Abstract：
:Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis and is considered as an attractive drug target. We generated two different antibody fragments, an antigen-binding fragment (Fab) and a single-chain variable fragment (scFv), derived from three distinct monoclonal antibodies (MAs) that inhibit the activation of TAFI by the thrombin/thrombomodulin complex (T/TM) and plasmin (MA-T1C10 and MA-T94H3) or by T/TM alone (MA-T12D11). The Fabs were obtained by papain digestion of the purified MAs, whereas the scFvs were cloned and subsequently expressed in bacteria. All antibody fragments revealed similar or slightly decreased affinities compared to those of the respective MAs, except scFv-T94H3. In the presence of a 16-fold molar excess of all antibody fragments, activation of TAFI by T/TM was completely blocked. Furthermore, Fab and scFv-derivatives from MA-T1C10 and MA-T94H3 were capable of interfering with the plasmin-mediated activation of TAFI. Addition of 850 nM of MA, Fab or scFv to an in-vitro clot lysis assay caused a significant reduction of clot lysis time (except for scFv-T94H3) and this effect was comparable to that of potato tuber carboxypeptidase inhibitor, a well-known TAFIa inhibitor. Dose-response experiments with the antibody (derivatives) in clot lysis and chromogenic assay revealed that the inhibitory capacity of the Fabs was comparable to that of the MAs, whereas the scFvs had a more reduced potency. In conclusion, these highly specific TAFI inhibitors are interesting tools to further evaluate the concept of TAFI inhibition in various in-vitro and in-vivo models.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Develter J,Dewilde M,Gils A,Declerck PJdoi
10.1160/TH08-09-0834subject
Has Abstractpub_date
2009-07-01 00:00:00pages
69-75issue
1eissn
0340-6245issn
2567-689Xpii
TH08-09-0834journal_volume
102pub_type
杂志文章abstract：:We previously reported a monoclonal antibody named IF-43 that specifically recognizes thrombin-modified fibrinogen (desAA- and desAABB- fibrin monomer) bound with fibrinogen or other D(1) domain-containing plasmic fragments such as fragments X,Y, and D(1), but not intact fibrinogen or cross-linked fibrin degradation p...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2003-05-01 00:00:00
abstract：:A synthetic hirudin55-65 C-terminal fragment analog was evaluated for anticoagulant activity and in models of experimental thrombosis in mice and rats. Intravenous injection caused dose-related inhibition of thrombin and anticoagulation in rat blood samples, protection from thromboembolism in mice and inhibition of st...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1991-04-08 00:00:00
abstract：:The structures of bovine and human vWF were compared by proteolysis with Staphylococcus aureus V8 protease and rattlesnake venom Protease I. Fragments were analyzed for chain composition, heparin binding, collagen binding, platelet agglutinating activity and recognition by a panel of monoclonal antibodies which reacte...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-06-28 00:00:00
abstract：:Endothelial dysfunction and increased platelet aggregation may be involved in the pathogenesis of normal tissue radiation toxicity. This study assessed clopidogrel, an inhibitor of ADP-induced platelet aggregation, as a modulator of intestinal radiation injury (radiation enteropathy). Rat small intestine was exposed t...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2002-01-01 00:00:00
abstract：:The effects of argatroban, a direct thrombin inhibitor, on the International Normalized Ratio (INR), activated partial thromboplastin time (aPTT) and functional factor X during warfarin co-administration were established to provide means to interpret INRs during argatroban/warfarin co-therapy. Twenty-four subjects rec...
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：2001-03-01 00:00:00
abstract：:Less than 60 cases of acquired factor (F)XIII deficiencies have been reported, most having distinct clinical features. To illustrate the therapeutic challenges of acquired FXIII inhibitors, we report a case of a 65-year-old patient with no previous bleeding history who suddenly developed massive haemorrhages associate...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH12-08-0604
更新日期：2013-03-01 00:00:00
abstract：:ADAMTS13 dysfunction has been involved in the pathogenesis of Thrombotic Thrombocytopenic Purpura. This disorder occurs more frequently in women and, in 13% of them, is associated with pregnancy. However, there is little information on the protease behaviour in normal pregnancy. We studied von Willebrand factor and AD...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-11-0683
更新日期：2004-12-01 00:00:00
abstract：:We report on three unrelated individuals with the same uncommon type of dysfibrinogenemia, originating from Bergamo, Essen and Perugia. None of them showed bleeding symptoms while the Bergamo patient and members of her family presented with a thrombotic tendency. The presence of a defective fibrinogen was suggested by...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-12-15 00:00:00
abstract：:A fibrinolysis inhibitor was purified in serum from post-traumatic patients by the use of flat bed electrofocusing of serum desalted by gel chromatography followed by affinity chromatography on a column of matrix-linked plasminogen. Disc gel electrophoresis yielded one protein band. The inhibitor protein was also foun...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1978-02-28 00:00:00
abstract：:Vitamin K-dependent protein S is a cofactor to the anticoagulant serine protease activated protein C (APC) in the proteolytic inactivation of the procoagulant, activated factor V (FVa) and factor VIII (FVIIIa). In the FVa degradation, protein S selectively accelerates the cleavage at Arg306, having no effect on the Ar...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2000-08-01 00:00:00
abstract：:A new genetic test has been developed for detection of the mutation known as factor V Leiden. The test employs heteroduplex technology and comprises a single PCR reaction followed immediately by PCR product analysis. It therefore represents the minimum practical route from blood/tissue sample to genetic result. A coho...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-01-01 00:00:00
abstract：:The use of exogenous oestrogen in women with otherwise unprovoked venous thromboembolism (VTE) could be considered sufficient explanation to classify VTE as provoked if the risk of recurrent VTE after 3-6 months of anticoagulant treatment is similar to the risk of recurrent VTE observed after a surgery or prolonged im...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH09-10-0685
更新日期：2010-09-01 00:00:00
abstract：:The clearance of radiolabeled human fibrinogen fragments X and Y was studied in the mouse model. Fragment X cleared rapidly from the circulation with less than 10% of the ligand remaining in the circulation at 4 hr. The clearance of fragment Y was somewhat slower, but was identical to the rate of clearance of fragment...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1983-04-28 00:00:00
abstract：:Deep-vein thrombosis (DVT) is a common condition that often leads to pulmonary thromboembolism (VTE) and death. The role of prostaglandin-endoperoxide synthase (PTGS)2 in arterial thrombosis has been well established, whereas its impact in venous thrombosis remains unclear. Here, we showed that PTGS2 deletion predispo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH16-12-0968
更新日期：2017-07-26 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：:Antiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and beta2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. How...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：:Aspirin prevents thrombotic events by inhibiting platelet cyclooxygenase-1 (COX-1), thus reducing thromboxane A2 formation and platelet aggregation. The C50T polymorphism of COX-1 is associated with an impaired inhibition of both thromboxane production and in-vitro platelet aggregation by aspirin. We studied whether t...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章
doi：10.1160/TH08-03-0172
更新日期：2008-07-01 00:00:00
abstract：:The evidence is reviewed and a model presented for two distinct receptors being involved in platelet activation induced by alpha-thrombin: a high affinity thrombin receptor constituting approximately 50 copies of a supercomplexed form of GPIb coupled to phospholipase A2 and a moderate affinity receptor constituting ap...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1997-07-01 00:00:00
abstract：:As an adjunct to a European multicentre prospective study, five quality assessment (QA) exercises, spanning a period of 2.5 years, were undertaken. In these, fifteen laboratories from eight countries each performed ten haemostatic factor assays. The design of the QA exercises allowed the between-duplicate, between-day...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：
更新日期：1991-02-12 00:00:00
abstract：:Underlying disorders of the coagulation system such as inhibitor deficiencies or decreased fibrinolysis are common in patients suffering from venous thrombosis. They may lead to the necessity of a lifelong prophylaxis. Prompt diagnosis is obviously to the patients benefit. We investigated 22 patients suffering from ve...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:Ridogrel (6.3 x 10(-6) to 10(-4) M) inhibited contractions of isolated rat caudal arteries and rabbit femoral arteries caused by U-46619. The slope of an Arunlakshana-Schild plot (pA2-value: 3.4 x 10(-6) M) on the caudal artery was slightly higher than one (1.14). This effect was maximal within 20 min of incubation of...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-08-13 00:00:00
abstract：:Graduated elastic compression stockings (GECS) are commonly used in the primary prevention of deep vein thrombosis (DVT); however, their role in preventing recurrent DVT and also post-thrombotic syndrome is less well established. The aim of this review was to investigate the effect of GECS after DVT. A literature sear...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：2006-10-01 00:00:00
abstract：:The endocannabinoid anandamide (AEA) has many neurovascular activities. However, it is not yet clear how AEA can be metabolized at the neurovascular interface, and how it can move through the vascular and the cerebral compartments. The results reported in this article show that isolated bovine brain microvessels, an e...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2006-01-01 00:00:00
abstract：:Platelet-monocyte aggregates are increasingly being used to quantify platelet activation. The variables that influence platelet-monocyte aggregates have not been well defined. We sought to determine the effect of blood collection, handling and processing techniques on detected levels of platelet-monocyte aggregates us...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2007-08-01 00:00:00
abstract：:We examined the ability of unfractionated heparin to modulate the procoagulant activities of stimulated endothelial cells (EC). Confluent human venous umbilical EC were incubated with heparin before or after stimulation, then rinsed extensively to eliminate any heparin in the solution. EC, stimulated for 4 h with endo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:The antithrombotic effect of MCI-9042, (+-)-2-(dimethyl-amino)-1-((o-(m- methoxyphenethyl)phenoxyl]methyl]ethyl hydrogen succinate hydrochloride was investigated in three different experimental thrombosis models in animals. Simultaneous injection of serotonin and collagen into the tail vein in mice induced acute pulmo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:Mature circulating endothelial cells (CECs) are novel cellular markers of endothelial damage/dysfunction. The two main techniques of CEC enumeration are flow cytometry (FC) and immunomagnetic bead (IB) isolation. Both quantify CECs accurately, but a direct comparison of both methods has not been reported. We sought to...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH06-04-0185
更新日期：2006-07-01 00:00:00
abstract：:Tissue factor pathway inhibitor (TFPI) is one of the main regulators of the tissue factor (TF) pathway of coagulation. To tether human TFPI to the cell surface, full length or truncated TFPI lacking the third Kunitz domain were fused with domains three and four and the carboxy-terminal sequence of human CD4. Construct...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-12-01 00:00:00
abstract：:A previous study of neurosurgical patients demonstrated an imbalance between thrombin and plasmin action following surgery. The present study was designed to determine the effect of intermittent pneumatic calf compression on postoperative enzyme activity. Fibrinopeptide A (FPA) and B beta 1-42 levels, reflecting throm...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-10-21 00:00:00
abstract：:Interactions between endothelial cell adhesion molecules and their beta2 integrin adhesive receptors on leukocytes are thought to play a role in the pathogenesis of inflammatory diseases and probably vasculitis. We describe a case in whom leukocytoclastic vasculitis was associated to a monoclonal immunoglobulin G2 kap...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-09-01 00:00:00
