Search results for "Factor VIIa"
showing 10 items of 25 documents
Identification of the integrin-binding site on coagulation factor VIIa required for proangiogenic PAR2 signaling.
2018
The tissue factor (TF) pathway serves both hemostasis and cell signaling, but how cells control these divergent functions of TF remains incompletely understood. TF is the receptor and scaffold of coagulation proteases cleaving protease-activated receptor 2 (PAR2) that plays pivotal roles in angiogenesis and tumor development. Here we demonstrate that coagulation factor VIIa (FVIIa) elicits TF cytoplasmic domain-dependent proangiogenic cell signaling independent of the alternative PAR2 activator matriptase. We identify a Lys-Gly-Glu (KGE) integrin-binding motif in the FVIIa protease domain that is required for association of the TF-FVIIa complex with the active conformer of integrin β1. A po…
Tissue factor at the crossroad of coagulation and cell signaling
2018
The tissue factor (TF) pathway plays a central role in hemostasis and thrombo-inflammatory diseases. Although structure-function relationships of the TF initiation complex are elucidated, new facets of the dynamic regulation of TF?s activities on cells continue to emerge. Cellular pathways that render TF non-coagulant participate in signaling of distinct TF complexes with associated proteases through the protease-activated receptor (PAR) family of G-protein coupled receptors. Additional coreceptors, including the endothelial protein C receptor (EPCR) and integrins, confer signaling specificity by directing subcellular localization and trafficking. We here review how TF is switchedbetween it…
Tissue factor prothrombotic activity is regulated by integrin-arf6 trafficking
2017
Objective— Coagulation initiation by tissue factor (TF) is regulated by cellular inhibitors, cell surface availability of procoagulant phosphatidylserine, and thiol-disulfide exchange. How these mechanisms contribute to keeping TF in a noncoagulant state and to generating prothrombotic TF remain incompletely understood. Approach and Results— Here, we study the activation of TF in primary macrophages by a combination of pharmacological, genetic, and biochemical approaches. We demonstrate that primed macrophages effectively control TF cell surface activity by receptor internalization. After cell injury, ATP signals through the purinergic receptor P2rx7 induce release of TF + microvesicles. T…
A prospective randomized trial of high and standard dosages of recombinant factor VIIa for treatment of hemarthroses in hemophiliacs with inhibitors.
2006
Summary. Aim: A multicenter randomized open-label crossover prospective trial was designed to compare the efficacy, safety, and cost of standard and high dosages of recombinant factor VIIa (rFVIIa) for home treatment of hemarthroses in hemophiliacs with inhibitors. Methods: Patients were instructed to treat, within 6 h from the onset of bleeding, four consecutive hemarthroses of ankles, knees, or elbows, either with the rFVIIa standard dose of 90 μg kg−1 (repeated as necessary every 3 h) or with a single high dose of 270 μg kg−1. Patients who did not achieve a clinical success within 9 h continued rFVIIa treatment with repeated standard doses. Response to treatment was assessed for up to 48…
Prevention of haemophilic arthropathy during childhood. May common orthopaedic management be extrapolated from patients without inhibitors to patient…
2008
We recommend prophylaxis in haemophilic children with an inhibitor as a way of preventing the musculoskeletal impairment that is likely to affect them. This approach has been used for children without inhibitors with excellent results. If prophylaxis is not feasible, we suggest that intensive on-demand treatment should be given. Two agents, recombinant activated FVII (rFVIIa) and activated prothrombin complex concentrates (aPCC), are currently used to control haemostasis either for prophylaxis or intensive on-demand treatment. As it is recombinant, rFVIIa would seem more appropriate to be employed in children. aPCC could be used in adults, or in the event of an unsatisfactory response to rF…
Successful treatment of life-threatening bleeding after cesarean section with recombinant activated factor VII.
2006
Hemorrhagic shock developed in a 29-year-old nullipara without coagulopathy after emergency caesarean section. Treatment with uterotonic drugs, prostaglandins, and conservative procedures with transfusion of packed red cells and fresh-frozen plasma failed to control the diffuse vaginal and uterine bleeding. Finally an intravenous bolus injection of 90 μg/kg recombinant activated factor VII (rFVIIa, NovoSeven®, Novo Nordisk A/S, Bagsvaerd, Denmark), was given and showed success within 20 minutes after administration, without any side effects.
Clinical and echographical control protocol of haemarthrosis in haemophilia patients with inhibitors: evaluation of the efficacy of recombinant facto…
2008
Summary. The intention of the ‘clinical and echographical protocol of evaluation the efficacy of recombinant activated factor VII in the haemarthrosis’ (EFFISEVEN protocol) was to provide an extensive study of the evolution of haemarthrosis, and second, of its repercussions on the degenerative process of joints. The clinical evaluation of haemarthroses and their evolution is based on a well-established methodology, although very few studies have sought to determine the correlation between pain, mobility and the objective data regarding the haemorrhage. We believe that it is necessary to unify criteria and that the EFFISEVEN protocol may contribute data that improve standards which, in turn…
Association of Inflammation Markers with Impaired Insulin Sensitivity and Coagulative Activation in Obese Healthy Women
2003
Abstract Insulin resistance is associated with a low chronic inflammatory state. In this study we investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. We examined 32 healthy obese women (body mass index ≥ 28), with normal insulin sensitivity (NIS, n = 14) or impaired insulin sensitivity (n = 18), and 10 nonobese women (body mass index < 25). Impaired insulin sensitivity patients had significantly higher levels of C-reactive protein (CRP), TGF-β1, plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragment 1 + 2 (F1 + 2) compared with either control s…
Reversal of rivaroxaban-induced alterations on hemostasis by different coagulation factor concentrates – in vitro studies with steady and circulating…
2015
BACKGROUND: Despite the good safety of rivaroxaban, there is limited information on strategies for urgent reversal of its antihemostatic effects.Methods and Results:Alterations of hemostasis induced by rivaroxaban (230 ng/ml) were assessed by using several tests applied to steady and circulating human blood. Effects on thrombin generation (TG) and thromboelastometry (TEM) parameters were measured. Modifications in platelet adhesive, aggregating and procoagulant activities were evaluated in studies with circulating blood. The potential reversal of prothrombin complex concentrates (PCCs; 50 IU/kg), activated PCCs (aPCCs; 75 IU/kg), or recombinant factor VIIa (rFVIIa; 270 μg/kg) was evaluated.…
Pharmacokinetic properties of recombinant FVIIa in inherited FVII deficiency account for a large volume of distribution at steady state and a prolong…
2014
Pharmacokinetic properties of recombinant FVIIa in inherited FVII deficiency account for a large volume of distribution at steady state and a prolonged pharmacodynamic effect -