of patients, 392 Paget–Schroetter syndrome, 9, 270 NSAID drugs, 115, 269 palpable purpura, 15, 149 and COX-2 inhibitors, effect on stroke risk, 452 pancytopenia interaction with aspirin, 353 from clopidogrel, 380 NSTEMI, 367 in Fanconi’s anemia, 106, 255 N-terminal side paradoxical prothrombotic drug effects of αIIb and β3 chains, 25, 156 and iatrogenic platelet disorders, 81, 230 nuclear factor kappa B (NF-κB), and hyperglycemia, 285 paraproteinemias, 85, 235 nucleoside triphosphate-diphosphohydrolases, 109, 265 parecoxib, 452 Nussmeier, N., 452 Paris Trousseau Syndrome (PTS), 62, 108, 211, 255, 311 Paris Trousseau Syndrome (PTS) O’Brien, J.R., 128 treatment, 316 OCS. See also open canalicular system (OCS) particulates oculocutaneous albinism, 25, 208 impact on cardiovascular morbidity and mortality, 63, 211 Ohmori, T., 355 impact on platelet activation in animal studies, 67, 215 OM2, 351 pathogen reduction oncoproteins, 315 for platelet transfusions, 87, 244 open canalicular system (OCS), 1, 3, 124, 127 pathological thrombi, 79, 228 granule release of contents, 15, 149 Patrono, C., 352 open heart surgery PDGF. See platelet-derived growth factor (PDGF) therapeutic platelet transfusions in, 98, 252 PDHRF. See platelet derived histamine releasing factor (PDHRF)

501

Index

PE. See pulmonary embolism (PE) phosphoinositide hydrolysis PECAM-1, 324 epinephrine and, 45, 186 Pen/Yuk, 27, 159 phosphoinositide in diabetic patients, 286

penicillins, bleeding and abnormal platelet function from, phospholipase A2 (PLA2), 109, 264, 341 82, 231 phospholipase C (PLC), 39, 93, 167, 246, 341, 343 pentasaccharides activation defects, 65, 213 antithrombotic therapy with, 370–372 activation of, 41, 168 pentoxifylline, 463 phospholipase Cβ (PLCβ)

pepducin, 350 Gq and activation of, 41, 171 percent platelet recovery (PPR), 93, 246 phospholipid-rich surfaces percutaneous coronary intervention (PCI) clotting complexes on, 84, 234 clopidogrel for, 415, 418 phospholipids, 107, 255 loading dose, 413, 416 in eukaryotic cells, 83, 232 GP IIb/IIIa inhibitors and, 419, 422 impaired liberation of arachidonic acid from, 63, 212 percutaneous endovascular revascularization phycoerythrin (PE), 8, 134 antiplatelet therapies in, 465 PI 3-kinases, 24, 43, 152, 172–175 percutaneous transluminal angioplasty (PTA), 465 picotamide, 461 pericytes, 315 plasma membrane peridinin-chlorophyllprotein (PerCP), 8, 134 of platelet surface, 1, 124 peripheral artery disease (PAD), 287 plasmapheresis, 27, 159 atherosclerosis and, 279, 458 plasminogen, 108, 261 future research, 467 α granules release of, 93, 247 platelets’ role in progression, 287 plasminogen activator inhibitor (PAI-1), 112, 266 risk factors for, 458 levels in diabetes mellitus-type II, 286 peripheral vascular disease, prostacyclin for, 349 platelet-activating factor (PAF), 109, 114, 264, 267, 327 peripheral vascular surgery, vitamin K antagonists (VKA) experimental animal studies of intravenous administration, for, 464, 465 329 peritoneal dialysis, 83, 232 platelet activation, 37, 155–165, 341 peroxisomes, 3, 126 and accelerated atherosclerosis, 293 peroxynitrite, 99, 253 and adhesion, 93, 246 perpetuation of platelet plug, 46–48, 190 as cause of mortality and morbidity, 341 other adhesion molecules, 47, 187 consequences of uncontrolled, 69, 227 integrins, adhesion and outside-in signaling, 46, 187 future research, 48, 191 ligand interactions at platelet gaps in signaling maps, 41, 168 platelet interface, 47, 189 mediators, 93, 246 petechiae in children preventing artefactual when drawing blood sample, 9, 137 from ITP,29, 163 rolling and, 294 petechiae, 13, 147 soluble markers, 10, 139 Peto, R., 438 b-thromboglobulin (βTG), 10, 139 PFA. See platelet function analyzer (PFA) glycoprotein (GP) V, 11, 139 PFA-100, 3, 7, 128, 133 platelet factor-4 (PF-4; CXCL-4), 10, 139 clinical utility, 7, 133 sP-selectin, 11, 139 variable influencing, 7, 133 in vivo, 39, 41, 167, 170 pharmacodynamic resistance, 352 whole blood flow cytometric assays pharmacokinetic resistance, 352 benefits, 9, 138 phenprocoumon platelet adhesion and uncontrolled bleeding, 23, 152 assay, 11, 140 phosphatidilinositol 3-kinase (PI3K) evaluating under shear-induced flow conditions, 8, 134 and Gas6 activities, 54, 194 shear conditions and, 341 phosphatidylethanolamine, 83, 233 platelet aggregation phosphatidylinositol 4, 5-bisphosphate (PIP2), 93, 246 inhibitors, 472 phosphatidylserine (PS), 66, 82, 213, 232 of thrombin-induced, 349 hypercoagulability and, 83, 232 with leukocytes, 159 in resting platelets, 108, 261 platelet aggregation primers, 53, 191 phosphodiesterase (PDE), 348 platelet aggregation tests

phosphodiesterase 3 (PDE3) agonist-induced, 5, 129 cilostazol inhibition of, 116, 270 impedance (whole blood) platelet aggregometry, 6, 132 phosphoinositide 3-kinase (PI3K), 61 optical (turbidometric) platelet aggregometry, 4, 128

502

Index

platelet activation under controlled shear conditions, 7, 133 Receptor Suppression Using Integrilin Therapy (PURSUIT) platelet function under ﬂow, 8, 134 trial, 422 VerifyNow, 6, 132 Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary platelet aggregometry, 86, 236 syndrome events in a Global Organization Network advantage of, 4, 129 (PARAGON)-B trial, 423 platelet count platelet inhibition goal during surgery or trauma, 97, 251 anti-inﬂammatory effects, 9, 270

normal range, 1, 125 ADP-receptor (P2Y12) antagonists, 115, 269 post-transfusion, 93, 246 COX inhibition and aspirin, 115, 268 platelet degranulation, 282 GPIIb/IIIa receptor antagonists, 116, 269 platelet-derived endothelial cell growth factor (PD-ECGF), phosphodiesterase inhibitors, 116, 270 315 platelet–leukocyte aggregates platelet-derived growth factor (PDGF), 109, 262, 315 formation, 8, 135 platelet release of, 330 platelet plug formation platelet-derived histamine releasing factor (PDHRF), 326 signaling initiated by epiniphrine and stability, 66, 214 platelet-derived lipid mediators, 327 platelet plug formation stages, 37–48, 190 platelet-derived microparticles (PMP) extension, 25, 37, 166, 187 and atherosclerosis, 284 ADP,43, 175 platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31), epinephrine, 45, 186 47, 98, 108, 187, 252, 261 G protein-mediated signaling, 41, 167

platelet–endothelial interaction, 94, 248 Gq and activation of phospholipase Cb, 41, 171

in inﬂammation, 95, 249 Gq G13 and actin cytoskeleton, 43, 171 in thrombosis and hemostasis, 94, 248 platelet activation in vivo, 41, 169

platelet “exhaustion,” 330 signaling through Gi family members, 43, 174 platelet factor-4 (PF-4; CXCL-4), 108, 114, 255, 267, 296 thrombin, 45, 176

measurement of plasma levels, 10, 139 thromboxane A2 (TxA2), 46, 186 and monocyte differentiation into macrophages, 298 initiation, 37, 39, 165, 166 platelet function analyzer (PFA), 86, 236, 391, t394 perpetuation, 37, 46–48, 166, 190 limitations for screening, 69, 226 other adhesion molecules, 47, 187 platelet function disorders integrins absence of predictive screening test, 69, 226 adhesion and outside-in signaling, 46, 187 acquired, 69, 225 ligand interactions at platelet β-lactam antibiotics, 82, 231 platelet interface, 47, 189 autoimmune platelet dysfunction, 85, 236 platelet primers clinical aspects, 70 classiﬁcation, 227 future research, 86, 237 platelet priming. See priming von Willebrand syndrome, 85, 235 platelet reactivity index (PR), 69, 227 and blood diseases, 83, 233 Platelet Receptor Inhibition for Ischaemic Syndrome leukemias, 84, 234 Management (PRISM) trial, 368, 423 multiple myeloma, 85, 235 Platelet Receptor Inhibition for Ischaemic Syndrome myeloproliferative disorders (MPD), 83, 233 Management in Patients Limited to Unstable Signs and correcting, 355 symptoms (PRISM- PLUS) trial, 368, 423 gene therapy, 355 platelet satellitism, 2, 125 disseminated intravascular coagulation, 83, 233 platelet transfusions. See also refractoriness to platelet iatrogenic acquired, 82, 227–232 transfusions

αIIb β3 blockers, 80, 229 adverse reactions, 93, 246 aspirin, 227 available products, 86, 242 causes unrelated to drugs, 82, 231 bacterial testing, 87, 243 paradoxical prothrombotic drug effects, 81, 230 extended stored platelets, 92, 244 thienopyridine, 79, 228 gamma irradiation, 92, 244 kidney disease and, 82, 232 leukoreduction, 86, 243 from liver disease, 83, 232 pathogen reduction, 82–87, 244 surgical issues, 86, 236 whole blood-derived platelet concentrates or apheresis platelet function testing, 353, 386 platelets, 86, 242 bleeding time (BT) as, 386 expected response ﬂow cytometric analysis, 391 in adults, 93, 244 for monitoring antiplatelet therapy, 386 in infants, 93, 245 Platelet GP IIb/IIIa in unstable angina future research, 108, 255

503

Index

platelet transfusions. (Contd.) primary secretion defects, 58, 67, 204, 214 for inherited platelet disorders, 68, 216 primary thrombocytosis. See clonal thrombocytosis (CT) mechanisms of poor responses, 93, 246 primers’ effect in vitro molecular typing and compatible donor pool size, 94, 248 cytokines, 25, 208 prophylactic, 96, 250 chemokines, 59–60, 207 dose, 97, 250 leptin, 60, 208 transfusion trigger, 97, 250 thrombopoietin (TPO), 58, 206 therapeutic, 99, 251–254 vascular endothelial growth factor (VEGF), 58, 205 platelet-rich plasma (PRP) method of platelet preparation, foreign substances, 63, 211 86, 242 hormones, 61–62, 209 platelets epinephrine, 61, 209 cellular cross talk with endothelial cells and leukocytes, 106, estrogens, 61, 209 255 histamine, 61, 209 coated, 86, 236 ions correcting disorders of number zinc, 62, 210 thrombocytopenia. See also thrombocytopenia, 353 lipopolysaccharides (LPS), 63, 211 thrombocytosis, 353 prostaglandins, 62, 210 function inhibition proteins, 23, 205 future research, 100, 254 Factor VIII, 54, 194 functions, 341 Gas6 (growth arrest-specific gene 6), 53, 193 main function of, 21, 150 gelatinase A (MMP-2), 55, 202 normal count, 1, 124 human fibroblast collagenase (MMP-1), 55, 202 physiological roles of, 341 low-density lipoproteins (LDL), 57, 204 release in vivo, 11, 140 matrix metalloproteinases (MMPs), 55, 201 requirements for, 37, 163–165 soluble CD40 lingand (sCD40L), 56, 204 size in ITP,24, 156 succinate, 64, 212 See also activated platelets primers’ effect in vivo platelet-type bleeding disorder, 21, 150 animal studies evidence, 64, 212 platelet-type von Willebrand disease (VWD), 55, 202 cytokines, 65, 213 Plateletworks, 227, 236 Gas6 mice studies, 64, 212 r aggregation kits, 390 matrix metalloproteinases, 65, 212 pluripotent stem cells sCD40L, 65, 213 megakaryocytes descendant from, 5, 131 human studies, 68, 215 PMP. See platelet-derived microparticles (PMP) cytokines, 69, 226 pneumococcaemia hormones, 69, 227 purpura fulminans and, 15, 149 prostaglandins, 69, 227 polyclonal antibodies (MoAbs) proteins, 68, 215 in whole blood flow cytometry, 137 priming, 53, 191 polycythemia vera (PV) Pro219 allele, 30, 165 VEGF and, 69, 226 procoagulant molecules, 108, 261 polymorphonuclear leukocytes progenitor cells in ischemic stroke, 288 platelet binding to, 300 polyploidization proinflammatory molecules in megakaryocyte regulation, 7, 132 activated platelet release, 107, 255 Post Coronary Artery Bypass Graft (Post CABG) trial, 375 promegakaryoblast, 6, 132 postsplenectomy thrombocytosis, 47, 187 promegakaryocyte, 6, 132 posttransfusion purpura prophylactic platelet transfusions, 96, 250 Pen/Yuk and, 27, 160 dose, 97, 250 PPACK (D-phenylalanyl-L-prolyl-L-arginine proplatelets, 8, 134 chloromethylketone), 1, 124 end amplification, 10, 139 PPR (percent platelet recovery), 93, 246 elongation prasugrel, 344, 429, 473 polymerization and, 10, 138 metabolism of, 344 ends prednisone for ITP,26, 158 generation for platelet production, 11, 140 in children, 30, 164 formation dependence on microtubule function, 9, 137 prekallikrein, 22, 151 release, 11, 140 premature coronary artery disease prostacyclin, 12, 140 and familial hypercholesterolemia (FH), 69, 216 for peripheral vascular disease, 349

504

Index

prostacyclin receptor (IP), 348 surface expression of, 108, 110, 261, 266 prostaglandin H-synthase, 342 and tumor progression, 312 prostaglandin pathway, 97, 250 P-selectin glycoprotein ligand-1 (PSGL-1), 351 prostaglandins, 53, 92, 191, 244 P-selectin/PSGL-1 axis, 81, 230 aspirin inhibition of production, 342 pseudopodia, 9, 138 for critical limb ischemia, 463 pseudo-resistance, 395 effect on platelet function, 97, 251 pseudothrombocytopenia, 2, 24, 125, 156 human studies, 69, 227 from anticoagulants, 381 mice studies pseudo-von Willebrand disease, 55, 202 in vivo effect, 66, 214 PSGL-1 (P-selectin glycoprotein ligand-1), 82, 112, 232, 267 platelet release of, 310 PSI-697, 351

as primer, 62, 210 PT2AC receptor, 343 synthesis, 97, 250 PTA (percutaneous transluminal angioplasty), 465 stages, 342 pulmonary embolism (PE), 108, 261, 367, 471 protease activated receptor (PAR) antagonists, 349 Pulmonary Embolism Prevention (PEP) trial, 271, 475 protease-activated receptor family of G protein coupled pulmonary megakaryocytes, 12, 140 receptors, 45, 186 purinergic receptors, 343 protease-activated receptors, 84, 234, 283, 430 in children in tumor cell lines, 313 purpura, 5–13, 147 proteases from ITP,29, 163 as platelet-derived mediators, 109, 264 posttransfusion protein kinase C, 39, 167 Pen/Yuk and, 27, 159 epinephrine and, 61, 209 purpura fulminans, 15, 149 protein kinase Cα (PKCα), 11, 139 protein S, 108, 261 Quebec platelet disorder (QPD), 62, 210 proteins, 53, 191 fibrinolytic inhibitor drugs for, 69, 216 coating microtubules, 4, 128 Quebec platelet syndrome, 85, 86, 235, 236 deficiency in gray platelets in α granules, 62, 210 quinidine platelets ability to make, 299 and thrombocytopenia, 41, 168 as primers Qureshi, A., 447 Factor VIII, 54, 194 Gas6 (growth arrest-specific gene 6), 53, 192 Rac family gelatinase A (MMP-2), 55, 202 monomeric G proteins, 41, 168 human fibroblast collagenase (MMP-1), 55, 202 Raccuglia, G., 61–62, 209 human studies, 68, 215 Radley, J.M., 8, 135 low-density lipoproteins (LDL), 57, 204 Randomised Evaluation in PCI Linking Bivalirudin to Reduced matrix metalloproteinases (MMPs), 55, 201 Clinical Events (REPLACE)-2 trial, 427 soluble CD40 lingand (sCD40L), 56, 204 Randomized Efficacy Study of Tirofiban for Outcomes and release idenfitication from activated platelets, 106, 255 Restenosis (RESTORE) trial, 422 synthesis by platelets, 107, 255 RANTES (Regulated on activation normal T cell expressed and proteome secreted), 60, 112, 207, 267, 296, 298 characterization of cell’s, 13, 141 and inflammation, 326 proteomics, 13, 48, 142, 190 and leukocyte activation, 114, 267 prothrombin G20210 A gene mutation, 310 PMPs as transfer system for, 284 prothrombin time (PT), 21, 150 Rao, A.K., 65, 213 prothrombinase rapid platelet function assay, 4, 128 impairment in δ-SPD platelets, 59–60, 208 Ratnoff method, 3, 127 P-selectin, 2, 80, 125, 126, 229 reactive oxygen species (ROS), 99, 253 microvesicles and, 85, 234 in hypertensive patients, 99, 254 MoAbs and, 9, 137 reactive thrombocytosis (RT) monocyte exposure to, 82, 231 vs. clonal, 53, 191 P-selectin (CD62P), 282, 324 conditions associated with, 45, 46, 186 α granules release of, 93, 247 receptors enhancement of monocyte adhesion to endothelial cells, 113, for Gas6, 53, 193 261–267 on platelet surface, 38, 166 and leukocyte tethering and rolling, 112, 267 in platelets, 21, 150 and platelet rolling, 296 recombinant FVIIa, 69, 216 response to inflammatory stimuli, 95, 250 recombinant hirudin, 372

505

Index

recombinant t-PA rituximab for ischemic stroke treatment, 288 for ITP,27, 160 refractoriness to platelet transfusions, 93, 246 side effects, 27, 161 alloimmunized, 93, 247 rivaroxaban management, 94, 248 for venous throboembolism prevention, 373 prevention, 93, 247 Rocca, B., 352 management strategies for persistent, 96, 250 rofecoxib, 452 nonimmune, 95, 248 rolling, 296 renal failure P-selectin and, 294 and elevated plasma levels of β-TG, 11, 139 Roncaglioni, M.C., 408 reocclusion after angioplasty Rotational TEG, 391 abciximab to reduce rate, 466 RT. See reactive thrombocytosis (RT) resistance, 392 Rumpel-Leede test, 14, 148 to antiplatelet agents, pharmacogenomic factors, 353 clinical, 352 S18886, 348 meaning of term, 351 Sanofi’s anti-thrombotic discovery programme, 343 pharmacodynamic, 352 sarprogelate, 463 pharmacokinetic, 352 sCD40L. See soluble CD40 lingand (sCD40L) pharmacologist’s definition, 352 SCH 530348, 430 RESISTOR trial (Research Evaluation to Study Individuals who Schulman, S., 317 show thromboxane or P2Y12 Resistance), 398 Scott syndrome, 66, 83, 84, 213, 233, 234 respiratory disorders, 329–332 scramblase enzyme, 83, 233 asthma, 159 scramblases, 108, 261 clinical studies, 330 screening programs experimental animal studies, 329 for AIT, 43, 172–175 chronic obstrctive pulmonary disease (COPD), 332 antenatal management, 43, 172 cystic fibrosis, 332 management, 43, 172 resting platelets SCUBE1 protein, 299

αIIbβ3 in, 26, 157 SDF-1α, 59, 207 ﬁlaments of, 4, 129 Sebastian Syndrome, 108, 255 intracellular components, 1, 124 Second Northwick Park Heart Study, 317 actin cytoskeleton, 4, 128 second-hand smoke and atherosclerosis, 109, 264 cytoskeleton, 3, 127 secretogranin III, 13, 142 granules, 1, 124 selectin, 324 marginal band of microtubules, 3, 128 and platelet-EC adhesion, 110, 265 membrane systems, 3, 127 selective serotonin reuptake inhibitors (SSRI’s), 351 organells, 3, 126 sepsis spectrin membrane skeleton, 5, 129 bacterial phosphatidyl serine (PS) in, 108, 261 from contamination of platelet transfusions, 87, structure, 1–5, 131 243 retention test Homberg, 69, 227 as splenectomy risk, 27, 161 reteplase, 428 Ser/Pro substitution, 30, 165 reversible platelet aggregation, 5, 130 serotonin reviparin, 370, 475 δ granule storage of, 325 rheumatoid arthritis, 334 dense granules release, 93, 247 Rho family in dense granules, 2, 126 low molecular weight GTP-binding proteins in, 43, and platelet activation, 93, 245 172 platelet receptors for, 341 monomeric G proteins, 41, 168 platelet release of, 310 riboﬂavin platelet storage of, 60, 207 adding to platelet transfusions, 92, 244 serotonylation, 86, 242 Ridker, P.,438 Sevitt, S., 472 ridogrel, 348 SFLLRN (thrombin receptor-activating peptide), 5, 131 rifampin shape of platelets, 1, 124 impact on clopidogrel, 353 change, 14, 41, 93, 147, 169, 246 ristocetin shear conditions and platelet aggregation, 5, 131 platelet activation under controlled, 7, 133 response to, 60, 207 and platelet behavior, 388

506

Index

shed blood vs. venous blood decision to defer, 11, 161 platelet number and MMP-2 content, 68, 216 thrombocytosis after, 46, 187 shiga-like toxin, 45, 176 splenectomy Sib alloantigen, 24, 155 and improved platelet increments, 95, 249 sibrafiban, 346 sP-selectin, 11, 139 sickle cell anemia, 82, 231 SSR126517 (biotynilated idraparinux), 371 signaling statins, and abnormal platelet function testing, 82, 231 cascade triggered by leptin, 60, 208 steel factor, 13, 141 signaling pathways ST-elevation MI (STEMI) identification of, 302 clopidogrel for patients with, 417 signal-transduction pathways abnormalities, 63, 212 GP IIb/IIIa inhibitors in patients with, 428–429 arachidonic acid (AA) impaired liberation from membrane stem cell factor, 13, 141 phospholipids, 63, 212 Stent Anticoagulation Restenosis Study (STARS) trial, 413 cyclooxygenase defects, 64, 212 stent implantation GTP-binding proteins abnormalities, 64, 212 aspirin with thienopyridine for, 415 phospholipase C activation defects, 65, 213 carotid, abciximab for, 447 thromboxane synthetase, 64, 212 clopidogrel sildenafil, 81, 231, 349 pretreatment and duration of treatment, 416 simian immunodeficiency virus, 357 vs. ticlopidine, 419 sirolimus-eluting stents, 417 treatment duration after, 416 Sistrurus miliarus barbouri, 346 combination clopidogrel/aspirin therapy after, 444 Sit alloantigen, 29, 163 ticlopidine after, 445 skeletal abnormalities stent thrombosis in Fanconi’s anemia, 106, 255 cilostazol with aspirin and clopidogrel to prevent, 349 skin template bleeding time, 3, 127 prevention of, 413 Sky receptor storage temperature for Gas6, 53, 193 and platelet function, 1, 124 SLAM (signaling lymphocytic activation molecule; CD150), stress fibers, 324 47, 189 stress platelets, 2, 126 SLE. See systemic lupus erythematosus (SLE) stroke, 108, 261, 288 SMAD proteins, 13, 147 anticoagulant role in preventing, in atrial fibrillation, 376 smoking, and cardiovascular disease, 109, 264 antiplatelet therapies in prevention, 438 sn-1, 2-diacylglycerol (DAG), 93, 246 aspirin and reduction of, 377 sodium citrate, 1, 124 COX-2 inhibitors and NSAIDs impact on risk, 452 Solomon, S., 452 etiologies and antiplatelet agents’ role, 437 soluble CD40 lingand (sCD40L) hemorrhagic, 437 in ischemic cardiovascular disorders, 68, 216 prevention of secondary as platelet primer, 56, 204 IIb/IIIa inhibitor for, 447 mouse studies, 65, 213 recurrence rates, 451 soluble CD40L, 82, 231 risk in PAD patients, 458 soluble platelet activation markers source of, 437 glycoprotein V (GPV), 11, 139 warfarin and reduction of, 377 granular contents, 10, 139 warfarin for prevention, 449 platelet adhesion assay, 11, 140 Stroke Prevention in Atrial Fibrillation (SPAF) study, 377 sP-selectin, 11, 139 Stroke Prevention in Atrial Fibrillation 1 (SPAF-1) trial, 439 Spanish National Study for Prevention of Embolism in Atrial Stroke Prevention in Atrial Fibrillation-III (SPAF III) trial, 451 Fibrillation (NASPEAF), 377 Stroke Prevention using an Oral Thrombin Inhibitor in atrial spectrin membrane skeleton, 5, 129 Fibrillation (SPORTIF) studies, 452 Speroff, T., 475 Stromorken syndrome, 66, 214 sphingosine 1-phosphate (S1P), 315 Study of Platelet Inhibition and Patient Outcomes (PLATO), spices, and platelet function in vitro, 82, 231 429 spleen, platelets pooled in, 92, 244 subendothelial matrix splenectomy platelet adhesion to, 23, 152 bacterial sepsis as risk, 27, 161 succinate failures, 9, 161 as primer, 64, 212 for ITP treatment, 27, 159 succinic acid, 64, 212 for ITP treatment superoxide, 99, 253 in children, 30, 165 surface of the platelet plasma membrane, 1, 124

507

Index

surgical procedure thrombin-induced platelet aggregation, inhibitors of, platelet count goal in, 97, 251 349 survivin, 7, 133 thrombin-receptor activating peptide (TRAP), 10, 84, 138, 234 Swedish Aspirin Low-Dose Trial (SALT), 440 thrombin-receptor antagonists systemic lupus erythematosus (SLE) future research, 430 and ITP,29, 163 thrombocythemia 125 systolic dysfunction and bleeding, 53, 191 anticoagulation for, 115, 269 clinical manifestations, 47, 189 drug induced, 167 T/C polymorphism, 30, 165 from heparin, 168 tachycardia epidemiology, 47, 189 and need for fluid replacement, 13, 147 essential (ET), 45, 47, 186, 187 tacrolimus and bleeding, 48, 191 impact on platelet transfusion outcome, 95, 250 clinical manifestations, 47, 189 telmisartan, 303 epidemiology, 47, 189 tenase future research, 54, 176, 194 extrinsic and intrinsic, 83, 232 inherited, 41, 165–167 tenecteplase (TNK), 428 children with, 29, 163 terbogrel, 348 myelodysplasia, 39, 167 TF. See tissue factor neonatal, 41, 169 TF/VIIa complex pathogenetic mechanisms, 46–48, 190 and coagulation, 83, 232 prognosis, 53, 193 TGF-β. See transforming growth factor-β (TGF-β) treatment, 54, 194 TGFβ1, 13, 147 thrombocytopenia, 2, 23–24, 125, 155, 309, 353 therapeutic platelet transfusions, 99, 251–254 congenital, management, 108, 255 Thiagarajan, P., 3, 127 dilutional, trauma and, 98, 252 thienopyridine effect, 69, 227 from drugs, 21, 150 thienopyridines, 371, 372, 473. in gray platelet syndrome, 62, 210 antiplatelet effects, 412 in infants, 106, 255 for arterial thrombosis treatment and prevention, 110, 265 congenital, 100, 254 with aspirin, for peripheral endovascular procedures, 466 X-linked congenital, 107, 255 and iatrogenic platelet disorders, 79, 228 macothrombocytopenias, 107, 255 mechanism of action, 344 and petechiae, 14, 148 for peripheral arterial disease, 460 as ticlopidine side effect, 461 resistance, 396 See also alloimmune thrombocytopenia (AIT); immune See also clopidogrel; ticlopidine thrombocytopenic purpura (ITP) Thiery, J.B., 8, 134 Thrombocytopenia and Absent Radius (TAR) syndrome, thombotic disorders 29, 61, 163, 209 sP-selectin as marker, 11, 140 thrombocytosis, 353 Thr/Met substitution, 24, 155 in cancer patients, 311 thrombin, 45, 176, 308, 349, 367 causes of, 45, 186 binding by, 84, 234 threshold platelet count, 45, 186 role in cancer, 313 thromboelastograph platelet mapping system, formation, 283 69, 227 GPIb/IX/V as high-affinity binding site for, 23, 152 thromboelastography (TEG), 86, 236, 391, 395 GPV levels and, 11, 139 thromboembolism impact on tumor dormancy, 317 arachidonic acid-induced platelet, 67, 214 inhibitors of, 350 high FVIII levels and, 54, 201 and initiation of platelet activation, 37, 166 Thrombolysis in Myocardial Infarction (TIMI) 8 trial, 372 platelet activation by Thrombolysis In Myocardial Infarction (TIMI) study whole blood measurement, 9, 138 group, 378 and platelet activation in vivo, 39, 166 thrombolytic agents platelet receptors for, 341 administration, 23, 152 platelet response to, 45, 186 thrombomodulin, 109, 265 production by coagulation system, 79, 228 thrombopoiesis unfractionated heparin (UFH) and, 367 rate of, 2, 126 thrombin activatable fibrinolysis inhibitor (TAFI), role for proplatelet formation, 8, 135 83, 232 thrombopoietin as regulator, 13, 141

508

Index

thrombopoietin, 8, 13, 135, 141, 354 defects, 23, 205 in vivo effect mice studies, 65, 213 measurement of, 391 levels in ITP,26, 157 and platelet activation, 93, 107, 245, 255 thrombopoietin (TPO) platelet receptors for, 341

as primer, 58, 206 thromboxane B2 (TxB2), 12, 140 human studies, 69, 226 in VTE, 472 and reactive thrombocytosis, 25, 187 thromboxane pathway inhibitors, 347 thrombopoietin (Tpo) receptor thromboxane synthetase and variation in normal platelet counts, 45, defects, 64, 212 186 thrombus thromboprophylaxis formation of pathological, 21, 150 antiplatelet agents effect on, 309 formation, 367 aspirin role in, 310 thromoembolic disorders

thrombosis urinary thromboxane B2 (TxB2) for diagnosing, 12, 140 abdominal vein (AVT), 47, 190 thymus and activation-regulated chemokine (TARC; CCL17), 59, managing ET-associated, 54, 194 108, 255 risk factors in ET, 53, 193 ticlopidine, 79, 115, 228, 269, 343, 413, 473 thrombosis. See also arterial thrombosis vs. clopidogrel for stent placement, 419

αIIbβ3 role in, 25, 156 lack of recommendation, 464 arterial and need for vascular surgery, 463 leptin and, 66, 213 PAD patients in trials using, 461 blood-borne TF role in, 81, 229 side effects, 380 and cancer, 227 tifacogin, 374 historical perspective, 311 tirofiban, 81, 229, 346, 368, 392, 419 laboratory findings in hypercoagulation, 311 vs. abciximab, 422 platelet role in metastasis, 312 for arterial thrombosis treatment and prevention, thrombin role, 313 112, 266 tissue factor role, 313 bleeding complications, 379 tumor cell adhesion, 312 for cerebrovascular disease, 444 chamber-based dosing regimen, 422 clinical presentation, 113, 267 pharmacokinetics, 419 risk factors for, 114, 267 thrombocytopenia from, 380 treatment and prevention, 115, 269 tissue factor (TF), 86, 242 clinical approach, 108, 261 role of arterial wall, 81, 229 future research, 272 blood-borne, 80, 229 high-shear vs. low-shear, 108, 261 and coagulation cascade, 283 platelet-endothelial interaction in, 94, 248 platelet products enhancing synthesis, 79, 228 PMPs and, 284 platelet products increasing production, 81, 230 Thrombosis Prevention Trial (TPT), 374, 408 platelet substances for stimulating synthesis, 82, 231 thrombospondin platelet synthesis, 299 α granules release of, 93, 247 tumor cells and, 313 surface level of, 86, 242 tissue factor pathway inhibitor (TFPI), 374 and tumor cell adhesion, 313 tissue inhibitors of metalloproteinases (TIMPs), 55, 202 Thrombostat 4000, 391 tissue regeneration, platelets and, 316 thrombotic thrombocytopenic purpura (TTP), 37, 43, 70, 165, toll-like receptors (TLRs), 324 175, 227 toll-like-receptor-4 (TLR4), 63, 211 as antiplatelet therapy side effect, 380 mice studies, 67, 215 ticlopidine and risk of, 445 total body irradiation (TBI), impact on platelet transfusion from ticlopidine, 413 outcome, 95, 250 thromboxane, 97, 251 TPO. See thrombopoietin (TPO) measuring levels for monitoring aspirin, 396 TRA-418, 348 platelet release of, 310 transcription factor NκB, 82, 231 thromboxane A2 (TxA2), 37, 46, 166, 186 transcriptome abnormal generation in ET, 48, 191 for platelets, 48, 190 and allergic inflammation, 327 transforming growth factor-α (TGF- α), 109, 262 aspirin and decrease in, 472 transforming growth factor-β (TGF-β), 109, 262, 315 aspirin effect and, 411 platelet release of, 330 aspirin inhibition of, 79, 227 transfusion-related acute lung injury (TRALI), 86, 242

509

Index

transfusions of platelets, 27, 159 urinary markers

for AIT TxA2 metabolites, 12, 140 intrauterine, 43, 173 TxB2, 12, 140 in neonates, 43, 175 US Physicians’ Health Study, 463 transient ischemic attack (TIA), 108, 261, 288 Ushikubi, F., 58, 205 transient megakaryocytic leukemia, 41, 169 UV-A light TRAP. See thrombin-receptor activating peptide (TRAP) platelet exposure to, 92, 244 trauma platelet count goal after, 97, 251 vaccines therapeutic platelet transfusions for, 97, 251 in ITP treatment in children, 31, 165 Treat angina with Aggrastat and determine Cost of Therapy valdecoxib, 452 with an Invasive or Conservative Strategy-Thrombolysis valsartan, 303 In Myocardial Infarction (TACTICS-TIMI) 18 trial, valvulopathy, thromboembolism from, 114, 115, 267, 268 425 Vane, J., 342 TRial to assess Improvement in Therapeutic Outcomes by Varon, D., 390 optimizing platelet InhibitioN with prasugrel vascular damage Thrombolysis In Myocardial Infarction 38 platelet reponse to, 13, 147 (TRITON-TIMI 38), 429 vascular disease, 3, 99, 126, 251–254 Trial To Reduce Alloimmunization to Platelets (TRAP Trial), vascular endothelial growth factor (VEGF) 93, 248 platelet release of, 313, 330 Triatoma infestans, 351 as primer, 58, 205 triﬂusal, 377 human studies, 69, 225 triplatins, 351 vascular endothelium tropomodulins, 5, 129 as antithrombotic surface, 97, 251 troponin elevation, 423 dysfunction, 93, 244 Trousseau, A., 311 and cardiac disease, 98, 252 tubular membranes, 8, 134 in vascular disease, 98, 252 tubulin, 9, 136 normal function, 92, 244 tumor necrosis factor (TNF) superfamily, 56, 203 substances impacting platelets tumor necrosis factor-α (TNF- α), 25, 187 ecto-ATPDase, 97, 251 CD40L and, 114, 267 nitric oxide (NO), 95, 250 Turpie, A., 452 prostaglandins, 97, 250 Twist gene, 313 surface-bound antiplatelet factors, 98, 252

TxA2. See thromboxane A2 (TxA2) PECAM-1, 98, 252

TxA2 metabolites, 12, 140 thromboregulatory systems of, 92, 244 aspirin inhibition of, 407 vascular injury type IV collagen thrombin generation at, 39, 166 and tumor cell adhesion, 313 vascular surgery, 463 tyrosine kinase receptors, 53, 193 vasodilator-stimulated phosphoprotein (VASP), 97, 251 tyrosine phosphorylation, 60, 208 VASP assay, 397 VCF. See velocardiofacial syndrome (VCF) U46619, 5, 131 velocardiofacial syndrome (VCF), 37, 166 ulcerative colitis, 333 veno-occlusive disease of the liver (VOD) Ultegra rapid platelet function analyzer, 6, 132, 390 impact on platelet transfusion outcome, 95, 250 See also VerifyNow venous thromboembolism unfractionated heparin (UFH) antiplatelet therapies for, 471 for anticoagulation, 367 orthopedic surgery as risk factor, 473 United Kingdom-TIA (UK-TIA) trial, 441 platelet aggregation inhibition, 472 unstable angina (UA), 367 platelets in pathogenesis, 471 uranafﬁn reaction preventing in δ-granules, 59, 207 air travel-related, 478 urban pollution future research, 479 impact on cardiovascular morbidity and mortality, 63, in high-risk patients, 473 211 recurrent, 478 uremia risk factors for, 471 in HUS, 45, 176 rivaroxaban for preventing, 373 platelet dysfunction and, 22, 232 venous thrombosis, 108, 261 uremic thrombocytopathy, 83, 232 clinical presentation, 116, 270

510

Index

consequences of, 108, 261 warfarin, 115, 269, 373 future research, 318 and antiplatelet therapy, 374 platelets role in, 280, 308 with aspirin, 374 prevention and treatment, 270 for PAD, 461 risk factors for, 107, 270 for preventing stroke, 452 VerifyNow, 5, 70, 132, 227, 390, 393, 395, 397 for atrial fibrillation, or aspirin, vs., placebo, 450 Aspirin assay, 79, 228 compared with clopidogrel and aspirin, 418 VerifyNow Aspirin cartridge, 395 vs. LMWH, for prophylaxis of VTE, 309 VERITAS (The Verify Thrombosis Risk Assessment) trial, 397 reduction of strokes, 377 vero toxin, 45, 176 for stroke treatment and secondary prevention, 448 Verona Diabetes Study, 287 and uncontrolled bleeding, 23, 152 vessel wall-derived substances, 92, 244 Warfarin and Antiplatelet Therapy in Chronic Heart Failure vincristine, 9, 138 (WATCH) trial, 376 Virchow’s triad, 108, 116, 261, 270, 471 Warfarin and Aspirin for Symptomatic Intracranial arterial vitamin C deficiency (scurvy) stenosis (WASID) trial, 449 and ecchymoses, 14, 148 Warfarin and Aspirin for the prevention of Recurrent iSchemic Vitamin E, in cystic fibrosis, 332 Stroke (WARSS) trial, 448 vitamin K, 22–23, 152 Warfarin/Aspirin Study in Heart Failure (WASH) study, 376 vitamin K antagonists (VKA), 373 Warfarin-Aspirin Re-Infarction Study-2 (WARIS-2) trial, 375 for arterial thrombosis treatment and prevention, 112, 267 WARIS (Warfarin Aspirin Reinfarction Study), 112, 267 to prevent recurrent VTE, 478 Weibel-Palade bodies, 95, 250, 296 for thromboprophylaxis, 471 Weiss, H.J., 59–60, 67, 208, 214 for vascular graft patients, 464, 465 Wells criteria, 9, 270 and VTE risk reduction, 479 White platelet syndrome (WPS), 63, 211 vitronectin, 345 whole blood aggregometry (WBA), 388 and tumor cell adhesion, 313 Wholey, M., 447 vitronectin receptor, 345 willow bark, 342 von den Borne, A.E., 27, 160 Wiskott–Aldrich syndrome, 2, 29, 39, 61, 126, 163, 166, 209 von Willebrand disease (VWD), 55, 67, 126, in infants, 107, 255 202, 215 Women’s Health Study, 408 aspirin impact, 128 Wang, R., 27, 160 PFA-100 for screening, 7, 133 wound healing, platelets and, 316 testing for, 69, 226 Wright, James Homer, 7, 133 type IIB, 39, 166 Wu, K.K., 67, 127, 214 von Willebrand factor (VWF), 108, 255, 282, 308 α granules release of, 93, 247 xemilofiban, 346

αIIbβ3 integrin as receptor, 24, 156 ximelagatran, 350, 373 binding to GPIb/IX/V, 23, 152 X-linked coagulation disorder, 15, 150 GPIb/IX/V as adhesive receptor for, 21, 150 X-linked congenital thrombocytopenias in infants, 107, levels in diabetes mellitus-type II, 286 255 MMP-2 and, 56, 203 X-linked thrombocytopenia multimers, 37, 165 with thalassemia (XLTT), 62, 210 in multivesicular bodies, 2, 126 X-linked thrombocytopenia (XLT), 39, 166 receptor, 3, 127 surface level of, 86, 237 Y-20811 inhibitor, 347 von Willebrand factor cleaving protease, 45, 175 Yusuf, S., 375 von Willebrand syndrome Zacharski, L., 316 acquired (AVWS), 53, 191 zinc bleeding in MPD and, 83, 233 as primer, 62, 210 and platelet function disorders, 85, 235 zinc binding motif (HEXXHXXGXXH), 55, 202 zymogen factor X, 83, 232 walking distance zyxin impaired arterial circulation and, 463 zinc and, 63, 211

511