The purpose of the aPCC-emicizumab safety study is to prospectively investigate the safety and hemostatic efficacy of a personalized dose of aPCC in children and adults with hemophilia A and inhibitors on emicizumab prophylaxis during acute bleeding events or prior to procedures.

开始日期2024-11-01

申办/合作机构

Emory University

[+1]

NCT06429787 / Not yet recruitingN/A

Post Marketing Observational Study on Safety of BALFAXAR® vs. KCENTRA for Reversal of Vitamin K Antagonist Induced Anticoagulation in Adults Undergoing Urgent Surgery or Invasive Procedure.

Post marketing observational study on safety of BALFAXAR vs. KCENTRA for Reversal of Vitamin K Antagonist Induced Anticoagulation in Adults Undergoing Urgent Surgery or Invasive Procedure

开始日期2024-06-30

申办/合作机构

Octapharma AG

100 项与 factor VII x F10 x factor IX x thrombin 相关的临床结果

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100 项与 factor VII x F10 x factor IX x thrombin 相关的转化医学

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0 项与 factor VII x F10 x factor IX x thrombin 相关的专利（医药）

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项与 factor VII x F10 x factor IX x thrombin 相关的文献（医药）

2017-06-01·Thrombosis Research3区 · 医学

Effect of platelet-derived β-thromboglobulins on coagulation

3区 · 医学

Article

作者: Ma, Hui ; Lennon, Aine ; Áinle, Fionnuala Ní ; Allen, Seamus ; Heemskerk, Johan W M ; Parsons, Martin ; van Geffen, Johanna P ; Egan, Karl ; Neary, Elaine ; O' Kennedy, Richard ; Wynne, Kieran ; Maguire, Patricia ; Kevane, Barry

BACKGROUNDβ-thromboglobulins are derived from the cleavage of the CXC chemokine platelet basic protein and are released in high concentrations by activated platelets. Platelet-derived β-thromboglobulins (βTG) share 70% homology with platelet factor 4 (PF4), another CXC chemokine released by activated platelets. PF4 modulates coagulation by inhibiting heparin-antithrombin interactions, promoting protein C activation, and attenuating the activity of activated protein C. In contrast, the effect of βTG on coagulation is unknown.AIM/METHODSClotting times, thrombin generation, chromogenic clotting factor assays, and surface plasmon resonance (SPR) were used to assess the effect of purified βTG on coagulation.RESULTSIn normal pooled plasma, βTG shortened the lagtime and time to peak thrombin generation of tissue factor (TF)-dependent and TF-independent thrombin generation. In factor VIII and factor IX-deficient plasmas, βTG induced thrombin generation in the absence of a TF stimulus and in the presence of anti-TF and factor VIIa inhibitory antibodies. The procoagulant effect was not observed when thrombin generation was independent of factor X activation (supplementation of factor X-deficient plasma with factor Xa). Cleavage of a factor Xa-specific chromogenic substrate was observed when βTG was incubated with factor X, suggesting a direct interaction between βTG and factor X. Using SPR, βTG were found to bind to immobilised factor X in a dose dependent manner.CONCLUSIONβTG modulate coagulation in vitro via an interaction with factor X.

2015-10-01·Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

Asymmetric processing of mutant factor X Arg386Cys reveals differences between intrinsic and extrinsic pathway activation

Article

作者: R.M. Camire ; M. Pinotti ; M. Baroni ; G. Pavani ; F. Bernardi ; A. Branchini

Alterations in coagulation factor X (FX) activation, mediated by the extrinsic VIIa/tissue factor (FVIIa/TF) or the intrinsic factor IXa/factor VIIIa (FIXa/FVIIIa) complexes, can result in hemorrhagic/prothrombotic tendencies. However, the molecular determinants involved in substrate recognition by these enzymes are poorly defined. Here, we investigated the role of arginine 386 (chymotrypsin numbering c202), a surface-exposed residue on the FX catalytic domain. The naturally occurring FX386Cys mutant and FX386Ala variant were characterized. Despite the unpaired cysteine, recombinant (r)FX386Cys was efficiently secreted (88.6±21.3% of rFXwt) and possessed normal clearance in mice. rFX386Cys was also normally activated by FVIIa/TF and displayed intact amidolytic activity. In contrast, rFX386Cys activation by the FIXa/FVIIIa complex was 4.5-fold reduced, which was driven by a decrease in the kcat (1.6∗10(-4) s(-1) vs 5.8∗10(-4) s(-1), rFXwt). The virtually unaltered Km (70.6 nM vs 55.6nM, rFXwt) suggested no major alterations in the FX substrate exosite. Functional assays in plasma supplemented with rFX386Cys indicated a remarkable reduction in the thrombin generation rate and thus in coagulation efficiency. Consistently, the rFX386Ala variant displayed similar biochemical features suggesting that global changes at position 386 impact the intrinsic pathway activation. These data indicate that the FXArg386 is involved in FIXa/FVIIIa-mediated FX activation and help in elucidating the bleeding tendency associated with the FX386Cys in a rare FX deficiency case. Taking advantage of the unpaired cysteine, the rFX386Cys mutant may be efficiently targeted by thiol-specific ligands and represent a valuable tool to study FX structure-function relationships both in vitro and in vivo.

2013-01-01·Thrombosis and Haemostasis2区 · 医学

The missense Thr211Pro mutation in the factor X activation peptide of a bleeding patient causes molecular defect in the clotting cascade

2区 · 医学

Article

作者: Yang, Likui ; Rezaie, Alireza R. ; Ding, Qiulan ; Wang, Xuefeng ; Shen, Yiping

SummaryFactor X (FX) is a vitamin K-dependent coagulation zymogen, which upon activation to factor Xa assembles into the prothrombinase complex to activate prothrombin to thrombin. FX can be activated by either factor VIIa-tissue factor or factor IXa-factor VIIIa in extrinsic and intrinsic pathways, respectively. In this study, we identified a bleeding patient with moderate FX deficiency who exhibits a clotting defect only in the intrinsic pathway. Exome sequencing revealed that the patient carries a novel homozygous missense mutation that results in substitution of Thr211 with Pro in the activation peptide of FX. Thr211 is the site of an O-linked glycosylation in the activation peptide of FX. We postulated that the lack of this post-translational modification specifically impacts the activation of FX by intrinsic Xase, thereby impairing thrombin generation in the subject. To test this hypothesis, we expressed both wild-type FX and FX containing this mutation in mammalian cells and following the purification of the zymogens to homogeneity characterized their properties in both purified and plasma-based assay systems. Analysis of the results suggests that Thr211 to Pro substitution renders the FX mutant a poor substrate for both physiological activators, however, at physiological concentration of the substrate, the clotting defect manifest itself only in the intrinsic pathway, thus explaining the bleeding phenotype for the patient carrying this mutation.