A
Abortion, spontaneous, 187, 189, 271. See also Embryo loss;
Fetal loss; Pregnancy loss chromosomal abnormalities-
related, 189, 368 definition of, 186 lupus anticoagulant in, 5 recurrent, 200–201, 202–203 aCL. See Anticardiolipin
antibodies Acquired immunodeficiency
syndrome (AIDS). See also Human immunodeficiency virus (HIV) infection platelet aggregation
impairment in, 577
“Acute cerebral distress syndrome,” 180–181 Addison’s disease, 5, 269
in children, 250 Adenoviruses, 539
Adhesion molecules, 360–361 in atherosclerosis, 506 in catastrophic APS, 180 deficiency of, 423 in thrombosis, 423, 424–425 Adrenal insufficiency, 359 Afro-Caribbean patients, Ig A
anticardiolipin antibody prevalence in, 262–267 Alarcon-Segovia, Donato, 6 Alzheimer’s disease, 76 Amaurosis fugax, 58, 81 American College of
Rheumatology, 3–4 American Physicians’ Study, 13 Amnesia, transient global, 81 Anemia
hemolytic, 11, 31, 163, 249 autoimmune, 34–36,
159–160, 235 in children, 251–252 Coombs’ test for, 31, 34 effect on syphilis test results,
537
Evans’ syndrome and, 36 idiopathic, 35–36 systemic lupus
erythematosus- related, 34–35
thrombotic
microangiopathic, 37–38
sickle cell, 38 Angioendotheliomatosis,
357–358, 359 Angioplasty, percutaneous
transluminal coronary (PTCA), 50–51 Ankle-brachial index (ABI), 15 Annexin II, 2-glycoprotein
binding with, 421, 427, 466 Annexin A4, antibodies against,
458
Annexin V, 445, 450–460 antibodies against. See Anti-
annexin V antibodies anticoagulant effects of,
450–451, 458 antiphospholipid antibody-
mediated targeting of, 453–457
in apoptosis, 499 in pregnancy, 381, 382
in placental pathology, 185, 373, 451–452 in vascular endothelium, 452 Annexin 11, antibodies against,
458
Anti-annexin V antibodies, 162 in placental pathology,
451–452, 453–455 in pregnancy loss, 337–338,
457–458
Anti-2-glycoprotein I antibodies, 575
in atherosclerosis, 510, 512 in children, 246
diagnostic applications of, 162–163
in endothelial cell activation, 425, 426–427 in fibrinolysis, 318 in hearing loss, 145–146 in infections, 539–540 in infertility, 202–203, 204, 205,
208 monoclonal, 38
neutralization of, 490 in multiple sclerosis, 78, 79 in normal populations, 24
phospholipid binding ability of, 299–300
in pregnancy loss
experimental (animal) models of, 380–382
in recurrent fetal loss, 26, 27 in primary antiphospholipid
syndrome, 163 production of, 388–389 specificity of, 161
species-specific, 336–337 in systemic lupus
erythematosus, 23, 25 in thrombocytopenia, 32 in thrombosis, 314–316, 443 tissue factor-inducing activity
of, 444
Anti-2-glycoprotein I antibody assays, 11–12, 288, 289, 336–337
Antibodies
binding sites of, 475–476 structure of, 475 Antibody specificity, in APS,
160–161
Anticardiolipin antibodies (aCL).
See also Immunoglobulin A anticardiolipin antibodies;
Immunoglobulin G anticardiolipin antibodies;
Immunoglobulin M anticardiolipin antibodies in children, 246
in cognitive dysfunction, 60–61, 74–75
definition of, 431 in end-stage renal disease,
108–109 ethnic differences in, 286 in idiopathic intracranial hypertension, 80 in infertility, 202, 204 in lupus anticoagulant, 12 in migraine headaches, 73 in multiple sclerosis, 78, 79 in myocardial infarction, 48–49,
59–60
in normal populations, 23, 24 children, 246
in psychosis, 76
Index
583
Anticardiolipin antibodies (aCL).
– cont.
in recurrent fetal/pregnancy loss, 26, 27, 167–168 in recurrent stroke, 552 in rheumatic fever, 247–248 in seizures, 72
specificity of, 161 in stroke, 26, 59–60 in syphilis, 538–539 in systemic lupus
erythematosus, 23, 25 in thrombosis, 12, 13, 15, 553 Anticardiolipin antibody (aCL) test, 279–294, 287, 295 anionic phospholipids in,
334–336 calibrators for, 282–284 false-positive results in, 280,
282 solid phase, 537
standardization of, 281–282 variations of, 284–285 Anticardiolipin syndrome, 3-4, 5.
See also Antiphospholipid syndrome (APS) Anticoagulation
annexin V-related, 450–451, 458
natural systems for, 431 Anticoagulation therapy, 554-555.
See also Coumadin anticoagulation therapy;
Heparin anticoagulation therapy; Warfarin anticoagulation therapy for catastrophic APS, 178–179 in children, 256
clinical trials of, 585
effect on valvular heart disease, 47, 48
hearing loss as indication for, 80
in heart valve replacement patients, 228, 229–230 as hemorrhage cause, 32 postpartum, 194–195 during pregnancy, 194, 304,
371, 372, 374, 559–560 for recurrent thrombosis
prevention, 366, 552–554
in renal transplant recipients, 109–111, 217, 218, 219–221, 222, 223–224 in vascular bypass graft
recipients, 231–232 Anti-endothelial cell protein C
receptor antibodies, 437–438, 439
Anti-erythrocyte antibodies, 35 Anti-idiotypic antibodies, 379,
380, 381
immunomodulatory effects of, 385
Antimitochondrial antibodies, 32
Antinuclear antibodies (ANA), 543
in elderly persons, 12 in infertility, 201, 204, 208 in primary APS, 17, 159–160 in sensorineural hearing loss,
144
Antiovarian antibodies, 201 Anti-phosphatidic acid antibody
assays, 334–335 Antiphosphatidylethanolamine
antibodies in infertility, 204, 208 in renal transplant recipients,
214, 217–218 Antiphosphatidylethanolamine
antibody assays, 336 Antiphosphatidylglycerol
antibody assays, 334–335 Antiphosphatidylinositol
antibody assays, 334–335 Antiphosphatidylserine
antibodies, in infertility, 204, 208
Antiphosphatidylserine antibody assays, 334–335 Antiphospholipid antibodies
(aPL), 160-161. See also Anticardiolipin antibodies (aCL); Lupus
anticoagulant (LA) antigenic targets of, 296–297,
573
apoptosis-induced, 496–504 in atherosclerosis, 426–427
2-glycoprotein I-dependent, 538, 539–540
2-glycoprotein I-independent, 538
in cancer, 16 in children
clinical associations of, 247–254, 256–257 in healthy children, 245–247 cofactors of
2-glycoprotein, 5, 6 prothrombin, 5, 6 in Crohn’s disease, 16 in cytomegalovirus infection,
16
definition of, 431, 443 endothelial cell effects of,
419–430
cell activation mechanisms in, 425–427 pleiotropic effects in,
423–425 in end-stage renal disease,
108–109 genetics of, 525–528
HLA haplotype, 526–528 in hepatitis C, 16 in HIV infection, 16
in idiopathic thrombocytopenic purpura, 26
immunization response of, 247
in infection, 16, 537–542 differentiated from
autoimmune APS, 537–539 in infections, 247 in infertility, 204, 208 in Lyme disease, 16
monoclonal, sequence analysis of, 474–495
antigen-driven, 483–484, 491 computer modeling in, 476,
486–488
in contact regions, 484–485 experimental (animal)
models of, 477 expression systems in,
488–490
gene-of-origin identification in, 475–476, 480, 482–483 of heavy chain genes, 476,
482, 488–489 in hybridoma cells, 475 as hypermutations, 477, 483 of light chain genes, 476,
482–483, 488–489 of pathogenic vs. non-
pathogenic antibodies, 486 sequence/structure/function
relationships in, 488–490
somatic mutation analysis, 476–477, 483–484, 491 therapeutic implications of,
490
in multiple sclerosis, 77–79 in mycoplasma infection, 16 in myocardial infarction, 49–50,
121
platelet interactions of, 573–576 in pregnancy loss, 12, 13 prevalence of, 9, 12, 18 in primary pulmonary
hypertension, 122–124 prosthetic material-induced,
233–234
protein C effects of, 431–442 thrombin paradox and,
435–437
in seizures/seizure disorders, 71–72
in children, 248 in Sjögren’s syndrome, 10 specificity of, 161 in syphilis, 16
in systemic hypertension, 114, 115, 117
in systemic lupus erythematosus, 9, 10 in thrombosis, 3, 13, 300, 554
pathogenic mechanisms of, 301–303
prophylactic management of, 554–555
as surface-mediated phenomenon, 301–303
thrombin paradox of, 435–437
“two-hit hypothesis” of, 301, 302
transplacental passage of, 255–256
in valvular heart disease, 44, 45 as vascular damage cause, 360 in vasculitis, 16
Antiphospholipid Antibodies in Stroke Study (APASS), 12, 13, 47, 59, 64, 65, 167, 553, 579
Antiphospholipid antibody (aPL) assays, 333
antibodies detected with, 334 indications for, 10–11 Antiphospholipid Standardization
Laboratory, 283 Antiphospholipid syndrome
(APS)
antibody specificity in, 160–161 antiphospholipid antibody-
negative, 333–341 catastrophic, 17, 174–183, 584
calciphylaxis in, 350, 351 in children, 252
classification criteria for, 175 clinical presentation of,
176–178 definition of, 174
demographic characteristics of, 175
differentiated from heparin- induced
thrombocytopenia, 270–271
liver transplantation-related, 224–225, 226 myocardiopathy in, 121 organic brain syndrome in,
62
osteonecrosis in, 132 pathogenesis of, 179–181 patients’ thrombotic history
in, 175–176 precipitating factors in, 176 primary, 169
pulmonary embolism in, 121 recurrent, 178
systemic lupus
erythrematosus in, 175
thrombotic
microangiography in, 57
Toll-like receptors in, 426 treatment of, 178–179 vascular pathology of, 350,
351, 352 categories of, 159 in children
catastrophic APS, 252 primary APS, 254–255 classification criteria for, 22–23 clinical criteria for, 9–10,
268–273
clinical features of, 4–5, 9, 17–18, 19 definition of, 9–10 demographics of, 9 diagnosis of
criteria for, 9–10, 268–273 delayed, 9
during pregnancy, 559 differential diagnosis of,
268–275
differentiated from systemic lupus erythematosus, 3–4, 5
epidemiology of, 22–30 first description of, 158–159 future of research in, 583–586 infectious etiology of,
experimental (animal) models of, 388–389 mortality and morbidity
associated with, 14 neonatal. See also Children
cardiovascular pathology of, 353
non-aPL autoantibodies in, 333–341
pediatric. See Children primary, 3–4, 5, 158–173, 572
anti-2-glycoprotein I antibodies in, 163 antibody sensitivity and
specificity in, 162–163 arthritis in, 137
catastrophic, 169 in children, 254–255 classification criteria for,
163–164, 165 clinical presentation of,
164–169 differentiated from
secondary APS, 16–17 differentiated from systemic
lupus erythematosus, 16–17, 159–160 dystonia in, 82 eye disorders in, 150 familial, 526 fetal loss in, 560 gender differences in, 160 hearing loss in, 145–146 myocardial infarction in, 48 osteonecrosis in, 132,
133–135
positive Coomb’s test in, 34 prevalence of, 15–16 progression to systemic
lupus erythematosus, 169
renal pathology in, 102, 103–105, 108, 110, 111 skin ulcers in, 91
thrombocytopenia in, 168–169 thrombosis in, 165 166 treatment of, 169
valvular heart disease in, 43, 44
secondary, 572 cancer-related, 159 conditions associated with,
15–16 drug-related, 159 infection-related, 159 osteonecrosis in, 132 seronegative, 17
thrombosis in. See Thrombosis treatment of. See also
Anticoagulation therapy in children, 256–257 Antiplatelet antibodies, 33 Antiplatelet therapy, for stroke
prevention, 63 Antiprothrombin antibodies
(APT), 323–332, 361, 388 clinical significance of, 326–328 epitopes recognized by, 300 IgA isotype of, 328–329 immunological characteristics
of, 325–326 pathogenic role of, 328–329 specificity of, 161–162 in thrombocytopenia, 32 in thrombosis, 326–327, 328,
443
Antiprothrombin antibody (APT) assays, 337
Antisperm antibodies, 201–202 Antithrombin deficiency, 251 Antithrombin III deficiency, 15,
165
Antithyroid antibodies, 201 Aortic regurgitation, 44, 45 Aortic stenosis, 44 Aortic valve. See also Aortic
regurgitation; Aortic stenosis
APS-related pathology of, 353, 354
Aortic valve replacement, 228 APASS (Antiphospholipid
Antibodies in Stroke Study), 12, 13, 47, 59, 64, 65, 167, 553, 579 APhL®ELISA Kit, 288–289, 290 aPL. See Antiphospholipid
antibodies (aPL) Apolipoprotein A, 464, 466,
468–469 Apolipoprotein B, 507 Apolipoprotein E receptor 2,
302–303, 316 Apolipoprotein H. See2-
Glycoprotein I Apoptosis, 496–504
definition of, 497–498 in vivo, 499–502 pathways of, 498–499 trophoblastic, 452 Apoptotic cells
antiphospholipid antibodies- induced activation of, 501–502
clearance of, 499, 500–501 production of, 499–500
APS. See Antiphospholipid syndrome (APS) APSCORE registry, 63, 584–585 Arginine, in antibody somatic
mutations, 476
Arterial occlusion. See also specific arteries
catastrophic APS-related, 176 Arteriosclerosis, anticardiolipin antibodies-related, 166 Arthralgias, APS-related, 137 Arthritis, 137
juvenile idiopathic, 248–249 rheumatoid arthritis
effect on syphilis test results, 537
hearing loss associated with, 142–143
oxidized LDL/ 2- glycoprotein I complexes in, 516, 517–518
Asparagine, in antibody somatic mutations, 476 Aspirin anticoagulation therapy
effect on in vitro fertilization outcomes, 206, 207, 208, 209
for ocular vaso-occlusive disease, 155 during pregnancy, 192, 194,
383, 555 as recurrent thrombosis
prophylaxis, 552, 553, 554
as stroke prophylaxis, 63, 64 as thrombocytopenia
treatment, 252 as thrombosis prophylaxis, 554
during pregnancy, 555, 559, 565
in recurrent thrombosis, 552, 553, 554
for valvular heart disease, 47, 48 in vascular bypass graft
recipients, 232 Atheroma, 3
Atherosclerosis
accelerated, 15, 505–524 anti-2-glycoprotein I
antibodies in, 316, 394 antiphospholipid antibodies
in, 116, 426–427 in experimental (animal)
models, 390, 394 as hypertension cause, 116 management of, 270 oxidized LDL/ 2-
glycoprotein I complexes in, 505–506, 509–513 oxidized LDL in, 505,
513–514 in systemic lupus
erythematosus, 48 adhesion molecules in, 506 pathogenesis of, 506
in renal transplant recipients, 216
Attention deficit/hyperactivity disorder, 76
Autoimmune disorders accelerated atherosclerosis in,
514–515, 516 as antiphospholipid antibody
test indication, 10 APS-related, 3
hearing loss in, 80
oxidized LDL/ 2-glycoprotein I complexes in, 516–519 Autoimmunity, to self- 2-
glycoprotein I, 540 Azathioprine, 227, 555, 564 B
Bacterial peptides, effect on antiphospholipid antibody-mediated thrombosis, 542 B cell tolerogen, 2-glycoprotein
I-domain I-specific, 490 Behçet’s disease, 5, 269–270 Biological false-positive (BFP-
STS), 536–537 Blood pressure. See also
Hypertension livedo reticularis-related
fluctuation in, 6 Boffa, Marie Claire, 6 Bone marrow transplantation,
234–239, 383 graft-versus-host disease
associated with, 236–237 Bone morphogenic protein
receptor type 2 (BMPR2), 120
Bos, K., 174
Brain. See also Central nervous system disorders effects of antiphospholipid
antibodies on, 70–71 small high-density lesions of,
82–83 Bromocriptine, 385
Budd-Chiari syndrome, 250, 269 liver transplantation-related,
224
primary APS-related, 166, 175–176
Bypass grafts. See Vascular bypass grafts
C
CADASIL, 270
Calciphylaxis, 350, 351, 352–353 Cancer, antiphospholipid
antibodies in, 10, 16 in children, 247
Carboxypeptidase B, 433, 470 Cardiac bypass grafts, 231–233 Cardiomyopathy, 51–52
livedo reticularis associated with, 51
Cardiovascular disorders, APS- related, 43–54, 350, 352–354
cardiomyopathy, 51–52 catastrophic APS-related, 177 coronary artery disease (CAD),
48–51, 353 angioplasty occlusion
restenosis, 50–51 coronary artery bypass
restenosis, 50–51 myocardial infarction,
48–50 unstable angina, 50 intracardiac thrombus, 51 valvular heart disease, 5, 11, 22,
23, 43–48, 165–166 anti-2-glycoprotein I
antibody-related, 390 clinical manifestations of,
45–47
echocardiographic findings in, 43–44, 45 experimental (animal)
models of, 390 pathogenesis of, 44–45 primary APS-related, 166 systemic lupus
erythematosus- related, 56 treatment of, 47–48 Catastrophic antiphospholipid
syndrome (APS). See Antiphospholipid syndrome (APS), catastrophic C5b-9, 409, 413–414 C4b binding protein, 433
antibodies against, 337 CD9, 573
CD36, 414 CD40, 506 CD59, 401-402, 405 CD62, 168-169 CD62p, 408, 574 CD63, 168–169, 408, 574 Central nervous system disorders,
APS-related, 55–69, 70–87 aPL in, 55
catastrophic APS-related, 176–177, 178 cerebral ischemia, 55, 56–60 cerebral venous sinus
thrombosis, 60 in children, 248, 253 cognitive dysfunction, 60–61,
62, 74–75 in primary APS, 60–61 in secondary APS, 61 dementia, 61–62
CADASIL-related, 270 multi-infarct, 74, 75–76 Sneddon’s syndrome-related,
61–62 vascular, 60
experimental (animal) models of, 389–390
neuroimaging studies of, 62–63 primary APS-related, 166–167 Cerebrovascular accidents. See
also Stroke; Transient ischemic attacks (TIAs) left ventricular assist systems-
related, 228, 230 migraine headaches associated
with, 73
Cerebrovascular pathology, of antiphospholipid syndrome, 357–359 C4 binding protein, 439 C4 deficiency, 528 Chilblains, 273 Children
anti-2-glycoprotein I antibodies in, 246 anticardiolipin antibodies in,
246
antiphospholipid antibodies in clinical associations of,
247–254, 256–257 in healthy children, 245–247 APS in
catastrophic APS, 252 primary APS, 254–255 thrombocytopenia associated
with, 32 treatment of, 255–256 attention deficit/hyperactivity
disorder in, 76 Evans’ syndrome in, 36 idiopathic thrombocytopenic
purpura in, 34 immunoglobulin G in, 246, 247 immunoglobulin M in, 246,
247
liver transplantation in, 225 lupus anticoagulant in, 246 migraine headaches in, 73 Chlorpromazine,
antiphospholipid antibody-inducing activity of, 16, 543
Cholesterol, oxidation of, 507 Chorea, 11, 77, 249
in children, 252
primary APS-related, 166–167 Chromosomal abnormalities, as
spontaneous abortion cause, 189, 368 Ciprofloxacin, as fetal loss
prophylaxis, 385 Coagulation. See also
Anticoagulation disseminated intravacular
(DIC), 37, 38, 179 Coagulation abnormalities, placental, 370–371 Coagulation factors. See also
specific coagulation factors
in apoptosis, 499 Cobalamin deficiency, 272 Cogan’s syndrome, hearing loss
in, 142–143, 146
Cognitive dysfunction, APS- related, 60–61, 62, 74–75 in primary APS, 60–61 in secondary APS, 61 Colaco, Bernie, 496 Cold agglutinins, 35
Collagen, platelet deposition on, 302–303
College of American Pathologists, 281–282
Complement, 399–405 activation of, 400–401
in pregnancy loss, 373–374, 402–403, 405 regulation of, 401–402 in thrombosis, 403–405 in antiphospholipid antibody-
platelet binding, 413–414 C5b-9, 409, 413–414 C4b binding protein, 433
antibodies against, 337 in pregnancy loss, 185, 373–374,
402–403, 405 Complementary determining
regions (CDRs), 475, 476–477
in experimental (animal) models, 477
somatic mutations of, 476–477, 483–485
Complement factor H, antibodies against, 337–338 Complement inhibitors,
401–402
Computer models, of monoclonal antibody sequence analysis, 476, 486–488 Congestive heart failure,
catastrophic APS-related, 177
Connective tissue diseases, 159 as indication for
antiphospholipid antibody testing, 10–11 mixed, 122, 123
pulmonary hypertension in, 119, 122, 125 Contraceptives. See Oral
contraceptives Coombs’ test, 31, 34 Coronary artery bypass grafts,
50–51, 231–232 repeat, 232 restenosis of, 50–51 Coronary artery disease (CAD),
48–51, 353 angioplasty occlusion
restenosis in, 50–51 coronary artery bypass
restenosis in, 50–51 myocardial infarction, 48–50
anticardiolipin antibodies in, 59–60, 166
antiphospholipid antibodies in, 23, 121
in children, 250, 251
antiprothrombin antibodies in, 163, 327 APS-related, 58 catastrophic APS-related,
176, 177 as indication for
antiphospholipid testing, 11 neonatal, 353, 354 systemic lupus
erythematosus- related, 48, 58 unstable angina, 50 Corticosteroids
neuropsychiatric effects of, 76 as osteonecrosis risk factor,
132, 133 as thrombocytopenia
treatment, 576, 577 Coumadin anticoagulation
therapy, in renal transplant recipients, 219, 220
C-reactive protein, 45, 47, 116, 520
CREST syndrome, 122 Crohn’s disease, 16 Cryoglobulinemia, 92, 539 Cyclophosphamide
as catastrophic APS treatment, 179
as pediatric APS treatment, 253, 256
Cyclosporine, 17, 215, 217, 227 Cystathionine- -synthase
deficiency, 272 Cytokines, in catastrophic APS,
179–180
Cytomegalovirus infections, 16, 539
D
Decay accelerating factor (DAF), 401
Deep venous thrombosis. See Thrombosis, deep venous Dementia
CADASIL-related, 270 multi-infarct, 74, 75–76 Sneddon’s syndrome-related,
61–62 vascular, 60 Demographics, of
antiphospholipid syndrome, 9. See also Ethnic groups Demyelinating syndrome, 11 Dermatitis, atopic, 248 Diabetes mellitus
immunoglobulin G anticardiolipin antibodies in, 248 livedoid vasculitis associated
with, 92
oxidized LDL/ 2-glycoprotein I complexes in, 520 as thrombosis risk factor, 270
Dilute Russell Viper Venom Time (dRVVT), 305, 306, 334 Disseminated intravascular
coagulation (DIC), 37, 38, 179
Drugs. See also names of specific drugs
antiphospholipid antibody- inducing activity of, 542–543, 544 DVT. See Thrombosis, deep
venous Dystonia, 81–82 E
Ear, in APS. See Hearing loss, sensorineural Echocardiographic findings, in
valvular heart disease, 43–44, 45
Eclampsia, 271
Elderly persons, antiphospholipid antibody prevalence in, 12 ELISA. See Enzyme-linked
immunosorbent assays (ELISA)
Embolism cardiac, 56 pulmonary, 354, 572
in lung transplant recipients, 230–231
during pregnancy, 271 as pulmonary hypertension
cause, 122 systemic lupus
erythematosus- related, 58 Embryo, development of, 86 Embryo loss, 187–188
antiphospholipid antibodies- related, 190 Endocarditis
infective, 45, 46–47
oxidized LDL/ 2-glycoprotein I complexes in, 520 Libman-Sacks, 44, 165–166,
390
Endothelial cell protein C receptor (EPCR), 433 antibodies against, 437–438 Endothelial cells
antibodies against, 360–361 in antiphospholipid syndrome,
2-glycoprotein production in,359 297
in catastrophic APS, 179–181 effects of antiphospholipid
antibodies on, 419–427 cell activation mechanisms
in, 425–427 pleiotropic effects, 423–425 effects of antiprothrombin
antibodies on, 328 in fibrinolysis, 465 human umbilical cord vein,
420, 421, 423
interaction with
antiphospholipid antibodies, 419–430
2-glycoprotein I, 420–423 phenotypes of, 360–361 plasminogen inactivator-1
secreted by, 468 prostacyclin release in, 419 in the “thrombin paradox,” 436 Endothelins, 360–361
in renal artery stenosis, 115 Enoxaparin, 222
Enzyme-linked immunosorbent assays (ELISA) for anti-2-glycoprotein I
antibodies, 313, 336–337 for anticardiolipin antibodies,
279, 282, 283, 285, 334–335, 537
for antiprothombin antibodies, 337
APhL®ELISA Kit, 288–289, 290
for oxidized LDL/ 2- glycoprotein I complexes, 512–513, 520 for phospholipids, 286–287 Epidermal growth factor-like
domains, 463 Epilepsy, 5, 72. See also
Seizures/seizure disorders in children, 248
Epitope mapping, of 2- glycoprotein I, 314 Epitopes
in anti-2-glycoprotein I antibody production, 388
of 2-glycoprotein I, 323, 528 fibrin-exposed, 465 neo-, 464–465
recognized by antiprothrombin antibodies, 300 Epstein-Barr virus infections, 537,
539
Erythema, palmo-plantar, 94 E-selectin, 420, 423, 424, 506 Ethnic groups, antiphospholipid
syndrome in
in Afro-Caribbean populations, 262–267
2-glycoprotein genetic polymorphisms in, 529 HLA (human leukocyte
antigen) and, 526 European Concerted Action on
Thrombophilia (ECAT), 304
European Dialysis and Transplant Assessment registry, 217 European Forum on
Antiphospholipid Antibodies, 174 European Lupus Study, 10, 13–14 European Phospholipid Project
Group, 48, 50, 58, 63, 72, 584–585
European Working Party on SLE, 58–59
Evans’ syndrome, 36, 235, 251–252 Experimental (animal) models,
379–389, 379–398 of atherosclerosis, 390, 394 of bone marrow
transplantation- associated APS, 238 of central nervous system
disorders, 389–390 of infectious etiology of APS,
388–389, 391
of pregnancy loss/reproductive failure, 185, 302, 380–386, 391–393 antiphospholipid antibodies
in, 203, 205
2-glycoprotein I deficiency in, 530
complement-mediated, 373–374, 402–403, 405 therapeutic interventions in,
383–386, 392–393 of thrombosis, 302, 328,
386–388, 391 therapeutic interventions in,
387–388
of valvular heart disease, 390 F
Fab fragments, 411–412 Fab2fragments, 302, 384 Factor II, 451
Factor V
activation of, 436 antibodies against, 162 Factor Va, 447, 451
inactivation of, 433–434, 438 Factor V Leiden, 15, 251, 531
during pregnancy, 271 Factor V Leiden mutation, protein
C resistance to, 60 Factor VIII
activation of, 436 inhibitors of, 304–306 Factor VIIIa, 316, 451 Factor X, 451
antibodies against, 162 Factor Xa, 316, 451, 563 Factor XII, 300
antibodies against, 337–338 Factor XII assays, 273 Factor XII deficiency, erroneous
diagnosis of, 273 Fas ligands, in apoptosis, 497, 498,
502
Fc fragments, 384, 411–412 Fc␥, gene polymorphisms of, 531 Fc␥ IIA receptors, 303, 411–413,
414
Fc␥ receptors, in atherosclerosis, 510, 512, 519
Fc receptors, 302–303 Femoral artery
in APS, 350, 352 occlusion of, 176
Femoral head, osteonecrosis of, 131, 134, 135–136 Fetal death
antiphospholipid antibodies- related, 190 common causes of, 188 recurrent, 187 Fetal loss, 366
catastrophic APS-related, 176 causes of, 188
evaluation of, 189 recurrent, 26, 27
systemic lupus erythematosus- related, 368, 369 Fetal surveillance, 193–194 Fetus, development of, 86 Fibrin
renal, 355, 357
as surface-anchoring structure, 464
Fibrin glue, antibodies to, 228 Fibrinogen, 270, 464 Fibrinolysis, 461–465
acceleration pathway of, 464 APS-related impairment of, 465 endothelial cell dysfunction
and, 465 vascular wall extracellular
proteolysis in, 461–462 Fibrinolytic therapy, 551 Fibrin thrombi, 349, 351, 360 Finger domains, 463–464 Fluvastatin, 446 Folate deficiency, 272 G
Gangrene cutaneous, 92–94 intestinal, 177 Gastrointestinal disorders,
catastrophic APS-related, 177
GDKV, 540
Genetic factors, in APS, 525–535 in 2-glycoprotein I deficiency,
529–530, 531
2-glycoprotein I-related, 528–520, 531 single nucleotide
polymorphisms (SNPs), 528–529 family studies of, 525–526 in systemic lupus
erythematosus, 526 Geographic variations, in APS,
262–267
Gharavi, Azzudin, 3–4, 6, 496 Glomerulonephritis, 105–106, 108,
539
Glomerulosclerosis, 105–106 Glycoprotein(s), of the
plasminogen activation system, 463–464
2-Glycoprotein I annexin II binding, 466 anti-2-glycoprotein I antibody
interactions, 313
antibodies against. See Anti-2- glycoprotein I antibodies
in anticardiolipin binding, 295, 296
in antiphospholipid antibodies- platelet interactions, 408, 410–411, 414 as antiphospholipid antibody
cofactor, 5, 6 apolipoprotein A interactions,
468–469 in apoptosis, 499 in atherosclerosis, 505–506 autoimmunity to, 540 cleavage of, 316–317 endothelial cell interactions of,
420–423 epitope mapping on, 314 epitopes of, 323
anticardiolipin-binding, 323 in fibrinolysis, 317
genetics of, 528–520, 531 single nucleotide
polymorphisms (SNPs), 528–529 in infection, 538–539 in lupus anticoagulant assays,
334
in nephropathy, 106–107 oral administration of, 383–384 oxidized LDL complexes with,
505–506, 509–513, 515 atherogenicity of, 519 in autoimmune diseases,
516–519
physiological functions of, 311, 313
plasma concentration of, 297 in plasminogen activation,
466–467 plasminogen-mediated
cleavage of, 466–467 in pregnancy, 566
in protein C dysfunction, 438 in protein C resistance, 434 protein S/C4Bp binding with, 439 in protein S resistance, 434 structure of, 296, 297, 311, 312,
466 in thrombosis, 424
2-Glycoprotein I-binding antibodies, sequence analysis of, 486, 491
2-Glycoprotein I deficiency, in pregnancy loss, 530
2-Glycoprotein I-dependent antiphospholipid antibodies, 538, 539–540
2-Glycoprotein I-dependent lupus anticoagulant, 299–300
2-Glycoprotein I dimers, recombinant, 30–2303
2-Glycoprotein I-independent antiphospholipid antibodies, 538
2-Glycoprotein I-related synthetic peptides, 384, 388
Glycoprotein Ib/IX, 33
autoantibodies against, 572, 573 Glycoprotein IIb/IIIa, 33
autoantibodies against, 572, 573 Glycoprotein IIIa, in
antiphospholipid antibody-platelet interactions, 414 Glycoprotein V, autoantibodies
against, 572, 573 Gonadotropin-releasing
hormone, 200
Graft-versus-host disease, 236–237 Granulocyte-macrophage colony-
stimulating factor (GM- CSF), 385
Greissman, S. G., 174 Guillain-Barré syndrome, 5, 81,
166–167 H
Haemophilia influenzae, 541–542 Hammersmith Hospital, 279–280,
496
Harris, Nigel, 4, 6, 174, 496 Headaches
APS-related, 72–74 migraine, 5, 11, 249
aPL as risk factor for, 73 CADASIL-related, 270 cerebral venous thrombosis-
related, 60 in children, 248 primary APS-related, 160,
166–167
systemic lupus erythematosus- related, 254
Hearing loss, sensorineural, 80, 142–148
APS-related, 144–146 in primary APS, 145–146 in secondary APS, 146 experimental (animal) models
of, 143
immunological profiles in, 144 Heart disease/failure. See also
Cardiovascular disorders;
Congestive heart failure left-sided
as pulmonary hypertension cause, 121 systemic lupus
erythematosus- related, 56 Heart-lung transplantation, 230 Heart transplantation, 226–230
thrombosis associated with, 239
Heart valve lesions. See Valvular heart disease
Heart valve replacement, 228–230 Heat shock proteins, 520 HELLP syndrome, 37, 176, 179
postpartum, 37
Hemocytopenias, 31–42 autoimmune
thrombocytopenia, 31–34
antiphospholipid antibodies in, 31, 33–34 antiplatelet antibodies in, 33 clinical features of, 32 primary APS-associated, 31,
32, 33
idiopathic thrombocytopenic purpura, 33–34 thrombotic and
microangiopathic hemocytopenia, 36–38 Hemodialysis access grafts,
233–236
Hemodialysis patients, renal transplantation in, 216, 217–218, 220
Hemolytic anemia. See Anemia, hemolytic
Hemolytic uremic syndrome (HUS), 37, 179 Hemorrhage
anticoagulation therapy- related, 552, 555, 556 subungual, 94–95, 97 thrombocytopenic, 32, 273 Hemostasis, mechanisms of, 431 Heparin anticoagulation therapy,
555
effect on in vitro fertilization outcomes, 206, 207, 208, 209
as fetal loss prophylaxis, 383 in heart valve replacement
patients, 228, 229 in liver transplant recipients,
224–225 as osteoporosis cause, 563 postpartum, 195
during pregnancy, 192, 193, 194, 271, 562–563, 565 in renal transplant recipients,
217, 219, 220–221 as skin lesion treatment, 98 as thrombocytopenia cause,
193
as thrombosis cause, 574–576 as thromobocytopenia cause,
563
as venous thrombosis treatment, 551 Heparin sulfate, 421 Heparin sulfate proteoglycan,
337–338
Hepatic artery, occlusion or thrombosis of in liver transplant recipients,
225–226 primary APS-related, 166 Hepatitis C
antiphospholipid antibodies in, 16, 537
as thrombosis cause, 539
2-glycoprotein I in, 539
in renal transplant recipients, 222–223
thrombocytopenia in, 38 HLA (human leukocyte antigen)
in APS, 526–527
lupus anticoagulant linkage of, 527
polymorphisms of, 527–528 Homocysteine, 15, 48, 520. See also Homocysteinuria;
Hyperhomocysteinemia Homocysteine MTHFR mutation
C677J, 271, 272 Homocysteinuria, s thrombosis
risk factor, 165 Honolulu Heart Program, 59 Hopkins Lupus Cohort Study, 23,
26, 28, 48, 133
HUCVEC (human umbilical cord vein endothelial cells), 420, 421, 423
Hughes, Graham, 3, 158, 496 Hughes syndrome. See also
Antiphospholipid syndrome (APS) history of, 3–8
Human chorionic gonadotropin (hCG), 200, 205, 372 Human herpesvirus 8, 120 Human immunodeficiency virus
(HIV) infection
antiphospholipid antibodies in, 16, 537
2-glycoprotein I in, 539 immunoglobulin G
anticardiolipin antibodies in, 131, 247 osteonecrosis associated with,
131–132
as pulmonary hypertension cause, 119
thrombocytopenia in, 38, 273 Human T lymphotropic virus-1
(HTLV-1), 539 Human umbilical cord vein
endothelial cells (HUCVEC), 420, 421, 423 HUS (hemolytic uremic
syndrome), 37, 179 Hybridomas, 475
Hydralazine, antiphospholipid- inducing activity of, 16 Hydroxychloroquine, 368–369,
374, 387, 554, 555 Hypercholesterolemia, 15, 506 Hypercoagulability
antiprothrombin antibodies in, 328
differential vascular effects of, 269
in hemodialysis access graft recipients, 233 in transplant recipients, 239
in renal transplant patients, 216, 220–221, 223 Hypereosinophilic syndrome,
269–270
Hyperhomocysteinemia as pregnancy loss risk factor,
272–273
as thrombosis risk factor, 270 Hyperlipidemia, as thrombosis
risk factor, 270 Hypertension
idiopathic intracranial, 80 portal, 121
pregnancy-related, 26. See also Eclampsia; Pre- eclampsia pulmonary, 119–128
antiphospholipid antibodies in, 122–124 APS-related, 120–125 in children, 250 chronic thromboembolic,
121–122 classification of, 119 definition of, 119 left-sided heart failure-
related, 121 in lung transplant recipients,
230
management of, 124–125 primary, 119, 122–124, 125 unexplained, 123, 124, 125 renovascular, 102, 114–116 systemic, 114–118
as thrombosis risk factor, 15, 270
thrombotic microangiography- related, 103–104, 105 Hypopituitarism, 269 Hypoprothrombinemia, 32 I
Immunizations, antiphospholipid antibody response to, 247 Immunoglobulin A anti-2-
glycoprotein I antibodies, as thrombosis cause, 314–315
Immunoglobulin A
anticardiolipin antibodies (IgA aCL), in APS, 22 in cognitive dysfunction, 61,
74–75
ethnic differences in, 286 Immunoglobulin A
anticardiolipin antibody assay, 285–286 Immunoglobulin G anti-2-
glycoprotein I antibodies, as thrombosis cause, 314–316
Immunoglobulin G
anticardiolipin antibodies (IgG aCL)
in Alzheimer’s disease, 76 as anticardiolipin test
calibrators, 282, 283 in children, 246, 247 in cognitive dysfunction, 61 cold-agglutinin activity of, 35 in diabetes mellitus, 248
in elderly persons, 12 in HIV infection, 131 in multiple sclerosis, 77 in normal populations, 24 prevalence of, 9 in recurrent myocardial
infarction, 49
in recurrent pregnancy loss, 26, 27, 189, 190–191 in systemic lupus
erythematosus, 47 in thrombosis, 554 in vascular heart disease, 47 Immunoglobulin G (IgG)
anticardiolipin antibody assays, 11
Immunoglobulin M
anticardiolipin antibodies (IgM aCL)
as anticardiolipin test calibrators, 282 in APS, 22
in children, 246, 247 in elderly persons, 12 in hemolytic anemia, 35 monoclonal sequence analysis
of, 478–479, 480 in normal populations, 24 prevalence of, 9 in recurrent myocardial
infarction, 49
in recurrent pregnancy loss, 26, 189, 190, 191, 560 Immunoglobulin M
anticardiolipin antibody assays, 11, 285 Immunoglobulin M (IgM) anti-
2-glycoprotein I antibody, in infertility, 203
Immunosuppressive therapy during pregnancy, 564 for thrombosis, 555 Infants, APS in, 255–256 Infarction
cerebral, 62
cortical meningeal, 358–359 placental, 372, 374 Infections, antiphospholipid
antibodies in, 16, 247, 537–542
Infertility
antiphospholipid antibodies- related, 199–211 definition of, 199 evaluation of, 199
Inflammatory bowel disease, 97 Crohn’s disease, 16 ulcerative colitis, hearing loss
associated with, 142–143
Interferon(s), in catastrophic APS, 179–180, 181
Interferon-␣, antiphospholipid antibody-inducing activity of, 16
Interferon-␥, 506
Interleukin-1, in catastrophic APS, 179–180, 181 Interleukin-1-receptor-activated
kinase (IRAIL), 425 Interleukin-3, 564
as fetal loss prophylaxis, 385 Interleukin-4, 506
Interleukin-6, in catastrophic APS, 179–180
International Antiphospholipid Symposium, 188–189, 583 International Congress on
Antiphospholipid Antibodies, 174 International normalized ratio
(INR), 552–553, 554, 555, 559
IntracelIular adhesion molecule (ICAM), 423
Intracytoplasmic sperm injection (ICSI), 200, 202 Intrauterine growth restriction
(IUGR), 168, 184, 185, 271, 366, 560, 561
Intravenous immunoglobulins (IVIG), 384, 387–388 In vitro fertilization,
antiphospholipid antibodies-related failure of, 199–211
Ischemia
cerebral, 55–69, 56–60 anticardiolipin antibodies-
related, 167 cerebrovascular, 357 renal cortical, 101, 107–108 Italian Registry of
Antiphospholipid Antibodies, 31, 59, 576, 577, 578
J
Jamaican neuropathy, 539 Jamaican patients, Ig A
anticardiolipin antibodies prevalence in, 262–267 Jejunum, vascular pathology of,
359, 360
Juvenile idiopathic arthritis, 248–249
K
Kaolin clotting time, 334 Kidney disease. See Renal disease Kininogens, antibodies against,
162 Koike, Takao, 6
Kringle domains, 297, 298, 300, 463, 464, 466–469 L
LA. See Lupus anticoagulant LDL. See Low-density lipoprotein
(LDL)
Left ventricular assist systems (LVAS), 227–228, 230 Legionnaire’s disease, 537
Leprosy, 537, 539 Leukoaraiosis, 556
Leukoencephalopathy, CADASIL- related, 270
Libman-Sacks endocarditis, 44, 165–166, 390
Linoleic acid, 507
Lipoprotein(a), 270, 462, 464, 467–469, 470 Livedo racemosa, 89
Livedo reticularis, 11, 88–90, 96, 249
cardiomyopathy-related, 51 cerebrovascular disorders-
related, 97 cerebrovascular lesions
associated with, 167 characteristics of, 348–349 in children, 252 coalescent, 352 histopathology of, 97 hypertension associated with,
116–117
pregnancy loss associated with, 116
primary APS-related, 160 with recurrent stroke. See
Sneddon’s syndrome relationship with
cerebrovascular accidents, 116 Liver, veno-occlusive disease of,
236 Liver transplantation
orthotopic, 224–226
thrombosis associated with, 239 LJP 1082, 490
Low-density lipoprotein (LDL) in atherosclerosis, 506 cross-reactivity with
antiphospholipid antibodies, 470 macrophage receptors for,
506–507, 513 oxidized, 507–509
in atherosclerosis, 505 complexed with 2-
glycoprotein I, 505–506, 509–513, 515, 516–519 interaction with
antiphospholipid antibodies, 185 Low-density lipoprotein
receptors, 421 Lung, in APS, 354, 355. See also
Embolism, pulmonary;
Pulmonary disorders Lung transplantation, 230–231 Lupus anticoagulant (LA), 158,
295–310
anticardiolipin antibodies in, 12 antigenic targets of, 305–306 in antiphospholipid syndrome,
2-glycoprotein I-dependent,163 299–300
