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Anamnestic immune response. See Immune response to heparin

Ancrod, 11, 26, 39, 41, 42, 263, 275, 289, 290, 304, 305, 322, 324, 326

Animal models, of HIT, 195 Annexin V-binding assay, 191, 229,

240 Antibodies antibivalirudin antibodies, 429-430

[Antibodies] antibody-containing immune complexes effects of, 172-173 importance, 173-174 cross-reactivity with danaparoid, 332-336. See also Danaparoid (Orgaran®) epitopes recognized by, 151-156 formation, 364-365 heparin-dependent, pathological mechanisms, 136-138 nature of, 26-27 Anticoagulants/anticoagulation. See also Argatroban therapy in HIT; Danaparoid (Orgaran®); Lepirudin for HIT treatment for cardiac surgery, 328 DTI dosing, 292-293 emerging anticoagulants and HIT, 441-461

drug development, progress in, 441

exploring treatment of HIT with, rationale for, 442-443 fondaparinux, 443-445. See also separate entry targeting factor Xa and thrombin, rationale for, 441-442 of HIT-associated thrombosis, 288-289

of HIT patients with thrombosis,

288-294 of HIT patients without thrombosis, 295-296 in HIT treatment, 289-290 longer-term anticoagulant management, 296-298 oral anticoagulants with danaparoid, 327 patient with a low or intermediate probability of HIT, management of, 298 pharmacologic and pharmacokinetic considerations in, 290-292 reexposure of the HIT patient to heparin, 298-299 tests for monitoring, 347-350

[Anticoagulants/anticoagulation] vitamin K antagonist (coumarin) therapy, 296-298 Antigen assays for HIT antibodies, 229, 240-247 activation and antigen assays, comparison, 245-247 fluid-phase EIA, 242-243 rapid assays, 243-245

particle immunofiltration assay, 245

solid-phase enzyme immunoassay

(EIA), 240 solid-phase PF4-polyvinylsulfonate antigen assay, 241-242 Antigen-antibody mechanism, 3 Antigen formation, recognized by HIT antibodies, 171-172 Anti-PF4/heparin antibodies, adverse prognosis and, 99-100, 286-288

Antiphospholipid antibody syndrome (APLAS), 262, 266-270 clinical features, 266 HIT and, clinical parallels between, 269

thrombocytopenia in patients with, 269

Antiplatelet agents, 303-304 acetylsalicylic acid, 303, 466 clopidogrel, 303

dextran, 289, 290, 303, 321-324, 524 dipyridamole, 303 platelet glycoprotein IIb/IIIa inhibitors, 303 Apixaban, 454

Apyrase, 192, 217, 228-230, 234, 235 Ardeparin sodium (Normiflo®), 174 ARG-911, 12, 290, 326, 364, 386-387

argatroban reexposure, 390 ARG-915, 12, 290, 326, 384, 387-389 Argatroban therapy in HIT, 12, 290, 379-408, 473 as anticoagulant in HD, 473-474 argatroban-915, 387-389 efficacy, 388 safety, 389 argatroban-treated patients with historical controls in, 387 assessments, 386

[Argatroban therapy in HIT] cardiovascular surgery or ECMO,

398-399 characteristics, 293 chemical description, 379-380 chemical structure, 380 clinical pharmacology, 380-383

distribution, metabolism, excretion, 380-381 mechanism of action, 380 clinical use of, 384 distinguishing features, 383

lack of cross-reactivity with HIT

antibody, 383 lack of effect on clot strength, 383 dosing and monitoring, practical aspects of, 391-394 dosing and dosage adjustments,

391-393 duration of therapy, 391 warfarin anticoagulation, conversion to, 393-394 drug-drug interactions, 382 efficacy and safety of, 384 efficacy, 386

geriatric or pediatric patients,

399-400 hemodialysis, 397-398 hypercoagulability states, 399

in intraoperative anticoagulation management, 492-494 patients with a history of HIT requiring acute anticoagulation, 390 in pediatric HIT, 510 percutaneous coronary intervention, 394-397. See also separate entry peripheral intervention, 397 pharmacokinetic-

pharmacodynamic relationship, 381 pregnant or nursing women, 399 reversal of, 383-384 safety, 387

special populations, 382 stroke, 398 study objectives, 385 study population, 385

[Argatroban therapy in HIT]

thrombin and, interaction between, 381

treatment, 386 Arixtra. See Fondaparinux (Arixtra®) Arterial thrombosis in HIT, 44-45

angiographic appearance, 45 Aspirin, 303, 466 Atherosclerotic tissue invested with PF4, 215 Autoimmune disorder, HIT as an, 9, 28-30, 132, 156-157

Bemiparin sodium (Hibor®), 174 Bivalirudin, 13, 409-439 administration, 416-418 adverse effects, 419 antibivalirudin antibodies, 429-430 for cardiac surgery in HIT, 429,

491-493 chemistry, 410 clearance of, 412 clinical use of, 419-426

in cardiac patients, major clinical studies using, 422 deep vein thrombosis, treatment of, 419-420 on-pump (CPB) cardiac surgery,

425, 491-493 OPCAB surgery, 424-425, 491-493 percutaneous transluminal angioplasty, 424 potential uses, 425-426 pregnancy and nursing mothers, 425

unstable angina and acute MI, 423-424 cost analysis with, 430 dosage, 415-416 drugs incompatible with, 418 for HIT treatment, 409-439

theoretical advantages of, 428 in intraoperative anticoagulation management, 491-492 treatment protocol for, 493 monitoring, 418-419 for PCI in HIT, 428-429 pharmacodynamics, 413-415

[Bivalirudin] pharmacokinetics, 411-413 in patients with renal impairment, 413 pharmacology, 410-411 reversal, 419 structure of, 411 Bone marrow and solid organ transplantation HIT in, 51-52 Bovine versus porcine origin, UFH of, 70, 74

Carbohydrate-based heparin alternatives danaparoid, 176-177 development of, 176-179 fondaparinux, 177 oligosaccharides, specifically designed, 178 pentasaccharides, 177-178 structural requirements of, 176 Cardiac or vascular surgery, 299-300, 328-329, 398-399, 409-410, 424-425, 429-430, 487-502 HIT following, 92-98, 505 management of patient following disappearance of HIT

antibodies, 300, 495-497 with acute or recent HIT, 299, 488-495

Cardiopulmonary bypass (CPB). See Cardiac or vascular surgery

Carmeda BioActive Surface (CBAS), 83

Caveats for HIT treatment, 304-306 ancrod, 305 LMWH, 304

platelet transfusions, 305 vena cava filters, 306 vitamin K antagonists, 304-305 Cerebral venous (dural sinus)

thrombosis, 22, 37, 42, 50, 51, 269, 504 Certoparin sodium

Children, HIT in, 503-517. See also Pediatric HIT cardiac interventions, 511-512 clinical complications, 504 frequency, 503-506

pediatric intensive care unit patients, 503-505 lepirudin in, 368-369 and neonates, HIT in, 51 pathophysiology, 503 prevention, 512 treatment, 301 Chlorpromazine hydrochloride, 418 Circuit thrombosis, extracorporeal, 45 Citrate-anticoagulated blood, activation assays using, 238-240 Citrated platelet-rich plasma (c-PRP) assays, 235 disadvantages, 239 HIT antibodies testing using, 239 platelets in, 229 Classic coumarin-induced skin necrosis (CISN), 40, 47 Clexane®, Lovenox®, 174. See also

Enoxaparin Clinical picture of HIT, 21-66 complications, 45-49. See also Complications of HIT definition, 247-249 thrombocytopenia, 21-32. See also separate entry thrombosis, 32-45. See also separate entry

Clinician's perspectives on HIT myths, 521-525 paradoxes, 520-521 realities, 525 Clivarin®, 174. See also Enoxaparin Clopidogrel, 191, 303, 414 Complications of HIT, 45-49. See also Venous limb gangrene; Warfarin-induced venous limb gangrene cardiac and neurological complications, 50 classic coumarin-induced skin necrosis (CISN), 47 heparin resistance, 49 histopathology, 45-46

[Complications of HIT] intravenous heparin bolus, ASRs following, 48-49 management, 46-47 skin lesions, 45-47. See also separate entry

Congenital hypercoagulability

HIT-associated thrombosis and, 44 odds ratios for thrombosis, 35 Continuous renal replacement therapy (CRRT), 321, 323, 329, 330 Continuous venovenous hemofiltration (CVVH), 348, 415, 428. See also Hemodialysis in HIT; Hemofiltration Coumarin coumarin-induced necrosis, 22, 38-42, 47, 263-264, 284, 296-297, 302, 304-305, 352, 454, 510. See also Venous limb gangrene in pediatric HIT, 510-511 vitamin K antagonist (coumarin) therapy, 41, 47-48, 296-298, 304-305 Critically ill patients, HIT frequency in, 78-81 Cryptic alloantigen(s) in HIT, 68,

68, 84, 132, 167, 228, 241, 243, Cutaneous type IV hypersensitivity reactions, 48 CXC chemokines other than PF4,131, 155

preexisting antibodies role in, 139

Dabigatran etixilate, 455 Dalteparin sodium (Fragmin®), 174, 333 Danaparoid (Orgaran®), 9,176-177, 290, 467 adverse effects, 336 availability of, 336 characteristics of, 291, 467-468 clinical use of, 321-336

in children and pregnant women, 330-331

in disorders other than HIT, 321

[Danaparoid (Orgaran®) clinical use of]

dosing schedules in HIT patients, 323

efficacy and safety outcomes of

HIT patients, 325-326 hemodialysis, 329 hemofiltration, 329 in patients with HIT, 321-331 intensive care use, 329 laboratory monitoring, 331-332

oral anticoagulants overlapping with, 327 in venous and arterial thromboembolism treatment, 322

cross-reactivity with HIT

antibodies, 85, 98, 99, 123, 177, 231, 238, 253-254, 268, 291, 293-294, 321, 332-336, 468, 509 for HIT treatment, 319-343 pharmacology, 319-320 pharmacokinetics, 320-321 chemistry, 319 in pediatric HIT, 509 Deep vein thrombosis (DVT), 30, 321 prevention of, 420-421 treatment of, 419-420 Delayed onset of HIT, 7, 9, 29-30, 131,

152, 171, 238, 522 Dermatan sulfate, 475. See also

Danaparoid (Orgaran®) Desmopressin, 352, 419 Dextran, 303. See also Antiplatelet agents

Diabetic ketoacidosis (DKA), 262, 266, 268

Diazepam, 418

Dipyridamole, 303

Direct thrombin inhibitors (DTIs),

289-293. See also Argatroban therapy in HIT; Lepirudin for HIT treatment; Bivalirudin. characteristics, 293 dosing, 292-293 oral DTIs, 455-456 Disaccharide unit of heparin, 168

Disseminated intravascular coagulation (DIC), 4, 6, 22, 29, 42, 48, 120, 302, 305, 350, 399, 468

acquired anticoagulant deficiency and, 42-44 clinical manifestations of, 43-44 danaparoid use for, 321, 335 pseudo-HIT, 261-266, 271-272, 274-275 Drug monitoring program, postmarketing, 361-362 efficacy outcomes, 361 safety outcomes, 362 Drug-induced immune thrombocytopenic purpura (DITP), 30-31 Duffy antigen/receptor for chemokines (DARC), 214

Ecarin clotting time (ECT), 292, 293, 347, 348-351, 367, 368, 418, 469, 471, 472, 474, 489-491 whole blood ECT, 489 Endocarditis, infective, 42, 262, 272, 273

Endothelial leukocyte adhesion molecule (ELAM), 210 Endothelium/endothelial cells (ECs), 290-225

anti-EC antibodies in HIT, 216-217 in hemostasis, 210-211 immune EC injury, 216 PF4 and, 211-216 Enoxaparin sodium (Clexane®,

Lovenox®), 174, 231, 424, 442, 445-448, 450 frequency of immunization or HIT

with, 75, 77-79, 97, 99,177 U.S. approvals, 14 use in laboratory testing for HIT antibodies, 231, 333, 451 Enzyme immunoassay (EIA), 229. See also Fluid-phase immunoassay anti-PF4/polyvinylsulfonate EIA from GTI, 241-242

[Enzyme immunoassay (EIA)] anti-PF4/heparin EIA from Stago, 240-241

appropriate diagnostic cutoff for EIA, 36, 250-253, 504, 507, 508, 523 EIA for heparin-dependent antibodies, 140 repeat testing, 253, 497 Extracorporeal membrane oxygenation (ECMO), 83, 398-400, 504, 510

Factor Xa, indirect inhibitors of. See

Fondaparinux (Arixtra®) Factor Xa, direct inhibitors of,

453-454 Fcg receptors. See Platelet and leukocyte Fcg receptors (FcgR) in HIT Flow cytometry, 191, 229, 230, 233,

238, 240 Fluid-phase immunoassay, 229, 242-243, 254 danaparoid cross-reactivity and, 293, 332-334, 451 Fluxum®, 174

Fondaparinux (Arixtra®), 14, 98-99, 177, 475-476 avoidance of HIT, 98-100, 524-525 chemical structure, 177 clinical use of, 98, 296, 446-453 cross-reactivity (negligible) of, 48,

100,171,177,254,448,450,451 immunization induced by, 14, 50,

indirect factor Xa inhibitor, 443-445 adverse effects, 445 chemistry, 443 dosage and administration,

444-445 history, 443 monitoring, 445 pharmacology, 444 reversal, 445 laboratory studies of, 448-451 observational studies, 451-452

[Fondaparinux (Arixtra®)] pediatric HIT, use in, 511 pharmacology, 453-454 pregnancy, use in, 50, 300-301, 444 prevention of venous thrombosis in other clinical settings, 446 prevention of VTE after orthopedic surgery, 446 prospective evaluation, 452-453

rationale, 448 treatment of ACS, 447-448 treatment of HIT, 294, 296, 442, 448-453 previous HIT, use in, 28 pros and cons, 294 treatment of VTE, 446-447 U.S. approvals, 14, 446-447 Fragmin®, 174, 333 Fraxiparin®, 174 Frequency of HIT, 67-117 in critically ill patients, 78-79, 80-81 during pregnancy, 79 early-versus late-onset thrombocytopenia, 68-69 immune HIT, 69-86. See also separate entry incidental UFH flushes role in, 79-83

in medical patients and normal volunteers, 74 treated with LMWH, 75-76 treated with porcine mucosal UFH, 74-75 risk factor interactions, 79 in surgical patients receiving LMWH compared with

UFH prophylaxis, 76-78 treated with porcine mucosal UFH, 76 of thrombosis complicating HIT, 86-91

variable frequency among prospective studies, 69 variable frequency, 100-102

Gel centrifugation technology,

243-245 Gender, HIT and, 79

b-1, 3-gIucan sulfates (GluS) HIT-associated antibodies cross-reaction with, 175-176

Glycoprotein IIb/IIIa antagonist-

induced thrombocytopenia, 273-274

GIycosaminogIycans (GAGs), 121, 132-133, 150-153, 159-161, 167,171-173,176,179, 211-213, 216, 319 Graft thrombosis in HIT, 45

Haemophilus influenzae infections, i97 Hemodialysis in HIT, 329, 352, 368, 463-485 in argatroban therapy, 397-398 clinical presentation, 464-465 heparin anticoagulation, resumption of, 476 heparin treatment, discontinuation,

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