Abstract:
:Eradication of factor VIII (FVIII) specific neutralizing antibodies (also known as inhibitors) by the traditional method of immune tolerance induction (ITI) is costly and unsuccessful in one out of three patients. Furthermore, effective inhibitor prevention strategies are presently lacking. An overview is given in this narrative review of antidrug antibody prevention or eradication strategies that have been used in disorders beyond hemophilia A, with the aim of analyzing what we can learn from these strategies for hemophilia A. Prevention of antidrug antibody formation using rituximab, methotrexate, and intravenous immunoglobulins in patients with Pompe's disease seems effective but carries a high risk of adverse events. Based on studies in patients with rheumatoid arthritis and inflammatory bowel disease, it seems likely that treatment with methotrexate alone would also be able to prevent inhibitor formation in hemophilia A patients. Besides side effects, it is unclear whether immune tolerance to FVIII would persist after cessation of immunomodulatory therapy with methotrexate. A combination of cyclophosphamide and corticosteroids, used to treat antibody-mediated pure red cell aplasia, could be further investigated to eradicate inhibitors in hemophilia A patients who are refractory to ITI. In summary, insights gained from research on antidrug antibody formation in other diseases could be helpful in devising alternative treatment strategies for inhibitor development.
journal_name
Semin Thromb Hemostjournal_title
Seminars in thrombosis and hemostasisauthors
Hassan S,Fijnvandraat K,van der Bom JG,Gouw SCdoi
10.1055/s-0038-1666823subject
Has Abstractpub_date
2018-09-01 00:00:00pages
531-543issue
6eissn
0094-6176issn
1098-9064journal_volume
44pub_type
杂志文章,评审abstract::Thrombocytosis is frequently (10 to 57%) observed in cancer patients. Although the mechanisms underlying thrombocytosis are not yet fully elucidated, tumor-derived factors with thrombopoietin-like activity, growth factors, platelet-derived microparticles, and factors released from bone marrow endothelial cells as well...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-991540
更新日期:2007-10-01 00:00:00
abstract::The age of the thrombus is probably a very important determinant of the outcome of thrombolysis. The clinical potential for rapidly dissolving thrombi by thrombolytic therapy is considerable because restoration of the blood flow can rescue the jeopardized district served by the occluded vessel such as for myocardial i...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-1002747
更新日期:1989-10-01 00:00:00
abstract::With the strides being made in the European, Canadian, and American prospective studies of von Willebrand disease (VWD) genotype and phenotype, genetics is increasingly playing a key role in the classification, understanding, and management of VWD. It is anticipated that as gene sequencing becomes easier and more comm...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0028-1103362
更新日期:2008-09-01 00:00:00
abstract::Bleeding typically results as a consequence of derangements of primary hemostasis, secondary hemostasis, or both, and can be dramatically amplified by the presence of other predisposing conditions, especially inherited bleeding disorders. Life-threatening hemorrhages are, however, almost exclusively caused by penetrat...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0032-1328936
更新日期:2013-02-01 00:00:00
abstract::There have been no reports on acute pulmonary embolism (APE) after earthquakes. Our aim was to clarify the actual the occurrence of APE following the 2004 Mid Niigata Prefecture earthquake in Japan, and to assess the risk factors for APE after the event. We sent questionnaires to 122 hospitals in the Niigata Prefectur...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,多中心研究
doi:10.1055/s-2006-955468
更新日期:2006-11-01 00:00:00
abstract::CD34 (+) progenitor cells are a promising source of regeneration in atherosclerosis or ischemic heart disease. However, as recently published, CD34(+) progenitor cells have the potential to differentiate not only into endothelial cells but also into foam cells upon interaction with platelets. The mechanism of platelet...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0030-1251499
更新日期:2010-03-01 00:00:00
abstract::Three commercial prothrombin complex concentrates (PCC) were compared in vitro. Differences in the activities or contents, respectively, of the PCC factors FII, FVII, FIX, FX and the proteins C, S, and Z (antigen) in particular were found. Global tests of activated factors did not reveal marked differences between the...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-995838
更新日期:1998-01-01 00:00:00
abstract::Oral anticoagulants (OAs) are the drugs of choice for the prevention of recurrence and death in patients with venous thromboembolism (VTE). Oral anticoagulant treatment (OAT) aims to retard blood coagulation to obtain maximum protection against thromboembolic events with the lowest risk of bleeding. The intensity of O...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2006-955460
更新日期:2006-11-01 00:00:00
abstract::Each bone marrow megakaryocyte (MK) releases thousands of platelets into the circulation, and the underlying molecular and cellular mechanisms recently have received intense scrutiny. Genetic studies are beginning to clarify the mechanisms by which transcription factors help distinguish MK progenitors from other blood...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2004-833474
更新日期:2004-08-01 00:00:00
abstract::Analogues of L-arginine that are chemically modified at the terminal guanidino nitrogen group, such as Nomega-monomethy-L-arginine (L-NMMA), have been used for nitric oxide synthase inhibition. However, L-NMMA and other methylated L-arginine analogues are also endogenously formed. Among these, asymmetric dimethylargin...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2000-13210
更新日期:2000-01-01 00:00:00
abstract::Measurement of D-dimer (fibrin degradation product) is important for determining not only the activation of fibrinolysis but also the severity of a hypercoagulable state. However, fibrin degradation products are in variable, and the reactivity to cross-linked fibrin degradation products produced during fibrin degradat...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2000-9811
更新日期:2000-01-01 00:00:00
abstract::Protein C inhibitor (PCI) is a serine protease inhibitor and was originally identified as an inhibitor of activated protein C (APC). However, PCI is not specific for APC and also inhibits several proteases involved in coagulation, fibrinolysis, cancer, wound healing, and fertility. The biological function of PCI is un...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0031-1276583
更新日期:2011-06-01 00:00:00
abstract::While lupus anticoagulant (LA), anticardiolipin antibodies (aCL), anti-β2 glycoprotein I (anti-β2GPI) antibodies represent the best available and the most widely used tests in the investigation for antiphospholipid syndrome (APS), evidence gathered in recent years indicates that other antiphospholipid antibodies (aPL)...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0037-1601328
更新日期:2018-07-01 00:00:00
abstract::Non-Shiga toxin-associated hemolytic uremic syndrome (atypical HUS) is a rare form of thrombotic microangiopathy that associates hemolytic anemia, thrombocytopenia, and acute renal failure. The disease has been demonstrated to be linked with a complement alternative pathway dysregulation due to genetic defects but als...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0030-1262885
更新日期:2010-09-01 00:00:00
abstract::Molecular linkages between von Willebrand factor (VWF) and the alternative complement pathway (AP) have recently been discovered. Endothelial cell (EC)-anchored ultra-large (UL) VWF multimeric strings function as an activating surface for the AP. C3 (in active C3b form) binds to the EC-anchored ULVWF strings, and prom...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0034-1383547
更新日期:2014-07-01 00:00:00
abstract:UNLABELLED:We present 25-year experience with inhibitors in previously untreated patients (PUPs) with severe hemophilia A in Slovakia, where safe factor VIII (FVIII) concentrates have been used since 1990. A prospective study focused on inhibitor incidence in PUPs was established in 1997. Out of a total 61 PUPs born be...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,多中心研究
doi:10.1055/s-0036-1581107
更新日期:2016-07-01 00:00:00
abstract::Clinical and laboratory data of children with von Willebrand disease (VWD) types have been derived from retrospective studies and small case series. This article reports on the clinical and laboratory data of a large pediatric cohort in one single Argentinian center. The biological and clinical responses to desmopress...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0031-1281043
更新日期:2011-07-01 00:00:00
abstract::Current evidence indicates that prolonged air travel predisposes to venous thrombosis and pulmonary embolism. An effect is seen once travel duration exceeds 6 to 9 hours and becomes obvious in long-haul passengers traveling for 12 or more hours. A recent records linkage study found that increase in thrombosis rate amo...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2005-863810
更新日期:2005-02-01 00:00:00
abstract::Hip replacement surgery carries a high risk of thromboembolic complications, and pharmacological prophylaxis is routinely adopted in clinical practice. Meta-analyses have indicated that low molecular weight heparins (LMWHs) are clinically superior to conventional prophylaxis with unfractionated heparin. These analyses...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-01-01 00:00:00
abstract::Venous thromboembolism is a common complication in patients with acute thrombotic stroke. Estimates of the frequency of deep vein thrombosis (DVT) in untreated patients range from 20 to 75%. This wide range reported depends on the methods used to detect DVT and, importantly, on the degree of lower limb paralysis. Most...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-996084
更新日期:1997-01-01 00:00:00
abstract::Antithrombin activity should probably be determined in persons with early onset of recurrent thrombosis, especially if a family history is present. The initial screening test should be a heparin cofactor assay optimized to reduce the contribution of heparin cofactor II. If the heparin cofactor assay is low, an antigen...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-1002664
更新日期:1990-04-01 00:00:00
abstract::A prospective randomized double-blind trial was performed comparing conventional low-dose heparin with a LMWH fragment (Kabi 2165, Fragmin) for thromboprophylaxis in elective general abdominal surgical patients. The first dose of the fragment was given in the evening before surgery, and thereafter every evening. There...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1990-10-01 00:00:00
abstract::Although the current therapeutic armamentarium of venous thrombosis encompasses the use of vitamin K antagonists, heparins, and direct oral anticoagulants, these drugs have several important drawbacks. Antisense oligonucleotides are relatively short single-stranded nucleic acid sequences, which hybridize with a target...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0035-1546466
更新日期:2015-03-01 00:00:00
abstract::Factor (F) VIII is a large gene located near the terminus of the long arm of the X chromosome. It contains 26 exons that code for a signal peptide and a 2332 amino acid polypeptide with three different types of domains, namely A1-A2-B-A3-C1-C2. The A domains are homologous with each other and those of ceruloplasmin; s...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2003-37935
更新日期:2003-02-01 00:00:00
abstract::Immunoblotting techniques for the qualitative and quantitative analysis of FXII, PK, and HMWK in whole plasma are presented. Sensitive, specific, and quantitative immunodetection of FXII and PK can be achieved by developing the blots with polyclonal antiserum followed by radiolabeled FXII or PK, respectively. This app...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-1003480
更新日期:1987-01-01 00:00:00
abstract::The catastrophic variant of the antiphospholipid syndrome (APS) is a condition characterized by multiple vascular occlusive events, usually affecting small vessels and evolving over a short period of time, together with laboratory confirmation of the presence of antiphospholipid antibodies. The pathogenesis of catastr...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0028-1082274
更新日期:2008-04-01 00:00:00
abstract::Statins are approved by the Food and Drug Administration (FDA) for the treatment of hypercholesterolemia and have shown remarkable activity in preventing cardiovascular morbidity and mortality. The versatility of statins is increasingly being appreciated, however, and lowering cholesterol is only one attribute among m...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2003-40964
更新日期:2003-06-01 00:00:00
abstract::Despite long-standing knowledge about the relationship between thrombosis and atherosclerosis, the specific role of thrombin in modulating atherosclerosis and the response to vascular injury is not well understood. Thrombin receptor stimulation in vitro signals many cellular events that are associated with the respons...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-999001
更新日期:1996-01-01 00:00:00
abstract::Total fibrinolytic activity in the vasculature is finely tuned by the balance between tissue plasminogen activator and plasminogen activator inhibitor type 1 (PAI-1). Although PAI-1 targets plasminogen activators, it also reacts with other serine proteases such as thrombin and factor Xa. The latter was shown to intera...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2000-9801
更新日期:2000-01-01 00:00:00
abstract::Platelet aggregometry has been the reference method employed to detect, diagnose, and monitor qualitative platelet disorders since the early 1960s. Lumiaggregometry and impedance-based whole blood lumiaggregometry have advantages over light transmittance aggregometry in that they provide for enhanced specimen manageme...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0029-1220325
更新日期:2009-03-01 00:00:00