Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Tissue factor pathway inhibitor ( TFPI ) is the factor Xa ( FXa ) dependent coagulation inhibitor . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Tissue factor pathway inhibitor ( TFPI ) FXa complexes form and inhibit TF / FVIIa . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
The sequence of AcAPc 2 as well as the utilization of an exo site on fXa distinguishes this inhibitor from the mammalian anticoagulant TFPI ( tissue factor pathway inhibitor ) , which is functionally equivalent with respect to fXa dependent inhibition of fIIa / TF . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Tissue Factor Pathway Inhibitor ( TFPI ) is a naturally occurring inhibitor of the TF FVIIa induced coagulation in the presence of FXa . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Tissue factor pathway inhibitor ( TFPI ) is an endogenous heparin releasable three domain Kunitz type coagulation inhibitor which inhibits the crucial tissue factor factor VIIa ( TF FVIIa ) dependent coagulation pathway in the presence of FXa . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Tissue factor pathway inhibitor ( TFPI ) is a potent inhibitor of blood coagulation factor Xa ( fXa ) and factor VIIa . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Activation of blood coagulation factor 10 to factor Xa ( FXa ) is inhibited by tissue factor pathway inhibitor ( TFPI ) . ^^^ |
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Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Human tissue factor pathway inhibitor fused to CD 4 binds both FXa and TF / FVIIa at the cell surface . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Tissue factor pathway inhibitor ( TFPI ) is a trivalent Kunitz type plasma proteinase inhibitor that regulates the initiation of coagulation by producing activated factor 10 ( FXa ) dependent feedback inhibition of the catalytic complex of FVIIa and tissue factor ( TF ) . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
We have recently demonstrated the inability of porcine tissue factor pathway inhibitor ( TFPI ) to adequately neutralize human factor Xa ( FXa ) , the aberrant activation of both human prothrombin and FXa by porcine EC and the failure of the porcine natural anticoagulant , thrombomodulin to bind human thrombin and hence activate human protein C . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
The physiological inhibitor of tissue factor ( TF ) . factor VIIa ( FVIIa ) , full length tissue factor pathway inhibitor ( TFPI ( FL ) ) in complex with factor Xa ( FXa ) , has a high affinity for anionic phospholipid membranes . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Further FXa generation by the FIXa FVIIIa Ca2+ phospholipid complex is required to sustain the coagulation mechanism , since the TF FVIIa complex is rapidly inactivated by Tissue Factor pathway inhibitor ( TFPI ) . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Reactivity of the free enzyme toward substrates and inhibitors is attenuated 4 20 fold ; relative to wild type fXa , Spectrozyme Xa ( TM ) hydrolysis is 25 % , inhibition by antithrombin 3 and the tissue factor pathway inhibitor is approximately 20 % , and prothrombin activation in the absence of the cofactor Va is only 5 % . ^^^ Q333D fXa is approximately 1 . 6 fold more reactive with Spectrozyme Xa ( TM ) , antithrombin 3 and tissue factor pathway inhibitor , and prothrombin than its glycosylated counterpart , Q333N fXa , but still quite abnormal relative to wild type fXa . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Plasma levels of tissue factor pathway inhibitor ( TFPI ) activated factor Xa ( FXa ) complex were measured in patients with disseminated intravascular coagulation ( DIC ) , pre DIC , and DIC . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
After the first FXa is formed , the tissue factor pathway inhibitor ( TFPI ) forms a complex with FXa . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
This study assessed whether porcine EC could be activated by factor Xa ( FXa ) and thrombin ( FIIa ) and whether expression of tissue factor pathway inhibitor ( TFPI ) CD 4 and hirudin CD 4 fusion proteins could prevent such activation . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
The inability of porcine tissue factor pathway inhibitor ( TFPI ) to adequately neutralize human factor Xa ( FXa ) , the aberrant activation of both human prothrombin and FXa by porcine EC and the failure of the porcine natural anticoagulant , thrombomodulin to bind human thrombin and hence activate human protein C may all be pathogenetic in the DIC following xenograft rejection . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Following purification to homogeneity and activation by the factor 10 activator from Russell viper venom , the mutants were characterized with respect to their ability to assemble into the prothrombinase complex to activate prothrombin and interact with target plasma fXa inhibitors , tissue factor pathway inhibitor ( TFPI ) and antithrombin . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
TF FVIIa is inhibited by tissue factor pathway inhibitor ( TFPI ) in two steps : first TFPI is bound to the active site of factor Xa ( FXa ) , and subsequently FXa TFPI exerts feedback inhibition of TF FVIIa . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
All drugs tested significantly delayed clot formation ; only those drugs targeting activated factor 10 ( FXa ) ( tissue factor pathway inhibitor , fondaparinux , and low molecular weight heparin ) accelerated fibrinolysis . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Our data also implicate loop 34 40 of FXa in the interaction with the tissue factor pathway inhibitor , in prevention of plasminogen activator inhibitor 1 binding , and in tempering inhibition by heparin activated antithrombin . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
The physical blanketing of an injured surface by platelets and fibrin in addition to the release of platelet tissue factor pathway inhibitor ( TFPI ) , prevents FIXa and FXa from diffusing more than a few tens of microns away from the vessel wall , far short of the 3 mm thickness needed for occlusive thrombosis . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Tissue factor pathway inhibitor ( TFPI ) is a potent inhibitor of TF induced coagulation by neutralizing FXa and inhibiting the TF FVIIa complex . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
METHODS AND RESULTS : Factor Xa ( FXa ) bound to tissue factor pathway inhibitor and prothrombin fragments F1+2 ( F1+2 ) were used as a measure for activated coagulation . ^^^ In AMI , tissue factor pathway inhibitor FXa but not F1+2 plasma levels were associated with circulating IL 8 ( P=0 . 01 ) . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Natural ( activated protein C , tissue factor pathway inhibitor , or antithrombin 3 ) or pharmacological anticoagulants readily offset the extrinsic hypercoagulation mainly through FVIIa , FXa or FIIa inhibition . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Here , we investigated the role of EGF 1 domains of FXa and FIXa during the activation of FVII TF and inhibition by tissue factor pathway inhibitor ( TFPI ) . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Parallel investigations demonstrate FV , FVII , FVIIa , FIX , FIXa , FXa , FXI , FXII , tissue factor ( TF ) and tissue factor pathway inhibitor ( TFPI ) in semen . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Further studies showed that an inactive Ser 195 to Ala mutant of fXa effectively competes with wild type fXa for binding to the non serpin inhibitors tissue factor pathway inhibitor and recombinant tick anticoagulant peptide , but does not compete for binding to ZPI . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
The proteolytic activity of fXa in plasma is primarily regulated by three physiological inhibitors , antithrombin ( AT ) , protein Z dependent protease inhibitor ( ZPI ) and tissue factor pathway inhibitor ( TFPI ) . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
BACKGROUND : Tissue factor pathway inhibitor ( TFPI ) is a 40 kDa , endogenous protein that inhibits tissue factor ( TF ) initiated coagulation by bonding with activated factor 10 ( FXa ) . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
TFPI requires the formation of an active TF VIIa complex and FXa generation before inhibition can occur . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
The inhibition of thrombus formation on procoagulant extracellular matrix by rTFPI seemed to be FXa dependent , and a result of TFPI ' s ability to bind and inhibit both TF activity as well as FXa . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Because persistent albeit decreased steady state levels of thrombin formation occurred in the presence of TFPI , we conclude that plasma TFPI does not inhibit FXa present in the prothrombinase complex . ^^^ The addition of FIX and FVIII to perfusates containing FVII and FX increased the FXa generation on endothelial matrices , and counteracted the inhibition of thrombin formation on endothelial cell matrices by TFPI . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Clotting assays with purified short form TFPI showed that it acted mainly via inhibition of FVIIa . tissue factor rather than FXa . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
The glycosylated multivalent three domain Kunitz inhibitor TFPI is a natural inhibitor of tissue factor FVIIa complex in the presence of FXa . ^^^ The effect mediated by this type of TFPI could primarily be due to an inhibition of FXa . . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
The present study investigates the changes in plasma TFPI in relation to markers of in vivo thrombin generation induced by injection of factor Xa ( FXa ) / phospholipids in baboons at dosages leading to partial ( 48 % ) or complete fibrinogen depletion . ^^^ TFPI levels , whether measured as antigen or activity , increased significantly in both treatment groups within few minutes , and were dependent on the dose of FXa / phospholipids . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
This enhanced FXa generation was not observed when the patient ' s IgG was depleted of anti beta2GPI IgG or when normal plasma was depleted of beta2PGPI or TFPI . ^^^ Taken together , these data indicate that antibodies to beta2GPI , circulating in patients with APS , suppress TFPI dependent inhibition of TF induced coagulation , which results in an increased FXa generation . . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
The median activated factor 10 ( FXa ) TFPI complex level in patients ( 0 . 13 nmol / l ) was lower than in controls ( 0 . 18 nmol / l ; P < 0 . 01 ) . ^^^ Only one patient had a FXa TFPI complex level above the normal range , while eight patients had levels below . ^^^ In conclusion , TFPI activity , free TFPI antigen and FXa TFPI complex levels vary considerably in DIC . ^^^ Subnormal FXa TFPI levels in DIC , possibly caused by consumption , may imply a reduced capacity to inactivate the triggering factor VIIa tissue factor complex . . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
TFPI was measured in PAPS patients using an amidolytic assay , dependent on the generation of activated factor 10 ( Fxa ) , and this was compared with 55 healthy subjects . ^^^ The difference was caused by a subset of five patients who had TFPI levels below the lower 99 % confidence interval of the normal reference range , representing increased FXa generation in the assay system . ^^^ IgG fractions were isolated from these five patients and five control subjects , then incorporated into normal plasma to measure FXa generation in the TFPI assay system . ^^^ FXa generation was increased when polyclonal rabbit anti human TFPI IgG ( P < 0 . 0001 ) or PAPS IgG ( P = 0 . 0001 ) were added to normal plasma , demonstrating inhibition of TFPI . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.57187553 |
FXa interacts stoichiometrically with tissue pathway inhibitor ( TFPI ) , regulating TF FVIIa activity by forming the TF FVIIa TFPI FXa quaternary complex . 0.57187553^^^ |
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Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.57576476 |
After the first FXa is formed , the TF pathway inhibitor ( TFPI ) forms a complex with FXa , and a quaternary complex is formed , TF / FVIIa / FXa / TFPI , which inhibits the first step of the hemostatic pathway . 0.57576476^^^ |
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Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
We now report that also the median plasma levels of the Factor Xa ( FXa ) TFPI complex were significantly higher in patients with solid tumours , compared to patients with haematological malignancy and healthy controls . ^^^ There were significant positive correlations between the FXa TFPI complex and total TFPI antigen ( r= . 47 , P= . 001 ) and TFPI activity ( r= . 33 , P < . 023 ) . ^^^ In plasma samples from patients with solid tumours , the ratio between the FXa TFPI complex and free TFPI was 3 . 4 times higher than in patients with haematological malignancies . ^^^ Increased levels of the FXa TFPI complex in solid tumour disease may reflect both increased FXa generation and the increased TFPI concentration in the patients . ^^^ It is speculated that high levels of the inhibitory FXa TFPI complex in cancer patients may protect against microthrombosis and organ failure , which are relatively rare in cancer despite long lasting hypercoagulation . . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
METHODS AND RESULTS : Transcardiac ( aorta / coronary sinus ) free and total TFPI ( free + lipoprotein bound form ) levels , as well as TFPI / factor Xa ( FXa ) complex levels , were measured in plasma samples obtained from patients with acute myocardial infarction undergoing primary PTCA and patients with unstable angina undergoing urgent PTCA . ^^^ In patients with ACS , both total and free TFPI plasma levels in the coronary sinus were significantly lower than the corresponding levels measured in the aorta at any time point of the study ; conversely , a significant increase in TFPI / FXa complex plasma levels was observed in the coronary sinus as compared with the aorta . ^^^ In contrast , in patients with stable angina , no differences were observed in TFPI and TFPI / FXa levels at baseline in the coronary sinus as compared with the aorta . ^^^ |
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Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
In contrast with human TFPI , Ixolaris binds tightly to the zymogen FX ( Factor 10 ) and to dansyl Glu Gly Arg chloromethyl ketone treated FXa ( DEGR FXa ; active site blocked FXa ) , indicating that exosites are involved in the FX ( a ) Ixolaris interaction . ^^^ |
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Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Because vascular endothelial cells synthesize and constitutively secrete TFPI and fXa may directly influence its cellular clearance , we sought to determine the effects of DX 9065a , a direct and selective fXa inhibitor , on TFPI kinetics in culture . ^^^ Although the mechanism has yet to be established , decreased fXa availability may limit fXa TFPI complex formation and its subsequent cellular uptake . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
In both tests FXa formation plays a major role , as the effect of FVIII and TFPI on the tests seems to be executed via FXa . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Surface TFPI activity was determined by a two stage chromogenic assay based on the ability of each form to inhibit FXa activation by FVIIa on cells with comparable amount of tissue factor ( TF ) . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
The levels and the dual inhibitor effect of TFPI on FXa and TF FVII / FVIIa complex offers insight into the mechanisms of various pathological conditions triggered by TF . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
In this article we uncover a mechanism in which protein S , which is well known as the cofactor of activated protein C , specifically inhibits TF activity by promoting the interaction between full length TF pathway inhibitor ( TFPI ) and factor Xa ( FXa ) . ^^^ The stimulatory effect of protein S on FXa inhibition by TFPI is caused by a 10 fold reduction of the K ( 1 ) of the FXa / TFPI complex , which decreased from 4 . 4 nM in the absence of protein S to 0 . 5 nM in the presence of protein S . ^^^ This decrease in K ( 1 ) not only results in an acceleration of the feedback inhibition of the TF mediated coagulation pathway , but it also brings the TFPI concentration necessary for effective FXa inhibition well within range of the concentration of TFPI in plasma . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
Differently from TFPI , ixolaris does not bind to the active site cleft of FXa . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
TFPI exerts its action by binding to factor Xa ( FXa ) forming a TFPI FXa complex that then , in a second step , binds and effectively inhibits the TF factor VIIa ( FVIIa ) complex . ^^^ The anticoagulant and antiplatelet actions of TFPI , its potency in inhibiting thrombin and FXa generation , as well as its favourable antithrombotic effectiveness seen in different animal models of venous and arterial thrombosis make this inhibitor a promising agent that could be potentially useful in several clinical indications . ^^^ |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P10646 and P00742 |
Pubmed |
SVM Score :0.0 |
NA |
|