Abstract：
:Clotting factor VIII (fVIII)-inhibitory antibodies represent a major problem in the treatment of haemophilia A. To understand the inactivation mechanisms and to pave the way towards modifications of recombinant clotting factors that reduce their immunogenicity, the exact localization of immunodominant epitopes is required. Here, a random peptide phage display library was employed to identify epitopes of polyclonal fVIII antibodies isolated from patient's plasma by affinity chromatography. FVIII-binding specificity and inhibitory activity of the isolated fVIII antibodies were confirmed by ELISA and Bethesda assays. Phage selection on the individual samples yielded several phages which were displaced from binding to the respective antibody preparation by fVIII. Their homology with amino acid motifs of human fVIII and immunoprecipitation results with radioactively labelled fVIII fragments suggested putative epitopes in the A1, A2 and C1 domains of fVIII for one and in the C2 domain for another patient. Synthetic peptides corresponding to the A2, C1 and C2 domain epitopes blocked antibody binding to fVIII and partially neutralized the inhibitory activity of the respective plasma in Bethesda assays. These results provide the proof of principle that random peptide libraries can be used for the mapping of epitopes in a polyclonal antibody preparation.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Mühle C,Schulz-Drost S,Khrenov AV,Saenko EL,Klinge J,Schneider Hdoi
10.1160/TH03-07-0473keywords:
subject
Has Abstractpub_date
2004-03-01 00:00:00pages
619-25issue
3eissn
0340-6245issn
2567-689Xpii
04030619journal_volume
91pub_type
杂志文章abstract：:Heparin-induced thrombocytopenia (HIT), a relatively common complication of heparin therapy, results of platelet activation, via the receptor for the Fc domain of IgG (FcgammaRIIa), by heparin-dependent-antibodies, commonly directed against the heparin-platelet factor 4 (H-PF4) antigenic complex. Our strategy was to u...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-06-01 00:00:00
abstract：:Thrombus formation at an artificial surface in contact with blood is a complex process that encompasses accretion of platelets from flowing blood and fibrin deposition. Platelet adhesion and fibrin formation are intimately intertwined reactions that are triggered by different sets of surface adsorbed plasma proteins. ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2002-04-01 00:00:00
abstract：:Many studies showed that the occurrence of cardiovascular and cerebrovascular events exhibits a seasonal and monthly variation. Evidences of a seasonal and monthly variation in the incidence of venous thromboembolism (VTE) are more conflicting. We conducted a systematic review and a meta-analysis of the literature to ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,meta分析,评审
doi：10.1160/TH11-02-0116
更新日期：2011-09-01 00:00:00
abstract：:Compared with Caucasian patients, East Asian patients have the unique risk-benefit trade-off and different responsiveness to antithrombotic regimens. The aim of this study was to compare pharmacodynamic profile in East Asian patients with acute coronary syndromes (ACS) treated with prasugrel standard-dose vs. de-escal...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验
doi：10.1055/a-1346-3300
更新日期：2021-01-05 00:00:00
abstract：:Hemorrhagic diathesis and widespread microthrombosis are common in heatstroke. To assess the early stages of coagulopathy in heatstroke, thrombin-antithrombin III (TAT), fibrin monomers, plasmin-alpha 2-antiplasmin (PAP), plasminogen and D-Dimer were measured in 16 heatstroke patients (means +/- SE rectal temperature ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:An experimental model incorporating cultured endothelial cells (EC) was used to study the "factor VIII bypassing" activity of prothrombin complex concentrates (PCC), a property exploited in the treatment of hemophiliacs with alloantibodies to factor VIII. Two PCC preparations were ineffective as stimuli of tissue fact...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:Studies examining the interaction of platelets with exposed subendothelium in vivo have reported conflicting results. To examine possible explanations for the apparently discrepant findings, we measured the platelet reactivity of subendothelium prepared by a number of methods both in vivo and in vitro. In addition, we...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1987-08-04 00:00:00
abstract：:Mouse mesothelium has been examined as a surface for supporting blood flow. We have examined ten pieces of intact mesothelium and ten pieces of damaged mesothelium following 10 min exposure to flowing blood in a Baumgartner chamber. Scanning electron microscopy of the intact specimens demonstrated no adhering blood pl...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-02-28 00:00:00
abstract：:Clopidogrel is a recently introduced platelet ADP receptor antagonist, belonging to the thienopyridine derivatives, like its analogue ticlopidine. Its potential advantage is to be safer than ticlopidine. At 75 mg/od clopidogrel significantly inhibits platelet aggregation in ambulatory patients with symptomatic atheros...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1999-11-01 00:00:00
abstract：:A new immunoadsorbent-amidolytic assay (IAA) for the specific differential detection of two-chain urokinase-type plasminogen activator (tcu-PA) and its single-chain precursor (scu-PA) in cell culture supernatants has been developed. The assay combines the selectivity of immunoassays with the specificity of enzyme acti...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-12-15 00:00:00
abstract：:The effects of mental stress (a colour word conflict test, CWT) and adrenaline infusions (0.1 and 0.4 nmol kg-1 min-1) on t-PA activity, t-PA antigen, PAI-1 activity and PAI-1 antigen were studied in 18 healthy male volunteers. Furthermore, the effects of metoprolol (200 mg/day during 1 week) or placebo (double-blind ...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章
doi：
更新日期：1990-06-28 00:00:00
abstract：:Heparin-coating improves the biocompatibility of blood contacting artificial surfaces. This led us to investigate the impact of heparin-coating (Carmeda AB, Stockholm) of polymetylmetacrylate on the expression of monocyte tissue factor procoagulant activity (TF-PCA) by surface adhesion. Also, the anticoagulant effect ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
abstract：:The technique of crossed immunoelectrophoresis has been used to study the binding to purified antithrombin III (At III) of heparin and other mucopolysaccharides. The technique was unable to detect differences among samples of whole heparin from various manufacturers, but proved useful in studying the binding of hepari...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1980-02-29 00:00:00
abstract：:Tissue factor-factor VIIa catalysed activation of factor IX is inhibited by the complex of tissue factor pathway inhibitor (TFPI) and factor Xa. At present, no information is available as to what extent the kinetics of complex formation between TFPI and factor Xa during factor X activation contribute to the overall ra...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:In patients with deep vein thrombosis (DVT), the factors which predispose to concomitant symptomatic pulmonary embolism (PE) have remained uncertain. From a prospective cohort of 5,451 consecutive patients with ultrasound-confirmed DVT, we analyzed 4,211 patients with a known status for presence (n=639) or absence (n=...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH04-09-0587
更新日期：2005-03-01 00:00:00
abstract：:Glucose intolerance, hyperinsulinaemia, dyslipoproteinaemia and multiple disturbances of haemostatic function are characteristics of young men with premature coronary artery disease. The relations between glucose, insulin and insulin propeptides, in the fasting state, and after an oral glucose load, and haemostatic fu...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:Factor Xa (fXa)-inhibitors are as effective and safer than vitamin-K-antagonists (VKA) in the treatment of venous thromboembolism (VTE). We previously classified the severity of clinical presentation and course of all major bleeding events from the EINSTEIN, AMPLIFY and HOKUSAI-VTE trials separately. The current aim w...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH16-12-0946
更新日期：2017-10-01 00:00:00
abstract：:The effect of IgGs from 4 patients with antiphospholipid antibodies and elevated excretion of urinary 11-dehydro-thromboxane B2 was evaluated on the production of prostacyclin by human endothelial cells in culture. After 6 h incubation, there was no change in 6-keto-prostaglandin F1 alpha in the supernatant. However p...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:We measured and compared the levels of plasma soluble (s) P-selectin, sCD40L, platelet-derived microparticles (PDMP), monocyte-derived microparticles (MDMP), and anti-oxidized LDL antibody, to obtain a better understanding of their potential contribution to vascular complications in acute coronary syndrome (ACS). The ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-04-0247
更新日期：2004-01-01 00:00:00
abstract：:A multicenter study of various types of von Willebrand's disease (vWD) was conducted in order to compare the different electrophoretic techniques used to evaluate von Willebrand factor multimers in plasma. Seven laboratories participated in the blind study of eight plasma samples from two healthy subjects and six vWD ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-12-17 00:00:00
abstract：:Prothrombin complex concentrates (PCC) are known to carry a risk of thromboembolism. We have chosen to reassess the problem of detecting in vivo signs of activation of the clotting mechanism by assaying fibrinopeptide A (FpA) after PCC administration in hemophilic patients during bleeding episodes. FpA was significant...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1980-10-31 00:00:00
abstract：:Research into cancer-associated thrombosis (CAT) entails managing dynamic data that pose an analytical challenge. Thus, methods that assume proportional hazards to investigate prognosis entail a risk of misinterpreting or overlooking key traits or time-varying effects. We examined the AGAMENON registry, which collects...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1055/s-0039-1694012
更新日期：2019-11-01 00:00:00
abstract：:Hemin is a heme oxygenase-1 (HO-1) inducer which provides endogenous carbon monoxide known for playing roles in cell proliferation, inflammation or aggregation process. The objective of the current study was to examine the effect of prophylactic treatment with hemin in a thrombosis vascular model. Three groups of Wist...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2007-09-01 00:00:00
abstract：:Defibrotide is an antithrombotic drug which enhances prostacyclin production and activates fibrinolytic system. The aim of this study was to investigate the improvement of walking distance in patients with intermittent claudication treated with defibrotide. DICLIS was a double blind, placebo-controlled study which inc...
journal_title：Thrombosis and haemostasis
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：2000-05-01 00:00:00
abstract：:We investigated the protective effects of DX-9065a, an orally active, newly synthesized and specific inhibitor of factor Xa, against two kinds of experimental disseminated intravascular coagulation (DIC) in rats. Endotoxin-induced experimental DIC was induced by a 4-h sustained infusion of endotoxin at a dose of 100 m...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:Congenital factor VII (FVII) deficiency is a rare bleeding disorder caused by mutations in F7 gene with autosomal recessive inheritance. A clinical heterogeneity with poor correlation with FVII:C levels has been described. It was the objective of this study to identify genetic defects and to evaluate their relationshi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH17-02-0085
更新日期：2017-08-01 00:00:00
abstract：:Peripheral vascular disease (PVD) is an indicator of diffuse atherosclerosis and is associated with a greatly increased incidence of coronary heart and cerebrovascular disease. Although several studies have assessed whether in vivo platelet activation takes place in patients with PVD, no data are available comparing d...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-12-01 00:00:00
abstract：:Most of the knowledge acquired on platelet function and biochemistry has been obtained from platelets prepared from blood anticoagulated with sodium citrate. Using washed platelets from human blood (PNB) to which no anticoagulants were added, we report on responses not observed with platelets prepared from citrate-ant...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-10-21 00:00:00
abstract：:Probands from 15 unrelated families with hereditary protein S deficiency type I, that is having a plasma total protein S concentration fifty percent of normal, were screened for abnormalities in their protein S genes by Southern analysis. Two probands were found to have a deviating DNA pattern with the restriction enz...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1989-11-24 00:00:00
abstract：:The burden of disease in haemophilia patients has wide ranging implications for the family and to society. There is evidence that having a current inhibitor increases the risk of morbidity and mortality. Morbidity is increased by the inability to treat adequately and its consequent disabilities, which then equates to ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH16-01-0049
更新日期：2016-08-31 00:00:00
